Hepatobiliary and pancreatic diseases are common and frequently occurring diseases in the digestive system,and several hepatobiliary and pancreatic diseases are difficult to diagnose and treat,with a high incidence rate of complications. With the development of minimally invasive devices and instruments and the application of various laparoscopic/endoscopic techniques,most hepatobiliary and pancreatic diseases can be diagnosed and treated by minimally invasive techniques. Traditional Chinese medicine plays an important synergistic role during the perioperative period for hepatobiliary and pancreatic diseases and can accelerate the recovery of patients. The team of Liaoning Provincial Center for Integrated Traditional Chinese and Western Medicine Therapy for Biliary and Pancreatic Diseases led by the authors has mastered various laparoscopic and endoscopic techniques and proposed the concept of SELECT( Spyglass,ERCP,Laparoscopy,EUS,Choledochoscopy,and traditional Chinese medicine) by summarizing the successful experience in the treatment of hepatobiliary and pancreatic diseases in recent years. The optimal combination of minimally invasive multi-endoscopic techniques is selected based on the features of different hepatobiliary and pancreatic diseases,and traditional Chinese medicine treatment is also applied in the perioperative period,so as to achieve minimally invasive,individualized,and precise integrated traditional Chinese and Western medicine therapy for hepatobiliary and pancreatic diseases.

Acute pancreatitis( AP) is one of the common digestive diseases. With the advances in technology,the treatment concept of AP has changed,more and more minimally invasive techniques have been applied in the treatment of AP,especially severe acute pancreatitis( SAP). Although there are various different minimally invasive treatment methods for AP,no reliable clinical studies have reported that one technique is significantly better than others. The therapeutic effect of integrated traditional Chinese and Western medicine therapy in acute pancreatitis( AP) has been widely recognized. In recent years,our team has accumulated rich experience in integrated traditional Chinese and Western medicine therapy for AP and has proposed the innovative SELECT concept( Spyglass,ERCP,Laparoscopy,EUS,Choledochoscopy,and Traditional Chinese Medicine) for diagnosis and treatment. The optimal combination of various endoscopies is SELECTed based on the severity and etiology of AP,and traditional Chinese medicine treatment can be used as well to realize the advantages of minimally invasive integrated traditional Chinese and Western medicine therapy in the treatment of AP. This article elaborates on the minimally invasive treatment methods for each clinical stage of SAP based on the SELECT concept.

Among digestive malignancies,compared with gastrointestinal tumors,biliary and pancreatic tumors are difficult to diagnose in the early stage and have fewer opportunities for radical surgical resection,with a shorter survival time and poorer quality of life,and the clinical diagnosis and treatment of such tumors remain a difficult issue that needs to be solved urgently in clinical practice. Based on the different locations and features of biliary and pancreatic tumors,the SELECT concept selects the optimal combination of minimally invasive endoscopies( laparoscopy,choledochoscopy,duodenoscopy,Spyglass,and endoscopic ultrasound) and applies traditional Chinese medicine treatment in the perioperative period,so as to achieve early diagnosis and treatment,prolong the survival time with tumor,improve quality of life,and strive to realize the goal of cure.

Pancreaticoduodenectomy is one of the most difficult abdominal operations,and the difficulty in resection and complicated digestive tract reconstruction have brought great challenges for surgeons. At present,laparoscopic pancreaticoduodenectomy has been widely used in clinical practice,and compared with traditional 2 D laparoscopy,3 D laparoscopy has the features of high magnification,high definition,and three-dimensional vision,which enables surgeons to see more clearly and operate more accurately,and thus it has great potential to be widely used in pancreaticoduodenectomy.

Since its official application in clinical practice in 2000,da Vinci robotic technology has developed rapidly in recent ten years,especially in the last two years,during which this technology has been widely promoted and used in China. However,in hepatopancreatobiliary( HPB) surgery,da Vinci robotic technology has only been applied in a few large medical centers in China,and its application in HPB surgery is significantly limited compared with that in gastrointestinal surgery,urological surgery,and gynecology,which may be associated with the complexity of HPB surgery and the high risk of postoperative complications. Therefore,how to further promote the application of da Vinci robotic technology in HPB surgery and expand its indications has become an important direction for HPB surgeons.

Laparoscopic hepatectomy has the advantages of little trauma,mild stress response,and rapid postoperative recovery. Due to the deep location and complex structure,tumors located in the upper right posterior areas of the liver( Ⅶ,Ⅷ,and Ⅳa segments) and the caudate lobe have limited surgical field and difficult exposure under laparoscopy,which brings great risk to surgical operation,and these locations are considered difficult locations in laparoscopic liver surgery. In recent years,with the improvement in the technology and concept of laparoscopic liver surgery,the upgrading of surgical instruments and equipment and the application of three-dimensional visualization technology have made it possible to remove liver tumors in difficult locations under laparoscopy. With reference to the authors' own experience,this article summarizes the key technical points of laparoscopic liver surgery in difficult locations,including adequate preoperative assessment,reasonable surgical planning,full exposure of surgical field through body position and trocar distribution,and prediction and prevention of the risk of bleeding. Various new techniques can be used to precisely locate the tumor and guide the partition of liver parenchyma,and with the help of a well-trained surgical anesthesia team,it is possible to ensure the safety and effectiveness of laparoscopic hepatectomy in difficult locations.

Objective To investigate the pharmacokinetic characteristics of sofosbuvir tablets,and to evaluate the bioequivalence and safety of two preparations. Methods Healthy volunteers were recruited through the platform of clinical trial recruitment in The Affiliated Hospital of Changchun University of Chinese Medicine. Screening physical examination was performed for fasting group on September 18,2018 and for postprandial group on September 28,2018,and the volunteers were enrolled after their physical examination results met the inclusion criteria. The fasting group and the postprandial group,with 40 volunteers in each group,were given oral administration of the test preparation sofosbuvir tablets or the reference preparation sofosbuvir tablets( SOVALDI,400 mg). This was a randomized,open-label,two-sequence,four-cycle,single-dose,and completely repeated cross-over bioequivalence test in the fasting or postprandial state in the healthy population; in the fasting group,20 volunteers each received oral administration of the test preparation and the reference preparation,and in the postprandial group,20 volunteers each received oral administration of the test preparation and the reference preparation. Liquid chromatography-tandem mass spectrometry was used to measure the content of sofosbuvir and its major metabolite GS-331007 in human EDTA-K2 plasma; the plasma concentration of sofosbuvir was measured at 15 time points from 0 hour to 8 hours after administration,and that of GS-331007 was measured at 16 time points from 0 hour to 72 hours after administration. WinNonlin software was used to calculate pharmacokinetic parameters and evaluate bioequivalence. Results After the administration of the test preparation and the reference preparation in the fasting state,when the pharmacokinetic parameters of sofosbuvir was used to evaluate the bioequivalence of the test preparation and the reference preparation,the ratios of the geometric means of Cmax,AUC0-t,and AUC0-infwere 90. 55%,97. 26%,and 94. 62%,respectively; when the pharmacokinetic parameters of GS-331007 was used to evaluate the bioequivalence of the test preparation and the reference preparation,the ratios of the geometric means of Cmax,AUC0-t,and AUC0-infwere 98. 91%,98. 98%,and 99. 46%,respec-tively. All of the above values were within the range of 80. 00%-125. 00%. An analysis of variance was performed after the pharmacokinetic parameters of sofosbuvir Cmax,AUC0-t,and AUC0-infwere transformed by natural logarithm,and the results showed that sequence,cycle,and preparation had no marked influence on Cmax,AUC0-t,and AUC0-inf( all P > 0. 05). Conclusion The test preparation of sofosbuvir tablets is bioequivalent to the reference preparation in the fasting and postprandial states.

