Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and effectiveness of endoscopic cold snare resection of small colorectal polyps and prophylactic hemostatic clip.Methods:A total of 260 patients diagnosed as having small colorectal polyps in Qinghai Provincial People's Hospital from January 2021 to March 2022 were randomly assigned to cold snare polypectomy (CSP) group (receiving CSP), CSP+hemostatic clip group (receiving CSP+prophylactic hemostatic clip), hot snare polypectomy (HSP) group, and HSP +hemostatic clip group (receiving HSP+prophylactic hemostatic clip). Each group had 65 cases. The treatment, incidence of bleeding, and other complications were compared.Results:There was no significant difference in the basic characteristics of patients or polyps among the four groups ( P>0.05). Immediate intraoperative bleeding occurred in 5 cases (7.69%), 4 cases (6.15%), 3 cases (4.62%), and 3 cases (4.62%) in the four groups respectively with no significant difference ( χ2=0.778, P=0.855), while only 1 delayed postoperative bleeding was observed in HSP group with no significant difference among the four groups ( χ2=3.012, P=0.390). The incidence of postoperative abdominal pain was the highest in the HSP group ( n=7, 10.77%) significantly different from those of the CSP group ( n=1, 1.54%) and the CSP+hemostatic clip group ( n=1, 1.54%) ( P<0.05). Polypectomy time of single polyp in CSP group was the shortest (2.18±1.07 min) , followed by HSP group (2.83±0.82 min), then CSP+hemostatic clip group (3.15±1.16 min), with HSP+hemostatic clip group (4.88±1.85 min) being the longest ( F=50.397, P<0.001). Conclusion:It is suggested to use CSP for small colorectal polyps. If there is no risk of bleeding or perforation during the operation, it is not necessary to use prophylactic hemostatic clips.

Objective To investigate ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (F_ST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm² in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm², the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm² in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm², the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective:To explore the clinical significance of standardized screening for diagnosis and treatment of early gastric cancer in Qinghai Province.Methods:Opportunistic early gastric cancer screening was conducted in outpatients of Digestive Department, Physical Examination Center and inpatients of Qinghai Provincial People′s Hospital from January 2016 to December 2020, according to the optimal cut-off values of serum pepsinogen (PG)Ⅰ, PGⅠ/PGⅡ ratio (PGR) and serum gastrin 17 (G17) obtained from the previous screening study of gastric cancer and precancerous diseases in different areas of Qinghai Province. At the same time, the standardized early gastric cancer screening program was applied in 10 municipal (county-level) hospitals in Qinghai Province. The detection rate, early diagnosis rate and endoscopic treatment rate of early gastric cancer in Qinghai Provincial People′s Hospital and the above 10 hospitals in the past five years were analyzed respectively.Results:In the five years, the total detection rate, early diagnosis rate and endoscopic treatment rate of early gastric cancer in Qinghai Provincial People′s Hospital were 0.214% (407/190 178), 17.54% (407/2 321) and 81.82% (333/407), respectively. The above indices in 10 other hospitals were 0.085% (264/309 217), 12.94% (264/2 040) and 37.12% (98/264), respectively. The overall detection rate of early gastric cancer was higher than 0.024% reported previously.Conclusion:The standardized early gastric cancer screening program can not only improve the diagnosis rate of early gastric cancer in Qinghai Province, but also save medical resources. It is an economical, efficient and feasible program, suitable for the highin-cidence area of gastric cancer in Qinghai Province.

