Stroke ranks as the third leading cause of death and the fourth leading cause of disability worldwide. Its high disability rate and prolonged recovery period not only severely impact patients' quality of life but also impose a significant burden on families and society. Primary prevention is the cornerstone of stroke control, as early intervention on risk factors can effectively reduce its incidence. Therefore, the development of predictive models for first-ever stroke risk holds substantial clinical value. In recent years, advancements in big data and artificial intelligence technologies have opened new avenues for stroke risk prediction. This article reviews the current research status of traditional methods and machine learning models in predicting first-ever stroke risk and outlines future development trends from three perspectives: First, emphasis should be placed on technological innovation by incorporating advanced algorithms such as deep learning and large models to further enhance the accuracy of predictive models. Second, there is a need to diversify data types and optimize model architectures to construct more comprehensive and precise predictive models. Lastly, particular attention should be given to the clinical validation of models in real-world settings. This not only enhances the robustness and generalizability of the models but also promotes physicians' understanding of predictive models, which is crucial for their application and dissemination.

To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

OBJECTIVES: Platelet-rich plasma (PRP) treatment has been reported to improve ovarian function in women, but the relationship between the dose and frequency of PRP treatment and its therapeutic effect remains unclear. This study aims to evaluate the efficacy of single and double PRP treatments for diminished ovarian reserve (DOR). METHODS: A total of 65 patients treated at the Reproductive Center of Xiangtan Central Hospital from September 2020 to October 2022 were randomly divided into 4 groups: A single PRP treatment group (21 patients, PRP treatment once), a double PRP treatment group (15 patients, PRP treatment twice), a blank control group (15 patients), and an artificial cycle control group (14 patients, treated with estrogen and progesterone). The differences in baseline follicle-stimulating hormone (FSH), antral follicle count (AFC), ovarian volume, number of oocytes retrieved, number of good quality embryos, and pregnancy outcomes before and after treatment were compared among the 4 groups. RESULTS: Compared to before treatment, both single and double PRP treatment groups showed a significant reduction in FSH, and an increase in AFC, ovarian volume, numbers of oocytes retrieved, and number of MII oocytes (all P<0.05). Compared to the blank control group, the single and double PRP groups showed a decrease in FSH, with an increase in AFC, number of oocytes retrieved, and number of MII oocytes (all P<0.05). The rates of good quality embryos, clinical pregnancy rate, and live birth rate in the single and double PRP groups were higher than those in the blank control group and artificial cycle control groups, but the differences were not statistically significant (all P>0.05). Compared to the single PRP treatment group, the double PRP group had lower FSH and higher AFC, but the differences were not statistically significant (both P>0.05). CONCLUSIONS Both single and double PRP ovarian injections can effectively improve ovarian reserve function in DOR patients and enhance ovarian response. Compared to single PRP ovarian injection, double PRP ovarian injection shows a trend of better improvement in ovarian reserve function.
Humans ; Female ; Platelet-Rich Plasma ; Ovarian Reserve/physiology* ; Adult ; Pregnancy ; Follicle Stimulating Hormone/blood* ; Pregnancy Rate ; Ovary ; Ovulation Induction/methods* ; Ovarian Follicle ; Oocyte Retrieval

Invasive angiomyxoma（AAM） is characterized by unclear boundaries, non enveloped glial growth, high recurrence rate, and belongs to a benign tumor, but it is invasive and grows slowly. A patient with recurrent left vestibular invasive angiomyxoma was admitted to the Otorhinolaryngology ward of Beijing Traditional Chinese Medicine Hospital Affiliated with Capital Medical University. The patient underwent two repeated surgeries and underwent a combined internal and external nasal approach for the removal of the nasal vestibular angiomyxoma. The patient recovered well after the surgery and has not recurred since follow-up.
Humans ; Myxoma/pathology* ; Neoplasm Recurrence, Local ; Nose Neoplasms/pathology*

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*