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.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a common chronic liver disease with the pathological feature of lipid accumulation in the liver， and it is closely associated with liver metabolic disorders. The latest research has shown that the pathogenesis of MAFLD is associated with the abnormal expression of specific genes， especially the fat mass and obesity-associated （FTO） gene. The abnormal activity of the FTO gene may lead to an imbalance in liver lipid metabolism， which manifests as the increase in fatty acid synthesis and the reduction in fatty acid oxidation， thereby promoting liver fat deposition and inflammatory response. Therefore， regulating the expression or activity of the FTO gene is considered one of the potential strategies for the treatment of MAFLD. At present， drug research targeting the function of the FTO gene has achieved preliminary results， and inhibition of the activity of the FTO gene can help to regulate liver lipid metabolism and alleviate liver inflammatory injury. This article reviews the mechanism of action of the FTO gene in the development and progression of MAFLD， summarizes the advances in drug research on the FTO gene and related metabolic pathways in recent years， and analyzes their application prospect in research and treatment.

This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods* ; Male ; Animals ; Swine ; Acupuncture Points ; Humans ; Swine, Miniature ; Needles

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Attention is the cornerstone of effective functioning in a complex and information-rich world. While the neural activity of attention has been extensively studied in the cortex, the brain-wide neural activity patterns are largely unknown. In this study, we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns. Our findings reveal that a wide range of brain regions are activated, notably in the high-order cortex, thalamus, and brain stem regions involved in advanced cognition and arousal regulation, with the central lateral nucleus of the thalamus as a strong hub, suggesting the crucial role of the thalamus in attention control. These results provide valuable insights into the neural network mechanisms underlying attention, offering a foundation for formulating functional hypotheses and conducting circuit-level testing.
Animals ; Attention/physiology* ; Mice ; Brain/physiology* ; Male ; Electroencephalography ; Reaction Time/physiology* ; Brain Mapping ; Mice, Inbred C57BL ; Choice Behavior/physiology* ; Proto-Oncogene Proteins c-fos/metabolism*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Predicting protein mutation effects is a key challenge in bioinformatics and protein engineering. Recent advancements in deep learning, particularly the development of protein language models (PLMs), have brought new opportunities to this field. This review summarizes the application of PLMs in predicting protein mutation effects, focusing on three main types of models: sequence-based models, structure-based models, and models that combine sequence and structural information. We analyze in detail the principles, advantages, and limitations of these models and discuss the application of unsupervised and supervised learning in model training. Furthermore, this paper discusses the main challenges currently faced, including the acquisition of high-quality datasets and the handling of data noise. Finally, we look ahead to future research directions, including the application prospects of emerging technologies such as multimodal fusion and few-shot learning. This review aims to provide researchers with a comprehensive perspective to further advance the prediction of protein mutation effects.
Mutation ; Proteins/chemistry* ; Computational Biology/methods* ; Deep Learning ; Protein Engineering

