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.

Objective:To analyze the relationship between serum GATA binding protein-3(GATA3)and eosinophilic cationic protein(ECP)and lung function indexes in children with obliterated bronchiolitis and their predictive value for poor prognosis.Methods:96 children with bronchiolitis obliterans admitted to our hospital from January 2022 to July 2024 were divided into mild group(34 cases)and moderate to severe group(62 cases)according to their severity.Serum GATA3,ECP levels and lung function indexes were detected in the two groups,and Pearson correlation was used to analyze the correlation between serum GATA3,ECP levels and lung function indexes.According to the levels of serum GATA3 and ECP,they were divided into high GATA3 group and low GATA3 group,high ECP group and low ECP group.The incidence of adverse prognosis in different groups was compared.Area under ROC curve(AUC)was used to evaluate the predictive efficacy of serum GATA3 combined with ECP for poor prognosis.Results:The levels of serum GATA3 and ECP in moderate and severe group were higher than those in mild group(P＜0.05).By Pearson correlation analysis,serum GATA3 and ECP levels were negatively correlated with tidal volume(VT),peak-to-expiratory volume(VPEFNE)and peak-to-time ratio(TPTEF/TE)in children with bronchiolitis obliterans(P＜0.05).The incidence of adverse prognosis in the high GATA3 group was higher than that in the low GATA3 group,and the incidence of adverse prognosis in the high ECP group was higher than that in the low ECP group(P＜0.05).ROC curve analysis showed that serum GATA3 combined with ECP had a sensitivity of 90.45％,specificity of 52.37％and AUC of 0.893 in predicting adverse prognosis of children with bronchiolitis obliterans.Conclusion:Serum GATA3 and ECP are closely related to pulmonary function indexes in children with bronchiolitis obliterans.The combined effect of GATA3 and ECP is better in predicting poor prognosis,and it has a certain suggestive role in evaluating the disease.

Patent foramen ovale(PFO)is a common congenital heart defect that has been linked to various conditions,including cryptogenic stroke,migraine with aura,and decompression sickness.With the rapid advancement of interventional cardiology,interventional treatment has become the preferred approach for PFO patients.Conventional PFO closure procedures predominantly use metallic disc occluders,which,despite their excellent surgical outcomes,come with unavoidable device-related complications.Consequently,there is an urgent need for a percutaneous PFO closure strategy that does not require the permanent implantation of an occluder,aligning with the"intervention without implantation,implantation without residue"green philosophy to address the limitations of traditional PFO occluders.Transcatheter PFO suturing represents a technique that better conforms to the anatomical and physiological requirements of PFO closure,capable of overcoming many of the device-related complications associated with conventional PFO closure,offering good safety and efficacy.This paper reviews the research advancements in transcatheter PFO suturing,aiming to provide novel perspectives for the clinical management of these conditions.

Objective To develop an objective and precise prognostic model for assessing severity and prognosis in elderly patients with community-acquired pneumonia(CAP)admitted to the emergency department.Methods A retrospective analysis was conducted on elderly patients with CAP admitted to Department of Emergency,Minhang Hospital,Fudan University between Jun 2018 and Dec 2020.With the primary outcome being the 30-day in-hospital mortality rate of elderly CAP patients,four systemic inflammatory response markers,including the neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammation index(SII)were evaluated using univariate and multivariate Logistic regression analyses.The predictive performance of different scoring systems was compared.Results A total of 421 elderly CAP cases were enrolled.The results of the multivariate Logistic regression analysis demonstrated that NLR was an independent risk factor for elderly inpatients with CAP.We combined NLR with the existing CURB-65 score for joint optimization to construct a scoring system or a clinical prognosis model,by quantifying and assigning optimal cut-off value of 11.4 for NLR,and established the NLR+CURB-65 score.The ROC curve was constructed to compare the areas under the curve of the three different scoring systems(NLR,CURB-65,and NLR+CURB-65).The area under the curve of the NLR+CURB-65 score was significantly higher than that of the CURB-65 score.Based on the optimal cut-off value of 3 for NLR+CURB-65 score,the patients were stratified into high-risk group(n=188)and low-risk group(n=233).The K-M survival curve was utilized and indicated that compared with high-risk group,low-risk group had a lower mortality rate and a higher discharge rate.Conclusion For elderly emergency hospitalized patients with CAP,the combination of NLR and CURB-65 score showed high predictive value for assessing disease severity and prognosis.

