YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold weather.YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis.But YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.Methods:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)group.The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining.In vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition.Compared to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac function.Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction.In hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite effect.Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS.In hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT inhibitor.Conclusion:YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway.It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

The link between dietary nutrients intake and cardiovascular diseases in cold regions

Background:The cold winter weather in northern China influences the dietary habits of its residents,contributing to a heightened risk of cardiovascular disorders,such as hypertension and coronary heart disease.Key factors include low vegetable consumption and high salt and fat intakes.This study aims to investigate the relationships between northern dietary nutrient intake in northern China and cardiovascular disorders during the winter season.Methods:A food frequency questionnaire tailored to the actual eating habits in northern China was designed.Retrospective data from 955 Chinese adults were collected from November to March between 2014 to 2023.Logistic regression was employed to analyze the relationship between dietary nutrients and cardiovascular diseases,with model performance assessed using receiver operating characteristic(ROC)curves.Results:Adjusted for gender,age,and body mass index(BMI),an inverse association was observed between vitamin A(OR=0.706,95%CI:0.550,0.907),nicotinic acid(OR=0.584,95%CI:0.447,0.762),phosphorus(OR=0.777,95%CI:0.608,0.994),selenium(OR=0.719,95%CI:0.560,0.923),zinc(OR=0.683,95%CI:0.531,0.880),methionine(OR=0.730,95%CI:0.569,0.936),arginine(OR=0.753,95%CI:0.588,0.964),lysine(OR=0.706,95%CI:0.550,0.907),aspartic acid(OR=0.730,95%CI:0.569,0.936)and hypertension.Additionally,a negative association was found between niacin(OR=0.752,95%CI:0.597,0.946)and coronary heart disease.Conversely,a positive association was identified between iodine and hypertension(OR=1.305,95%CI:1.020,1.669)and coronary heart disease(OR=1.301,95%CI:1.037,1.634).Conclusion:Our study suggests that maintaining a balanced dietary intake of vitamin A,niacin,phosphorus,selenium,zinc,methionine,arginine,lysine,and aspartic acid can be beneficial in preventing hypertension.Adequate niacin intake is associated with a lower risk of coronary heart disease.However,excessive iodine intake may contribute to hypertension and coronary heart disease.

Clinical characteristics and north-south differences of inflammatory bowel disease in China: A cross-sectional study and meta-analysis

Objective:This study aimed to estimate the incidence rate and clinical characteristics of inflammatory bowel disease(IBD)in the Chinese population,specially comparing the North and South regions.Methods:We designed a questionnaire survey for patients diagnosed with IBD and conducted a systematic literature search in PubMed,China National Knowledge Internet,and Wanfang digital database,covering studies published between 2012 and 2022.Meta-analysis was performed to determine the overall incidence rate and prevalence of clinical manifestations of Crohn's disease(CD)and ulcerative colitis(UC)in China's Mainland.Clinical phenotypes and demographic characteristics were calculated with 95%confidence intervals(CI).A comparison between the northern and southern regions was also conducted.Results:The questionnaire survey included 440 patients,and 64 publications were included for Meta-analysis.The overall incidence rates of IBD,CD,and UC were 1.36(95%CI:0.79-2.33)per 100,000 person-years,0.23(95%CI:0.09-0.58)per 100,000 person-years,and 1.12(95%CI:0.69-1.80)per 100,000 person-years,respectively.The incidence rates of IBD,CD,and UC were all higher in southern China compared to the North.Clinical characteristics of 440 IBD patients from the questionnaire and 2,821 CD patients and 12,809 UC patients from the literature were analyzed.There were more male patients compared to female patients.CD cases in the North exhibited earlier disease diagnosis(P<0.01),more upper gastrointestinal lesions(P<0.01),and higher hospitalizations rates(P<0.01)compared to the South.UC cases in the North had higher severity(P<0.01),anemia rates(P<0.01),and weight loss(P<0.01)compared to the South.Conclusions:The incidence rates of IBD,CD,and UC were higher in southern China than in the North.Northern patients exhibited more severe symptoms compared to their southern counterparts.

Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance.The Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt signaling.The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.Methods:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction surgery.The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction analyses.Inflammatory cell necrosis and infiltration were confirmed through H&E and Masson staining.The expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast transformation.Results:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation.Furthermore,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts.Additionally,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway.Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.Conclusion:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis.Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.

