Environment pollutants exposure affects the endogenous activation of within-host Mycobacterium tuberculosis.

OBJECTIVE: Epidemiological studies have linked ambient pollutants with tuberculosis (TB) risk, but the association has not been fully understood. Here, for the first time, we applied whole-genome sequencing (WGS) to assess the reproductive state of Mycobacterium tuberculosis (MTB) by profiling the mutation rate of MTB (MTBMR) during within-host endogenous reactivated progression, intending to dissect the actual effects of ambient pollutants on the endogenous reactivation. METHODS: We conducted a retrospective cohort study on bacteriologically confirmed TB patients and followed them for relapse in Jiangsu and Sichuan Province, China. Endogenous and exogenous activation were distinguished by WGS of the pathogen. The average concentration of air pollution was estimated by considering a lag of 0-1 to 0-12 months. We applied a generalized additive model with a Poisson function to evaluate the relationships between ambient pollutants exposure and MTBMR. RESULTS: In the single-pollutant adjusted models, the maximum effect for PM10 (MTBMR increase: 81.87%, 95% CI: 38.38, 139.03) and PM2.5 (MTBMR increase: 73.91%, 95% CI: 22.17, 147.55) was observed at a lag of 0-12 months for every 10 µg/m³ increase. For SO2, the maximum effect was observed at lag 0-8 months, with MTBMR increasing by 128.06% (95% CI: 45.92, 256.44); and for NO2, the maximum effect was observed at lag 0-9 months, with MTBMR increasing by 124.02% (95% CI: 34.5, 273.14). In contrast, the O3 concentration was inversely associated with MTBMR, and the maximum reduction of MTBMR was 6.18% (95% CI: -9.24, -3.02) at a lag of 0-9 months. Similar results were observed for multi-pollutant models. CONCLUSIONS: Increased exposure to ambient pollutants (PM10, PM2.5, SO2, and NO2) contributed to a faster MTBMR, indicating that MTB exhibits increased reproductive activity, thus accelerating within-host endogenous reactivation. O3 exposure could decrease the MTBMR, suggesting that MTB exerts low reproductive activity by inhibiting within-host endogenous activation.

Serum LDL-C/HDL-C ratio and the risk of carotid plaques: a longitudinal study.

BACKGROUND: Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population. METHODS: We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55-2.58) and over 60 years (HR: 3.36, 95% CI: 2.47-4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01-1.56), diabetes (HR: 1.46, 95% CI: 1.06-2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07-1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12-1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction < 0.05). CONCLUSION: A high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation.

Association of ABO blood group and antituberculosis drug-induced liver injury: A case-control study from a Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Antituberculosis drug-induced liver injury (ATLI) is a serious adverse drug reaction, and its pathogenic mechanism is still largely unknown. Rifampin (RIF) has been reported to cause haemolysis due to the production of drug-dependent antibodies, and haemolysis results in an increased level of free haem, which affects the function of hepatocytes. Blood group determinants can act as specific receptor sites for drug-antibody complexes, causing erythrocyte destruction in the presence of RIF. RIF-induced immune haemolysis may be a potential mechanism for ATLI. Thus, the study aimed to explore the role of ABO blood group systems in Chinese ATLI patients. METHODS: A 1:4 matched case-control study was conducted among 146 ATLI cases and 584 controls. Multivariable conditional logistic regression and Cox proportional regression were used to estimate the association between ABO blood group and risk of ATLI by odds ratio (OR), hazards ratio (HR) and 95% confidence intervals (CIs), and liver disease history and taking hepatoprotectant were used as covariates. RESULTS AND DISCUSSION: Patients in the A, B, AB and non-O blood groups had a significantly higher risk of ATLI than those in the O blood group (OR = 1.832, 95% CI: 1.126-2.983, P = .015; OR = 1.751, 95% CI: 1.044-2.937, P = .034; OR = 2.059, 95% CI: 1.077-3.938, P = .029; OR = 1.822, 95% CI: 1.173-2.831, P = .007, respectively). After considering the time of ALTI occurrence, similar results were found in the A, B, AB and non-O blood groups (HR = 1.676, 95% CI: 1.072-2.620, P = .024; HR = 1.620, 95% CI: 1.016-2.584, P = .043; HR = 2.010, 95% CI: 1.130-3.576, P = .018; HR = 1.701, 95% CI: 1.138-2.542, P = .010, respectively). Furthermore, subgroup analysis also detected a significant association between ABO blood group and ATLI in patients taking RIF (P < .05). However, no significant difference was observed in patients not taking RIF (P > .05). WHAT IS NEW AND CONCLUSION: The present study is the first to evaluate the role of ABO blood group systems in Chinese ATLI cases. Based on the present matched case-control study, the ABO blood group may be associated with susceptibility to ATLI in the Chinese antituberculosis population, especially in patients with blood groups A, B and AB who are taking RIF.

Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population.

OBJECTIVE: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population. PATIENTS AND METHODS: A 1 : 2 matched case-control study was carried out of 235 ATDH cases and 470 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATDH by odds ratios with 95% confidence intervals, and weight and hepatoprotectant use were used as covariates. RESULTS: Patients with a polymorphism at rs10946737 in the FAM65B gene were at an increased risk of moderate and severe liver injury under the dominant model (adjusted odds ratio=2.147, 95% confidence interval: 1.067-4.323, P=0.032). No other genotypes or genetic risk scores were found to be significantly related to ATDH. CONCLUSION: This is the first study to explore and validate the relationships between seven SNPs in the FAM65B, AGBL4, and CUX2 genes and ATDH in a Chinese population. On the basis of this case-control study, SNP rs10946737 in FAM65B may be associated with susceptibility to ATDH in Chinese Han anti-TB treatment patients. Further research is warranted to explain the role of the FAM65B gene and its contribution toward individual differences in susceptibility to ATDH.

Relevance of NAT2 genotype to anti-tuberculosis drug-induced hepatotoxicity in a Chinese Han population.

BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. The slow acetylator status of N-acetyl transferase 2 (NAT2) is a well-established risk factor for ATDH. One novel tagging single nucleotide polymorphism (tagging SNP), rs1495741, in NAT2 has been found to be highly predictive of the NAT2 phenotype. The present study aimed to validate the relationships between tagging SNP rs1495741 and ATDH in a Chinese Han population. METHODS: A 1:2 matched case-control study was conducted using 235 ATDH cases and 470 controls. Conditional or unconditional logistic regression analysis was used to estimate the association between genotypes and the risk of ATDH according to the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Patients carrying the AA genotype of tagging SNP rs1495741 were at higher risk of ATDH than those carrying the GG genotype (OR = 1.653, 95% CI = 1.050-2.601; p = 0.030). Subgroup analysis suggested that the AA genotype was a risk factor for ATDH in patients aged older than 50 years (OR = 2.486, 95% CI = 1.313-4.706; p = 0.005), weighing over 50 kg (OR = 1.757, 95% CI = 1.016-3.038; p = 0.044) or using a hepatoprotectant (OR = 1.611, 95% CI = 1.009-2.572; p = 0.046). Tagging SNP rs1495741 was not a significant risk factor for moderate and severe hepatotoxicity but appears to be relevant to risk of mild hepatotoxicity specifically. CONCLUSIONS: The present study is the first to validate the relationships between the tagging SNP rs1495741 and ATDH in a Chinese population. Based on this case-control study, the NAT2 rs1495741 polymorphism is a risk factor for mild but not more severe ATDH in Chinese Han patients.

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study.

WHAT IS KNOWN AND OBJECTIVE: Reactive metabolites from anti-tuberculosis (anti-TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti-TB drug-induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS. The present study aimed to investigate the associations between HMOX1 and NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. METHODS: A matched case-control study was conducted using 314 ATLI cases and 628 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATLI by the odds ratios (ORs) with 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. RESULTS AND DISCUSSION: Patients carrying the GG genotype at rs2071748 in HMOX1 were at a higher risk of ATLI than those with the AA genotype (adjusted OR = 1.503, 95% CI: 1.005-2.249, P = 0.047), and significant differences were also found under the recessive (P = 0.015) and additive (P = 0.045) models. Subgroup analysis confirmed the relationship in mild hepatotoxicity cases under the recessive and additive models (adjusted OR = 1.714, 95% CI: 1.169-2.513, P = 0.006; adjusted OR = 1.287, 95% CI: 1.015-1.631, P = 0.037, respectively). WHAT IS NEW AND CONCLUSION: This is the first study to explore the relationship between HMOX1, NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. Based on a matched case-control study, genetic polymorphisms of HMOX1 may be associated with susceptibility to ATLI in the Chinese population.

Inactivated COVID-19 vaccine booster dose shortened the viral shedding time of patients infected with the Omicron variant BA.2.

OBJECTIVES: We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2. METHODS: We performed a real-world study by analyzing the outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (zero and one dose), fully vaccinated (two doses), and booster-vaccinated (three doses). RESULTS: A total of 4443 patients infected with COVID-19 were included in the analysis. The proportion of viral shedding within 14 days in the three groups was 94.7%, 95.5%, and 96.7%, respectively (P <0.001). After adjusting for sex, age, underlying conditions, and clinical symptoms, the booster vaccination had a 29% increased possibility (hazard ratio: 1.29, 95% confidence interval: 1.18-1.41) of no detectable viral shedding within 14 days, whereas the fully vaccinated group had an 11% increased possibility of no detectable viral shedding (hazard ratio: 1.11, 95% confidence interval: 1.01-1.23). The effect of booster vaccination was more significant in males, the elderly, and people with underlying conditions or symptomatic infections. CONCLUSION: Our study confirmed that the booster vaccination could significantly shorten the viral shedding time of patients infected with the Omicron variant BA.2.

Effects of short-term PM2.5 exposure on blood lipids among 197,957 people in eastern China.

Globally, air pollution is amongst the most significant causes of premature death. Nevertheless, studies on the relationship between fine particulate matter (PM2.5) exposure and blood lipids have typically not been population-based. In a large, community-based sample of residents in Yixing city, we assessed the relationship between short-term outdoor PM2.5 exposure and blood lipid concentrations. Participants who attended the physical examination were enrolled from Yixing People's hospital from 2015 to 2020. We collected general characteristics of participants, including gender and age, as well as test results of indicators of blood lipids. Data on daily meteorological factors were collected from the National Meteorological Data Sharing Center ( http://data.cma.cn/ ) and air pollutant concentrations were collected from the China Air Quality Online Monitoring and Analysis Platform ( https://www.aqistudy.cn/ ) during this period. We applied generalized additive models to estimate short-term effects of ambient PM2.5 exposure on each measured blood lipid-related indicators and converted these indicators into dichotomous variables (non- hyperlipidemia and hyperlipidemia) to calculate risks of hyperlipidemia associated with PM2.5 exposure. A total of 197,957 participants were included in the analysis with mean age 47.90 years (± SD, 14.28). The increase in PM2.5 was significantly associated with hyperlipidemia (odds ratio (OR) 1.003, 95% CI 1.001-1.004), and it was still significant in subgroups of males and age < 60 years. For every 10 µg/m3 increase in PM2.5, triglyceride levels decreased by 0.5447% (95% CI - 0.7873, - 0.3015), the low-density lipoprotein cholesterol concentration increased by 0.0127 mmol/L (95% CI 0.0099, 0.0156), the total cholesterol concentration increased by 0.0095 mmol/L (95% CI 0.0053, 0.0136), and no significant association was observed between PM2.5 and the high-density lipoprotein cholesterol concentration. After excluding people with abnormal blood lipid concentrations, the associations remained significant except for the high-density lipoprotein cholesterol concentration. PM2.5 was positively correlated with low-density lipoprotein cholesterol and total cholesterol, and negatively correlated with triglyceride, indicating PM2.5 can potentially affect health through blood lipid levels.

Air pollutants in bronchoalveolar lavage fluid and pulmonary tuberculosis: A mediation analysis of gene-specific methylation.

Particulate matter (PM) exposure could alter the risk of tuberculosis, but the underlying mechanism is still unclear. We enrolled 132 pulmonary tuberculosis (PTB) patients and 30 controls. Bronchoalveolar lavage fluid samples were collected from all participants to detect organochlorine pesticides, polycyclic aromatic hydrocarbons, metal elements, and DNA methylation of immunity-related genes. We observed that γ-HCH, Bap, Sr, Ag, and Sn were related to an increased risk of PTB, while Cu and Ba had a negative effect. IFN-γ, IL-17A, IL-2, and IL-23 had a higher level in the PTB group, while IL-4 was lower. The methylation of 18 CpG sites was statistically associated with PTB risk. The methylation at the IL-4_06_121 site showed a significant mediating role on γ-HCH, Sr, and Sn. Our study suggests that PM exposure can increase the risk of tuberculosis by affecting DNA methylation and cytokine expression.

Preliminary study of the significance of reverberation by IVUS detection for patients with severe calcified lesions.

To explore the potential significance of the reverberation of calcification by comparing both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) measurement post manual coregistration. The reverberation phenomenon is often detected by IVUS for severe calcified lesions post rotational atherectomy (RA), which is thought to be due to the glassy and smooth inner surfaces of calcifications. Because of the poor penetration of IVUS, it is impossible to measure the thickness of calcifications, and the relationship between multiple reverberations and the thickness of calcification lesions has not been reported before. A total of forty-nine patients with severe calcified coronary lesions that were detected by IVUS and OCT simultaneously were enrolled in our retrospective study. If reverberation phenomena were detected by IVUS, intravascular imaging (IVI) data (including distance between the IVUS catheter center and the inner surface of the reverberation signal, the intervals between all adjacent reverberation signals, the number of layers of reverberation in IVUS, and the thickness of the calcification in OCT) were measured at the same position and same direction (each cross-section had 4 mutually perpendicular directions) at 1-mm intervals. The correlation between each reverberation observational value and OCT data was the primary target in this retrospective study, and the correlation between reverberation and calcium crack post predilatation was analyzed in other 15 patients. Four hundred twenty-eight valid observational points were analyzed simultaneously by IVUS and OCT; among them, 300 points had a single layer of reverberation, 83 had double layers of reverberation and 42 had multiple layers (≥ 3 layers) of reverberation by IVUS detection post-RA. Multivariate logistic regression analysis showed that the number of layers of reverberation by IVUS was significantly related to the thickness of calcifications by OCT at the same point and in the same direction (p < 0.001). Single, double, and multiple layers of reverberation in IVUS correspond to median calcification thicknesses (interquartile ranges (IQRs)) of 0.620 mm (0.520-0.720), 0.950 mm (0.840-1.040) and 1.185 mm (1.068-1.373), respectively, by OCT detection. Another 100 points in other 15 patients with integrated IVUS data pre- and post-predilatation showed that only single layer of reverberation was related to calcium crack (p < 0.001). The number of layers of reverberation signal detected by IVUS is positively correlated with the thickness of calcifications measured by OCT post-RA and single layer of reverberation is correlated to calcium crack post-predilatation.

Morphologies and composition changes in nonculprit subclinical atherosclerosis in diabetic versus nondiabetic patients with acute coronary syndrome who underwent long-term statin therapy.

Although patients are undergoing similar lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in diabetic mellitus (DM) and non-DM patients are different. Clinical data of 239 patients in this observational study with acute coronary syndrome was from our previous randomized trial were analyzed at 3 years, and 114 of them underwent OCT detection at baseline and the 1-year follow-up were re-anlayzed by a novel artificial intelligence imaging software for nonculprit subclinical atherosclerosis (nCSA). Normalized total atheroma volume changes (ΔTAVn) of nCSA were the primary endpoint. Plaque progression (PP) was defined as any increase in ΔTAVn. DM patients showed more PP in nCSA (ΔTAVn; 7.41 (- 2.82, 11.85) mm3 vs. - 1.12 (- 10.67, 9.15) mm3, p = 0.009) with similar reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 1-year. The main reason is that the lipid component in nCSA increases in DM patients and non-significantly decreases in non-DM patients, which leads to a significantly higher lipid TAVn (24.26 (15.05, 40.12) mm3 vs. 16.03 (6.98, 26.54) mm3, p = 0.004) in the DM group than in the non-DM group at the 1-year follow-up. DM was an independent predictor of PP in multivariate logistic regression analysis (OR = 2.731, 95% CI 1.160-6.428, p = 0.021). Major adverse cardiac events (MACEs) related to nCSA at 3 years were higher in the DM group than in the non-DM group (9.5% vs. 1.7%, p = 0.027). Despite a comparable reduction in LDL-C levels after LLT, more PP with an increase in the lipid component of nCSA and a higher incidence of MACEs at the 3-year follow-up was observed in DM patients.Trial registration: ClinicalTrials.gov. identifier: NCT02140801.

Effects of short-term ambient particulate matter exposure on the risk of severe COVID-19.

OBJECTIVES: Previous studies have suggested a relationship between outdoor air pollution and the risk of coronavirus disease 2019 (COVID-19). However, there is a lack of data related to the severity of disease, especially in China. This study aimed to explore the association between short-term exposure to outdoor particulate matter (PM) and the risk of severe COVID-19. METHODS: We recruited patients diagnosed with COVID-19 during a recent large-scale outbreak in eastern China caused by the Delta variant. We collected data on meteorological factors and ambient air pollution during the same time period and in the same region where the cases occurred and applied a generalized additive model (GAM) to analyze the effects of short-term ambient PM exposure on the risk of severe COVID-19. RESULTS: A total of 476 adult patients with confirmed COVID-19 were recruited, of which 42 (8.82%) had severe disease. With a unit increase in PM10, the risk of severe COVID-19 increased by 81.70% (95% confidence interval [CI]: 35.45, 143.76) at a lag of 0-7 days, 86.04% (95% CI: 38.71, 149.53) at a lag of 0-14 days, 76.26% (95% CI: 33.68, 132.42) at a lag of 0-21 days, and 72.15% (95% CI: 21.02, 144.88) at a lag of 0-28 days. The associations remained significant at lags of 0-7 days, 0-14 days, and 0-28 days in the multipollutant models. With a unit increase in PM2.5, the risk of severe COVID-19 increased by 299.08% (95% CI: 92.94, 725.46) at a lag of 0-7 days, 289.23% (95% CI: 85.62, 716.20) at a lag of 0-14 days, 234.34% (95% CI: 63.81, 582.40) at a lag of 0-21 days, and 204.04% (95% CI: 39.28, 563.71) at a lag of 0-28 days. The associations were still significant at lags of 0-7 days, 0-14 days, and 0-28 days in the multipollutant models. CONCLUSIONS: Our results indicated that short-term exposure to outdoor PM was positively related to the risk of severe COVID-19, and that reducing air pollution may contribute to the control of COVID-19.

Tuberculosis reinfection and relapse in eastern China: a prospective study using whole-genome sequencing.

OBJECTIVES: Tuberculosis recurrence after an initial successful treatment episode can occur from either reinfection or relapse. In a population-based sample and whole genome sequencing in eastern China, we aimed to evaluate risk factors for tuberculosis recurrence and assess the proportion of recurrence because of either reinfection or relapse. METHODS: Successfully treated pulmonary tuberculosis patients with sputum culture positive results were recruited from five cities in Jiangsu Province from 2013 to 2015 and followed for 2 years for tuberculosis recurrence. Among patients developing a second tuberculosis episode, whole genome sequencing was performed to distinguish relapse or reinfection through a distance threshold of 6-single-nucleotide polymorphisms. We analyzed risk factors for recurrence and epidemiological characteristics of different types of recurrent patients. RESULTS: Of 1897 successfully treated tuberculosis patients, 7.4% (141/1879) developed recurrent tuberculosis. Compared with nonrecurrent tuberculosis, patients were at higher risk of recurrence in older age (adjusted odds ratio, 1.02 for each additional year; 95% CI, 1.01 to 1.03, p = 0.003), patients previously treated for tuberculosis (adjusted odds ratio = 2.22; 95% CI, 1.52 to 3.26, p < 0.001), or with bilateral cavities (adjusted odds ratio, 1.56; 95% CI, 1.05 to 2.32, p = 0.029). Among 27.0% (38/141) recurrent tuberculosis patients with successfully sequenced pairs, relapse was substantially more common than reinfection (71.1% vs 28.9%, p = 0.014). DISCUSSION: Endogenous relapse was significantly more common than exogenous reinfection in the first 2 years after treatment in eastern China. Prioritization of high-risk groups for recurrence, such as the elderly, with a previous tuberculosis diagnosis, or with bilateral cavities, may provide opportunities to reduce post-tuberculosis morbidity.

Effectiveness of inactivated COVID-19 vaccines against severe illness in B.1.617.2 (Delta) variant-infected patients in Jiangsu, China.

BACKGROUND: The SARS-CoV-2 B.1.617.2 (Delta) variant has caused a new surge in the number of COVID-19 cases. The effectiveness of inactivated vaccines against this variant is not fully understood. METHODS: Using data from a recent large-scale outbreak of B.1.617.2 SARS-CoV-2 infection in Jiangsu, China, we conducted a real-world study to explore the effect of inactivated vaccine immunization on the course of disease in patients infected with the Delta variant. RESULTS: Of 476 patients with B.1.617.2 infection, 184 were unvaccinated, 105 were partially vaccinated, and 187 were fully vaccinated. A total of 42 (8.8%) patients developed severe illness, of whom, 27 (14.7%), 13 (12.4%), and 2 (1.1%) were unvaccinated, partially vaccinated, and fully vaccinated, respectively (P <0.001). All 15 (3.2%) patients who required mechanical ventilation were unvaccinated. After adjusting for age, sex, and comorbidities, fully vaccinated patients had an 88% reduced risk of progressing to severe illness (ORadjusted: 0.12, 95% CI: 0.02-0.45). However, this protective effect was not observed in partially vaccinated patients (ORadjusted: 1.11, 95% CI: 0.51-2.36). Full immunization offered 100% protection from severe illness among women. The effect of the vaccine was potentially affected by underlying medical conditions (ORadjusted: 0.26, 95% CI: 0.03-1.23). CONCLUSION: Full vaccination with inactivated vaccines is highly effective in preventing severe illness in Delta variant-infected patients. However, partial vaccination does not offer clinically meaningful protection against severe disease.

Risk factors for types of recurrent tuberculosis (reactivation versus reinfection): A global systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis (PROSPERO number: CRD42021243204) is to perform extensive and penetrating analyses on the risk factors associated with reactivation or reinfection. METHODS: We searched PubMed and Embase using search terms. Risk factors (including gender, length of time between first onset and recurrent diagnosis, extrapulmonary tuberculosis, sputum smear, pulmonary cavity, Beijing family strains, diabetes, HIV infection, history of imprisonment, and immigration) were analyzed. The pooled risk ratio (RR) and 95% confidence interval (CI) were calculated with STATA 15.1. Heterogeneity was evaluated by I2 and P values. RESULTS: The meta-analysis included 25 studies with a total of 1,477 recurrent patients. After subgroup analysis, sensitivity analysis, and testing for publication bias, it was concluded that time spanning less than two years (RR = 1.56, 95% CI: 1.33-1.85) was a risk factor for endogenous reactivation, whereas coinfection with HIV (RR = 0.72, 95% CI: 0.63-0.83), Beijing family genotype (RR = 0.46, 95% CI: 0.32-0.67), history of imprisonment (RR = 0.36, 95% CI: 0.16-0.81), and immigration (RR = 0.66, 95% CI: 0.53-0.82) were associated with exogenous reinfection. CONCLUSIONS: The recurrence interval is a risk factor for the endogenous reactivation of tuberculosis. Infection with Beijing family strains, coinfection with HIV, imprisonment, and immigration contribute to the risk of exogenous reinfection.

Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up.

BACKGROUND AND AIMS: We aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome. METHODS: The primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years. RESULTS: This was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125-11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040). CONCLUSIONS: LR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.

Downregulation of lncRNA HCP5 has inhibitory effects on gastric cancer cells by regulating DDX21 expression.

LncRNA HCP5 has been confirmed to play crucial roles in many types of cancers. However, the role of lncRNA HCP5 in regulating the occurrence and development of gastric cancer (GC) remains unknown. In the current study, we aimed to investigate the precise effects of lncRNA HCP5 on cell proliferation, migration and invasion and molecular mechanisms in gastric cancer. Using RT-qPCR analysis, we found that lncRNA HCP5 was differentially expressed in GC cell lines. CCK-8, wound healing and transwell assay indicated that the proliferation, migration and invasion of gastric cancer cells were inhibited by downregulation of lncRNA HCP5 and lncRNA HCP5 overexpression exhibited the opposite effects in gastric cancer cells. Mechanistically, RNA binding protein immunoprecipitation and dual luciferase reporter assay confirmed the interaction between lncRNA HCP5 and DDX21. The effects of lncRNA HCP5 overexpression the proliferation, migration and invasion of GC cells were partly rescued by DDX21 silencing. Taken together, downregulation of lncRNA HCP5 exerted inhibitory effects on GC cell proliferation, migration and invasion through modulation of DDX21 expression, demonstrating the function of lncRNA HCP5 and DDX21 in GC progression.

Effect of short-term ambient PM2.5 exposure on fasting blood glucose levels: A longitudinal study among 47,471 people in eastern China.

As a common health indicator in physical examinations, fasting blood glucose (FBG) level measurements are widely applied as a diagnostic method for diabetes mellitus. Uncertain conclusions remained regarding the relationship between PM2.5 exposure and FBG levels. We enrolled 47,471 subjects who participated in annual physical examinations between 2017 and 2019. We collected their general characteristics and FBG levels, and environmental factors simultaneously. We applied the generalized additive model to evaluate the impact of short-term outdoor PM2.5 exposure on FBG levels. Among the entire population, the single-pollutant models showed that a 10 µg/m3 increase in PM2.5 significantly contributed to 0.0030, 0.0233, and 0.0325 mmol/L increases in FBG at lag 0-7 days, lag 0-21 days, and lag 0-28 days, respectively. Accordingly, in multipollutant models, when PM2.5 increased by 10 µg/m3, there was an elevation of 0.0361, 0.0315, 0.0357, and 0.0387 mmol/L in FBG for 8-day, 15-day, 22-day, and 29-day moving averages, respectively. Similarly, we observed a significant positive association between them in the normal population. Moreover, the effects could be modified by age in both the entire and normal populations. Decreasing the ambient PM2.5 concentrations can alleviate the elevation of FBG, which may significantly impact the burden of diabetes mellitus.

Meteorological factors contribute to the risk of pulmonary tuberculosis: A multicenter study in eastern China.

BACKGROUND: Most studies on associations between meteorological factors and tuberculosis (TB) were conducted in a single city, used different lag times, or merely explored the qualitative associations between meteorological factors and TB. Thus, we performed a multicenter study to quantitatively evaluate the effects of meteorological factors on the risk of pulmonary tuberculosis (PTB). METHODS: We collected data on newly diagnosed PTB cases in 13 study sites in Jiangsu Province between January 1, 2014, and December 31, 2019. Data on meteorological factors, air pollutants, and socioeconomic factors at these sites during the same period were also collected. We applied the generalized additive mixed model to estimate the associations between meteorological factors and PTB. RESULTS: There were 20,472 newly diagnosed PTB cases reported in the 13 study sites between 2014 and 2019. The median (interquartile range) weekly average temperature, weekly average wind speed, and weekly average relative humidity of these sites were 17.3 °C (8.0-24.1), 2.2 m/s (1.8-2.7), and 75.1% (67.1-82.0), respectively. In the single-meteorological-factor models, for a unit increase in weekly average temperature, weekly average wind speed, and weekly average relative humidity, the risk of PTB decreased by 0.9% [lag 0-13 weeks, 95% confidence interval (CI): -1.5, -0.4], increased by 56.2% (lag 0-16 weeks, 95% CI: 32.6, 84.0) when average wind speed was <3 m/s, and decreased by 28.1% (lag 0-14 weeks, 95% CI: -39.2, -14.9) when average relative humidity was ≥72%, respectively. Moreover, the associations remained significant in the multi-meteorological-factor models. CONCLUSIONS: Average temperature and average relative humidity (≥72%) are negatively associated with the risk of PTB. In contrast, average wind speed (<3 m/s) is positively related to the risk of PTB, suggesting that an environment with low temperature, relatively high wind speed, and low relative humidity is conducive to the transmission of PTB.

[A comparative study of time series models in predicting COVID-19 cases].

Objective: To compare the performances of different time series models in predicting COVID-19 in different countries. Methods: We collected the daily confirmed case numbers of COVID-19 in the USA, India, and Brazil from April 1 to September 30, 2020, and then constructed an autoregressive integrated moving average (ARIMA) model and a recurrent neural network (RNN) model, respectively. We applied the mean absolute percentage error (MAPE) and root mean square error (RMSE) to compare the performances of the two models in predicting the case numbers from September 21 to September 30, 2020. Results: For the ARIMA models applied in the USA, India, and Brazil, the MAPEs were 13.18%, 9.18%, and 17.30%, respectively, and the RMSEs were 6 542.32, 8 069.50, and 3 954.59, respectively. For the RNN models applied in the USA, India, and Brazil, the MAPEs were 15.27%, 7.23% and 26.02%, respectively, and the RMSEs were 6 877.71, 6 457.07, and 5 950.88, respectively. Conclusions: The performance of the prediction models varied with country. The ARIMA model had a better prediction performance for COVID-19 in the USA and Brazil, while the RNN model was more suitable in India.