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.

ObjectiveTo evaluate the clinical efficacy and safety of Xiaozhen Formula （消疹方） in preventing skin toxicity induced by epidermal growth factor receptor inhibitors （EGFRIs） in patients with EGFR-mutant non-small cell lung cancer （NSCLC）. MethodsA randomized， double-blind， placebo-controlled， multicenter clinical study was conducted. A total of 120 patients with EGFR-mutant NSCLC from seven centers were enrolled and randomly assigned to a treatment group （60 cases） or a control group （60 cases）. On the basis of EGFRI-targeted therapy， patients in the treatment group received Xiaozhen Formula granules， whereas those in the control group received Xiaozhen Formula placebo granules， both at 10 g twice daily for 4 consecutive weeks. The primary outcomes were the grading of skin toxicity evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events （NCI-CTCAE） version 5.0 and the incidence of rash. Secondary outcomes included the time to onset and time to resolution of the highest-grade rash， the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 （EORTC QLQ-C30） scores， the Hospital Anxiety and Depression Scale （HADS） scores， and disease control rate， together with safety assessments. ResultsBased on the full analysis set （FAS）， the incidence of skin toxicity in the treatment group was 18.33% （11/60）， significantly lower than 45.00% （27/60） in the control group （P＜0.01）， with the highest severity of skin toxicity in both groups was grade 2. Among patients who developed rash， the resolution rate in the treatment group was 90.91% （10/11）， higher than that 33.33% （9/27） in the control group. The median time to resolution was 15 days （95%CI： 8-17 days） in the treatment group and it was not reached in the control group； the distribution of time to resolution differed significantly between groups （P＜0.001）. After treatment， the treatment group had higher EORTC QLQ-C30 functional scale and global health status/quality-of-life scores， and lower symptom scale， single-item scores， as well as HADS-A， and HADS-D scores than the control group （P＜0.05）. In the FAS analysis， the disease control rate （DCR） was 85.0% （51/60） in the treatment group， lower than 100.0% （60/60） in the control group （P=0.003）， whereas no significant between-group difference was observed in the per-protocol set （PPS） analysis （P=0.464）. The incidence of adverse events did not differ significantly between the two groups （P＞0.05）， and no definite safety signals related to the investigational drug were observed. ConclusionXiaozhen Formula can reduce the incidence of EGFRI-induced skin toxicity， and improve the outcome of rash regression， the patients' quality of life and psychological status in EGFR-mutant NSCLC patients.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Objective To investigate the mechanism by which artesunate(ART)attenuates intestinal mucosal barrier damage in acute graft-versus-host disease(aGVHD)and the synergistic effect of ART in combination with dexamethasone(DXM)in the treatment of aGVHD mice.Methods The aGVHD mouse model was established by bone marrow haematopoietic stem cell transplantation.The mice were divided into 9 groups,including normal mice control(Ctrl),aGVHD mice(aGVHD),normal mice receiving ART[30 mg/(kg·d)],aGVHD mice receiving low-dose ART[10 mg/(kg·d)],aGVHD mice receiving medium-dose ART[30 mg/(kg·d)],aGVHD mice receiving high-dose ART[50 mg/(kg·d)],aGVHD mice receiving DXM[20 mg/(kg·d)],aGVHD mice receiving ART[30 mg/(kg·d)]and DXM[20 mg/(kg·d)],and aGVHD mice receiving ART[30 mg/(kg·d)]and halved DXM[10 mg/(kg·d)].Survival rate and clinical parameters were assessed.HE staining and Alcian blue-periodic acid-Schiff(AB-PAS)staining were used to observe the histopathological changes in the intestinal mucosa of the mice;Real-time PCR,Western blotting and immunohistochemistry were used to detect the structure of the intestinal mucosal barrier,the T cell differentiation related transcription factors and cytokines,and the key enzymes of energy metabolism.Flow cytometry was used to detect the T helper cell 17(Th17)and regulatory T cells(Treg).Results After 30 days of ART treatment,aGVHD mice showed significant relief of systemic symptoms and increase in survival rate.In aGVHD mice treated with ART,the intestinal mucosal barrier structure was restored,and the intestinal mucosal permeability was reduced.The activity of AMP-activated protein kinase(AMPK)/mTOR pathway was inhibited,and the energy metabolism pattern of T cells was dominated by fatty acid synthesis.The balance of Th17/Treg was restored due to the decrease of Th 17 and the increase of Treg.The effect of ART+DXM treatment on aGVHD mice was comparable to that of DXM treatment alone,and the survival rate of mice was higher.In particular,the recovery of the intestinal mucosal barrier function was most obvious in the mice treated with ART+half-dose DXM.Conclusion ART reduces the immune injury of allo-T cells to the intestinal mucosal barrier by recovering the Th17/Treg balance,thus maintaining the integrity of the intestinal mucosal barrier function.The synergistic effect of ART and DXM combination treatment in aGVHD mice can reduce the incidence of DXM side effects by decreasing the dosage of DXM.

