Objective To analyze the relationship between Chemokine IP10 and its receptor CXCR3 during prion infection. Methods We investigated the increases in IP10 signals, primarily localized in neurons within the brains of scrapie-infected mice, using western blotting, ELISA, co-immunoprecipitation, immunohistochemistry, immunofluorescence assays, and RT-PCR. Results Both CXCR3 levels and activation were significantly higher in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. Enhanced CXCR3 expression was predominantly observed in neurons and activated microglia. Morphological colocalization of PrPC/PrPSc with IP10/CXCR3 was observed in scrapie-infected mouse brains using immunohistochemistry and immunofluorescence. immunohistochemistry (IHC) analysis of whole brain sections further revealed increased accumulation of IP10/CXCR3 specifically in brain regions with higher levels of PrPSc deposits. Co-immunoprecipitation and biomolecular interaction assays revealed the molecular interactions between PrP and IP10/CXCR3. Notably, a significantly larger amount of IP10 accumulated within prion-infected SMB-S15 cells than in the normal partner cell line, SMB-PS. Importantly, resveratrol treatment effectively suppressed prion replication in SMB-S15 cells, thereby restoring the accumulation and secretion pattern of cellular IP10 similar to that observed in SMB-PS cells. Conclusion Our data demonstrate that the activation of IP10/CXCR3 signaling in prion-infected brain tissues coincides with PrPSc deposition. Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.
Objective Our study aimed to conduct genomic characterization of Salmonella strains carrying the blaNDM-1 gene in the intestinal tract of healthy individuals. The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations, and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes.Methods We performed antimicrobial susceptibility testing and employed second- and third-generation sequencing techniques to analyze Salmonella strains harboring the blaNDM-1 gene, to surveil drug-resistant bacteria in the intestines of healthy subjects. Sequence comparison was conducted using both core- and pan-genome approaches. Concurrently, conjugation experiments were carried out to assess the efficiency of plasmid transfer.Results We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China. This strain harbored an IncHI2/IncHI2A plasmid carrying blaNDM-1 along with multiple antibiotic resistance genes (ARGs). Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs. Pan-genomic analysis revealed that blaNDM-1-positive plasmids could traverse bacterial species barriers, facilitating cross-host transmission.Conclusion This study marks the first detection of blaNDM-1 in Salmonella strains isolated from healthy individuals. We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying blaNDM-1, which have the potential to be harbored and transmitted among healthy individuals. Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
Objective To comprehensively examine the molecular epidemiological characteristics of human rhinovirus (HRV) in Beijing.Methods A total of 7,151 children and adults with acute respiratory tract infections (ARTIs) were recruited from 35 sentinel hospitals in Beijing between 2018 and 2022. Their respiratory samples were obtained, and epidemiological and clinical data were collected. Nucleic acid testing for 11 respiratory pathogens, including HRV, was performed on the specimens. We sequenced VP4/VP2 or 5’UTR of HRV isolates to identify their genotypes using phylogenetic analyses.Results HRV was detected in 462 (6.5%) cases. A total of 105 HRV genotypes were successfully identified in 359 (77.7%) specimens, comprising 247 (68.8%) with HRV-A, 42 (11.7%) with HRV-B, and 70 (19.5%) with HRV-C. No predominant genotype was observed. HRV was prevalent year-round with two weak peaks in spring and autumn. HRV detection declined gradually between 2018 and 2022, with seven genotypes disappearing and five genotypes emerging. HRV detection rate decreased by age without resurge among old people. HRV-C was more common among children aged less than 5 years with severe community-acquired pneumonia compared to HRV-A and HRV-B. Adults infected with HRV-B had higher rates of hospitalization, intensive care unit admission, and complications than those infected with HRV-A and HRV-C.Conclusion HRV epidemics in Beijing were highly dispersed in genotypes, which probably resulted in a high prevalence of HRV infection, attenuated its seasonality, and made it more difficult to establish effective population immunity.
Objective To analyze the epidemiological characteristics of measles, mumps, and rubella (MMR) between 2014 and 2021 and identify potential strategies and measures for the prevention and control of MMR in China.Methods Data on MMR was obtained from China’s National Notifiable Disease Reporting System for the period from 2014 to 2021. Spatiotemporal distributions were analyzed using SaTScan; temporal trends were analyzed using JoinPoint; and clusters were visualized using ArcGIS.Results A total of 1,808,067 cases of MMR were reported from 2014 to 2021 in China’s mainland, most of which were children and students under the age of 20. The incidence of measles declined during 2014–2021, whereas that of mumps and rubella peaked in 2019. MMR-reported cases generally peaked from March to July; however, high numbers of mumps cases were reported from September to November in 2020–2021. Measles and rubella clusters predominantly occurred in Western China, whereas clusters of mumps were generally found in the southern region.Conclusion The relatively heterogeneous epidemiological characteristics of MMR have highlighted the weaknesses and gaps in surveillance and timely control of MMR transmission in China’s mainland. Real-time and intelligent monitoring data should be collected for evidence-based early interventions.
