Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

Microbial detection and control of traditional Chinese medicine(TCM) decoction pieces are crucial for the quality control of TCM preparations. It is also a key area of research in the measurement technology and equipment development for TCM manufacturing. Guided by TCM manufacturing measurement methodologies, this study presented a design of a novel portable microbial detection device, using Atractylodis Macrocephalae Rhizoma decoction pieces as a demonstration. Immunomagnetic separation technology was employed for specific isolation and labeling of target microorganisms. Enzymatic signal amplification was utilized to convert weak biological signals into colorimetric signals, constructing an optical biosensor. A self-developed smartphone APP was further applied to analyze the colorimetric signals and quantify target concentrations. A portable and automated detection system based on Arduino microcontroller was developed to automatically perform target microbial separation/extraction, as well as mimetic enzyme labeling and catalytic reactions. The developed equipment specifically focuses on the rapid and quantitative microbial analysis of TCM active pharmaceutical ingredients, intermediates in TCM manufacturing, and final TCM products. Experimental results demonstrate that the equipment could detect Salmonella in samples within 2 h, with a detection limit as low as 5.1 × 10~3 CFU·mL~(-1). The equipment enables the rapid detection of microorganisms in TCM decoction pieces, providing a potential technical solution for on-site rapid screening of microbial contamination indicators in TCM. It has broad application prospects in measurement technology for TCM manufacturing and offers strong technical support for the modernization, industrialization, and intelligent development of TCM.
Drugs, Chinese Herbal/analysis* ; Atractylodes/microbiology* ; Rhizome/microbiology* ; Biosensing Techniques/methods* ; Medicine, Chinese Traditional ; Colorimetry/instrumentation* ; Quality Control

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

BACKGROUND: The beneficial effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on adverse cardiac outcomes in diabetic patients are well-established. However, the effects of SGLT2i against cancer therapy-related cardiotoxicity remain understudied. We investigated the association between SGLT2i and cardiac outcomes in cancer patients. METHODS: PubMed, Embase, and the Cochrane Library were searched from their inception until September 30, 2024 for studies evaluating the effects of SGLT2i in patients with cancer. The primary outcomes included incident heart failure (HF), HF exacerbation, HF hospitalization, atrial fibrillation/atrial flutter (AF/AFL), myocardial infarction, and all-cause mortality. The secondary outcomes included acute kidney injury and sepsis. Odds ratio (OR) with 95% CI was pooled. RESULTS: Thirteen studies with 85,596 patients were included. Compared to non-SGLT2i use, SGLT2i treatment was associated with lower risks of incident HF (OR = 0.51, 95% CI: 0.32-0.79, P = 0.003), HF exacerbation (OR = 0.74, 95% CI: 0.63-0.87, P < 0.001), AF/AFL (OR = 0.67, 95% CI: 0.55-0.82, P < 0.001), myocardial infarction (OR = 0.61, 95% CI: 0.41-0.90, P = 0.01), and all-cause mortality (OR = 0.44, 95% CI: 0.28-0.69, P < 0.001), but not for HF hospitalization (OR = 0.58, 95% CI: 0.22-1.55, P = 0.28). As for safety outcomes, SGLT2i use was associated with lower risks of acute kidney injury (OR = 0.68, 95% CI: 0.57-0.81, P < 0.001) and sepsis (OR = 0.32, 95% CI: 0.23-0.44, P < 0.001). CONCLUSIONS SGLT2i were associated with lower risks of incident HF, HF exacerbation, AF/AFL, myocardial infarction, all-cause mortality, acute kidney injury, and sepsis in cancer patients.

OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

OBJECTIVES: The Charlson comorbidity index reflects overall comorbidity burden and has been applied in cardiovascular medicine. However, its role in predicting in-hospital mortality in patients with acute myocardial infarction (AMI) complicated by ventricular arrhythmias (VA) remains unclear. This study aims to evaluate the predictive value of the Charlson comorbidity index in this setting and to construct a nomogram model for early risk identification and individualized management to improve outcomes. METHODS: Using the open-access critical care database MIMIC-IV (Medical Information Mart for Intensive Care IV), we identified intensive care unit (ICU) patients diagnosed with AMI complicated by VA. Patients were grouped according to in-hospital survival. The predictive performance of the Charlson comorbidity index and other clinical variables for in-hospital mortality was analyzed. Key predictors were selected using the least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable Logistic regression. A nomogram model was constructed based on the regression results. Model performance was assessed using receiver operating characteristic (ROC) curves and calibration plots. RESULTS: A total of 1 492 patients with AMI and VA were included, of whom 340 died and 1 152 survived during hospitalization. Significant differences were observed between survivors and non-survivors in sex distribution, vital signs, comorbidity burden, organ function, and laboratory parameters (all P<0.05). The area under the curve (AUC) of the Charlson comorbidity index for predicting in-hospital mortality was 0.712 (95% CI 0.681 to 0.742), significantly higher than albumin, international normalized ratio (INR), hemoglobin, body temperature, and platelet count (all P<0.001), but comparable to Sequential Organ Failure Assessment (SOFA) score (P>0.05). LASSO regression identified seven key predictors: the Charlson comorbidity index (quartile groups: T1, <6; T2, ≥6-<7; T3, ≥7-<9; T4, ≥9), ventricular fibrillation, age, systolic blood pressure, respiratory rate, body temperature, and SOFA score. Multivariate Logistic regression showed that compared with T1, mortality risk increased significantly in T2 (OR=1.996, 95% CI 1.135 to 3.486, P=0.016), T3 (OR=3.386, 95% CI 2.192 to 5.302, P<0.001), and T4 (OR=5.679, 95% CI 3.711 to 8.842, P<0.001). Age (OR=1.056, P<0.001), respiratory rate (OR=1.069, P<0.001), SOFA score (OR=1.223, P<0.001), and ventricular fibrillation (OR=2.174, P<0.001) were independent risk factors, while systolic blood pressure (OR=0.984, P<0.001) and body temperature (OR=0.648, P<0.001) were protective factors. The nomogram incorporating these predictors achieved an AUC of 0.849 (95% CI 0.826 to 0.871) with high discrimination and good calibration (mean absolute error=0.014). CONCLUSIONS The Charlson comorbidity index is an independent predictor of in-hospital mortality in AMI patients complicated by VA, with performance comparable to the SOFA score. The nomogram model based on the Charlson comorbidity index and additional clinical variables effectively estimates mortality risk and provides a valuable reference for clinical decision-making.
Humans ; Nomograms ; Hospital Mortality ; Myocardial Infarction/complications* ; Male ; Female ; Comorbidity ; Middle Aged ; Aged ; Arrhythmias, Cardiac/complications* ; ROC Curve ; Intensive Care Units

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Objective:To discuss the clinical characteristics,diagnosis processes,and treatment methods of one patient with congenital intrabdominal hernia,and to summarize the potential misconceptions during the diagnostic and treatment processes,and to improve the clinicians'awareness of this disease.Methods:The clinical data and auxiliary examination results of one patient with congenital intrabdominal hernia were collected and analyzed,and the related literatures were reviewed.Results:The patient,a 65-year-old male,sought care at the local hospital due to upper abdominal pain before 2 d;there were no significant abnormalities in the examination results at the cocal hospital;blood glucose>25 mmol·L-1.After receiving hypoglycemic,rehydration,and blood purification treatment,the condition of the patient was worsened,presenting with confusion,hypotension,and respiratory distress;the patient admitted in our hospital for further diagnosis and treatment.After admission,the patient was given despite fluid resuscitation,mechanical ventilation,and supportive treatment,but there was no improvement in the symptoms;interventional radiology was performed angiography of the abdominal artery and right femoral vein,which showed no significant vascular abnormalities in the abdomen.An abdominal paracentesis yielded a mixed bloody fluid,suggesting the concealed intraperitoneal disease;exploratory laparotomy was performed.During operation,the intrabdominal hernia with small intestine necrosis and septic shock were diagnosed,and partial small intestine resection,anastomosis,adhesiolysis,and abdominal irrigation and drainage were carried out.The patient had a good recovery and was discharged on the 14th day after operation.Conclusion:Congenital intrabdominal hernia is a very rare cause of intestinal obstruction in the adults,and high suspicion for intrabdominal hernia is one of the differential diagnosis for atypical acute abdomen;early multidisciplinary intervention can be lifesaving for the patients.