Objective To investigate the bioequivalence and safety of the generic drug entecavir versus the original drug entecavir tablets in healthy Chinese subjects. Methods A randomized,open,two-cycle,two-cross,fasting trial was designed and performed for 28 healthy subjects,and the subjects were given single oral administration of the test preparation or the reference preparation at a dose of 0. 5 mg in the two cycles,respectively. Liquid chromatography-tandem mass spectrometry was used to measure plasma concentration at 16 different time points within 72 hours after administration,and the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞were calculated to evaluate bioequivalence. WinNonlin software was used to calculate pharmacokinetic parameters and perform bioequivalence evaluation. Results After the oral administration of the test preparation or the reference preparation in the fasting state,the main geometric means( 90% confidence interval) of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞were 98. 18%( 91. 36%-105. 50%),101. 97%( 98. 32%-105. 74%),and 103. 07%( 96. 30%-110. 32%),respectively,all of which were within the range of 80. 00%-125. 00%.After the pharmacokinetic parameters Cmax,AUC0-t,AUC0-∞were transformed by natural logarithm,the variance analysis was carried out. The P value test results showed that the difference between the dosing weeks( P < 0. 05),the dosing sequence and differences in formulation factors( P > 0. 05). Meet the criteria of bioequivalence. Conclusion The two preparations are bioequivalent and have good safety in healthy Chinese subjects.

Objective To investigate the efficacy and safety of elbasvir/grazoprevir in patients with genotype 1 hepatitis C in the real world.Methods A total of 35 patients with hepatitis C who received elbasvir/grazoprevir treatment in Guangzhou Eighth People's Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine,and Guangdong General Hospital from August 2018 to March 2019 were enrolled,treated for 12 weeks,and then followed up for 12 weeks after drug withdrawal. The patients were observed in terms of sustained virologic response at week 12 after drug withdrawal( SVR12),biochemical response,and incidence rate of adverse events during treatment and follow-up. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups,and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the risk factors for virologic response in patients with hepatitis C.Results Among the 35 patients with HCV infection,97. 1%( 34/35) had genotype 1 b HCV and 2. 9%( 1/35) had genotype 1 a HCV; of all patients,28( 80%) were non-cirrhotic patients with chronic hepatitis C and 7( 20%) had compensated liver cirrhosis. At the end of treatment,the virologic response rate of 100%( 28/28) and SVR12 was 94. 74%( 18/19). In addition,age,sex,baseline HCV RNA load,previous treatment history,presence or absence of liver cirrhosis,renal function,and presence or absence of other diseases did not affect the treatment outcome( all P > 0. 05). There were significant changes in the levels of alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transpeptidase,and albumin from baseline to the end of 12-week treatment( Z =-7. 131,-6. 797,-3. 060,and-2. 875,all P < 0. 05). No patient experienced drug withdrawal during treatment. Conclusion This study confirms that elbasvir/grazoprevir has good efficacy and safety in the treatment of hepatitis C in domestic real-world studies.

Objective To investigate the changes of T helper 9( Th9) cells,interleukin-9( IL-9),and related transcription factors in previously untreated patients with chronic hepatitis C,as well as their association with clinical indices. Methods A total of 29 previously untreated patients with chronic hepatitis C who attended Hainan Provincial People's Hospital from December 2018 to July 2019 were enrolled,and 15 healthy individuals were enrolled as healthy controls. The patients with chronic hepatitis C received sofosbuvir/velpatasvir antiviral therapy for 12 weeks,and then plasma and peripheral mononuclear cells( PBMCs) were isolated. Flow cytometry was used to measure the percentage of CD3+CD4+IL-9+Th9 cells in PBMCs; ELISA was used to measure the plasma level of IL-9; quantitative real-time PCR was used to measure the relative mRNA expression of IL-9 and the transcription factors PU. 1 and Foxo1 in PBMCs. The t-test or the paired t-test was used for comparison between two groups,and a Pearson correlation analysis was used to investigate correlation. Results Compared with the healthy controls,the previously untreated chronic hepatitis C patients had significantly lower percentage of peripheral Th9 cells( 0. 92% ± 0. 14% vs 1. 14% ± 0. 21%,t = 4. 31,P < 0. 001) and plasma IL-9 level( 248. 2 ± 66. 97 pg/ml vs 309. 02 ± 88. 48 pg/ml,t = 2. 63,P = 0. 012). The previously untreated chronic hepatitis C patients had significantly lower relative mRNA expression of IL-9 and PU. 1 than the healthy controls( t = 20. 67 and 23. 21,both P < 0. 001),while there was no significant difference in the relative mRNA expression of Foxo1 between the previously untreated chronic hepatitis C patients and the healthy controls( P > 0. 05). In the previously untreated chronic hepatitis C patients,the percentage of peripheral Th9 cells,IL-9 level,and mRNA expression of IL-9 and PU. 1 were negatively correlated with HCV RNA( r =-0. 46,-0. 38,-0. 52,and-0. 41,all P < 0. 05),but they were not correlated with the level of alanine aminotransferase( all P > 0. 05). Sofosbuvir/velpatasvir antiviral therapy achieved virologic response in 29 chronic hepatitis Cpatients,and the percentage of peripheral Th9 cells and the mRNA expression of PU. 1 after antiviral therapy were significantly higher than those at baseline( t = 2. 20 and 6. 52,both P < 0. 05),while there were no significant changes in the plasma level of IL-9 and the relative mRNA expression of IL-9 from baseline to after treatment( both P > 0. 05). Conclusion Chronic hepatitis C virus infection may suppress the activation of Th9 cells,suggesting that Th9 cells might be involved in the chronicity of hepatitis C virus infection.

Objective To investigate the value of peripheral blood long non-coding RNA-LET( lncRNA-LET) in the diagnosis of chronic hepatitis B( CHB) cirrhosis,and to provide a basis for early clinical diagnosis and treatment of liver cirrhosis. Methods A total of 175 CHB patients who attended The Affiliated Hospital of Chengde Medical University from March 2017 to May 2019 were enrolled,among whom52 patients with hepatitis B cirrhosis were enrolled as cirrhosis group and 123 patients without the pathological changes of liver cirrhosis were enrolled as non-cirrhosis group. A total of 40 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as normal control group. Liver function parameters and the level of lncRNA-LET in peripheral blood were measured for all subjects. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups,and the Kruskal-Wallis H test was used for comparison of ranked data. A Pearson correlation analysis was performed to investigate correlation. The receiver operating characteristic( ROC) curve was used to investigate the value of peripheral blood lncRNA-LET in predicting liver cirrhosis. Results Compared with the normal control group,the cirrhosis group and the non-cirrhosis group had significantly higher serum levels of the liver function parameters total bilirubin( TBil),total bile acid( TBA),albumin( Alb),and alanine aminotransferase( ALT)( all P < 0. 05) and a significantly lower serum level of cholinesterase( ChE)( P < 0. 05); compared with the non-cirrhosis group,the cirrhosis group had significantly higher serum levels of TBil,TBA,Alb,and ALT( all P < 0. 05) and a significantly lower serum level of ChE( P < 0. 05). Compared with the normal control group,the cirrhosis group and the non-cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood( P < 0. 05),and the cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood than the non-cirrhosis group( P < 0. 05). The relative expression of lncRNA-LET decreased significantly with the increase in liver fibrosis stage( P < 0. 05). In the patients with CHB,the relative expression of lncRNA-LET in peripheral blood was negatively correlated with liver fibrosis stage,TBil,TBA,Alb,and ALT( r =-0. 352,-0. 372,-0. 364,and-0. 410,all P < 0. 001) and was positively correlated with ChE( r = 0. 340,P < 0. 001). The ROC curve was used to analyze the value of peripheral blood lncRNA-LET in predicting liver cirrhosis,and the area under the ROC curve was 0. 934,with an optimal cut-off value of 0. 833,a sensitivity of 84. 57%,and a specificity of 80. 57%. Conclusion The expression level of lncRNA-LET in peripheral blood decreases with the progression of liver fibrosis and has a good value in the diagnosis of CHB cirrhosis,and therefore,it can be used as a potential biological indicator for the diagnosis of liver cirrhosis.

