BACKGROUND:The causal relationship between modifiable factors such as lifestyle,metabolic characteristics,and nutritional intake and joint sports injuries has been increasingly recognized in clinical studies.However,the exact causal relationship between these modifiable factors and joint sports injuries remains unclear. OBJECTIVE:To investigate the causal relationship between modifiable factors and joint sports injuries using Mendelian randomization to provide a basis for sports injury prevention. METHODS:The GWAS dataset of intervening factors and joint sports injuries was obtained from publicly available data.The causal relationships between lifestyle,metabolic characteristics,nutritional intake,and joint sports injuries were explored using the inverse variance weighting method,the MR-Egger method,and the weighted median method.For sensitivity analyses,Cochran's Q test,MR-Egger regression,leave-one-out method,and MR-PRESSO were used to verify the stability and reliability of the results. RESULTS AND CONCLUSION:(1)In terms of lifestyle,coffee(OR=0.29,95%CI:0.10-0.79,P=0.016),and tea consumption(OR=0.41,95%CI=0.19-0.85,P=0.017)were associated with a decreased risk of ankle and foot joint sports injuries,and coffee consumption(OR=3.31,95%CI=1.02-10.73,P=0.046)was potentially causally associated with an increased risk of shoulder joint sports injuries;and never smoking(OR=0.78,95%CI=0.70-0.87,P=1.49×10-5)was significantly causally associated with a decreased risk of ankle and foot joint sports injuries.(2)In terms of metabolic characteristics,calcium levels(OR=0.88,95%CI=0.79-0.98,P=0.017)were potentially causally associated with a decreased risk of wrist and hand joint sports injuries.(3)In terms of nutritional intake,vitamin A intake(OR=1.08,95%CI:1.02-1.13,P=0.007)was potentially causally associated with increased risk of knee joint sports injury.(4)For the sensitivity analysis,Cochran's Q test showed the existence of heterogeneity(P<0.05),so the random effect model was used for the analysis.MR-Egger regression and MR-PRESSO test did not find evidence of pleiotropy(P>0.05),and the leave-one-out method showed that the results were stable after eliminating single nucleotide polymorphisms one by one.(5)This study preliminarily reveals the effects of modifiable factors,such as lifestyle,metabolic characteristics,and nutritional intake,on the risk of joint sports injuries.It provides valuable research evidence and guidance for the prevention of joint sports injuries.

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry

This study aims to investigate the mechanism through which Xiangshao Granules treat anxiety and depression using metabolomics and gut microbiota techniques, combined with animal experiments. Sixty female ICR mice were selected for the experiment and randomly divided into six groups: a control group, a model group, a low-dose Xiangshao Granules group, a medium-dose Xiangshao Granules group, a high-dose Xiangshao Granules group, and an estradiol(positive drug) group. Except for the control group, rats in other groups were induced for anxiety and depression model by ovariectomy(OVX) combined with chronic unpredictable mild stress(CUMS). After successful modeling, the mice received oral administration of Xiangshao Granules or estradiol for three weeks. Anxiety and depression behaviors in mice were evaluated using light-dark box tests, open field tests, and elevated plus-maze tests. The levels of substances closely related to anxiety and depression, such as serotonin(5-HT) and estrogen(E_2), were quantified in plasma and hippocampal tissue using enzyme-linked immunosorbent assay(ELISA). Metabolomics and 16S rDNA amplicon sequencing techniques were employed to analyze the regulatory effects of Xiangshao Granules on plasma metabolites and metabolic pathways in anxiety and depression mice, as well as their impact on the distribution of gut microbiota. Finally, the correlation between plasma metabolites and differential gut microbiota was constructed using the Spearman correlation coefficient method. Behavioral experimental results indicated that, compared to the control group, the model group exhibited significantly decreased dwell time in the light box, reduced total distance in the open field, and diminished dwell time in the open arm. In contrast, high dose of Xiangshao Granules were found to increase the dwell time in the light box and total distance in the open field. ELISA results indicated that the levels of 5-HT, gamma-aminobutyric acid(GABA), E_2 were significantly decreased, luteinizing hormone(LH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) were significantly elevated in the anxiety and depression mice, and treatment with middle, high dose of Xiangshao Granules reversed the levels of these substances. Additionally, in the anxiety and depression mouse model, the levels of follicle-stimulating hormone(FSH) were significantly increased, whereas middle, high dose of Xiangshao Granules decreased FSH levels. Metabolomics analysis revealed that Xiangshao Granules significantly changed the metabolic profile of the anxiety and depression mice, affecting central carbon metabolism, amino acid biosynthesis, and ABC transporter pathways. The results from 16S rDNA amplicon sequencing showed that Xiangshao Granules improved the relative abundance of genera such as Bacteroidia, Bacilli, Lactobacillales, and Lactobacillus. Spearman correlation analysis indicated a close association between specific differential gut microbiota and plasma differential metabolites. This study suggests that Xiangshao Granules significantly ameliorate anxiety and depression symptoms in mice by altering the levels of substances associated with these conditions, including 5-HT, GABA, E_2, LH, and ACTH. The metabolomics and gut microbiota data suggest that the therapeutic mechanism may be closely related to the regulation of amino acid biosynthesis, central carbon metabolism, and the alteration of key microbial community compositions.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety/microbiology* ; Depression/microbiology* ; Gastrointestinal Microbiome/drug effects* ; Mice ; Female ; Mice, Inbred ICR ; Metabolomics ; Serotonin/metabolism* ; Humans ; Disease Models, Animal ; Rats ; Behavior, Animal/drug effects*