Peroxisome proliferator-activated receptors gama ameliorates liver fibrosis in non-alcoholic fatty liver disease by inhibiting TGF-β/Smad signaling activation

Background:Nonalcoholic fatty liver disease(NAFLD)is a chronic condition characterized by a progressive decline in liver function,leading to disruptions in liver integrity and metabolic function,resulting in lipid deposition and excessive accumulation of extracellular matrix(ECM).The pathogenesis of NAFLD is complex and not yet fully understood,contributing to the absence of specific therapeutic strategies.Peroxisome proliferator-activated receptor gamma(PPARγ)is a ligand-activated transcription factor pivotal in regulating lipid and glucose metabolism.However,the impacts of PPARγon NAFLD remains insufficiently explored.Thus,this study aimed to investigate the role of PPARγin NAFLD and its underlying molecular mechanisms.Methods:Chemical detection kits were utilized to quantify collagen content,alanine aminotransferase(ALT),and aspartate aminotransferase(AST)level variations.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells,while western blotting was conducted to analyze the levels of both PPARγand the TGF-β/Smad signaling pathway.Results:Our findings unveiled significantly reduced PPARγexpression in a rat model of NAFLD,leading to subsequent activation of the TGF-β/Smad signaling pathway.Furthermore,PPARγactivation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen production.On a cellular level,PPARγactivation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9),along with inflammatory response genes interleukin(IL)-1βand IL-6.Additionally,PPARγactivation led to a significant decrease in the levels of ALT and AST.At the molecular level,PPARγnotably down-regulated the TGF-β/Smad signaling pathway,which is known to promote liver fibrosis.Conclusion:These groundbreaking findings underscore PPARγactivation as a promising therapeutic approach to delay NAFLD progression by targeting the TGF-β/Smad signaling pathway in hepatic cells.This highlights the potential of PPARγas a promising therapeutic target for NAFLD management in clinical settings.

Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway

Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.

Hydroxychloroquine induces long QT syndrome by blocking hERG channel

Objective:In March 2022,more than 600 million cases of Corona Virus Disease 2019(COVID-19)and about 6 million deaths have been reported worldwide.Unfortunately,while effective antiviral therapy has not yet been available,chloroquine(CQ)/hydroxychloroquine(HCQ)has been considered an option for the treatment of COVID-19.While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients'lives,controversial results have also been reported.One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval(LQT),an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias.Yet,the mechanisms for this cardiotoxicity of HCQ remained incompletely understood.Materials and methods:Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes.HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene(hERG)K+channels were used for whole-cell patch-clamp recordings of hERG K+channel current(IhERG).Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels,respectively.Results:electrocardiogram(ECG)recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits.Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state.HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90(Hsp90)/hERG complex.Moreover,the expression levels of connexin 43(CX43)and Kir2.1,the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias,were decreased by HCQ,while those of Cav1.2,the main Ca2+handling proteins,remained unchanged and SERCA2a was increased.Conclusion:HCQ could induce LQT but did not induce arrhythmias,and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future.

Advancements in understanding inflammatory responses and the development of cardiovascular diseases under cold stimulation

Cold stimulation has been linked to acute myocardial infarction and other cardiovascular diseases.Residents in the frigid zones,such Heilongjiang Province,experience a higher incidence of adverse cardiovascular events during winter,posing a significant health threat and increasing the overall medical burden.Cold stimulation serves as an detrimental stressor,inducing inflammation in the body.Therefore,understanding the role of inflammatory responses induced by cold stimulation in the occurrence and development of cardiovascular diseases is of paramount importance.Given the impact of cold on inflammation in cardiovascular diseases and the expanding array of anti-inflammatory methods for the treatment of cardiovascular diseases,delving into the inflammatory responses mediated by can significantly complement cardiovascular disease management.This review explorest the synergistic relationship between cold stimulation and inflammation induction,elucidating how this interplay influences the occurrence and progression of cardiovascular diseases.

