BACKGROUND:Synthetic polymers,such as polypropylene and polyester,used for the treatment of abdominal wall defects not only lack biodegradability and bioactivity but also fail to meet the demands of complex and irregular wounds.Therefore,finding bioactive materials with low immunogenicity and good histocompatibility has become a hot spot in the repair of abdominal wall defects. OBJECTIVE:To prepare methacryloyl modified dermal extracellular matrix hydrogel and explore its potential application in abdominal wall defect. METHODS:(1)The porcine dermis was acellular with 0.25%trypsin and 1%Triton X-100 in turn to obtain the dermal extracellular matrix.After pepsin digestion and methacrylic anhydride modification,the methacrylated dermal extracellular matrix hydrogel was formed by photocrosslinking.The microscopic morphology of the hydrogel was observed by scanning electron microscope,and its rheological properties,swelling properties and other physical and chemical properties were tested.(2)Mice fibroblasts(L929)were inoculated into methacrylated dermal extracellular matrix hydrogel to detect the cell compatibility.(3)Totally 12 SD rats were randomly divided into two groups(n=6)to create abdominal wall defect model with peritoneum preserved.The defect site of the polypropylene group was filled with polypropylene material,and the hydrogel group was filled with methacrylated dermal extracellular matrix hydrogel.The wound skin of both groups was covered with polypropylene material.The wound healing was observed and histological analysis was carried out. RESULTS AND CONCLUSION:(1)Enzymatic hydrolysis had a good decellularization effect on porcine dermis after decellularization,and the original glycosaminoglycans and collagen were well retained.Scanning electron microscope observation revealed that the dermal extracellular matrix hydrogel presented loose and porous structure.The aperture was between 70 and 120 μm.The swelling ratio was(16.88±3.24)%and the water absorption was(94.24±1.11)%.The rheological property test showed that the methacrylated dermal extracellular matrix hydrogel was stable and had shear thinning characteristics,with injectability.(2)CCK-8 assay and live/dead staining showed that methacrylated dermal extracellular matrix hydrogel had good cell compatibility.(3)The results of animal experiments showed that the skin wound healing rate of the experimental group was higher than that of the control group at 7,10,and 14 days after operation(P<0.05).Hematoxylin-eosin and Masson staining of skin and muscle tissue exhibited that compared with the polypropylene group,the skin wound epithelialization,hair follicle formation,collagen fiber arrangement,and neovascularization were better in the hydrogel group 14 days after surgery.The skin wound new tissue structure was similar to the normal tissue at 28 days after surgery,and scar hyperplasia was less.A small amount of muscle regeneration was observed on day 28 after operation.(4)The results show that the methacrylated dermal extracellular matrix hydrogel can promote wound skin healing and muscle tissue regeneration in rats with abdominal wall defect.

BACKGROUND:It has been confirmed that ferroptosis is closely related to the mechanism of various nervous diseases.However,the pathological mechanisms of ferroptosis and peripheral nerve injury need to be further studied and clarified.OBJECTIVE:To review the role and mechanism of ferroptosis in the treatment of peripheral nerve injury.METHODS:The articles related to ferroptosis and nervous system injuries were searched in CNKI and PubMed databases from database inception to May 2024.The keywords were"ferroptosis,peripheral nerve injury,antioxidant defense system,Schwann cells,macrophage,neuroinflammation,neuropathic pain"in Chinese and English,respectively.Sixty eligible articles were finally included for review.RESULTS AND CONCLUSION:The occurrence of ferroptosis is closely related to abnormal intracellular iron metabolism,reactive oxygen species accumulation and lipid peroxidation.Ferroptosis occurs in both Schwann cells and macrophages after peripheral nerve injury,leading to changes in the microenvironment and further inducing diseases such as neuroinflammation and neuropathic pain.Increasing studies have shown that nerve injury is closely related to ferroptosis,and inhibition of ferroptosis can promote tissue repair and functional recovery after peripheral nerve injury.Therefore,it is of great significance to study the mechanism underlying the occurrence and regulation of ferroptosis after peripheral nerve injury.Current research on the role and regulation of ferroptosis after peripheral nerve injury is still in its infancy,and more in-depth studies are needed to provide more strategies to promote repair after peripheral nerve injury.

