BACKGROUND: Children's respiratory health demonstrates particular sensitivity to air pollution. Existing evidence investigating the association between short-term ozone (O₃) exposure and childhood pneumonia remains insufficient and inconsistent, especially in low- and middle-income countries (LMICs). METHOD: To provide more reliable and persuasive evidence, we implemented a multi-city, time-stratified case-crossover design with a large sample size, using data from seven representative children's hospitals across major geographical regions in China. To avoid the impact of the COVID-19 pandemic, individual-level medical records of inpatient children under 6 years of age diagnosed with pneumonia during 2016-2019 were collected. Conditional logistic regression models were fitted for each city, and city-specific estimates were pooled through a meta-analysis using a random-effects model. RESULTS: In total, the study included 137,470 pediatric pneumonia hospital admissions. The highest pooled estimate for O₃ occurred at lag0-1, with a 10 µg/m³ increase in O₃ associated with a 1.57% (95% CI: 0.67%-2.48%) higher risk of pediatric pneumonia hospital admissions. Stratified analyses indicated that the effects of O₃ were robust across different sexes, age groups, and admission seasons. We also observed a statistically significant increase in risk associated with O₃ concentrations exceeding the World Health Organization Air Quality Guidelines (WHO-AQGs). CONCLUSIONS This study revealed a significant positive association between O₃ and pediatric pneumonia hospital admissions. Our findings substantially strengthen the evidence base for the adverse health impacts of O₃, underscoring the importance of O₃ pollution control and management in reducing the public health burden of pediatric pneumonia.
Humans ; Ozone/analysis* ; China/epidemiology* ; Pneumonia/chemically induced* ; Child, Preschool ; Male ; Female ; Infant ; Cross-Over Studies ; Air Pollutants/analysis* ; Hospitalization/statistics & numerical data* ; Child ; Cities/epidemiology* ; Air Pollution/adverse effects* ; Infant, Newborn ; Environmental Exposure/adverse effects*

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Objective:To design and synthesize a 18F-labeled small molecule PET imaging probe targeting carbonic anhydrase Ⅸ (CAⅨ), named as 18F-single-acetazolamide (SAZ), and to evaluate its biological properties preliminarily. Methods:Acetazolamide was used as raw material to synthesize the precursor SAZ, and the target probe 18F-SAZ was obtained through nucleophilic substitution and other reactions. The radiochemical yield, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-SAZ were determined. Cancer cell lines OS-RC-2 (CAⅨ-positive) and HCT116 (CAⅨ-negative) were used for cell uptake experiments, and corresponding tumor-bearing mice were constructed for microPET imaging. Biodistribution of the probe in OS-RC-2 tumor-bearing mice was analyzed. The difference among groups was analyzed by repeated measures analysis of variance and Bonferroni method. Results:The probe 18F-SAZ was successfully prepared with the labelling yield of (5.60±0.51)%, specific activity of (7.90±0.62)MBq/nmol, radiochemical purity more than 99%, and the lipid water partition coefficient log P of -0.38±0.01. After incubation with PBS or mouse serum for 4 h, the radiochemical purity was still more than 99%. The uptake of 18F-SAZ in OS-RC-2 cells reached (1.47±0.24) percentage of the added radioactivity dose (%AD) at 30min, which was significantly higher than the uptake in the blocked group and that in HCT116 cells ((0.60±0.07)%AD, (0.50±0.05)%AD; F=24.31, P values: 0.012, 0.013 (Bonferroni correction method)). The results of microPET imaging showed that the uptake of 18F-SAZ in OS-RC-2 tumors reached the maximum at 30min ((2.92±0.07) percentage activity of injection dose per gram of tissue (%ID/g)), while the maximum uptakes in the blocked group and HCT116 tumors were only (1.36±0.02) and (1.12±0.07)%ID/g, respectively. 18F-SAZ was mainly distributed in tumors and organs including kidney, intestine, liver, stomach in OS-RC-2 tumor-bearing mice. Conclusions:The probe 18F-SAZ is successfully synthesized. It has high radiochemical purity and good stability in vitro, and can specifically target tumor cells with high expression of CAⅨ. It is expected to be a new CAⅨ-targeting PET imaging probe.