Objective The optimum formulation process was selected to prepare the ethosomes of Cortex Dictamni-Fructus Kochiae,and its prescription was verified and its properties were studied.Methods The formulation was optimized by single factor and response surface test.The appearance,particle size,Zeta potential and stability were investigated.The encapsulation rate was used as the evaluation index.Results The optimum preparation process of ethosomes of Cortex Dictamni-Fructus Kochiae is as follows:Using the dosage of lyophilized powder 409.06 mg,soybean lecithin 258.07 mg,cholesterol 90.87 mg,ethanol volume fraction 22.76％,stirred for 2 hours at 700 r·min-1 at 50 ℃ water bath temperature,The appearance of the prepared ethosomes suspension was light yellow,and the particles were nearly spherical in shape.The average particle size was(103.1±0.78)nm,the Zeta potential was(-36.0±3.65)mV,and the average encapsulation rates of Xibutanone,ash,and saponin Ⅰc were(89.25±0.91)％,(80.16±1.52)％,(86.59±0.58)％,respectively.After 14 days of storage at room temperature,the results showed that:The ethosomal suspension is still a light yellow,uniform,and stable liquid,and there is no stratified precipitation phenomenon.Conclusion The method of ethanol injection is easy to operate,high encapsulation rate and good stability,which lays a foundation for further study on the skin administration of this preparation.

Alzheimer's disease(AD)is the most common neurodegenerative disorder worldwide,characterized primarily by cognitive impairment and memory dysfunction.Its pathological mechanisms involve the toxic accumulation of amyloid β-protein(Aβ),hyperphosphorylation of Tau protein leading to neurofibrillary tangles,mitochondrial dysfunction,synaptic impairment,cholinergic system dysfunction,neuroinflammation,and oxidative stress.Current clinical treatments for AD include acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists,which can improve cognitive function but fail to slow disease progression and often have side effects.Research indicates that traditional Chinese medicine(TCM)may regulate the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway,promoting neuronal survival,inhibiting neuroinflammation,reducing oxidative stress,preventing apoptosis,and decreasing Aβ deposition,thus improving the symptoms of AD.This review summarizes the mechanisms by which individual TCM components,extracts,and formulas may regulate the PI3K/AKT pathway in the treatment of AD,with the aim of providing a theoretical foundation for the application of TCM in AD therapy.

Alzheimer's disease(AD)is the most common neurodegenerative disorder worldwide,characterized primarily by cognitive impairment and memory dysfunction.Its pathological mechanisms involve the toxic accumulation of amyloid β-protein(Aβ),hyperphosphorylation of Tau protein leading to neurofibrillary tangles,mitochondrial dysfunction,synaptic impairment,cholinergic system dysfunction,neuroinflammation,and oxidative stress.Current clinical treatments for AD include acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists,which can improve cognitive function but fail to slow disease progression and often have side effects.Research indicates that traditional Chinese medicine(TCM)may regulate the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway,promoting neuronal survival,inhibiting neuroinflammation,reducing oxidative stress,preventing apoptosis,and decreasing Aβ deposition,thus improving the symptoms of AD.This review summarizes the mechanisms by which individual TCM components,extracts,and formulas may regulate the PI3K/AKT pathway in the treatment of AD,with the aim of providing a theoretical foundation for the application of TCM in AD therapy.

Objective To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in passenger drivers and its influencing factors. Methods A total of 951 passenger drivers in Guangdong Province were selected as the research subjects using the judgmental sampling method. A Musculoskeletal Injury Questionnaire was employed to assess the prevalence of WMSDs in the past year. Results The prevalence of WMSDs in passenger drivers was 41.11%. The result of multivariable logistic regression analysis showed that married drivers had a higher risk of WMSDs than single drivers (P<0.05). The lower the frequency of physical exercise, the longer the driving time per week, the longer the continuous driving time, the more restricted the driving working space, the poorer the foot comfort during driving, and the more affected the normal meal, the higher the risk of WMSDs (all P<0.05). The risk of WMSDs in drivers with sleep time ≤ 8.0 h/d was higher than that in drivers with sleep time > 8.0 h/d (P<0.01), and the risk of WMSDs in drivers with the same posture for a long time on the shoulder was higher than that in drivers without this poor working posture (P<0.01). Conclusion WMSDs were prevalent among passenger drivers, which was associated with demographic and adverse ergonomic factors. Intervention on lifestyle and adverse ergonomic factors could further reduce the risk of WMSDs of passenger drivers.

