OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Coronavirus disease 2019(COVID-19)is highly infectious,severe and critically ill patients have high mortality and lack specific treatment,so it is urgent to find safe and effective treatment methods.Mesenchymal stem cells(MSCs)have biologi-cal properties such as immune regulation,tissue repair,regeneration,migration and homing,antiviral and anti-inflammatory.At present,studies on use of MSCs in treatment of COVID-19 have been gradually carried out.This paper reviews pathogenesis of 2019 novel coronavirus(2019-nCoV),potential regulatory mechanisms and challenges of MSCs in treatment of COVID-19.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective To investigate the mechanism of Zuogui Pills (ZGP) on improving the stemness of ovarian germline stem cells (OSCs) in ovarian aging rats through the gap junction protein connexin 43 (Cx43) phosphorylation based on the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Methods Eight-week-old female SD rats were randomly divided into control(CON),model(cyclophosphamide,CTX),ZGP and dehydroepiandrosterone(DHEA) groups,six rats in each group. CTX was injected intraperitoneally for 15 days to establish a model for ovarian aging,and then ZGP (1.85 g·kg-1) or DHEA (8.1 mg·kg-1) was administered by gavage once daily for 30 days. Follicle count at different stages and pathological changes of ovarian tissues were observed by HE staining. ELISA was used to detect serum levels of anti-mullerian hormone (AMH),follicle-stimulating hormone (FSH),and estradiol(E2). The expression levels of related proteins (PCNA,MVH,Oct4,Cx43,p-Cx43,EGFR,AKT、p-AKT) in ovarian tissue were detected by Western Blot. Results Compared with the CON group,rats in CTX group had significantly reduced body mass(P<0.05) and ovarian mass(P<0.05). The number of primordial follicles decreased significantly(P<0.01). Serum FSH level increased remarkably(P<0.01),while AMH and E2 levels showed a downward trend (P>0.05). The protein expressions of Oct4,MVH,PCNA,EGFR,p-AKT/AKT,p-Cx43(Ser368)/Cx43 and Cx43 in ovarian tissue were obviously decreased(P<0.05,P<0.01). Compared with the model group,the body mass of rats in ZGP group was significantly increased (P<0.05),as well as ovarian mass and ovarian coefficient were remarkably increased (P<0.01). The number of primordial follicles were increased significantly (P<0.01),and E2 level increased significantly (P<0.05). The protein expressions of Oct4,MVH,PCNA,EGFR,p-AKT/AKT,p-Cx43(Ser368)/Cx43 and Cx43 in ovarian tissue were all increased significantly (P<0.05,P<0.01). Conclusion ZGP may ameliorate ovarian aging by maintaining the stemness of OSCs. Its mechanism of actions is related to the PI3K/AKT signaling pathway and gap junction protein phosphorylation.

With the acceleration of the aging process of the population,more and more elderly pa-tients need to receive surgical treatment,and studies have found that elderly patients are prone to periopera-tive neurocognitive disorders(PND).PND may effects patients'postoperative rehabilitation.Therefore,early identification of high-risk patients with PND and strengthening preoperative prehabilitation are extremely important for perioperative brain health and postoperative rehabilitation of patients.In this paper,preoperative risk factors,simple assessment methods and prehabilitation strategies of perioperative neurocog-nitive disorders in elderly patients were summarized,so as to provide references for clinical screening and prehabilitation of high-risk elderly patients.

Objective To investigate the association between famine exposure in different life cycles and the risk of central obesity. Methods A total of 2234 spermanent residents were recruited to participate in the China Multi-Ethnic Cohort (CMEC) Study ,they were grouped into four birth cohorts of fetal-exposed (born between January 1,1959, and December 31,1961,95 cases), childhood-exposed (born between January 11,949, and December 31,1958,533 cases), adolescence/adult-exposed (born between January 1,1931, and December 31,1948,256 cases),unexposed cohorts（born after January 1, 1975，871 cases).we used logistic regression model to assess the effect of famine exposure on central obesity in adulthood. Results After adjusting for confounding factors, females in the fetal/infant exposure group（OR=3.283,95%CI：1.472～7.321,P＜0.001）、childhood- exposed group (OR=3.557,95%CI：2.374～5.313,P＜0.001) and adolescence/adult-exposed group (OR=5.785，95%CI：3.536～9.492，P＜0.001) had a higher risk of adult central obesity than the control group.After excluding the subjects with coronary heart disease、cancer、diabetes、stroke or obesity, sensitivity analysis was carried out. The risk of central obesity increased in the female / fetal、childhood、adolescent / adult exposure group,which was unfound in males. Conclusion Severe famine exposure in fetal/infant、childhood and adolescence/adulthood can increase the risk of central obesity in adulthood in females. Therefore, the prevention and control of central obesity in female should start from the early life.

