Programmed death protein 1 (PD-1) and programmed death protein ligand-1 (PD-L1) play pivotal roles in maintaining immune homeostasis and a crucial link in tumour immune evasion. PD-1/PD-L1 inhibitors have achieved significant efficacy in many cancer immunotherapy, but the effect in the treatment of pancreatic cancer is limited, and the effect of monotherapy is suboptimal. The combined therapeatic effect of PD-1/PD-L1 and chemotherapy, radiotherapy, and molecular targeted therapy were explored. This article summarises the advancements in PD-1/PD-L1 inhibitor combination therapy in the treatment of pancreatic cancer.

Pancreaticoduodenectomy (PD) is the mainstay of treatment for periampullary space-occupying disease. The occurrence of pancreatic fistula after PD is still an unsolved clinical problem, which seriously affects the safety of surgery. Various methods have been reported in clinical practice to reduce the incidence of pancreatic fistula, such as improving pancreaticoenteric anastomosis, using biological sealants, applying somatostatin analogs, and continuous peritoneal irrigation, etc., but the incidence of pancreatic fistula remains at 5%-30%. There are many risk factors related to pancreatic fistula after PD, in which reasonable selection of suture materials is an important factor and also an important factor affecting the curative effect of surgery. The authors analyze the characteristics and shortcomings of various sutures used in PD, in order to provide help to improve the safety of surgery and reduce the incidence of pancreatic fistula after PD.

Objective:To investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) examination in clinical diagnosis of gallbladder tumor with perigallbladder invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 80 gallbladder tumor patients with perigallbladder invasion who were admitted to 3 medical centers (21 cases in The First Affiliated Hospital of Northwest University, 42 cases in The First Affiliated Hospital of the Air Force Medical University, 17 cases in The First Affiliated Hospital of Dalian Medical University) from January 2021 to December 2022 were collec-ted. There were 45 males and 35 females, aged (56±4)years. Observation indicators: (1) CT and MRI examinations; (2) surgical conditions. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) CT and MRI examinations. Of 80 patients, cases with gallbladder cancer and gallbladder adenoma were 73 and 7, respectively. Cases with endoluminal nodular type, mass type and localized thick-walled type were 33, 39 and 8, respectively, with tumor diameter as 1.55 cm×1.35 cm×1.33 cm, 1.64 cm×1.37 cm×1.36 cm and 5.72 cm×4.07 cm×4.36 cm. Results of CT examination of endoluminal nodular type showed local nodular protrusions into the endoluminal area, and local enhancement on enhanced scanning. Results of CT examination of localized thick-walled type showed the cavity wall of lesion was locally or diffusely irregul-arly thickened, with a thickness of 1.10(range, 1.10-2.21)cm. Of 80 patients, results of CT and MRI examinations showed invasion of liver parenchyma in 68 cases, which was manifested as local mass, blurred demarcation, and abnormal protrusion. The maximum depth was (4.22±0.25)cm, (4.22±0.22)cm, (4.28±0.16)cm of cross-sectional, coronal, sagittal view in CT examination, respectively. The minimum depth was (0.22±0.10)cm, (0.25±0.08)cm, (0.24±0.12)cm. The depth of liver parenchyma invaded was (1.64±1.38)cm, (1.68±1.46)cm, (1.66±1.40)cm. Results of CT and MRI examinations showed invasion of perigallbladder, which was manifested as local invasion of the gastric antrum in 12 cases. (2) Surgical conditions. Of 80 patients, results of CT and MRI examina-tions showed that 60 patients had localized masses in the gallbladder cavity with or without infiltration of surrounding tissues. After confirming the absence of other organs and distant metastasis, cases undergoing radical resection and palliative resection were 44 and 16, respectively. Results of CT and MRI examina-tions showed that 20 patients had malignant gallbladder tumors with peri-pheral liver infiltration and multiple intrahepatic metastases with distant organ metastases, which were unresectable.Conclusion:For patients with gallbladder cancer and perigallbladder invasion, CT or MRI examina-tions can show their structural characteristics.

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Objective To investigate the inhibitory effect of Glycyrrhizin in MHCC97-H cell line in vitro and explore the relevant mechanism.Methods MHCC97-H cells were cultured in vitro and treated with Glycyrrhizin in different concentrations and then cell viability was assayed at different time points.The concentration and time were selected with 50％ cell viability.MHCC97-H cell plate clone formation assay and invasion-migration experiment were also performed to study the tumor-suppressor efficacy of Glycyrrhizin.Acridine orange staining was used to evaluate the formation of autophagic vacuoles.Meanwhile,3-MA and Atg7-siRNA were both employed to avoid the autophagy activation in MHCC97-H cells and cell viability was reassessed.Western-blot was carried out to study the expression of autophagic proteins of LC3B,p-mTOR and p-ERK1/2.Results It showed Glycyrrhizin significantly inhibited MHCC97-H cell viability and the concentration and time at 50％ cell viability were 2 mmol/L and 48 h respectively.Clone number in Glycyrrhizin group was significantly smaller than that in the control group (176.7 ± 14.5 vs.410.0 ± 32.1).Invasion-migration rate was also lower in Glycyrrhizin group compared with the control group (41.0％ ±3.8％ vs.100％).Autophagic vacuoles was increased in MHCC97-H cells when treated with Glycyrrhizin and expression of LC3B-Ⅱ was enhanced and LC3B-Ⅱ/I Ratio was increased,at the same time degradation of P62 was accelerated.Reduced p-mTOR in concurrence with upregulated p-ERK1/2 could be observed in MHCC97-H cells administered with Glycyrrhi-zin.Cell groups additionally treated with 3-MA or Atg7-siRNA exerted higher cell viability (64.3％ vs.45.9％ and 67.7％ vs.47.1％,respectively).Conclusion Glycyrrhizin can induce excessive autophagy in hepatocellular carcinoma cells to cause autophagic cell death and exhibit great potential in clinical application.

Objective To investigate the effect of microvascular invasion (MVI) on tumor recurrence of hepatocellular carcinoma (HCC) patients after hepatectomy,the efficacy of sequential transcatheter arterial chemoembolization (TACE) on positive MVI patients after hepatectomy,and the effect of comprehensive treatment on the prognosis of patients with tumor recurrence.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 136 HCC patients who underwent hepatectomy in the First Affiliated Hospital of Air Force Medical University from February 2015 to December 2016 were collected.Patients were treated with TACE,radiofrequency ablation (RFA) and molecular-targeted drugs after hepatectomy,and patients with tumor recurrence selected 1 or 2 above treatments.The patient received postoperatively outpatient reexaminations every 3 months to detect tumor recurrence and survival.Follow-up was from the day of the surgery to death or December 2017.Observation indicators:(1) treatment after hepatectomy;(2) effect of MVI on tumor recurrence of HCC patients after hepatectomy:clinicopathological features and tumor recurrence rate between positive and negative MVI patients;(3) efficacy of TACE on positive MVI patients:clinicopathological features and tumor recurrence rate in positive MVI patients with or without TACE;(4) effect of comprehensive treatment on the prognosis of patients with tumor recurrence.Measurement data with normal distribution were represented as x±s and analyzed using the independent-samples t test.Comparisons of count data were analyzed using chi-square test or Fisher exact probalility.The tumor recurrence rate and survival rate were calculated by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Treatment after hepateetony:of 136 patients undergoing hepatectomy,117 underwent single hepatectomy and 19 combined sequential TACE;59 had HCC recurrence,including 22 receiving comprehensive treatment.(2) Effect of MVI on tumor recurrence of HCC patients after hepatectomy:① Clinicopathological features:of 117 patients undergoing single hepatectomy,positive MVI was detected in 49 patients,including 44 males and 5 females,with an age of (52-± 10)years old;49 patients were in Child-Pugh grade A,including 36 combined with liver cirrhosis and 13 without liver cirrhosis;positive and negative alpha-fetoproteins (AFPs) were respectively detected in 34 and 15 patients.Negative MVI was detected in 68 patients,including 54 males and 14 females,with an age of (55± 11)years old;65 and 3 patients were respectively in Child-Pugh grade A and B,including 52 combined with liver cirrhosis and 16 without liver cirrhosis;positive and negative AFPs were respectively detected in 39 and 29 patients.There was no statistically significant difference in gender,age,Child-Pugh score of liver function,liver cirrhosis and comparison of AFP between positive and negative MVI patients (x2 =2.258,t =-1.626,x2 ＝ 0.804,0.138,1.758,P＞0.05).② Tumor recurrence rate:The 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 30.77％,30.61％ in 117 patients undergoing single hepatectomy and 42.86％,51.02％ in 49 of 117 patients with positive MVI and 22.06％,27.94％ in 68 of 117 patients with negative MVI,showing statistically significant differences in 6-month and 1-year tumor recurrence rates between positive and negative MVI patients (x2 =5.738,6.465,P＜0.05).(3) Efficacy of TACE on positive MVI patients:① Clinicopathological features of 56 patients with positive MVI,7 received postoperatively sequential TACE,including 7 males,with an age of (50±4) years old;56 patients were in Child-Pugh grade A,including 5 combined with liver cirrhosis and 2 without liver cirrhosis;positive and negative AFPs were respectively detected in 2 and 5 patients.Forty-nine patients didn't combine sequential TACE,including 44 males and 5 females,with an age of (52± 10)years old;49 patients were in Child-Pugh grade A,including 36 combined with liver cirrhosis and 13 without liver cirrhosis;positive and negative AFPs were respectively detected in 34 and 15 patients.There was no statistically significant difference in gender,age,Child-Pugh score of liver function,liver cirrhosis and comparison of AFP between patients with and without sequential TACE (x2 =0.784,t =-0.512,x2 =0.013,2.844,P＞0.05).② Tumor recurrence:the 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 0,28.57％ in 7 positive MVI patients with sequential TACE and 42.86％,51.02％ in 49 positive MVI patients without sequential TACE,showing a statistically significant difference in 6-month tumor recurrence rate (x2=4.800,P＜0.05) and no statistically significant difference in 1-year tumor recurrence rate (x2 =1.236,P ＞ 0.05).(4) Effect of comprehensive treatment on the prognosis of patients with tumor recurrence:of 59 patients with tumor recurrence,37 didn't receive comprehensive treatment,34 of 37 died within 1-year postoperatively,including 30 deaths within 6-month postoperatively,and 1-year survival rate was 8.10％;22 received comprehensive treatment,including 4 deaths within 1-year postoperatively,and 1-year survival rate was 81.80％,showing a statistically significant difference in 1-year survival rate (x2=32.698,P＜0.05).Conclusions MVI is one of the important risk factors affecting HCC recurrence and metastasis after hepatectomy.The combined TACE after hepatectomy can reduce the HCC recurrence rate of MVI positive patients,and active comprehensive treatment after HCC recurrence can significantly prolong the survival time of patients.

Objective To study the effect of S-adenomethionine on early stage recovery of transplanted liver.Methods From January 2010 to October 2012,57 liver transplantation patients were divided into 2 groups beginning the first day:group A,23 patients were treated with routine liver-protecting therapy,including glycyrrhizin,glutathione,albumin; group B,34 patients treated with additional S-adenomethionine (Transmetil).AST,ALT,T-BIL,D-BIL,γ-GT,ALB and ALP were compared between the two groups at pre-operation and post-operation day 1,day 4,day 7 and day 14.Results All patients suffered from preoperative hyperbilirubinemia,decreased ALB and elevated concentration of AST,ALT,γ-GT and ALP.On the first day after transplant,AST,ALT,T-BIL,D-BIL and γ-GT elevated and ALB decreased significantly in all cases compared with that before operation (respectively t =10.493,7.089,6.584,15.134,5.164,10.344,5.289,13.034,3.389,4.366,all P ＜ 0.01).On the contrary,the value of ALB was lower (respectively t =8.239,11.662,all P ＜ 0.05).On the fourth day posttransplant,ALB level was higher and that of other parameters were lower in group B when compared with group A (respectively t =2.536,2.736,2.218,3.318,4.804,2.892,all P ＜ O.05).This tendency of liver function improvement continued till postoperative day 7 in all cases while the differences between the two groups remained significant (respectively t =6.107,3.256,2.929,11.688,8.964,2.857,all P ＜ 0.05)except for γ-GT.On day 14,while T-BIL and D-BIL in group B were lower than that in group A (respectively t =4.413,8.493,all P ＜0.001),differences of liver functions were not significant between the two groups (respectively t =1.916,1.414,1.168,1.035,1.604,all P ＞ 0.05).Conclusions Transmetil promotes the recovery of transplanted liver's function,elevates the concentrantion of ALB and reduces the concentration of AST,ALT,T-BIL,D-BIL,γ-GT and ALP at early stage after liver transplant.

Epithelial architecture is formed in tissues and organs when groups of epithelial cells are organized into polarized structures.The epithelial function as well as signaling across the epithelial layer is organized by polarity proteins.Epithelial polarity complexes form and regulate epithelial integrity.Polarity proteins establish and maintain cell polarity,regulate tight junctions and adherens junctions.Polarity proteins act as neoplasms suppressors in mammals and interact with oncogenes,disrupt cell polarity,induce tumorigenesis.Therefore,polarity mechanisms of epithelial cell could therapeutic targets for clinical therapy.

Objective To improve the pancreaticoenterostomy technique and drainage in panereatieoduodenectomy, so as to prevent postoperative pancreatic leakage. Methods One hundred and thirty-eight panereaticoduodenectomy cases underwent parachute continuous running suture of pancreaticojejunostomy and extra drainage of the anastomotic stoma. Results The average time of the double-deck continuous invaginated pancreaticoenterostomy was 11 minutes, and there was no pancreaticoenterostomy leakage in all cases, lntraoperative blood loss was 353±61 ml, the average hospital stay was 19.2 days. Pulmonary infection developed in 6 cases, three cases suffered from postoperative upper gastrointestinal bleeding due to stress ulcer, two cases from functional delayed gastric emptying. All these complications were cured by conservative treatment, and there was no mortality in these series. Conclusions The parachute continuous running suture of pancreaticojejunostomy and extra drainage has the advantages of easy performance, saving time and less complications, and is an effective way in the prevention of panereatieojejunostomy leakage.

ObjectiveTo study the effect of aprotinin and tumor necrosis factor alpha(TNF-α) antibody on preventing postoperative abdominal adhesion in mice.Methods96 BALB/c mice were randomly divided into 4 groups:normal saline group(n=24),aprotinin group(n=24),TNF-α antibody group(n=24),and aprotinin combined with TNF-α antibody group(n=24).After an identical peritoneal injury operation,all mice were treated intraperitoneally with normal saline , aprotinin,TNF-α antibody and aprotinin combined with TNF-α respectively at the time of abdominal closure .The mice were killed 20 days after operation,the abdominal incisions and the development of intraabdominal adhesions were observed.Adhesion score was based on an overall assessment of the extent,location,and type of adhesions .ResultsAprotinin combined with TNF-α antibody group showed significantly lower adhesion score and 2-3 grade adhesion(advanced significant adhesion) rate was lower than that of other groups(P<0.01).Conclusions The intraperitoneal administration of aprotinin and TNF-α antibody can inhibit postoperative adhesion formation.