Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

Objective:To analyze the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma (HCCA).Methods:Clinical data of 72 patients with HCCA undergoing radical resection at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to January 2022 were retrospectively analyzed, including 36 males and 36 females, aged 57(47, 63) years old. According to surgical approach, patients were divided into the laparoscopic group ( n=39) and open group ( n=33). The surgical safety, tumor radicality, postoperative recovery, complications and survival time were compared between the two groups. Results:Operative time was comparable between the two groups [(6.4±2.6) h vs. (6.3±2.4) h, P>0.05], while the intraoperative blood loss was lower in the laparoscopic group [(531.9±273.3) ml vs. (674.6±330.0) ml]. Data were also comparable between the two groups in terms of R0 resection rate [92.3% (36/39) vs. 93.9% (31/33)], the number of lymph node dissection (7.7±2.6 vs. 7.6±2.4), and the incidence of postoperative complications [20.5% (8/39) vs. 18.2% (6/33)] (all P>0.05). However, the laparoscopic group was superior to the open group in terms of postoperative analgesia time [(2.0±0.7)d vs. (2.8±0.9)d], postoperative resumption of feeding time [(1.6±0.5)d vs. (3.9±0.9)d], and postoperative hospitalization time [(8.6±1.5)d vs. (12.8±2.2)d] ( t=4.04, 8.23, 9.47, respectively, all P<0.001). Postoperative cumulative survival was comparable between the two groups ( χ2=0.50, P=0.480). Conclusion:Laparoscopic radical resection of HCCA has similar efficacy to open surgery and has the advantage of less invasiveness and enhanced recovery.

Objective To evaluate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP)-based comprehensive minimally invasive treatment for biliary anastomotic stenosis (BAS) after liver transplantation. Methods Clinical data of 60 BAS recipients after liver transplantation were retrospectively analyzed, 54 male and 6 female, aged (48±10) years. ERCP was initially carried out. If it succeeded, plastic or metallic stents were placed into the biliary tract. If it failed, percutaneous transhepatic cholangial drainage (PTCD) or single-operator cholangioscopy (SpyGlass) was adopted to pass through the stenosis. If all these procedures failed, magnetic anastomosis or other special methods were delivered. The incidence and treatment of BAS after liver transplantation were summarized. The efficacy, stent removal and recurrence were observed. Results The median time of incidence of BAS after liver transplantation was 8 (4, 13) months. Within postoperative 1 year, 1-2 years and over 2 years, 39, 16 and 5 recipients were diagnosed with BAS, respectively. All 60 BAS recipients after liver transplantation were successfully treated, including 56 cases initially receiving ERCP, and 41 completing BAS treatment, with a success rate of 73%. The failure of guide wire was the main cause of ERCP failure. The success rates of PTCD, SpyGlass and magnetic anastomosis were 5/9, 5/7 and 7/8, respectively. Two recipients were successfully treated by percutaneous choledochoscope-assisted blunt guide wire technique and stent placement in the biliary and duodenal fistula. After 3 (3, 4) cycles of ERCP and 13 (8, 18) months of stent indwelling, 38 recipients reached the stent removal criteria, including 25 plastic stents and 13 metallic stents. The indwelling time of plastic stents was longer than that of metallic stents (P < 0.05). Six cases suffered from stenosis recurrence at 12 (8, 33) months after stent removal, and the recurrence rate was 16%. Six patients were treated with ERCP, and 5 of them did not recur after the stents were successfully removed. Multivariate analysis showed that delayed diagnosis of stenosis and frequent ERCP before stent removal were the independent risk factors for BAS recurrence (both P < 0.05). Conclusions ERCP-based comprehensive minimally invasive treatment may improve the success rate of BAS treatment after liver transplantation and yield satisfactory long-term efficacy. Delayed diagnosis of BAS and high frequent ERCP required for stent removal are the independent risk factors for BAS recurrence.