Objective To investigate the effect of direct-acting antiviral( DAA) on the recurrence of hepatitis C virus( HCV)-related hepatocellular carcinoma( HCC) after curative treatment. Methods PubMed,Web of Science,Cochrane Library,CNKI,CBM,Wanfang Data,and VIP were searched for the clinical studies of DAA and the recurrence of HCV-related HCC published up to April 2020. Stata14. 0 software was used to perform the meta-analysis. The Cochran Q test was used to evaluate heterogeneity between studies; the fixed effects model was used for non-heterogeneous data,and the random effects model was used for heterogeneous data. The Egger regression method or the Begg rank correlation method was used to evaluate the presence or absence of publication bias. Results A total of 10 articles( 11 studies) were included in our study,among which 8 articles( 9 studies) compared the effect of DAA versus the absence of anti-HCV therapy on the recurrence of HCC after curative treatment. There were 991 patients in DAA group and 808 patients in untreated group. The results of the meta-analysis showed that DAA reduced the recurrence rate of HCC after curative treatment in patients with HCV infection( hazard ratio [HR]= 0. 42,95% confidence interval [CI]: 0. 28? 0. 36,P < 0. 001). Three articles compared the effect of DAA versus interferon for the treatment of hepatitis C on the recurrence of HCC after curative treatment,with 267 patients in DAA group and 212 in interferon group,and the results of the meta-analysis showed that DAA and interferon had a similar effect on the recurrence rate of HCV-related HCC( HR = 0. 85,95% CI: 0. 64-1. 15,P = 0. 298). Conclusion Both interferon and DAA can significantly reduce the recurrence risk of HCV-related HCC after curative treatment,with no significant difference between them.

Objective To investigate the clinical effect and safety of transcatheter arterial chemoembolization( TACE) combined with microwave ablation( MWA) in the treatment of advanced primary liver cancer. Methods A total of 186 patients with advanced primary liver cancer who were treated in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to June 2019 were enrolled and divided into study group and control group using a random number table,with 93 patients in each group. Both groups of patients underwent TACE,and the patients in the study group were treated with ultrasound-guided percutaneous MWA. The two groups were compared in terms of clinical outcome and complications. Quantitative real-time PCR was used to measure the serum level of microRNA-202( miR-202),ELISA was used to measure the serum levels of fragile histidine triad( FHIT) and P16 protein,and the changes in the above three indices at3 months after treatment were compared. The two-independent-samples t test was used for comparison of continuous data between two groups,and the paired t-test was used for comparison within one group before and after treatment; The chi-square testwas used for comparison of categorical data between groups. Results The study group had a significantly higher objective response rate than the control group( 47. 32% vs 27. 96%,χ2= 7. 422,P = 0. 006),and there was no significant difference in disease control rate between the two groups( P >0. 05). Both groups had significant increases in the serum levels of miR-202,FHIT,and P16 protein at 3 months after treatment( all P<0. 05),and compared with the control group,the study group had significantly higher serum levels of miR-202( 0. 84 ± 0. 14 vs 0. 58 ±0. 17,t = 11. 385,P < 0. 001),FHIT( 1126. 35 ± 73. 05 pg/ml vs 762. 87 ± 56. 71 pg/ml,t = 37. 904,P < 0. 001),and P16 protein( 52. 86 ± 6. 51 pg/ml vs 39. 06 ± 5. 37 pg/ml,t = 15. 770,P < 0. 001). Conclusion Ultrasound-guided MWA in addition to TACE canimprove the short-term response of patients with advanced primary liver cancer and increase the serum levels of miR-202,FHIT,and P16 protein,with relatively high safety.

Objective To investigate the effect of kaempferol on the proliferation,migration,invasion,and apoptosis of human hepatoma Bel-7402 cells and related molecular mechanism. Methods Hepatoma Bel-7402 cells cultured in vitro were randomly divided into control group and low-,middle-,and high-concentration experimental groups. The experimental groups were treated with low-,middle-,and high-concentration kaempferol( 25,50,and 100 μmol/L),and the control group was treated with an equal volume of dimethyl sulfoxide. CCK-8 assay was used to observe the effect of kaempferol on the viability of Bel-7402 cells; plate colony formation assay was used to evaluate the effect of kaempferol on cell colony formation ability; wound healing assay and Transwell chamber were used to observe the effect of kaempferol on cell migration and invasion; Western blot was used to measure the expression of apoptosis-and cycle-related proteins. A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results After 24 hours of treatment,the cell viability was 100. 00% ± 2. 72% in the control group and 75. 70% ± 2. 42%,62. 79% ± 2. 45%,and 43. 41% ± 2. 11%,respectively,in the low-,middle-,and high-concentration experimental groups,and compared with the control group,the experimental groups had a significant reduction in cell viability( all P < 0. 05).The number of cell colonies was 923. 3 ± 35. 2 in the control group and 682. 7 ± 24. 4,464. 0 ± 22. 0,and 327. 3 ± 14. 0,respectively,in the low-,middle-,and high-concentration experimental groups,and compared with the control group,the experimental groups had a significant reduction in cell colony formation ability( all P < 0. 05). After 24 hours of treatment,the relative migration rate was 100. 00% ± 1. 11% in the control group and 63. 33% ± 1. 16%,51. 72% ± 3. 23%,and 37. 18% ± 2. 71%,respectively,in the low-,middle-,and high-concentration experimental groups,and the number of transmembrane cells was 212. 0 ± 3. 0 in the control group and 134. 0 ± 2. 0,71. 0 ±2. 0,and 34. 0 ± 1. 0,respectively,in the low-,middle-,and high-concentration experimental groups; compared with the control group,the experimental groups had significant reductions in relative migration rate and number of transmembrane cells( all P < 0. 05). After48 hours of treatment,compared with the control group,the low-,middle-,and high-concentration experimental groups had a significant reduction in the expression of the anti-apoptotic protein Bcl-2( all P < 0. 05),a significant increase in the expression of the pro-apoptotic protein Bax( all P < 0. 05),and a significant reduction in the expression of C < italic/> yclinD1( all P < 0. 05). Conclusion Kaempferol can inhibit the proliferation,migration,and invasion of human hepatoma Bel-7402 cells and promote the apoptosis of such cells,possibly by regulating the apoptosis proteins Bax and Bcl-2 and downregulating the expression of CyclinD1.

Objective To investigate the effect of arsenic trioxide-loaded CalliSpheres beads( CBATO) in transarterial chemoembolization( TACE) in the treatment of rabbits with VX2 liver tumor. Methods A total of 120 tumor-bearing rabbits were divided into control group,CalliSpheres beads( CB) group( blank beads for TACE),CBATO group,and conventional TACE( cTACE) group( arsenic trioxide lipiodol for TACE) using a random number table,with 30 rabbits in each group. Five rabbits in each group were sacrificed at 12 hours and on days 3,7,and 14 after TACE,and immunohistochemistry was used to measure the proliferation index and apoptosis percentage of tumor cells in the residual tumor area. The tumor necrotic volume was measure on day 7 after TACE,and the growth rate and necrosis rate of tumor cells were calculated. Ten rabbits were randomly selected from each group for the observation of survival time. An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups; the Kaplan-Meier survival analysis was used to evaluate survival time,and the log-rank test was used for comparison.Results On day 7 after TACE,the CBATO group had a significantly lower growth rate and a significantly higher necrosis rate of tumor cells than the cTACE group,the CB group,and the control group( all P < 0. 05). At each time point after TACE,there were significant differences in the proliferation index and apoptosis percentage of tumor cells between the CBATO group and the other three groups( all P < 0. 05).The median survival time was 26 days in the CBATO group,18. 5 days in the CB group,22 days in the cTACE group,and 15. 5 days in the control group,and the CBATO group had a significantly longer survival time than the other three groups( χ2= 3. 95,8. 99,and 13. 47,P =0. 049,P = 0. 003,and P < 0. 01). Conclusion CBATO has a better effect than cTACE and CB in the treatment of rabbits with VX2 liver tumor and can significantly improve tumor necrosis rate,promote the apoptosis of tumor cells,and prolong the survival time of experimental animals.