Silicon dioxide nanoparticles inhibit the effects of cold exposure on metabolism and inflammatory responses in brown adipocytes

Objective:Nanoparticles(NPs)in haze are potentially hazardous to health,which is more severe in the winter.Brown adipose tissue(BAT)plays important roles in obesity,insulin resistance,and diabetes.Though the toxicology of NPs has been intensively studied,few studies have been reported on the antagonistic effects between Silicon dioxide(SiO_(2))NPs and cold exposure in brown adipocytes.Materials and methods:We evaluated changes by quantitative real-time reverse-transcriptase polymerase chain reaction(qRT-PCR)on metabolism genes,plasticity genes and the inflammatory responses genes in brown adipocytes in vitro.Results:The expression of adipogenic genes PRDM16,Dio2,PGC-1αand UCP1 was upregulated upon cold exposure(P<0.05),but downregulated by SiO_(2) NPs(P<0.05).The results demonstrated that there was antagonistic effect between SiO_(2) NPs and cold exposure on the plasticity genes and metabolism genes in brown adipocytes,where the main effects of SiO_(2) NPs or cold exposure on the plasticity genes and metabolism genes were significant(P<0.05).Moreover,the levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-αwere upregulated by SiO_(2) NPs or cold exposure(P<0.05).The factorial analysis indicated that there was also antagonistic effect between SiO_(2) NPs and cold exposure on the toxic effects in brown adipocytes,in which the main effects of cold exposure and/or SiO_(2) NPs on the toxic effects were significant(P<0.05).Conclusion:SiO_(2) NPs inhibit the effect of cold exposure on metabolic genes and inflammatory responses genes in brown adipocytes.

Association of point in range withβ-cell function and insulin sensitivity of type 2 diabetes mellitus in cold areas

Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.

Low ambient temperature and air pollution are associated with hospitalization incidence of coronary artery disease:Insights from a cross-sectional study in Northeast China

Background:Previous studies have established a link between fluctuations in climate and increased mortality due to coronary artery disease(CAD).However,there remains a need to explore and clarify the evidence for associations between meteorological changes and hospitalization incidences related to CAD and its subtypes,especially in cold regions.This study aimed to systematically investigate the relationship between exposure to meteorological changes,air pollutants,and hospitalization for CAD in cold regions.Methods:We conducted a cross-sectional study using hospitalization records of 86,483 CAD patients between January 1,2009,and December 31,2019.Poisson regression analysis,based on generalized additive models,was applied to estimating the influence of hospitalization for CAD.Results:Significant associations were found between low ambient temperature[-10℃,RR=1.65;95%CI:(1.28-2.13)]and the incidence of hospitalization for CAD within a lag of 0-14 days.Furthermore,O_(3)[95.50μg/m^(3),RR=12;95%CI:(1.03-1.21)]and NO_(2)[48.70μg/m^(3),RR=1.0895%CI:(1.01-1.15)]levels were identified as primary air pollutants affecting the incidence of CAD,ST-segment-elevation myocardial infarction(STEMI),and non-STEMI(NSTEMI)within the same lag period.Furthermore,O_(3)[95.50μg/m^(3),RR=1.12;95%CI:(1.03-1.21)]and NO_(2)[48.70μg/m^(3),RR=1.0895%CI:(1.01-1.15)]levels were identified as primary air pollutants affecting the incidence of CAD,ST-segment-elevation myocardial infarction(STEMI),and non-STEMI(NSTEMI)within the same lag period.The effect curve of CAD hospitalization incidence significantly increased at lag days 2 and 4 when NO_(2)and O_(3)concentrations were higher,with a pronounced effect at 7 days,dissipating by lag 14 days.No significant associations were observed between exposure to PM,SO_(2),air pressure,humidity,or wind speed and hospitalization incidences due to CAD and its subtypes.Conclusion:Our findings suggest a positive correlation between short-term exposure to low ambient temperatures or air pollutants(O_(3)and NO_(2))and hospitalizations for CAD,STEMI,and NSTEMI.These results could aid the development of effective preparedness strategies for frequent extreme weather events and support clinical and public health practices aimed at reducing the disease burden associated with current and future abnormal weather events.

Clinical characteristics,management,and prevention of coronavirus disease 2019

Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly the emerging variants of the virus.The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome,thrombosis,abnormal angiogenesis,and multiple organ dysfunction.Despite only few licensed treatments to date,rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines.However,three pillars of preventative and control measures-proactive contact tracing,wearing facial masks,and social distancing-are essential to combat the ongoing pandemic.As the number of patients recovering from COVID-19 rapidly increases,the world has entered the era of caring for patients during the convalescence phase.This phase still represents a largely unmet medical need globally.

