1.Clinical Application and Mechanism of Buyang Huanwutang in Treatment of Chronic Heart Failure: A Review
Zejun DU ; Linping ZHU ; Xueying WU ; Xiaotong LYU ; Mei ZHAO ; Yuhong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):286-294
Chronic heart failure (CHF) is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body, or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health, necessitating attention and active intervention. At present, western medicine treatment of CHF is mainly based on diuretics, intravenous vasodilators, intravenous positive inotropic drugs, etc., which, however, have problems such as long medication cycles, serious side effects, and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway, multi-component, and multi-target manner, showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi, activating blood, and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients, which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients, which helps to improve the accuracy of efficacy evaluation. However, there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition, the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment, Buyang Huanwutang can be used alone, or modified, or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance, protecting the mitochondrial structure and function, and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.
2.Efficacy test of mp-MRI-based VI-RADS score for diagnosis of muscle-invasive bladder cancer,a Meta-analysis
Qingyang YU ; Kangkang CHEN ; Tonglei ZHAO ; Weipu MAO ; Zejun WANG ; Xinyang PENG ; Zihui ZHAO ; Xingui PENG ; Ming CHEN ; Jianping WU
Chinese Journal of Urology 2025;46(6):430-438
Objective:To evaluate the diagnostic performance of the Vesical Imaging-Reporting and Data System(VI-RADS)based on multiparametric magnetic resonance imaging(mp-MRI)for muscle-invasive bladder cancer(MIBC).Methods:A systematic search was conducted in PubMed,Web of Science,and Embase databases for studies published between September 2018 and December 2023 that investigated the use of VI-RADS for diagnosing MIBC. Inclusion criteria were studies utilizing mp-MRI-based VI-RADS scoring to determine MIBC. Exclusion criteria were studies with fewer than 10 patients,overlapping study populations,or those failing to assess the diagnostic performance of VI-RADS for MIBC. After quality assessment,RevMan 5.4 and Stata 15.1 were used to calculate pooled sensitivity and specificity,generate forest plots and summary receiver operating characteristic(SROC)curves,and determine the area under the curve(AUC). Publication bias was assessed using Deeks funnel plot. Heterogeneity was evaluated using the I2 statistic,with meta-regression and subgroup analyses to explore its sources. Results:Twenty-nine studies involving 3 577 patients were included. At a VI-RADS cutoff of 3,the pooled sensitivity and specificity for MIBC diagnosis were 93%(95%CI 0.90-0.95)and 82%(95%CI 0.76-0.88),respectively. At a cutoff of 4,these values were 83%(95%CI 0.78-0.87)and 93%(95%CI 0.90-0.95). The hierarchical SROC(HSROC)AUCs were 0.95 and 0.94 for cutoffs of 3 and 4,respectively. Subgroup and meta-regression analyses revealed that at a cutoff of 3,patient sample size,study design,MRI field strength,number of radiologists,surgical approach,and DWI/DCE imaging planes contributed to sensitivity heterogeneity( P < 0.05). All factors except study design and DWI plane were sources of specificity heterogeneity( P < 0.05). At a cutoff of 4,all factors significantly influenced heterogeneity in both sensitivity and specificity( P < 0.05). Meta-regression confirmed that both cutoffs(3 and 4)were significant sources of heterogeneity( P < 0.05). Conclusions:VI-RADS demonstrates excellent diagnostic performance for MIBC at both cutoffs(3 and 4),with VI-RADS ≥ 3 showing superior sensitivity and VI-RADS ≥ 4 offering higher specificity. The cutoff of 3 provides better overall diagnostic efficacy.
3.Construction and validation of a risk prediction model for high altitude de-acclimatization syndrome
Yu DING ; Zejun WANG ; Jiaxin XIE ; Siyu ZHAO ; Gang ZHANG
Journal of Army Medical University 2025;47(1):20-29
Objective To construct risk models for predicting the occurrence of high altitude de-acclimatization syndrome(HADAS)in the population returning from the plateau to the plain based on different machine learning algorithms and validate the predicting efficiency of these models.Methods Field or online surveys were conducted on the individuals who had ended their high-altitude living and returned to the plain areas from November 2020 to February 2024.Basic information,chronic mountain sickness(CMS),HADAS symptoms and other data were collected.With the inclusion and exclusion criteria,totally 1 095 individuals were subjected and assigned into the modeling group.Positive events were defined as HADAS score>5.Then the modelling group was divided into a training set(n=766)and an internal test set(n=329)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression was used to select independent variables.Risk prediction models for high-altitude adaptation symptoms were built based on 8 machine learning methods,including multiple factor logistic regression(LR),decision tree(DT),random forest(RF),eXtreme gradient boosting(XGB),support vector machine(SVM),K-nearest neighbor(KNN),light gradient boosting(LGB)and na?ve bayes(NB).The models were compared and evaluated using receiver operating characteristic(ROC)curves,calibration curves and confusion matrices in the internal test set.The final model was presented using a nomogram or Shapley additive explanations(SHAP)algorithm.In August 2024,another 132 individuals who returned to the plains and met the same criteria were recruited and served as the external validation group.Results There were 549 individuals(50.14%)out of the 1 095 subjects having HADAS symptoms.LASSO regression identified CMS score,age and duration of high-altitude residence as significant predictors.Among the 8 machine learning algorithms,the LR model was identified as the best,with an area under the curve(AUC)value of 0.819(95%CI:0.789~0.850)and 0.841(95%CI:0.799~0.884),and an F1 score of 0.801 in the internal test set,respectively,and the AUC value and F1 score of the LR model were the largest among the 8 models in the internal test set.Spiegelhalter Z test of the calibration curve of the LR model indicated that its P=0.703 in the training set while P=0.281 in the internal test set.The AUC value of the LR model was 0.867(95%CI:0.765~0.969)in the external validation set.Conclusion The LR model constructed based on indicators including CMS score,age and duration of high-altitude residence has a good overall performance in the internal test set,and good discriminating effect in the external validation set.The constructed nomogram is convenient for application.
