OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective:To investigate the diagnostic and differential diagnostic values of midbrain morphological measurements at the mammillary body level on axial cranial MRI in progressive supranuclear palsy (PSP).Methods:This cross-sectional study included 50 patients with clinically diagnosed, probable or possible PSP, admitted to Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2023 to December 2024. Additionally, 44 patients with Parkinson's disease (PD), 30 patients with multiple system atrophy-cerebellar type (MSA-C), and 35 gender- and age-matched healthy controls recruited from the community were chosen. The following midbrain morphological parameters on axial cranial MRI were measured in all participants: distance from the interpeduncular fossa to the aqueduct (IF-AQ), distance from the lateral mesencephalic sulcus to the interpeduncular cistern (LS-IC), distance between the bilateral lateral mesencephalic sulci (D-BMS), cerebral peduncle angle (CPA), distance between the medial aspects of the cerebral peduncles (D-MP), and distance from the line connecting the highest points of the cerebral peduncle to the interpeduncular fossa (PP-IF). Differences in these measurements among the 4 groups were compared, and the diagnostic and differential diagnostic performances of each parameter in PSP was evaluated using receiver operating characteristic (ROC) curve.Results:The PSP group exhibited significantly shorter IF-AQ, LS-IC, and D-BMS distances compared with the other 3 groups ( P<0.05). (1) ROC curve analysis of PSP group versus non-PSP group (MSA-C patients, PD patients, and healthy controls) showed that IF-AQ had an area under the curve (AUC) of 0.977 (95% CI: 0.959-0.995, P<0.001), and at a cutoff of 10.895 mm, IF-AQ demonstrated a sensitivity of 96.0% and a specificity of 89.9% for diagnosing PSP; LS-IC had an AUC of 0.917 (95% CI: 0.868-0.966, P<0.001), and at a cutoff of 10.82 mm, LS-IC demonstrated a sensitivity of 82.0% and a specificity of 89.0% for diagnosing PSP; D-BMS had an AUC of 0.785 (95% CI: 0.704-0.866, P<0.001), and at a cutoff of 20.01 mm, D-BMS demonstrated a sensitivity of 66.0% and a specificity of 83.5% for diagnosing PSP. (2) In distinguishing PSP from MSA-C, IF-AQ achieved an AUC of 0.939 (95% CI: 0.889-0.988, P<0.001), with a sensitivity of 84.0% and a specificity of 90.0% at a cutoff of 10.385 mm; LS-IC achieved an AUC of 0.846 (95% CI: 0.756-0.936, P<0.001), with a sensitivity of 80.0% and a specificity of 76.7% at a cutoff of 10.710 mm; D-BMS achieved an AUC of 0.696 (95% CI: 0.578-0.813, P<0.001), with a sensitivity of 60.0% and a specificity of 80.0% at a cutoff of 19.810 mm. (3) In discriminating PSP from PD, IF-AQ yielded an AUC of 0.986 (95% CI: 0.970-1.000, P<0.001), with a sensitivity of 96.0% and a specificity of 89.2% at a cutoff of 10.955 mm; LS-IC achieved an AUC of 0.937 (95% CI: 0.885-0.988, P<0.001), with a sensitivity of 82.0% and a specificity of 95.5% at a cutoff of 10.820 mm; D-BMS had an AUC of 0.825 (95% CI: 0.740-0.909, P<0.001), with a sensitivity of 60.0% and a specificity of 95.5% at a cutoff of 19.820 mm. Conclusion:IF-AQ, LS-IC, and D-BMS distances on axial cranial MRI at the mamillary body level can diagnose and differentiate PSP to a certain extent, with IF-AQ enjoying the best efficacy.