BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Sinusitis is a prevalent nasal disease in children, characterized by chronic and difficult-to-treat symptoms. Its onset is related to nasal stagnation, gallbladder and lung dysfunctions. This article explores the root cause based on Huangdi Neijing by considering the physiological and pathological characteristics of children. The core pathogenesis of pediatric sinusitis is the transmission of heat from the gallbladder and lung to the brain and nose, disrupting normal nasal function. Wind and heat pathogens often persist, accumulate, and transform into turbid qi, which are common triggers of the disease. Evil qi retention and yin depletion are internal factors that cause the prolonged and unhealed condition of the disease. This article emphasizes individualized treatment approaches based on disease duration and the severity of pathogenic factors. If external pathogens remain uncleared, treatment should focus on dispelling wind, clearing heat, dispersing with pungent medicinals, and dredging nasal orifices. If internal fire is exuberant, clearing lung qi, inhibiting hyperactive liver yang, and clearing exuberant fire should be used to relieve stagnation. In chronic cases with residual pathogens and liver-kidney yin deficiency, nourishing yin, clearing fire, and moistening the nasal orifices are essential. When exuberant heat has subsided, but the symptom of a persistent runny nose continues, leading to the loss of healthy qi and damage to the lung and spleen, treatments that tonify the spleen, benefit the lung, and reinforce healthy qi should be adopted to relieve stagnation. These treatments aim to restore the balance of the body′s vital qi by addressing both the lingering symptoms and the underlying weakness of the lung and spleen. The diagnosis and treatment of pediatric sinusitis based on the theory of "the transmission of heat from gallbladder and lung" can help reduce the recurrence of sinusitis and alleviate symptoms, with the aim of broadening the approach of traditional Chinese medicine in treating this condition.

Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

Colorectal cancer （CRC） is a prevalent malignant tumor of the digestive tract， with a high incidence and high mortality. The majority of patients are diagnosed at the middle or advanced stage， which severely influences and threatens their physical health. Current treatment modalities such as surgery， radiotherapy， and chemotherapy often encounter challenges including metastasis， recurrence， and drug resistance. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway serves as a classical regulator that regulates physiological processes such as cell cycle， autophagy， apoptosis， and proliferation. Overexpression of this pathway is observed in various tumors. In the context of CRC， the activation of this pathway can facilitate the proliferation， invasion， and migration， inhibit the autophagy and apoptosis， promote the epithelial-mesenchymal transition of CRC cells， enhance angiogenesis within the tumor， and contribute to chemotherapy resistance and radiation resistance in CRC. Traditional Chinese medicine （TCM） treatment can exert an anti-CRC effect by inhibiting this pathway， thereby improving clinical efficacy and safety. This article retrieves relevant research literature published domestically and internationally regarding the regulation of the PI3K/Akt/mTOR signaling pathway by TCM in the treatment of CRC and conducts detailed classification and summary. The active components of TCM include glycosides， flavonoids， alkaloids， terpenoids， polyphenols， and naphthoquinones. The volatile oils and extracts of TCM include Angelicae Sinensis Radix volatile oil， Astragali Radix polysaccharides， Caryophylli Flos extract， Forsythiae Fructus extract， Curcumae Longae Rhizoma extract， and Celastrus orbiculatus extract. The compound formulas of TCM include Banxia Xiexin decoction， Jianpi Qingre Huoxue formula， and Chanling Plaster. Through summary and analysis， it is discovered that the abovementioned TCM can produce effects such as blocking the cell cycle， inducing autophagy and apoptosis， inhibiting angiogenesis， suppressing proliferation and migration， and reversing chemotherapy resistance and radiotherapy resistance by inhibiting the PI3K/Akt/mTOR pathway in CRC cells. TCM holds promise in the research and application of targeting the PI3K/Akt/mTOR signaling pathway for CRC treatment. The summary and conclusion of this article aim to provide references for subsequent research and the development of new drugs.

Colorectal cancer （CRC） is a prevalent malignant tumor of the digestive tract， with a high incidence and high mortality. The majority of patients are diagnosed at the middle or advanced stage， which severely influences and threatens their physical health. Current treatment modalities such as surgery， radiotherapy， and chemotherapy often encounter challenges including metastasis， recurrence， and drug resistance. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway serves as a classical regulator that regulates physiological processes such as cell cycle， autophagy， apoptosis， and proliferation. Overexpression of this pathway is observed in various tumors. In the context of CRC， the activation of this pathway can facilitate the proliferation， invasion， and migration， inhibit the autophagy and apoptosis， promote the epithelial-mesenchymal transition of CRC cells， enhance angiogenesis within the tumor， and contribute to chemotherapy resistance and radiation resistance in CRC. Traditional Chinese medicine （TCM） treatment can exert an anti-CRC effect by inhibiting this pathway， thereby improving clinical efficacy and safety. This article retrieves relevant research literature published domestically and internationally regarding the regulation of the PI3K/Akt/mTOR signaling pathway by TCM in the treatment of CRC and conducts detailed classification and summary. The active components of TCM include glycosides， flavonoids， alkaloids， terpenoids， polyphenols， and naphthoquinones. The volatile oils and extracts of TCM include Angelicae Sinensis Radix volatile oil， Astragali Radix polysaccharides， Caryophylli Flos extract， Forsythiae Fructus extract， Curcumae Longae Rhizoma extract， and Celastrus orbiculatus extract. The compound formulas of TCM include Banxia Xiexin decoction， Jianpi Qingre Huoxue formula， and Chanling Plaster. Through summary and analysis， it is discovered that the abovementioned TCM can produce effects such as blocking the cell cycle， inducing autophagy and apoptosis， inhibiting angiogenesis， suppressing proliferation and migration， and reversing chemotherapy resistance and radiotherapy resistance by inhibiting the PI3K/Akt/mTOR pathway in CRC cells. TCM holds promise in the research and application of targeting the PI3K/Akt/mTOR signaling pathway for CRC treatment. The summary and conclusion of this article aim to provide references for subsequent research and the development of new drugs.