Objective To investigate the etiology of liver diseases with negative hepatotropic virus,and to provide ideas for the clinical diagnosis and treatment of liver diseases. Methods A retrospective analysis was performed for the clinical data and liver biopsy results of 113 patients with negative hepatotropic virus who were admitted to The Affiliated Hospital of Xuzhou Medical University from July 2018 to December 2019. According to sex,they were divided into male group with 41 patients and female group with 72 patients,and according to age,they were divided into youth group with 42 patients,middle-aged group with 56 patients,and elderly group with 15 patients. The chi-square test was used for comparison of categorical data between groups. Results Among the 113 patients with negative hepatotropic virus,111( 98. 23%) were given a confirmed diagnosis,among whom 43( 38. 05%) were diagnosed with nonalcoholic fatty liver disease( NAFLD),40( 35. 40%) were diagnosed with drug-induced liver injury( DILI),16( 14. 15%) had autoimmune liver disease( AILD),8( 7. 08%) had alcoholic liver disease,3( 2. 65%) had biliary disease,and 1( 0. 88%) had diseases in other systems which involved the liver. Among the male patients,53. 49% had NAFLD,100% had ALD,and 15% had DILI,while among the female patients,85% had DILI,46. 51% had NAFLD,and 93. 75% had AILD. For DILI,there were significantly more female patients than male patients( χ2=40. 000,P < 0. 001),and for AILD,there were also significantly more female patients than male patients( χ2= 12. 250,P < 0. 001). In the youth group,NAFLD( 55. 81%),DILI( 20%),and ALD( 75%) were the main causes of disease,and DILI was the main cause in the middle-aged group and the elderly group. Among the patients with NAFLD,there were significantly more patients in the youth group than in the elderly group( χ2= 16. 333,P < 0. 001); among the patients with DILI,there were significantly more patients in the middle-aged group than in the youth group( χ2= 8. 000,P = 0. 005); among the patients with AILD,there were significantly more patients in the middle-aged group than in the youth group( χ2= 8. 333,P = 0. 004). Conclusion Most liver diseases with negative hepatotropic virus can be diagnosed by liver biopsy,and NAFLD,DILI,and AILD are the main causes. Patients with different sexes and ages have different etiologies.

Objective To investigate the expression and clinical significance of OX40/OX40 L( CD134/CD134 L) in CD4 + T cells,CD8 +T cells,monocytes,and B lymphocytes in peripheral blood of patients with autoimmune hepatitis( AIH),primary biliary cholangitis( PBC),and their overlap syndrome before and after standardized treatment. Methods A total of 74 patients with AIH,PBC,and their o-verlap syndrome who were diagnosed in Subei People's Hospital of Jiangsu from August 2015 to August 2019 were enrolled,and according to related diagnostic criteria,they were divided into AIH group( group A) with 29 patients,PBC group( group P) with 26 patients,and overlap syndrome group( group C) with 19 patients. A healthy control group with 30 individuals was also established. Peripheral blood samples were collected before and after standardized treatment to measure the expression of OX40/OX40 L on the surface of peripheral blood cells by immunofluorescence flow cytometry,and the expression of OX40/OX40 L was compared before and after treatment and between the three groups and the healthy control group to investigate its clinical significance. A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups; the paired t-test was used for comparison of paired samples between two groups. Results There were no significant differences in sex composition and age composition between the three groups( P > 0. 05). Before treatment,the positive rate of OX40 in peripheral blood CD4+T cells gradually increased in groups A,P,and C,and groups A,P,and C had a significantly higher positive rate of OX40 than the control group( 14. 80% ± 4. 99%/17. 11% ± 2. 71%/25. 18% ± 5. 55% vs 6. 67% ± 2. 26%,F = 14. 823,P < 0. 001); groups A,P,and C had a significantly higher positive rate of OX40 in CD8+T cells than the control group( 4. 86% ± 1. 54%/6. 40% ± 1. 88%/7. 33% ± 2. 12% vs 4. 09% ± 2. 69%,F =5. 486,P < 0. 001); the positive rate of OX40 L in CD14+monocytes was 19. 84% ± 6. 11% in group A,21. 17% ± 4. 35% in group P,29. 13% ± 6. 32% in group C,and 4. 86% ± 2. 34% in the control group,and there was a significant difference between groups( F =17. 004,P < 0. 001); the positive rate of OX40 L in CD19+B cells was 17. 62% ± 3. 86% in group A,14. 75% ± 4. 32% in group P,10. 13% ± 2. 56% in group C,and 4. 50% ± 1. 38% in the control group,showing a trend of gradual reduction,and groups A,P,and C had a significantly higher positive rate than the control group( F = 12. 221,P < 0. 001). After treatment,the positive rate of OX40 in CD8+T cells decreased significantly to a similar level as the control group,and there was no significant difference between groups( F =0. 731,P = 0. 538). For the other three types of cells,although there were varying degrees of reduction in the positive rate of OX40/OX40 L after treatment,groups A,P,and C still had a significantly higher positive rate than the control group; in CD4+T cells,the positive rate of OX40 was 11. 00% ± 1. 98% in group A,13. 72% ± 1. 03% in group P,19. 72% ± 3. 47% in group C,and 6. 67% ± 2. 26% in the control group,and groups A,P,and C had a significantly higher positive rate than the control group( F = 11. 365,P < 0. 001); in CD14+monocytes,the positive rate of OX40 L was 11. 82% ± 2. 23% in group A,15. 19% ± 4. 42% in group P,24. 51% ± 4. 09% in group C,and 4. 86% ± 2. 34% in the control group,and groups A,P,and C had a significantly higher positive rate than the control group( F =13. 748,P < 0. 001); in CD19+B cells,the positive rate of OX40 L was 9. 09% ± 3. 25% in group A,6. 81% ± 2. 20% in group P,7. 48% ± 2. 85% in group C,and 4. 50% ± 1. 38% in the control group,and groups A,P,and C had a significantly higher positive rate than the control group( F = 8. 052,P < 0. 001). Groups A,P,and C had significant reductions in the expression of OX40/OX40 L in peripheral blood CD4+T cells,CD8+T cells,CD14+monocytes,and CD19+B lymphocytes after treatment( all P < 0. 05). Conclusion The expression of OX40/OX40 L in peripheral blood increases in patients with AIH,PBC,and their overlap syndrome and decreases after treatment,indicating that the OX40/OX40 L pathway is involved in the pathogenesis of the above diseases,and the role of OX40 on the surface of CD8+T cells may better reflect the treatment outcome.