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective To analyze the epidemiological characteristics and spatiotemporal clustering of varicella in Lu'an City from 2005 to 2023, and to provide a scientific basis for optimizing varicella prevention and control strategies. Methods Data on varicella cases were collected through the Chinese Center for Disease Control and Prevention Information System. Descriptive epidemiology, temporal trend analysis, seasonal analysis, spatiotemporal clustering analysis, and spatial autocorrelation analysis were conducted using QGIS, JoinPoint, SaTScan and GeoDa software. Results The average annual reported incidence rate of varicella in Lu'an City from 2005 to 2023 was 34.55/100,000, showing a trend of initial increase followed by a decrease. The peak incidence occurred from October to January of the following year (RR=1.97, LLR=1743.95, P=0.001). Students aged 0 to 19 was the primary affected group. Spatiotemporal scan analysis revealed four types of spatiotemporal clusters, with the cluster in Jin'an District from October 2017 to December 2023 being particularly prominent (RR=2.87，LLR=1734.15，P<0.001). Spatial autocorrelation analysis indicated significant clustering of varicella cases in the main urban area (Moran's I=0.216，Z=4.786，P=0.003). Conclusion The incidence of varicella in Lu'an City exhibits distinct seasonal and spatial clustering, and schools and kindergartens in the main urban area are the key to varicella prevention and control. It is necessary to enhance the monitoring of disease outbreaks during peak periods and in key areas, and to increase the two-dose vaccination rate for varicella in areas with case aggregation and among key populations.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Objective To explore the relationship between plasma amyloid-β(Aβ)and cognitive impairment.Methods A total of all villagers(aged 40 years and above)from two villages of Xi'an,China,were enrolled.A validated Chinese version of the Mini-Mental State Examination and neuropsychological battery were used to assess cognition.Levels of fasting plasma Aβ1-42 and Aβ1-40 were tested using commercial enzyme-linked immunosorbent assay(ELISA).Relationship between plasma Aβ and cognitive impairment was analyzed using Logistic regression analysis.Results Of the 1 314 enrolled subjects,1 180(89.80％)had normal cognition,85(6.47％)had suspected cognitive impairment,and 49(3.73％)had probable cognitive impairment.Univariate analysis showed that plasma Aβ1-42/Aβ1-40 ratio was higher in the suspected cognitive impairment group than in the probable cognitive impairment group(P＜0.05)and normal cognitive group(P＜0.05);plasma Aβ1-42 level in the suspected cognitive impairment group was higher than that in normal cognitive group(P＜0.05).The level of Aβ1-40 did not differ between the three groups.After correcting for confounding factors(including age,gender,degree of education,cognitive impairment risk factors,habits of living)in the multivariate Logistic regression analysis,the results were consistent with those in the univariate analysis.Conclusion Levels of plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio were elevated in patients with suspected cognitive impairment,indicating that elevated plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio may be more pronounced in early stage of cognitive impairment.They may be early biomarkers for cognitive impairment,which can help identify and intervene the disease earlier.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective To explore the relationship between plasma amyloid-β(Aβ)and cognitive impairment.Methods A total of all villagers(aged 40 years and above)from two villages of Xi'an,China,were enrolled.A validated Chinese version of the Mini-Mental State Examination and neuropsychological battery were used to assess cognition.Levels of fasting plasma Aβ1-42 and Aβ1-40 were tested using commercial enzyme-linked immunosorbent assay(ELISA).Relationship between plasma Aβ and cognitive impairment was analyzed using Logistic regression analysis.Results Of the 1 314 enrolled subjects,1 180(89.80％)had normal cognition,85(6.47％)had suspected cognitive impairment,and 49(3.73％)had probable cognitive impairment.Univariate analysis showed that plasma Aβ1-42/Aβ1-40 ratio was higher in the suspected cognitive impairment group than in the probable cognitive impairment group(P＜0.05)and normal cognitive group(P＜0.05);plasma Aβ1-42 level in the suspected cognitive impairment group was higher than that in normal cognitive group(P＜0.05).The level of Aβ1-40 did not differ between the three groups.After correcting for confounding factors(including age,gender,degree of education,cognitive impairment risk factors,habits of living)in the multivariate Logistic regression analysis,the results were consistent with those in the univariate analysis.Conclusion Levels of plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio were elevated in patients with suspected cognitive impairment,indicating that elevated plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio may be more pronounced in early stage of cognitive impairment.They may be early biomarkers for cognitive impairment,which can help identify and intervene the disease earlier.