Nationwide genome surveillance of carbapenem-resistant Pseudomonas aeruginosa in Japan.

Japan is a country with an approximate 10% prevalence rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020. CRPA exhibited susceptibility rates of 52.9%, 26.4%, and 88.0% against piperacillin-tazobactam, ciprofloxacin, and amikacin, respectively, whereas 27.7% of CRPA isolates was classified as difficult-to-treat resistance P. aeruginosa. Of the 148 sequence types detected, ST274 (9.7%) was predominant, followed by ST235 (7.6%). The proportion of urine isolates in ST235 was higher than that in other STs (P = 0.0056, χ2 test). Only 4.1% of CRPA isolates carried the carbapenemase genes: blaGES (2) and blaIMP (13). One ST235 isolate carried the novel blaIMP variant blaIMP-98 in the chromosome. Regarding chromosomal mutations, 87.1% of CRPA isolates possessed inactivating or other resistance mutations in oprD, and 28.8% showed mutations in the regulatory genes (mexR, nalC, and nalD) for the MexAB-OprM efflux pump. Additionally, 4.7% of CRPA isolates carried a resistance mutation in the PBP3-encoding gene ftsI. The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions.

Association of Serum Folate and Vitamin B 12 Concentrations with Obesity in Chinese Children and Adolescents.

Objective: This study aimed to evaluate the associations of serum folate and/or vitamin B 12 concentrations with obesity among Chinese children and adolescents. Methods: A cross-sectional study was conducted including 3,079 Chinese children and adolescents, aged 6 to 17 years, from Jiangsu, China. Anthropometric indices, such as, children's body mass index (BMI), BMI z-scores, waist circumference, and waist-to-height ratio were utilized. Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B 12 levels with anthropometric indices and odds of obesity. Results: We observed that serum vitamin B 12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity [odds ratio ( OR) = 0.68; 95% confidence interval ( CI) = 0.59, 0.78] and abdominal obesity ( OR = 0.68; 95% CI = 0.60, 0.77). When compared to participants with both serum vitamin levels in the two middle quartiles, those with both serum folate and vitamin B 12 levels in the highest quartile were less prone to general ( OR = 0.31, 95% CI = 0.19, 0.50) or abdominal obesity ( OR = 0.46, 95% CI = 0.31, 0.67). Conversely, participants with vitamin B 12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity ( OR = 2.06, 95% CI = 1.09, 3.91). Conclusion: Higher serum vitamin B 12 concentrations, but not serum folate concentrations, were associated with lower odds of childhood obesity. Children and adolescents with high levels of vitamin B 12 and folate were less likely to be obese.

Loneliness, Living Alone, and Risk of Cardiovascular Disease Among Older Adults in China.

BACKGROUND: Older adults are prone to live alone and feel lonely. The main objective of this study was to assess the associations of loneliness and living alone with cardiovascular disease (CVD) among community-dwelling older individuals in China. METHODS: We conducted a longitudinal analysis on 3 661 participants aged older than 65 years from the latest 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. Cox proportional hazards models were used to assess the associations of loneliness and living alone with CVD risk, with adjustment for confounding factors. RESULTS: A total of 616 incident CVD cases were identified during follow-up. Participants who reported feeling lonely experienced a 28% increased risk of developing CVD after adjustment for sociodemographic characteristics, lifestyle factors, and baseline health status (adjusted hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.01-1.62; ptrend = .046). In contrast, no significant association was observed between living alone and CVD risk. Subgroup analyses showed that among those individuals who lived alone, often feeling lonely doubled the risk of CVD compared to never being lonely (HR: 2.17, 95% CI: 1.20-3.93; ptrend = .007). CONCLUSIONS: Loneliness was an independent risk factor for CVD among Chinese older adults. Our findings underscore the importance of addressing loneliness in the prevention of CVD among older individuals, especially those who live alone.

The study of loading mode with in-vitro fatigue testing for mitral annuloplasty ring.