Immune checkpoint inhibitors(ICIs)represent the most widely used immunotherapeutic approach for antitumor treatment,yet the understanding of their associated hepatotoxicity remains incomplete.This article delves into and analyzes the similarities and differences among the management guidelines on ICI-related hepatotoxicity issued by the Chinese Society of Clinical Oncology(CSCO),the National Comprehensive Cancer Network(NCCN)of the United States,and the American Society of Clinical Oncology(ASCO),aiming to provide a more comprehensive management strategy for clinical practice.By reviewing and analyzing the latest guidelines,this study compares the differences and similarities in the diagnosis,assessment,grading criteria,and treatment strategies for ICI-related liver toxicity among these guidelines.The definitions and diagnostic criteria for ICI-related liver toxicity are generally consistent across different guidelines,primarily relying on the elevated levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),bilirubin,and alkaline phosphatase(ALP)for grading.Notably,the ASCO guidelines place a stronger emphasis on the assessment of symptoms of hepatic dysfunction.In terms of treatment strategies,all guidelines recommend using corticosteroids or immunosuppressants based on the toxicity grade.However,there are discrepancies in management strategies among the guidelines.Clinicians should tailor management strategies by considering the specific conditions of patients and integrating the recommendations from various guidelines.Additionally,given the current inadequate understanding of ICI-induced hepatotoxicity primarily manifested as cirrhosis in the existing guidelines,it is imperative to continuously update and refine these management guidelines as research progresses and clinical experience accumulates.

Objective:To analyze the relationship between serum GATA binding protein-3(GATA3)and eosinophilic cationic protein(ECP)and lung function indexes in children with obliterated bronchiolitis and their predictive value for poor prognosis.Methods:96 children with bronchiolitis obliterans admitted to our hospital from January 2022 to July 2024 were divided into mild group(34 cases)and moderate to severe group(62 cases)according to their severity.Serum GATA3,ECP levels and lung function indexes were detected in the two groups,and Pearson correlation was used to analyze the correlation between serum GATA3,ECP levels and lung function indexes.According to the levels of serum GATA3 and ECP,they were divided into high GATA3 group and low GATA3 group,high ECP group and low ECP group.The incidence of adverse prognosis in different groups was compared.Area under ROC curve(AUC)was used to evaluate the predictive efficacy of serum GATA3 combined with ECP for poor prognosis.Results:The levels of serum GATA3 and ECP in moderate and severe group were higher than those in mild group(P＜0.05).By Pearson correlation analysis,serum GATA3 and ECP levels were negatively correlated with tidal volume(VT),peak-to-expiratory volume(VPEFNE)and peak-to-time ratio(TPTEF/TE)in children with bronchiolitis obliterans(P＜0.05).The incidence of adverse prognosis in the high GATA3 group was higher than that in the low GATA3 group,and the incidence of adverse prognosis in the high ECP group was higher than that in the low ECP group(P＜0.05).ROC curve analysis showed that serum GATA3 combined with ECP had a sensitivity of 90.45％,specificity of 52.37％and AUC of 0.893 in predicting adverse prognosis of children with bronchiolitis obliterans.Conclusion:Serum GATA3 and ECP are closely related to pulmonary function indexes in children with bronchiolitis obliterans.The combined effect of GATA3 and ECP is better in predicting poor prognosis,and it has a certain suggestive role in evaluating the disease.

