Objective:To investigate the impact of metformin on the Beh?et's disease (BD) mice model via the Treg/Th17 axis.Methods:The BD mice model was established by subcutaneous injection of HSV-1. Four groups were established, including healthy control group, model group, high-dose metformin group, and low-dose metformin group. The HSV-1 DNA copy number in the peripheral blood was measured using qRT-PCR. Plasma levels of TGF-β 1, IL-10, IL-17, IL-23, IL-6, and TNF-α were assessed by ELISA. Flow cytometry was employed to determine the proportion of Treg and Th17 cells in the spleen. One-way analysis of variance was used for inter-group comparisons, pairwise comparisons were performed using SNK- q test. Results:Thirty-eight BD models were successfully established, with 28 survived. Compared to the BD model group, the metformin treatment groups showed faster healing of genital ulcers, joint redness/swelling, and skin ulcers, along with better mental status. HSV-1 copy numbers decreased in the metformin groups compared to the model group at 20 and 30 days post-treatment. Compared to the healthy control group, the model group exhibited elevated levels of TGF-β 1, IL-17, IL-6, IL-23, and TNF-α, but a decrease in IL-10. Following high-dose metformin treatment, TGF-β 1, IL-17, IL-6, IL-23, and TNF-α were significantly reduced ( q=16.17, P<0.001; q=8.76, P<0.001; q=6.78, P=0.004; q=4.45, P=0.020; q=12.08, P<0.001), accompanied by elevated IL-10 (specific value) ( q=6.28, P<0.001). Compared with the control group [Treg: (1.82±0.68)%; Th17: (2.12±0.86)%], the model group showed significantly elevated proportions of Treg cells[(6.03±2.42)%] ( q=5.01, P<0.001) and Th17 cell [(3.40±0.58)%] ( q=2.96, P=0.017). After high-dose metformin treatment, both Treg cell proportion [(3.20±1.66)%] and Th17 cell proportion [(2.16±0.78)%] decreased compared to the model group ( q=3.05, P=0.014). No significant differences were observed between the high-and low-dose metformin groups across all measured indicators, indicating similar efficacy. Conclusion:Metformin could reduce HSV-1 virus replication, reduce the levels of inflammatory cytokines and regulate Treg/Th17 axis to alleviate the BD symptoms. This study provides evidence for repurposing metformin in the treatment of Beh?et's disease.

Objective:To investigate the impact of metformin on the Beh?et's disease (BD) mice model via the Treg/Th17 axis.Methods:The BD mice model was established by subcutaneous injection of HSV-1. Four groups were established, including healthy control group, model group, high-dose metformin group, and low-dose metformin group. The HSV-1 DNA copy number in the peripheral blood was measured using qRT-PCR. Plasma levels of TGF-β 1, IL-10, IL-17, IL-23, IL-6, and TNF-α were assessed by ELISA. Flow cytometry was employed to determine the proportion of Treg and Th17 cells in the spleen. One-way analysis of variance was used for inter-group comparisons, pairwise comparisons were performed using SNK- q test. Results:Thirty-eight BD models were successfully established, with 28 survived. Compared to the BD model group, the metformin treatment groups showed faster healing of genital ulcers, joint redness/swelling, and skin ulcers, along with better mental status. HSV-1 copy numbers decreased in the metformin groups compared to the model group at 20 and 30 days post-treatment. Compared to the healthy control group, the model group exhibited elevated levels of TGF-β 1, IL-17, IL-6, IL-23, and TNF-α, but a decrease in IL-10. Following high-dose metformin treatment, TGF-β 1, IL-17, IL-6, IL-23, and TNF-α were significantly reduced ( q=16.17, P<0.001; q=8.76, P<0.001; q=6.78, P=0.004; q=4.45, P=0.020; q=12.08, P<0.001), accompanied by elevated IL-10 (specific value) ( q=6.28, P<0.001). Compared with the control group [Treg: (1.82±0.68)%; Th17: (2.12±0.86)%], the model group showed significantly elevated proportions of Treg cells[(6.03±2.42)%] ( q=5.01, P<0.001) and Th17 cell [(3.40±0.58)%] ( q=2.96, P=0.017). After high-dose metformin treatment, both Treg cell proportion [(3.20±1.66)%] and Th17 cell proportion [(2.16±0.78)%] decreased compared to the model group ( q=3.05, P=0.014). No significant differences were observed between the high-and low-dose metformin groups across all measured indicators, indicating similar efficacy. Conclusion:Metformin could reduce HSV-1 virus replication, reduce the levels of inflammatory cytokines and regulate Treg/Th17 axis to alleviate the BD symptoms. This study provides evidence for repurposing metformin in the treatment of Beh?et's disease.

The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration.In healthy livers,the Wnt signaling pathway is mostly inactive,but it is continuously overactivated during cell renewal or regeneration processes,as well as in certain pathological conditions,diseases,precancerous states,and cancers.Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis,liver cirrhosis,and liver cancer.This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases,so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.

