Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.
Animals ; Humans ; Medicine, Chinese Traditional/adverse effects* ; Cardiotoxicity ; Induced Pluripotent Stem Cells ; Arrhythmias, Cardiac/chemically induced* ; Myocytes, Cardiac ; Organoids ; Drugs, Chinese Herbal/adverse effects*

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.
Chemometrics ; Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Scutellaria ; Tandem Mass Spectrometry/methods*

OBJECTIVE: To establish an immune gene prognostic model of acute myeloid leukemia (AML) and explore its correlation with immune cells in bone marrow microenvironment. METHODS: Gene expression profile and clinical data of TCGA-AML were downloaded from TCGA database. Immune genes were screened by LASSO analysis to construct prognosis prediction model, and prediction accuracy of the model was quantified by receiver operating characteristic curve and area under the curve. Survival analysis was performed by Log-rank test. Enriched pathways in the different immune risk subtypes were evaluated from train cohort. The relationship between immune prediction model and bone marrow immune microenvironment was verified by flow cytometry in the real world. RESULTS: Patients with low-risk score of immune gene model had better prognosis than those with high-risk score. Multivariate analysis showed that the immune gene risk model was an independent prognostic factor. The risk ratio for AML patients in the training concentration was HR=24.594 (95%CI: 6.180-97.878), and the AUC for 1-year, 3-year, and 5-year overall survival rate was 0.811, 0.815, and 0.837, respectively. In addition, enrichment analysis of differential gene sets indicated activation of immune-related pathways such as cytokines and chemokines as well as autoimmune disease-related pathways. At the same time, real world data showed that patients with high immune risk had lower numbers of CD8⁺T cells and B lymphocytes compared with low immune risk patients. CONCLUSION We constructed a stable prognostic model for AML, which can not only predict the prognosis of AML, but also reveal the dysregulation of immune microenvironment.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Prognosis ; ROC Curve ; Risk Factors ; Transcriptome ; Tumor Microenvironment/genetics*

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)₃ gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)₃ gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Objective: To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI) and the risk factors of all-cause mortality at 30 days after operation. Methods: This is a retrospective case series study. A total of 69 patients with post-AMI VSR, underwent percutaneous closure of VSR from October 2013 to May 2020 in Department of Cardiology of Henan Provincial People's Hospital and Department of Cardiology of Central China Fuwai Hospital, were included. Patients were divided into survival group (53 cases) and non-survival group (16 cases) according to the status at 30 days after operation. Clinical data were collected and analyzed during hospitalization. Telephone follow-up was performed 30 days after operation. The primary safety endpoint was occlusion failure and all-cause mortality at 30 days post operation. The secondary safety endpoint was the operation related or non-operation related complications. Efficacy endpoint included NYHA classification of cardiac function, index measured by right heart catheterization and echocardiography. Multivariate logistic regression was performed to analyze the risk factors of all-cause mortality at 30 days after operation. Results: A total of 69 patients, aged 67 (64, 71) years, including 42 women (60.9%), were enrolled in this study. All-cause death occurred in 16 patients (23.2%), including 13 in-hospital death and 3 death during follow-up. There were 4 cases of closure failure (5.8%). Among the 65 patients with successful closure, 12 (18.5%) experienced operation-related complications, among which 8 (12.3%) experienced valve injury. The mortality was significantly higher in patients with operation-related complications than that in patients without operation-related complications (41.7% (5/12) vs. 13.2% (7/53), P = 0.022). One case received percutaneous closure of VSR and PCI, this patient experienced new-onset AMI immediately post procedure and died thereafter (1.5%). One case (1.5%) developed multiple organ failure and 2 cases (3.1%) developed gastrointestinal bleeding post operation. All of the 65 patients with successful occlusion completed postoperative echocardiography, 56 patients completed cardiac function assessment at discharge, and 53 patients who survived up to 30 days post discharge completed clinical follow up by telephone. The NYHA cardiac function at discharge and 30 days after operation were significantly improved as compared to that before operation (P<0.001), the ratio of NYHA Ⅰ and Ⅱ patients was significantly higher post operation at these two time points as compared to baseline level (76.8% (43/56) vs. 23.1% (15/65), P<0.001, 77.4% (41/53) vs. 23.1% (15/65), P<0.001). The pulmonary circulation/systemic circulation blood flow ratio (Qp/Qs), pulmonary artery systolic pressure (PASP) and left ventricular end-diastolic diameter (LVDd) were decreased, aortic systolic pressure (ASP) and left ventricular ejection fraction (LVEF) were increased post operation (P<0.05). Multivariate logistic regression analysis showed that WBC>9.8×10⁹/L (OR=20.94, 95%CI 1.21-362.93, P=0.037) and NT-ProBNP>6 000 ng/L (OR=869.11, 95%CI 2.93-258 058.34, P=0.020) were the independent risk factors of mortality at 30 days. Conclusions: Percutaneous closure in VSR after AMI is safe and effective. The increase of WBC and NT-ProBNP are the independent risk factors of all-cause mortality at 30 days after operation.
Aftercare ; Female ; Hospital Mortality ; Humans ; Myocardial Infarction ; Patient Discharge ; Percutaneous Coronary Intervention ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left ; Ventricular Septal Rupture/surgery*

BACKGROUNDS: Cervical posterior decompression surgery is used to relieve ventral compression indirectly by incorporating a backward shift of the spinal cord, and this indirect decompression is bound to be limited. This study aimed to determine the decompression limit of posterior surgery and the effect of the decompression range. METHODS: We retrospectively reviewed the data of 129 patients who underwent cervical open-door laminoplasty through 2008 to 2012 and were grouped as follows: C4-C7 (n = 11), C3-C6 (n = 61), C3-C7 (n = 32), and C2-C7 (n = 25). According to the relative location of spinal levels within a decompression range, the type of decompression at a given level was categorized as external decompression (ED; achieved at the levels located immediately external to the decompression range margin), internal decompression (ID; achieved at the levels located immediately internal to the decompression range margin), and central decompression (CD; achieved at the levels located in the center, far from the decompression range margin). The vertebral-cord distance (VCD) was used to evaluate the decompression limit. The C2-C7 angle and VCD on post-operative magnetic resonance images were analyzed and compared between groups. The relationship between VCD and decompression type was analyzed. Moreover, the relationship between the magnitude of the ventral compressive factor and the probability of post-operative residual compression at each level for different decompression ranges was studied. RESULTS: There was no significant kyphosis in cervical curvature (> -5°), and there was no significant difference among the groups (F = 2.091, P = 0.105). The VCD of a specific level depended on the decompression type of the level and followed this pattern: ED < ID < CD (P < 0.05). The decompression type of a level was sometimes affected by the decompression range. For a given magnitude of the ventral compressive factor, the probability of residual compression was lower for the group with the larger VCD at this level. CONCLUSIONS Our study suggests that the decompression range affected the decompression limit by changing the decompression type of a particular level. For a given cervical spinal level, the decompression limit significantly varied with decompression type as follows: ED < ID < CD. CD provided maximal decompression limit for a given level. A reasonable range of decompression could be determined based on the relationship between the magnitude of the ventral compressive factor and the decompression limits achieved by different decompression ranges.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

BACKGROUND: Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population. METHODS: We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed. RESULTS: In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05). CONCLUSION Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.
Alzheimer Disease ; Amyloid beta-Peptides ; Biomarkers ; Case-Control Studies ; Cognition ; Cross-Sectional Studies ; Humans ; Peptide Fragments ; tau Proteins