ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Based on the opening-closing-pivot theory， this paper proposes that adolescent bipolar disorder is closely associated with taiyin （太阴）， shaoyang （少阳）， and jueyin （厥阴） channels. The principal pathogenesis involves dysfunction of the opening function of taiyin， impaired pivot function of shaoyang， and failure of the closing function of jueyin. Accordingly， the therapeutic principles include regulating taiyin to restore the ascending and descending movement of qi， harmonizing shaoyang to facilitate the pivot mechanism， and balancing yin and yang to reinforce the closing and storing function of jueyin. In clinical practice， Yihuang Powder （益黄散） and Tongxie Important Formula （痛泻要方） are commonly prescribed to regulate the qi movement of taiyin and restore its ascending and transporting functions， while Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散） are used to regulate the shaoyang pivot， and Wumei Pill （乌梅丸）， Danggui Sini Decoction （当归四逆汤）， and Huanglian Ejiao Decoction （黄连阿胶汤） combined with Shaoyao Gancao Decoction （芍药甘草汤） are employed to harmonize the jueyin closing mechanism. In addition， traditional daoyin （导引） exercise yi jin jing （易筋经） is incorporated to simultaneously regulate the body and mind by guiding internal regulation through external movement， thereby calming the body and tranquilizing the mind.

Based on the opening-closing-pivot theory， this paper proposes that adolescent bipolar disorder is closely associated with taiyin （太阴）， shaoyang （少阳）， and jueyin （厥阴） channels. The principal pathogenesis involves dysfunction of the opening function of taiyin， impaired pivot function of shaoyang， and failure of the closing function of jueyin. Accordingly， the therapeutic principles include regulating taiyin to restore the ascending and descending movement of qi， harmonizing shaoyang to facilitate the pivot mechanism， and balancing yin and yang to reinforce the closing and storing function of jueyin. In clinical practice， Yihuang Powder （益黄散） and Tongxie Important Formula （痛泻要方） are commonly prescribed to regulate the qi movement of taiyin and restore its ascending and transporting functions， while Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散） are used to regulate the shaoyang pivot， and Wumei Pill （乌梅丸）， Danggui Sini Decoction （当归四逆汤）， and Huanglian Ejiao Decoction （黄连阿胶汤） combined with Shaoyao Gancao Decoction （芍药甘草汤） are employed to harmonize the jueyin closing mechanism. In addition， traditional daoyin （导引） exercise yi jin jing （易筋经） is incorporated to simultaneously regulate the body and mind by guiding internal regulation through external movement， thereby calming the body and tranquilizing the mind.

Metabolic dysfunction-associated fatty liver disease is a common chronic liver disease worldwide， and its incidence rate continues to rise. The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors. Necroptosis is an inflammatory form of death with both the morphological characteristics of necrosis and the signaling mechanism of apoptosis， and the core of necroptosis lies in the receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like pseudokinase signaling axis. This pathway directly leads to the death of hepatocytes， and it triggers an inflammatory response and promotes the fibrosis process by releasing damage-associated molecular patterns； the pathway is also closely associated with the metabolic reprogramming of the liver. This review summarizes the activation mechanism of necroptosis in metabolic dysfunction-associated fatty liver disease， analyzes its effect on liver inflammation， fibrosis， and metabolism， and explores its therapeutic strategies and application prospects.

Objective To compare the long-term prognosis of elderly patients with stageⅠnon-small cell lung cancer (NSCLC) after lobectomy or segmentectomy. Methods Data of elderly patients with stageⅠNSCLC between 2010 and 2020 were collected from the SEER database. According to the resection method, patients were divided into a lobectomy group and a segmentectomy group. The overall survival (OS) and lung cancer-specific survival (LCSS) of the two groups were compared by propensity score matching (lobectomy : segmentectomy=2 : 1). Results A total of 9990 patients were included, including 5840 (58.46%) females and 4150 (41.54%) males, with an average age of (70.48±6.47) years. Among them, 9029 patients were in the lobectomy group and 961 patients were in the segmentectomy group. After propensity score matching, a total of 2883 patients were matched, including 1 922 patients in the lobectomy group and 961 patients in the segmentectomy group. There was no statistical difference in baseline data between the two groups (P>0.05). The 10-year OS rate and LCSS rate of the lobectomy group were higher than those of the segmentectomy group (OS: 51.15% vs. 38.35%, P<0.01; LCSS: 79.68% vs. 71.52%, P<0.01). Subgroup analysis showed that the survival advantage of lobectomy was found in patients aged 60-<70 years and ≥80 years; for patients 70-<80 years, there was no statistical difference in OS or LCSS between the two surgical methods (P>0.05). In addition, for patients with tumor diameter ≤2 cm (stages ⅠA1-ⅠA2), lymph node dissection number≥10, and receiving adjuvant radiotherapy/chemotherapy, segmentectomy could also achieve a similar prognosis as lobectomy. Conclusion Overall, for elderly patients with stage ⅠNSCLC, lobectomy can achieve better OS and LCSS. However, individual differences, tumor characteristics, and perioperative treatment plans should be considered comprehensively to determine the surgical method for elderly patients with stageⅠNSCLC.