4.Value of multiparametric MRI-based radiomics in predicting HER2 expression in bladder cancer
Tonglei ZHAO ; Weipu MAO ; Zihui ZHAO ; Zejun WANG ; Dakun ZHANG ; Ming CHEN ; Jianping WU
Journal of Modern Urology 2025;30(8):662-670,688
Objective To evaluate the value of radiomics models and comprehensive models based on multiparametric magnetic resonance imaging(mpMRI)in predicting the expression of human epidermal growth factor receptor 2(HER2)in bladder cancer(BCa).Methods A total of 76 pathologically confirmed BCa patients undergoing pelvic mpMRI during Jan.2022 and Nov.2024 at the Affiliated Zhongda Hospital of Southeast University were retrospectively included.After the volume of interest(VOI)was sketched,7 modal features were obtained,including T2WI,DWI,DCE,T2WI+DWI,T2WI+DCE,DWI+DCE,and T2WI+DWI+DCE,which were analyzed with logistic regression to obtain the predictive values.After that,the best sequences were screened with receiver operating characteristic(ROC)curves,and then combined with support vector machine,logistic regression,K-nearest neighbor,plain Bayes and adaptive enhancement,to construct the radiomics prediction models.Logistic regression analysis was used to screen the predictors of high HER 2 expression and to construct a comprehensive prediction model and a nomogram.Finally,decision curve analysis(DCA)was used to quantify the clinical benefits.Results Among the radiomics models based on the T2WI+DWI+DCE sequence,the AdaBoost model demonstrated the best predictive performance,with area under the ROC curve(AUC)being 0.863(95%CI:0.807-0.920)in the training set and 0.716(95%CI:0.601-0.830)in the validation set.Based on radiomics features and clinical imaging characteristics,logistic regression analysis identified tumor pedicle and risk group as the predictors of high HER2 expression.The comprehensive prediction model based on the two factors achieved the AUC of 0.869(95%CI:0.772-0.965)in the training set and 0.875(95%CI:0.712-0.986)in the validation set.Conclusion The radiomics model based on the T2WI+DWI+DCE sequence has high accuracy in predicting HER2 expression,outperforming single-sequence models.The nomogram based on the comprehensive prediction model has high clinical decision-making efficacy and is useful for non-invasive identification of HER2 expression.
5.Identification of a Fetal De Novo Splice Variant in ARCN1 Associated With Growth and Skeletal Abnormalities
Wencong HE ; Zejun YANG ; Jianjian CUI ; Ruilin MA ; Hui TAO ; Yanan LI ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(1):9-14
Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.
6.Multicenter Retrospective Evaluation of the Chinese Expert Consensus Scoring System for the Diagnosis of Obstetrical DIC
Jianjian CUI ; Ziyang LIU ; Wencong HE ; Ruifen SU ; Ruilin MA ; Hui TAO ; Zejun YANG ; Lei SUN ; Shaoqi CHEN ; Yanan LI ; Zhishan JIN ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(4):216-227
Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.
7.Research on the causal association of gut microbiota with senile osteoporosis
Xinghua JI ; Yifan KANG ; Enzhe ZHAO ; Xiaoqiong LI ; Zejun XING
Chinese Journal of Geriatrics 2025;44(11):1522-1528
Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.
8.Identification of a Fetal De Novo Splice Variant in ARCN1 Associated With Growth and Skeletal Abnormalities
Wencong HE ; Zejun YANG ; Jianjian CUI ; Ruilin MA ; Hui TAO ; Yanan LI ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(1):9-14
Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.
9.Multicenter Retrospective Evaluation of the Chinese Expert Consensus Scoring System for the Diagnosis of Obstetrical DIC
Jianjian CUI ; Ziyang LIU ; Wencong HE ; Ruifen SU ; Ruilin MA ; Hui TAO ; Zejun YANG ; Lei SUN ; Shaoqi CHEN ; Yanan LI ; Zhishan JIN ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(4):216-227
Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.
10.Research on the causal association of gut microbiota with senile osteoporosis
Xinghua JI ; Yifan KANG ; Enzhe ZHAO ; Xiaoqiong LI ; Zejun XING
Chinese Journal of Geriatrics 2025;44(11):1522-1528
Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.

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