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*

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.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Aortic valve stenosis,as a common heart valve disease,progresses rapidly and has a poor clinical prognosis.In the case of combined acute heart failure,the pumping function of the heart is severely impaired,which may lead to a significant decrease in cardiac output,resulting in a state of shock.Transcatheter aortic valve replacement(TAVR)has become a first-line treatment for elderly patients with aortic valve stenosis since its first successful case in 2002.In China,with the advancement of technology and the strengthening of physician training,the capacity of grassroots hospitals in TAVR treatment is increasing.This case reports a patient with severe aortic valve stenosis accompanied by acute heart failure and shock status who received emergency TAVR treatment at a grassroots hospital.Due to limitations in conditions,TAVR was urgently implemented without extracorporeal circulation and extracorporeal membrane oxygenation support.The patient's blood pressure immediately rose to 105/65 mmHg after valve dilation during surgery,and the postoperative symptoms were significantly relieved.Follow up color Doppler ultrasound showed that the stenosis was relieved and the heart function was significantly improved.The success of this surgery provides a reference for emergency TAVR treatment in patients with severe aortic valve stenosis and heart failure in grassroots hospitals.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

ObjectiveTo investigate the feasibility of multiparametric MRI （mpMRI） combined with histogram analysis of apparent diffusion coefficient （ADC） in the assessment of patients with variant histology （VH） of urothelial carcinoma （UC）. MethodWe retrospectively analyzed the data of patients pathologically diagnosed with UC who underwent mpMRI in the First Affiliated Hospital of Sun Yat-sen University between March 2015 and March 2023. The patients were divided into VH group （urothelial carcinoma mixed with other histologies） and non-VH group （pure urothelial carcinoma） according to pathological results. We performed propensity score 1：1 nearest-neighbor matching on the two groups based on age and gender and 49 patients were included in each group. The regions of interest （ROIs） of the whole tumor were delineated manually by using ITK-SNAP software and Pyradiomics was applied to extract ADC histogram parameters. We compared the clinicopathological data， MRI morphological features and ADC histogram parameters between the groups. Multivariate logistic regression was used to identify independent risk factors and construct the prediction model. Receiver operating characteristic （ROC） curve analyses were performed to evaluate the diagnostic performance of these parameters for determining VH of UC. ResultsMRI morphological features including the lesion shape， vesical imaging-reporting and data system （Ⅵ-RADS）score， enhancement pattern and suspicious lymph node metastasis were markedly different between the two groups （all P < 0.05）. ADC _mean， ADC _median， ADC_25th， ADC_75th， ADC_10th and ADC_90th were significantly lower in patients with VH than those in non-VH group （all P<0.05）. Multivariate logistic regression analysis showed enhancement pattern， ADC_25th， ADC_75th and ADC mean were independent predictors （P < 0.05）. The combined model yielded the best predictive performance， with an area under the ROC curve （AUC） of 0.91 （95% CI： 0.83-0.96）. ConclusionsMpMRI combined with whole-tumor histogram analysis of ADC can serve as a reliable method for evaluating the presence of VH in UC， further to assist the clinical decision making.

Objective: To explore the relationship between DNA methylation and occupational noise-induced hearing loss. Methods: A case-control study was conducted. People with hearing loss induced by occupational noise were recruited as the case group and those with normal hearing but still exposed to occupational noise were recruited as the control group. A total of 60 participants were included, of which 30 participants were in the case group and 30 in the control group. The methylation level was detected by 850k genome-wide DNA methylation chip technology. The significance of differential methylated position (DMP) was tested by R-packet 'Champ'. The differential methylated region (DMR) was analyzed by using Champ's Bumphunter algorithm. Cluster profiler was used to analyze the gene list for GO and KEGG pathway enrichment. Results: There was significant difference between two groups in binaural high-frequency average hearing threshold (P<0.05), but there was no significant difference in age, smoking, drinking, hypertension, physical exercise and cumulative noise exposure. The results of DMP and DMR analysis showed that 713875 sites were detected in the case group and the control group, and 439 methylation sites with significant difference, accounting for 0.06%; 650 regions were detected, and 72 methylation regions with significant differences, accounting for 11.08%. Compared with the control group, the results of GO enrichment analysis showed that the case group had statistically significant differences in four pathways: axogenesis of projection neurons in the central nervous system, neuronal development in the central nervous system, axogenesis of neurons in the central nervous system and neuronal differentiation in the central nervous system. KEGG enrichment analysis showed that there were significant differences in sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis pathway between the case group and the control group. Conclusion: The occurrence of occupational noise-induced hearing loss may be related to the regulation of gene expression related to axogenesis of projection neurons in the central nervous system, development of neurons in the central nervous system, axogenesis of neurons in the central nervous system, differentiation of neurons in the central nervous system, sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis and gene methylation related to metabolism.
Aldosterone ; Bile Acids and Salts ; Case-Control Studies ; DNA Methylation ; Hearing Loss, Noise-Induced/genetics* ; Humans ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure ; Sphingolipids

Objective: To explore the effect of herb-partitioned moxibustion (HPM) on tight junctions (TJs) of intestinal epithelial cells in Crohn disease (CD) mediated by tumor necrosis factor-α (TNF-α)-nuclear factor kappa B (NF-κB)-myosin-light- chain kinase (MLCK) pathway. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an HPM group and a mesalazine (MESA) group, with 12 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was administered to establish CD models. When the model was confirmed a success, the HPM group rats were treated with HPM at Tianshu (ST 25) and Qihai (CV 6), while the MESA group rats were given MESA solution by lavage. When the intervention finished, the colonic epithelial tissues were separated, purified and cultured in each group to establish the intestinal epithelial barrier model in vitro, and TNF-α was added (100 ng/mL) in the culture medium and maintained for 24 h to establish an increased epithelial permeability model. Transepithelial electrical resistance (TEER) was used to examine the permeability of the barrier; Western blot was used to observe the expressions of the proteins related to TJs of intestinal epithelial cells mediated by TNF-α-NF-κB-MLCK pathway; immunofluorescence staining was used to observe the expressions and distributions of tight junction proteins in the intestinal epithelium. Results: After TNF-α induction, compared with the MC+TNF-α group, the TEER value increased significantly in the HPM+TNF-α and MESA+TNF-α groups (both P<0.001); the expressions of nuclear factor kappa B (NF-κB) p65, MLCK, myosin light chain (MLC), tumor necrosis factor receptor-associated factor 6 (TRAF6) and receptor interaction protein-1 (RIP1) decreased significantly (P<0.01 or P<0.05), and the expression of zinc finger protein A20 (A20) increased significantly (P<0.01); the expressions of occludin, claudin-1, zonula occludens protein 1 (ZO-1) and F-actin also increased significantly (all P<0.01). Compared with the MESA+TNF-α group, the expressions of MLC, occludin, claudin-1, ZO-1 and F-actin increased significantly in the HPM+TNF-α group (P<0.01 or P<0.05). Conclusion: HPM can protect or repair the damage of intestinal epithelial barrier in CD rats, which may be achieved through modulating the abnormal TJs in intestinal epithelium mediated by TNF-α-NF-κB-MLCK pathway.

Chemical constituents of water extracts of Asplenium ruprechtii were investigated. Five compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC, and their structures were identified by various spectral analyses as aspleniumside G(1), trans-p-coumaric acid(2), trans-p-coumaric acid 4-O-β-D-glucoside(3), cis-p-coumaric acid 4-O-β-D-glucoside(4), and(E)-ferulic acid-4-O-β-D-glucoside(5). Among them, compound 1 is a new 9,19-cycloartane glycoside.
Chromatography, High Pressure Liquid ; Glucosides ; Glycosides ; Triterpenes