Beijing University of Chinese Medicine and Pharmacology

Purpose This study aimed to explore the potential causal relationship between dietary habits and Gastroesophageal Reflux Disease (GERD). Methods Using the inverse-variance weighted method, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between 22 dietary habits and GERD. The stability and reliability of the results were assessed using leave-one-out analysis, heterogeneity tests, and tests for horizontal pleiotropy based on the effect measure odds ratio (OR) and 95% confidence interval (CI). Results The results of the MR analysis indicated a positive association between alcohol drinking (OR=1.472; 95% CI, 1.331 to 1.629; p<1.0×10-3) and salt added to food (OR=1.270; 95% CI, 1.117 to 1.443; p<1.0×10-3) with the risk of GERD. Conversely, bread intake (OR=0.613; 95% CI, 0.477 to 0.790; p<1.0×10-3), cereal intake (OR=0.613; 95% CI, 0.391 to 0.677; p<1.0×10-3), cheese intake (OR=0.709; 95% CI, 0.593 to 0.846; p<1.0×10-3), dried fruit intake (OR=0.535; 95% CI, 0.404 to 0.709; p<1.0×10-3), fresh fruit intake (OR=0.415; 95% CI, 0.278 to 0.619; p<1.0×10-3), and oily fish intake (OR=0.746; 95% CI, 0.633 to 0.879; p<1.0×10-3) were negatively associated with the risk of GERD. Sensitivity analysis showed no evidence of reverse causation, pleiotropy, or heterogeneity. Conclusion Alcohol and salt added to food raised GERD risk, while bread intake, cereal intake, cheese intake, intake of certain dried fruits and certain fresh fruits, and oily fish lowered it. Our study affirms the potential causal link between these diets and GERD, offering insights into targeted prevention strategies.

Background This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission. Methods This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell’s C-index, calibration plots, DCA, and K-M curve. Result Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836–0.881), 0.773 (0.746–0.799), 0.736 (0.701–0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723–0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model’s good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P < 0.0001). Conclusion The nomogram can provide valuable guidance for clinical practitioners to early predict the probability of RF occurrence in AECOPD patients, take relevant measures, prevent RF, and improve patient outcomes.

This meta-analysis aims to evaluate the safety and efficacy of restarting immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) after experiencing immune-related adverse events (irAEs). A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted to identify studies investigating the safety and efficacy of restarting ICIs in NSCLC patients after irAEs. Outcome measures, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) after ICI restarting, were extracted. Meta-analysis was performed using the R meta-package. Four studies involving a total of 326 subjects were included, comprising 137 patients who restarted ICI treatment after irAEs and 189 patients who did not restart ICI treatment. The results revealed that ICI restarting was associated with an increased ORR (OR = 2.36, 95% CI 1.49–3.84), prolonged PFS (HR = 0.60, 95% CI 0.42–0.86), and prolonged OS (HR = 0.65, 95% CI 0.43–0.99) compared to non-restarting. The incidence of irAEs after ICI restarting was 45% (95% CI 0.27–0.63). Restarting ICI treatment after discontinuation due to previous irAEs appears to be a reasonable option for NSCLC patients. However, a comprehensive assessment of the potential benefits and risks to individual patients is crucial, and close monitoring of irAEs is warranted.

Aims Patients with heart valvular regurgitation is increasing; early screening of potential patients developing heart failure (HF) is crucial. Methods From 1 November 2019 to 31 October 2023, a total of 509 patients with heart valvular regurgitation hospitalized in the Department of Cardiovascular Disease of the First Affiliated Hospital of Guangzhou University of Traditional Medicine were enrolled. Three hundred fifty‐six cases were selected as the training set for modelling, and 153 cases were selected as the validation set for the internal validation of the model. Results A predictive model of heart failure with the following nine risk factors was developed: atrial fibrillation (AF), pulmonary infection (PI), coronary artery disease (CAD), creatinine (CREA), low‐density lipoprotein cholesterol (LDL‐C), d‐dimer (DDi), left ventricular end‐diastolic diameter (LVEDd), mitral regurgitation (MR) and aortic regurgitation (AR). The model was evaluated by the C‐index [the training set: area under curve (AUC) 0.937, 95% confidence interval (CI) 0.911–0.963; the validation set: AUC 0.928, 95% CI 0.890–0.967]. Hosmer–Lemeshow test (the training set: χ² 10.908, P = 0.207; the validation set: χ² 4.896, P = 0.769) revealed that both the training and validation sets performed well in terms of model differentiation and calibration. Decision curve analysis showed that both the training and validation sets have higher net benefits, indicating that the model has good utility. Ten‐fold cross‐validation showed that the training set has high similarities with the validation set, which means that the model has good stability. Conclusions The occurrence of heart failure in patients with valvular regurgitation has a significant correlation with AF, PI, CAD, CREA, LDL‐C, DDi, LVEDd, MR and AR. Based on these risk factors, a prediction model for heart failure was developed and validated, which showed good differentiation and utility, high accuracy and stability, providing a method for predicting heart failure.

To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.

