ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

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

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective To explore the relationship between serum chitosinase 3-like protein 1(CHI3L1)and Syndecan-1(SDC1)levels and bone metabolism in elderly patients with type 2 diabetes mellitus and their predictive efficacy on osteoporosis.Methods A total of 412 elderly patients with type 2 diabetes admitted to this hospital from May 2019 to May 2023 were included in this study,and were divided into normal bone mass group(n=151),reduced bone mass group(n=138)and osteoporosis group(n=123)according to the iffer-ences in bone mineral density.Serum CHI3L1 and SDC1 levels were detected by enzyme-linked immunosor-bent assay,and serum levels of type 1 collagen cross-linked carboxyl terminal peptide(CTX),25-hydroxyvita-min D[25-(OH)D],osteocalcin(OC),and type 1 procollagen N-terminal propeptide(P1NP)were deter-mined by automatic chemiluminescence immunoassay.Pearson correlation analysis was used to investigate the relationship between serum CHI3L1,SDC1 and bone metabolism in elderly patients with type 2 diabetes.Re-ceiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of serum CHI3L1 and SDC1 on osteoporosis in elderly patients with type 2 diabetes.Multivariate Logistic regression analysis was used to investigate the influencing factors of osteoporosis in elderly patients with type 2 diabetes.Results There were significant differences in diabetes course,fasting blood glucose,HbA1c and HDL-C a-mong normal bone mass group,decreased bone mass group and osteoporosis group(P＜0.05).The levels of serum CHI3L1,25-(OH)D,P1NP and osteocalcin in osteoporosis group were lower than those in osteopenia group,and those in osteopenia group were lower than those in normal bone mass group,the differences were statistically significant(P＜0.05).Serum SDC1 and CTX levels in osteoporosis group were higher than those in osteopenia group,and those in osteopenia group were higher than those in normal bone mass group,the differences were statistically significant(P＜0.05).Serum CHI3L1 was positively correlated with 25-(OH)D,P1NP and OC(P＜0.05),and negatively correlated with CTX(P＜0.05).Serum SDC1 was negatively correlated with 25-(OH)D,P1NP,OC(P＜0.05),and positively correlated with CTX(P＜0.05).The area under the curve(AUC)of serum CHI3L1,SDC1 and their combination predicted osteoporosis in elderly pa-tients with type 2 diabetes were 0.851,0.772 and 0.904,respectively.Multivariate Logistic regression analysis showed that long duration of diabetes,increased HbA1c,high expression of OC,CHI3L1＞4.16 ng/mL,SDC1≥50.94 ng/mL were all influential factors for osteoporosis in elderly patients with type 2 diabetes(P＜0.05).Conclusion Low expression of CHI3L1 and high expression of SDC1 in serum are associated with ab-normal bone metabolism in elderly patients with type 2 diabetes.These two indexes are expected to be used as biological markers to predict osteoporosis in elderly patients with type 2 diabetes.

Objective:To explore the effects of Qingre Qudu Decoction for fumigation combined with three-gap drainage on wound healing and serum inflammatory factors in patients with acute perianal abscess.Methods:Randomized controlled trial was conducted. A total of 117 patients with acute perianal abscess in the hospital were enrolled as the observation objects between August 2022 and May 2024. According to random number table method, they were divided into observation group (59 cases) and control group (58 cases). Both groups received three-gap drainage therapy. On basis of three-gap drainage, control group was given potassium permanganate, while observation group was given Qingre Qudu Decoction for fumigation. All patients were treated for 14 d. The growth of granulation tissue and wound secretions before and after treatment was evaluated. VAS scale was used to evaluate the degree of incision pain, and Wexner score was used to assess incontinence; ELISA was used to detect serum activator A (ACTA), immunoturbidimetry was used to detect serum CRP, and radioimmunoassay was used to detect serum IL-6 levels. The occurrence of complications and abscess recurrence during treatment was recorded, and clinical efficacy was evaluated.Results:The total effective rate of the observation group was 96.61% (57/59), while that of the control group was 82.76% (48/58), with statistical significance ( χ2=6.10, P=0.014). After treatment, scores of granulation tissue growth and wound secretions in observation group, and scores of VAS and Wexner incontinence in observation group were lower than those in the control group ( t=9.66, 5.00, 7.98, 3.65, P<0.001), and wound healing time was shorter than that in control group ( t=8.41, P<0.001). After treatment, levels of serum ACTA, CRP and IL-6 in observation group were lower than those in control group ( t=15.30, 2.08, 19.34, P<0.01 or P<0.05). The incidence of postoperative complications in the observation group was 6.78% (4/59), while in the control group it was 27.59% (16/58), with statistical significance ( χ2=8.93, P=0.003). Conclusion:Qingre Qudu Decoction for fumigation combined with three-gap drainage can relieve postoperative incision pain, inhibit inflammatory response, accelerate the recovery of wound and promote the recovery of anal function and improve clinical efficacy.