Objective To investigate the pathology,clinical features,population features,and etiology of non-viral hepatitis-related abnormal liver function in the elderly. Methods A retrospective analysis was performed for 50 elderly patients,with abnormal liver function as disease onset for the first time,who were hospitalized and treated in Beijing YouAn Hospital,Capital Medical University,from January2017 to September 2019. Abnormal liver function was defined as elevated alanine aminotransferase( ≥2 × upper limit of normal),with or without the increases in the serum levels of aspartate aminotransferase,total bilirubin,alkaline phosphatase,and gamma-glutamyl transpeptidase,and there was no limit for the duration of abnormal liver function. According to the method for obtaining pathological specimens,the patients were divided into percutaneous liver biopsy group and transjugular liver biopsy group. The etiology of abnormal liver function was analyzed,and clinical features and laboratory markers were summarized. The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results A total of 50 patients were enrolled,with a mean age of 64. 7 ± 3. 7 years,and there were 19 male patients and 31 female patients. Of all patients,21 underwent transjugular liver biopsy and 29 underwent percutaneous liver biopsy. Pathological examination showed that 20 patients( 40. 0%) were diagnosed with drug-induced liver injury,among whom 3 had autoimmune phenomena,1 had liver failure,and 4 had hepatic veno-occlusive disease/hepatic sinusoidal obstruction syndrome; 5 patients( 10. 0%) were diagnosed with autoimmune liver disease,among whom 3 had primary biliary cholangitis and 2 had autoimmune hepatitis( 1 patient already had liver cirrhosis); 4 patients( 8. 0%) were diagnosed with nonalcoholic fatty liver disease. The etiology was not determined for 16 patients( 32. 0%),among whom 8 had liver cirrhosis,6 had hepatitis,and 2 had bile duct disease. In addition,there were 2 patients with non-cirrhotic portal hypertension( 4. 0%),1 patient with amyloidosis( 2. 0%),and 2 patients with liver failure( 4. 0%). Conclusion Drug-induced liver injury has the highest incidence rate among non-viral hepatitis-related abnormal liver function in the elderly,which is often associated with the use of drugs for chronic diseases and Chinese patent drugs. Transjugular liver biopsy may help to determine the etiology of severe liver diseases.

Objective To investigate the clinical features and causes of death after transjugular intrahepatic portosystemic shunt( TIPS) in patients with hepatic sinus obstruction syndrome( HSOS),as well as the prevention and treatment measures to further improve the survival rate of such patients. Methods A retrospective analysis was performed for 293 patients with HSOS who were admitted to Nanjing Drum Tower Hospital from January 2013 to December 2019,among whom 20 patients died after TIPS. General information,laboratory examination,and clinical treatment regimen were analyzed,and clinical indices and complications were compared at different stages of the disease.The paired t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. Results The mean survival time was 15. 15 ± 4. 21 weeks for the 20 patients who died,among whom there were 15 male patients and 5 female patients,with a mean age of 67. 60 ± 7. 01 years;there were 17 patients( 85%) aged ≥60 years,and more than 90% of the patients had abdominal distention and oliguria. Among the 20 patients who died,9( 45%) had chronic underlying diseases,and 5( 25%) had more than two underlying diseases. Portal venous pressure decreased from 21. 67 ± 5. 15 mm Hg before surgery to 8. 17 ± 4. 98 mm Hg after surgery( t = 10. 318,P < 0. 05). The levels of total bilirubin,direct bilirubin,and D-dimer were significantly higher than the normal values before surgery,and there were significant increases in these levels on day 5 after surgery( Z = 3. 823,3. 823,2. 756,all P < 0. 05); the hemoglobin level,platelet count,and creatinine level tended to decrease on day 5 after surgery( t = 4. 979,t = 2. 147,Z =-3. 125,all P < 0. 05). Three patients had hepatic encephalopathy before surgery,while 10 patients( 50%) had hepatic encephalopathy after surgery. Causes of death included acute liver failure,infectious shock,and multiple organ failure syndrome( MODS). Conclusion The possible risk factors for death after TIPS in HSOS patients include underly-ing diseases,high bilirubin,and complications such as hepatic encephalopathy and renal dysfunction. Causes of death mainly include acute liver failure and MODS. Ultrasound and laboratory markers should be reexamined during anticoagulation therapy to identify the patients with progression to severe diseases as early as possible,and in case of progressive deterioration of indices,TIPS should be selected as early as possible to improve the survival rate and prognosis of such patients. In addition,hemobilia should be observed during and after surgery,and intervention measures should be adopted in time to further reduce mortality rate.

Objective To investigate the etiology and clinical manifestations of liver failure in pregnancy and the value of TPL predictive model based on total bilirubin( TBil),prothrombin activity( PTA),and lactic acid( LACT) in evaluating the prognosis of liver failure in pregnancy. Methods A total number of 69 pregnant patients who were diagnosed with liver failure in The Third Affiliated Hospital of Guangzhou Medical University from January 1,2009 to December 31,2019 were enrolled,and according to prognosis,they were divided into death group with 22 patients and survival group with 47 patients. The two groups were compared in terms of etiology,clinical manifestation,laboratory markers,and prognosis. A multivariate logistic regression analysis was used to investigate the independent risk factors for death in patients with liver failure in pregnancy,and a TPL predictive model was established. The t-test was used for comparison of normally distributed continuous data between two groups,and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic( ROC) curve was plotted,and the area under the ROC curve( AUC) was used to analyze the value of TPL model in predicting the prognosis of patients with liver failure in pregnancy. Results Of all 69 patients,22 died and 47 survived,with a mortality rate of31. 9%. Acute fatty liver of pregnancy( AFLP) was the most common cause of liver failure in pregnancy( 37. 7%),followed by viral hepatitis( 27. 5%). There was no significant difference in mortality rate between the patients with different etiologies( χ2= 4. 013,P > 0. 05).Jaundice was the most common clinical manifestation of liver failure in pregnancy( 79. 7%),followed by poor appetite( 63. 8%) and edema of both lower limbs( 52. 2%). There were no significant differences in clinical manifestations between the survival group and the death group( P > 0. 05). Compared with the survival group,the death group had significantly higher TBil,LACT,and international normalized ratio and significantly lower PTA and platelet count( Z =-2. 691,Z =-1. 998,Z =-2. 640,t =-2. 545,Z =-2. 222,all P < 0. 05). The multivariate logistic regression analysis was used to include TBil,PTA,and LACT into an equation and establish the TPL model( all P<0. 05),and the TPL model had a sensitivity of 90. 9%,a specificity of 68. 1%,a positive predictive value of 57. 1%,and a negative predictive value of 94. 1%. The TPL model had an AUC of 0. 833( 95% confidence interval [CI]: 0. 771-0. 965,P < 0. 05),and the TPL model had a significantly higher AUC than the TBil model( AUC = 0. 702,95% CI: 0. 594-0. 805,P < 0. 05),PTA model( AUC =0. 673,95% CI: 0. 550-0. 796,P < 0. 05),and LACT model( AUC = 0. 650,95% CI: 0. 494-0. 772,P < 0. 05). According to the cut-off value of the ROC curve,patients' mortality rate increased with the increase in the score of the TPL model( χ2= 20. 312,P <0. 05). Conclusion AFLP and viral hepatitis are common causes of liver failure in pregnancy,and jaundice,poor appetite,and edema of both lower limbs are common clinical manifestations of liver failure in pregnancy. The TPL predictive model is more accurate than the single index in predicting the prognosis of liver failure in pregnancy and has a better clinical guiding value.

