ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveTo observe the clinical efficacy of modified Xiangsha Liujunzi Decoction （香砂六君子汤， XLD） in the treatment of abemaciclib-related diarrhea of spleen-stomach deficiency type， and its regulatory effect on immune function in patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative （HR+/HER2-） breast cancer. MethodsA prospective， randomized， open-label， blinded-endpoint （PROBE） study was conducted. A total of 70 patients with advanced HR+/HER2- breast cancer and abemaciclib-related diarrhea were randomly divided into two groups， with 35 cases in each group. In addition to abemaciclib， the control group was treated with oral loperamide， while the trial group was treated with oral modified XLD. Both groups received treatment for 7 days as one course. The efficacy for diarrhea after treatment was compared between groups. Traditional Chinese medicine （TCM） syndrome score， Karnofsky performance status （KPS） score， inflammatory markers including interleukin-6 （IL-6） and C-reactive protein （CRP）， and immune function indicators including CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio were compared between groups before and after treatment. Adverse events during the study were recorded， and safety was assessed. ResultsDuring the study， 1 case in the trial group and 2 cases in the control group， were lost to follow-up leaving 34 cases in the trial group and 33 cases in the control group for final analysis. The total effective rate of diarrhea in the trial group was 94.12% （32/34）， higher than 72.73% （24/33） in the control group （P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， increased KPS scores， increased CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio， and decreased IL-6 and CRP levels （all P＜0.05）. Compared to the control group， the trial group had higher KPS scores， CD4⁺ levels， and CD4⁺/CD8⁺ ratios， and lower TCM syndrome scores and IL-6， CRP， and CD8⁺ levels （P＜0.05）. The incidence of adverse events in the trial group was 20.59% （7/34）， with an incidence of adverse drug reactions of 14.71% （5/34） after causality assessment； in the control group， the corresponding rates were 45.45% （15/33） and 39.39% （13/33）， respectively. The incidence of adverse events in the trial group was significantly lower than that in the control group （P＜0.05）. ConclusionModified XLD can effectively alleviate abemaciclib-related diarrhea in patients with advanced HR+/HER2- breast cancer of the spleen-stomach deficiency type， reduce levels of inflammatory cytokines， and regulate immune function， with a favorable safety profile.

Peroxynitrite anion(ONOO-),which is originated from the reaction of nitric oxide(NO)and superoxide anion(O2-),plays a pivotal role in immune defense and signal regulation.Excessive levels of ONOO-may induce the occurrence of various diseases such as Alzheimer's disease,inflammation,cardiovascular disease and cancer,etc.Existing detection methods for ONOO-have limitations such as complexity,time consumption,and low cell biocompatibility.In this study,a novel fluorescent probe QFPD was developed using quinoline and diphenylphosphinamide as fluorescent keleton and recognition group,respectively.The strong oxidizing property of ONOO-triggerd the cleavage of phosphoramide bond,leading to fluorescence quenching and a visible color change of the solution from yellow to purple,thereby enabling"ON-OFF"type recognition of ONOO-.QFPD exhibited excellent characteristics including good selectivity and high sensitivity in fluorescence detection(Limit of detection of 1.37 μmol/L),large Stokes shift(130 nm),rapid response(10 min),and strong anti-interference ability.Additionally,QFPD demonstrated good biocompatibility and could realize real-time dynamic monitoring of endogenous ONOO-.Furthermore,QFPD was successfully applied to environmental toxicology research by visualizing the oxidative stress effects induced by microplastics polymethyl methacrylate(PMMA)and Hg2+exposure,which might be a novel tool for the mechanism research on oxidative stress associated with microplastic pollution and heavy metal exposure.