To maintain the physiological dynamics of the mitral annulus, mitral annuloplasty rings (MAR) must be flexible. Enhanced flexibility implies decreased resistance to fatigue and potential for fatigue fracture. This study established new methods to test the flexible fatigue life of MAR in-vitro using numerical analysis; the purpose is that the fatigue test could reflect the real stress distribution in-vivo. Based on the conventional test methods (C1, D1), this paper presents a novel test method (C2, D2). Four testing methods for open-end annuloplasty rings (C1, C2) and closed-end annuloplasty rings (D1, D2) were modelled and their stress distribution calculated by finite element analysis. The mean absolute error (Χ) and the Pearson correlation coefficient (Φ) were used to quantify the difference in stress distribution between the loading modes in-vivo and in-vitro. For closed-end annuloplasty rings, the novel test method (D2) is not obvious better than conventional test methods(D1) in duplicating the stress distribution (ΦD1 = 0.88 vs ΦD2 = 0.92). However, the maximum values of stress in the novel test method are closer to the maximum value of stress under in-vivo loading (ΧD1 = 5.2Mpa vs ΧD2 = 4.4Mpa). For open-end annuloplasty rings, the novel test method(C2) is obviously superior to the conventional test method(C1) in duplicating both the stress distribution and the stress peak values of the in-vivo loading (ΦC1 = 0.22 vs ΦC2 = 0.98; ΧC1 = 59.1Mpa vs ΧC2 = 11.0Mpa). The in-vitro loading methods described in this article more closely approximated in-vivo conditions compared to traditional methods. They are simpler to operate, more efficient and can help manufacturers expedite new product development, assist regulatory agencies with product quality oversight.

Complete sequence of carbapenem-resistant Ralstonia mannitolilytica clinical isolate co-producing novel class D ß-lactamase OXA-1176 and OXA-1177 in Japan.

In 2020, the Ralstonia mannitolilytica strain JARB-RN-0044 was isolated from a midstream urine sample of an elderly hospitalized patient in Japan and was highly resistant to carbapenem (i.e., imipenem, meropenem, and doripenem). Whole-genome sequencing revealed that the complete genome consists of two replicons, a 3.5-Mb chromosome and a 1.5-Mb large non-chromosomal replicon which has not been reported in R. mannitolilytica, and referred to as the "megaplasmid" in this study based on Cluster of Orthologous Group of proteins functional analysis. The strain JARB-RN-0044 harbored two novel OXA-60 and OXA-22 family class D ß-lactamase genes blaOXA-1176 and blaOXA-1177 on the megaplasmid. Cloning experiments indicated that Escherichia coli recombinant clone expressing blaOXA-1176 gene showed increased minimum inhibitory concentrations (MICs) of imipenem, meropenem, and doripenem, indicating that blaOXA-1176 gene encodes carbapenemase. In contrast, E. coli recombinant clone expressing blaOXA-1177 gene showed increased MICs of piperacillin and cefazolin, but not of carbapenem. Interestingly, the 44.6 kb putative prophage region containing genes encoding phage integrase, terminase, head and tail protein was identified in the downstream region of blaOXA-1176 gene, and comparative analysis with some previously reported R. mannitolilytica isolates revealed that the prophage region was unique to strain JARB-RN-0044. The existence of a highly carbapenem-resistant R. mannitolilytica isolate may raise human health concerns in Japan, where the population is rapidly aging.IMPORTANCERalstonia mannitolilytica is an aerobic non-fermenting Gram-negative rod commonly found in aquatic environments and soil. The bacteria can occasionally cause severe hospital-acquired bloodstream infections in immunocompromised patients and it has been recently recognized as an emerging opportunistic human pathogen. Furthermore, some R. mannitolilytica isolates are resistant to various antimicrobial agents, including ß-lactams and aminoglycosides, making antimicrobial therapy challenging and clinically problematic. However, clinical awareness of this pathogen is limited. To our knowledge, in Japan, there has been only one report of a carbapenem-resistant R. mannitolilytica clinical isolate from urine by Suzuki et al. in 2015. In this study, whole-genome sequencing analysis revealed the presence and genetic context of novel blaOXA-1176 and blaOXA-1177 genes on the 1.5 Mb megaplasmid from highly carbapenem-resistant R. mannitolilytica isolate and characterized the overall distribution of functional genes in the chromosome and megaplasmid. Our findings highlight the importance of further attention to R. mannitolilytica isolate in clinical settings.

mtDNA extramitochondrial replication mediates mitochondrial defect effects.

A high ratio of severe mitochondrial defects causes multiple human mitochondrial diseases. However, until now, the in vivo rescue signal of such mitochondrial defect effects has not been clear. Here, we built fly mitochondrial defect models by knocking down the essential mitochondrial genes dMterf4 and dMrps23. Following genome-wide RNAi screens, we found that knockdown of Med8/Tfb4/mtSSB/PolG2/mtDNA-helicase rescued dMterf4/dMrps23 RNAi-mediated mitochondrial defect effects. Extremely surprisingly, they drove mtDNA replication outside mitochondria through the Med8/Tfb4-mtSSB/PolG2/mtDNA-helicase axis to amplify cytosolic mtDNA, leading to activation of the cGAS-Sting-like IMD pathway to partially mediate dMterf4/dMrps23 RNAi-triggered effects. Moreover, we found that the Med8/Tfb4-mtSSB/PolG2/mtDNA-helicase axis also mediated other fly mitochondrial gene defect-triggered dysfunctions and Drosophila aging. Overall, our study demarcates the Med8/Tfb4-mtSSB/PolG2/mtDNA-helicase axis as a candidate mechanism to mediate mitochondrial defect effects through driving mtDNA extramitochondrial replication; dysfunction of this axis might be used for potential treatments for many mitochondrial and age-related diseases.

Temporal and spatial variations in the sub-daily precipitation structure over the Qinghai-Tibet Plateau (QTP).

Precipitation is a vital component of the global atmospheric and hydrological cycles and influencing the distribution of water resources. Even subtle changes in precipitation can significantly impact ecosystems, energy cycles, agricultural production, and food security. Therefore, understanding the changes in the precipitation structure under climate change is essential. The Qinghai-Tibet Plateau (QTP) is a region sensitive to global climate change and profoundly impacts the atmospheric water cycle in Asia and even globally, rendering it a hot topic in climate change research in recent years. Few studies have examined on the sub-daily scale precipitation structure over the QTP. In this paper, the characteristics of sub-daily precipitation on the QTP were systematically investigated from multiple perspectives, including the concentration index, skewness (the third standardized moment of a distribution), and kurtosis (the fourth standardized moment of a distribution). The results indicated that the frequency of moderate-intensity nighttime precipitation on the QTP generally increased, and the analysis of both the concentration index and kurtosis (skewness) suggested that extreme precipitation was more frequent in the southwestern foothills of the QTP. Furthermore, potential high-risk areas for natural disasters were identified on the QTP, and found that the southeastern part of the plateau constituted a potential hotspot area for flood disasters. Given the complexity of climate change, a comprehensive analysis of the spatiotemporal characteristics of diurnal and nighttime precipitation changes on the QTP could help reveal the regularity of precipitation changes. This has significant implications for forecasting, warning, disaster preparedness, and mitigation efforts on the QTP.

Trimethylamine N-oxide, ß-alanine, tryptophan index, and vitamin B6-related dietary patterns in association with stroke risk.

BACKGROUND AND AIMS: The aim of this study was to examine the associations of dietary patterns derived by reduced-rank regression (RRR) model reflecting variation in novel biomarkers (trimethylamine N-oxide, ß-alanine, tryptophan index, and vitamin B6) with stroke risk. METHODS AND RESULTS: We performed analyses based on a community-based cohort study "the Prospective Follow-up Study on Cardiovascular Morbidity and Mortality in China (PFS-CMMC)". Factor loadings were calculated by RRR using 11 food groups collected via a validated food frequency questionnaire and the four response variables based on its nested case-control data (393 cases of stroke vs. 393 matched controls). Dietary pattern scores were derived by applying the factor loadings to the food groups in the entire cohort (n = 15,518). The associations of dietary pattern with the stroke risk were assessed using Cox proportional hazards models. The dietary pattern characterized with higher intakes of red meat and poultry but lower intakes of fresh vegetables, fresh fruits, and fish/seafoods were identified for further analyses. The hazard ratios (HR) for the highest vs. lowest quartile was 1.55 [95 % confidence interval (CI): 1.18-2.03, P trend = 0.001] for total stroke, 2.96 [95 % CI: 1.53-5.71, P trend <0.001] for non-ischemic stroke, after adjustment for sex, age, educational attainment, current smoking, current drinking, body mass index, total energy intake, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate. CONCLUSION: Our findings highlight the importance of limited meat intake and increased intakes of fresh vegetables, fruits, and fish/seafoods in the prevention of stroke among Chinese adults.