Network pharmacology-based approach for exploring the biotargets and mechanisms of vitamin A for the treatment of diabetic foot ulcers

Background:In some developing countries,people have little knowledge about the causes of diabetic foot ulcers.Therefore,public health education for patients on these conditions is a prerequisite for effective pharmacological treatment.Diabetic foot ulcers are a complex symptom of diabetes and are hard to cure due to the lack of efficacious medicine and alternative treatment approaches.Vitamin A(VA)is known to have potent biological functions,including skin repair and immunoregulation.However,the potential pharmacological effects and molecular mechanisms of VA on foot ulcers are still to be discovered.Methods:By using bioinformatic/computational analyses,including network pharmacology,gene ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis,we aimed to identify and reveal the pharmacological targets,molecular mechanisms,biological functions,and signaling pathways of VA in the treatment of diabetic foot ulcers.Results:A total of 66 intersection genes were identified as candidate targets of VA,which are related to diabetic foot ulcers.Therein,18 core genes/targets,namely JUN,MAPK1,THRB,MAPK14,MTNR1B,CXCR3,ESR1,AR,HDAC1,IL-10,CNR1,DRD2,EGFR,ADRA2A,CCND1,RXRB,RARA,and RXRA,were further identified.Furthermore,the biological processes,cell components,and molecular functions which may underlie the effects of VA against diabetic foot ulcers were characterized.Conclusion:Based on our findings,we concluded that the pharmacological effects of VA on diabetic foot ulcers primarily involve the promotion of cellular regeneration and proliferation and the inhibition of inflammatory response.The core genes/targets may potentially serve as promising biomarkers for the diagnosis of diabetic foot ulcers.

Cold exposure promotes coronavirus infection by altering the gut microbiota and lipid metabolism to reduce host immunity

Objective:Cold exposure has been suggested to be advantageous for the spread and infection of the coronavirus,and the gut microbiota influences the severity of the infection by modulating host inflammatory and immune responses.However,it remains unclear whether the promotion of viral infection through cold exposure is linked to the gut microbiota.Methods:In this study,we performed an unbiased analysis of gut microbiota,serum,and lung tissue metabolome changes in cold-exposed and virus-infected mice,alongside the assessment of immune-inflammatory indicators in serum and lung tissue.Results:The results revealed that both cold exposure and viral infection significantly decreased the percentage of peripheral blood lymphocytes(CD4^(+)T cells,CD8^(+)T cells,and B cell)and increased the expression of inflammatory factors(IL-6,IL-1β,TNF-α,and IFN-γ).Meanwhile,cold exposure disrupted the homeostasis of gut microbiota,elevating the abundance of pathogenic bacteria(Staphylococcus)and diminishing the abundance of beneficial bacteria(Alistipes).Notably,in virus-infected mice exposed to a cold environment,the reduction in the abundance of beneficial bacteria Alistipes was more pronounced than in cases of single virus infection and cold exposure.Analysis of altered serum and lung tissue metabolites highlighted glycerophospholipids,fatty acids,and eicosanoids as the most affected metabolites by cold exposure.These metabolites,closely associated with virus infection,exhibited a significant correlation with immune-inflammatory indicators.Conclusion:These findings establish a mechanistic connection between cold exposure and virus infection,suggesting that cold exposure-induced dysregulation of gut microbiota and lipid metabolism diminishes host immunity,promoting virus infection.

The effects of cold region meteorology and specific environment on the number of hospital admissions for chronic kidney disease:An investigate with a distributed lag nonlinear model

Objective:To explore the effects of daily mean temperature(°C),average daily air pressure(hPa),humidity(%),wind speed(m/s),particulate matter(PM)2.5(μg/m3)and PM10(μg/m3)on the admission rate of chronic kidney disease(CKD)patients admitted to the Second Affiliated Hospital of Harbin Medical University in Harbin and to identify the indexes and lag days that impose the most critical influence.Methods:The R language Distributed Lag Nonlinear Model(DLNM),Excel,and SPSS were used to analyze the disease and meteorological data of Harbin from 01 January 2010 to 31 December 2019 according to the inclusion and exclusion criteria.Results:Meteorological factors and air pollution influence the number of hospitalizations of CKD to vary degrees in cold regions,and differ in persistence or delay.Non-optimal temperature increases the risk of admission of CKD,high temperature increases the risk of obstructive kidney disease,and low temperature increases the risk of other major types of chronic kidney disease.The greater the temperature difference is,the higher its contribution is to the risk.The non-optimal wind speed and non-optimal atmospheric pressure are associated with increased hospital admissions.PM2.5 concentrations above 40μg/m3 have a negative impact on the results.Conclusion:Cold region meteorology and specific environment do have an impact on the number of hospital admissions for chronic kidney disease,and we can apply DLMN to describe the analysis.

