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.

Objective To compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P＞0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.

AIM: To compare the effects of different nucleus chopping methods on the central corneal thickness, corneal endothelial cell(CEC)count and tear inflammatory indicators in patients with hard nucleus cataract.METHODS: Retrospective study. Totally 89 patients(89 eyes)with hard nucleus cataract who treated in our hospital were included from January 2020 to December 2022. According to different intraoperative nucleus chopping methods, the patients were divided into reverse prechop group(46 eyes)and phaco-chop group(43 eyes). The total effective rate of surgery and visual acuity recovery were compared between the two groups. Corneal related indicators(central corneal thickness, CEC count, CEC area), tear inflammatory indicators and tear film function [tear film break-up time(BUT), Chinese Dry Eye Questionnaire(CDEQ), Schirmer Ⅰ test(SⅠt)] were observed before and after surgery in both groups, and the degree of corneal edema was evaluated.RESULTS: The effective phaco time, phaco energy and cumulative complex energy parameters in the phaco-chop group were longer or higher than those in the reverse prechop group(P<0.05). The macular retinal thickness in the reverse prechop group at 7 d and 1 mo after surgery was thinner than that in the phaco-chop group, the central corneal thickness at 3 and 7 d after surgery was also thinner than that in the phaco-chop group, the CEC count at 3 mo after surgery was more than that in the phaco-chop group, the CEC loss rate was lower than that in the phaco-chop group, and the CEC area at 3 mo after surgery was smaller than that in the phaco-chop group(P<0.05). The levels of tear TNF-α and IL-6 at 7 d and 1 mo after surgery in the reverse prechop group were lower than those in the phaco-chop group(P<0.05). The BUT at 1 and 3 mo after surgery was longer in the reverse prechop group than that in the phaco-chop group(P<0.05). The CDEQ score in the reverse prechop group was lower than that in the phaco-chop group at 1 and 3 mo after surgery(P<0.05). The SⅠt at 1 and 3 mo after surgery was higher in the reverse prechop group compared with that in the phaco-chop group(P<0.05). The degree of corneal edema at 1 d after surgery was milder in the reverse prechop group than that in the phaco-chop group(P<0.05). CONCLUSION: Compared with phaco-chop, the application of reverse-chopper prechop combined with phacoemulsification can better reduce the ultrasonic energy in the treatment of hard nuclear cataract, and it is more conducive to reducing the postoperative inflammatory degree, improving the tear film function and relieving the corneal edema degree.

Cerebral blood flow directly affects the metabolism of substances and neural activity in the brain, and is closely associated with the occurrence and development of cerebral small vessel disease (CSVD). Multiple studies have revealed that various imaging biomarkers in patients with CSVD, such as lacunar infarction, enlarged perivascular spaces, cerebral microbleeds, cerebral atrophy, and white matter hyperintensities, are closely associated with cerebral autoregulation (CA) function. Therefore, understanding the regulatory mechanism of CA in patients with CSVD is of great significance for delaying the further development of CSVD, improving cerebral ischemia and cognitive impairment. This article reviews the correlation and mechanism between CA and CSVD.

Objective To investigate the epidemiological trends,temporal and spatial distribution characteristics of pulmonary tuberculosis in Lanping County.Methods Based on tuberculosis management data and basic information systems from the"China Disease Prevention and Control Information System,"pulmonary tuberculosis data from Lanping County for 2018-2023 were obtained.Descriptive epidemiology,concentration method,circular distribution method,and spatial autocorrelation analysis were used to conduct epidemiological and spatial analyses of the pulmonary tuberculosis data.Results A total of 2836 TB cases were reported in Lanping County from 2018 to 2023,with an average annual incidence rate of 233.26 per 100000,showing a declining trend.The male-to-female ratio was 1.95∶1,with the highest incidence among individuals aged 60 and above(932 cases,32.86%).Cases were predominantly among farmers(91.01%)and the Lisu ethnic group(52.68%).TB incidence showed weak seasonality with a bimodal distribution,with primary peak occurring from October to March and secondary peak from June to August.Tu'e Township(324.74 per 100,000),Shideng Township(307.42 per 100000),and Jinding Town(260.98 per 100,000)had the highest incidence rates,accounting for 1,284 cases or 45.28%of the county's total cases.In 2020,the incidence of pulmonary tuberculosis in Lanping County showed a spatial clustering distribution(global Morans's I value<0,P value<0.05),with Shideng Township consistently showing high-low aggregation characteristics.Conclusion Between 2018-2023,while the tuberculosis incidence rate in Lanping County has declined,it still falls short of Yunnan Province's tuberculosis prevention and control targets,and the prevention and control work continues to face significant challenges.Strengthening screening of high-risk populations and providing medical support to remote areas will be key measures for future prevention and treatment.

Background Nitrogen dioxide (NO₂) is one of the main air pollutants, and though China's NO₂ pollution has been improving year by year, it maintains at a high level, threatening the health of the population. Objective To investigate the effect of short-term exposure to atmospheric NO₂ on the coagulation indexes in obese and normal-weight young individuals and potential modification effect of temperature. Methods Based on a parallel control panel study design, this study recruited 53 normal-weight and 44 obese young individuals. Three prospective follow-ups were conducted. Air pollution data were obtained from the fixed monitoring station closest to the participant's residences, and personal air pollution exposure was simulated based on time-activity log and infiltration factor for the week before every follow-up. Temperature was collected from China Meteorological Data Service Center. Venous blood samples were taken to measure platelet (PLT) count, mean platelet volume (MPV), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), platelet aggregation rate (PAgT), and plasminogen activator inhibitor type-1 (PAI-1) during every follow-up. A linear mixed-effect model was used to assess the association between short-term atmospheric NO₂ exposure and the coagulation indexes of weight grouped young individuals, and a stratified analysis was used to explore potential modification effect of temperature. Results The median [interquartile range (IQR)] of personal atmospheric NO₂ exposure concentrations was 21.47 (8.01) µg·m⁻³. Short-term exposure to atmospheric NO₂ was significantly associated the increase of sCD40L and PAgT in the obese individuals, while the most significant association appeared at 5 d lag, and for each IQR increase in the average sliding exposure concentration of atmospheric NO₂ with a 5 d lag, sCD40L increased by 27.4% (95%CI: 4.2%, 56.6%) and PAgT increased by 37.5% (95%CI: 12.2%, 68.6%); short-term exposure to atmospheric NO₂ was significantly associated with the decrease of PLT and PAgT in the normal-weight individuals, while the most significant association appeared at 5 d lag or 7 d lag, and for each IQR increase in the average sliding exposure concentration of atmospheric NO₂ with a 5 d lag, PLT decreased by 11.8% (95%CI: −17.8%, −5.3%), and for each IQR increase in the average sliding exposure concentration of atmospheric NO₂ with a 7 d lag, PAgT decreased by 16.8% (95%CI: −30.6%, −0.4%). We didn't find statistically significant association of short-term exposure to atmospheric NO₂ with PLT in the obese individuals or sCD40L in the normal-weight individuals, nor statistically significant association between short-term exposure to atmospheric NO₂ and PAI-1, MPV, and sP-selectin in different weight grouped individuals. The stratified analysis found that short-term exposure to atmospheric NO₂ was significantly associated with PAgT in the normal-weight individuals, or with PLT, sCD40L, and sP-selectin in the obese individuals only at high temperature. Conclusions Short-term exposure to atmospheric NO₂ has adverse effects on the coagulation indexes of different weight grouped young individuals, and the obese individuals are more sensitive to it than the normal-weight individuals. High temperature can enhance the adverse health effect of short-term exposure to atmospheric NO₂.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

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.