Objective To investigate the causal relationship between obstructive sleep apnea(OSA)and common types of dementia by using Mendelian randomization(MR)analysis methods.Methods Based on summary data from large-scale genome-wide association studies(GWAS),single nucleotide polymorphisms(SNP)highly associated with OSA,Alzheimer's disease(AD),vascular dementia(VaD),dementia with Lewy bodies(DLB),and frontotemporal dementia(FTD)were selected as instrumental variables.The inverse variance weighted method(IVW)was employed as the primary analytical method,and stability tests were conducted by using the simple median method,weighted median method(WME),MR-Egger regression meth-od,simple mode(SM)and weighted mode(WM).Additionally,F-statistics,Cochran'Q test,MR-Egger re-gression intercept test,and leave-one-out method were used for weak instrument variables bias testing,hetero-geneity testing,pleiotropy analysis,and sensitivity analysis,respectively.Causal associations were evaluated by using odds ratios(OR)and 95%CI.Results MR analysis showed that OSA was associated with an increased risk of VaD(OR=1.829,95%CI:1.024-3.266,P<0.05).All F-statistics were>10,indicating no weak in-strumental variables.Cochran'Q test and MR-Egger regression intercept test revealed no heterogeneity and horizontal pleiotropy(P>0.05).Conclusion Genetic-level prediction suggests that OSA is associated with an increased risk of VaD.Early prevention and treatment of OSA may help improve patients'quality of life.

OBJECTIVE To re-evaluate the use of systematic evaluation/meta-analysis of anti-VEGF drugs in the treatment of diabetic macular oedema(DME),aiming to provide evidence-based support for the clinical application of this medication.METHODS A comprehensive search was conducted across a range of databases,including CNKI,Wanfang data,VIP,CBM,PubMed,Web of Science,Embase,and Cochrane Library.The objective was to identify systematic evaluation/meta-analysis of anti-VEGF drugs for DME,with search time from the inception of the databases to March 2024.The report quality,methodological quality,and evidence quality were assessed by using PRISMA2020 statement,AMSTAR2 scale and GRADE tool.A comprehensive analysis of systematic evaluation/meta-analysis results was also conducted.RESULTS A total of 22 articles were included.According to the PRISMA2020 statement evaluation,13 studies provided relatively complete information(≥21 points),while 9 studies had information deficiencies(18-＜21 points).The AMSTAR 2 scale evaluation revealed that 21 studies had very low methodological quality,and one study had low methodological quality.The GRADE tool evaluation showed that out of 89 outcome indicators,28(31.46%)were classified as high-quality evidence,34(38.20%)as moderate-quality evidence,24(26.97%)as low-quality evidence,and 3(3.37%)as very low-quality evidence.The comprehensive quality analysis results demonstrated that,compared with laser photocoagulation,anti-VEGF drugs significantly enhanced the improvement in best-corrected visual acuity(BCVA),as well as significant change in retinal thickness at 1 and 6 months,and 1 and 2 years post-treatment,and also in BCVA and retinal thickness at 1,3,and 6 months post-treatment(P＜0.05).Compared with placebo,patients treated with anti-VEGF drugs showed significant improvement in BCVA after 1 year of treatment(P＜0.05).However,when compared with corticosteroid drugs,patients treated with anti-VEGF drugs exhibited a significant increase in retinal thickness after 6 months of treatment(P＜0.05).Compared with corticosteroid drugs,the incidence of adverse events related to the eyes,cataract formation and intraocular pressure were significantly decreased in patients treated with anti-VEGF drugs(P＜0.05).Compared with laser photocoagulation,the incidence of ocular adverse events was significantly decreased in patients treated with anti-VEGF drugs,while the incidence of fatal adverse events was significantly increased(P＜0.05).CONCLUSIONS Anti-VEGF therapy for DME may possess certain advantages in terms of efficacy and safety,but it is associated with a higher risk of fatal adverse events;the evidence included in systematic reviews/meta-analyses is of moderate to high quality.