Present situation of rational drug use in plateau area

Plateau is characterized by low oxygen,low pressure,strong radiation,cold and dryness,among which low oxygen is the main factor that affects the normal life activities of human body.Altitude hypoxia leads to significant changes in the metabolic characteristics of drugs in vivo,which in turn affects the efficacy and adverse actions of drugs.This paper summarizes the present situation of rational drug use in plateau area and pinpoints the existing problems.Meanwhile,we posit the strategies and measures for realizing rational and precise pharmacotherapy of plateau residents.First,we need to acquire a panoramic view of differential and relative pharmacokinetics and pharmacodynamics in between plateau area and plain area by carrying out comparative studies on drug metabolisms and on comprehensive drug efficacies and mechanisms.Second,we must apply the findings from basic research to clinical practice and formulate guidelines and recommendations of drug use for plateau habitants.Finally,we should eventually achieve precise and individualized drug use for plateau habitants based on their characteristic etiology and pathogenesis.

Multiple inducible thermogenic mechanisms in the development of cold acclimatization

Extreme cold environment can threaten human health and life through increasing the risk of myocardial infarction,stroke,frostbite,and hypothermia.Insufficient heat production to maintain core body temperature is a major cause of cold injury.To cope with cold stress,human and other mammals have developed the capacity of cold acclimatization to adapt to such a harsh environment.Adaptive non-shivering thermogenesis is a ubiquitous form of cold acclimatization.This review article systematically summarizes the role of three inducible thermogenic forms,including food intake,circadian rhythms,and cold exposure in mediating non-shivering thermogenesis under cold exposure and presents the potential interventions for minimizing the adverse health consequences of cold temperature.

The effects of cold stimulation and exercise on human health

Cold stimulation and exercise are two independent stimulus variables,each yielding unique impacts on human health.However,in many cases,individuals often encounter both factors simultaneously,particularly in colder regions where outdoor physical activity is prevalent.Despite numerous studies exploring the effects of cold exposure and exercise independently,only a limited number of comprehensive reviews have evaluated their combined influence on health.This review aims to bridge this gap by meticulously examining the potential benefits and detriments of both cold stimulation and exercise on human health.Specifically,the review focuses on their impacts on cardiovascular,respiratory,and immune function,as well as the favorable effects of moderate exercise on the human body.While evidence suggests that cold exposure can enhance health outcomes in certain disease contexts,it also poses risks,particularly for vulnerable populations.Furthermore,while moderate exercise is generally beneficial,engaging in physical activity in cold weather conditions can increase the risk of hypothermia,frostbite,and other cold-related injuries.Consequently,there is an urgent need to develop safe and effective guidelines for exercising in cold weather,particularly for individuals living in colder regions.This review emphasizes the necessity for further research on the combined effects of cold stimulation and exercise,with the goal of informing public health policies and guidelines for physical activity in cold weather conditions.

Comparisons of different statistical models for analyzing the effects of meteorological factors on COVID-19

Objective:This general non-systematic review aimed to gather information on reported statistical models examing the effects of meteorological factors on coronavirus disease 2019(COVID-19)and compare these models.Methods:PubMed,Web of Science,and Google Scholar were searched for studies on"meteorological factors and COVID-19"published between January 1,2020,and October 1,2022.Results:The most commonly used approaches for analyzing the association between meteorological factors and COVID-19 were the linear regression model(LRM),generalized linear model(GLM),generalized additive model(GAM),and distributed lag non-linear model(DLNM).In addition to these classical models commonly applied in environmental epidemiology,machine learning techniques are increasingly being used to select risk factors for the outcome of interest and establishing robust prediction models.Conclusion:Selecting an appropriate model is essential before conducting research.To ensure the reliability of analysis results,it is important to consider including non-meteorological factors(e.g.,government policies on physical distancing,vaccination,and hygiene practices)along with meteorological factors in the model.