Objective:To explore the characteristics of biliary stricture after liver transplantation (LT) under SpyGlass peroral choledochoscopy and to investigate its treatment value for difficult stricture.Method:A total of 24 patients of biliary stricture after LT at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University underwent SpyGlass examination from January 2019 to December 2020, 15.5 months (2-58 months) after surgery. The characteristics of different types of strictures and the selective guidewire placement results by SpyGlass were recorded and analyzed.Results:Of the 24 patients, 9 were anastomostic strictures (AS) and 15 others were non-anastomostic strictures (NAS). The main characteristic of 5 initial AS patients was scar constriction. Whether treated or not, all of the 15 NAS patients showed evident inflammatory hyperplasia in hilar bile duct under SpyGlass, 80% (12/15) of which were accompanied with intrahepatic biliary stones. The strictures disappeared with mild hyperplasia in 8 patients (4 AS and 4 NAS) whose biliary stents were extracted. Eleven patients (5 AS and 6 NAS) needed guidwire placement under SpyGlass, six (54.5%) of whom succeeded. The successful rate in AS patients was higher than that of NAS (4/5 VS 2/6).Conclusion:The main characteristic of AS is scar constriction and that of NAS is inflammatory hyperplasia. Selective guidewire placement can be achieved by SpyGlass peroral choledochoscopy with a satisfactory successful rate in the difficult AS.

Objective:To investigate the diagnosis and treatment of hepatic artery thrombosis (HAT) after adult orthotopic liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 411 patients who underwent adult orthotopic liver transplantation in the First Affiliated Hospital of Xi ′an Jiaotong University from December 2011 to July 2018 were collected. There were 328 males and 83 females, aged from 21 to 66 years, with a median age of 46 years. Observation indicators: (1) incidence of HAT and its clinical characteristics; (2) diagnosis of HAT; (3) treatment of HAT; (4) follow-up. Follow-up using outpatient service, telephone interview or WeChat group communication was conducted to detect the incidence of biliary stricture and survival of patients up to August 2018. Measurement data with normal distribution were represented as Mean± SD, measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Survival rate was estimated using the Kaplan-Meier method. Results:(1) Incidence of HAT and its clinical characteristics: 11 of 411 patients had HAT after orthotopic liver transplantation with the incidence of 2.68%(11/411), including 10 males and 1 female, aged 44 years(range, 22-63 years). The time to occurrence of postoperative HAT was 4 days(range, 1-15 days). The etiologies of 11 patients included 6 cases of hepatitis B virus-related cirrhosis, 1 case of hapatitis related cirrhosis, 1 case of hepato-cellular carcinoma, 1 case of liver cirrhosis, 1 case of alcoholic hepatitis related cirrhosis, 1 case of wilson disease. All the 11 patients were ABO compatible. The cold ischemic time and warm ischemic time of donor liver were (316±89)minutes and (13±4)minutes, respectively. Type Ⅰ arterial anasto-mosis was conducted in 11 patients. The clinical manifestations included asymptomatic type in 10 patients and sepsis type in 1 patient. (2) Diagnosis of HAT: all the 11 patients were confirmed with HAT by endovascular angiography, including 7 cases showed no arterial flow under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. Two patients showed increased hepatic artery resistance index under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated 1 case of HAT and 1 case of anastomotic stenosis. One patient showed slow velocity of hepatic artery blood flow and low resistance index under color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. One patient showed slight blood flow signals under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. (3) Treatment of HAT: 11 patients received endovascular therapy. Six patients had HAT completely disappeared after thrombolytic therapy, 5 patients with residual thrombosis continued thrombolytic therapy with microcatheter urokinase. Six patients with complications were improved after symptomatic treatment. HAT completely disappeared after (6.7±2.6)days of treatment and the clinical success rate was 11/11. (4) Follow-up: 11 patients were followed up for 19-1 722 days, with a median follow-up time of 46 days. During the follow-up, 4 patients had biliary stricture and underwent stent implantation. Nine patients survived with 1-, 3-, 5-year overall survival rates of 75%, 75%, 75%, and 2 patients died.Conclusions:The incidence of HAT after adult orthotopic liver transplantation is low and clinical manifestations are atypical. Contrast enhanced ultrasound can improve diagnosis of suspected thrombosis. Endovascular therapy is safe and effective, which can significantly improve the blood flow of hepatic artery.