Objective To explore the application value of predictive model based on nutritional status combined with clinical data in infectious complications after radical gastrectomy for gastric canc-er.Methods The clinical data on 394 gastric cancer patients who underwent radical gastrectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2017 to July 2024 were retrospec-tively collected.According to whether the patients developed infection after surgery,they were divided into infection group(n=73)and non-infection group(n=321)based on whether they developed postoperative infections or not.The least absolute shrinkage and selection operator(LASSO)method was used to obtain the optimal related features associated with infectious complications after radical gas-trectomy for gastric cancer.Multivariate Logistic regression analysis was conducted to screen for risk factors of infectious complications after radical gastrectomy.R software was used to randomly select 70％of data as training set(for establishing the nomogram model)and 30％of data as test set.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve,Bootstrap sampling validation,and decision curve analysis(DCA)were used to assess the value of the predictive model.Results of the 394 gastric cancer patients,73 developed postoperative infectious complications,in-cluding 53.42％with lung infections,17.81％with intra-abdominal infections,16.44％with uri-nary tract infections,and 12.33％with wound infections.Age,diabetes mellitus,preoperative nu-tritional risk,high preoperative PIV,combined organ resection,and prolonged operation time were identified as risk factors for infectious complications after radical gastrectomy(P＜0.05).In the training set,the AUC of the nomogram model was 0.898,and the AUC validated in the test set was 0.891.Bootstrap sampling validation with 1,000 iterations showed that the average errors between the predicted probabilities and actual values in the training and test sets were 0.019 and 0.024,re-spectively.DCA results indicated that the model had clinical utility.Conclusion Infectious com-plications after gastrectomy for gastric cancer are common,and the predictive model based on nutri-tional assessment combined with clinical data has high value in predicting the risk of infectious com-plications after gastrectomy.

Objective:To evaluate the effect of sevoflurane on mitochondrial-associated endoplasmic reticulum membranes (MAMs) in mouse microglia and the relationship with silent information regulator-related enzyme 3 (SIRT3)/adenosine triphosphatase family protein 3A (ATAD3A) signaling pathway.Methods:After normal culture of mouse microglia (BV-2 cell line), the cells were divided into 4 groups ( n=33 each) by a random number table method: empty adenovirus-control group (group C), empty adenovirus-sevoflurane exposure group (group Sev), SIRT3 overexpression adenovirus-control group (group SIRT3 + C) and SIRT3 overexpression adenovirus-sevoflurane exposure group (group SIRT3 + Sev). The cells were infected with SIRT3 overexpression adenovirus 100 pmol/well in SIRT3+ C group and SIRT3+ Sev group and with empty adenovirus 100 pmol/well in C group and Sev group. After 48 h of infection, the cells were routinely cultured for 48 h in C group and SIRT3+ C group, the cells were incubated with 3% sevoflurane for 2 h, once a day for 3 consecutive days, followed by routine culture for 48 h in Sev group and SIRT3+ Sev group. The contents of mitochondrial Ca 2+ and reactive oxygen species (mtROS) were measured by flow cytometry. The mitochondrial membrane potential (MMP) was measured by JC-1 probe. The mitochondrial ATP content was measured by luciferase luminescence method. The expression of SIRT3 was detected by Western blot. The expression of acetylated ATAD3A was detected by immunoprecipitation. The co-localization of endoplasmic reticulum and mitochondria was determined by confocal fluorescence microscopy, and the Manders co-localization coefficient was calculated to evaluate the development of MAMs. Results:Compared with group C, the contents of mitochondrial Ca 2+ and mtROS were significantly increased, the contents of MMP and mitochondrial ATP were decreased, the expression of SIRT3 was down-regulated, the expression of acetylated ATAD3A was up-regulated, and the development of MAMs was increased in group Sev ( P<0.05). Compared with Sev group, the contents of mitochondrial Ca 2+ and mtROS were significantly decreased, the contents of MMP and mitochondrial ATP were increased, the expression of SIRT3 was up-regulated, the expression of acetylated ATAD3A was down-regulated, and the development of MAMs was decreased in SIRT3 + Sev group ( P<0.05). Compared with SIRT3+ C group, the contents of mitochondrial Ca 2+ and mtROS were significantly increased, the contents of MMP and mitochondrial ATP were decreased, the expression of SIRT3 was down-regulated, the expression of acetylated ATAD3A was up-regulated, and the development of MAMs was increased in SIRT3+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane induces mitochondrial dysfunction in mouse microglia may be related to the inhibition of SIRT3/ATAD3A signaling pathway, leading to excessive development of MAMs.