Objective: To investigate the influencing factors and population attributable risk percent (PAR%) of low back pain in automobile assemblers. Methods: A total of 634 assemblers from 11 automobile manufacturers in Shiyan City, Hubei Province were chosen as research subjects using judgment sampling method. The prevalence of low back pain in the past one year was investigated using Musculoskeletal Disorders Questionnaire. PAR% was used to analyze the contribution of influencing factors to low back pain. Results: The annual prevalence of low back pain was 68.8%. The results of multivariate logistics regression showed that length of service>15 years, high school or secondary college education or above, standing most of the time, sitting most of the time, the proportion of cumulative time of poor posture in work shift time ≥1/8, and bending for insufficient height of working space were the risk factors for low back pain (all P<0.05). The PAR% of the proportion of cumulative time of poor posture in work shift time ≥1/8 was 43.0%, 37.8% for standing most of the time, and 12.8% for bending for insufficient height of working space. Conclusion: The annual prevalence of low back pain was higher in automobile assemblers. The influencing factors included individual factors and occupational factors. The proportion of cumulative time of poor posture in work shift time ≥1/8, standing most of the time and bending for insufficient height of working space should be taken as the priority intervention factors to reduce the prevalence of low back pain among assemblers in this enterprise.

Objective:To explore the effects of standard meal and treadmill exercise test on body surface gastrointestinal electrogram in healthy subjects, and to provide more evidence for the clinical application of gastrointestinal electrogram.Methods:From January to June 2021, a total of 100 healthy asymptomatic volunteers underwent gastrointestinal electrogram after fasting, standard meal and treadmill exercise test. After the subjects fasted for more than 8 hours, the gastrointestinal electrogram was performed after the subjects were lying flat, quiet, and breathing steadily, electrodes were placed on the the body surface projection positions of the gastric body, the lesser curvature, the greater curvature, the antrum, the ascending colon, the transverse colon, the descending colon, and the rectum. The fasting gastrointestinal electrogram was recorded for 6 min. Then lay for 5 to 10 min after the standard meal (100 g bread, 250 mL milk), the postprandial gastrointestinal electrogram was recorded for 6 min. And lay for 5 to 10 min after treadmill exercise test, then the postexercise gastrointestinal electrogram was recorded for 6 min. The frequency and amplitude of gastrointestinal electrogram waveforms of the three time points were compared, and the percentage of gastrointestinal electrical rhythm disorder, and slow wave frequency instability coefficient were also compared. Stratified analysis of gastric motility was performed according to age, sex and body mass index. Paired t-test, Pearson Chi-squared test, continuity correction Chi-squared test, Fisher′s exact method and Speraman correlation were used for statistical analysis. Results:The standard meal did not obviously affect the mean frequency of the gastric electrocardiogram, however the mean amplitude of gastric electrocardiogram significantly increased after standard meal compared with that of fasting, especially in the electrodes placed at lesser curvature((148.5±8.7) μV vs.(113.2±5.0)μV ), greater curvature((176.3±11.3) μV vs.(126.1±7.3) μV), and antrum((161.8±10.6) μV vs.(117.6±4.91) μV), and the differences were statistically significant( t=4.63, 4.63 and 3.99, all P< 0.001). There were no significant changs in rhythm and stability of the gastric electrocardiogram. The mean frequency of intestinal electrograms at the ascending colon, the transverse colon, the descending colon, and the rectum decreased after the standard meal compared with that of fasting ((10.8±0.2) count per minute(cpm) vs.(11.5±0.2) cpm, (10.5±0.2) cpm vs.(11.2±1.6) cpm, (10.9±0.2) cpm vs.(11.7±0.2) cpm, (11.1±0.2) cpm vs.(11.8±0.2) cpm), and the differences were statistically significant ( t=3.82, 4.55, 4.39, and 3.98, all P<0.001); the mean amplitude of the ascending colon, the transverse colon, and the rectum increased compared with that of fasting ((129.8±6.1) μV vs. (110.9±6.4) μV, (119.6±4.1) μV vs. (101.3±4.7) μV, (124.1±4.6) μV vs. (106.2±5.7) μV), and the differences were statistically significant ( t=2.62, 3.76, and 3.16; P=0.010, <0.001, =0.002); and the number of leads with enteroelectric rhythm disorder increased (398 vs. 389, the total number of leads is 400), and the difference was statistically significant( χ2=7.31, P=0.026). The mean frequency of gastric electricity after treadmill exercise in electrode placed at antrum increased compared with that after standard meal ((3.4±0.4) cpm vs.