OBJECTIVES: Recent advancements in single-cell RNA sequencing (scRNA-seq) have revolutionized the study of cellular heterogeneity, particularly within the hematological system. However, accurately annotating cell types remains challenging due to the complexity of immune cells. To address this challenge, we develop a PAN-blood single-cell Data Annotator (scPANDA), which leverages a comprehensive 10-million-cell atlas to provide precise cell type annotation. METHODS: The atlas, constructed from data collected in 16 studies, incorporated rigorous quality control, preprocessing, and integration steps to ensure a high-quality reference for annotation. scPANDA utilizes a three-layer inference approach, progressively refining cell types from broad compartments to specific clusters. Iterative clustering and harmonization processes were employed to maintain cell type purity throughout the analysis. Furthermore, the performance of scPANDA was evaluated in three external datasets. RESULTS: The atlas was structured hierarchically, consisting of 16 compartments, 54 classes, 4,‍460 low-level clusters (pd_cc_cl_tfs), and 611 high-level clusters (pmid_cts). Robust performance of the tool was demonstrated in annotating diverse immune scRNA-seq datasets, analyzing immune-tumor coexisting clusters in renal cell carcinoma, and identifying conserved cell clusters across species. CONCLUSIONS scPANDA exemplifies effective reference mapping with a large-scale atlas, enhancing the accuracy and reliability of blood cell type identification.
Humans ; Single-Cell Analysis/methods* ; Sequence Analysis, RNA/methods* ; Blood Cells

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To compare the therapeutic efficacy and safety of local anesthesia and spinal anesthesia for the patients with varicocele (VC) who underwent microsurgical varicocelectomy (MV). METHODS: We retrospectively analyzed the data of VC patients who underwent MV treatment at the Andrology Department of the Affiliated Ruikang Hospital of Guangxi University of Chinese Medicine from May 2020 to March 2023. Cases with complete clinical data and follow-up evaluation were selected and divided into a control group (spinal anesthesia) and an observation group (local anesthesia) according to different anesthesia methods. The surgical time (including anesthesia time), visual analogue scale (VAS) score for pain, hospital stay, treatment cost, sperm concentration, forward motile sperm rate, and normal sperm morphology rate after three months of surgery, as well as postoperative complications and recurrence rate were compared between the two groups. RESULTS: A total of 107 eligible cases were included, with 56 cases in the control group and 51 cases in the observation group. There was no significant difference in the VAS score for pain during and after four hours of surgery, as well as postoperative complications, and recurrence rate between the two groups (P> 0.05). There was an significant increase in sperm concentration, forward motile sperm rate, and normal sperm morphology rate in both of two groups after three months of surgery (P<0.05). However, there was no significant difference between the two groups three months after surgery (P>0.05). The surgical time and hospital stay were shorter than those of the control group (P<0.05). And the treatment cost in observation group was lower than that of the control group (P<0.05). CONCLUSION Both local anesthesia and lumbar anesthesia for MV treatment of VC have good efficacy and safety. However, patients treated with MV under local anesthesia for VC have obvious advantages in terms of operation time (including anesthesia time), hospital stay, and treatment cost, which is worthy of clinical promotion and application.
Humans ; Male ; Varicocele/surgery* ; Retrospective Studies ; Microsurgery ; Anesthesia, Spinal ; Adult ; Treatment Outcome ; Anesthesia, Local