Associations of prior pulmonary tuberculosis with the incident COPD: a prospective cohort study.

BACKGROUND: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. OBJECTIVES: This study aimed to investigate the association of prior PTB with the risk of COPD. DESIGN: Prospective cohort study. METHODS: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). RESULTS: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, p = 0.008), male with aHR of 2.37 (1.47-3.83, p < 0.001), obesity with aHR of 3.35 (2.16-5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, p < 0.001), current drinking with aHR of 1.98 (1.47-3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, p = 0.019). CONCLUSION: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Associations of prior pulmonary tuberculosis with the incident COPDPrior pulmonary tuberculosis (PTB) indicates that an individual has a history of PTB. The impact of prior PTB on the risk of incident chronic obstructive pulmonary disease (COPD) has not been studied in a large prospective cohort study of European population. Here, we investigated the association between prior PTB and risk of COPD in 216,130 participants from the UK biobank (a large biomedical database). After a median follow up of more than 12 years, 2,788 incident COPD cases were recorded. Individuals with prior PTB at baseline had an 87% higher risk of developing incident COPD compared to those without history of PTB. Specifically, individuals with prior PTB presented with a higher risk of incident COPD among those who were older than 50 years, male, obese, had a previous history of smoking, are currently drinking, have low physical activity, and have a low and high genetic predicted lung function. This study suggested prior PTB as an important and independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

DNA hypomethylation-mediated upregulation of GADD45B facilitates airway inflammation and epithelial cell senescence in COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typically characterized by chronic airway inflammation, with emerging evidence highlighting the driving role of cellular senescence-related lung aging. Accelerated lung aging and inflammation mutually reinforce each other, creating a detrimental cycle that contributes to disease progression. Growth arrest and DNA damage-inducible (GADD45) family has been reported to involve in multiple biological processes, including inflammation and senescence. However, the role of GADD45 family in COPD remains elusive. OBJECTIVES: To investigate the role and mechanism of GADD45 family in COPD pathogenesis. METHODS: Expressions of GADD45 family were evaluated by bioinformatic analysis combined with detections in clinical specimens. The effects of GADD45B on inflammation and senescence were investigated via constructing cell model with siRNA transfection or overexpression lentivirus infection and animal model with Gadd45b knockout. Targeted bisulfite sequencing was performed to probe the influence of DNA methylation in GADD45B expression in COPD. RESULTS: GADD45B expression was significantly increased in COPD patients and strongly associated with lung function, whereas other family members presented no changes. GADD45B upregulation was confirmed in mice exposed by cigarette smoke (CS) and HBE cells treated by CS extract as well. Moreover, experiments involving bidirectional modulation of GADD45B expression in HBE cells further substantiated its positive regulatory role in inflammatory response and cellular senescence. Mechanically, GADD45B-facilitated inflammation was directly mediated by p38 phosphorylation, while GADD45B interacted with FOS to promote cellular senescence in a p38 phosphorylation-independent manner. Furthermore, Gadd45b deficiency remarkably alleviated inflammation and senescence of lungs in CS-exposed mice, as well as improved emphysema and lung function. Eventually, in vivo and vitro experiments demonstrated that GADD45B overexpression was partially mediated by CS-induced DNA hypomethylation. CONCLUSION: Our findings have shed light on the impact of GADD45B in the pathogenesis of COPD, thereby offering a promising target for intervention in clinical settings.

Alpinetin ameliorates bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood. METHODS: A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-ß/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-ß. CONCLUSION: In general, ALP may exert therapeutic effects on pulmonary fibrosis by modulating the differentiation, proliferation, and apoptosis of fibroblasts. Although its safety has been demonstrated in mice, further studies are required to investigate the efficacy of ALP in treatment of patients with IPF.

The incidence of tuberculous pleurisy in mainland China from 2005 to 2018.