Objective To investigate the correlation between body fat parameters and the severity of acute pancreatitis( AP) and the value of body fat parameters in predicting the severity of AP. Methods A retrospective analysis was performed for the clinical data of 229 patients with AP who were treated in Department of Gastroenterology in The Affiliated Hospital of Southwest Medical University from June 2016 to June 2019. According to the diagnostic criteria for AP,the patients were divided into mild acute pancreatitis( MAP) group,moderate-severe acute pancreatitis( MSAP) group( all P < 0. 05),and severe acute pancreatitis( SAP) group,and CT images were used to calculate related body fat parameters [visceral adipose tissue( VAT),subcutaneous adipose tissue( SAT),total adipose tissue( TAT),abdominal muscle area( AMA),VAT/TAT ratio( VTR),and visceral fat-to-muscle ratio( VMR) ]. A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. A logistic regression analysis was used to investigate the correlation of the body fat parameters with AP severity. The receiver operating characteristic( ROC) curve was established for each body fat parameter and the area under the ROC curve( AUC) was calculated,and then the Youden index was calculated to determine the optimal cut-off value. Results There were significant differences in age,VAT,TAT,AMA,VTR,and VMR between the three groups( F = 4. 15,35. 25,73. 02,7. 09,462. 30,and 139. 4,all P < 0. 05),and further comparison showed that compared with the MAP group,the MSAP group and the SAP group had significant increases in VAT,TAT,VTR,and VMR( all P<0. 05) and a significant reduction in AMA( all P < 0. 05). The SAP group had significantly higher VAT,VTR,and VMR than the MSAP group( all P < 0. 05). VMR had the largest AUC of 0. 84( 95% confidence interval: 0. 76-0. 92) in predicting MSAP and SAP,and had the cut-off value of 1. 38 in predicting the severity of AP,with a sensitivity of 67. 5% and a specificity of 90. 6%. Conclusion Body fat parameters are correlated the severity of AP. VMR has a unique value in predicting the severity of AP and can be included in the future scoring models for predicting AP severity.

Objective To investigate the value of hyponatremia in predicting the severity of acute pancreatitis( AP). Methods Clinical data were collected from 459 AP patients who attended The Affiliated Hospital of Southwest Medical University from January to December2019,and according to the serum Na+level at the time of onset,the patients were divided into hyponatremia group with 123 patients and non-hypernatremia group with 336 patients. The two groups were analyzed and compared in terms of baseline data,complications,mortality rate,and AP-related scores. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis was used to identify the influencing factors for moderate-to-severe AP( M-SAP),acute necrotic collection( ANC),and systemic inflammatory response syndrome( SIRS),and the receiver operating characteristic( ROC) curve was used to evaluate the value of related indices. Results Compared with the non-hyponatremia group,the hyponatremia group had a significantly younger age and significantly higher body mass index and proportion of patients with diabetes,and most patients had hyperlipidemic AP( all P < 0. 05). Compared with the non-hyponatremia group,the hyponatremia group had significantly higher triglyceride,blood glucose,hematocrit,C-reactive protein,procalcitonin,neutrophil-to-lymphocyte ratio,and proportion of patients with CT severity index > 2 on admission( all P<0. 05). Compared with the non-hyponatremia group,the hyponatremia group had a significantly higher proportion of patients with M-SAP or SAP,acute peripancreatic fluid accumulation,ANC,SIRS,acute respiratory distress syndrome,and multiple organ failure( all P <0. 05). The multivariate logistic regression analysis showed that hyponatremia( odds ratio [OR]= 5. 272,95% confidence interval [CI]:2. 771-10. 029,P < 0. 001),age( OR = 0. 976,95% CI: 0. 956-0. 995,P = 0. 011),Ranson score >2( OR = 10. 437,95% CI:4. 116-26. 465,P < 0. 001,and alcoholic AP( OR = 3. 249,95% CI: 1. 214-8. 694,P = 0. 019) were independent risk factors for M-SAP,and the combination of these four indices had an area under the ROC curve( AUC) of 0. 759; hyponatremia( OR = 1. 931,95% CI:1. 007-3. 700,P = 0. 047; OR = 3. 792,95% CI: 2. 193-6. 556,P < 0. 001) and Ranson score > 2( OR = 2. 621,95% CI: 1. 304-5. 271,P = 0. 007; OR = 5. 845,95% CI: 3. 066-11. 143,P < 0. 001) were independent risk factors for ANC and SIRS,and the combination of these two indices had AUCs of 0. 677 and 0. 742,respectively,in predicting ANC and SIRS. Conclusion Hyponatremia can be used as a simple reference index for evaluating disease severity in patients with AP.

Objective To investigate the risk factors for new-onset diabetes after incipient acute pancreatitis( AP). Methods A retrospective analysis was performed for 95 patients with post-acute pancreatitis diabetes mellitus( PPDM-A) after incipient AP who were admitted to The Affiliated Hospital of Southwest Medical University from June 2013 to January 2020( PPDM-A group),and 190 patients without diabetes after incipient AP during the same period of time were selected at a ratio of 2 ∶ 1 and were enrolled as non-PPDM-A group. Baseline data and clinical data were collected. The t-test or the U test was used for comparison of continuous data,and the chi-square test or the Fisher's exact test was used for comparison of categorical data; a logistic regression analysis was used for multivariate analysis. Results There were significant differences between the two groups in body mass index( BMI),body weight,and proportion of patients with a drinking history,hyperuricemia,or fatty liver disease( all P < 0. 05),while there were no significant differences between the two groups in age,male sex,and proportion of patients with a smoking history,a family history of diabetes,or hypertension( all P > 0. 05).There were also significant differences in etiologies( biliary,hyperlipidemic,and alcoholic AP) between the two groups( P < 0. 05). Compared with the non-PPDM-A group,the PPDM-A group had significantly higher triglyceride,blood glucose,white blood cell count( WBC),C-reactive protein,and proportion of patients with blood glucose > 11. 1 mmol/L on admission( all P < 0. 05),while there were no significant differences in Ca2 +,blood amylase,and blood lipase between the two groups( all P >0. 05). Compared with the non-PPDM-A group,the PPDM-A group had significantly higher incidence rates of acute peripancreatic necrotic collections and acute peripancreatic fluid collections,proportion of patients with multiple onset of AP,and proportion of patients with CTSI score > 4( all P < 0. 05),while there were no significant differences in the proportion of patients with systemic inflammatory response syndrome and disease severity between the two groups( both P > 0. 05). The multivariate analysis showed that the outcome of PPDM-A in alcoholic AP patients was 5. 868 times that in biliary AP patients( 95% confidence interval [CI]: 1. 607-21. 418,P = 0. 007),and the outcome of PPDM-A in hyperlipidemic AP patients was 3. 312 time that in biliary AP patients( 95% CI: 1. 593-6. 887,P = 0. 001). The outcome of PPDM-A in overweight patients was 3. 694 times that in patients with normal BMI( 95% CI: 1. 575-8. 667,P = 0. 003),and the outcome of PPDM-A in obese patients was 5. 964 times that in patients with normal BMI( 95% CI: 2. 516-14. 139,P < 0. 001). Multiple onset of AP( OR = 4. 522,95%CI: 2. 298-8. 900,P < 0. 001),blood glucose on admission > 11. 1 mmol/L( OR = 6. 749,95% CI: 3. 381-13. 469,P < 0. 001),CTSI score > 4( OR = 1. 176,95% CI: 1. 008-1. 371,P = 0. 039),and WBC( OR = 1. 082,95% CI: 1. 009-1. 160,P = 0. 026) were independent risk factors for PPDM-A. Conclusion Multiple onset of AP,alcoholic AP,hyperlipidemic AP,blood glucose on admission > 11. 1 mmol/L,overweight or obesity,CTSI score > 4,and WBC are independent risk factors for PPDM-A,which can provide a reference for formulating strategies to prevent or reduce the onset of PPDM-A.

