Objective To investigate the correlation between gut microbiota characteristics and immunotherapy efficacy in patients with advanced microsatellite stable (MSS) advanced gastrointestinal tumors. Methods Thirty patients with advanced MSS gastrointestinal tumors, including fourteen cases of gastric cancer and sixteen cases of colorectal cancer, who were admitted from November 1, 2022, to July 31, 2025 were enrolled. All patients underwent gut microbiota testing and received corresponding interventions on the basis of the results, followed by treatment with antiangiogenic agents combined with immunotherapy. Some patients additionally received probiotics or fecal microbiota transplantation. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess potential prognostic factors. Results Among the thirty patients, no complete response was observed. Two cases of partial response (PR), twelve cases of stable disease, and sixteen cases of progressive disease were recorded. The ORR was 6.7%, and the DCR was 46.7%. The median PFS was 6.4 months, and the median OS was 8.3 months. Both PR patients were classified as having a medium risk of gut microbiota dysbiosis and exhibited a Bacteroides-dominated enterotype. Multivariate analysis indicated that tumor type, liver metastasis, and bone metastasis were potential prognostic factors for PFS and OS. Conclusion Patients with a medium risk of gut dysbiosis may exhibit a relatively favorable response to immunotherapy, suggesting that gut microbiota status could serve as a potential biomarker for predicting treatment efficacy in advanced MSS gastrointestinal tumors.

Chronic excessive alcohol consumption is a major global public health concern that severely endangers human health. Excessive alcohol intake disrupts the functions of multiple organs and systems in the human body through diverse mechanisms. The alcohol-sensitive microbiota-gut-brain axis plays a critical role in maintaining systemic homeostasis， immune maturation， and endocrine metabolism. Chronic excessive alcohol consumption not only alters the composition of the gut microbiota and the levels of its metabolites， but also compromises intestinal barrier integrity， increases intestinal permeability， and allows harmful metabolites to enter the systemic circulation， thereby triggering a variety of diseases including alcohol-related brain injury. Alcohol-related brain injury is one of the most severe consequences of unrecognized or inadequately treated alcohol use disorder （AUD）， which can lead to extensive neuronal damage and neurocognitive dysfunction. Although the potential role of the microbiota-gut-brain axis in alcohol-related brain injury has been proposed， the exact underlying mechanisms have not yet been fully elucidated. Therefore， in this review， we systematically analyze the associations among chronic excessive alcohol consumption， the microbiota-gut-brain axis， and alcohol-related brain injury， and explore the potential mechanisms underlying alcohol-induced brain damage via this axis.

Objective To explore the application of serum signal transducer and activator of transcription 3(STAT3),histone deacetylase 2(HDAC2),and developmental endothelial locus-1(Del-1)levels in the evaluation of disease severity and prognosis of children with respiratory syncytial virus pneumonia(RSVP).Methods A total of 109 children with RSVP admitted to Jiamusi Central Hospital from November 2023 to March 2025 were enrolled as the RSVP group.Based on disease severity,RSVP patients were categorized into a low-risk group(n=31),a medium-risk group(n=42),and a high-risk group(n=36).According to the prognosis after 7 days of treatment,they were divided into a favorable prognosis group(n=78)and a poor prognosis group(n=31).Additionally,109 healthy children undergoing physical examination at the same hospital during the same period were selected as the normal control group(NC group).ELISA method was used to detect serum levels of STAT3,HDAC2,and Del-1.Pearson correlation analysis was used to explore the correlations between serum STAT3,HDAC2,Del-1 levels and pulmonary function indices.Multivariate logistic regression analysis was used to explore the factors affecting the prognosis of children with RSVP.Moreover,ROC curve was used to explore the predictive value of serum STAT3,HDAC2,and Del-1 levels for the prognosis of children with RSV.Results Compared with the NC group,the RSVP group had higher serum STAT3 and HDAC2 levels,and lower serum Del-1 levels(P<0.05).Serum STAT3 and HDAC2 levels progressively increased from the low-risk group,medium risk group,to high-risk group,while the time to peak ratio(time to peak tidal expiratory flow to total expiratory time ratio,TPTEF/TE),peak volume ratio(volume to peak expiratory flow to total expired volume ratio,VPEF/VE),and serum Del-1 levels progressively decreased(P<0.05).TPTEF/TE and VPEF/VE were prominently negatively correlated with serum STAT3 and HDAC2 levels,and prominently positively correlated with Del-1 levels(P<0.05).Compared with the favorable prognosis group,the poor prognosis group had significantly lower initial blood oxygen saturation,serum Del-1 levels,and significantly higher serum STAT3 and HDAC2 levels(P<0.05).High expression levels of STAT3 and HDAC2 were independent risk factors affecting the prognosis of children with RSVP,while high expression of Del-1 was an independent protective factor(P<0.05).The AUC values of serum STAT3,HDAC2,and Del-1 levels alone in predicting the prognosis of children with RSV were 0.824,0.818,and 0.842,respectively.The combined prediction AUC was 0.947,which was superior to individual predictions(ZSTAT3-joint=2.436,ZHDAC2-joint=2.570,ZDel-1-joint=2.611,all P<0.05).Conclusion Serum expression of STAT3 and HDAC2 is upregulated,while the expression of Del-1 is down-regulated in children with RSVP.The three markers are closely related to the disease severity and pulmonary function indices,and are important factors affecting the prognosis of children with RSVP.Combined detection of these markers demonstrates high efficacy for prognosis evaluation.