Background: Currently, tuberculous pleurisy (TP) remains a serious problem affecting global public health, including in China. Our purpose was to comprehensively understand and identify the incidence of TP in mainland China between 2005 and 2018. Methods: The data on registered TP cases from 2005 to 2018 were acquired from the National Tuberculosis Information Management System. We analyzed the demographics, epidemiology, and time-space distribution of TP patients. Then, the effects of potentially influential factors on TP incidences, such as medical expenses per capita, GDP per capita, and population density, were assessed using the Spearman correlation coefficient. Results: The incidence of TP increased in mainland China from 2005 to 2018, with a mean incidence of 2.5 per 100,000 population. Interestingly, spring was the peak season for TP, with more notified cases. Tibet, Beijing, Xinjiang, and Inner Mongolia had the highest mean annual incidence. A moderate positive relationship was found between TP incidence, medical expenses per capita, and GDP per capita. Conclusions: The notified incidence of TP had an elevated trend from 2005 to 2018 in mainland China. The findings of this study provide insight into the knowledge of TP epidemiology in the country, which can help optimize resource allocation to reduce the TP burden.

Methanotrophs dominate methanogens and act as a methane sink in a subterranean karst cave.

Karst caves are potential sinks of atmospheric methane due to microbial consumption. However, knowledge gaps on methanogens (methane producing microorganisms) and their interaction with methane-oxidizing bacteria (MOB) hinder our further understanding about methane dynamics in karst caves. Here we reported methanogenic community composition and their interaction with MOBs in the Heshang Cave to comprehensively understand methane cycling in subsurface biosphere. MOBs in karst cave were dominated by high-affinity MOB, upland soil cluster (USC), with USCγ pmoA gene abundance within the range of 1.34 × 104 to 1.8 × 107 copies·g-1 DW. In contrast, methanogens were dominated by Methanoregula and cluster ZC-I. The mcrA numbers were 7.21 × 103 to 8.31 × 104 copies·g-1 DW, 1-3 orders of magnitude lower than those of MOB. The inter-domain network analysis indicated that MOBs and methanogens cooperated more in the interior of the cave. Despite of the higher number of methanogenic nodes in the network, MOB dominated the keystone taxa, suggesting a leading functional role of MOB. MOB in caves showed a comparable with or higher potential methane oxidizing rate (PMOR, 0.63 ng CH4·g-1 DW·h-1 in sediment versus 11.02 ng CH4·g-1 DW·h-1 in weathered rock) than those in soils, whereas methane produced by methanogens was undetected. Collectively, high absolute abundances of MOB, high PMORs, the dominance of methanotrophic keystone taxa in the inter-domain network confirmed the superiority of MOBs over methanogens in the oligotrophic karst cave, mounting new evidence on caves as an important methane sink in terms of the interaction between methanogens and MOBs.