Objective: To evaluate the effects of a multidisciplinary weight management intervention, so as to provide a reference for the formulation of overweight and obesity intervention measures. Methods: From April to September 2025, overweight and obese residents aged 18-60 years who participated in a weight loss competition at the Health Management Center of Beilun People's Hospital in Ningbo City were selected as study subjects. They were divided into a control group and an intervention group. The control group received conventional weight management, while the intervention group received the multidisciplinary integrated weight management in addition to the conventional weight management, for a total intervention period of 8 weeks. Weight, body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio, fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood pressure were collected before and after the intervention through physical examinations and laboratory tests. The generalized estimating equations (GEE) method was employed to analyze the differences in indicators between the two groups before and after the intervention. Results: The control group comprised 241 participants, including 161 females (66.80%), with a mean age of (35.66±7.80) years. The intervention group consisted of 127 participants, including 86 females (67.72%), with a mean age of (36.80±7.05) years. No statistically significant differences were observed between the two groups at baseline in terms of age, gender, weight, BMI, or waist-to-hip ratio (all P>0.05). Results from the GEE analysis indicated significant interactions between group and time for weight, BMI, waist circumference, and hip circumference (all P<0.05) with greater reductions in these parameters observed in the intervention group compared to the control group before and after the intervention. Similarly, significant interactions between group and time were observed for FBG, TG, TC, and LDL-C (all P<0.05), with the intervention group demonstrating larger decreases in these markers compared to the control group. However, no statistically significant interactions between group and time were observed for waist-to-hip ratio, HDL-C, systolic blood pressure, and diastolic blood pressure (all P>0.05). Following the intervention, a weight loss exceeding 10% was achieved by 13 participants (5.39%) in the control group and 62 participants (48.82%) in the intervention group. The proportion of individuals with a weight loss exceeding 10% was significantly higher in the intervention group compared to the control group (P<0.05). Conclusion Compared to conventional weight management, multidisciplinary integrated weight management demonstrated greater efficacy in improving weight-related indicators and blood glucose, blood lipids, and enhancing weight loss outcomes among overweight and obese residents.

BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models

The bidirectional closed-loop motor imagery brain-computer interface (MI-BCI) is an emerging method for active rehabilitation training of motor dysfunction, extensively tested in both laboratory and clinical settings. However, no standardized method for evaluating its rehabilitation efficacy has been established, and relevant literature remains limited. To facilitate the clinical translation of bidirectional closed-loop MI-BCI, this article first introduced its fundamental principles, reviewed the rehabilitation training cycle and methods for evaluating rehabilitation efficacy, and summarized approaches for evaluating system usability, user satisfaction and usage. Finally, the challenges associated with evaluating the rehabilitation efficacy of bidirectional closed-loop MI-BCI were discussed, aiming to promote its broader adoption and standardization in clinical practice.
Brain-Computer Interfaces ; Humans ; Imagination/physiology* ; Imagery, Psychotherapy/methods*

Protein structure determines function, and structural information is critical for predicting protein thermostability. This study proposes a novel method for protein thermostability prediction by integrating graph embedding features and network topological features. By constructing residue interaction networks (RINs) to characterize protein structures, we calculated network topological features and utilize deep neural networks (DNN) to mine inherent characteristics. Using DeepWalk and Node2vec algorithms, we obtained node embeddings and extracted graph embedding features through a TopN strategy combined with bidirectional long short-term memory (BiLSTM) networks. Additionally, we introduced the Doc2vec algorithm to replace the Word2vec module in graph embedding algorithms, generating graph embedding feature vector encodings. By employing an attention mechanism to fuse graph embedding features with network topological features, we constructed a high-precision prediction model, achieving 87.85% prediction accuracy on a bacterial protein dataset. Furthermore, we analyzed the differences in the contributions of network topological features in the model and the differences among various graph embedding methods, and found that the combination of DeepWalk features with Doc2vec and all topological features was crucial for the identification of thermostable proteins. This study provides a practical and effective new method for protein thermostability prediction, and at the same time offers theoretical guidance for exploring protein diversity, discovering new thermostable proteins, and the intelligent modification of mesophilic proteins.
Neural Networks, Computer ; Algorithms ; Protein Stability ; Proteins/chemistry* ; Protein Conformation ; Temperature

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged