ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

OBJECTIVE To explore the mechanism of steam-processed Polygonatum sibiricum polysaccharides(SPSP) in prophylaxis and treatment of mice with blood deficiency syndrome(BDS) by RNA sequencing(RNA-seq) technology. METHODS The mice were randomly divided into five groups(10 mice in each group), namely normal group, model group, SPSP groups(0.1, 0.4 g·kg−1), Danggui Buxue oral liquid(DOL) group. BDS model was induced in mice by acetylphenyl-hydrazine and cyclophosphamide. Blood routine, body weight and body temperature were tested after a consecutive administration for 14 d. The differential expressed genes(DEGs) related to anti-BDS by SPSP were screened through the transcriptome sequencing of the hepatic tissue in BDS mice. Functional annotation and enrichment analysis were performed to screen out the gene expression signaling pathways related to the treatment of SPSP on BDS mice. Quantitative polymerase chain reaction(qPCR) was used to verify the experiment. RESULTS Compared with the model group, SPSP(0.4 g·kg−1) could elevate the blood routine indexes such as red blood cell, white blood cell, hemoglobin, platelet, mean corpuscular hemoglobin concen-tration(P<0.01), and reverse the body weight and body temperature to normal(P<0.01 or P<0.05). The result of transcriptomic analysis showed that the underlying mechanism was mainly related to hematopoietic cell line, retinol metabolism, steroid hormone biosynthesis, platelet activation, B cell receptor signaling pathway, and leukocyte transendothelial migration, etc. The result of qPCR showed that SPSP(0.4 g·kg−1) could elevate the expression of JAK1, STAT1 and GATA1 mRNA (P<0.01 or P<0.05). CONCLUSION SPSP has therapeutic effects on BDS. The key DEGs in the treatment of BDS by SPSP are mainly related to the restoration of hematopoietic function, regulation of hormone and immune function. The mechanism of SPSP on treatment of BDS might be the regulation of JAK1/STAT1 signaling pathway.

OBJECTIVE To observe the regulation of aerobic oxidation mediated by HIF-1α/PDHK1 pathway by PNS, and to explore its mechanism of promoting the differentiation of Naive CD4+T cells into Treg cells. METHODS Naive CD4+T cells were isolated from the spleen of C57BL/6 mice by magnetic beads and induced to differentiate into Treg cells for in vitro culture. Naive CD4+T cells were divided into PNS treatment group(5, 10, 20 μg·mL−1), PNS combined with HIF-1α inhibitor(PX-478) group, and the control group was set up. The proportion of Treg cells differentiation was detected by flow cytometry. The expression of HIF-1α and PDHK1 protein was detected by Western blotting. The expression of HIF-1α, PDHK1 and FOXP3 mRNA was detected by real-time fluorescence quantitative PCR. The level of IL-10 in cell culture supernatant was detected by enzyme-linked immunosorbent assay. RESULTS PNS could significantly increase the proportion of Treg cells and the secretion level of IL-10, and increase the expression of FOXP3 mRNA in cells. At the same time, the expression of HIF-1α and PDHK1 protein and mRNA was inhibited. When the cells were treated with 10 μmol·L−1 PX-478 and then treated with 10 μg·mL−1 PNS, the expression of PDHK1 and FOXP3 and the differentiation ratio of Treg cells were not significantly different from those treated with 10 μmol·L−1 PX-478 alone. CONCLUSION PNS can reduce the expression level of PDHK1 by HIF-1α to enhance the aerobic oxidation of Naive CD4+T cells and promote their differentiation into Treg cells.

The American College of Gastroenterology published the clinical guideline on alcohol-associated liver disease(ALD)in January 2024 in American Journal of Gastroenterology.This guideline elaborates on the epidemiology and disease burden of ALD and alcohol use disorder,the risk factors for ALD,the diagnosis and treatment of alcohol use disorder,the disease spectrum of ALD,the management of ALD,and public policy and prevention.This article gives an excerpt of the recommendations and key points/statements in this guideline.

Objective:To explore the impact of different six-character qigong training modes on respiratory muscle function early after a stroke.Methods:Sixty-six stroke survivors in the early stage of recovery were randomly divided into a control group, a modified training group, and an ancient training group, each of 22. In addition to routine rehabilitation training, the control group received conventional respiratory training. The modified training and ancient training groups were trained in modified six-character qigong or ancient six-character qigong, respectively, for two weeks. Before the treatment, after the two weeks and one month later, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), forced expiratory volume in one second, forced vital capacity, peak expiratory flow, maximum mid-expiratory flow, and peak inspiratory flow were measured. Diaphragm mobility during quiet inspiration and maximum inspiration were also quantified.Results:After 2 weeks of treatment and at 1 and 3 months after the end of the treatment, all three groups showed significant improvement in MIP, MEP and the pulmonary ventilation indicators, but the average improvement in the modified training group was significantly greater than in the other two groups. Their average diaphragm mobility was also significantly greater.Conclusion:Modified six-character qigong respiratory training is more effective than its ancient counterpart in improving respiratory muscle function, pulmonary ventilation, and diaphragm mobility early after a stroke, with effects which persist for at least one month.