Objective Antiretroviral drugs covered by medical insurance have been gradually used by people living with human immunodeficiency virus (PLWH) in recent years in China. This study aimed to analyze their willingness to pay (WTP) for antiretroviral drugs.Methods A mixed-methods study design involving a cross-sectional survey and in-depth interviews was conducted. A cross-sectional survey was performed to collect data on the general characteristics, economic status, antiretroviral therapy (ART) status, and WTP of PLWH in 18 Chinese cities from August 2022 to February 2023. Multivariate logistic regression was used to analyze the factors associated with WTP. Representatives of PLWH were interviewed via in-depth interviews, and the data were thematically analyzed.Results Among the 941 PLWH, 271 (28.80%) were willing to pay for antiretroviral drugs covered by medical insurance. For basic medical insurance for urban and rural residents, PLWH with the following characteristics were more willing to pay: an educational level of senior high school or technical secondary school, having an undergraduate degree or higher, frequently working away from their hometowns, and homosexual transmission. Off-farm workers and recipients of government medical aid were more unwilling to pay. For basic medical insurance for urban employees, PLWH with the following characteristics were more willing to pay: frequently working away from their hometowns; homosexual transmission; personal annual income ≥ 100,000 CNY; and adverse events of antiretroviral drugs. The main reasons for PLWH’s WTP for antiretroviral drugs covered by medical insurance were that the drugs had fewer adverse events and were easier to administer. The main reasons for PLWH’s unwillingness to pay were financial difficulties and privacy concerns.Conclusion Nearly one-third of PLWH are willing to pay for antiretroviral drugs covered by medical insurance. In the future, PLWH with a high WTP can be guided to use these drugs.
Objective We aimed to analyze the current indoor radon level and estimate the population risk of radon-induced lung cancer in urban areas of China.Methods Using the passive monitoring method, a new survey on indoor radon concentrations was conducted in 2,875 dwellings across 31 provincial capital cities in Chinese mainland from 2018 to 2023. The attributable risk of lung cancer induced by indoor radon exposure was estimated based on the risk assessment model.Results The arithmetic mean (AM) and geometric mean (GM) of indoor radon concentrations were 65 Bq/m³ and 55 Bq/m³, respectively, with 13.6% of measured dwellings exceeding 100 Bq/m³ and 0.6% exceeding 300 Bq/m³. The estimated number of lung cancer deaths induced by indoor radon exposure was 150,795, accounting for 20.30% (95% CI: 20.21%–20.49%) of the lung cancer death toll.Conclusion This study provided the most recent data on national indoor radon levels in urban areas and the attributable risk of lung cancer. These results served as an important foundation for further research on the disease burden of indoor radon exposure and radon mitigation efforts.
Objective We aimed to understand the willingness and barriers to the acceptance of tuberculosis (TB) preventive treatment (TPT) among people with latent TB infection (LTBI) in China. Methods A multicenter cross-sectional study was conducted from May 18, 2023 to December 31, 2023 across 10 counties in China. According to a national technical guide, we included healthcare workers, students, teachers, and others occupations aged 15–65 years as our research participants.Results Overall, 17.0% (183/1,077) of participants accepted TPT. There were statistically significant differences in the acceptance rate of TPT among different sexes, ages, educational levels, and occupations (P < 0.05). The main barriers to TPT acceptance were misconceptions that it had uncertain effects on prevention (57.8%, 517/894), and concerns about side effects (32.7%, 292/894).Conclusion An enhanced and comprehensive understanding of LTBI and TPT among people with LTBI is vital to further expand TPT in China. Moreover, targeted policies need to be developed to address barriers faced by different groups of people.
Tuberculosis (TB) remains a significant global health challenge, ranking second only to COVID-19 as the leading cause of death from a single infectious agent, with 1.3 million TB-related deaths reported in 2022. Treatment efficacy has been compromised by the emergence of drug-resistant strains, including rifampin-resistant TB (RR-TB), multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Although first-line drugs like isoniazid, rifampicin, pyrazinamide, and ethambutol form the cornerstone of TB therapy, the rise of resistant strains necessitates the use of second-line drugs, which often come with increased toxicity and limited accessibility. Recent advances have focused on repurposing existing compounds and developing new drugs with novel mechanisms of action. Promising agents such as second-generation bedaquiline analogs (TBAJ-587, TBAJ-876), sudapyridine (WX-081), delamanid, pretomanid, and TBI-166 (pyrifazimine) have shown efficacy against resistant Mtb strains. Innovative treatment regimens like the BPaLM protocol—combining bedaquiline, pretomanid, linezolid, and moxifloxacin—offer shorter, all-oral therapies with higher cure rates. Personalized treatment durations and dose optimizations are becoming feasible through risk stratification algorithms and pharmacokinetic/pharmacodynamic studies. Immunotherapy is emerging as a complementary strategy to enhance the host’s immune response against Mtb. Agents such as vitamin D, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), statins, metformin, and biological agents like interleukins and granulocyte-macrophage colony-stimulating factor are under exploration. Additionally, cell therapies involving mesenchymal stem cells and immune effector cells present new therapeutic avenues. Despite these advancements, significant challenges remain in achieving the World Health Organization’s “End TB Strategy” goals, particularly as the COVID-19 pandemic has diverted resources and attention. Ongoing research and global collaboration are crucial to develop novel therapeutic strategies, optimize treatment regimens, and ultimately reduce the global burden of TB.
Neurosyphilis (NS) is an infectious disease caused by Treponema pallidum invading the central nervous system. It can manifest at any stage of syphilis, and is often misdiagnosed due to its atypical and progressive symptoms. The increasing incidence of NS underscores the necessity for early and accurate diagnosis. Here, we present a case where routine cerebrospinal fluid metagenomic next-generation sequencing (mNGS) was used to diagnose a patient with neurosyphilis. The patient exhibited cognitive impairment and was initially diagnosed with cerebral infarction due to syphilitic cerebral arteritis. Thus, the patient was treated with dual antiplatelet therapy (aspirin and clopidogrel) and statins to stabilize the plaques. Neurosyphilis was treated with penicillin sodium injections, resulting in significant improvement in the patient’s mental state. This case is a rare instance of neurosyphilis associated with cerebral infarction. These findings suggest that mNGS is a valuable tool in diagnosing neurosyphilis, potentially improving diagnostic accuracy and patient outcomes.
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