To improve the quality evaluation system of Hibisci Mutabilis Folium, this study established high performance liquid chromatography(HPLC) fingerprints of Hibisci Mutabilis Folium and evaluated the quality differences of medicinal materials from different places of production by chemometrics. Furthermore, a content measurement method of differential components was established based on quantitative analysis of multi-components by single-marker(QAMS). The fingerprints of 17 batches of Hibisci Mutabilis Folium from different places of production were constructed, with a total of 19 common peaks marked and seven components confirmed. The similarity between the sample fingerprints and the reference fingerprints ranged from 0.890 to 0.974. By utilizing principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA), the chemical patterns of fingerprints were identified. Five components that could be used to evaluate the quality differences of Hibisci Mutabilis Folium were screened, namely peak 6(quercetin 3-O-β-robinobioside), peak 7(rutin), peak 9(kaempferol-3-O-β-robinobioside), peak 10(kaempferol-3-O-rutinoside), and peak 14(tiliroside). The relative correction factors of isoquercitrin, kaempferol-3-O-β-robinobioside, kaempferol-3-O-rutinoside, kaempferol-3-O-β-D-glucoside, and tiliroside were measured with rutin as the internal reference. The QAMS method was established for the content measurement of six flavonoids, and the results showed there was no significant difference compared to the results obtained by an external standard method. In summary, the HPLC fingerprints and QAMS method established in the study, demonstrating stability and accuracy, can provide a reference for the overall quality evaluation of Hibisci Mutabilis Folium.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Principal Component Analysis

OBJECTIVE: To screen out the key metabolites related to diabetic foot (DF) by integrating genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS). METHODS: The literature databases such as PubMed and China national knowledge infrastructure(CNKI), as well as genomics databases such as PAN UKBB, FinnGen, and IEU Open GWAS were systematically retrieved from database estobilishment to November 2024 on DF-related single nucleotide polymorphisms and genome-wide association studies. DF-single nucleotide polymorphism-metabolite network was constructed by mGWAS package and mGWAS-Explorer platform. The causal relationship between key factors was evaluated by two-sample Mendelian randomization. The genetic correlation between DF and 575 metabolites (source:IEU Open GWAS) was evaluated by linkage disequilibrium score regression. In vitro experiments were conducted to induce injury of human umbilical vein endothelial cells with 30 mM glucose and intervene with 20 μM γ-tocopherol. Changes in cell migration, scratch healing and tube formation function were detected. RESULTS: Twenty-senen literatures on single nucleotide polymorphism literatures and 3 studies on GWAS were included. Genetic analysis results showed DF-related single nucleotide polymorphisms were enriched in vascular endothelial dysfunction-related pathways (such as fluid shear stress and atherosclerosis). The results of metabolic network analysis screened out 19 associated metabolites, among which 12 such as γ -tocopherol and pyruvate had significant genetic correlations with DF. Mendelian randomization suggested matrix metalloproteinase-9(MMP-9) might be a potential driver of DF (β=0.658, P=0.063 8), and the occurrence of DF could reduce the level of high-density lipoprotein (β=-0.002, P=0.015 2). The results of in vitro experiments confirmed that γ -tocopherol could improve endothelial dysfunction induced by high glucose, specifically manifested as an increase in the number of cell migrations, improvement in the scratch healing rate, and recovery of tubule formation ability (P<0.05). CONCLUSION DF has a genetic basis centered on vascular endothelial dysfunction, and its occurrence can lead to further metabolic disorders. The key single nucleotide polymorphism loci integrated provided molecular markers for the risk stratification of foot ulcers in diabetic patients. In addition, γ -tocopherol has demonstrated clinical application potential as a therapeutic drug for DF by significantly improving the function of vascular endothelial cells in a high-glucose environment.
Humans ; Diabetic Foot/drug therapy* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genomics ; Metabolomics ; Metabolome