Objective:To compare the immunogenicity of the prefusion (PreF) and postfusion (PostF) conformations of the respiratory syncytial virus (RSV) F protein.Methods:The expression of PreF and PostF recombinant proteins was analyzed by SDS-PAGE and Western blot. The binding affinity between F protein and its specific antibodies was detected by Octet. The binding antibodies and neutralizing antibodies in immune serum were detected after immunizing mice with PreF or PostF recombinant protein.Results:PreF protein was stable in the form of a trimer after modification with higher binding affinity with monoclonal antibodies such as D25, 8897, AM14, Palivizumab and Motavizumab. PostF protein lacked the antigenic site ? and showed a monomer conformation. Besides, it was unable to bind to D25, 8897 and AM14 antibodies. Animal experiments showed that AS01 adjuvant was better than aluminum adjuvant in inducing binding antibodies and neutralizing antibodies against RSV Long strains. The binding antibodies induced by PreF and PostF recombinant proteins had similar binding ability to PreF protein, while the binding antibodies induced by PostF recombinant protein showed stronger binding ability to PostF than to PreF.Conclusions:PreF has more epitopes and the trimer form of PreF recombinant protein after modification is more stable and can induce stronger neutralizing antibodies. Moreover, the immunopotentiating effect of AS01 adjuvant is better than that of aluminum adjuvant. Therefore, stabilization-based trimer structure modification of PreF and the development of adjuvants are crucial for the development of RSV vaccines.

Given the systematic, rigorous, and practical characteristics of medical disciplines, ensuring the teaching quality of online courses has become a significant focus. In traditional teaching models, teaching supervision is an important method to guarantee instructional quality, and introducing teaching supervision into online teaching activities is of great significance. This article systematically reviews and summarizes the domestic and international experience of conducting online medical courses. We explore the instructional supervision of online medical courses from the following perspectives: the meaning of supervision, the necessity of online supervision, online supervision methods and technical approaches, the feedback and application of supervision information, and the establishment of a standardized online supervision process.

Granulocytic myeloid-derived suppressor cells(G-MDSCs)are one of the main subgroups of MD-SCs,which are widely enriched in most cancers.It can inhibit the killing function of T-lymphocyte through the expression of arginase-1(Arg-1)and reactive oxygen species(ROS),reshape the tumor immune microenvironment,and promote the oc-currence and development of tumors.In recent years,more and more studies have found that G-MDSCs are significantly cor-related with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer,and the use of drugs specifi-cally targeting the recruitment,differentiation and function of G-MDSCs can effectively inhibit tumor progression.This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.

Attention deficit and hyperactive disorder(ADHD)is a chronic neurodevelopmental disorder characterized by inattention,hyperactivity-impulsivity,and working memory deficits.Social dysfunction is one of the major challenges faced by children with ADHD.It has been found that children with ADHD can't perform as well as typically developing children on facial expression recognition(FER)tasks.Generally,children with ADHD have some difficulties in FER,while some studies suggest that they have no significant differences in accuracy of specific emotion recognition compared with typically developing children.The neuropsychological mechanisms underlying these difficulties are as follows.First,neuroanatomically.Compared to typically developing children,children with ADHD show smaller gray matter volume and surface area in the amygdala and medial prefrontal cortex regions,as well as reduced density and volume of axons/cells in certain frontal white matter fiber tracts.Second,neurophysiologically.Children with ADHD exhibit increased slow-wave activity in their electroencephalogram,and event-related potential studies reveal abnormalities in emotional regulation and responses to angry faces when facing facial stimuli.Third,psychologically.Psychosocial stressors may influence FER abilities in children with ADHD,and sleep deprivation in ADHD children may significantly increase their recognition threshold for negative expressions such as sadness and anger.This article reviews research progress over the past three years on FER abilities of children with ADHD,analyzing the FER deficit in children with ADHD from three dimensions:neuroanatomy,neurophysiology and psychology,aiming to provide new perspectives for further research and clinical treatment of ADHD.