Objective:To investigate the risk factors for abdominal infection after liver transplantation (LT).Methods:The retrospective case-control study was conducted. The clinical data of 356 patients who underwent LT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2015 to December 2018 were collected. There were 273 males and 83 females, aged from 21 to 67 years, with the median age of 46 years. Observation indications: (1) abdominal infec-tion after LT and distribution of pathogens; (2) analysis of risk factors for abdominal infection after LT; (3) follow-up and survival. Follow-up was performed using outpatient examination and tele-phone interview to detect postoperative 1-year survival rate and cases of death up to June 2020. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were described as M(range). Count data were expressed as absolute numbers or percentages. Univariate analysis was conducted using the chi-square test, t test, Mann-Whitney U test and Fisher exact probability. Multivariate analysis was done using the Logistic regression model. The Kaplan-Meier method was used to calculate sruvival time and survival rates. Log-Rank test was used for survival analysis. Results:(1) Abdominal infection after LT and distribution of pathogens: 63 of 356 recipients had abdominal infection after LT, with the overall incidence of 17.70%(63/356). Of the 63 recipients, 41 cases had abdominal infection within postoperative 2 weeks, 17 cases had multi-drug resistant organism infection. A total of 116 strains of bacteria were isolated from 63 recipients with abdominal infection, 52 of which were gram-negative bacteria, 48 were gram-positive bacteria, 16 were fungi. (2) Analysis of risk factors for abdominal infection after LT: results of univariate analysis showed that preoperative model for end-stage liver disease (MELD) score, preoperative serum albumin, preoperative leukocytes, preoperative prothrombin time, preoperative alanine aminotransferase, preoperative aspartate aminotransferase, operation time, volume of intraoperative blood loss, days of postoperative antibiotic use, postoperative renal failure, postoperative delayed graft function,duration of postoperative intensive care unit stay were related factors for abdominal infection after LT ( Z=-2.456, t=-1.982, Z=-3.193, -2.802, -2.336, -2.276, -2.116, -3.217, χ2=15.807, 10.395, 6.750, Z=-4.468, P<0.05). Liver retransplantaiton and postoperative bile leakage were related factors for abdominal infection after LT ( P<0.05). Results of multivariate analysis showed that preoperative MELD score>20 and liver retransplantation were independent risk factors for abdominal infection after LT ( odds ratio=2.871, 12.875, 95% confidence interval as 1.106-7.448, 1.290-128.521, P<0.05). (3) Follow-up and survival: 356 recipients were followed up for 1-66 months, with a median follow-up time of 32 months. The postoperative 1-year overall survival rate of 63 recipients with abdominal infection and 293 recipients without abdominal infection were 84.60% and 97.03%, respectively, showing a significant difference ( χ2=11.660, P<0.05). During the follow-up, 58 recipients died. Conclusion:Preoperative MELD score>20 and liver retransplantation are independent risk factors for abdominal infection after LT.

Objective:To study our initial experience on feasibility and safety of magnetic compression anastomosis in laparoscopic pancreaticoduodenectomy(LPD).Methods:A retrospective analysis was conducted on the data of 7 patients who underwent LPD with laparoscopic magnetic compression choledochojejunostomy (LMC-CJ) or pancreaticojejunostomy (LMC-PJ) at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University from May 2018 to September 2019. There were 6 males and 1 female. The median age of patients was 63 (56-83) years. Data analyzed included the model of the magnetic anastomosis device, operation time of the LMC-CJ or LMC-PJ, other operation-related parameters, postoperative complications, time to perform magnetic anastomosis, and time of discharge of the magnet from patients’ body.Results:All 7 patients completed LPD successfully, including 7 LMC-CJ and 2 LMC-PJ. The median operation time was 340 (310-450) minutes. The median diameter of the biliary-enteric magnetic anastomosis ring used was 10 (9-12) mm, and the median time of the biliary-enteric magnetic anastomosis was 11 (8-16) min. The diameter of the pancreaticojejunal magnetic anastomosis ring was 5 mm in the two anastomoses, and the times taken were 12 min and 15 min. Complications occurred in 4 patients, including 1 patient each for grade A and grade B pancreatic fistula, 2 patients with abdominal infection, 2 patients with postoperative gastric emptying disorder, and 1 patient with abdominal hemorrhage. All patients responded to conservative treatment. There was no biliary or pancreatic fistula at the magnetic anastomoses. Pancreaticojejunostomy functioned at 24 and 30 days after operation. The median time for the magnets to pass out from the body of all patients was 50 (40-170) days. The median follow-up was 11 (4-18) months. No biliary-enteric or pancreaticojejunostomy stenosis was detected.Conclusion:Magnetic compressive anastomosis was simple, feasible, and safe for choledochojejunostomy or pancreaticojejunostomy in LPD.

