Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective To investigate the effect of lidocaine medicated plaster （LMP） combined with pregabalin （PGB） on patients with postherpetic neuralgia （PHN）, and the impact on serum pain mediators. Methods 108 PHN patients admitted in our hospital from January 2024 to December 2024 were selected and grouped according to the time point of receiving treatment, 54 PHN patients treated with PGB from January 2024 to June 2024 were included in the PGB group, and 54 PHN patients treated with LMP on top of the PGB group from July 2024 to December 2024 were included in the PGB+LMP group. Comparisons were made between the two groups in terms of pain score, serum pain mediator levels, dosage of PGB, and incidence of adverse reactions. Results After 4 weeks of treatment, both groups showed a decrease in Pain Rating Index scores （sensory score and affective score）, Present Pain Intensity score, Visual Analog Scale score, and total score. Meanwhile, above scores of the PGB+LMP group were lower than those of the PGB group （P<0.05）. After 4 weeks of treatment, the levels of substance P（SP） and neuropeptide Y （NPY） in both groups were lower than those before treatment, while serum 5-hydroxytryptamine （5-HT） levels were higher than those before treatment. Moreover, the levels of SP and NPY were lower, and 5-HT level was higher in the PGB+LMP group than in the PGB group （P<0.05）. The dosages of PGB in the PGB+LMP group at T1, T, T3 and T4 were significantly lower than those in the PGB group （P<0.05）. The incidence of adverse reactions was 1.85%（1/54） in the PGB+LMP group. Compared to 5.56%（3/54） in the PGB group, and the difference was not statistically significant （P>0.05）. Conclusion LMP combined with PGB was effective in the treatment of patients with PHN, which could effectively alleviate pain and lower the levels of serum pain mediators, with good safety.

OBJECTIVE To investigate the current status of self-medication behaviors and the demand preferences for pharmaceutical services among residents in Xining， providing a basis for developing pharmaceutical service intervention strategies tailored to regional characteristics. METHODS A self-designed questionnaire， developed based on literature review and revised after expert panel discussion and a pre-survey， was used to conduct anonymous surveys among residents purchasing medicines at 12 retail pharmacies in Xining area from April 2023 to April 2024. Descriptive analysis， Chi-square test， and Spearman correlation analysis were employed to analyze the characteristics and influencing factors of residents’ self-medication behaviors， and pharmaceutical service needs. RESULTS A total of 859 valid questionnaires were collected， with 605 respondents （70.43%） reporting self-medication behaviors. The primary reason for self-medication was mild symptoms （46.94%）. The main conditions treated were gastrointestinal discomfort （38.51%） and cold， fever， headache （35.37%）. Chinese patent medicines were the most commonly used （58.68%）. Drug selection relied mainly on recommendations by pharmacy staff （52.07%）， and retail pharmacies were the primary source of medicines （65.95%）. Dosage and administration were determined primarily by referring to the drug package insert （67.27%）， while a minority relied on personal experience （9.92%）. Notably， 20.33% of respondents never read the package insert before medication， with a higher tendency observed among ethnic minorities， farmers， and individuals with chronic diseases （P＜0.05）. While 65.29% of respondents reported partially understanding the insert content， those aged ≥60 years， ethnic minorities， and individuals with chronic diseases qhsrmyy-28） were more likely to report being completely unable to understand it （P＜0.05）. Self-medication was “often effective” for 52.73% of respondents， whereas 7.77%“ often experienced adverse drug reactions”； farmers were more prone to poor efficacy or adverse reactions （P＜0.05）. A majority （72.89%） of respondents residents believed it necessary to learn about self- medication knowledge， and 47.11% preferred to obtain pharmaceutical services through WeChat public accounts or mobile applications （APP）. CONCLUSIONS Self-medication is common among residents in Xining area. Issues such as neglecting to read package inserts and relying on personal experience are evident. It is essential to develop science popularization programs suitable for the characteristics of the local population and utilize digital platforms like WeChat public accounts and APP to disseminate self- medication knowledge， thereby enhancing residents’ awareness and capacity for rational medication use.

Objectives:To evaluate the efficacy and safety of the self-fixing and self-detachable drainage stent in pancreaticojejunostomy and to provide supportive data for the follow clinical trials.Methods:This is an experimental research in animals which completed from February 2022 to September 2022. A self-fixing and self-detachable pancreaticojejunostomy drainage stent was designed for Hong′s pancreaticojejunostomy technique based on the theory of “fistula healing” in pancreaticojejunostomy. Ten biocompatibility tests were completed invitro before this study. Twenty-five Bama minipigs were selected and double-ligated in the neck of the pancreas to dilate the distal main pancreatic duct. Twenty-three of them were successfully modelled and divided into three groups by a stratified random method: pancreaticojejunostomy drainage stent group (referred to as stent group) with 11 pigs, pancreatic duct to jejunal mucosa anastomosis group (referred to as manual suture group) with 8 pigs, sham operation group with 4 pigs. The anastomic time,amylase content in postoperative abdominal drainage fluid and the tolerable pressure value of pancreaticojejunostomy were compared between the stent group and the manual suture group. An abdominal X-ray fluoroscopy examination was adopted to detect the detach time of the stent. A postoperative pathological examination was performed to verify the healing time,the type of treatment and the stricture rate of pancreaticojejunostomy. Quantitative data was analyzed by independent sample t-test. The classified data were analyzed by Fisher′s exact test. Results:There were no significant differences in the diameter of the pancreatic duct and pancreatic texture,the time of pancreaticojejunostomy,the amylase content in postoperative peritoneal drainage fluid,and the tolerable pressure value of the pancreaticojejunostomy between the stent group and the manual suture group(all P>0.05). Abdominal X-ray fluoroscopy showed that the stents gradually detached and were removed from the body 21 days after operation,and all stents were detached in the follow 3 months after operation. Pancreaticojejunostomy healed 7 days after operation based on fistula formation in the stent group,and 14 days in the manual suture group. The incidence of anastomotic stricture within 35 days after operation was 2/8 in the stent group and 6/8 in the manual suture group (Fisher′s exact test: P=0.132). Conclusion:The stent method is safer and simpler than the manual suture method in pancreaticojejunostomy of Bama minipigs, with shorter anastomotic healing time and lower stricture rate.