BACKGROUND:Much of the current research on M2 macrophage-derived exosomes focuses on their effects on wound healing and osteoblast proliferation and differentiation,while few studies have focused on their role in regulating microglia phenotype.OBJECTIVE:To discuss the role and molecular mechanisms of M2 macrophage-derived exosomes in the phenotypic regulation of microglia.MERHODS:(1)Bone marrow primary macrophages were extracted and then stimulated with 50 ng/mL interleukin 4 for 24 hours to promote macrophage M2-type polarization.Flow cytometry and cellular immunofluorescence were used to identify the M2-type macrophage marker CD206.(2)M2 macrophage-derived exosomes were extracted and identified.(3)Microglia BV2 were randomly divided into three groups:control group,lipopolysaccharide group,and treatment group.No treatment was done in the control group.500 ng/mL lipopolysaccharide was added to the intervention for 24 hours in the lipopolysaccharide group.500 ng/mL lipopolysaccharide and 25 μg/mL M2 macrophage-derived exosomes were added simultaneously to the treatment group for 24 hours.ELISA was performed to detect the secretion of tumor necrosis factor α and interleukin 10 in the culture supernatant.qRT-PCR was performed to detect the mRNA expression of inducible nitric oxide synthase,arginase 1,interleukin 1β,and interleukin 10 in the cells.Western blot assay was performed to detect the protein expression of inducible nitric oxide synthase,arginase 1,and nuclear factor-κB signaling pathway related protein expression.RESULTS AND CONCLUSION:(1)ELISA results showed that the secretion of tumor necrosis factor α was significantly increased in the lipopolysaccharide group compared with the control group.The secretion of tumor necrosis factor α was reduced and the secretion of interleukin 10 was increased in the treatment group compared with the lipopolysaccharide group.(2)The qRT-PCR results showed that compared with the control group,the mRNA expression of interleukin 1β and inducible nitric oxide synthase increased in the lipopolysaccharide group.Compared with the lipopolysaccharide group,the mRNA expression of interleukin 1β and inducible nitric oxide synthase decreased,and the mRNA expression of interleukin 10 and arginase 1 increased in the treatment group.(3)Western blot assay results showed that the expression of inducible nitric oxide synthase protein was increased in the lipopolysaccharide group compared with the control group.The expression of inducible nitric oxide synthase protein was decreased and the expression of arginase 1 protein was elevated in the treatment group compared with the lipopolysaccharide group.(4)Compared with the control group,the expression of p65 and p-IκB-α proteins in the nuclear factor-κB signaling pathway was reduced in the lipopolysaccharide group,whereas the expression of p65 and p-IκB-α proteins was elevated in the treatment group compared with the lipopolysaccharide group.The results showed that M2-type macrophage-derived exosomes could significantly inhibit lipopolysaccharide-induced inflammatory responses in microglia,enhance the expression of the anti-inflammatory factor interleukin 10,suppress the expression of the pro-inflammatory factors tumor necrosis factor α and interleukin 1β,and promote microglial cell phenotypes polarized from the M1-type to the M2-type.The mechanism may be related to the inhibition of nuclear factor-κB signaling pathway activation by M2-type macrophage-derived exosomes.

Objective To propose an improved Bouc-Wen model to alleviate the nonlinear effect of the hysteresis displacement of piezoceramics and enhance the motion control accuracy of the nano-displacement platform.Methods Firstly,two fine-tuning parameters including the asymmetric term and the input bias term were added to the classical Bouc-Wen model to eliminate the deviation of the starting and ending positions of the hysteresis curve,so as to obtain an improved Bouc-Wen model simulating the hysteresis displacement characteristics of piezoceramics on the nano-displacement platform.Secondly,the parameters of the improved Bouc-Wen model were identified based on the particle swarm optimization algorithm,and an inverse feedforward structure was adopted to realize the linearized control of the output displacement.Finally,an experimental system was built to verify the linearized control effect of the improved Bouc-Wen model.Results The hysteresis curve of the improved Bouc-Wen model fitted the actual voltage-displacement curve of piezoceramics significantly better when compared with that of the traditional model,which had a 56%reduction in the fitting error and a 0.03 μm error between the desired and actual displacements during the linearized output control with a driving voltage of 0-60 V and a maximum travel of about 4 μm.Conclusion The improved Bouc-Wen model behaves well in hysteresis displacement fitting and linearized output control,and a new idea is provided for enhancing the motion control accuracy of the nano-displacement platform.[Chinese Medical Equipment Journal,2025,46(8):25-31]

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

Objective To design a high altitude adaptive oxygen generator for the crews to alleviate their high altitude reaction in high altitude environment and meet their requirements for oxygen supply.Methods A high altitude adaptive oxygen generator based on the mature pressure swing adsorption oxygen production method was designed with the key technologies of discharge capacity compensation of air compression pump and airway fusion of molecular sieve tower,which had the components of molecular sieve tower,air compression pump,controller,cooling fan,cooler,solenoid valve,regulator,flow meter and etc.Trials were carried out at the simulated altitude and field plateau environment so as to verify the high altitude adaptive performance of the oxygen generator developed.Results The trial results showed the oxygen generator met the desired objectives and the requirements for oxygen volume fraction in GJB 2799-1996 General specification for medical oxygen generator using molecular sieve method.Conclusion The oxygen generartor provides oxygen supply effectively for vehicle operators in plateau environments or the ones rushing into the plateau.[Chinese Medical Equipment Journal,2025,46(4):29-34]