Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective To analyze the risk factors for adverse drug reactions(ADRs)caused by montelukast sodium in the treatment of children with community-acquired pneumonia(CAP),and to construct and verify prediction model for ADRs.Methods The clinical data of CAP children who received montelukast sodium treatment in Suzhou Hospital Affiliated to Anhui Medical University from April 2023 to June 2024 were retrospectively collected.The patients were randomly divided into modeling group and verification group according to the 3∶2 ratio,and the modeling group were divided into the ADR subgroup and non-ADR subgroup based on the presence or absence of ADR.The modeling group data was used for model construction,and multivariate Logistic analysis were used to analyze the influencing factors of ADR and establish a predictive model.The verification group data was used for model validation.The model's predictive ability,calibration,and clinical net benefits were evaluated using the receiver operating characteristic(ROC)analysis,calibration curves,and decision curves.Results A total of 241 pediatric patients were included,including 144 in the modeling group and 97 in the validation group.A total of 50 children in the modeling group developed ADR,with an incidence rate of 34.72％.Multivariate Logistic regression results indicated that nebulized inhalation[OR=2.370,95％CI(1.099,5.111),P=0.028],use of methylprednisolone[OR=2.481,95％CI(1.057,5.824),P=0.037],and extrapulmonary complications[OR=7.411,95％CI(1.382,39.738),P=0.019]were independent risk factors for montelukast sodium related ADRs in children with CAP.The areas under the curve of the modeling group and validation group were 0.964 and 0.869,respectively.The calibration curve and decision curve showed good consistency between the predicted and actual values of the model,indicating good clinical net benefits.Conclusions Aerosol inhalation,methylprednisolone use,and extrapulmonary complications were independent risk factors for the occurrence of montelukast sodium-related adverse reactions in children with CAP.This model could help screen and identify ADR high-risk children.

Objective To evaluate the clinical efficacy of selective expansive open-door laminoplasty(SEOLP)with preservation of C7 spinous process in the treatment of multisegmental cervical spondylotic myelopathy and its impact on changes in sagittal parameters of cervical spine.Methods A retrospective analysis was conducted on the clinical data and radiological information of 73 patients who underwent expansive open-door laminoplasty(EOLP)for cervical spondylotic myelopathy in our department between March 2018 and June 2022.Patients were divided into the SEOLP group(n=35)and the EOLP group(n=38)based on the surgical method.Follow-up was conducted for one year.The operation time,blood loss,axial symptom scores,JOA scores,VAS scores and neck disability index(NDI)were recorded in two groups of patients.Radiological data were also recorded for both groups during the perioperative period,and the C2-7 Cobb angle,C2-7 SVA and T1 slope were measured.The cervical curvature index(CCI)and cervical range of motion(ROM)were calculated.The perioperative clinical outcomes and changes in cervical sagittal parameters were observed,and their correlations were analyzed.Results There were no significant differences in blood loss,operation time,JOA scores at various follow-up time points between the two groups(P＞0.05).During postoperative follow-up,axial symptoms were observed in 5 patients in SEOLP group and 14 patients in EOLP group.There were statistically significant differences in axial symptom scores,incidence and severity of axial symptoms between the two groups(P＜0.05).The NDI indices at one year after operation were 21.1±2.3 for SEOLP group and 24.8±3.5 for EOLP group respectively(P＜0.01).There were no statistically significant differences in T1 slope and C2-7 Cobb angle at various follow-up time points after surgery between the two groups(P＞0.05).One year after operation,CCI indices for two groups were(13.4±2.7)and(12.1±2.4),respectively,with a statistically significant difference(t=2.178,P＜0.05).The C2-C7 SVA values for two groups at one year after operation were(22.4+3.8)mm and(26.7±5.9)mm,respectively(t=3.667,P＜0.01).The results of the correlation analysis showed that there was a significant negative correlation between clinical functional improvement(NDI)and changes of the radiological parameter C2-C7 SVA in both groups of patients.Conclusion After SEOLP,the recovery of C2-C7 SVA is faster and has less impact on cervical spine function,and the occurrence degree and incidence of axial symptoms are lower.

Objective To analyze the risk factors for adverse drug reactions(ADRs)caused by montelukast sodium in the treatment of children with community-acquired pneumonia(CAP),and to construct and verify prediction model for ADRs.Methods The clinical data of CAP children who received montelukast sodium treatment in Suzhou Hospital Affiliated to Anhui Medical University from April 2023 to June 2024 were retrospectively collected.The patients were randomly divided into modeling group and verification group according to the 3∶2 ratio,and the modeling group were divided into the ADR subgroup and non-ADR subgroup based on the presence or absence of ADR.The modeling group data was used for model construction,and multivariate Logistic analysis were used to analyze the influencing factors of ADR and establish a predictive model.The verification group data was used for model validation.The model's predictive ability,calibration,and clinical net benefits were evaluated using the receiver operating characteristic(ROC)analysis,calibration curves,and decision curves.Results A total of 241 pediatric patients were included,including 144 in the modeling group and 97 in the validation group.A total of 50 children in the modeling group developed ADR,with an incidence rate of 34.72％.Multivariate Logistic regression results indicated that nebulized inhalation[OR=2.370,95％CI(1.099,5.111),P=0.028],use of methylprednisolone[OR=2.481,95％CI(1.057,5.824),P=0.037],and extrapulmonary complications[OR=7.411,95％CI(1.382,39.738),P=0.019]were independent risk factors for montelukast sodium related ADRs in children with CAP.The areas under the curve of the modeling group and validation group were 0.964 and 0.869,respectively.The calibration curve and decision curve showed good consistency between the predicted and actual values of the model,indicating good clinical net benefits.Conclusions Aerosol inhalation,methylprednisolone use,and extrapulmonary complications were independent risk factors for the occurrence of montelukast sodium-related adverse reactions in children with CAP.This model could help screen and identify ADR high-risk children.