Background The risk of asthma in patients with psoriasis has been identified in previous studies, but the bidirectional association between the two has not been fully explored. Methods We thoroughly searched PubMed, Embase, and the Cochrane Library to find relevant observational studies published from the inception of these databases to October 2023. All the risk and bias assessments were analyzed by STATA 16.0. Where the heterogeneity was less than 50%, the fixed effect model was utilized. While where the level of heterogeneity was more than 50%, the random effect model was applied. Moreover, to identify publication bias, a visual funnel chart, and Egger’s test were applied. Results A total of 12,396,911 participants from 16 studies, published between 2011 and 2023 were included in this meta-analysis. We found that psoriasis patients had a higher risk of developing asthma (OR = 1.48, 95%CI 1.28–1.68). Meanwhile, asthma patients also had a higher overall risk of developing psoriasis (OR = 1.33, 95%CI 1.23–1.44). In the subgroup analysis, we found that the type of study, age, and severity of the psoriasis were significant factors in the survey of asthma risk in psoriasis patients. Conclusions In the present systematic review and meta-analysis, we found a bidirectional association between psoriasis and asthma with significantly increased risk. As a result, clinicians should make patients aware of the connection between the two, particularly adolescents or patients with moderate to severe psoriasis who need to be informed about the rising likelihood of developing asthma. Trial registration Registration number CRD42023390111.

Maintaining a balanced bile acids (BAs) metabolism is essential for lipid and cholesterol metabolism, as well as fat intake and absorption. The development of obesity may be intricately linked to BAs and their conjugated compounds. Our study aims to assess how BAs influence the obesity indicators by Mendelian randomization (MR) analysis. Instrumental variables of 5 BAs were obtained from public genome-wide association study databases, and 8 genome-wide association studies related to obesity indicators were used as outcomes. Causal inference analysis utilized inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Sensitivity analysis involved MR-PRESSO and leave-one-out techniques to detect pleiotropy and outliers. Horizontal pleiotropy and heterogeneity were assessed using the MR-Egger intercept and Cochran Q statistic, respectively. The IVW analysis revealed an odds ratio of 0.94 (95% confidence interval: 0.88, 1.00; P = .05) for the association between glycolithocholate (GLCA) and obesity, indicating a marginal negative causal association. Consistent direction of the estimates obtained from the weighted median and MR-Egger methods was observed in the analysis of the association between GLCA and obesity. Furthermore, the IVW analysis demonstrated a suggestive association between GLCA and trunk fat percentage, with a beta value of −0.014 (95% confidence interval: −0.027, −0.0004; P = .04). Our findings suggest a potential negative causal relationship between GLCA and both obesity and trunk fat percentage, although no association survived corrections for multiple comparisons. These results indicate a trend towards a possible association between BAs and obesity, emphasizing the need for future studies.

Background Global antipsychotic usage, including off-label prescriptions, has increased in recent decades. However, trends in China, particularly for children and adolescents, remain unclear. This study explored these trends from 2016 to 2021 and identified factors associated with off-label prescriptions. Methods In this retrospective study, we analyzed on-label and off-label prescriptions based on drug information approved by the China National Medical Products Administration. To identify factors associated with off-label prescriptions, we conducted multivariate logistic regression analysis. Results Our study included 48,258 antipsychotic prescriptions, 52.4% (25,295) of which were prescriptions for males. Of these, 61.7% (29,813) were off-label. Over time, the number of antipsychotics and the percentage of off-label prescriptions for children and adolescents overall increased from 2016 to 2021. The use of atypical antipsychotics increased, whereas that of typical antipsychotics decreased. For off-label usage, all of the factors in our study were associated with off-label usage, including age, sex, year, region, department, reimbursement, antipsychotic type, drug expense, number of polypharmacy and diagnoses. Additionally, tiapride (15.8%) and aripiprazole (18.6%) were the most common typical and atypical antipsychotics, respectively. For pediatric diseases, common diagnoses included mood or affective disorders (31.7%) and behavioral and emotional disorders, with onset usually occurring in childhood and adolescence (29.1%). Furthermore, a depressive state was the most common diagnosis for which antipsychotic polypharmacy was used for treatment. Conclusion In this retrospective study, off-label antipsychotic prescriptions were common, with trends generally increasing among children and adolescents from 2016 to 2021. However, there is a lack of evidence supporting off-label usage, thus emphasizing the need for studies on the efficacy and safety of these treatments.

The human vagina harbours diverse microorganisms—bacteria, viruses and fungi—with profound implications for women’s health. Genome-level analysis of the vaginal microbiome across multiple kingdoms remains limited. Here we utilize metagenomic sequencing data and fungal cultivation to establish the Vaginal Microbial Genome Collection (VMGC), comprising 33,804 microbial genomes spanning 786 prokaryotic species, 11 fungal species and 4,263 viral operational taxonomic units. Notably, over 25% of prokaryotic species and 85% of viral operational taxonomic units remain uncultured. This collection significantly enriches genomic diversity, especially for prevalent vaginal pathogens such as BVAB1 (an uncultured bacterial vaginosis-associated bacterium) and Amygdalobacter spp. (BVAB2 and related species). Leveraging VMGC, we characterize functional traits of prokaryotes, notably Saccharofermentanales (an underexplored yet prevalent order), along with prokaryotic and eukaryotic viruses, offering insights into their niche adaptation and potential roles in the vagina. VMGC serves as a valuable resource for studying vaginal microbiota and its impact on vaginal health.

Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe²⁺, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.