Objective:To investigate the effects of free triiodothyronine/free thyroxine(FT3/FT4) and one carbon metabolites on metabolic syndrome(MetS) in patients with severe mental illness(SMI).Methods:Retrospective case-control study was conducted to select 328 patients with SMI who were hospitalized in Beijing Huilongguan Hospital from January 2022 to August 2023 as the study subjects, including 180 patients with schizophrenia (SZ), 74 patients with bipolar disorder (BD), and 74 patients with major depression (MDD). Another 74 healthy subjects in the same period were selected as the control group. The levels of thyroid hormones and one-carbon metabolites [ folic acid, vitamin B12 (VitB12) and homocysteine (HCY) ] were compared between the two groups. At the same time, clinical data and MetS related information of SMI patients were collected. Partial correlation analysis and Logistic regression analysis were used to study the relationship between FT3/FT4 and one-carbon metabolites and MetS risk factors and insulin resistance in SMI patients, respectively.Results:There were statistically significant differences in gender, age, course of disease, smoking rate, body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG)/HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), antipsychotic drug use rate, mood stabilizer use rate, antidepressant drug use rate and hypoglycemic treatment among SZ, BD and MDD groups in SMI patients (all P<0.05).Compared with the control group, FT3/FT4, folic acid and VitB12 in patients with SMI were significantly lower ( Z=-4.315, P<0.001; Z=-8.216, P<0.001; Z=-6.021, P<0.001), HCY increased significantly ( Z=-8.789, P<0.001);Partial correlation analysis showed that FT3/FT4 in patients with SMI was positively correlated with TG( r=0.303, P<0.001), TG/HDL-C( r=0.228, P<0.001), insulin resistance index(HOMA-IR)( r=0.204, P<0.001), triglyceride glucose index(TyG)( r=0.284, P<0.001), triglyceride glucose body mass index(TyG-BMI)( r=0.211, P<0.001) and body mass index(BMI)( r=0.154, P=0.005), and negatively correlated with insulin sensitivity index(QUICKI)( r=-0.205, P<0.001). VitB12 was positively correlated with HDL-C( r=0.144, P=0.009) and QUICKI( r=0.115, P=0.038), and negatively correlated with TyG-BMI ( r=-0.122, P=0.028) and BMI ( r=-0.127, P=0.022). HCY was positively correlated with TyG ( r=0.114, P=0.039) and TyG-BMI ( r=0.188, P=0.001). Multivariate ordinal logistic regression analysis showed that smoking( OR=1.602,95% CI=1.004-2.558), female( OR=1.736,95% CI=1.041-2.895), FT3/FT4( OR=17.811,95% CI=1.596-198.764), HCY ( OR=1.026,95% CI=1.009-1.043) and BD ( OR=2.150,95% CI=1.092-4.232) were the influencing factors of the number of risk factors for MetS in patients with SMI, while VitB12 ( OR=0.997,95% CI=0.995-0.998) was a protective factor; binary Logistic regression analysis showed that patients with SMI with long course of disease( OR=1.024,95% CI=1.008-1.041) and high level of HCY ( OR=1.033,95% CI=1.014-1.052) were more likely to have MetS. Conclusion:Dynamic monitoring of FT3/FT4 and one-carbon metabolites levels is helpful to identify the risk of MetS in patients with SMI and provide reference for prevention and treatment.

Objective:To explore the effects of the intervention of ginger baixiao moxibustion combined with probiotics on immune function, liver and kidney function of colorectal cancer patients after surgery, so as to provide a theoretical basis for clinical intervention methods to promote postoperative rehabilitation of patients.Methods:This study was a randomized controlled trial, and 180 patients with colorectal cancer radical resection from the Cancer Hospital of Guangxi Medical University were randomly divided into 4 groups, namely control group, probiotic group, ginger baixiao moxibustion group, and combination group, with 45 cases in each group. The control group was given routine nursing before and after surgery. In the probiotic group, probiotics were used for 3 d in routine preoperative care and 4 d from the first day after surgery. The preoperative routine care of the ginger baixiao moxibustion group was supplemented by ginger baixiao moxibustion for 3 d, and the intervention was carried out on the first day after surgery for 4 d. The combined group was treated with probiotics before and after surgery, and the specific intervention methods were the same as those of the probiotics group and the ginger baixiao moxibustion group. The differences in postoperative immune function, liver and kidney function and and other indexes among the four groups were compared.Results:Forty-five cases were ultimately selected from each of the 4 groups. There were 31 males and 14 females, aged (56.67 ± 10.13) years old in the control group. There were 27 males and 18 females, aged (55.33 ± 13.02) years old in the probiotic group. There were 20 males and 25 females, aged (57.87 ± 12.43) years old in the ginger baixiao moxibustion group. There were 26 males and 19 females, aged (57.67 ± 11.63) years old in the combination group. The IgA at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (1.46 ± 0.42), (1.71 ± 0.49), (1.72 ± 0.58), (1.97 ± 0.72) g/L, and the IgM were (0.96 ± 0.20), (1.13 ± 0.33), (1.11 ± 0.35), (1.18 ± 0.52) g/L, and the IgG were (8.45 ± 1.68), (9.57 ± 1.71), (9.41 ± 2.14), (10.40 ± 2.16) g/L, and the differences among the four groups were statistically significant ( F=6.20, 10.64, 7.69, all P<0.05). The CD3 + values at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were 0.616 ± 0.094, 0.671 ± 0.101, 0.653 ± 0.119, 0.723 ± 0.091, and CD4 + were 0.408 ± 0.060, 0.444 ± 0.063, 0.441 ± 0.103, 0.483 ± 0.069, and CD4 +/CD8 + were 2.173 ± 0.715, 2.367 ± 0.963, 2.204 ± 1.137, 2.803 ± 1.064, and the differences among the four groups were statistically significant ( F=8.58, 7.43, 3.93, all P<0.05). The alanine aminotransferases at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (16.22 ± 11.56), (15.87 ± 10.69), (12.91 ± 7.45), (11.31 ± 8.31) U/L, and the aspartate aminotransferases were (26.13 ± 7.97), (25.84 ± 7.89), (25.67 ± 10.85), (21.84 ± 5.51) U/L, and the differences among the four groups were statistically significant ( F=2.71, 2.70, both P<0.05). Conclusions:The combination of ginger baixiao moxibustion and probiotics intervention can effectively improve the immune function of colorectal cancer patients after surgery, and improve the liver function and other indexes of patients to a certain extent, so as to benefit patients.