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*

Objective To explore the correlation between gallbladder stones and small intestinal bacterial overgrowth(SIBO).Methods A retrospective analysis was conducted on the clinical data of 393 patients who attended the Department of Gastroenterology of the Sixth Medical Center of Chinese PLA General Hospital from January 2021 to September 2023.They were divided into gallbladder stones group(n=190)and control group(n=203)based on the presence of gallbladder stones.Their general clinical data,laboratory test results,and abdominal symptoms were compared.Multivariate logistic regression was used to analyze the risk factors for gallbladder stones.Additionally,the total population was divided into SIBO-positive group(n=239)and SIBO-negative group(n=154),and their clinical characteristics were analyzed by logistic regression to explore the risk factors for SIBO.Results Univariate analysis revealed that gallbladder stones group had a higher rate of age,body mass index(BMI),fasting plasma glucose(FPG),glutaminase levels,prevalence of hypertension,diabetes,coronary heart disease,non-alcoholic fatty liver disease,gallbladder polyps,and SIBO,as well as a higher prevalence of CH4-positive and H2-positive in SIBO group than control group(P＜0.05).In terms of abdominal symptoms,the incidence of bad breath(48.4%vs.35.5%),dyspepsia(38.4%vs.28.6%),abdominal pain(30.5%vs.14.8%),bloating(42.1%vs.28.6%),diarrhea(20.5%vs.7.4%),and more exhaustion(46.8%vs.34.5%)were significantly higher in gallbladder stones group than those in control group(P＜0.05).Multivariate logistic regression analysis showed that independent positive determinants for incident gallbladder stones were age,BMI,FPG,total bilirubin(TBIL),coronary heart disease,gallbladder polyps,and SIBO.Univariate analysis revealed that age,prevalence of gallbladder stones,proportion of single stones,triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)were significantly higher in SIBO-positive group than those in SIBO-negative group(P＜0.05).Multivariate logistic regression analysis showed that the risk factors for SIBO were age,coronary heart disease,and gallbladder stones,while the protective factor for SIBO was high-density lipoprotein cholesterol(HDL-C).Conclusion There is a significant correlation between gallbladder stones and small SIBO;interventions on related factors of gallbladder stones and small SIBO may help reduce their incidence.

Objective: To investigate the molecular mechanism of NOD-like receptor(NLR) signaling pathway induced cellular focal death in mouse kidney tissues under plateau hypoxia based on transcriptomic sequencing technology. Methods: Animal models were constructed in high-altitude kidney test group(HKT group) and plain kidney control group(PKC group),and C57/BL6 mice were bred at an altitude of 4 200 m and 400 m,respectively.Kidney tissues were aseptically taken out after 30 d and used for observation of renal histopathological changes and transcriptomics sequencing,respectively,and then differentially expressed genes(DEGs) were enriched by KEGG and GO analysis.Key gene and protein expression levels were verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot analysis. Results: Hematoxylin-eosin(HE) staining showed that the renal tubules of HKT mice were disorganized,and the tubular epithelial cells were edematous with inflammatory cell aggregation.Transcriptomics sequencing analysis revealed that a total of 3 007 DEGs were identified in the HKT group,and KEGG analysis showed that DEGs were significantly enriched in the NLR signaling pathway.The mRNA expression of the key differentially expressed genes,CASP1,CASP11,GSDMD,IFI16,NAIP5,IRF9,and the downstream inflammatory factors,IL-1β and IL-18,was upregulated,and protein expression of CASP1,CASP11,and GSDMD was up-regulated. Conclusion The plateau hypoxic environment induces cellular pyroptosis by regulating the expression of NLR signaling pathway and releases downstream inflammatory factors to cause inflammatory responses.