AIM: To investigate the potential causal relationship between gut microbiota(GM)and primary open-angle glaucoma(POAG)based on a two-sample Mendelian randomization(MR)analysis.METHODS: The exposure data was derived from the Genome-Wide Association Studies(GWAS)of GM at the University of Bristol, while the outcome data for POAG was sourced from the MRC Integrative Epidemiology Unit(IEU)Open GWAS database. In this study, inverse variance weighted(IVW), MR Egger, weighted median(WM), Simple Mode, and Weighted Mode were analyzed to investigate the potential causal relationships between GM and POAG. IVW was used as the primary method for this study, and sensitivity analysis was conducted to assess the reliability of the MR analysis.RESULTS: The IVW analysis revealed that Butyrivibrio(OR=1.170, 95%CI: 1.057-1.295, P=0.002), Howardella(OR=1.188, 95%CI: 1.043-1.355, P=0.010), and LachnospiraceaeUCG001(OR=1.229, 95%CI: 1.016-1.485, P=0.033)were correlated with the risk of POAG. Conversely, Candidatus Soleaferrea(OR=0.810, 95%CI: 0.670-0.981, P=0.031), Ruminococcustorquesgroup(OR=0.656, 95%CI: 0.453-0.950, P=0.026), and RuminococcaceaeUCG013(OR=0.770, 95%CI: 0.598-0.990, P=0.041)were protective factors for POAG. Sensitivity analysis showed that there were no heterogeneity and pleiotropy among the instrumental variables.CONCLUSION: The MR study indicated a causal relationship between GM and POAG. Given the sight-threatening characteristic of POAG, early identification and intervention in the relative factors was significant for the prognosis of POAG.

Objective:To explore the correlation between the early neurological deterioration and the poor short-term outcome after intravenous thrombolysis with recombinant tissue Plasmin activator (rt PA) in patients with acute ischemic stroke.Methods:A retrospective analysis of 268 patients with acute ischemic stroke who received recombinant tissue Plasmin activator(rt-PA) intravenous thrombolytic therapy in the Department of Neurology of Civil Aviation General Hospital from January 2019 to October 2022 was performed. The modified Rankin scale(mRS) was used to evaluate short-term outcome at 14 days after thrombolysis, with a score of 0 to 2 defined as good outcome and a score of 3 to 5 or death defined as poor outcome. Clinical, laboratory and imaging data of the two groups were collected. Univariate analysis was used to compare the baseline data of the two groups, and multivariate Logistic regression analysis was used to determine the independent risk factors for poor short-term outcomes.Results:Univariate analysis showed that age, baseline NIHSS score, fasting blood sugar, glycated hemoglobin, the proportion of coronary heart disease, proportion of atrial fibrillation, proportion of paraventricular high signal (3 score), proportion of hemorrhage transformation, proportion of END, proportion of double circulation infarction, proportion of new cortical infarction, proportion of new internal capsule infarction, proportion of large atherosclerosis of TOAST classification, and proportion of cardiogenic embolism of TOAST classification in the good outcome group were higher than those in the poor outcome group(68.00 (59.00, 80.00) years old vs 64.00 (54.50, 72.00) years old, 9 (6, 13) points vs 5 (3, 7) points, 6.85 (5.25, 9.20) mmol/L vs 5.64 (4.90, 6.75) mmol/L, 6.40 (5.70, 7.75)% vs 6.00 (5.60, 6.80)%, 31.3% (31/99) vs 17.7% (30/169), 28.3% (28/99) vs 9.5% (16/169), 26.3% (26/99) vs 13.0% (22/169), 19.2% (19/99) vs 5.9%(10/169), 53.5% (53/99) vs 21.9% (37/169), 10.1% (10/99) vs 2.4% (4/169), 44.4% (44/99) vs 22.5% (38/169), 41.4% (41/99) vs 27.8% (47/169), 33.3% (33/99) vs 17.8% (30/169), 25.3% (25/99) vs 6.5% (11/169)), the proportion of small artery occlusion and others of TOAST classification ,platelets were lower than the poor outcome group (29.3%(29/99) vs 53.8%(91/169),12.1%(12/99) vs 21.8%(37/169),199(163,240)×10 9/L vs 221(179,259)×10 9/L). The differences were statistically significant(the statistical values were U=2.80, U=7.94, U=3.24, U=2.29, χ 2=6.53, χ 2=16.11, χ 2=7.45, χ 2=11.40, χ 2=28.02, χ 2=7.54, χ 2=14.18, χ 2=5.24, χ 2=34.44, and U=2.16, respectively; P values were 0.005, <0.001, 0.001, 0.022, 0.011, <0.001, 0.006, 0.001, <0.001, 0.006, <0.001, 0.002, <0.001, and 0.031, respectively). Multivariate Logistic analysis showed that only baseline NIHSS score ( OR=1.212, 95% CI :1.123-1.309, P<0.001) and END ( OR=3.397, 95% CI:1.763-6.546, P<0.001) were independently related to the poor short-term outcome after intravenous thrombolysis in acute ischemic stroke patients. Conclusions:END and High baseline NIHSS score were independent risk factors for poor short-term outcome after intravenous thrombolysis in acute ischemic stroke patients.

Objective To investigate the pharmacodynamic effects of Poria triterpenes on tumor suppression in mice with ascites tumors,and to detect and identify the chemical components of Poria triterpenes using HPLC-LTQ-Orbitrap method,and to explore the potential mechanism of action of Poria triterpenes on tumor suppression in mice with ascites tumors based on both of them using non-labeled definitive proteomics techniques.Methods Poria triterpene parts were extracted by solvent method,and the main components were detected and identified by HPLC-LTQ-Orbitrap liquid mass spectrometer;mice were randomly divided into model group,Poria triterpene group and positive control group(mushroom polysaccharide group),after 21 days of continuous administration,to establish After continuous administration for 21 days,the H22 ascites tumor mouse model was established,and the effect of each drug group on the amount of ascites,spleen index,thymus index,liver index,serum TNF-Alpha and IL-2 in H22 ascites tumor mice was observed after one week of continued administration;then H22 cells were extracted from the ascites of mice,and the H22 cells in the model group and Poria triterpene group were detected by non-lable-free quantitative proteomics technique.The differentially expressed proteins(DEPs)were screened out by using GO,KEGG and other analyses.Results The abdominal water volume in the mouse Poria triterpene group was significantly lower than that in the model group(P<0.05);the thymus index in the mouse Poria triterpene group was significantly higher than that in the model group(P<0.05);the serum levels of TNF-Alpha in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01),and the serum levels of IL-2 in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01).Through the analysis of the chemical composition of Poria triterpene parts,a total of 19 triterpenoids were identified,with four main structural types.A total of 188 differentially expressed proteins were identified in the Poria triterpene group compared with the model group,of which 86 differentially expressed proteins were up-regulated and 102 differentially expressed proteins were down-regulated;GO database analysis showed that the differentially expressed proteins in the Poria triterpene group were mainly involved in the regulation of interleukin-1 production The KEGG database analysis showed that the differentially expressed proteins in the Poria triterpene group were involved in signaling pathways closely related to tumor,mainly MAPK,Apoptosis,mTOR,Wnt and p53 pathways,etc.The genes coding for the seven representative differential proteins were validated at the mRNA level by RT-qPCR.Conclusion The pharmacodynamic study found that Poria triterpenes had tumor suppressive effect on H22 ascites tumor mice,then by proteomics found Poria triterpenes group ascites H22 cell protein compared to the model group changed significantly,the study thus showed that Poria triterpenes for mice ascites tumor mechanism of tumor suppressive effect mainly involves apoptosis,inflammatory response and immune process.

Objective To investigate the association between the overall burden of cerebral small vascular disease （CSVD） and the hemorrhagic transformation of acute ischemic stroke after intravenous thrombolysis. Methods A retrospective analysis was performed for 268 patients with acute ischemic stroke who received rt-PA intravenous thrombolysis in our hospital from January 2019 to October 2022, and according to the presence or absence of hemorrhagic transformation after thrombolysis, they were divided into hemorrhagic transformation group and non-hemorrhagic transformation group. Related data were collected for both groups, including demographic information （sex, age）, smoking history, medical history （hypertension, diabetes, hyperlipidemia, coronary heart disease, atrial fibrillation, and ischemic stroke）, and clinical data after onset, such as onset-to-treatment time （OTT）, systolic pressure/diastolic pressure/blood glucose at baseline, laboratory findings within 24 hours after onset [fasting blood glucose, glycated hemoglobin, homocysteine, creatinine, triglyceride, total cholesterol, high-density lipoprotein cholesterol （HDL-C）, low-density lipoprotein cholesterol （LDL-C）, uric acid, platelet, prothrombin time （PT）, international normalized ratio （INR）, fibrinogen, fibrinogen, C-reactive protein （CRP）], location of infarction （anterior circulation or posterior circulation）, TOAST typing, and the overall burden of CSVD （mild, moderate or severe）. The two groups were compared in terms of baseline data, clinical data, and CSVD score, and the logistic regression analysis was used to investigate the association between the overall burden of CSVD and hemorrhagic transformation after intravenous thrombolysis. Results A total of 268 patients with acute ischemic stroke who received intravenous thrombolysis were enrolled, with an age of 23-97 years （mean 65.5 years）, and male patients accounted for 70.5% （189/268）. The baseline NIHSS score was 7.5 （0, 27） points, and OTT was 151.2 （20, 270） minutes. Among these patients, 138 （51.4%） had moderate to severe WMH, 193 （72.0%） had lacunar infarction, 56（20.8%） had cerebral microbleeds,and 106（39.5%） had perivascular spaces. There were 115 patients（42.9%） in the mild CSVD group,65（24.2%） in the moderate CSVD group,and 88 （32.8%） in the severe CSVD group. There were 29 patients with hemorrhagic transformation （10.3%）. Atrial fibrillation （odds ratio OR=5.628,95%CI 1.862-17.009,P=0.002）,cerebral microbleeds （OR=4.062,95%CI 1.437-11.485,P=0.008）, and baseline NIHSS score （OR=1.182,95%CI 1.082-1.292,P<0.001） were independent risk factors for hemorrhagic transformation after thrombolysis, and with mild CSVD as the reference, severe CSVD（OR=0.694,95%CI 1.458-9.360,P=0.006） was independently associated with hemorrhagic transformation. Conclusion The overall burden of CSVD in patients with acute ischemic stroke is closely associated with hemorrhagic transformation after intravenous thrombolysis, and severe CSVD is an independent risk factor for hemorrhagic transformation after intravenous thrombolysis.

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.
Antimalarials/pharmacology* ; China/epidemiology* ; Drug Combinations ; Drug Resistance/genetics* ; Folic Acid Antagonists/pharmacology* ; Humans ; Mutation ; Plasmodium vivax/genetics* ; Prevalence