Objective:To study the anti-inflammatory and protective effects of electroacupuncture on rats with cardiopulmo-nary resuscitation based on cholinergic anti-inflammatory pathway(CAP).Methods:Sixty male SD rats were randomly divided into sham operation group(Sham group),cardiopulmonary resuscitation group,electroacupuncture group,antagonist of α7-nicotinic ace-tylcholine receptor(α7nAChR)α Bungarus toxin group(αBGT group,1 μg/kg)and agonist of α7nAChR 3-(2,4-dimethoxybenzyli-dene)anabaseine(GTS-21)group(5 mg/kg),with 12 rats in each group.Model of cardiac arrest was established by inducing ventric-ular fibrillation in rats with percutaneous epicardial electrical stimulation,and routine resuscitation was performed,the defibrillation times,cardiopulmonary resuscitation duration and 72 h survival rate of rats in each group were observed and recorded.Neurological damage of rats in each group was scored(NDS score).Levels of inflammatory factors TNF-α,IL-1β and IL-6 in serum,heart,lung and brain of rats were measured by ELISA.HE staining was applied to evaluate the degree of tissue damage of heart,lung and brain tis-sues of rats in each group.Expressions of α7nAChR,NF-κB/MAPKs signal pathway related proteins in heart,lung and brain of rats in each group were detected by Western blot.Results:Compared with Sham group,the number of defibrillations,duration of cardiopul-monary resuscitation,NDS score,levels of TNF-α,IL-1β and IL-6 in serum,heart,lung and brain tissues,and NF-κB p65 protein in heart,lung and brain tissues in cardiopulmonary resuscitation group increased greatly(P<0.05),the 72 h survival rate,phosphory-lation levels of α7nAChR protein,ERK1/2,JNK and p38MAPK in heart,lung and brain tissues decreased greatly after restoration of spontaneous circulation(P<0.05),cells and neurons in the CA1 region of heart,lung and hippocampus were severely damaged.Com-pared with cardiopulmonary resuscitation group,change trend of relevant indicators in electroacupuncture group was opposite to the above,damage of cells and neurons in rat heart,lung and brain tissue was reduced(P<0.05).αBGT reduced the anti-inflammatory effect of electroacupuncture on cardiopulmonary resuscitation rats(P<0.05).GTS-21 enhanced the anti-inflammatory protection of electroacupuncture on cardiopulmonary resuscitation rats(P<0.05).Conclusion:Electroacupuncture has anti-inflammatory and pro-tective effects on cardiopulmonary resuscitation rats based on CAP,and NF-κB/MAPKs participate in α7nAChR mediated CAP.

In recent years,the incidence and mortality of heatstroke have been increasing annually alongside global warming,with a marked rise in cases exhibiting atypical symptoms.To address the increasingly complex challenges in heatstroke prevention and treatment,Heatstroke Prevention and Treatment Research Center of Chinese PLA,Expert Group of Heatstroke Prevention and Treatment of Chinese PLA,and Chinese PLA Professional Committee of Critical Care Medicine have jointly developed this guideline(2025 edition).Utilizing the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system,Appraisal of Guidelines for Research and Evaluation(AGREE)criteria,and Reporting Items for Practice Guidelines in Healthcare(RIGHT)standards,and based on the 2015 draft"Expert Consensus on the Standardized Diagnosis and Treatment of Heatstroke"and the 2019"Chinese Expert Consensus on the Diagnosis and Treatment of Heatstroke",this guideline has been crafted.This guideline provides 25 evidence-based recommendations to guide the prevention,treatment and research of heatstroke,which thoroughly covers 8 critical domains:clinical classification,pathophysiological mechanisms,clinical manifestations,diagnostic criteria,differential diagnosis,treatment protocols,rehabilitation and return to work,and prevention.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To investigate the associations of immune cells,CD8+and CD4+T cells,and high-sensitivity C-reactive protein(hs-CRP)with cognitive function,and to explore the relation-ships among immunity,chronic inflammation,and Alzheimer's disease-related cognitive impair-ment.Methods A cross-sectional study was conducted on 101 patients with primary complaints of memory decline who visited the Alzheimer's Disease Clinic of Dongzhimen Hospital from June to December 2024.Mini-Mental State Examination(MMSE)and Delayed Story Recall Task(DSR)were performed to assess their cognitive function,and according to the results,they were divided into observation group(cognitively impaired,60 cases)and control group(cognitively normal,41 cases).Peripheral blood levels of CD8+T cells,CD4+T cells,and hs-CRP were compared between the two groups.Results The observation group exhibited significantly lower total scores and scores of different dimensions of MMSE and DSR scores,but notably higher activities of daily liv-ing scores than the control group(P＜0.05,P＜0.01).Serum hs-CRP level was obviously elevated in the observation group than the control group(P＜0.05).Binary logistic regression analysis revealed that CD8+T cells(OR=0.998,95％CI:0.996-1.000,P=0.038)and body mass index(OR=0.843,95％CI:0.719-0.990,P=0.037)were protective factors,while hs-CRP(OR=2.004,95％CI:1.215-3.306,P=0.006)was an independent risk factor for cognitive impairment.Spearman's rank correlation analysis showed a significant positive correlation between hs-CRP and CD4+T cells(P=0.011),but no significant association with CD8+T cells(P＞0.05).Conclusion Chronic inflammation and immune dysregulation synergistically contribute to cogni-tive decline.Hs-CRP may serve as a potential screening biomarker for cognitive impairment in pri-mary care settings.