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.

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a significant cause of disease morbidity. One-third of patients with ASUC are steroid refractory. Rescue therapy may not successfully induce remission, necessitating colectomy. We aimed to identify predictors of rescue therapy and colectomy in ASUC assessed within 24 h of admission for early risk stratification. METHODS: We conducted a retrospective cohort study of 58 admissions for ASUC among 47 patients from August 2002 to January 2022. Serum biomarkers assessed were measured on admission. Primary outcomes were the need for rescue therapy during the same admission and colectomy within 1 year of admission. RESULTS: Rescue therapy (all with infliximab) was given in 20 (34.5%) of the admissions. Colectomy was done within 1 year for nine (15.5%) of the admissions. An elevated C-reactive protein (CRP) of >30 mg/L (relative risk [RR] 1.63), a CRP-albumin ratio of >0.85 (RR 1.63), and a composite factor of both CRP > 30 mg/L and age ≥60 years (RR 2.37) were significantly associated with the need for rescue therapy. Hypoalbuminaemia ≤ 25 g/L (RR 4.35) and the use of biologics at presentation (RR 1.54) were significantly associated with colectomy within 1 year of admission, while a CRP of ≥ 80 mg/L was a significant protective factor (RR 0.70). CONCLUSION Patients with ASUC who have elevated CRP or CRP-albumin ratio on admission should be considered at risk for steroid-refractory disease. Those with hypoalbuminaemia on admission and using biologics at presentation are more likely to require colectomy in the first year after admission for ASUC.
Humans ; Colitis, Ulcerative/therapy* ; Colectomy ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult ; C-Reactive Protein/metabolism* ; Infliximab/therapeutic use* ; Biomarkers/blood* ; Acute Disease ; Aged ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

OBJECTIVES: To identify risk factors for recurrent plastic bronchitis (PB) among children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: The clinical data of children with MPP complicated by PB who underwent bronchoscopy at Gansu Province Maternity and Child Health Hospital between July 2023 and January 2025 were retrospectively analyzed. Patients were grouped into a single-episode PB group and a recurrent PB group according to the number of PB episodes. Multivariable logistic regression was used to identify risk factors for recurrent PB. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of individual and combined predictors. RESULTS: A total of 264 children were included; 188 (71.2%) had a single episode of PB and 76 (28.8%) had recurrent PB. Multivariable logistic regression analysis showed that decreased serum albumin, atelectasis, and fever persisting beyond 72 hours after the initial bronchoscopy were significantly associated with recurrent PB (all P<0.05). The combination of these predictors yielded a sensitivity of 82.9%, specificity of 61.7%, and an area under the ROC curve of 0.777 (95%CI: 0.714-0.839), outperforming any single predictor (P<0.05). CONCLUSIONS In children with MPP complicated by PB, decreased serum albumin, the presence of atelectasis, and fever persisting beyond 72 hours after the initial bronchoscopy are associated with an increased risk of PB recurrence. In such cases, early repeat or multiple bronchoscopic interventions should be considered.
Humans ; Pneumonia, Mycoplasma/complications* ; Male ; Female ; Risk Factors ; Recurrence ; Child, Preschool ; Bronchitis/etiology* ; Child ; Retrospective Studies ; Logistic Models ; Infant ; ROC Curve ; Adolescent

OBJECTIVE: To investigate the effect of chrysophanol, a phytochemical derived from Radix et Rhizoma Rhei on HepG2 liver cancer cells. METHODS: HepG2 cell line was treated with different concentrations chrysophanol (0-100 μmol/L) for 24 h. The cell counting kit 8 assay was employed to assess cell viability. Intracellular calcium levels were examined using Fluo-4 AM and Mag-fluo-4 AM staining, followed by flow cytometry analysis. Mitochondrial membrane potential was measured with JC-1 assay kit. Additionally, the expressions of key proteins such as p-JNK, Bax, cytochrome c (Cyt C), cleaved caspase-3 (cCaspase-3), and caspase-8 were analyzed by Western blot. The inhibitory effects of chrysophanol on the invasion of cells were determined using a Transwell assay. Analysis of invasiveness was conducted by wound healing assay. RESULTS: Chrysophanol significantly reduced the proliferation of HepG2 liver cancer cells by affecting intracellular calcium distribution, diminishing mitochondrial membrane potential, and enhancing the expressions of p-JNK, Bax, Cyt C, cCaspase-3, and caspase-8 in the groups treated with 75 or 100 μmol/L chrysophanol compared to the control group (P<0.05). Additionally, 75 and 100 μmol/L chrysophanol exhibited inhibitory effects on cell migration and wound healing. CONCLUSION Chrysophanol demonstrates potential against HepG2 liver cancer cells, suggesting its potential use as a therapeutic agent for liver cancer treatment.
Humans ; Calcium/metabolism* ; Hep G2 Cells ; Liver Neoplasms/metabolism* ; Neoplasm Invasiveness ; Membrane Potential, Mitochondrial/drug effects* ; Anthraquinones/pharmacology* ; Cell Proliferation/drug effects* ; Cell Death/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Cell Survival/drug effects*

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.