BACKGROUND: Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. METHODS: This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. RESULTS: From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management. CONCLUSIONS The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans ; China/epidemiology* ; Stroke/mortality* ; Rural Population/statistics & numerical data* ; Male ; Female ; Urban Population/statistics & numerical data* ; Middle Aged ; Aged ; Aged, 80 and over ; Adult

The increasing prevalence of aging has led to a rising incidence of comorbidity of sarcopenia and obesity, posing significant burdens on socioeconomic and public health. Current research has systematically explored the pathogenesis of each condition; however, the mechanisms underlying their comorbidity remain unclear. This study reviews the current literature on sarcopenia and obesity in the aging population, focusing on their shared biological mechanisms, which include loss of autophagy, abnormal macrophage function, mitochondrial dysfunction, and reduced sex hormone secretion. It also identifies metabolic mechanisms such as insulin resistance, vitamin D metabolism abnormalities, dysregulation of iron metabolism, decreased levels of nicotinamide adenine dinucleotide, and gut microbiota imbalances. Additionally, this study also explores the important role of genetic factors, such as alleles and microRNAs, in the co-occurrence of sarcopenia and obesity. A better understanding of these mechanisms is vital for developing clinical interventions and preventive strategies.
Humans ; Sarcopenia/physiopathology* ; Obesity/physiopathology* ; Aging/physiology* ; Autophagy/physiology* ; Insulin Resistance ; Comorbidity ; Vitamin D/metabolism* ; Gonadal Steroid Hormones/metabolism* ; Gastrointestinal Microbiome ; Mitochondria ; MicroRNAs

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

OBJECTIVE: To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue. METHODS: Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g^-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g^-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed. RESULTS: The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR. CONCLUSION The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals ; MicroRNAs/metabolism* ; Mice ; Male ; Brain/metabolism* ; Ziziphus/chemistry* ; Bone Development/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology*

OBJECTIVE: To investigate the clinical efficacy and safety of single Kirschner wire assisted poking and closed reduction in the treatment of Gartland type Ⅲ supracondylar humeral fractures in children. METHODS: A retrospective analysis was performed on patients diagnosed with Gravland type Ⅲ supracondylar humeral fractures between January 2022 and June 2023. A total of 46 patients were treated with closed reduction assisted by Kirschner wires and percutaneous Kirschner wire internal fixation.There were 25 males and 21 females. The age ranged from 5 to 10 years old, with an average of (5.8±1.8) years old. The left side was involved in 28 patients and the right side in 18 patients. Record the operative duration for patients, the number of fluoroscopic exposures, fracture healing time, postoperative carrying angle, Baumann angle, elbow joint function score at three months post-operation, and any associated complications. RESULTS: All 46 patients were followed up for a period of 12 to 16 weeks, with an average of (13.74±1.44 )weeks. The operation duration was (30.7±5.1) minutes, the fluoroscopy count was (10.2±2.7) times, the postoperative carrying angle of the elbow joint was (8.7±2.2) degrees, and the Baumann angle was (71.5±2.9) degrees. All fractures achieved successful union in all patients, with a mean healing time of (25.5±1.7) days.At the final follow-up, elbow joint function was assessed using the Flynn criteria, with 43 patients rated as excellent and 3 patients rated as good. No complications were observed, including cubitus varus, nerve injury, or local infection. CONCLUSION The use of a single Kirschner wire assisted prying reduction for treating Gartland type Ⅲ supracondylar humeral fractures in children demonstrates excellent clinical efficacy and safety.
Humans ; Male ; Female ; Child ; Bone Wires ; Child, Preschool ; Humeral Fractures/physiopathology* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Fracture Healing

PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.