Objective To investigate the value of early fluid resuscitation endpoints in evaluating blood volume in patients with acute pancreatitis. Methods A retrospective analysis was performed for the clinical data of 445 previously untreated patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Guangxi Medical University from 2003 to 2016 and had an onset time of less than 24 hours,and according the fluid resuscitation endpoints of mean arterial pressure( MAP),hematocrit( HCT),and blood urea nitrogen( BUN),the patients were divided into standard-reaching group( MAP > 65 mm Hg,BUN < 7. 14 mmol/L,and HCT ≥0. 35 and ≤0. 44,n = 219) and non-standard-reaching group( MAP ≤65 mm Hg or BUN ≥7. 14 mmol/L or HCT > 0. 44 or < 0. 35,n = 226).The standard-reaching group represented normal volume,while the non-standard-reaching group represented insufficient volume. The two groups were compared in terms of symptoms,signs,etiology,severity,complication,and prognosis. The chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups,and the Mann-Whitney U test was used for comparison of continuous data between two groups. Results Compared with the standard-reaching group,the non-standard-reaching group had significant increases in white blood cell count,BUN,and Computed Tomography Severity Index of the pancreas( Z =-2. 85,-6. 725,and-2. 293,all P < 0. 01). As for local complications,compared with the non-standard-reaching group,the standard-reaching group had significantly lower incidence rates of peripancreatic exudation( 45. 2% vs 54. 9%,χ2= 4. 15,P < 0. 05) and pancreatic necrosis( 10. 0% vs 18. 6%,χ2= 6. 59,P < 0. 05). As for systemic complications,compared with the non-standard-reaching group,the standard-reaching group had significantly lower incidence rates of acute respiratory distress syndrome( ARDS)( 0. 5% vs 4. 4%,χ2= 7. 26,P < 0. 05) and renal dysfunction( 1. 4% vs 6. 6%,χ2= 7. 95,P < 0. 05). The standard-reaching group had significantly lower proportion of patients with severe pancreatitis and hospital costs than the non-standard-reaching group( both P < 0. 05). Conclusion Fluid resuscitation endpoints can be used to evaluate the blood volume of patients with acute pancreatitis in the early stage after admission,and the patients not reaching the standard of fluid resuscitation tend to develop the complications such as peripancreatic exudation,pancreatic necrosis,ARDS,and renal dysfunction and may have higher hospital costs.

Objective To investigate the therapeutic effect of magnolol on severe acute pancreatitis( SAP) with acute lung injury from the aspect of the functional block of intestinal lymphatic circulation by magnolol. Methods A total of 30 healthy male Sprague-Dawley rats were randomly divided into sham-operation group,SAP group,and magnolol treatment group,with 10 rats in each group. The rats in the sham-operation group were given laparotomy to flip the pancreas,followed by abdominal closure; the rats in the SAP group were given retrograde pancreaticobiliary injection of 3. 75% sodium taurocholate to establish a rat model of SAP; the rats in the magnolol treatment group were given injection of magnolol 0. 2 mg/kg via the penile vein at 15 minutes before modeling. The three groups were compared in terms of pathological changes of the lung and the intestine,pathological score,the levels of D-lactic acid( DLA),diamine oxidase( DAO),high-mobility group box 1( HMGB1),receptor for advanced glycation end products( RAGE),interleukin-1β( IL-1β),interleukin-8( IL-8),interleukin-10( IL-10),and tumor necrosis factor-α( TNFα) in serum,lymphatic fluid,and tissue homogenate of the lung and the intestine,and the level of Toll-like receptor 4( TLR4) in lymphatic fluid. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. Results The SAP group had congestion,edema,inflammatory cell infiltration,and bleeding in the pulmonary interstitium,and the magnolol treatment group had mild bleeding and inflammatory cell infiltration in the pulmonary interstitium,with a significantly lower degree than the SAP group. Compared with the SAP group,the magnolol treatment group had significantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE( all P < 0. 05) and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE in the lymphatic fluid( all P < 0. 05). Compared with the SAP group,the sham-operation group had sig-nificantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE( all P < 0. 05) and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE in the lymphatic fluid( all P < 0. 05). Compared with the SAP group,the magnolol treatment group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1,and RAGE in lung tissue( all P < 0. 05) and intestinal tissue( all P < 0. 05). Compared with the SAP group,the sham-operation group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1,and RAGE in lung tissue( all P < 0. 05) and intestinal tissue( all P < 0. 05). Compared with the SAP group,the magnolol treatment group and sham-operation group had a significant reduction in the protein expression of TLR4 in the lymphatic fluid( all P < 0. 05). Conclusion Magnolol can improve intestinal barrier function and alleviate lung injury in SAP by blocking intestinal lymphatic circulation,reducing the levels of inflammatory factors,and inhibiting the HMGB1-TLR4/NF-κB signal transduction pathway.

Objective To investigate the association of metabolic syndrome( MS) and its components with the overall survival of pancreatic cancer( PC) patients who do not receive antitumor therapy. Methods A retrospective analysis was performed for the data of patients who were diagnosed with PC in The Affiliated Hospital of Southwest Medical University from August 2013 to November 2018. Related data were collected,including age,sex,body weight,body height,body mass index( BMI),smoking,drinking,medical history of chronic pancreatitis,medical history of biliary tract diseases and gastritis,medical history of chronic hepatitis B/C,medical history of other tumors,presence or absence of PC in first-grade relatives,blood glucose,blood pressure,high-density lipoprotein cholesterol( HDL-C),triglyceride( TG),MS,and TNM stage. The log-rank test was used for comparison of survival curves between groups,and the univariate and multivariate Cox regression analyses were used to investigate the influencing factors for survival. Results A total 269 PC patients were enrolled in this study,with an average survival time of 3 months. The survival analysis showed no significant difference in survival time between the patients with MS and those without MS( P = 0. 754). There was no significant difference in median survival time between the patients with hypertension,high TG,high HDL-C,or abnormal BMI and those without such abnormality( all P > 0. 05). There was a significant difference in median survival time between the patients with hyperglycemia and those without hyperglycemia( hazard ratio [HR]= 1. 322,95%confidence interval [CI]: 0. 985-1. 775,P = 0. 028),and the multivariate Cox regression analysis achieved consistent results( HR =1. 481,95% CI: 1. 043-2. 104,P = 0. 028). The analysis of the influencing factors for survival time in patients with stage Ⅳ PC showed that the patients with hyperglycemia had a significant reduction in median survival time( HR = 1. 524,95% CI: 1. 046-2. 218,P =0. 004). Conclusion MS is not an influencing factor for the survival of PC patients,but hyperglycemia is an independent risk factor for poor prognosis in PC patients,especially in those with advanced PC.

T helper 17( Th17) cells,differentiated from nave CD4 + T cells,can secrete a series of cytokines including interleukin-17,interleukin-21,and interleukin-22 and are meanwhile regulated by a variety of cytokines and genes,playing an important role in various inflammatory diseases. Th17 cells are widely distributed in vivo and are associated with diseases in many systems. They are involved in the regulation of chronic inflammatory/autoimmune diseases by secreting pro-inflammatory factors and antagonizing the immunosuppressive effect of regulatory T cells. This article reviews the recent studies on the association between Th17 cells and the pathogenesis of various chronic inflammatory liver diseases,so as to provide a reference for scientific research and clinical treatment.

A large number of studies in recent years have shown that long non-coding RNAs( lncRNAs) play an important regulatory role in the progression of liver fibrosis. This article briefly describes the definition,classification,and biological functions of lncRNAs and summarizes recent reports on the regulatory role of lncRNAs in liver fibrosis by acting as competitive endogenous RNA,including downregulated maternally expressed gene 3,growth arrest-specific transcript 5,and long intergenic non-coding RNA-p21 and upregulated lung adenocarcinoma-associated transcript 1,lncRNA-activated by transforming growth factor beta,plasmacytoma variant translocation 1,homeobox transcript antisense RNA,lncRNA-H19,and small nuclear RNA host gene 7,so as to provide insights into the diagnosis of liver fibrosis,the screening of therapeutic targets,and the development of clinical treatment regimens for the reversal of liver fibrosis.

Esophagogastric variceal bleeding is one of the main causes of death in patients with liver cirrhosis,and therefore,early monitoring of esophageal and gastric varices may help to improve the prognosis of patients; however at present,hepatic venous pressure gradient and upper gastrointestinal endoscopy used as the gold standard for diagnosis are invasive examinations,which may not help with long-term follow-up. This article introduces the noninvasive evaluation of esophageal and gastric varices in cirrhotic patients by shear-wave ultrasound elastography.