The Global, Regional, and National Burden and Trends of NAFLD in 204 Countries and Territories: An Analysis From Global Burden of Disease 2019.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) poses a substantial socioeconomic burden and is becoming the fastest growing driver of chronic liver disease, potentially accompanied by a poor prognosis. OBJECTIVE: We aim to elucidate the global and regional epidemiologic changes in NAFLD during the past 30 years and explore the interconnected diseases. METHODS: Data on NAFLD incidence, prevalence, death, and disability-adjusted life-years (DALYs) were extracted from the Global Burden of Disease Study 2019. The age-standardized incident rate (ASIR), age-standardized prevalent rate (ASPR), age-standardized death rate (ASDR), and age-standardized DALYs were calculated to eliminate the confounding effects of age when comparing the epidemiologic changes between different geographical regions. In addition, we also investigated the correlation between the NAFLD burden and the sociodemographic index (SDI). Finally, the associations of the 3 common comorbidities with NAFLD were determined. RESULTS: Globally, the incidence and prevalence of NAFLD both increased drastically during the past 3 decades (incidence: from 88,180 in 1990 to 172,330 in 2019, prevalence: from 561,370,000 in 1990 to 1,235,700,000 in 2019), mainly affecting young adults who were aged from 15 to 49 years. The ASIR increased slightly from 1.94 per 100,000 population in 1990 to 2.08 per 100,000 population in 2019, while ASPR increased from 12,070 per 100,000 population in 1990 to 15,020 per 100,000 population in 2019. In addition, the number of deaths and DALYs attributable to NAFLD increased significantly as well from 93,760 in 1990 to 168,970 in 2019 and from 2,711,270 in 1990 to 4,417,280 in 2019, respectively. However, the ASDR and age-standardized DALYs presented decreasing trends with values of estimated annual percentage change equaling to -0.67 and -0.82, respectively (ASDR: from 2.39 per 100,000 population in 1990 to 2.09 per 100,000 population in 2019; age-standardized DALYs: from 63.28 per 100,000 population in 1990 to 53.33 per 100,000 population in 2019). Thereinto, the burden of death and DALYs dominated the patients with NAFLD who are older than 50 years. Moreover, SDI appeared to have obvious negative associations with ASPR, ASDR, and age-standardized DALYs among 21 regions and 204 countries, although there is no marked association with ASIR. Finally, we found that the incidence and prevalence of NAFLD were positively related to those of diabetes mellitus type 2, stroke, and ischemic heart disease. CONCLUSIONS: NAFLD is leading to increasingly serious health challenges worldwide. The morbidity presented a clear shift toward the young populations, while the heavier burden of death and DALYs in NAFLD was observed in the aged populations and in regions with relatively low SDI. Comprehensive acquisition of the epidemiologic pattern for NAFLD and the identification of high-risk comorbidities may help policy makers and clinical physicians develop cost-effective prevention and control strategies, especially in countries with a high NAFLD burden.

Parental cadmium exposure during the spawning period reduces cadmium sensitivity through the antioxidant system in rare minnow (Gobiocypris rarus) larvae.

Cadmium (Cd) is a noxious heavy metal widely dispersed in aquatic systems. Parental Cd exposure of fish species at environmental concentrations has been shown to cause deformities and stunted growth in their offspring. However, the long-term effects and the mechanisms underlying parental Cd exposure in fish species on Cd sensitivity in their offspring remain unclear. To explore the impacts of parental Cd exposures on Cd sensitivity, rare minnow (Gobiocypris rarus) larvae whose parents were exposed to Cd at 0, 5 or 10 µg/L for 28 days were established. Results showed that parental Cd exposure in rare minnow increased the Cd content of its larvae. In terms of malformation rate, mortality rate and total length at 7 days of rare minnow larvae, parental Cd exposure at 5 or 10 µg/L reduced Cd sensitivity. Further mechanistic investigation demonstrated that parental Cd exposure significantly upregulated the expression of antioxidant gene regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-кB) in rare minnow larvae. In addition, parental Cd exposure significantly elevated the level of reactive oxygen species (ROS) and malondialdehyde (MDA), but markedly decreased catalase (CAT), superoxide dismutase (SOD) and oxidized glutathione (GST) activity. The impact of parental Cd exposure to metallothionein (MT) content and the expression of MT mRNA, a detoxifying metallothionein, showed that parental Cd exposure of rare minnow induced oxidative stress in the larvae. Meanwhile, these results indicated that parental Cd exposure in rare minnow reduced the Cd sensitivity of the larvae via activating the Nrf2-mediated antioxidant system. This project helps us to further understand the toxicological mechanism of Cd in fish species and properly assess its potential ecological risk.

Global, Regional, and National Burden and Trends of Down Syndrome From 1990 to 2019.