(rsFC)and their relationship with negative symptoms in schizophrenia patients with predominant negative symptoms(PNS).Methods Fifty-four schizophrenia patients with PNS and sixty-one healthy controls underwent resting-state functional magnetic resonance imaging(fMRI)scans.Data were collected on general demographic information,the Positive and Negative Syndrome Scale(PANSS),the Scale for the Assessment of Negative Symptoms(SANS),and the Temporal Experience of Pleasure Scale(TEPS).Twelve striatal subregions were selected as regions of interest(ROIs)to analyze the rsFC between each ROI and whole-brain voxels.The rsFC values of areas with significant differences were extracted for Pearson correlation analysis with negative symptoms.Results Compared with healthy controls,schizophrenia patients with PNS exhibited decreased rsFC between the right dorsal caudal putamen(DCP)and right insula,left middle frontal gyrus(MFG),right median cingulate and paracingulate gyri(MCC);between the left DCP and right putamen,left insula,left MFG;between the right dorsal rostral putamen(DRP)and bilateral MFG,left insula,right MCC;between the left DRP and right insula,left rolandic operculum;between the right ventral rostral putamen(VRP)and bilateral putamen,left MFG,right MCC;between the left VRP and right insula,left putamen,bilateral MFG,right MCC,left inferior parietal gyrus,excluding supramarginal and angular gyri.Decreased rsFC was also observed between the left ventral caudate/nucleus accumbens(inferior)and right insula,left anterior cingulate cortex,supracallosal,bilateral precuneus(a threshold of P<0.001 in voxel-level with P<0.05 in cluster-lever,corrected for family-wise error,PFWE<0.05/12=0.004).No regions showed increased rsFC in schizophrenia patients with PNS relative to healthy controls.And no significant correlations were found between striatal rsFC and negative symptoms(PBonferroni>0.05).Conclusion Schizophrenia patients with PNS exhibited widespread cortical-striatal functional connectivity abnormalities,particularly reduced rsFC between the putamen and the MFG,MCC and insula.

Objective:To investigate the relationship of several adiposity-related anthropometric parameters, including BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP) and indoles in plasma with the incidence of atherosclerotic cardiovascular disease (ASCVD) in adults in China.Methods:In China Kadoorie Biobank (CKB) study, blood samples were collected from 2 183 participants in the first resurvey in 2008 to detect indoles. Participants' body weight, body height, WC, hip circumference, and BFP were measured at baseline survey in 2004 and resurvey in 2008, the BMI and WHR were calculated with standardized methods. The long-term follow-up of all participants started from the completion of the resurvey in 2008 until the occurrence of incident ASCVD, death, loss to follow-up or until December 31, 2018. CKB ascertained outcome status (incident ASCVD) through death and disease registries and national health insurance databases, supplemented by active follow-up. Multivariate linear regression model was used to estimate the associations of anthropometric measurements at baseline survey and the first resurvey, and changes in these measurements with 3 indoles [indole, indole-3-acetic acid (IAA), and indole-3-propionic acid (IPA)]. Cox proportional hazard regression model was used to estimate the associations between indoles and the risk for ASCVD.Results:Anthropometric measurements at baseline survey or the first resurvey were negatively associated with plasma IPA level. The regression coefficient ( β) of baseline BMI (per 1.0 kg/m 2) with 0.1 standard deviation ( SD) IPA was -0.23 (95% CI: -0.36 - -0.10) (false discovery rate=0.004). After adjusting for baseline BMI, the β of baseline WC, WHR and BFP with 0.1 SD IPA were -0.09 (95% CI: -0.18 - -0.01), -0.12 (95% CI: -0.19 - -0.05), and -0.20 (95% CI: -0.32 - -0.08), respectively. The annual change in BMI (difference between BMI in 2008 and 2004 divided by the time interval) was associated with indole and IAA, with β of 1.40 (95% CI: 0.58 - 2.21) and -1.07 (95% CI: -1.91 - -0.23), respectively, at each 0.1 increase of SD. Over a median ( Q1, Q3) follow-up of 10.46 (10.36, 10.53) years after 2008 resurvey, 236 cases of ASCVD were recorded. IAA and IPA levels were negatively associated with the risk for ASCVD, with hazard ratios for one SD increase of IAA and IPA of 0.87 (95% CI: 0.76 - 0.99) and 0.84 (95% CI: 0.73 - 0.96), respectively. Conclusions:Our results suggested that anthropometric measurements and their changing trends affect the levels of plasma imicrobial tryptophan metabolite levels, decreased levels of IAA and IPA levels are associated with increased risk of ASCVD and indoles in plasma including IPA and IAA might be the mediating factors for adiposity-induced ASCVD.