Objective:To explore the association between short-term exposures to fine particulate matter (PM 2.5) on blood lipids in the elderly. Methods:In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM 2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM 2.5 exposure at different lag with blood lipids and dyslipidemia. Results:The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m 2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 μg/m 3 increase in PM 2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95% CI: 1.22%-2.32%), 1.90% (95% CI: 1.18%-2.63%), 1.99% (95% CI: 1.37%-2.60%) and 1.74% (95% CI: 1.11%-2.37%), and the OR values (95% CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion:There is a significant association of short-term PM 2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Objective:To explore the association between short-term exposures to fine particulate matter (PM 2.5) on blood lipids in the elderly. Methods:In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM 2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM 2.5 exposure at different lag with blood lipids and dyslipidemia. Results:The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m 2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 μg/m 3 increase in PM 2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95% CI: 1.22%-2.32%), 1.90% (95% CI: 1.18%-2.63%), 1.99% (95% CI: 1.37%-2.60%) and 1.74% (95% CI: 1.11%-2.37%), and the OR values (95% CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion:There is a significant association of short-term PM 2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Evaluate the effect of the fresh air purification system on the improvement of indoor PM 2.5 levels in a primary school classroom in Jinan City, Shandong Province. Our purpose is to explore the optimal operating time of the fresh air system and the main factors that affect the fresh air purification system to improve indoor air quality. From December 9, 2019 to December 10, 2019, two classrooms of the same area on the third floor of a primary school building in Jinan City, Shandong Province were selected as monitoring points. During the operation of the fresh air purification system, the PM 2.5 concentration in the classroom is reduced by an average of 48.1%-61.5% compared to the outdoor PM 2.5 concentration. After running for about 2 hours, the indoor PM 2.5 concentration decreased to a relatively stable concentration level. The operating time of the fresh air purification system, student activities between classes, indoor temperature, indoor relative humidity, and outdoor PM 2.5 concentration are important factors that affect the indoor particulate removal rate. In the case of a certain amount of fresh air and indoor area, closing doors and windows and appropriately extending the operation time of the fresh air purification system can improve the air quality in the classroom to a certain extent and protect the health of students.

Evaluate the effect of the fresh air purification system on the improvement of indoor PM 2.5 levels in a primary school classroom in Jinan City, Shandong Province. Our purpose is to explore the optimal operating time of the fresh air system and the main factors that affect the fresh air purification system to improve indoor air quality. From December 9, 2019 to December 10, 2019, two classrooms of the same area on the third floor of a primary school building in Jinan City, Shandong Province were selected as monitoring points. During the operation of the fresh air purification system, the PM 2.5 concentration in the classroom is reduced by an average of 48.1%-61.5% compared to the outdoor PM 2.5 concentration. After running for about 2 hours, the indoor PM 2.5 concentration decreased to a relatively stable concentration level. The operating time of the fresh air purification system, student activities between classes, indoor temperature, indoor relative humidity, and outdoor PM 2.5 concentration are important factors that affect the indoor particulate removal rate. In the case of a certain amount of fresh air and indoor area, closing doors and windows and appropriately extending the operation time of the fresh air purification system can improve the air quality in the classroom to a certain extent and protect the health of students.

OBJECTIVE: To retrospectively analyze non-invasive prenatal screening (NIPS) data from two centers. METHODS: The NIPS results of 10 840 samples were analyzed, including 21/18/13 trisomies (T21/T18/T13), sex chromosome and other autosomal aneuploidies, and copy number variants (CNVs). The maternal age, gestational week, body mass index and concentration of free fetal DNA (cffDNA) were also analyzed. RESULTS: The average gestational age of the 10 840 pregnant women was (32.34±5.04) year old, and the average gestational week for NIPS was (17.60±3.55) week. The overall false positive rate for T21/T18/T13 was 0.11%, sensitivity was 100%, specificity was 99.89%, and positive predictive value was 81.5%. The positive predictive values for sex chromosome and other autosomal aneuploidies and CNVs were 56.67%, 11.76% and 83.33%, respectively. The incidence of T21/T18 in the elder women (35 years or elder) was 2.12 times(P<0.01) and 1.81 times (P> 0.05) that of young women. cffDNA was in proportion to gestational week (r = 0.207) and in inverse proportion to body mass index (r = -0.177). It has increased slowly before 15 weeks of gestation and thereafter at a rate of 0.5% per week after the 16th week. CONCLUSION The performance of NIPS in this study is by large close to the reported in the literature, and the results can provide a reference for further study.