(3.3±0.3) cpm), and the differences were statistically significant( t=2.45, P=0.016), and the mean amplitude of gastric electricity in electrodes placed at gastric body, lesser curvature and antrum increased compared with those after standard meal((160.2±8.6) μV vs. (133.9±6.4) μV, (178.1±10.0) μV vs. (148.5±8.7) μV, (202.5±10.2) μV vs. (161.8±10.6) μV), and the differences were statistically significant ( t=2.30, 2.35, and 2.48; P=0.024, 0.021, and 0.015). Treadmill exercise affected the rhythm and stability of gastric electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (25 vs. 1, the total number of electrodes is 400), and the difference was statistically significant( χ2=22.90, P<0.001). There was no significant change in the mean frequency of the colonic electricity after treadmill exercise compared with that after standard meal, however the mean amplitude of intestinal electrical waveform at the ascending colon, the transverse colon, the descending colon, and the rectum increased compared with those after standard meal((171.2±8.4) μV vs. (129.8±6.1) μV, (166.1±7.7) μV vs. (119.6±4.1) μV, (147.2±7.2) μV vs. (121.1±4.9) μV, (149.6±7.3) μV vs. (124.1±4.6) μV), and the differences were statistically significant( t=3.51, 5.49, 3.09, and 2.83; P=0.001, <0.001, =0.003, and=0.006), which affected the rhythm and stability of the colonic electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (10 vs. 3, the total number of electrodes is 400, χ2=4.04, P=0.040). Gender was correlated with mean frequency of gastric electricity after standrdmeal and treadmill exercise test and mean amplitude of fasting and standard postprandial gastric electricity( r=0.242, -0.272, 0.286, 0.242; P=0.015, 0.006, 0.004, 0.015), and with mean amplitude of fasting and standard postprandial electricity( r=0.225, 0.460; P=0.024, <0.001). Age was only associated with mean frequency of fasting gastric electricity( r=-0.214, P=0.033). Body mass index was correlated with mean gastric electrical amplitude after fasting, standard meal and treadmill exercise( r=-0.347, -0.260, -0.211; P<0.001, =0.009, =0.036), as well as with the mean gastric electricity frequency after treadmill exercise ( r=0.242, P=0.016). Body mass index was correlated with the mean amplitude and frequency of fasting and standard postprandial intestinal electricity ( r=-0.261, -0.296, -0.400, -0.286; P=0.009, =0.003, < 0.001, =0.003). In the healthy volunteers with female gender and body mass index < 24 kg/m 2, there were statistically significant differences in the changes of gastric motility after standard meal (Fisher′s exact method, P=0.022 and 0.024). Conclusion:Both standard meal and treadmill exercise test affect gastrointestinal electrical activity, and exercise caused more changes in gastrointestinal electrical activity than standard meal.

Objective : To analyze the trends in incidence of thyroid cancer in Huangpu District, Shanghai from 2002 to 2017, so as to provide insights into the management of thyroid cancer. Methods : The incidence of thyroid cancer in Shanghai from 2002 to 2017 was collected from the cancer registration system created by Shanghai Center for Disease Control and Prevention. The crude and standardized incidence of thyroid cancer were estimated by year, gender and age groups, and annual change percentage ( APC ) was calculated to analyze the trends in incidence of thyroid cancer. Results : A total of 2 854 new cases of thyroid cancer were reported in Huangpu District from 2002 to 2017, and the crude and standardized incidence rates of thyroid cancer were 19.57/105 and 13.47/105, with APC of 18.15% and 17.93% ( P<0.05 ), respectively. The crude and standardized incidence rates of thyroid cancer were 10.02/105 and 7.06/105 in men, with APC of 19.58% and 19.04% ( P<0.05 ), and were 28.90/105 and 19.95/105 in women, with APC of 17.33% and 16.99% ( P<0.05 ), respectively. The crude incidence of thyroid cancer was higher in women than in men ( P<0.05 ). In addition, there were two peaks in the crude incidence of thyroid cancer in patients at age of 35 to 39 and 60 to 64 years, with crude incidence rates of 28.98/105 and 33.36/105, respectively. Conclusions The incidence of thyroid cancer appeared a tendency towards a rise in Huangpu District from 2002 to 2017, and much attention should be paid to females and patients aged 60 to 64 years.