The gut microbiota is regarded as the "eighth organ" of the human body and plays a critical regulatory role in the occurrence and progression of various diseases. Ulcerative colitis （UC） is a chronic inflammatory bowel disease with a complex etiology and a tendency toward recurrent episodes. In recent years， studies have shown that gut microbiota dysbiosis plays a key role in its pathological processes. Meanwhile， an increasing number of studies have demonstrated that imbalances in the gut microbiota and abnormalities in its metabolites are closely associated with the development of atrial fibrillation （AF）. Although UC and AF belong to diseases of the digestive system and cardiovascular system， respectively， both exhibit systemic inflammatory characteristics and are often accompanied by gut microbiota dysregulation and abnormal metabolic products. However， systematic investigations into the mechanisms by which gut microbiota-derived metabolites act in these two diseases remain limited. Based on this， the present study adopts literature review and theoretical analysis methods， taking the "gut microbiota-gut-heart" axis as the entry point， to systematically summarize the signaling networks of three key classes of metabolites， i.e.， short-chain fatty acids （SCFAs）， bile acids （BAs）， and trimethylamine N-oxide （TMAO）， in the comorbidity mechanism of UC and AF. The findings indicate that these metabolites may activate key inflammatory pathways， such as NF-κB and NLRP3， thereby synergistically mediating intestinal barrier dysfunction and systemic inflammation and constructing a potential comorbidity network. On this basis， potential intervention strategies for the treatment of UC-AF comorbidity， including probiotic intervention and fecal microbiota transplantation， are further discussed. This study aims to provide new theoretical evidence and research perspectives for prevention and treatment strategies of cross-system diseases.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Objective To identify genes regulated by ME2 and to explore their roles as well as underlying mecha-nisms in liver cancer progression.Methods RNA-seq data of siME2-transfected cells were subjected to differential expression analysis,clustering,GO and KEGG enrichment analyses.The mRNA level of the potential target gene SHCBP1 was measured by quantitative real-time PCR(qPCR)following ME2 knockdown or overexpression in HepG2 cells.The effect of ME2 and SHCBP1 on the downstream pathway was examined by Western blot.Cell pro-liferation,wound healing,and colony formation assays were conducted to evaluate SHCBP1's role in liver cancer cell proliferation and migration.Survival analysis of the TCGA-LIHC cohort was performed to determine the prog-nostic value of SHCBP1 in liver cancer patients.Results Differentially expressed genes in siME2-transfected cells were significantly enriched in biological processes including the PI3K-Akt signaling pathway,cell cycle,and serine phosphorylation.In HepG2 cells,ME2 knockdown led to a reduction in SHCBP1 mRNA level,whereas ME2 over-expression resulted in enhanced SHCBP1 mRNA level,demonstrating a positive correlation between ME2 and SHCBP1 expression.Western blot analysis revealed that ME2 enhanced PI3K-Akt signaling pathway activation through SHCBP1.qPCR results confirmed that SHCBP1 was significantly over-expressed in liver cancer cells and promoted both proliferation and migration,contributing to poor prognosis in liver cancer patients.Conclusions ME2 promotes liver cancer progression by regulating SHCBP1 to activate the PI3K-Akt signaling pathway,presen-ting a novel therapeutic target for liver cancer treatment.

Objective To investigate the value of constructing a risk prediction model of brain metastasis in lung cancer based on clinical-CT imaging.Methods The clinical and CT imaging data of 208 patients with lung cancer confirmed by surgical pathology or puncture biopsy were analyzed retrospectively,including 98 patients in the metastasis group and 110 patients in the non-metastasis group.Univariable and binary logistic regression analyses were performed between the two groups,and the clinical,CT imaging,and clinical-CT imaging models were constructed according to the selected independent risk factors.Prediction model performance was eval-uated with receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results Multivariate analysis showed that T stage,pathological type,radiotherapy and chemotherapy,surgery,long diameter(LD),short diameter(SD),minimum CT value(CTmin)were the independent risk factors for predicting brain metastasis in lung cancer(P<0.05).The area under the curve(AUC)of clinical,CT imaging and clinical-CT imaging models were 0.925,0.764,0.941,respectively.DeLong test analysis showed that the AUC of clinical-CT imaging model,clinical model and CT imaging model was statistical difference(Z=2.093,5.777,all P<0.05).The calibration curve suggested a good fit of the clinical-CT imaging model.The DCA suggested that the clinical-CT imaging model demonstrates good clinical benefits.Conclusion The clinical-CT imaging model can effectively predict the occurrence of brain metastasis in lung cancer,which is helpful to guide the development of accurate diagnosis and treatment plan.