Minimal hepatic encephalopathy( MHE) refers to a state of neuropsychological or neurophysiological abnormality and normal cognitive function in patients with liver cirrhosis,which is commonly seen in patients with liver cirrhosis. Early diagnosis and treatment of MHE can improve the quality of life of patients and reduce accidental deaths. At present,Psychometric Hepatic Encephalopathy Score is mainly used for the diagnosis of MHE,but its operation is complicated and time-consuming and is affected by age and educational level,with unsatisfactory reliability in clinical diagnosis. Serum biomarkers are objective reference indicators with simple and convenient measurement and can easily be promoted in clinical practice. Potential serum biomarkers such as S100β,3-nitrotyrosine,and arterial blood ammonia have their own advantages and disadvantages in specificity,sensitivity,and diagnostic value. This article reviews the above-mentioned serum biomarkers.

Alcoholic liver disease( ALD) is a common cause of liver dysfunction and death due to liver-related diseases,which brings great harm to human health and social development. Many factors are involved in the development and progression of ALD,such as oxidative stress,change in gut microbiota,genetic variation,autophagy inhibition,and microRNAs. This article summarizes the mechanism of action of these factors in ALD,in order to provide a basis for the treatment of ALD and the discovery of new drug targets.

The incidence rate of nonalcoholic steatohepatitis is gradually increasing year by year,which calls for an urgent need for effective therapeutic drugs. In recent years,various drugs have been developed,including anti-oxidative stress drugs,insulin sensitizers,PPAR agonists,thyroid receptor agonists,farnesoid X receptor agonists,ASK1 inhibitors,and pan-caspase inhibitors. This article reviews the clinical studies on the therapeutic drugs for nonalcoholic steatohepatitis and summarizes the efficacy and safety of each drug,in order to provide a reference for clinical practice.

Nonalcoholic fatty liver disease is a group of diseases with unclear pathophysiological mechanism and is closely associated with metabolic syndrome. Bacterial components and metabolites produced by gut microbiota can regulate glucose and lipid metabolism,inflammatory response,and oxidative stress,and bile acids regulate immune function,energy metabolism,and material metabolism through various signaling pathways after activating their receptors. Gut microbiota and bile acids interact with each other through enterohepatic circulation,and the changes of their structure and function are involved in the development and progression of nonalcoholic fatty liver disease. This article reviews the effect of the homeostatic dysregulation of gut microbiota and bile acids and their interactions on nonalcoholic fatty liver disease.

Hepatocellular carcinoma has a low early diagnostic rate,and there is a lack of highly sensitive and specific tumor markers. In recent years,fluid biopsy technique,represented by circulating free DNA( cfDNA),has become an auxiliary method for the diagnosis of cancer and has attracted more and more attention due to its advantages of noninvasiveness,convenience,and repeatability. With reference to the recent studies in China and foreign countries,this article summarizes and analyzes the advances in cfDNA in the diagnosis and treatment of hepatocellular carcinoma from the aspects of biological characteristics,detection techniques,and clinical application,so as to provide a basis for clinical diagnosis and treatment.

There are complex mechanisms in the development and progression of hepatocellular carcinoma,which have not been fully clarified at present. Zinc finger protein family is the largest transcription factor family in human genome,and more and more evidence has shown that zinc finger proteins play an important role in the development and progression of hepatocellular carcinoma and are expected to become new tumor biomarkers and therapeutic targets for hepatocellular carcinoma. This article reviews the structure and biological functions of zinc finger proteins and their role and regulatory mechanisms in hepatocellular carcinoma.

Hepatic sclerosing hemangioma( HSH) is a rare benign tumor that is considered fibrosis and hyaline change caused by degenerative changes of cavernous angioma,and changes in pathological features cause the changes in imaging features,making this atypical hemangioma easily misdiagnosed as primary or metastatic malignant tumor. Although there are many studies on the imaging findings of this disease,it is still difficult to diagnose and most patients underwent resection since it is misdiagnosed as malignant tumor. There is still a low rate of confirmed diagnosis before surgery. This article elaborates on the etiology,clinical manifestations and pathological features,imaging findings,diagnosis,and treatment of HSH,in order to provide a reference for the diagnosis and treatment of this disease.

As a novel form of programmed cell death different from cell necrosis,apoptosis,and autophagy discovered in recent years,pyroptosis is characterized by cell membrane rupture and release of cell contents and proinflammatory factors mediated by gasdermin,thus leading to cell death. Pyroptosis signaling pathways can be classified into classical pathways dependent on caspase-1 and non-classical pathways dependent on caspase-4/5/11; the activation of caspase-1 in classical pathways depends on the function of inflammasome,while the direct activation of caspase-4/5/11 is observed in non-classical pathways,which leads to the lysis of gasdermin D and induce the formation of membrane pores,the maturation and release of interleukin-1β and interleukin-18,and the rupture of cell membrane to cause pyroptosis. Latest research has shown that pyroptosis plays an important role in the development and progression of chronic liver diseases. This article introduces the mechanism of pyroptosis and summarizes the role of pyroptosis in the development and progression of nonalcoholic fatty liver disease,alcoholic liver disease,viral hepatitis,liver cirrhosis,and hepatocellular carcinoma,in order to provide new ideas and methods for the prevention and treatment of liver diseases in clinical practice.

In recent years,more and more studies have shown that myeloid-derived suppressor cells( MDSCs) participate in the development and progression of various chronic liver diseases including chronic viral hepatitis,alcoholic liver disease,nonalcoholic fatty liver disease,autoimmune liver diseases,and liver cancer. As a type of cells derived from bone marrow progenitor cells and immature myeloid cells,MDSCs play an important role in the development,progression,and repair of liver diseases by regulating inflammatory response and the differentiation and function of immune cells. This article reviews the research advances in the association between MDSCs and various liver diseases,in order to provide new thoughts for the clinical diagnosis,prognosis,and treatment of chronic liver diseases.

Cholangiocarcinoma is a malignant tumor originating from the epithelium of bile ducts,and although it has a low incidence rate,most patients are in the end stage at the time of diagnosis since there are no prominent clinical manifestations at disease onset. Since there are problems such as insufficient treatment options,poor prognosis,and low survival rates,it is urgent to find new treatment methods to make breakthroughs in the treatment of cholangiocarcinoma. With the in-depth studies on cholangiocarcinoma gene mapping and the development of next-generation sequencing technologies,a number of potential targets have been discovered,such as FGFR and IDH1/2,making targeted therapy for cholangiocarcinoma a feasible treatment option. Targeted therapy is a treatment modality that blocks the growth of tumor cells by interfering with the specific molecules involved in tumor cell growth,with the advantages of high specificity,low toxicity,and considerable therapeutic effect. In recent years,targeted therapy has become a research hotspot in the treatment of cholangiocarcinoma. This article elaborates on the current status and challenges in targeted therapy for cholangiocarcinoma.

The incidence rate of hypertriglyceridemic pancreatitis( HTGP) is gradually increasing,and its complex pathogenesis has not been fully elucidated,which causes the difficulty in treatment. At present,there are no recommended guidelines for the treatment of HTGP.According to the process of the development and progression of HTGP,this article reviews related articles in China and foreign countries from the aspects of treatment during acute exacerbation,treatment for the special population,and long-term prevention of recurrence.

A large amount of information,such as clinical hematological data and imaging images,can be extracted by artificial intelligence to form various quantifiable features,analyze the association between different features and problems concerned( such as diagnosis),and thus solve complex medical problems. This article elaborates on the efficiency of various artificial intelligence algorithms in the diagnosis of pancreatic cancer,hepatic fibrosis,and esophageal varices,so as to help clinicians with clearer understanding and better decision-making.