OBJECTIVE: To evaluate the clinical significance of a hemizygous c.1042-10G>C variant of the SLC9A7 gene NM_001257291.2) previously identified in individuals with neurodevelopmental disorders, and to provide an evidence-based guidance for prenatal genetic counseling. METHODS: Four families presented at the Medical Genetics Center of Henan Provincial People's Hospital between December 2022 and July 2024 were included in this study. Phenotypic information and biological samples were collected from family members. Genomic DNA was extracted and subjected to whole-exome sequencing and copy number variation analysis to identify candidate pathogenic variants. Sanger sequencing was performed for familial co-segregation analysis. Reverse-transcription PCR was used to assess the RNA splicing pattern of the variant in peripheral blood samples. Quantitative PCR was employed to analyze the expression profiles of various SLC9A7 transcripts in fetal brain tissue and peripheral blood samples. Pathogenicity of the variant was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: Six hemizygous males carrying the SLC9A7 c.1042-10G>C variant were identified among the four families, which included three adult males and two male infants with normal phenotypes. Only one affected male from family 3 exhibited global developmental delay, short neck, webbed neck, ocular dysplasia, and congenital corneal leukoma. He also had a history of perinatal asphyxia and carried an additional hemizygous variant HUWE1 c.12283C>G. Reverse-transcription PCR showed no aberrant splicing in heterozygous or hemizygous carriers compared to healthy controls, suggesting that the variant does not affect RNA splicing. Quantitative PCR revealed that NM_001257291.2 is the predominant transcript expressed in fetal brain tissue and peripheral blood. CONCLUSION The SLC9A7 c.1042-10G>C variant does not alter RNA splicing and is present in multiple phenotypically normal males, which supported its classification as a benign variant.
Humans ; Male ; Female ; Genetic Counseling ; Pedigree ; Adult ; DNA Copy Number Variations/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of an infertile woman carrying a novel PADI6 gene variant. METHODS: An infertile woman who visited the Medical Genetics Center of Henan Provincial People's Hospital on April 29, 2024 was selected as the study subject. Clinical data of the proband and her family members were collected. Peripheral blood samples were obtained from the proband and her husband for genomic DNA extraction. Whole-exome sequencing (WES) was performed. Candidate variant was verified among the family members by Sanger sequencing. The pathogenicity of candidate variant was classified according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. Relevant literature on the pathogenic variants of the PADI6 gene was reviewed for genotype-phenotype correlation analysis. This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: The proband was a 35-year-old woman who underwent two oocyte retrieval cycles, yielding a total of five oocytes, with all embryos arrested at day 3 post-fertilization. WES identified a homozygous PADI6 variant, c.367+4_367+7del. In vitro splicing assay confirmed that this variant can cause skipping of exon 3, leading to a frameshift and alterations in the protein structure or premature termination of translation. Literature review identified 12 relevant publications, and the PADI6 c.367+4_367+7del was determined to be a novel variant. CONCLUSION The homozygous PADI6 c.367+4_367+7del variant probably underlay the pathogenesis of infertility in the proband.
Humans ; Female ; Infertility, Female/genetics* ; Adult ; Protein-Arginine Deiminase Type 6/genetics* ; Pedigree ; Exome Sequencing ; Mutation

Strengthening the construction of platforms,talents,and disciplines is a crucial strategy to enhance the core competitiveness and promote the high-quality development of national regional medical centers.It outlines the theoretical framework and implementation path for building the"Platform-Talent(Team)-Discipline"develop-ment system during the establishment of the National Regional Medical Center at Henan Children's Hospital Zheng-zhou Children's Hospital.By creating a collaborative innovation platform integrating medical services,education,and research,implementing talent development programs,optimizing mechanisms for talent recruitment,cultivation,and retention,and advancing discipline development projects,the center has achieved significant progress in its core competencies.This exploration provides valuable insights and references for the development of national regional medical centers and the high-quality growth of public hospitals.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

Objective To study the clinical value of stroboscopic laryngoscope combined with narrow band imaging endoscope in the diagnosis of benign and malignant glottic lesions.Methods A total of 60 patients(84 sides of vocal cord)who visited our department from June 2022 to January 2023 with hoarseness as the main complaint and were found to have glottic lesions by electronic nasopharyngoscopy were selected.In all 60 patients with 84 sides of vocal cord degenerative lesions,stroboscopic laryngoscopy and narrow band imaging(NBI)endoscopy were com-pleted.The examination results were evaluated and graded separately.The same operative group performed the re-section biopsy of vocal cord lesions under general anesthesia and laryngoscope respectively,and the pathological re-sults were used as the diagnostic gold standard.With sensitivity,specificity,accuracy,false negative rate,and false positive rate as the main evaluation indexes,the differences in diagnostic accuracy between single test technique and combined application of the two techniques were analyzed.Results Pathological results showed squamous cell carci-noma on 18 sides,carcinoma in situ on 4 sides,severe dysplasia on 4 sides,mild and moderate dysplasia on 13 sides,and papilloma,chronic,mucosal,nflammation,hyperplasia,hypokeratosis,hyperkeratosis on 45 sides.The sensitivity of strobe laryngoscopy detection was 53.06％and specificity was 60.34％.The sensitivity of NBI endo-scopic detection was 88.46％,and the specificity was 89.66％.The sensitivity of strobe laryngoscopy combined with NBI endoscopy was 96.15％,and the specificity was 94.83％.The areas under the ROC curve of strobe laryn-goscopy,NBI endoscopy and white light imaging combined with narrowband imaging were 0.888(95％CI:0.820～0.957),0.943(95％CI:0.885～1),0.970(95％CI:0.942～0.999),respectively.The area under the curve of the combined method was higher than that of the single method,and the difference was statistically significant(P＜0.05).Conclusion Stroboscopic laryngoscope combined with NBI endoscope can improve the diagnostic accuracy of benign and malignant glottic lesions.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.