Lipid metabolism,as the basis of life maintenance,is a prerequisite for cell survival,and lipid homeostasis can rapidly respond to metabolic changes in a coordinated manner.In cancers,there is an increase in lipid metabolism in cancer cells to meet the requirements for plasma membrane synthesis and energy production.Abnormal lipid metabolism plays an important role in the progression of primary liver cancer.This article reviews the association between abnormal lipid metabolism and primary liver cancer,in order to find targets for the prevention and treatment of primary liver cancer.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Objective To investigate the imaging anatomy and clinical significance of the inferior pancreaticoduodenal veins (IPDVs).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 42 patients with pancreatic head ductal adenocarcinoma who were admitted to Peking Union Medical College Hospital from January to June 2018 were collected.There were 24 males and 18 females,aged from 41 to 78 years,with an average age of 61 years.Patients received preoperative contrast-enhanced computed tomography (CT) examination with 1 mm slice thickness,and underwent corresponding surgery according to the preoperative evaluation.Observation indicators:(1) results of preoperative CT examination;(2) surgical situations.Normality of measurement data was analyzed using Shapiro-Wilk test.Measurement data with skewed distribution were described as M (QR) or M (range),and comparison between groups was analyzed by the Mann-Whitney U test.Count data were described as absolute number or percentage,and comparison between groups was analyzed by the chi-square test.Results (1) Results of preoperative CT examination:42 patients received preoperative contrast-enhanced CT examination with 1 mm slice thickness.① The first jejunal venous trunk was identified in all the 42 patients.The first jejunal venous trunk crossed dorsal to the superior mesenteric artery (SMA) in 34 patients and ventral to the SMA in 8 patients.② Of 42 patients,2 showed no IPDV,and 40 showed IPDV including 23 with 1 IPDV,13 with 2 IPDVs,3 with 3 IPDVs,and 1 with 4 IPDVs.A total of 62 IPDVs were identified in the 42 patients,with an average IPDV number of 1 (range,0-4).There were 43 IPDVs drained into first or second jejunal venous trunks and 19 IPDVs drained into superior mesenteric vein (SMV).③ Of 42 patients,type Ⅰ IPDV was identified in 32 patients including 20 with 1 IPDV drained into jejunal venous trunk at dorsal side of SMA,7 with 2 IPDVs drained into jejunal venous trunk at dorsal side of SMA,2 with 3 IPDVs drained into jejunal venous trunk at dorsal side of SMA,and 3 with 1 IPDV drained into jejunal venous trunk at ventral side of SMA,and non-type Ⅰ IPDV was identified in 10 patients;type Ⅱ IPDV was identified in 18 patients including 17 with 1 IPDV drained into SMV and 1 with 2 IPDVs drained into SMV,and non-type Ⅱ IPDV was identified in 24 patients.Some patients can simultaneously had type Ⅰ and type Ⅱ IPDV.(2) Surgical situations:42 patients underwent pancreatoduodenectomy,14 of which underwent laparoscopic surgery and 28 underwent open surgery.There were 5 cases with SMV or portal vein reconstruction,and 18 with intraoperative blood transfusion.All the 42 patients were diagnosed as pancreatic ductal adenocarcinoma by postoperative pathological examination,including 30 of R0 resection and 12 of R1 resection.The volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with R0 and R1 resection (situation of surgical margin),cases with SMV or portal vein reconstruction were 650 mL(853 mL),15,20,12,4 in the 32 patients with type Ⅰ IPDV,aod 475 mL (480 mL),3,10,0,1 in the 10 patients with non-type Ⅰ IPDV;there were significant differences in the volume of intraoperative blood loss and situation of surgical margin (Z=94.000,x2=5.250,P＜ 0.05).There was no significant difference in the cases with intraoperative blood transfusion,cases with SMV or portal vein reconstruction between patients with type Ⅰ and non-type Ⅰ IPDV (x2 =0.045,0.886,P＞0.05).Conclusions IPDVs can be distinguished on the contrast-enhanced CT with slice thickness,and classified as IPDVs drained into SMV or jejunal venous trunk.It is necessary to carefully deal with IPDVs drained into jejunal venous trunk in the pancreaticoduodenectomy due to its more volume of intraoperative blood loss and lower R0 resection rate.

Objective: To discuss the impact of updated definition and classification system of pancreatic fistula published in 2016 on the postoperative classification of pancreatic fistula. Methods: Retrospective analysis was made on patients who underwent pancreatic surgery at ward 1 in Department of General Surgery, Peking Union Medical College Hospital from January 2015 to December 2016.A total of 408 patients were included in this retrospective study, male/female was 184/224, aged from 9 to 81 years with mean age of 51.6 years.One hundred and fifty-two cases were performed pancreaticoduodenectomy, 125 cases for distal pancreatectomy, 43 cases for spleen preservation distal pancreatectomy, 61 cases for partital pancreatectomy or enucleation, 8 cases for middle pancreatectomy, 6 cases for pancreaticojejunostomy and 13 cases for other procedures.Clinical data including postoperative drainage fluid volume, amylase concentration, duration of hospitalization and drainage were obtained, revaluated and re-analyzed, classified grounded on 2005 edition and 2016 edition, respectively.t-test was adopted for data analysis. Results: According to the previous standards, the incident rate of pancreatic fistula was 57.4%, and the incident rate of B-level plus C-level pancreatic fistula was 35.8%, which decreased to 13.7% based on 2016 edition.Nine patients who received percutaneous puncture or endoscopic drainage was regraded from C-level to B-level. The average duration of postoperative hospitalization of patients without pancreatic fistula was (12.5±6.0)days, demonstrating no significant difference compared to (14.1±7.7)days, duration of postoperative hospitalization of A-level(under 2005 edition of criteria) pancreatic fistula group(t=1.66, P=0.09) and (12.4±6.1)days, duration of postoperative hospitalization of biochemical leakage group(t=0.14, P=0.89). Nevertheless, there was statistical significant difference between the average postoperative duration of hospitalization(30.7±16.9) days of B-level(under 2016 criteria) pancreatic fistula patients and pancreatic fistula-free patients as well as the biochemical leakage group patients (t=7.10, 7.13; both P<0.01). Conclusions Based on the new diagnostic criteria, the incidence of postoperative pancreatic fistula decreased dramatically.New classification system downgraded part of cases graded C-level pancreatic fistula to B-level and some B-level to biochemical fistula.The new diagnostic classification and criteria facilitated clinical practice, accomplished better conformity to clinical reality and potentially enacted clinical outcome.