BACKGROUND: Children's respiratory health demonstrates particular sensitivity to air pollution. Existing evidence investigating the association between short-term ozone (O₃) exposure and childhood pneumonia remains insufficient and inconsistent, especially in low- and middle-income countries (LMICs). METHOD: To provide more reliable and persuasive evidence, we implemented a multi-city, time-stratified case-crossover design with a large sample size, using data from seven representative children's hospitals across major geographical regions in China. To avoid the impact of the COVID-19 pandemic, individual-level medical records of inpatient children under 6 years of age diagnosed with pneumonia during 2016-2019 were collected. Conditional logistic regression models were fitted for each city, and city-specific estimates were pooled through a meta-analysis using a random-effects model. RESULTS: In total, the study included 137,470 pediatric pneumonia hospital admissions. The highest pooled estimate for O₃ occurred at lag0-1, with a 10 µg/m³ increase in O₃ associated with a 1.57% (95% CI: 0.67%-2.48%) higher risk of pediatric pneumonia hospital admissions. Stratified analyses indicated that the effects of O₃ were robust across different sexes, age groups, and admission seasons. We also observed a statistically significant increase in risk associated with O₃ concentrations exceeding the World Health Organization Air Quality Guidelines (WHO-AQGs). CONCLUSIONS This study revealed a significant positive association between O₃ and pediatric pneumonia hospital admissions. Our findings substantially strengthen the evidence base for the adverse health impacts of O₃, underscoring the importance of O₃ pollution control and management in reducing the public health burden of pediatric pneumonia.
Humans ; Ozone/analysis* ; China/epidemiology* ; Pneumonia/chemically induced* ; Child, Preschool ; Male ; Female ; Infant ; Cross-Over Studies ; Air Pollutants/analysis* ; Hospitalization/statistics & numerical data* ; Child ; Cities/epidemiology* ; Air Pollution/adverse effects* ; Infant, Newborn ; Environmental Exposure/adverse effects*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To study and establish the UPLC fingerprint and multi-index content determination methods of Hedyotidis chrysotricahae Herba; To provide a reference for the quality control of Hedyotidis chrysotricahae Herba.Methods:The chromatographic column was ACQUITY UPLC HSS T3 (100 mm×2.1 mm,1.8 μm). The mobile phase was acetonitrile-0.1% phosphoric acid solution with gradient elution; the detection wavelength was 254 nm; the flow rate was 0.30 ml/min and column temperature was 35 ℃. The method could determine content and fingerprint of rutin, Kaempferol-3-O-rutinoside, Narcissoside, Neochlorogenic aci, Chlorogenic Acid, Cryptochlorogenic acid and have quality analysis to 17 batches of Hedyotidis chrysotricahae Herba based on the variance of fingerprint, similarity evaluation, clustering analysis along with principal component analysis (PCA) at the same time.Results:The common pattern of UPLC specific chromatogram of Hedyotidis chrysotricahae Herba was established. The 11 common peaks were marked out, among which 7 peaks were identified. 17 batches Hedyotidis chrysotricahae Herba could be divided into 4 categories according to different origins. Quality content of six indicators of Hedyotidis chrysotricahae Herba was in slight difference between different origins, among which the content quality of Hedyotidis chrysotricahae Herba from Duyun in Guizhou Province was the highest.Conclusion:The established UPLC fingerprint and content determination method of 6 indicators from the study can be used for the quality control of Hedyotidis chrysotricahae Herba, which can also provide a theoretical basis for the standard improvement of Hedyotidis chrysotricahae Herba.

Objective To investigate the diagnostic value of magnetic resonance imaging(MRI)-based intratumoral and peritumoral radiomics of prostate cancer(PCa)for bone metastases.Methods A total of 211 patients diagnosed with PCa by biopsy pathology at Gansu Provincial People's Hospital from January 2018 to January 2023 were retrospectively analyzed.These patients were randomly divided into a training set(n=147)and a validation set(n=64)in a 7:3 ratio.Regions of interest(ROIs)were delineated from the patients'T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),and apparent diffusion coefficient imaging(ADC)sequences to extract radiomic features.Z-score(normalization)and the LASSO algorithm were used for feature dimensionality reduction,selection,and construction.A predictive model was then built using a logistic regression(LR)machine learning classifier.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to assess the model's performance.Calibration curves and decision curves(DCA)were plotted to evaluate the model's fit and clinical net benefit.Results Radiomic features were extracted from the tumor and peritumoral regions in each patient's T2WI,DWI,and ADC images,with a total of 312 features from each region.The LASSO regression model ultimately identified 10 intratumoral radiomic features closely related to bone metastasis,including 2 T2 sequence features,7 DWI features,and 1 ADC sequence feature;and 9 peritumoral radiomic features,including 4 T2 sequence features,3 DWI features,and 2 ADC sequence features.The predictive model based on intratumoral radiomic features achieved an AUC of 0.845(95%CI 0.747-0.943),while the predictive model based on peritumoral radiomic features had an AUC of 0.818(95%CI 0.716-0.919).A combined nomogram model incorporating intratumoral features,peritumoral radiomic features,and clinical features(including Gleason score,total prostate specific antigen,and body mass index)yielded an AUC of 0.936(95%CI 0.902-0.970).Calibration curves indicated that the combined model had good fit,and DCA demonstrated that the combined model provided better clinical net benefit.Conclusions Peritumoral radiomics has excellent predictive value for bone metastasis in newly diagnosed PCa.Combining with intratumoral radiomics features and clinical features,it significantly enhances the predictive capability of the model.

Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.