Objective:To investigate the effects of free triiodothyronine/free thyroxine(FT3/FT4) and one carbon metabolites on metabolic syndrome(MetS) in patients with severe mental illness(SMI).Methods:Retrospective case-control study was conducted to select 328 patients with SMI who were hospitalized in Beijing Huilongguan Hospital from January 2022 to August 2023 as the study subjects, including 180 patients with schizophrenia (SZ), 74 patients with bipolar disorder (BD), and 74 patients with major depression (MDD). Another 74 healthy subjects in the same period were selected as the control group. The levels of thyroid hormones and one-carbon metabolites [ folic acid, vitamin B12 (VitB12) and homocysteine (HCY) ] were compared between the two groups. At the same time, clinical data and MetS related information of SMI patients were collected. Partial correlation analysis and Logistic regression analysis were used to study the relationship between FT3/FT4 and one-carbon metabolites and MetS risk factors and insulin resistance in SMI patients, respectively.Results:There were statistically significant differences in gender, age, course of disease, smoking rate, body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG)/HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), antipsychotic drug use rate, mood stabilizer use rate, antidepressant drug use rate and hypoglycemic treatment among SZ, BD and MDD groups in SMI patients (all P<0.05).Compared with the control group, FT3/FT4, folic acid and VitB12 in patients with SMI were significantly lower ( Z=-4.315, P<0.001; Z=-8.216, P<0.001; Z=-6.021, P<0.001), HCY increased significantly ( Z=-8.789, P<0.001);Partial correlation analysis showed that FT3/FT4 in patients with SMI was positively correlated with TG( r=0.303, P<0.001), TG/HDL-C( r=0.228, P<0.001), insulin resistance index(HOMA-IR)( r=0.204, P<0.001), triglyceride glucose index(TyG)( r=0.284, P<0.001), triglyceride glucose body mass index(TyG-BMI)( r=0.211, P<0.001) and body mass index(BMI)( r=0.154, P=0.005), and negatively correlated with insulin sensitivity index(QUICKI)( r=-0.205, P<0.001). VitB12 was positively correlated with HDL-C( r=0.144, P=0.009) and QUICKI( r=0.115, P=0.038), and negatively correlated with TyG-BMI ( r=-0.122, P=0.028) and BMI ( r=-0.127, P=0.022). HCY was positively correlated with TyG ( r=0.114, P=0.039) and TyG-BMI ( r=0.188, P=0.001). Multivariate ordinal logistic regression analysis showed that smoking( OR=1.602,95% CI=1.004-2.558), female( OR=1.736,95% CI=1.041-2.895), FT3/FT4( OR=17.811,95% CI=1.596-198.764), HCY ( OR=1.026,95% CI=1.009-1.043) and BD ( OR=2.150,95% CI=1.092-4.232) were the influencing factors of the number of risk factors for MetS in patients with SMI, while VitB12 ( OR=0.997,95% CI=0.995-0.998) was a protective factor; binary Logistic regression analysis showed that patients with SMI with long course of disease( OR=1.024,95% CI=1.008-1.041) and high level of HCY ( OR=1.033,95% CI=1.014-1.052) were more likely to have MetS. Conclusion:Dynamic monitoring of FT3/FT4 and one-carbon metabolites levels is helpful to identify the risk of MetS in patients with SMI and provide reference for prevention and treatment.