Association of Fine Particulate Matter and Residential Greenness With Risk of Pulmonary Tuberculosis Retreatment: Population-Based Retrospective Study.

Background: The evidence on the association of fine particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) with pulmonary tuberculosis (PTB) retreatment is limited. There are no data on whether greenness exposure protects air pollution-related PTB retreatment in patients with prior PTB. Objective: In a population-based retrospective study, we aimed to investigate the influence of PM2.5 and residential greenness on the risk of PTB retreatment. Methods: A total of 26,482 patients with incident PTB, registered in a mandatory web-based reporting system between 2012 and 2019 in Zhengzhou, China, were included in the analysis. The exposure to PM2.5 was assessed based on the China High Air Pollutants dataset, and the level of greenness was estimated using the Normalized Difference Vegetation Index (NDVI) values. The associations of PTB retreatment with exposure to PM2.5 and greenness were evaluated, respectively, considering the local socioeconomic level indicated by the nighttime light index. Results: Among the 26,482 patients (mean age 46.86, SD 19.52 years) with a median follow-up time of 1523 days per patient, 1542 (5.82%) PTB retreatments were observed between 2012 and 2019. Exposure to PM2.5 was observed to be significantly associated with the increased risk of PTB retreatment in fully adjusted models with a hazard ratio of 1.97 (95% CI 1.34-2.83) per 10 µg/m3 increase in PM2.5. Patients living in the regions with relatively high quartiles of NDVI values had a 45% lower risk of PTB retreatment than those living in the regions with the lowest quartile for the 500 m buffers (hazard ratio 0.55, 95% CI 0.40-0.77). Such a protective effect of residential greenness was more pronounced among patients living in lower nighttime light areas. The strength of the association between PM2.5 exposure and the risk of PTB retreatment was attenuated by greenness. No significant association was observed between NDVI and the incidence of drug resistance. Conclusions: Long-term exposure to PM2.5 might be a risk factor for PTB retreatment, while an increased level of residential greenness was found to be associated with reduced risks of PTB retreatment. Our results suggest strengthening the control of ambient air pollution and improving residential greenness may contribute to the reduction of PTB retreatment.

Machine learning for the identification of neoantigen-reactive CD8 + T cells in gastrointestinal cancer using single-cell sequencing.

BACKGROUND: It appears that tumour-infiltrating neoantigen-reactive CD8 + T (Neo T) cells are the primary driver of immune responses to gastrointestinal cancer in patients. However, the conventional method is very time-consuming and complex for identifying Neo T cells and their corresponding T cell receptors (TCRs). METHODS: By mapping neoantigen-reactive T cells from the single-cell transcriptomes of thousands of tumour-infiltrating lymphocytes, we developed a 26-gene machine learning model for the identification of neoantigen-reactive T cells. RESULTS: In both training and validation sets, the model performed admirably. We discovered that the majority of Neo T cells exhibited notable differences in the biological processes of amide-related signal pathways. The analysis of potential cell-to-cell interactions, in conjunction with spatial transcriptomic and multiplex immunohistochemistry data, has revealed that Neo T cells possess potent signalling molecules, including LTA, which can potentially engage with tumour cells within the tumour microenvironment, thereby exerting anti-tumour effects. By sequencing CD8 + T cells in tumour samples of patients undergoing neoadjuvant immunotherapy, we determined that the fraction of Neo T cells was significantly and positively linked with the clinical benefit and overall survival rate of patients. CONCLUSION: This method expedites the identification of neoantigen-reactive TCRs and the engineering of neoantigen-reactive T cells for therapy.

Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study.

Objective: The association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. Methods: People who had participated in health check-ups in 2006-2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). Results: During 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01-1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01-1.13). Besides, the HR was 1.10 (95 % CI=1.06-1.15), 1.13 (95 % CI=1.08-1.18), and 1.22 (95 % CI=1.16-1.30) (P for trend <0.001) in (10-20], (20-30], and (30-40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. Conclusion: People with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China.

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis, combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans.

CD8+ T cell response in QuantiFERON-TB Gold Plus testing was associated with tuberculosis recurrence: a 2-year prospective study.

BACKGROUND: Recurrence posed an important challenge to pulmonary tuberculosis (PTB) control in China. The prospective study aimed to identify potential risk factors and to explore the value of QuantiFERON-TB Gold Plus (QFT-Plus) in identifying at-risk individuals with treated prior PTB history. METHODS: All eligible individuals aged ≥18 years who had been diagnosed with PTB before 2016 in Zhongmu County, where with an average level of TB prevalence in China, were included and received baseline survey including chest radiography, QuantiFERON-TB Gold In-Tube (QFT-GIT) and QFT-Plus, then PTB recurrence was tracked through a 2-year follow-up. RESULTS: Half of 1068 (52.34%, 559/1068) included eligible participants were QFT-Plus positive at baseline and 21 of them recurred active TB in 2-year follow-up. Individuals aged ≥ 60 years, who had a recent history of TB and smokers were associated with increased risk of TB recurrence with an adjusted odds ratio (aOR) of 3.97 (95% confidence interval (CI): 1.29-12.24), 7.71 (95% CI: 1.74-34.25) and 4.56 (95% CI: 1.62-12.83), respectively. Compared to QFT-Plus negatives, those who were TB2+/TB1- (aOR = 15.34) exhibited stronger association with the risk of TB recurrence than those who were TB1+/TB2+ (aOR = 6.06). A dose response relationship was also found between the risk of TB recurrence with the baseline level of TB2-TB1 (p for trend < 0.001). CONCLUSIONS: High burden of TB infection and high risk of PTB recurrence were observed in the study population. Those with recent onset of prior TB, elderly smokers and QFT-Plus positives especially with TB2 single positive deserved further attention in active TB surveillance.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Impact of fine particulate matter on latent tuberculosis infection and active tuberculosis in older adults: a population-based multicentre cohort study.

Evidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 µg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.