Objective To evaluate the clinical efficacy of selective expansive open-door laminoplasty(SEOLP)with preservation of C7 spinous process in the treatment of multisegmental cervical spondylotic myelopathy and its impact on changes in sagittal parameters of cervical spine.Methods A retrospective analysis was conducted on the clinical data and radiological information of 73 patients who underwent expansive open-door laminoplasty(EOLP)for cervical spondylotic myelopathy in our department between March 2018 and June 2022.Patients were divided into the SEOLP group(n=35)and the EOLP group(n=38)based on the surgical method.Follow-up was conducted for one year.The operation time,blood loss,axial symptom scores,JOA scores,VAS scores and neck disability index(NDI)were recorded in two groups of patients.Radiological data were also recorded for both groups during the perioperative period,and the C2-7 Cobb angle,C2-7 SVA and T1 slope were measured.The cervical curvature index(CCI)and cervical range of motion(ROM)were calculated.The perioperative clinical outcomes and changes in cervical sagittal parameters were observed,and their correlations were analyzed.Results There were no significant differences in blood loss,operation time,JOA scores at various follow-up time points between the two groups(P＞0.05).During postoperative follow-up,axial symptoms were observed in 5 patients in SEOLP group and 14 patients in EOLP group.There were statistically significant differences in axial symptom scores,incidence and severity of axial symptoms between the two groups(P＜0.05).The NDI indices at one year after operation were 21.1±2.3 for SEOLP group and 24.8±3.5 for EOLP group respectively(P＜0.01).There were no statistically significant differences in T1 slope and C2-7 Cobb angle at various follow-up time points after surgery between the two groups(P＞0.05).One year after operation,CCI indices for two groups were(13.4±2.7)and(12.1±2.4),respectively,with a statistically significant difference(t=2.178,P＜0.05).The C2-C7 SVA values for two groups at one year after operation were(22.4+3.8)mm and(26.7±5.9)mm,respectively(t=3.667,P＜0.01).The results of the correlation analysis showed that there was a significant negative correlation between clinical functional improvement(NDI)and changes of the radiological parameter C2-C7 SVA in both groups of patients.Conclusion After SEOLP,the recovery of C2-C7 SVA is faster and has less impact on cervical spine function,and the occurrence degree and incidence of axial symptoms are lower.

Objective To explore the role and molecular mechanism of major vault protein (MVP) in tumor-associated macrophages in the occurrence and development of liver cancer. Methods The expression of MVP in macrophages was analyzed by bioinformatics method and multi-fluorescent immunohistochemical staining. Mice with MVP deficiency in macrophages were constructed by Cre/LoxP recombinant enzyme system. The proliferation and migration abilities of tumor cells were detected by cloning formation and Transwell migration assays. The effect of MVP in macrophages on tumorigenesis and development was investigated by mouse primary liver cancer model and subcutaneous tumor transplantation model. The effect of MVP on the tumor microenvironment was investigated by multi-fluorescent immunohistochemical staining. The effect of MVP on CD8⁺ T cells was detected by cell co-culture, flow cytometry, qPCR, and ELISA. Results The high expression of MVP in tumor-associated macrophages. The downregulation of the expression of MVP in tumor-associated macrophages compared with para-carcinoma tissues. MVP deficiency in macrophages promoted the proliferation and migration of tumor cells (P<0.05), promoted the development of tumor in vivo (P<0.05), formed an immunosuppressive microenvironment and weakened CD8⁺ T cell-mediated anti-tumor immunity (P<0.05). Conclusion MVP deficiency in macrophages can promote the occurrence and development of liver cancer by suppressing the function of CD8⁺ T cells.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective:To analyze the current status of global clinical trial for botulinum toxin (BTX) drugs, and to provide a reference for BTX drug research priorities and trends.Methods:All registered BTX drug-related clinical trials from the inception of the platforms until December 2024 were retrieved from the International Clinical Trials Registry Platform (ICTRP) and the Center for Drug Evaluation (CDE) Clinical Trial Registration and Information Disclosure Platform of the National Medical Products Administration of China (referred to as the CDE Platform). The data were statistically analyzed using Excel 2021. The analysis was conducted from aspects such as registration volume and annual trend, distribution of conducting countries, drug type, study type and recruitment situation, and indications.Results:A total of 2 053 clinical trials related to BTX were included. The total number of registered trials showed an increasing trend year by year. The country with the largest number of clinical trials was the United States, with 571 trials, while China ranked third with 190 trials. Among the drug formulations, the injection form accounted for the highest proportion (99.02%, 2 033/2 053). A few new formulations included topical ointments, nasal sprays, and eye drops. In terms of drug serotypes and sources, the wild-type BTX-A projects accounted for a relatively high proportion (97.86%, 2 009/2 053), and also included a few wild-type BTX-B, wild-type BTX-E, recombinant BTX-AB, and recombinant BTX-A projects. In terms of research types, 90.4% (1 856/2 053) were intervention studies, 87.5% (1 796/2 053) of the clinical trials did not restrict gender, 90.7% (1 862/2 053) of the clinical trials recruited subjects covering adults, and 9.3% (191/2 053) of the clinical trials only recruited minors. The research indications covered various disciplines, such as skin beauty, neurology, urology, orthopedics, and ophthalmology. In recent years, the types of diseases registered for clinical trials had expanded significantly on the basis of the originally approved indications.Conclusion:Innovative directions in BTX drug research, including BTX drugs of different serotypes, recombinant BTX based on recombinant gene technology, BTX formulations for non-injectable delivery, and innovative areas of clinical application, are driving its continued clinical research.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.