Objective:To evaluate the screening value of serum pepsinogen (PG) Ⅰ, pepsinogen ratio (PGR, PG Ⅰ/PG Ⅱ) and gastrin 17 (G17) levels combined with gastroscopy for early-stage gastric cancer in high incidence areas of gastric cancer in Qinghai Province.Methods:A total of 2 700 cases were identified as the appropriate age (40-69 years) target population through the questionnaire survey from 25 000 local residents in high incidence areas of gastric cancer in Qinghai Province. The serum PGⅠ, PGⅡ and G17 levels of the 2 700 target population were determined by ELISA, and PGR were calculated. And then 949 patients with abnormal levels of PG and G17 were screened out as a high-risk group of gastric cancer to receive gastroscopy and pathologic biopsy. According to the results of gastroscopy and biopsy, the patients were divided into non-atrophic gastritis group, atrophic gastritis group, peptic ulcer group, early-stage gastric cancer group, and advanced gastric cancer group. The optimal threshold and its sensitivity and specificity of serum PG Ⅰ, PGR and G17 levels for diagnosis of early-stage and advanced gastric cancer were determined based on the receiver operator characteristic curve (ROC).Results:Totally 949 cases received gastroscopy and 649 cases received pathological biopsy, including 239 cases of non-atrophic gastritis, 500 cases of atrophic gastritis, 197 cases of peptic ulcer, 5 cases of early-stage gastric cancer, and 8 cases of advanced gastric cancer. The level of serum PG Ⅰ in the early-stage gastric cancer group (70.00±12.35 μg/L) and advanced gastric cancer group (38.39±2.77 μg/L) was significant lower than that in the non-atrophic gastritis group (103.89±37.45 μg/L, both P<0.05), and the value of early-stage gastric cancer group was obviously higher than that of advanced gastric cancer group ( P<0.05). The PGR of the early-stage gastric cancer group (3.74±1.40) and the advanced gastric cancer group (2.05±0.59) was significantly lower than that in the non-atrophic gastritis group (9.18±4.10, both P<0.05), and the value of early-stage gastric cancer group was significantly higher than that of the advanced gastric cancer group ( P<0.05). The level of serum G17 in the early gastric cancer group (18.03±4.52 pmol/L) and the advanced gastric cancer group (25.15±3.76 pmol/L) was significantly higher than that in the non-atrophic gastritis group (14.99±7.12 pmol/L, both P<0.05), and the level of early-stage gastric cancer group was significantly lower than that of advanced gastric cancer group ( P<0.05). According to the analysis of ROC in the diagnosis of early-stage gastric cancer, the best threshold of PG Ⅰ, PGR and G17 was 71.85 μg/L, 5.04, and 15.65 pmol/L, respectively, and the corresponding sensitivity and specificity was 80.0% and 59.0%, 100.0% and 70.4%, and 80.0% and 69.3%, respectively, for PG Ⅰ, PGR and G17. The analysis of ROC in the diagnosis of advanced gastric cancer showd that the best critical value of PG Ⅰ, PGR and G17 was 42.55 μg/L, 2.79 and 20.55 pmol/L, respectively, and the corresponding sensitivity and specificity was 100.0% and 95.3%, 100.0% and 92.1%, and 100.0% and 89.7%, respectively. Conclusion:Using serological detection of PG and G17 to screen high-risk group of gastric cancer, and then making diagnosis by gastroscopy and biopsy is an effective, low-cost and non-invasive approach for the early-stage gastric cancer in high incidence areas of gastric cancer in Qinghai Province.

Purpose: Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy,which is associated with the progression of carcinoma. Yet, it is still unclear whetherLC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aimto explore the predictive value of LC3B on prognosis of ICC, and to establish a novel andavailable nomogram to predict relapse-free survival (RFS) and overall survival (OS) for thesepatients after curative-intent hepatectomy. Materials and Methods: From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the ThirdAffiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolledpatients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. Results: The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariateCox regression analysis, independent risk factors for 5-year OS were cancer antigen 125,microvascular invasion, LC3B expression and lymph node metastasis. Except for the above4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factorsfor 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and0.747, respectively. Conclusion The nomograms based on LC3B can be considered as effective models to predict postoperativesurvival for ICC patients.

Objective To investigate the influence of preoperative splenectomy on the prognosis after liver transplantation.Methods The retrospective cohort study was conducted.The clinical data of 95 patients who underwent liver transplantation in the Third Affiliated Hospital of Sun Yat-sen University between January 2004 and January 2014 were collected.Thirty-five patients undergoing preoperative splenectomy and pericardial devascularization and 60 undergoing spleen-preserving liver transplantation were allocated into the study group and control group,respectively.All patients received modified piggyback liver transplantation by the same team.Observation indicators:(1) intra-and post-operative situations;(2) follow-up and survival.The follow-up using telephone interview and outpatient examination was performed once every a week within 3 months postoperatively,once every one month within 6 months postoperatively and once every 3 months after 1 year postoperatively up to January 2016,including routine blood test,plasma-drug concentration of immunosuppressive agent and function of liver and kidney.Ultrasound and abdominal CT were used to monitor the long-term complication and survival.The measurement data with normal distribution were represented as (x)±s,and comparison between groups was done by the t test.Comparison of count data was done by the chi-square test.Results (1) Intra-and post-operative situations:all patients underwent successful liver transplantation.The operation time,volumes of intraoperative blood loss and blood transfusion were (483 ± 136) minutes,(5 683±2 950) mL,(4 887±3 682) mL in the study group and (392± 103)minutes,(3 522± 1 885)mL,(3 455±2 630)mL in the control group,respectively,with statistically significant differences between groups (t=3.683,4.358,2.202,P＜0.05).Six patients in the study group had intraoperative portal vein thrombosis (PVT),including 4 in level 1,1 in level 2 and 1 in level 3,and no patients in the control group,showing a statistically significant difference between groups (x2 =1.979,P＜0.05).Five patients with PVT in level 1 or 2 underwent thrombectomy and then end-to-end anastomosis of PV.One patient with PVT in level 1 had PVT recurrence and was cured by postoperative thrombolytic therapy.One patient with PVT in level 3 received PV reconstruction using artificial blood vessels,and had PVT recurrence and then was cured.There was no PV stenosis between groups.The levels of platelet at 1,3 and 7 days postoperatively were (75±60)× 109/L,(71± 45)×109/L,(111±73)×109/L in the study group and (57±32) ×109/L,(52±46) ×109/L,(87±53)×109/L in the control group,respectively,with statistically significant difference between groups (t =1.909,1.957,1.848,P＜ 0.05).The levels of platelet at 14 and 30 days postoperatively were respectively (230± 152)× 109/L,(310± 140)× 109/L in the study group and (193± 125)× 109/L,(286±62)× 109/L in the control group,with no statistically significant difference between groups (t=1.284,1.199,P＞0.05).The cases with postoperative infection,acute rejection,new-onset PVT in level 1-2 and 3-4 and PV stenosis were respectively 23,0,2,0,2 in the study group and 35,1,2,0,1 in the control group,with no statistically significant difference between groups (x2 =1.171,0.590,0.547,1.184,P＞0.05).Patients with postoperative infection and acute rejection were improved by symptomatic treatment.Two patients in the study group with PVT underwent anticoagulant and thrombolytic therapy,including 1 receiving interventional thrombectomy therapy.Two patients in the control group with new-onset PVT were cured by anticoagulant and thrombolytic therapy.Three patients with PV stenosis underwent percutaneous transhepatic portography (PTA) for balloon dilation,including 1 in the study group with good improvement after stent implantation.(2) Follow-up and survival:95 patients were followed up for 3-24 months,with an average time of 18 months.During the follow-up,the rate of chronic rejection in study and control groups was 5.7％(2/35) and 5.0％(3/60),showing no statistically significant difference between groups (x2 =0.023,P＞0.05).The 1-and 2-year accumulative survival rates were respectively 91.4％ (32/35),82.9％ (29/35) in the study group and 93.3％ (56/60),76.7％(46/60) in the control group,with no statistically significant difference between groups (x2 =0.780,P＞0.05).Conclusion The splenectomy before liver transplantation is easy to form PVT,increase time and difficulty of transplantation surgery,however,it doesn't increase complication risk after transplantation and affect postoperative survival.