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective:To investigate the diagnostic and differential diagnostic values of midbrain morphological measurements at the mammillary body level on axial cranial MRI in progressive supranuclear palsy (PSP).Methods:This cross-sectional study included 50 patients with clinically diagnosed, probable or possible PSP, admitted to Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2023 to December 2024. Additionally, 44 patients with Parkinson's disease (PD), 30 patients with multiple system atrophy-cerebellar type (MSA-C), and 35 gender- and age-matched healthy controls recruited from the community were chosen. The following midbrain morphological parameters on axial cranial MRI were measured in all participants: distance from the interpeduncular fossa to the aqueduct (IF-AQ), distance from the lateral mesencephalic sulcus to the interpeduncular cistern (LS-IC), distance between the bilateral lateral mesencephalic sulci (D-BMS), cerebral peduncle angle (CPA), distance between the medial aspects of the cerebral peduncles (D-MP), and distance from the line connecting the highest points of the cerebral peduncle to the interpeduncular fossa (PP-IF). Differences in these measurements among the 4 groups were compared, and the diagnostic and differential diagnostic performances of each parameter in PSP was evaluated using receiver operating characteristic (ROC) curve.Results:The PSP group exhibited significantly shorter IF-AQ, LS-IC, and D-BMS distances compared with the other 3 groups ( P<0.05). (1) ROC curve analysis of PSP group versus non-PSP group (MSA-C patients, PD patients, and healthy controls) showed that IF-AQ had an area under the curve (AUC) of 0.977 (95% CI: 0.959-0.995, P<0.001), and at a cutoff of 10.895 mm, IF-AQ demonstrated a sensitivity of 96.0% and a specificity of 89.9% for diagnosing PSP; LS-IC had an AUC of 0.917 (95% CI: 0.868-0.966, P<0.001), and at a cutoff of 10.82 mm, LS-IC demonstrated a sensitivity of 82.0% and a specificity of 89.0% for diagnosing PSP; D-BMS had an AUC of 0.785 (95% CI: 0.704-0.866, P<0.001), and at a cutoff of 20.01 mm, D-BMS demonstrated a sensitivity of 66.0% and a specificity of 83.5% for diagnosing PSP. (2) In distinguishing PSP from MSA-C, IF-AQ achieved an AUC of 0.939 (95% CI: 0.889-0.988, P<0.001), with a sensitivity of 84.0% and a specificity of 90.0% at a cutoff of 10.385 mm; LS-IC achieved an AUC of 0.846 (95% CI: 0.756-0.936, P<0.001), with a sensitivity of 80.0% and a specificity of 76.7% at a cutoff of 10.710 mm; D-BMS achieved an AUC of 0.696 (95% CI: 0.578-0.813, P<0.001), with a sensitivity of 60.0% and a specificity of 80.0% at a cutoff of 19.810 mm. (3) In discriminating PSP from PD, IF-AQ yielded an AUC of 0.986 (95% CI: 0.970-1.000, P<0.001), with a sensitivity of 96.0% and a specificity of 89.2% at a cutoff of 10.955 mm; LS-IC achieved an AUC of 0.937 (95% CI: 0.885-0.988, P<0.001), with a sensitivity of 82.0% and a specificity of 95.5% at a cutoff of 10.820 mm; D-BMS had an AUC of 0.825 (95% CI: 0.740-0.909, P<0.001), with a sensitivity of 60.0% and a specificity of 95.5% at a cutoff of 19.820 mm. Conclusion:IF-AQ, LS-IC, and D-BMS distances on axial cranial MRI at the mamillary body level can diagnose and differentiate PSP to a certain extent, with IF-AQ enjoying the best efficacy.

Acute B-lymphoblastic leukemia (B-ALL) is the most common type of acute lymphoblastic leukemia. Chemotherapy is the main treatment for most patients, but there are serious side effects. CD19 is generally highly expressed in B-lineage malignancies and plays a key role in B cell signal transduction, activation and development. Therefore, it has become one of the effective targets for treatment of B-cell malignancies. At present, a variety of therapies targeting CD19 have been developed, including antibody drug conjugates, monoclonal antibodies, bispecific antibodies and chimeric antigen receptors cell therapies. This paper reviews the clinical trial progress of CD19-targeted therapy for B-ALL.