Patent foramen ovale(PFO)is a common congenital heart defect that has been linked to various conditions,including cryptogenic stroke,migraine with aura,and decompression sickness.With the rapid advancement of interventional cardiology,interventional treatment has become the preferred approach for PFO patients.Conventional PFO closure procedures predominantly use metallic disc occluders,which,despite their excellent surgical outcomes,come with unavoidable device-related complications.Consequently,there is an urgent need for a percutaneous PFO closure strategy that does not require the permanent implantation of an occluder,aligning with the"intervention without implantation,implantation without residue"green philosophy to address the limitations of traditional PFO occluders.Transcatheter PFO suturing represents a technique that better conforms to the anatomical and physiological requirements of PFO closure,capable of overcoming many of the device-related complications associated with conventional PFO closure,offering good safety and efficacy.This paper reviews the research advancements in transcatheter PFO suturing,aiming to provide novel perspectives for the clinical management of these conditions.

Objective To develop an objective and precise prognostic model for assessing severity and prognosis in elderly patients with community-acquired pneumonia(CAP)admitted to the emergency department.Methods A retrospective analysis was conducted on elderly patients with CAP admitted to Department of Emergency,Minhang Hospital,Fudan University between Jun 2018 and Dec 2020.With the primary outcome being the 30-day in-hospital mortality rate of elderly CAP patients,four systemic inflammatory response markers,including the neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammation index(SII)were evaluated using univariate and multivariate Logistic regression analyses.The predictive performance of different scoring systems was compared.Results A total of 421 elderly CAP cases were enrolled.The results of the multivariate Logistic regression analysis demonstrated that NLR was an independent risk factor for elderly inpatients with CAP.We combined NLR with the existing CURB-65 score for joint optimization to construct a scoring system or a clinical prognosis model,by quantifying and assigning optimal cut-off value of 11.4 for NLR,and established the NLR+CURB-65 score.The ROC curve was constructed to compare the areas under the curve of the three different scoring systems(NLR,CURB-65,and NLR+CURB-65).The area under the curve of the NLR+CURB-65 score was significantly higher than that of the CURB-65 score.Based on the optimal cut-off value of 3 for NLR+CURB-65 score,the patients were stratified into high-risk group(n=188)and low-risk group(n=233).The K-M survival curve was utilized and indicated that compared with high-risk group,low-risk group had a lower mortality rate and a higher discharge rate.Conclusion For elderly emergency hospitalized patients with CAP,the combination of NLR and CURB-65 score showed high predictive value for assessing disease severity and prognosis.

Immune checkpoint inhibitors(ICIs)represent the most widely used immunotherapeutic approach for antitumor treatment,yet the understanding of their associated hepatotoxicity remains incomplete.This article delves into and analyzes the similarities and differences among the management guidelines on ICI-related hepatotoxicity issued by the Chinese Society of Clinical Oncology(CSCO),the National Comprehensive Cancer Network(NCCN)of the United States,and the American Society of Clinical Oncology(ASCO),aiming to provide a more comprehensive management strategy for clinical practice.By reviewing and analyzing the latest guidelines,this study compares the differences and similarities in the diagnosis,assessment,grading criteria,and treatment strategies for ICI-related liver toxicity among these guidelines.The definitions and diagnostic criteria for ICI-related liver toxicity are generally consistent across different guidelines,primarily relying on the elevated levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),bilirubin,and alkaline phosphatase(ALP)for grading.Notably,the ASCO guidelines place a stronger emphasis on the assessment of symptoms of hepatic dysfunction.In terms of treatment strategies,all guidelines recommend using corticosteroids or immunosuppressants based on the toxicity grade.However,there are discrepancies in management strategies among the guidelines.Clinicians should tailor management strategies by considering the specific conditions of patients and integrating the recommendations from various guidelines.Additionally,given the current inadequate understanding of ICI-induced hepatotoxicity primarily manifested as cirrhosis in the existing guidelines,it is imperative to continuously update and refine these management guidelines as research progresses and clinical experience accumulates.