Objective:To analyze the functional outcomes of arthrodesis for the first metatarsophalangeal joint.Methods:A retrospective study was conducted to analyze the 21 patients who had undergone arthrodesis for the first metatarsophalangeal joint at Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital from August 2013 to October 2019. The cohort included 6 males and 15 females. One patient underwent bilateral surgery, 10 cases the left side surgery and 10 cases the right side surgery. Their ages averaged (63.1±9.2) years. There were 12 cases of simple hallux valgus, 5 cases of rheumatoid arthritis combined with hallux valgus, and 4 cases of gout combined with hallux valgus. The visual analog scale (VAS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score, foot function index (FFI) score, hallux valgus angle (HVA), and intermetatarsal angle (IMA) were compared between preoperation and the last follow-up. The proximal phalangeal inclination angle (PPIA) was measured postoperatively. Postoperative satisfaction was evaluated using the Coughlin rating scale. Complications were documented.Results:All patients were followed up for 71.0 (69.8, 75.0) months. In all patients at the last follow-up, VAS [1(0, 3) points], FFI [4.8 (1.6, 8.6) points], HVA [23.4° (14.3°, 28.5°)], and IMA (9.6°±3.2°) were significantly lower than the preoperative values [4 (3, 7) points, 30.4 (16.7, 46.8) points, 43.5° (31.5°, 48.2°), and 13.0°±4.5°], and the AOFAS forefoot score [80.0 (70.8, 90.0) points] was significantly higher than the preoperative one [46.0 (32.8, 55.3) points] ( P<0.05). The postoperative PPIA was 7.7°±10.1°. According to the Coughlin rating scale, 12 cases were rated as excellent, 5 as good, 2 as fair, and 3 as poor. All patients reported relief from painful plantar calluses, most ones experienced complete resolution of plantar calluses, and some ones had stiffness of the metatarsophalangeal joint after fusion. Conclusion:Arthrodesis for the first metatarsophalangeal joint is a reliable treatment for degenerative changes in the metatarsophalangeal joint, because it can well restore the postoperative foot function, significantly relieve pain, and lead to high patient satisfaction.

Objective To investigate the value of constructing a risk prediction model of brain metastasis in lung cancer based on clinical-CT imaging.Methods The clinical and CT imaging data of 208 patients with lung cancer confirmed by surgical pathology or puncture biopsy were analyzed retrospectively,including 98 patients in the metastasis group and 110 patients in the non-metastasis group.Univariable and binary logistic regression analyses were performed between the two groups,and the clinical,CT imaging,and clinical-CT imaging models were constructed according to the selected independent risk factors.Prediction model performance was eval-uated with receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA).Results Multivariate analysis showed that T stage,pathological type,radiotherapy and chemotherapy,surgery,long diameter(LD),short diameter(SD),minimum CT value(CTmin)were the independent risk factors for predicting brain metastasis in lung cancer(P<0.05).The area under the curve(AUC)of clinical,CT imaging and clinical-CT imaging models were 0.925,0.764,0.941,respectively.DeLong test analysis showed that the AUC of clinical-CT imaging model,clinical model and CT imaging model was statistical difference(Z=2.093,5.777,all P<0.05).The calibration curve suggested a good fit of the clinical-CT imaging model.The DCA suggested that the clinical-CT imaging model demonstrates good clinical benefits.Conclusion The clinical-CT imaging model can effectively predict the occurrence of brain metastasis in lung cancer,which is helpful to guide the development of accurate diagnosis and treatment plan.

