Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71％,the highest in-cidence rate of grade 3/4 abnormality was 2.58％;the highest incidence of creatinine abnormality was 2.32％,the highest incidence rate of grade 3/4 abnormality was 0.37％in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14％,for aspartate transaminase(AST)was 0.11％,for alka-line phosphatase(ALP)was 0.16％,for alanine aminotransferase(ALT)was 0.06％and for total bilirubin(TBIL)was 0.07％,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.

Laparoscopic common bile duct exploration(LCBDE), as a safe and feasible surgical procedure for the treatment of choledocholithiasis, has been widely applied in clinical practice.However, due to the generally declined organ function, comorbidities, and polypharmacy associated with elderly patients, there is currently no unified consensus on the application of LCBDE in elderly patients with choledocholithiasis.This review aims to summarize the current status of LCBDE for the treatment of choledocholithiasis in the elderly patients, in order to provide reference for clinicians to select appropriate treatment strategies.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

ObjectiveTo investigate the safety and feasibility of intra-biliary drainage tube placement after laparoscopic common bile duct exploration in elderly patients with choledocholithiasis， and to provide more options for surgical procedures in the clinical management of elderly patients with choledocholithiasis. MethodsA retrospective analysis was performed for the clinical data of 52 elderly patients with choledocholithiasis who were admitted to Department of Hepatobiliary Surgery， Affiliated Dalian Friendship Hospital of Dalian Medical University， from November 2021 to October 2024. According to the biliary drainage method after surgery， the patients were divided into internal drainage group with 24 patients and T-tube drainage group with 28 patients， and there were 19 patients in each group after propensity score matching. The two groups were compared in terms of perioperative parameters and postoperative complications. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the T-tube drainage group， the internal drainage group had a significantly shorter length of postoperative hospital stay and a significantly lower volume of postoperative bile loss （Z=-2.845 and -5.633， both P<0.05）， while there were no significant differences between the two groups in time of operation， intraoperative blood loss， and drainage tube indwelling time （all P>0.05）. There were no significant differences between the two groups in postoperative bile leak， stone recurrence， biliary stricture， and drainage tube-related complications， and the internal drainage group had a significantly lower total complication rate than the T-tube drainage group ［1 （5.3%） vs 7 （36.8%）， P<0.05］. ConclusionFor elderly patients with choledocholithiasis， intra-biliary drainage tube placement after laparoscopic common bile duct exploration can shorten the length of postoperative hospital stay， reduce bile loss， and lower the incidence rate of postoperative complications， thereby helping to accelerate postoperative recovery.

Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P＜0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P＜0.05),decreased in SOD activity and GSH content(P＜0.01),and increased in the levels of ROS,LDH,and MDA levels(P＜0.01).In all SA dose,cell apoptosis reduced(P＜0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P＜0.05).In high dose group,the S-phase cells ratio increased(P＜0.05).And in medium/high dose groups,ROS(P＜0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P＜0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P＜0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P＜0.05);and Cytochrome C reduced in all SA groups(P＜0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.

Objective:To investigate the expression of erythropoietin-producing hepatocyte kinase receptor A10 (EphA10) in gastric cancer and adjacent tissues, and analyze its correlation with clinical features and prognosis.Methods:The clinical data of 112 patients with gastric cancer from January 2018 to December 2023 in Eastern Theater Command Air Force Hospital were retrospectively analyzed. The expression of EphA10 in gastric cancer and adjacent tissues was detected by EnVision immunohistochemical staining. The relationship between EphA10 expression and clinicopathological features was analyzed. The Kaplan-Meier survival curve was drawn, and the comparison used the log-rank test. Multivariate Cox regression was used to analyze the independent risk factors of the overall survival time in patients with gastric cancer.Results:The positive expression rate of EphA10 in gastric cancer tissues was significantly higher than that in adjacent tissues: 44.6% (50/112) vs. 0, and there was statistical difference ( χ2 = 64.37, P<0.01). In patients with gastric cancer, the positive expression of EphA10 in gastric cancer tissues was correlated with tumor long diameter, differentiation, TNM stage and lymph node metastasis ( P<0.01 or <0.05), but without age, gender and distant metastasis ( P>0.05). Kaplan-Meier survival curve analysis result showed that the median overall survival time in patients with positive EphA10 expression was significantly lower than that in patients with negative EphA10 expression: 18 months vs. 48 months, and there was statistical difference (log-rank χ2 = 53.66, P<0.01). Multivariate Cox regression analysis result showed that tumor long diameter ≥3 cm, TNM stage Ⅲ to Ⅳ, lymph node metastasis and EphA10 positive expression were the independent risk factors of the overall survival time in patients with gastric cancer ( HR = 1.250, 1.515, 1.321 and 0.831; 95% CI 1.143 to 1.368, 1.267 to 1.813, 1.168 to 1.497 and 0.756 to 0.913; P<0.01 or <0.05). Conclusions:The expression level of EphA10 in gastric cancer tissues is up-regulated, and its expression level is correlated with the clinicopathological features. EphA10 can be used as one of the reference indicators for clinical prognosis evaluation in patients with gastric cancer.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71％,the highest in-cidence rate of grade 3/4 abnormality was 2.58％;the highest incidence of creatinine abnormality was 2.32％,the highest incidence rate of grade 3/4 abnormality was 0.37％in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14％,for aspartate transaminase(AST)was 0.11％,for alka-line phosphatase(ALP)was 0.16％,for alanine aminotransferase(ALT)was 0.06％and for total bilirubin(TBIL)was 0.07％,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.