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.

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 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 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 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.

Objective:To explore the impacts of smoking on the need for respiratory support and mortality in patients hospitalized with pneumonia.Methods:A total of 24 367 patients hospitalized with pneumonia from 2009 to 2017 in the China Kadoorie Biobank, were included. Smoking status was self-reported, and data regarding respiratory support during hospitalization and mortality during follow-up were obtained from medical claims and death registries, respectively. OR, HR, and 95% CI were calculated and adjusted for potential confounders using logistic regression models and Cox proportional hazards regression models, respectively. Results:Among males, current smokers or those who quit smoking due to illness had higher risks of requiring respiratory support ( OR=1.15, 95% CI: 1.03-1.29), 1-year mortality ( HR=1.66, 95% CI: 1.32-2.08), and 5-year mortality ( HR=1.32, 95% CI: 1.13-1.54) following pneumonia hospitalization compared to nonsmokers. Male smokers who started smoking at a younger age or with longer smoking duration had the highest mortality risks (trend test both P<0.05). Female current smokers or those who quit smoking due to illness had higher risks of 1-year mortality ( HR=1.62, 95% CI: 1.17-2.23) and 5-year mortality ( HR=1.33, 95% CI: 1.06-1.67). We found no statistically significant difference in 90-day mortality between current smokers/those who quit smoking due to illness and nonsmokers. Conclusions:Smoking was associated with higher risks of requiring respiratory support and mortality in patients hospitalized with pneumonia, especially among males and heavy smokers. These findings highlight the need for targeted strategies to promote smoking cessation in patients hospitalized with pneumonia.

Objective:To identify individuals with accelerated aging under the frailty index (FI) as a proxy indicator of biological age, and to investigate the associations of age at menarche, age at menopause, and reproductive lifespan with frailty status and multi-timepoint FI trajectories among Chinese adult women.Methods:The current study included 302 471 women from the China Kadoorie Biobank 2004-2008 baseline survey data. Their age at menarche and menopause were self-reported, and the duration of reproductive lifespan was calculated by subtracting the two ages. The baseline FI was constructed using 28 baseline variables, including diseases, symptoms, and anthropometric measurements. Frailty status was categorized into three groups: non-frail (FI≤0.10), pre-frail (0.10

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the relationship between individual and combined exposure to ambient air pollutants and vitamin D, as well as the potential role of ultraviolet radiation (UVR) in mediating the relationships.Methods:This study included 6 967 participants from the China Kadoorie Biobank, whose baseline (2004-2008) blood 25-hydroxyvitamin D had been tested. The average monthly concentrations of pollutants (PM 2.5, PM 10, NO 2, O 3) and the UVR estimates in the month of blood sample collection were derived from the ChinaHighAirPollutants and ultraviolet datasets covering China, respectively. Linear models and multinomial logistic regression models were used to analyze the associations of each air pollutant with vitamin D concentrations and groups. Principal component analysis integrated with quantile-based g-computation was applied to evaluate the co-effects and relative contribution weights of air pollutants. Mediation analyses were performed to investigate the potential role of UVR. Results:PM 2.5, PM 10, NO 2, and O 3 were individually associated with vitamin D concentrations, as well as vitamin D groups: insufficiency (20-30 ng/ml) and deficiency (<20 ng/ml). For each 10 μg/m3 increase in monthly PM 2.5, PM 10, NO 2, and O 3, the percentage changes (95% CIs) in vitamin D concentrations were -1.71% (-2.16% - -1.26%), -1.30% (-1.60% - -1.00%), -3.77% (-4.60% - -2.93%), and 1.27% (0.91%-1.63%), respectively, with corresponding ORs (95% CIs) for vitamin D deficiency of 1.17 (1.06-1.29), 1.12 (1.05-1.19), 1.66 (1.38-2.00), and 0.81 (0.74-0.89). The mixture of the first principal component of PM 2.5 and PM 10 (PM), along with NO 2 and O 3, was negatively correlated with vitamin D. The percentage change (95% CI) in vitamin D concentrations for a one-quintile increase in the mixture was -2.20% (-3.56%- -0.82%), with NO 2 contributing the most (83%), followed by PM (17%). UVR-mediated association was 12.2% (95% CI：2.5%-23.0%) for PM 2.5 and 4.9% (95% CI：2.2%-8.0%) for PM 10 with vitamin D concentrations, respectively. Conclusion:Higher concentrations of particulate matter, NO 2, and a mixture of air pollutants were associated with lower vitamin D concentrations in Chinese adults, with reduced UVR acting as a partial mediator in the particulate matter-vitamin D relationship.