Hyaluronan delays human amniotic epithelial stem cell senescence by regulating CD44 isoform switch to activate AKT/mTOR signals.

The replicative senescence of human amniotic epithelial stem cells (hAECs) is a major concern towards its clinical application. This study found that a 300-kDa hyaluronic acid (HA) could effectively delay the replicative senescence of hAECs, as indicated by the downregulation of cellular senescence markers and alteration of the cell cycle, and substantially improve the differentiation capacities of hAECs. HA was confirmed to regulate the CD44 isoform switch by upregulating the CD44s and downregulating the CD44v, thus exerting an anti-aging effect. We further found that HA induced the upregulation of hyaluronan synthase (HAS) 2, resulting in the activation of epithelial splicing regulatory protein 1 (ESRP1) and alternative splicing of CD44 mRNA, thereby promoting CD44s expression and inhibiting CD44v expression. Knockdown of HAS2 blocked ESRP1 expression and attenuated the anti-aging effects of HA. Hermes-1, a specific blocker of CD44, caused partial loss of the anti-aging effect of HA, upregulated senescence markers, and downregulated stemness markers. Furthermore, CD44s receptor activation was shown to initiate the AKT/mTOR downstream signaling. Conclusively, the study suggested that HA delayed hAEC senescence by regulating CD44 isoform switch to activate the AKT/mTOR signaling pathway, and there is potential for the clinical application of hAECs in combination with HA.

Plasma levels of urea cycle related amino acids in association with risk of ischemic stroke: Findings from a nested case-control study.

OBJECTIVES: The role of urea cycle related amino acids in the development of ischemic stroke (IS) remains unclear. The study aimed to evaluate the association of these amino acids with IS. MATERIALS AND METHODS: We conducted a case-control study nested within a cohort study in Changshu, Eastern China. A total of 321 cases and 321 controls matched by age and gender were finally included. Plasma levels of ornithine, arginine, spermidine, and proline were measured using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Odds ratios (ORs) and their 95 % confidence intervals (CIs) were calculated by conditional logistic regression analyses. RESULTS: Plasma ornithine was inversely associated with risk of IS [crude OR: 0.62 (95 % CI: 0.40-0.97)]. After adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate, and total cholesterol, the corresponding ORs for the highest compared to the lowest quartiles was essentially unchanged [adjusted OR: 0.62 (95 % CI: 0.39-0.99)]. The risk association remained significant after repeating the analyses by excluding the first two years of follow-up. Plasma arginine, spermidine, and proline were not associated with the risk of IS. CONCLUSION: We observed that higher plasma levels of ornithine were associated with a lower risk of incident IS. Our novel findings suggest a protective role of ornithine in the pathogenesis of IS.

National genomic surveillance integrating standardized quantitative susceptibility testing clarifies antimicrobial resistance in Enterobacterales.

Antimicrobial resistance is a global health concern; Enterobacterales resistant to third-generation cephalosporins (3GCs) and carbapenems are of the highest priority. Here, we conducted genome sequencing and standardized quantitative antimicrobial susceptibility testing of 4,195 isolates of Escherichia coli and Klebsiella pneumoniae resistant to 3GCs and Enterobacterales with reduced meropenem susceptibility collected across Japan. Our analyses provided a complete classification of 3GC resistance mechanisms. Analyses with complete reference plasmids revealed that among the blaCTX-M extended-spectrum ß-lactamase genes, blaCTX-M-8 was typically encoded in highly similar plasmids. The two major AmpC ß-lactamase genes were blaCMY-2 and blaDHA-1. Long-read sequencing of representative plasmids revealed that approximately 60% and 40% of blaCMY-2 and blaDHA-1 were encoded by such plasmids, respectively. Our analyses identified strains positive for carbapenemase genes but phenotypically susceptible to carbapenems and undetectable by standard antimicrobial susceptibility testing. Systematic long-read sequencing enabled reconstruction of 183 complete plasmid sequences encoding three major carbapenemase genes and elucidation of their geographical distribution stratified by replicon types and species carrying the plasmids and potential plasmid transfer events. Overall, we provide a blueprint for a national genomic surveillance study that integrates standardized quantitative antimicrobial susceptibility testing and characterizes resistance determinants.