Objective:To investigate the impact of preoperative sarcopenia on chronic postsurgical pain(CPSP)after cardiac surgery in elderly patients.Methods:Elderly patients undergoing elective open-chest cardiac surgery at the Affiliated Hospital of Xuzhou Medical University from September 2022 to May 2024 were collected.According to the updated diagnostic criteria and revised by the Asian Working Group for Sarcopenia(AWGS2019)in 2019, patients were classified into sarcopenia and non-sarcopenia groups Elderly patients were divided into two groups based on the occurrence of chronic pain at 3 months postoperatively: CPSP group and non-CPSP group.Indicators with statistically significant differences in univariate regression analysis were included in multifactorial regression to analyze the influencing factors of chronic pain after cardiac surgery in elderly patients.The receiver operating characteristic(ROC)curve was plotted and the area under the curve(AUC)was calculated to compare the predictive efficacy of sarcopenia, commonly used clinical pain assessment tools(gender+ acute postoperative pain), and(gender+ acute postoperative pain+ sarcopenia)in predicting CPSP after cardiac surgery in elderly patients.Results:The study ultimately included 379 patients, consisting of 238 males(62.8%), with an average age of(66.6 ± 5.3)years.Among them, 83 patients had sarcopenia, and 119 patients developed CPSP.Univariate regression analysis showed that gender, history of atrial fibrillation, acute postoperative pain, American Society of Anesthesiologists(ASA)Physical Status Classification System, New York Heart Association(NYHA)Classification of Cardia Function, sarcopenia, and duration of extracorporeal circulation were associated with the occurrence of CPSP after cardiac surgery in elderly patients.However, after adjusting for all possible confounders, multifactorial regression analysis showed that gender, acute postoperative pain, and sarcopenia were independent risk factors for CPSP after cardiac surgery in elderly patients(all P<0.05), with sarcopenia patients having a 2.913-fold risk of developing CPSP compared with non-sarcopenia patients.The AUCs of the ROC curves for commonly used clinical perioperative pain assessment tools and those with the addition of sarcopenia determination were 0.731 and 0.802, respectively. Conclusions:Preoperative sarcopenia is an independent risk factor for the development of chronic pain after cardiac surgery in elderly patients, and the inclusion of sarcopenia determination in commonly used clinical pain assessment tools can significantly improve the predictive efficacy for chronic pain.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective To evaluate the effects of the method of blood-cooling and blood stasis-resolving on heart function and prognosis in patients with sepsis-induced myocardial dysfunction(SIMD).Methods Sixty patients with SIMD admitted to the department of critical care medicine of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2022 to October 2024 were enrolled as study subjects.The patients were divided into treatment group and control group according to random number table,with 30 patients in each group.All patients received conventional treatments,the patients in the treatment group were given Taohe Chengqi decoction(Persicae Semen 12 g,Chinese rhubarb 12 g,Cinnamon twig 6 g,Licorice root 6 g and Sodium Sulfate 6 g),the decoction was concentrated to 200 mL and taken in 2 divided doses in the morning and evening,one dose daily;and the patients in the control group were given the same amount of warm water.The total course of treatment lasts for 7 days.The differences in indicators of cardiac function[brain natriuretic peptide(BNP),cardiac troponin I(cTnI),MB isoenzyme of creatine kinase(CK-MB),aspartate aminotransferase(AST)]and echocardiographic parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),mitral orifice early/late diastolic blood flow velocity ratio(E/A ratio),E/mitral and tricuspid valve ostia and the peak early diastolic velocity(E/e')]at admission,at 1st and 7th day after treatment,and prognosis indexes[mechanical ventilation time,intensive care unit(ICU)length of stay,total hospital stay,28-day survival rate]were compared between two groups.Draw the Kaplan-Meier survival curve and compare the difference in the 28-day cumulative survival rate between the two groups of patients.Results After 7 days therapy,LVEF of the treatment group was significantly higher than that the control(0.524±0.132 vs.0.458±0.118,P<0.05)and E/e'ratio of the treatment group was significantly lower than the control group[11.17(9.57,12.04)vs.11.82(11.28,13.72),P<0.05].There were no significant differences in the 28-day mortality and total hospital stay time between the two groups,but mechanical ventilation time[days:7.00(0.00,11.00)vs.12.50(3.50,21.75),P<0.05]and stay time of ICU[days:14.50(7.75,25.00)vs.21.00(14.25,31.50),P<0.05]in the treatment group were shorter than those in the control group.The Kaplan-Meier survival showed that the cumulative 28-day survival rate was similar between two groups(Log-Rank:χ2=1.448,P=0.229).Conclusion The method of blood-cooling and blood stasis-resolving could decrease mechanical ventilation time and length of stay in ICU of SIMD patients and could increase LVEF in the treatment group.