Objective:To analyze the prospective associations between liver biomarkers and mortality among Chinese middle-aged and elderly populations and to evaluate the mortality risk predictive value.Methods:A total of 22 758 participants from the 3 rd resurvey of the China Kadoorie Biobank were included. Cox proportional hazard models were used to analyze the prospective associations of 5 liver biomarkers with mortality. These liver biomarkers included two liver imaging biomarkers (liver fat attenuation parameter, liver stiffness measurement) and three serum liver enzyme biomarkers [gamma-glutamyl transferase (GGT), ALT, and AST]. Restricted cubic spline was used to assess the nonlinear associations between biomarkers and mortality. The area used the receiver operating characteristic curve (AUC) to evaluate the predictive ability of the models after incorporating liver biomarkers into traditional prediction models for mortality. Results:The mean age of the participants was (65.2±9.1) years, with a median follow-up of 1.5 years, during which 307 deaths occurred. Compared to individuals without hepatic steatosis, those with severe hepatic steatosis had a 79% higher risk of mortality, with a HR of 1.79 (95% CI: 1.06-3.03). Compared to individuals without hepatic fibrosis, those with advanced fibrosis and cirrhosis had higher mortality risks of 48% and 91%, respectively (both P<0.05). For each standard deviation increase in GGT, the mortality risk increased by 10% ( HR=1.10, 95% CI: 1.05-1.15), with the positive association plateauing at higher GGT levels. AST exhibited a U-shaped association with mortality risk. The AUC of the prediction model adding liver biomarkers into traditional prediction factors was 0.718 (95% CI: 0.679-0.757), with an increase of 0.030 ( P<0.001) compared with the traditional model. Conclusions:Severe hepatic steatosis, higher levels of hepatic fibrosis, and elevated GGT levels are significantly associated with higher mortality risk. AST shows a U-shaped nonlinear association with mortality risk. Incorporating liver biomarkers into traditional risk prediction models enhance the ability to predict mortality.

Objective:To evaluate the association between body mass index (BMI) and bone mineral density of calcaneus in adults.Methods:Data of the second resurvey of China Kadoorie Biobank study from Tongxiang of Zhejiang Province were used. A total of 2 896 participants aged 44-84 years were included in the final analysis. Overweight was defined as 23.0 kg/m 2≤BMI<25.0 kg/m 2, and obesity was defined as BMI ≥25.0 kg/m 2 based on the criteria recommended by WHO/West Pacific Region. Multiple linear regression model was used to evaluate the association between BMI and calcaneus bone mineral density. Restricted cubic splines were used to investigate the dose-response relationship between BMI and calcaneus bone mineral density. Results:The calcaneus bone mineral density in the study subjects were as follow ( x± SE): the broadband ultrasound attenuation was (109.4±12.1) dB/MHz, the speed of ultrasound was (1 545.9±33.8) m/s, and the stiffness index was 85.7±15.8. After adjusting for socio-demographic factors, lifestyle, waist circumference, diabetes and hypertension prevalence, BMI was positively associated with calcaneus stiffness index in non-overweight and non-obese adults, with β of 2.30 (95% CI: 1.11-3.49) for men ( P<0.001) and 1.08 (95% CI: 0.38-1.78) for women ( P=0.003), respectively. In addition, BMI was positively associated with calcaneus stiffness index in overweight and obese women ( β=0.90, 95% CI: 0.38-1.42) ( P<0.001), and null association was found in overweight and obese men ( β=0.06, 95% CI: -0.92-1.04) ( P=0.900). Restricted cubic spline model showed a nonlinear dose-response relationship between BMI and calcaneus stiffness index. Conclusion:Non-linear association was found between BMI with calcaneus bone mineral density in adults.

Objective:To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults.Methods:This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models.Results:The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95% CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model ( P<0.001). Conclusions:Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.

Objective:To describe the prevalence of preserved ratio impaired spirometry (PRISm) in participants from the China Kadoorie Biobank (CKB) and explore the influencing factors.Methods:The CKB project conducted the baseline survey, the first and the second resurvey in 2004-2008, 2008, and 2013-2014, respectively. Based on the lung function tests, the participants were categorized into three groups: regular, PRISm, and airflow obstruction. The prevalence of PRISm was reported by gender, age, and region at the baseline survey. The secular trend in the prevalence of PRISm was described during the three surveys. Finally, we used the multiple logistic regression model to examine the factors related to PRISm in the baseline survey.Results:After standardization for gender, age, and region according to the sixth national census data in 2010, the overall prevalence of PRISm and airflow obstruction among the 434 760 participants at baseline was 24.8% and 6.1%, respectively. The prevalence of PRISm was higher in rural (25.4%) than that in urban areas (24.3%). Of the 10 study regions, Gansu had the highest prevalence of PRISm (56.0%), while Henan had the lowest (15.4%). After standardization for gender, age, and region according to the baseline population, the prevalence of PRISm decreased from 24.9% at baseline to 15.7% in the second resurvey, and the prevalence of airflow obstruction increased from 5.9% to 21.4%. Unmarried status, current smoking, using solid fuels for cooking, low body weight, being overweight, obesity, and central obesity were associated with an increased risk of PRISm. In contrast, higher education attainments, increased household income, and maintaining a specific degree of physical activity were associated with a reduced risk of PRISm.Conclusions:The prevalence of PRISm was high in adults aged 40 years and above in China, and it varied by sociodemographic and lifestyle factors.