Emergence of colistin-resistant Enterobacter cloacae and Raoultella ornithinolytica carrying the phosphoethanolamine transferase gene, mcr-9, derived from vegetables in Japan.

IMPORTANCE: Plasmid-mediated mobile colistin-resistance genes have been recognized as a global threat because they jeopardize the efficacy of colistin in therapeutic practice. Here, we described the genetic features of two mcr-9.1-carrying Gram-negative bacteria with a colistin-resistant phenotype derived from vegetables in Japan. The colistin-resistant mcr-9.1, which has never been detected in vegetables, was located on a large plasmid in Enterobacter cloacae CST17-2 and Raoultella ornithinolytica CST129-1, suggesting a high chance of horizontal gene transfer. To the best of our knowledge, this is the first report of mcr-9 in R. ornithinolytica. This study indicates that fresh vegetables might be a potential source for the transmission of mcr-9 genes encoding resistance to frontline (colistin) and clinically relevant antimicrobials. The study also provides additional consideration for colistin use and the relevance of routine surveillance in epidemiological perspective to curb the continuous spread of mcr alleles.

Potential short-term effects of earthquake on the plant-soil interface in alpine grassland of the Qinghai-Tibetan Plateau.

Earthquakes are environmental disturbances affecting ecosystem functioning, health, and biodiversity, but their potential impacts on plant-soil interface are still poorly understood. In this study, grassland habitats in areas near and away from the seismo-fault in Madou, a region typical of alpine conditions on the Qinghai-Tibetan Plateau, were randomly selected. The impacts of earthquake on soil properties and plant nutrient content in the short term were emphasized, and their potential relationships with community diversity and productivity were examined. According to the findings of the study, the Maduo earthquake led to a decrease in soil nutrient content in alpine grassland ecosystems, especially soil TC, TN, TP, TCa, AP, AK, NH4 +-N, and SOC, and inhibited the absorption of N, Ca, and Mg nutrients by plants. In addition, the diversity and productivity of communities were affected by both direct and indirect earthquake pathways. The negative impacts of seismic fracture on soil structure had the most significant direct impact on plant community diversity. Earthquakes also indirectly reduced community productivity by reducing the soil N content and inhibiting the absorption of plant nutrients. Our findings suggested that earthquakes could potentially decrease the stability of the alpine grassland ecosystem on the QTP by affecting nutrient availability at the plant-soil interface.

Genetic and phenotypic characterizations of IncX3 plasmids harboring bla NDM-5 and bla NDM-16b in Japan.

IMPORTANCE: IncX3 plasmids harboring bla NDM-5 play a major role in the spread of carbapenem resistance in Asia, particularly in China, in clinical and environmental settings. In this study, we present that Enterobacterales isolates carrying IncX3 plasmids harboring bla NDM-5 have been disseminated in Japan, where their identification was previously rare. In addition, bla NDM-16b, a single-nucleotide variant of bla NDM-5, was found to be carried by an identical IncX3 plasmid. A comparative sequence analysis revealed that the bla NDM-16b gene emerged from a single nucleotide substitution on an IncX3 plasmid harboring bla NDM-5. The bla NDM-16b gene did not confer elevated carbapenem resistance compared to bla NDM-5 in our assay using transformants carrying the plasmid harboring either of these genes, although the A233V substitution was reported to confer stability to the enzyme in ion-depleted conditions. Nevertheless, vigilance regarding the emergence of novel variants is required.

HIV/AIDS-related knowledge and attitudes towards HIV rapid testing among Chinese college students: Findings from a cross-sectional survey.

Data of the awareness level of college students in China about Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) knowledge are limited. Also, the attitudes towards HIV rapid testing remain unknown among this population. Therefore, this study aimed to evaluate the awareness of HIV/AIDS knowledge and attitudes towards HIV rapid testing among Chinese college students. An online cross-sectional survey was performed in 2020. A total of 1,474 participants were finally included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine associated factors for the cognitive levels and attitudes by multivariable logistic regression. Spearman rank correlation was used to examine the relationship between HIV/AIDS-related knowledge and attitudes. About 91% of participants had a high cognitive level on HIV/AIDS-related knowledge and 84.7% held a positive attitude towards the HIV rapid testing. Postgraduates (OR = 1.75, 95% CI: 1.16-2.66) and females (OR = 1.69, 95% CI: 1.13-2.52) were more knowledgeable. Females' attitudes towards the HIV rapid testing were more positive (OR = 1.91, 95% CI: 1.40-2.62). Moreover, the knowledge was positively correlated with attitudes towards the rapid testing (Spearman r = 0.14, p < 0.001). In conclusion, the Chinese college students had a high cognitive level on HIV/AIDS knowledge and positive attitudes towards HIV rapid testing. A high cognitive level of knowledge paralleled with positive attitudes. Special strategies such as tailored education via HIV/AIDS curriculum and awareness campaigns are needed for undergraduates and male students to minimize the gaps regarding HIV/AIDS-related knowledge and attitudes.

AAV-Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging-associated metabolic dysfunctions.

Sarcopenia is characterized of muscle mass loss and functional decline in elder individuals which severely affects human physical activity, metabolic homeostasis, and life quality. Physical exercise is considered effective in combating muscle atrophy and sarcopenia, yet it is not feasible to elders with limited mobility. PGC-1α4, a short isoform of PGC-1α, is strongly induced in muscle under resistance training, and promotes muscle hypertrophy. In the present study, we showed that the transcriptional levels and nuclear localization of PGC1α4 was reduced during aging, accompanied with muscle dystrophic morphology, and gene programs. We thus designed NLS-PGC1α4 and ectopically express it in myotubes to enhance PGC1α4 levels and maintain its location in nucleus. Indeed, NLS-PGC1α4 overexpression increased muscle sizes in myotubes. In addition, by utilizing AAV-NLS-PGC1α4 delivery into gastrocnemius muscle, we found that it could improve sarcopenia with grip strength, muscle weights, fiber size and molecular phenotypes, and alleviate age-associated adiposity, insulin resistance and hepatic steatosis, accompanied with altered gene signatures. Mechanistically, we demonstrated that NLS-PGC-1α4 improved insulin signaling and enhanced glucose uptake in skeletal muscle. Besides, via RNA-seq analysis, we identified myokines IGF1 and METRNL as potential targets of NLS-PGC-1α4 that possibly mediate the improvement of muscle and adipose tissue functionality and systemic energy metabolism in aged mice. Moreover, we found a negative correlation between PGC1α4 and age in human skeletal muscle. Together, our results revealed that NLS-PGC1α4 overexpression improves muscle physiology and systematic energy homeostasis during aging and suggested it as a potent therapeutic strategy against sarcopenia and aging-associated metabolic diseases.

Outcomes of catheter-directed thrombolysis versus systemic thrombolysis in the treatment of pulmonary embolism: a meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) versus systemic thrombolysis (ST) in the treatment of pulmonary embolism (PE). METHODS: The Cochrane Library, PubMed, and Embase databases were searched to collect the literature on the comparison of the results of CDT and ST in the treatment of PE from the beginning of their records to May 2020, and meta-analysis was performed by STATA software (version 15.1). Using standardized data-collection forms, the authors screened the studies and independently extracted data, and assessed the quality of the studies using the Newcastle-Ottawa Scale for cohort studies. Cohort studies that examined the following results were included in the current study: in-hospital mortality, all-cause bleeding rate, gastrointestinal bleeding rate, intracranial hemorrhage rate, the incidence of shock, and hospital length of stay. RESULTS: A total of eight articles, with 13,242 participants, involving 3962 participants in the CDT group and 9280 participants in the ST group were included. CDT compared with ST in the treatment of PE can significantly affect in-hospital mortality rate [odds ratio (OR) = 0.41, 95% CI: 0.30-0.56, P < 0.05], all-cause bleeding rate (OR = 1.20, 95% CI: 1.04-1.39, P = 0.012), gastrointestinal bleeding rate (OR = 1.43, 95% CI: 1.13-1.81, P = 0.003), the incidence of shock (OR = 0.46, 95% CI: 0.37-0.57, P < 0.05), and hospital length of stay [standard mean difference (SMD) = 0.16, 95% CI: 0.07-0.25, P < 0.05]. However, there was no significant effect on intracranial hemorrhage rate in patients with PE (OR = 0.70, 95% CI: 0.47-1.03, P = 0.070). CONCLUSIONS: CDT is a viable alternative to ST in the treatment of PE, as it can significantly reduce in-hospital mortality rate, all-cause bleeding rate, gastrointestinal bleeding rate, and incidence of shock. However, CDT may prolong hospital length of stay to a certain extent. Further research is needed to evaluate the safety and efficacy of CDT and ST in the treatment of acute PE and other clinical outcomes.

Comorbidities are associated with self-reported sleep-disordered breathing and insomnia: a cross-sectional study from China.

PURPOSE: We aimed to examine the associations of comorbidities with self-reported sleep-disordered breathing (SDB) and insomnia among Chinese adults. METHODS: The study used data from a community-based cross-sectional survey performed in China in 2018-2020. Multivariable logistic regression models were used to analyze the associations of 12 comorbidities with SDB and insomnia. RESULTS: A total of 4329 Han Chinese adults aged ≥ 18 years were enrolled. Of these, 1970 (45.5%) were male, with a median age of 48 years (interquartile range: 34-59). Compared with the participants without any conditions, adjusted ORs for SDB and insomnia for those with ≥ 4 comorbidities were 2.33 (95% CI: 1.58, 3.43, P-trend < 0.001) and 3.89 (95% CI: 2.69, 5.64, P-trend < 0.001), respectively. Seven comorbidities (hypertension, hyperlipidemia, coronary heart disease (CHD), bone and joint disease, neck or lumbar disease, chronic digestive diseases, and chronic urological disease) were positively associated with both SDB and insomnia. Cancer and chronic obstructive pulmonary disease (COPD) were also independently associated with insomnia. Of all comorbidities, cancer was most strongly associated with insomnia (OR = 3.16; 95% CI: 1.78, 5.63; P < 0.001), and CHD was most strongly associated with SDB (OR = 1.77; 95% CI: 1.19, 2.64; P < 0.001). CONCLUSIONS: The findings showed that adults with an increasing number of comorbidities had higher odds for SDB and insomnia, which were independent of sociodemographic and lifestyle factors.

Effect of lifestyle intervention on HbA1c levels in overweight and obese adults with type 2 diabetes across ethnicities: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Weight reduction is fundamental for the management and remission of diabetes. We aimed to assess ethnic differences in the effects of lifestyle weight-loss interventions on HbA1c levels in overweight or obese adults with type 2 diabetes mellitus (T2DM). METHODS: We systematically searched PubMed/MEDLINE and Web of Science online databases up to 31 Dec 2022. Randomized controlled trials using lifestyle weight-loss interventions in overweight or obese adults with T2DM were selected. We performed subgroup analyses to explore the heterogeneity across different ethnicities (Asians, White/Caucasians, Black/Africans and Hispanics). A random effects model was applied to calculate weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: Thirty studies including 7580 subjects from different ethnicities were identified according to the predefined inclusion and exclusion criteria. HbA1c levels were significantly reduced by lifestyle weight-loss intervention. Notably, a significantly beneficial effect on HbA1c was observed in White/Caucasians (WMD = -0.59, 95% CI: -0.90, -0.28, P < 0.001) and Asians (WMD = -0.48, 95% CI: -0.63, -0.33, P < 0.001), but not in the Black/African or Hispanic group (both P > 0.05). The findings remained essentially unchanged in the sensitivity analysis. CONCLUSIONS: Lifestyle weight-loss interventions had distinct beneficial effects on HbA1c levels in different ethnic groups with T2DM, especially in Caucasians and Asians.