Objective To explore the effect of sex on the incidence of immune-related cutaneous adverse event (ircAE) during immunotherapy for gastric cancer, and to further analyze the correlation between sex, ircAE and prognosis. Methods A retrospective analysis was conducted on patients with advanced gastric cancer who received immune checkpoint inhibitors at the Department of Oncology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, from February 1, 2022, to December 31, 2024. Clinicopathological characteristics, occurrence of ircAE, and survival data were collected. The incidence of ircAE was compared between male and female patients. Kaplan-Meier method was used to plot survival curves, and univariate Cox regression analysis was performed to assess prognostic factors. Results A total of 116 patients with advanced gastric cancer were enrolled, including 76 males (65.5%) and 40 females (34.5%). The overall incidence of ircAE was 23.28%, with a higher incidence in male patients than in female patients (28.95% vs 12.50%, P＝0.046). Kaplan-Meier survival analysis on 86 patients with complete follow-up data indicated that patients with ircAE had longer overall survival (OS) than those without ircAE (P＝0.045). Univariate Cox regression analysis showed that male (HR＝0.43, 95%CI 0.22–0.83, P＝0.012) was associated with prolonged OS. Conclusions In gastric cancer immunotherapy, male patients are more likely to develop ircAE and have longer OS than female patients, and the occurrence of ircAE may be related to prolonged OS.

Objective To explore the influencing factors of neonatal pneumonia complicated with myocardial damage and Th1/Th2 cytokines,and construct a line chart model.Methods A total of 390 neonates with pneumonia who were treated in Mianyang People's Hospital were selected as the study subjects and randomly divided into a modeling cohort(n=273)and a validation cohort(n=117)according to a 7∶3 ratio.They were further divided into myocardial damage group and non-myocardial damage group according to whether they had concurrent myocardial damage.Enzyme linked immunosorbent assay(ELISA)was used to measure Th1/Th2 cytokines(IFN-γ,IL-6,TNF-α,IL-4,IL-2 and IL-10),and the Mindray BS-280 automatic biochemical analyzer was used to measure hs-cTn I,CK-MB,LDH and CK.Logistic regression equation was used to screen the influencing factors of neonatal pneumonia complicated with myocardial damage.R software was used to construct a line chart model,and the receiver operating characteristic curve(ROC)and area under the ROC curve(AUC)were used to analyze the predictive ability of the model.The Hosmer-Lemeshow goodness-of-fit test was used,and a calibration curve was drawn to evaluate the calibration of the model.The decision curve analysis(DCA)was used to evaluate the clinical effectiveness.Results The incidence of myocardial damage in 390 neonates with pneumonia was 28.21%.Modeling cohort and validetion cohort,the 1min Apgar score in the myocardial damage group was lower than that in the non-myocardial damage group(t=3.314,2.619),and CK-MB,LDH,CK,hs-cTnI,IL-2,IFN-γ,TNF-α,IL-6,IL-10 and IL-4 were higher than those in the non-myocardial damage group(t=5.805～18.914),and the proportions of severe pneumonia,low birthweight infant,premature infants were higher than those in the non-myocardial damage group(χ2=4.464～41.497),and the differences were statistically significant(all P<0.05),respectively.The Logistic regression equation showed that low birth weight,1-minute Apgar score,premature birth,hs-cTnI,IL-2,IFN-γ,IL-6 and IL-4 were factors affecting neonatal pneumonia complicated with myocardial damage(Wald χ2=10.330～14.328,all P<0.05).The AUC(95%CI)of the nomogram model constructed based on the factors affecting neonatal pneumonia complicated with myocardial damage was 0.880(0.839～0.921)in the modeling cohort and 0.910(0.856～0.964)in the validation cohort,with slopes of the calibration curves close to 1,and the clinical net benefit rate was the highest in the ranges of 0.1～0.8 and 0.0～0.7.Conclusion The nomogram model,which includes Th1/Th2 cytokines,hs-cTnI,1-minute Apgar score,premature infants and low-birth-weight infants has high predictive value for neonatal pneumonia complicated with myocardial damage.It can help clinicians identify high-risk populations,take reasonable diagnostic and treatment measures,and reduce the risk of myocardial damage.

Objective To explore the influencing factors of neonatal pneumonia complicated with myocardial damage and Th1/Th2 cytokines,and construct a line chart model.Methods A total of 390 neonates with pneumonia who were treated in Mianyang People's Hospital were selected as the study subjects and randomly divided into a modeling cohort(n=273)and a validation cohort(n=117)according to a 7∶3 ratio.They were further divided into myocardial damage group and non-myocardial damage group according to whether they had concurrent myocardial damage.Enzyme linked immunosorbent assay(ELISA)was used to measure Th1/Th2 cytokines(IFN-γ,IL-6,TNF-α,IL-4,IL-2 and IL-10),and the Mindray BS-280 automatic biochemical analyzer was used to measure hs-cTn I,CK-MB,LDH and CK.Logistic regression equation was used to screen the influencing factors of neonatal pneumonia complicated with myocardial damage.R software was used to construct a line chart model,and the receiver operating characteristic curve(ROC)and area under the ROC curve(AUC)were used to analyze the predictive ability of the model.The Hosmer-Lemeshow goodness-of-fit test was used,and a calibration curve was drawn to evaluate the calibration of the model.The decision curve analysis(DCA)was used to evaluate the clinical effectiveness.Results The incidence of myocardial damage in 390 neonates with pneumonia was 28.21%.Modeling cohort and validetion cohort,the 1min Apgar score in the myocardial damage group was lower than that in the non-myocardial damage group(t=3.314,2.619),and CK-MB,LDH,CK,hs-cTnI,IL-2,IFN-γ,TNF-α,IL-6,IL-10 and IL-4 were higher than those in the non-myocardial damage group(t=5.805～18.914),and the proportions of severe pneumonia,low birthweight infant,premature infants were higher than those in the non-myocardial damage group(χ2=4.464～41.497),and the differences were statistically significant(all P<0.05),respectively.The Logistic regression equation showed that low birth weight,1-minute Apgar score,premature birth,hs-cTnI,IL-2,IFN-γ,IL-6 and IL-4 were factors affecting neonatal pneumonia complicated with myocardial damage(Wald χ2=10.330～14.328,all P<0.05).The AUC(95%CI)of the nomogram model constructed based on the factors affecting neonatal pneumonia complicated with myocardial damage was 0.880(0.839～0.921)in the modeling cohort and 0.910(0.856～0.964)in the validation cohort,with slopes of the calibration curves close to 1,and the clinical net benefit rate was the highest in the ranges of 0.1～0.8 and 0.0～0.7.Conclusion The nomogram model,which includes Th1/Th2 cytokines,hs-cTnI,1-minute Apgar score,premature infants and low-birth-weight infants has high predictive value for neonatal pneumonia complicated with myocardial damage.It can help clinicians identify high-risk populations,take reasonable diagnostic and treatment measures,and reduce the risk of myocardial damage.

OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

Objective To investigate the effect of psychological intervention combined with venlafaxine and risperidone in the treatment of refractory depression and its influence on the quality of life .Methods 97 patients with refractory depression were selected .According to the random number table , they were divided into the observation group(50 cases) and the control group(47 cases).The control group was given venlafaxine combined with risperidone treatment,the observation group received psychological intervention on basis of the control group .The Hamilton depression scale ( HAMD) of patients in the two groups before treatment ,4,8 and 12 weeks after treatment were recorded .The curative effect after 12 weeks of treatment was evaluated ,the adverse reaction was evaluated by the side effects scale ( TESS ) , and the quality of life ( WHOQOL-100 ) of the two groups before treatment , 12 weeks after treatment were compared .Results The HAMD score of the two groups had no statistically significant difference before treatment(t=0.307,P>0.05).After treatment for 4,8,12 weeks,the HAMD scores of the two groups were significantly lower than before treatment (t=5.743,17.756,27.288,4.595,15.801,23.247,all P<0.05),and the HAMD scores in the observation group after treatment for 8 weeks and 12 weeks were significantly lower than those in the control group(t=0.887,3.717,5.854,all P<0.05).After 12 weeks of treatment,the total effective rate of the observation group was significantly higher than that of the control group (90.00％ vs.74.47％,χ2 =4.043,P <0.05 ).There was no statistically significant difference in incidence rate of adverse reactions between the two groups (26.00％vs.25.52％,χ2 =0.003,P >0.05).The WHOQOL-100 scores of the two groups had no statistically significant differences before treatment(t=0.597,0.497,0.378,0.923,0.136,all P>0.05).The WHOQOL-100 scores of the two groups after treatment were significantly higher than those before treatment ( t =11.668,8.701, 6.857,7.053,2.247,4.815,4.639,2.999,4.117,2.011,all P<0.05).After treatment,the psychological and physiological independence and social relationship domain scores in the observation group were significantly higher than those in the control group(t=5.618,3.295,4.335,3.603,all P<0.05).Conclusion Psychological interven-tion combined with venlafaxine and risperidone in the treatment of refractory depression can significantly improve the clinical efficacy ,improve the clinical symptoms and the quality of life of patients .

The present study aimed to research pathogenesis and therapeutics of hepatocellular carcinoma (HCC) with the method of tissue metabolomics.A combined gas chromatography-mass spectrometry (GC-MS) method was developed suitable for analyzing the endogenous small molecule of liver cancer tissues and adjacent tissues.The unidimensional and multidimensional statistics were used to look for differential metabolites.And then,the KEGG and HMDB database were utilized to find related differential pathways and pathogenesis of HCC.The PCA and PLS-DA showed that there were significant differences on the endogenous small molecule of liver cancer tissues and adjacent tissues.Through the OPLS-Loading plot analysis,there were 25 differential metabolites and 36 relevant pathways.The differential pathways belong to carbohydrate metabolism,amino acid metabolism and mitochondrial transfer.There were 16 metabolites' area under the ROC curve which was bigger than 0.8,which were related with ATP-binding cassette (ABC) transporters,galactose metabolism,amino sugar and nucleotide sugar metabolism.It was concluded that the Warburg effect exists in HCC cells.The energy of HCC cell was from glycolytic function,because the glycolysis was enhanced and the citric acid cycle decreased.Mitochondrial dysfunction and the increased cobalt content may correlate with the Warburg effect,which may be one of the pathogenesis of liver cancer,and expected to become the breakthrough point of a new targeting therapeutic approach.