Introduction: Down syndrome (DS) is the leading cause of genetically defined intellectual disability and congenital birth defects worldwide. A large population of people diagnosed with DS globally is posing an enormous socioeconomic burden. However, the global burden and trends of DS have not been reported. Methods: Based on the data from the Global Burden of Disease database in 2019, we analyzed the incidence, prevalence, disability-adjusted life years (DALYs), and death of DS from 1990 to 2019 according to sex, age, regions, and social-demographic index (SDI). Then, age-standardized rates (ASRs) and estimated annual percentage change (EAPC) of these aforementioned indexes were calculated to evaluate the temporal trend of DS. Finally, the association of SDI with DS epidemiological parameters was assessed. Results: In the past 30 years, the incident cases, age-standardized incident rate (ASIR), and age-standardized prevalent rate (ASPR) of DS first decreased slightly and subsequently increased globally. The number of prevalent cases increased steadily, while the number and age-standardized rate (ASRs) of DALYs and deaths decreased gradually from 1990 to 2019. In the meantime, disease burdens were different across various SDI regions. The prevalent cases and ASPR for both sexes were increasing in all SDI regions except for the high-middle SDI region. At the national level, Brunei Darussalam, Ireland, and Haiti were the top three countries with the highest ASIR in 2019. Georgia was in the top three with the highest increase in ASRs of four parameters, while Serbia was consistently ranked in the top three with fastest declining. Furthermore, we found that ASIR and ASPR were positively correlated with SDI, yet the age-standardized DALYs and age-standardized death rate (ASDR) were negatively correlated with SDI. Conclusion: In the past 30 years, the burden and trends of DS were heterogeneous across different regions and countries with different sociodemographic characteristics. Great improvements had been achieved in reducing DALYs and deaths globally. However, the increased number and ASRs of incident and prevalent cases in some regions, especially in low SDI regions, were contributing to numerous challenges to public health. The findings may provide valuable information to the development or implementation of more effective measures.

Niche differentiation of atmospheric methane-oxidizing bacteria and their community assembly in subsurface karst caves.

Karst caves are recently proposed as atmospheric methane sinks in terrestrial ecosystems. Despite of the detection of atmospheric methane-oxidizing bacteria (atmMOB) in caves, we still know little about their ecology and potential ability of methane oxidation in this ecosystem. To understand atmMOB ecology and their potential in methane consumption, we collected weathered rocks and sediments from three different caves in southwestern China. We determined the potential methane oxidization rates in the range of 1.25 ± 0.08 to 1.87 ± 0.41 ng CH4  g-1 DW h-1 , which are comparable to those reported in forest and grassland soils. Results showed that alkaline oligotrophic caves harbour high numbers of atmMOB, particularly upland soil cluster (USC), which significantly correlated with temperature, CH4 and CO2 concentrations. The absolute abundance of USCγ was higher than that of USCα. USCγ-OPS (open patch soil) and USCγ-SS (subsurface soil) dominated in most samples, whereas USCα-BFS (boreal forest soil) only predominated in the sediments near cave entrances, indicating niche differentiation of atmMOB in caves. Overwhelming dominance of homogenous selection in community assembly resulted in convergence of atmMOB communities. Collectively, our results demonstrated the niche differentiation of USC in subsurface alkaline caves and their non-negligible methane-oxidizing potential, providing brand-new knowledge about atmMOB ecology in subsurface biosphere.

Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension.

Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific mechanisms of MBD2 in CS-induced PH remain to be elucidated. Herein, the differential expression of MBD2 was tested between the controls and the PH patients' pulmonary arteries, CS-exposed rat models' pulmonary arteries, and primary human pulmonary artery smooth muscle cells (HPASMCs) following cigarette smoke extract (CSE) stimulation. As a result, PH patients and CS-induced rats and HPASMCs showed an increase in MBD2 protein expression compared with the controls. Then, MBD2 silencing was used to investigate the function of MBD2 on CSE-induced HPASMCs' proliferation, migration, and cell cycle progression. As a consequence, CSE could induce HPASMCs' increased proliferation and migration, and cell cycle transition, which were suppressed by MBD2 interference. Furthermore, RNA-seq, ChIP-qPCR, and MassARRAY were conducted to find out the downstream mechanisms of MBD2 for CS-induced pulmonary vascular remodeling. Subsequently, RNA-seq revealed MBD2 might affect the transcription of BMP2 gene, which furtherly altered the expression of BMP2 protein. ChIP-qPCR demonstrated MBD2 could bind BMP2's promotor. MassARRAY indicated that MBD2 itself could not directly affect DNA methylation. In sum, our results indicate that increased MBD2 expression promotes CS-induced pulmonary vascular remodeling. The fundamental mechanisms may be that MBD2 can bind BMP2's promoter and downregulate its expression. Thus, MBD2 may promote the occurrence of the CS-induced PH.

Human epididymis protein 4 aggravates airway inflammation and remodeling in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic inflammation and airway remodeling. Human epididymis protein 4 (HE4) plays a critical role in various inflammatory or fibrotic diseases. However, the role of HE4 in COPD remains unidentified. METHODS: HE4 expression was determined in the lung tissues from COPD patients and cigarette smoke (CS)-exposed mice using immunohistochemical staining, qPCR, or western blot. The plasma level of HE4 was detected by ELISA. The regulations of HE4 in the expressions of CS extract (CSE)-induced inflammatory cytokines in human bronchial epithelial cells (HBE) were investigated through knockdown or overexpression of HE4. The role of secretory HE4 (sHE4) in the differentiation and proliferation in human pulmonary fibroblast cells (HPF) was explored via qPCR, western blot, CCK8 assay or 5-ethynyl-2'-deoxyuridine (EdU) staining. The probe of related mechanism in CSE-induced HE4 increase in HBE was conducted by administrating N-acetylcysteine (NAC). RESULTS: HE4 was up-regulated in both the lung tissue and plasma of COPD patients relative to controls, and the plasma HE4 was negatively associated with lung function in COPD patients. The same enhanced HE4 expression was verified in CS-exposed mice and CSE-induced HBE, but CSE failed to increase HE4 expression in HPF. In vitro experiments showed that reducing HE4 expression in HBE alleviated CSE-induced IL-6 release while overexpressing HE4 facilitated IL-6 expression, mechanistically through affecting phosphorylation of NFκB-p65, whereas intervening HE4 expression had no distinctive influence on IL-8 secretion. Furthermore, we confirmed that sHE4 promoted fibroblast-myofibroblast transition, as indicated by promoting the expression of fibronectin, collagen I and α-SMA via phosphorylation of Smad2. EdU staining and CCK-8 assay demonstrated the pro-proliferative role of sHE4 in HPF, which was further confirmed by enhanced expression of survivin and PCNA. Pretreatment of NAC in CSE or H2O2-induced HBE mitigated HE4 expression. CONCLUSIONS: Our study indicates that HE4 may participate in airway inflammation and remodeling of COPD. Cigarette smoke enhances HE4 expression and secretion in bronchial epithelium mediated by oxidative stress. Increased HE4 promotes IL-6 release in HBE via phosphorylation of NFκB-p65, and sHE4 promotes fibroblastic differentiation and proliferation.

Detection of the Disorders of Glycerophospholipids and Amino Acids Metabolism in Lung Tissue From Male COPD Patients.

Background: At present, few studies have reported the metabolic profiles of lung tissue in patients with COPD. Our study attempted to analyze the lung metabolome in male COPD patients and to screen the overlapping biomarkers of the lung and plasma metabolomes. Methods: We performed untargeted metabolomic analysis of normal lung tissue from two independent sets (the discovery set: 20 male COPD patients and 20 controls and the replication set: 47 male COPD patients and 27 controls) and of plasma samples from 80 male subjects containing 40 COPD patients and 40 controls. Results: We found glycerophospholipids (GPs) and Amino acids were the primary classes of differential metabolites between male COPD patients and controls. The disorders of GPs metabolism and the valine, leucine and isoleucine biosynthesis metabolism pathways were identified in lung discovery set and then also validated in the lung replication set. Combining lung tissue and plasma metabolome, Phytosphingosine and l-tryptophan were two overlapping metabolites biomarkers. Binary logistic regression suggested that phytosphingosine together with l-tryptophan was closely associated with male COPD and showed strong diagnostic power with an AUC of 0.911 (95% CI: 0.8460-0.9765). Conclusion: Our study revealed the metabolic perturbations of lung tissues from male COPD patients. The detected disorders of GPs and amino acids may provide an insight into the pathological mechanism of COPD. Phytosphingosine and l-tryptophan were two novel metabolic biomarkers for differentiating COPD patients and controls.

The Global, Regional, and National Burden and Trends of Infective Endocarditis From 1990 to 2019: Results From the Global Burden of Disease Study 2019.

Introduction: Infective endocarditis (IE) presents with increasing incidence and mortality in some regions and countries, as well as serious socioeconomic burden. The current study aims to compare and interpret the IE burden and temporal trends globally and in different regions from 1990 to 2019. Methods: Data on the incidence, deaths and disability-adjusted life years (DALYs) caused by IE were extracted and analyzed from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPC) were adopted to quantify the change trends of age-standardized rates (ASRs). Besides, potential contributors of serious IE burden were also evaluated including age, gender, social-demographic index (SDI), and age-standardized incident rate (ASIR) in 1990. Results: Globally, the number of IE cases and deaths has increased sharply during the past 30 years from 478,000 in 1990 to 1,090,530 in 2019 and from 28,750 in 1990 to 66,320 in 2019, and both presented an upward temporal trend annually (EAPC:1.2 for incidence and 0.71 for death). However, the EAPC of age-standardized DALYs demonstrated a negative temporal trend despite increasing DALYs from 1,118,120 in 1990 to 1,723,590 in 2019. Moreover, older patients and men were more severely affected. Meanwhile, different SDI regions had different disease burdens, and correlation analyses indicated that SDI presented a positive association with ASIR (R = 0.58, P < 0.0001), no association with age-standardized death rate (R = -0.06, P = 0.10), and a negative association with age-standardized DALYs (R = -0.40, P < 0.0001). In addition, the incidence of IE increased in most countries during the past 30 years (190 out of 204 countries). However, the change trends of deaths and DALYs were heterogeneous across regions and countries. Finally, we discovered positive associations of the EAPC of ASRs with the SDI in 2019 among 204 countries and territories but few associations with the ASIR in 1990. Conclusion: Generally, the global burden of IE is increasing, and there is substantial heterogeneity in different genders, ages and regions, which may help policy-makers and medical staff respond to IE and formulate cost-effective interventional measures.

Global, regional, and national burden of urinary tract infections from 1990 to 2019: an analysis of the global burden of disease study 2019.

PURPOSE: We aimed to estimate the burden of UTIs by age, sex, and socioeconomic status in 204 countries and territories from 1990 to 2019. METHODS: We used data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to analyse the incidence, mortality, and disability-adjusted life-years (DALYs) due to UTIs at the global, regional, and national levels. Estimates are presented as numbers and age-standardised or age-specific rates per 100,000 population, with 95% uncertainty intervals (UIs). We further explored the associations between the incidence, mortality, DALYs, and socio-demographic index (SDI) as a proxy for the development status of regions and countries. RESULTS: In 2019, more than 404.6 million (95% UI 359.4-446.5) individuals had UTIs globally and nearly 236,786 people (198,433-259,034) died of UTIs, contributing to 5.2 million (4.5-5.7) DALYs. The age-standardised incidence rate increased from 4715.0 (4174.2-5220.6) per 100,000 population in 1990 to 5229.3 (4645.3-5771.2) per 100,000 population in 2019. At the GBD regional level, the highest age-standardised incidence rate in 2019 occurred in Tropical Latin America (13,852.9 [12,135.6-15,480.3] per 100,000 population). At the national level, Ecuador had the highest age-standardised incidence rate (15,511.3 [13,685.0-17,375.6] per 100,000 population). The age-standardised death rates were highest in Barbados (19.5 [13.7-23.5] per 100,000 population). In addition, age-standardised incidence, death, and DALY rates generally increased across the SDI. CONCLUSIONS: Our study results suggest a globally rising trend of UTI burden between 1990 and 2019.

MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema.

Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro. Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD.

Twelve-Month Systemic Consequences of Coronavirus Disease 2019 (COVID-19) in Patients Discharged From Hospital: A Prospective Cohort Study in Wuhan, China.

BACKGROUND: Follow-up study of coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. RESULTS: 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological, or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, and liver functions are common in patients who recovered from coronavirus disease 2019 (COVID-19) up to 12 months post-discharge.

The global burden and trends of maternal sepsis and other maternal infections in 204 countries and territories from 1990 to 2019.

BACKGROUND: Maternal sepsis and other maternal infections (MSMI) have considerable impacts on women's and neonatal health, but data on the global burden and trends of MSMI are limited. Comprehensive knowledge of the burden and trend patterns of MSMI is important to allocate resources, facilitate the establishment of tailored prevention strategies and implement effective clinical treatment measures. METHODS: Based on data from the Global Burden of Disease database, we analysed the global burden of MSMI by the incidence, death, disability-adjusted life year (DALY) and maternal mortality ratio (MMR) in the last 30 years. Then, the trends of MSMI were assessed by the estimated annual percentage change (EAPC) of MMR as well as the age-standardized rate (ASR) of incidence, death and DALY. Moreover, we determined the effect of sociodemographic index (SDI) on MSMI epidemiological parameters. RESULTS: Although incident cases almost stabilized from 1990 to 2015, the ASR of incidence, death, DALY and MMR steadily decreased globally from 1990 to 2019. The burden of MSMI was the highest in the low SDI region with the fastest downward trends. MSMI is still one of the most important causes of maternal death in the developed world. Substantial diversity of disease burden and trends occurred in different regions and individual countries, most of which had reduced burden and downward trends. The MMR and ASR were negatively correlated with corresponding SDI value in 2019 in 204 countries/territories and 21 regions. CONCLUSION: These findings highlight significant improvement in MSMI care in the past three decades, particularly in the low and low-middle SDI regions. However, the increased burden and upward trends of MSMI in a few countries and regions are raising concern, which poses a serious challenge to maternal health. More tailored prevention measures and additional resources for maternal health are urgently needed to resolve this problem.

NIR-II Responsive Hydrogel as an Angiogenesis Inhibition Agent for Tumor Microenvironment Reprogramming.

Regulation of angiogenesis is a great challenge for effective anticancer therapy. Generally, anti-angiogenic therapies are focused on inhibition of inducers involved in pro-angiogenic communication pathways. Despite the great potential of anti-angiogenic therapy, engineering efficient angiogenesis inhibition agents (AIAs) is still a formidable challenge, since most anti-angiogenic therapies are limited due to the cancer recurrence via compensatory expression of different angiogenic mediators. Herein, we present a new strategy of near-infrared-II (NIR-II) responsive hydrogel AIAs, constructed by incorporation of nitric oxide (NO) precursor (BNN6) and 2D WO2.9 nanosheets within hydrogel (WB@hydrogel). Because of the defect/2D engineering, the bandgap of the WO2.9 nanosheets narrows, which extends the absorption to the NIR-II region. It offers a favorable NIR-II controlled manner for NO generation through irradiation time and light intensity. The continuous supply of NO can activate the expression of wild-type p53 protein and further reverse the transcriptional expression of pro- and anti-angiogenic factors of the tumor microenvironment (TME), subsequently alternating pro-angiogenic TME to anti-angiogenic TME. In the murine tumor model, this method achieved high tumor growth inhibition (TGI) rate and excellent anti-recurrence efficiency.

Global, regional, and national dengue burden from 1990 to 2017: A systematic analysis based on the global burden of disease study 2017.

BACKGROUND: Dengue is one of the most common vector-borne diseases globally, however, its burden is poorly quantified. Hence, we aimed to report the dengue burden in 195 countries and territories between 1990 and 2017, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. METHODS: Following the methodology framework and analytical strategies used in the Global Burden of Disease Study 2017, we analysed the incidence, mortality, and disability-adjusted life years (DALYs) of dengue in geographically defined populations worldwide between 1990 and 2017. We also determined the association between development levels and dengue burden. All estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals. FINDINGS: Globally, the total number of dengue cases increased from 23 283 274 (95% UI 453 180.7-51 840 670) in 1990 to 104 771 911 (95% UI 63 759 019-158 870 031) in 2017. The age-standardised incidence rate increased from 431.6 (8.4-961.0) per 100 000 population in 1990 to 1371.3 (834.5-2079.3) per 100 000 population in 2017. In addition, the number of deaths due to dengue increased from approximately16 957 (7 613-30 091) in 1990 to 40 467 (17 620-49 778) in 2017. Meanwhile, the global age-standardised death rate increased from 0.31 (0.14-0•56) per 100 000 population in 1990 to 0.53 (0.23-0•65) per 100 000 population in 2017. Overall, there were 2 922 630 DALYs (1 629 424-3 967 492) attributed to dengue in 2017 globally, an increase of 107.6% since 1990 (1 407 571 DALYs [624 016.4-2 510 025]), and the age-standardised DALY rate increased from 26.10 (11.57-46.53) per 100 000 population to 38.25 (21.33-51.93) per 100 000 population between 1990 and 2017. The association between socio-demographic index (SDI) and dengue-related DALYs suggested that the lowest age-standardised DALY rates were found in countries in the low and high-SDI quintile in 2017, and from 1990 to 2017, the age-standardized DALY rate tended to increase in regions with the lowest SDI but declined in regions with the highest SDI. There was a nonlinear association between the socio-demographic index and the healthcare access and quality index and age-standardised DALY rates. INTERPRETATION: Dengue is a major public health challenge worldwide. While there is remarkable international variation in its incidence, the dengue burden is increasing globally. The results of this study could be useful for policy makers to implement cost-effective interventions and reduce the dengue burden, particularly in countries with high incidence or increasing burden. FUNDING: This work was supported by a grant from the National Natural Science Foundation of China (NSFC) (grant numbers 81,800,041 and 82,000,078).

Early fibroproliferative signs on high-resolution CT are associated with mortality in COVID-19 pneumonia patients with ARDS: a retrospective study.

OBJECTIVES: To investigate the chest high-resolution computed tomography (HRCT) findings in coronavirus disease 2019 (COVID-19) pneumonia patients with acute respiratory distress syndrome (ARDS) and to evaluate its relationship with clinical outcome. MATERIALS AND METHODS: In this retrospective study, 79 COVID-19 patients with ARDS were recruited. Clinical data were extracted from electronic medical records and analyzed. HRCT scans, obtained within 3 days before clinical ARDS onset, were evaluated by three independent observers and graded into six findings according to the extent of fibroproliferation. Multivariable Cox proportional hazard regression analysis was used to assess the independent predictive value of the computed tomography (CT) score and radiological fibroproliferation. Patient survival was determined by Kaplan-Meier analysis. RESULTS: Compared with survivors, non-survivors showed higher rates of lung fibroproliferation, whereas there were no significant differences in the area of increased attenuation without traction bronchiolectasis or bronchiectasis. A HRCT score <230 enabled the prediction of survival with 73.5% sensitivity and 93.3% specificity, 100% negative predictive value (NPP), 83.3% positive predictive value (PPV) and 88.6% accuracy (Area Under the Curve [AUC] = 0.9; 95% confidence Interval [CI] 0.831-0.968). A multivariate Cox proportional hazards model showed that the HRCT score is a significant independent risk factor for mortality (Hazard Ratio [HR] 9.94; 95% CI 4.10-24.12). Kaplan-Meier analysis revealed that a HRCT score ⩾230 was associated with a higher fatality rate. Organ injury occurred less frequently in patients with a HRCT score <230 compared to those with a HRCT score ⩾230. CONCLUSION: Early pulmonary fibroproliferative signs on HRCT are associated with increased mortality and susceptibility to organ injury in COVID-19 pneumonia patients with early ARDS.