Background Atherosclerotic cardiovascular disease (ASCVD) is a major contributor to the global burden of cardiovascular diseases. However, evidence from meta-analyses on the association between ambient ozone exposure and ASCVD risk remains relatively insufficient. Objective To explore the epidemiological association between ambient ozone exposure and ASCVD, providing scientific evidence for ASCVD prevention and control from the perspective of environmental risk factor management. Methods We systematically searched PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang Database, CBM, and VIP for published epidemiological studies on the relationship between ambient ozone exposure and ASCVD from January 2007 to December 2023. We performed quality assessment and data extraction of the included studies, and utilized meta-analysis to evaluate the effects of short-term and long-term ozone exposure on different ASCVD outcomes, including mortality and incidence of ischemic heart disease (IHD) and ischemic stroke (IS). Results A total of 24 studies were included based on a set of predetermined eligibility criteria. The meta-analysis results indicated that short-term ozone exposure was associated with an increased risk of ASCVD mortality and incidence. Specifically, short-term ozone exposure was significantly associated with an elevated risk of IHD mortality (combined RR=1.011, 95%CI: 1.008, 1.015; P < 0.05). Additionally, short-term ozone exposure was significantly linked to increased IS mortality (combined RR=1.005, 95%CI: 1.003, 1.008; P < 0.05) and incidence (combined RR=1.015, 95%CI: 1.003, 1.027; P < 0.05). Conclusion Short-term exposure to ambient ozone significantly elevates acute cardiovascular disease risk. However, the epidemiological association between long-term ozone exposure and ASCVD remains inconclusive. Future high-quality cohort studies with refined exposure assessment methods are warranted to elucidate the chronic cardiovascular effects of ozone exposure.

Objective To explore the effect of miR-125a-5p on thymic regulatory T cell(Treg)in mice with experimental auto-immune myasthenia gravis(EAMG).Methods The EAMG model was established by immunoinduction with murine-derived acetylcho-line receptor α subunit 97-116 peptide and randomly divided into control group and EAMG group,and the mice were subjected to Len-non scoring and low-frequency repetitive electrical stimulation experiments to evaluate the model.To further explore the effect of miR-125a-5p on Treg cells,EAMG mice were injected with negative control adenovirus and miR-125a-5p-inhibited adenovirus by tail vein injection respectively,and the experimental groups were the negative control group and miR-125a-5p inhibiting group.The mRNA expression levels of miR-125a-5p and forkhead box protein P3(Foxp3)were detected by real-time fluorescence quantitative polymer-ase chain reaction(RT-qPCR),while the protein expression level of Foxp3 was detected by Western blot.The percentage of the number of Treg cells was detected by flow cytometry,and serum concentrations of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)were assessed using enzyme-linked immunosorbent assay(ELISA).Results The EAMG mouse model was successfully established.Compared to the control group,the EAMG group exhibited a significantly higher Lennon score,positive responses to low-frequency repetitive electrical stimulation at 5Hz,and an upregulated expression of miR-125a-5p,downregulated of Foxp3mRNA and protein,reduced percentage number of Treg cells,and decreased expression of IL-10 and TGF-β1.Upon inhibition of miR-125a-5p expression in EAMG mice,compared with the negative control group,the expression of miR-125a-5p in the miR-125a-5p inhibiting group was decreased,and the Lennon score was decreased,Foxp3mRNA and protein expression were increased,with a significant in-crease in the percentage of Treg cells and enhanced expression of IL-10 and TGF-β1,and the differences were all statistically signifi-cance(P＜0.05).Conclusion The expression of miR-125a-5p was upregulated in EAMG.Inhibition of miR-125a-5p expression led to upregulation of Foxp3,an increase in the number of Treg cells,elevated levels of IL-10 and TGF-β1,and attenuation of myas-thenia gravis symptoms in EAMG mice.These results suggest that miR-125a-5p may be involved in developing myasthenia gravis dis-ease by affecting Foxp3,leading to decreased Treg cell numbers and abnormal function.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To identify the core constitutions and prodromal symptoms of relapse in schizophrenia patients using network analysis,and to analyze their relationships as well as gender differences.Methods Schizophrenia patients hospitalized in the psychiatry department of Hunan Brain Hospital in Hunan Province between October 2022 and December 2023 were selected as survey participants.A general information questionnaire,a Traditional Chinese Medicine Constitution Scale,and a Schizophrenia Prodromal Symptoms of Relapse Scale were used for investigation.Network anal-ysis was conducted using R language.Results The core constitutions of schizophrenia patients were qi deficiency constitution[Expected Influence(EI)=1.08]and dampness-heat constitution(EI=1.00),and the core prodromal symptoms of relapse were depression/withdrawal(EI=0.84)and ini-tial psychotic manifestations(EI=0.81).There were statistically significant differences in constitutions of traditional Chinese medicine and prodromal symptoms of relapse between patients of different genders(P＜0.05).Females mainly exhibited qi deficiency constitution(EI=1.20)with anxiety as the core prodromal symptom(EI=0.98),while males mainly exhibited yin deficiency constitution(EI=1.05)with depression/withdrawal as the core prodromal symptom(EI=1.00).Conclusion Healthcare professionals can early identify core prodromal symptoms of relapse by core imbalanced constitutions of schizophrenia patients,and develop precise intervention strategies,thereby promoting changes in their network structure,preventing disease relapse,and improving patients'quality of life.

