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.

Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

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 compare the effects of antibiotic-loaded bone cement coverage and negative pressure wound therapy (NPWT) on diabetic foot ulcer wound healing. Methods A total of 113 patients with diabetic foot ulcers were selected as study subjects and randomly divided into control group (57 patients receiving NPWT) and experimental group (56 patients receiving antibiotic-loaded bone cement coverage) using the double-color ball randomization method. Both groups underwent routine debridement. The treatment outcomes, positive detection rate of wound bacterial culture, lower limb nerve conduction function (tibial nerve motor conduction velocity, common peroneal nerve sensory conduction velocity), Doppler ultrasound indicators (vessel diameter, blood flow velocity, resistance index, pulsatility index), inflammatory indicators (tumor necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein), and granulation tissue growth were observed and compared between the two groups. Results The effective treatment rate was 85.71% in the experimental group, which was higher than 70.18% in the control group (P < 0.05). Before treatment, there were no statistically significant differences between the two groups in terms of positive detection rate of wound bacterial culture, tibial nerve motor conduction velocity, common peroneal nerve sensory conduction velocity, blood flow velocity, vessel diameter, resistance index, pulsatility index, granulation tissue growth, and serum levels of tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein (P>0.05). After 3, 7, and 15 days of treatment, the positive detection rate of wound bacterial culture in the experimental group was lower than that in the control group (P < 0.05). After treatment, the tibial nerve motor conduction velocity, common peroneal nerve sensory conduction velocity, vessel diameter, blood flow velocity, resistance index, and pulsatility index in both groups were higher or greater than those before treatment, and those in the experimental group were higher or greater than those in the control group (P < 0.05). After treatment, the granulation tissue area, coverage rate, and granulation tissue growth rate in the experimental group were higher than those in the control group (P < 0.05). After treatment, the serum levels of tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein in both groups were lower than those before treatment, and those in the experimental group were lower than those in the control group (P < 0.05). Conclusion Compared with NPWT, antibiotic-loaded bone cement coverage has a higher effective treatment rate for diabetic foot ulcers, and provides a more effective local antibacterial environment, thereby promoting wound healing and tissue repair, and simultaneously improving nerve function and vascular status.

ObjectiveTo observe the effect of bilateral sequential repetitive transcranial magnetic stimulation on the motor function of upper limbs in stroke patients. MethodsFrom December, 2020 to December, 2022, 62 stroke inpatients in the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine were included. They were randomly divided into control group (n = 31) and observation group (n = 31). Both groups accepted conventional medicine and rehabilitation, as well as electroacupuncture antagonistic muscle therapy. Before electroacupuncture, the observation group acceped low-frequency repetitive transcranial magnetic stimulation at primary motor cortex (M1) on the healthy side, followed by intermittent theta burst stimulation at M1 on the affected side, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), modified Barthel Index (MBI) and modified Ashworth Scale (MAS), and motor evoked potential (MEP) latency was compared before and after treatment. ResultsOne patient dropped down in the observation group, and no adverse event happened. After treatment, the scores of FMA-UE and MBI significantly increased (|t| > 9.953, P < 0.001), and the score of MAS and the latency of MEP significantly decreased (|t| > 5.043, P < 0.001) in both groups; while all of them were better in the observation group than in the control group (|t| > 2.237, P < 0.05). ConclusionBilateral sequential repetitive transcranial magnetic stimulation can effectively promote the recovery of upper limb motor function in stroke patients.

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 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.

OBJECTIVE To establish the ion mobility mass spectrometry method for simultaneous determination of epiberberine， berberine， coptisine， palmatine， calycosin-7-glucoside， 3，5-O-dicaffeoylquinic acid， 4，5-O-dicaffeoylquinic acid and chlorogenic acid in Jinqi jiangtang tablets. METHODS Ion mobility mass spectrometry method was used. The determination was performed on Waters ACQUITY UPLC HSS T3 （2.1 mm×50 mm， 1.8 μm） with mobile phase consisted of 0.1% formic acid solution-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and the injection volume was 5 μL. The contents of 8 components in Jinqi jiangtang tablets were determined by scanning detection under positive and negative ion modes with an electric spray ion source， and setting ion mobility mass parameters according to the peak response of each component. RESULTS The results showed that the linear relationship of the eight components was good within their respective ranges （r≥0.999）； RSDs of precision， repeatability and stability （24 h） tests were not more than 4.0%； average recoveries were 94.6%-101.2% ， RSDs were 2.6%-3.9% （n＝9）. The contents of the above eight components in three batches of Jinqi jiangtang tablets were 3.060-3.545， 24.50-26.74， 2.795-4.149， 1.437-2.501， 0.204-0.242， 0.950-1.281， 2.272-2.828， 7.314- 7.960 mg/g， respectively. CONCLUSIONS The established method has high sensitivity and good reproducibility， and can provide reference for the quality control of the preparation.