Objectives:To evaluate the efficacy and safety of the self-fixing and self-detachable drainage stent in pancreaticojejunostomy and to provide supportive data for the follow clinical trials.Methods:This is an experimental research in animals which completed from February 2022 to September 2022. A self-fixing and self-detachable pancreaticojejunostomy drainage stent was designed for Hong′s pancreaticojejunostomy technique based on the theory of “fistula healing” in pancreaticojejunostomy. Ten biocompatibility tests were completed invitro before this study. Twenty-five Bama minipigs were selected and double-ligated in the neck of the pancreas to dilate the distal main pancreatic duct. Twenty-three of them were successfully modelled and divided into three groups by a stratified random method: pancreaticojejunostomy drainage stent group (referred to as stent group) with 11 pigs, pancreatic duct to jejunal mucosa anastomosis group (referred to as manual suture group) with 8 pigs, sham operation group with 4 pigs. The anastomic time,amylase content in postoperative abdominal drainage fluid and the tolerable pressure value of pancreaticojejunostomy were compared between the stent group and the manual suture group. An abdominal X-ray fluoroscopy examination was adopted to detect the detach time of the stent. A postoperative pathological examination was performed to verify the healing time,the type of treatment and the stricture rate of pancreaticojejunostomy. Quantitative data was analyzed by independent sample t-test. The classified data were analyzed by Fisher′s exact test. Results:There were no significant differences in the diameter of the pancreatic duct and pancreatic texture,the time of pancreaticojejunostomy,the amylase content in postoperative peritoneal drainage fluid,and the tolerable pressure value of the pancreaticojejunostomy between the stent group and the manual suture group(all P>0.05). Abdominal X-ray fluoroscopy showed that the stents gradually detached and were removed from the body 21 days after operation,and all stents were detached in the follow 3 months after operation. Pancreaticojejunostomy healed 7 days after operation based on fistula formation in the stent group,and 14 days in the manual suture group. The incidence of anastomotic stricture within 35 days after operation was 2/8 in the stent group and 6/8 in the manual suture group (Fisher′s exact test: P=0.132). Conclusion:The stent method is safer and simpler than the manual suture method in pancreaticojejunostomy of Bama minipigs, with shorter anastomotic healing time and lower stricture rate.

Objective:To analyze the performance characteristics of the energy output of defibrillation device at different lifecycle stages of the equipment,and to improve the level of management,so as to ensure the safety and effectiveness of using the device.Methods:A total of 90 defibrillation devices of using 10 types included 861290 and CardioServ(included scrapped devices)during the period of 2015-2022 were retrospectively analyzed.The detected data of energy output of defibrillation device were analyzed as statistical method,and the error of releasing energy was calculated.A total of 36 defibrillation devices that were in the early stages of use(at the first three years of device use)were divided into the first year,the second year and the third year,and the data of energy outputs of devices among three years were compared.The data of the type A and type B defibrillation devices,which were the largest number of devices in the normal stage of use(the middle stage of use),were calibrated according to the energy release in the three years between 2018 and 2000.The difference of releasing energy at the preseted value of 100J between the two types of devices was analyzed.Finally,the errors of energy releases of 8 devices,which energy outputs exceeded the deadline,in the scrap period between 2015 and 2022 were summarized.Results:In the data of three groups of devices in the early stages of use,the differences at the first and second year of device use among 100J,150J and 200J of the energy releases of the preseted values were significant(t=-0.17,-0.17,-0.58,P>0.05).The difference of the measured values between the first and third years of device use was not significant(Z=-0.70,-0.38,-0.86,P>0.05).The results of variance analysis of repeated measurement of the energy releases of the devices in normal stage indicated that the difference of the energy release at 100J preseted point among different types of 41 devices was significant(F=4.40,P<0.05).The energy release of type X defibrillator appeared constantly high,and the relative error increased with the increasing of preseted values.The repeatability of the device was better,and the relationship between preseted energy(x)and release energy(y)conformed to linear relationship(R2=0.9985).In these defibrillation devices that were using,the qualified rate of energy output of>100J preseted point was 97.68%.Conclusion:There is slight difference in the mean value of energy release between different type of defibrillation devices within the qualified range,and the energy release still is a performance indicator that should be highly focused for defibrillation devices.We should combine with the maintenance and repair data of device to conduct in-depth analysis,so as to grasp the operating status of the device,and optimize the strategy of quality control,and ensure the safety of defibrillator in clinical use.