Objective The optimum formulation process was selected to prepare the ethosomes of Cortex Dictamni-Fructus Kochiae,and its prescription was verified and its properties were studied.Methods The formulation was optimized by single factor and response surface test.The appearance,particle size,Zeta potential and stability were investigated.The encapsulation rate was used as the evaluation index.Results The optimum preparation process of ethosomes of Cortex Dictamni-Fructus Kochiae is as follows:Using the dosage of lyophilized powder 409.06 mg,soybean lecithin 258.07 mg,cholesterol 90.87 mg,ethanol volume fraction 22.76％,stirred for 2 hours at 700 r·min-1 at 50 ℃ water bath temperature,The appearance of the prepared ethosomes suspension was light yellow,and the particles were nearly spherical in shape.The average particle size was(103.1±0.78)nm,the Zeta potential was(-36.0±3.65)mV,and the average encapsulation rates of Xibutanone,ash,and saponin Ⅰc were(89.25±0.91)％,(80.16±1.52)％,(86.59±0.58)％,respectively.After 14 days of storage at room temperature,the results showed that:The ethosomal suspension is still a light yellow,uniform,and stable liquid,and there is no stratified precipitation phenomenon.Conclusion The method of ethanol injection is easy to operate,high encapsulation rate and good stability,which lays a foundation for further study on the skin administration of this preparation.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Background Pesticides like organophosphorus and pyrethroids are extensively utilized, and associated potential human health risks arising from multi-route exposure, including environmental sources and dietary intake, cannot be overlooked. Conducting human exposure studies using pesticide exposure biomarkers is essential for an objective evaluation of human pesticide exposure levels. Objective To develop a rapid and precise liquid chromatography-tandem mass spectrometry method for the detection of 12 pesticide metabolites in urine, including 5 metabolites of organophosphorus pesticide, 4 metabolites of pyrethroid pesticide, 2 metabolites of herbicides, and 1 metabolite of insecticide. Methods After overnight enzymatic hydrolysis, urine samples were subjected to extraction and purification using Oasis HLB 96-well solid-phase extraction. Subsequently, the samples were analyzed by liquid chromatography-tandem mass spectrometry and quantified using the isotope internal standard method. The developed method was employed to analyze 143 urine samples from a general population to assess its effectiveness and to evaluate pesticide exposure levels. Results All 12 target compounds exhibited good linear ranges, with their correlation coefficients of calibration curves exceeding 0.999. The limits of detection (LOD) ranged from 0.02 to 0.19 μg·L⁻¹, while the limits of quantitation (LOQ) ranged from 0.06 to 0.27 μg·L⁻¹. The recoveries at three spiked levels ranged from 84% to 112%, and the inter- and intra- day precisions of targeted analystes were 0.43%-9.6% and 1.6%-9.7% respectively. Using this method, 143 urine samples from residents in Jiangsu region were analyzed, and 11 pesticides were detected except N,N-diethyl-m-toluamide (DEET). Conclusion The established method of solid-phase extraction combined with liquid chromatography-tandem mass spectrometry has the characteristics of low detection limit, good repeatability, and high throughput, which is suitable for quantitative detection of selected 12 pesticides in large batches of human urine samples, and provides technical support for pesticide internal exposure monitoring and health risk assessment.