OBJECTIVE To investigate the mechanism of catalpol affecting the differentiation of helper T cell 17 （Th17） by interfering the expressions of pyruvate kinase M2 （PKM2） and lactate dehydrogenase A （LDHA）. METHODS The naive CD4+ T cells were selected from the spleen of C57BL/6 mice， and were differentiated into Th17 cells by adding directional differentiation stimulants for 72 hours. At the same time， the cells were treated with 0 （directed control）， 20， 40 and 80 μg/mL catalpol. The flow cytometry was used to detect the proportion of Th17 cell differentiation in cells； the colorimetric method was adopted to detect the levels of pyruvate and lactate in cell culture supernatant； mRNA expressions of retinoid-related orphan nuclear receptor gamma t （RORγt）， PKM2 and LDHA were detected by qRT-PCR method； Western blot was used to detect the expression levels of PKM2， LDHA， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated STAT3 （p-STAT3） proteins in cells. RESULTS Compared with the directed control group， after 72 hours of treatment with 20， 40， 80 μg/mL catalpol， the differentiation ratio of Th17 cells were decreased by 6.74%， 8.41%， 9.24%， and the levels of pyruvate and lactate in the cell culture supernatant， the mRNA expressions of PKM2， LDHA and RORγt as well as the protein expressions of PKM2 and LDHA and the phosphorylation of STAT3 were significantly reduced （P＜0.05）. CONCLUSIONS Catalpol can reduce the glycolysis level by down-regulating the expressions of PKM2 and LDHA， thereby inhibiting the differentiation of Th17 cells.

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Objective To explore the potential mechanism of Benzo(K)fluoranthene(BkF)on male reproductive injury in mice by proteomics and metabolomics.Methods Twenty healthy and clean male Kunming mice(6 weeks old,18±2 g)were randomly divided into control group(corn oil group),low-,medium-and high-dose BkF groups(7.5,15.0 and 30.0 mg/kg),with 5 mice in each group.The corresponding agents were gavaged at a dose of 10 mL/kg,5 d per week,for 35 consecutive days.After modeling,the rats were fasted for 10 h,and then sperm samples and testicular tissues were harvested.Computer assisted sperm analysis(CASA)was used to detect and analyze semen parameters.HE staining was employed to observe the histopathological structure of the testicular tissue.Bioinformatics analysis was applied to analyze the differential protein pathways.Volcano plot were conducted to analyze the top 10 differentially expressed proteins(DEPs)in the control and high-dose BkF group.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)untargeted metabolomics techniques were utilized to screen out differential metabolites.KEGG signaling pathway and KEGG annotation analyses and GO enrichment analysis were used to analyze the differential metabolites.Results Compared with the control group,the sperm number and motility of BkF-treated mice showed a decreased trend,with statistical differences(P＜0.05).Pathological observation showed that BkF treatment resulted in dilated seminal tubules and badly-arranged spermatogenic cells when compared with the control group.Proteomics analysis found that the protein levels of Spata46 and Rab5b were decreased,while those of Zscan21 and Aifm2 were increased(P＜0.01).Proteomic KEGG enrichment analysis showed that it was mainly involved in phagosome,protein export,ribosome and other pathways.GO enrichment analysis indicated that it was mainly involved in male meiosis I,histone acetylation,regulation of p53 signaling pathway,positive regulation of cell cycle,positive regulation of cell death and other signaling pathways.Metabonomics KEGG displayed that amino sugar and nucleotide sugar metabolism were most closely related to other metabolic pathways.Conclusion Proteomics and metabolomics analyses show that BkF exposure is associated with spermatogenesis,apoptosis and cell cycle,DNA damage,amino sugar and nucleotide sugar metabolism.

Objective To investigate the changes in G protein-coupled receptor 124 (Gpr124) expression in human retinal microvascular endothelial cells (HRMEC)under high-glucose condition and the regulatory effect of Gpr124 interference on HRMEC.Methods Immunofluorescence assay was used to observe the expression of Gpr124 in HRMEC.The cells were divided into a blank group and a high glucose group.CCK-8 assay and EdU cell proliferation assay were used to detect cell viability and proliferation,respectively.The Gpr124 expression was knocked down by transducting lentiviral virus carrying shRNA targeting Gpr124.Thus,the cells were divided into a blank control group,a high glucose control group,a high glucose+shRNA group,and a high glucose+Gpr124 shRNA group.Cell scratch test was performed to evaluate cell migration,and Matrigel plug assay was employed to assess the cell tubule formation.Western blotting was applied to detect the protein levels of Gpr124,VEGFA,MMP9,and β-catenin.Results The HRMEC from the high glucose group showed enhanced cell viability and increased number of proliferating cells compared to the cells of the blank group (P<0.01).High glucose treatment also induced increased expression levels of Gpr124,VEGFA and MMP9 (P<0.01),and larger migratory area and in vitro angiogenic area as well as longer tube diameter at all time points when compared with the conditions in the blank control group (P<0.01).However,knockdown of Gpr124 resulted in a significant decrease in HRMEC migration and in vitro angiogenic capacity,accompanied by decreases in protein expression of VEGFA,MMP9 and β-catenin (P<0.01).Conclusion Gpr124 can regulate the proliferation,migration,and tube formation ability of HRMEC under high-glucose condition,and also inhibit the overexpression of VEGFA and MMP9,which may be through regulating the classical Wnt/β-catenin pathway.