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.

Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Objective:To explore mechanism of Caspase-11/GSDMD non-classical cell pyroptosis pathway in inflammatory response of RAW264.7 monocyte macrophages induced by ricin toxin.Methods:Cell pyroptosis model induced by LPS+Nigericin was used as a positive control,and cells were induced with 40 ng/ml and 80 ng/ml of ricin toxin for 8 hours.Cell release of lactate dehydro-genase(LDH)was measured by LDH cell release assay;cell viability was assessed by flow cytometry(Annexin Ⅴ/PI double staining);gene expressions of Caspase-11,GSDMD,IL-1β and IL-18 were measured by RT-qPCR;protein levels of Caspase-11 and GSDMD were measured by Western blot;secretion levels of inflammatory cytokines IL-1β and IL-18 in cell supernatant were measured by ELISA.Results:Compared with normal control group,RAW264.7 cells treated with ricin toxin showed swelling,cell membrane rupture,significantly increased LDH release(P<0.001),significantly increased pyroptosis rate(P<0.001),significantly increased expression of pyroptosis-related genes Caspase-11,GSDMD,IL-1β and IL-18(P<0.05),significantly increased protein expressions of Caspase-11 and GSDMD(P<0.05),and significantly increased secretion levels of IL-1β and IL-18 in cell supernatant(P<0.05).Results of ricin toxin treatment group were consistent with LPS+Nigericin cell pyroptosis positive control group.Conclu-sion:Ricin toxin may induce cell pyroptosis in RAW264.7 cells through Caspase-11/GSDMD non-classical pathway,thereby promoting inflammatory response.

Objective:To construct an indicator system for entrustable professional activities (EPAs) in the general practice enhancement stage of pediatric specialist physician training.Methods:A draft indicator system for EPAs in the general practice enhancement stage of pediatric physician training was developed through core EPAs working group discussion, literature review, nominal group discussion, and expert consultation. Subsequently, the indicator system was preliminarily implemented and revised.Results:The core EPAs working group consisted of nine specialist physician trainers. In the initial brainstorming stage, a "potential list" of 30 activities was established. After literature review and collation, the draft indicator system included eight EPAs. Through nominal group discussion, the connotation of the draft was enriched, and the importance of the EPAs was ranked and modified. Finally, through expert consultation, the EPAs for the general practice enhancement stage of pediatric specialist physician training were determined. These included basic operations for the treatment of critically ill children, identification and management of critical illnesses, referral of critically ill children, perioperative management, in-hospital consultation, medical and teaching management and system improvement, doctor-patient communication and dispute handling, and response to public health events. During the preliminary implementation stage, a total of nine specialist physicians who participated in the training were evaluated. Based on the problems found in the pre-evaluation, the indicators of EPAs were revised, and a corresponding curriculum training system was developed.Conclusions:Through multiple rounds of nominal group discussion and expert consultation, the indicator system for EPAs in the general practice enhancement stage of pediatric specialist physician training was formulated. The system was preliminarily implemented and revised, and a curriculum system was constructed.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

AIM:To investigate the biological functions and molecular mechanisms of long noncoding RNA LINC01615 in head and neck squamous cell carcinoma(HNSCC)cells.METHODS:Transcriptome sequencing data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to analyze the expres-sion level of LINC01615 in HNSCC cells and its correlation with patient survival.RT-qPCR was used to detect the expres-sion levels of LINC01615 in HNSCC and normal control cells.An siRNA-mediated LINC01615 knockdown HNSCC cell model was established,and high-content screening cell counting,ATP and CCK8 assays were performed to analyze cell proliferation.Transwell assays were conducted to assess cell migration and invasion.Bioinformatics analysis was em-ployed to predict potential target genes of LINC01615 and the biological processes and signaling pathways involved.RT-qPCR and Western blot were used to validate the regulatory effect of LINC01615 on the candidate target gene TEAD2.Transcriptome data from TCGA and GEO databases were analyzed to determine the expression pattern of TEAD2 in HN-SCC.Functional cell experiments were performed to investigate the impact of TEAD2 knockdown on HNSCC proliferation,migration,and invasion.Rescue experiments were conducted to examine whether LINC01615 influenced the malignant phenotypes(proliferation,migration,and invasion)of HNSCC cells by regulating TEAD2 expression.RESULTS:The expression levels of LINC01615 were significantly higher in HNSCC tissues and cells than those in normal control tissues and cells,respectively(P<0.01).Knockdown of LINC01615 significantly inhibited HNSCC proliferation,migration,and invasion(P<0.01).Bioinformatics analysis identified 134 candidate target genes of LINC01615,which were primarily en-riched in tumor-related biological processes and signaling pathways,including angiogenesis,regulation of endothelial cell proliferation,regulation of cell migration,HPV infection,Hippo signaling pathway,and PI3K-Akt signaling pathway.Knockdown of LINC01615 led to a significant decrease in TEAD2 expression in HNSCC cells(P<0.01).Functional cell studies demonstrated that TEAD2 knockdown suppressed HNSCC proliferation,migration,and invasion,whereas TEAD2 overexpression reversed the inhibitory effects of LINC01615 knockdown on these malignant phenotypes.CONCLUSION:LINC01615 is upregulated in HNSCC tissues and cells,functioning as an oncogene.Mechanistic studies reveal that LINC01615 promotes HNSCC proliferation,migration,and invasion by upregulating TEAD2,a key transcription factor in the Hippo signaling pathway.These findings may provide a novel potential biomarker for the clinical diagnosis and treat-ment of HNSCC.

Objective To investigate the changes in the concentration of endothelial cell-specific molecule-1(ESM-1)in cerebrospinal fluid during the acute phase of patients with moderate to severe traumatic brain injury(TBI)and its relationship with injury severity and outcomes.Methods Eighty-four patients with moderate to severe TBI who underwent ventriculostomy for intracranial pressure(ICP)monitoring at Department of Neurosurgery,Jinshan Hospital,Fudan University from Jan 2020 to Dec 2023 were selected as the study subjects,and their clinical data were collected.Based on the Glasgow Coma Scale(GCS)upon admission,TBI patients were divided into moderate TBI group(GCS 9-12,n=48)and severe TBI group(GCS 3-8,n=36).According to the Glasgow Outcome Scale(GOS)at three months post-injury,the moderate to severe TBI patients were categorized into poor outcome group(GOS 1-3)and good outcome group(GOS 4-5).Patients were also classified based on ICP monitoring values into a normal ICP group(ICP≤15 mmHg),a mildly elevated ICP group(15 mmHg