Surgical treatment for bone and soft tumors of pelvis and sacrum presents a big challenge, because of the complex anatomy of sacropelvic region, large tumor volume at presentation, rich blood supply to the tumor and visceral involvemen, et al. Therefore, surgical excision and reconstruction are technically difficult for sacropelvic tumors. Extensive intraoperative haemorrhage could be life-threatening, and this issue remains a major concern. How to effectively control bleeding during surgery is critical for successful operation and patient's favorable prognosis. Some previous attempts, such as interventional selective internal iliac artery embolization or manual ligation through an additional anterior approach, were tested to be ineffective. Inspired by the success of resuscitative endovascular balloon occlusion of the aorta (REBOA) which resemble an endovascular tourniquet for traumatic hemorrhagic shock, some researchers have applied this techinique to control surgical bleeding during pelvic or sacral tumor resection.The authors have performed REBOA for more than 1 500 sacropelvic tumr surgeries since 2003 in Peking University People's Hospital. The patient age, the diameter of femoral artery and aorta, atherosclerosis, as well as tumor location, volume and expansion and blood suppy, have to be thoroughly evaluated prior to REBOA administration. Admittedly, the application of REBOA do reduce intraoperative bleeding, shorten the operation duration, improve the safety of surgery, yet some complications were observed including local hematoma at the puncture site, acute arterial thrombosis, femoral artery pseudoaneurysm or occlusio, et al. The purpose of this study is to review the literature on REBOA administration in pelvic and sacral tumors excision, with the focus on its indications, performing procedure, the safety and efficacy, and complications. Moreover, in order to popularize the clinical application of aortic balloon occlusion in the future, we summarize our experience of abdominal aortic balloon occlusion over 10 years.

Objective:To discuss the type, treatment and results of different therapies of biliary fistula after orthotopic liver tansplantation(OLT).Methods:Data of 24 patients who developed biliary fistula after OLT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to March 2019 were retrospectively analyzed. Patients with biliary fistula were classified into 4 types according to presence or absence of stricture. All patients were treated by endoscopic retrograde cholangiopancreatography (ERCP) or interventional therapy, including endoscopic nasobiliary drainage (ENBD), endoscopic retrograde biliary drainage (ERBD) or percuteneous transhepatic cholangial drainage (PTCD). Main outcome measurements were the onset time of biliary fistula, the site of biliary fistula, the complications of ERCP or PTCD, the time of removing abdominal or biliary drainage tube, and the onset of new biliary stricture.Results:Biliary fistula was found in (46.5±36.6) days (6-122 days) after OLT. The numbers of patients in four types of biliary fistula were 6, 14, 2 and 2, respectively. Biliary fistula was cured in 22 patients, with clinical cure rate of 91.7%. All patients underwent ERCP first, and the technical success rate and clinical cure rate were 87.5% (21/24) and 85.7% (18/21), respectively. The clinical cure rates of ERCP forⅠ-Ⅳ biliary fistula were 6/6, 84.6%(11/13), 1/2, and 0, respectively. The clinical cure rates of ENBD and ERBD were 8/10 and 6/8, respectively. Five cases in whom ERCP failed, underwent PTCD, with technical success and clinical cure rates of 4/5 and 3/4 respectively. Eight patients(33.3%)developed cholangitis after treatment, and the incidence rate seemed higher in type Ⅱ biliary fistula than that in type Ⅰ [35.7% (5/14) VS 16.7% (1/6)]. Incidence of cholangitis was higher in patients with non-anastomotic stricture than those with anastomotic stricture [83.3%(5/6) VS 16.7%(3/18)].Conclusion:The first line treatment for biliary fistula after OLT is ERCP, followed by PTCD. The best procedures of biliary fistula typeⅠ-Ⅳ were ENBD, ENBD combined with ERBD, ENBD and PTCD, respectively.

Objective:To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis.Methods:Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC.Results:A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group ( HR=0.53,95% CI:0.31 to 0.91, P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development ( HR=0.55, 95%CI:0.32 to 0.95, P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group ( P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ2=7.029, P=0.008). Conclusion:Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.