Objective To explore the effect of miR-125a-5p on thymic regulatory T cell(Treg)in mice with experimental auto-immune myasthenia gravis(EAMG).Methods The EAMG model was established by immunoinduction with murine-derived acetylcho-line receptor α subunit 97-116 peptide and randomly divided into control group and EAMG group,and the mice were subjected to Len-non scoring and low-frequency repetitive electrical stimulation experiments to evaluate the model.To further explore the effect of miR-125a-5p on Treg cells,EAMG mice were injected with negative control adenovirus and miR-125a-5p-inhibited adenovirus by tail vein injection respectively,and the experimental groups were the negative control group and miR-125a-5p inhibiting group.The mRNA expression levels of miR-125a-5p and forkhead box protein P3(Foxp3)were detected by real-time fluorescence quantitative polymer-ase chain reaction(RT-qPCR),while the protein expression level of Foxp3 was detected by Western blot.The percentage of the number of Treg cells was detected by flow cytometry,and serum concentrations of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)were assessed using enzyme-linked immunosorbent assay(ELISA).Results The EAMG mouse model was successfully established.Compared to the control group,the EAMG group exhibited a significantly higher Lennon score,positive responses to low-frequency repetitive electrical stimulation at 5Hz,and an upregulated expression of miR-125a-5p,downregulated of Foxp3mRNA and protein,reduced percentage number of Treg cells,and decreased expression of IL-10 and TGF-β1.Upon inhibition of miR-125a-5p expression in EAMG mice,compared with the negative control group,the expression of miR-125a-5p in the miR-125a-5p inhibiting group was decreased,and the Lennon score was decreased,Foxp3mRNA and protein expression were increased,with a significant in-crease in the percentage of Treg cells and enhanced expression of IL-10 and TGF-β1,and the differences were all statistically signifi-cance(P＜0.05).Conclusion The expression of miR-125a-5p was upregulated in EAMG.Inhibition of miR-125a-5p expression led to upregulation of Foxp3,an increase in the number of Treg cells,elevated levels of IL-10 and TGF-β1,and attenuation of myas-thenia gravis symptoms in EAMG mice.These results suggest that miR-125a-5p may be involved in developing myasthenia gravis dis-ease by affecting Foxp3,leading to decreased Treg cell numbers and abnormal function.

Objective:To accurately ascertain the whole genome sequencing and the composition of open reading frames (ORFs) of non-replicating Tiantan strain of vaccinia virus (NTV) using next-generation long-read sequencing technology.Methods:NTV, obtained from our laboratory stock, was amplified and purified on chicken embryo fibroblast cells(CEFs), and the full-length genomic nucleic acid of NTV was extracted. The PacBio HiFi sequencing platform was utilized for de novo assembly to obtain the complete genomic sequence of NTV. Using a homology annotation strategy, we identified its ORF composition and compared it with known non-replicating vaccinia virus strains. Results:The total length of NTV′s genome was 171 729 bp, with a GC content of 33%. Its unique inverted terminal repeat (ITR) region comprised hairpin structures, two tandem repeat regions, and three non-repeat regions. NTV contained 166 ORFs, with major differences observed in the ITR and its surrounding regions when compared to MVA-BN and NYVAC. These three strains shared a common set of 138 ORFs. NTV encoded six unique ORFs related to virus evasion of host antiviral response.Conclusions:This study accurately determines the whole genome sequencing and ORFs composition of NTV, and reveals its similarities and differences with other replication-deficient vaccinia virus strains, which pave a way for the development and application of the next generation of monkeypox vaccines and novel viral vectors.

Ferroptosis is a form of regulated cell death that depends on iron and reactive oxygen spe-cies.Different from apoptosis,necrosis,and autophagy,ferroptosis is characterized by the accumulation of lipid peroxides in cells.Studies have discovered that ferroptosis is closely associated with the occurrence and develop-ment of tumors and inducing ferroptosis in tumor cells can enhance the therapeutic effects of drugs on tumors.This article summarizes the latest research progress in ferroptosis regarding its mechanisms and associations with tumors,aiming to provide a reference for further understanding the interaction mechanisms between ferroptosis and tumors and offering new insights and targets for the treatment of tumors.

Age-related hearing loss(ARHL)is a common chronic disease that poses a serious threat to the physical and mental health of the elderly in an aging society.It is a sensorineural hearing loss characterized by the loss of auditory hair cells,stria vascularis lesions,apoptosis of spiral ganglia,and degeneration of the audi-tory central nervous system,reducing the quality of life of the patients.This article reviews the research progress in the relationship of ARHL with Alzheimer's disease,depression,and frailty,as well as the daily intervention in ARHL.This review aims to improve people's awareness and attention to the health hazards of ARHL and to delay the occurrence and development of ARHL by implementing daily intervention measures to form a healthy lifestyle.

Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination