摘要：Objective: Long noncoding RNAs (lncRNAs) play an important role in regulating the occurrence and development of cardiovascular diseases. However, the role of lncRNAs in heart aging remains poorly understood. The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging.Materials and methods: Echocardiography was used to detect the cardiac function of 18-months (aged) and 3-months (young) old C57BL/6 mice. Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs, and qRT-PCR to verify the highly dysregulated lncRNAs. Results: Our results demonstrated that the heart function in aged mice was impaired relative to young ones. Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated, and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts. Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function, cell proliferation, copper ion response, and cellular cation homeostasis. KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, and the NF-kappa B signaling pathway. Conclusion: These results imply that the differentially expressed lncRNAs may regulate the development of heart aging. This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.

摘要：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(SiO2)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-1α and UCP1 was upregulated upon cold exposure(P＜0.05),but downregulated by SiO2 NPs(P＜0.05).The results demonstrated that there was antagonistic effect between SiO2 NPs and cold exposure on the plasticity genes and metabolism genes in brown adipocytes,where the main effects of SiO2 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)-α were upregulated by SiO2 NPs or cold exposure(P＜0.05).The factorial analysis indicated that there was also antagonistic effect between SiO2 NPs and cold exposure on the toxic effects in brown adipocytes,in which the main effects of cold exposure and/or SiO2 NPs on the toxic effects were significant(P＜0.05).Conclusion:SiO2 NPs inhibit the effect of cold exposure on metabolic genes and inflammatory responses genes in brown adipocytes.

摘要：Metformin as the first-line treatment for type 2 diabetes mellitus has been discovered to exert beneficial effects on many diseases for nearly ten years, but its specific mechanism is still unclear. As a new class of gene expression regulators with pleiotropic properties, microRNAs (miRNAs) participate in multiple physiological processes such as cell differentiation, proliferation, survival, and metabolism, which drive them to play a regulatory role in the occurrence, development and even treatment of various diseases. A substantial body of research has found the relationship between metformin and miRNAs, in which metformin can alter the expression profiles of miRNAs in multiple disease states and on the other hand the signal pathways involving miRNAs may contribute to the pharmacological actions of metformin. This review summarizes the effects of metformin on miRNAs and their relationship in different diseases (like tumor, metabolic diseases, etc.), which should be of a great help for our better understanding of the mechanism of metformin for treating multiple diseases.

摘要：Objective: To study the incidence and risk factors of hyperuricemia in young males who rapid entered into the plateau of 4500 m. Methods: The study contained 390 males aged 18-35 years (21.6 ± 2.5 years), who rapidly entered the plateau with an altitude of 4500 m. According to their basic level of uric acid (UA), they were divided into two groups, high uric acid (HUA) group and normal uric acid (NUA) group. The characteristics and physiological index, such as the body weight and the height, of them were recorded. For the test of the biochemical indicators, the venous blood samples were collected at the altitude of 4500 m in the morning. The count of blood cells, blood urea nitrogen (BUN), serum creatinine (SCR), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IDBIL) were compared between the two groups. Results: The incidence of hyperuricemia was 65.1％ (254/390) at 4500 m. At the altitude of 4500 m, the mean hemoglobin concentration (MCHC) of red blood cells in the HUA group was significantly lower than that in the NUA group. Hemoglobin (HGB), mean red blood cell volume (MCV), TBIL, IDBIL, BUN, SCR and LDH in the HUA group were significantly higher than those in the NUA group, though without statistically significant differences in the other variables. Meanwhile, multivariate analysis showed at the altitude of 4500 m, the risk of HUA increased by 0.982, 1.038 and 1.045 times when MCHC decreased by one unit and TBIL and SCR increased by one unit, respectively. Conclusion: The incidence of hyperuricemia was high of 65.1％ rush entry into the plateau of young male. Decreased MCHC and elevated TBIL and SCR were independent risk factors for hyperuricemia when rapid enter into 4500 m.

摘要：A frigid zone is usually a region of low latitude or high altitude. In terms of temperature, the criterium for defining a frigid zone is that the average temperature of the coldest month is below 0℃. In China, the frigid zone accounts for 43.5％ of the total land area; therefore, health management and disease research in frigid zone are universal and necessary.

摘要：Objective: There exist conflicting data on the efficacy and safety of ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome (ACS). We performed a meta-analysis to evaluate whether ticagrelor or clopidogrel produces better outcomes for East Asian patients with ACS. Methods: We searched for randomized controlled trials reporting associations between ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome in PubMed, EMBASE, web of science and Cochrane central register of controlled trials. Results: Ten studies involving 3715 participants were qualified for our analysis. The major adverse cardiovascular events (MACE) were significantly decreased in patients with ticagrelor treatment compared to those with clopidogrel (risk ratio [RR]: 0.61; 95％ confidence interval [CI]: 0.38-0.98; P = 0.042). There was no significant difference in all-cause death (RR: 0.89; 95％ CI: 0.61-1.29; P = 0.540), cardiovascular death (RR: 0.86; 95％ CI: 0.58-1.27; P = 0.451), myocardial infarction (RR: 0.91; 95％ CI: 0.65-1.27; P = 0.575) and stroke (RR: 0.77; 95％ CI: 0.44-1.36; P = 0.372) between ticagrelor and clopidogrel. Ticagrelor was associated with a significantly higher risk of bleeding compared to clopidogrel (RR: 1.71; 95％ CI: 1.37-2.13; P = 0.000). Conclusion: The present meta-analysis demonstrates that ticagrelor reduced the incidence of MACE in ACS patients from East Asia compared with clopidogrel. However, it increased the risk of bleeding.

摘要：Background: Apelin, an endogenous ligand of G-protein coupled receptor (GPCR), is a secreted peptide involved in the development of various tumors. However, the relationship between apelin and non-small cell lung cancer (NSCLC) is not quite clear. This study was designed to investigate the effect and mechanism of apelin on cell proliferation, migration and invasion of NSCLC cells. Methods: Twelve NSCLC specimens were collected for hematoxylin-eosin (HE) staining and immunohistochemistry analyses. Cell proliferation was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell migration and invasion were assessed using wound-healing and transwell assays. The subcellular location of yes associated protein 1 (YAP1) in A549 cells was determined by immunofluorescence. The mRNA and protein levels in NSCLC tissues and cell lines were measured by qRT-PCR and western blot, respectively. Results: Apelin was upregulated in tumor tissues compared with the adjacent tissues. Apelin promoted proliferation, migration, and invasion of A549 and H460 cells, which was reversed by competitive apelin receptor (APJ) antagonist ML221. Additionally, apelin upregulated YAP1 expression, whereas silence of YAP1 by small interfering RNA (siRNA) attenuated apelin-induced cell proliferation, migration and invasion and suppressed epithelial-mesenchymal transition progression. Conclusion: Apelin promotes NSCLC cells proliferation, migration, and invasion by modulating YAP1 and might be a potential therapeutic target for NSCLC treatment.

摘要：Objective: Sorafenib resistance has been a major factor limiting its clinical use as a targeted drug in liver cancer. The present study aimed to investigate whether cryptotanshinone can enhance the sensitivity of liver cancer and reduce the resistance to sorafenib.Methods: Sorafenib-resistant cells were established based on HepG2 and Huh7 cell lines. And the anti-tumor effect of sorafenib combined with cryptotanshinone on the sorafenib-resistant cells was verified by MTT, colony formation, transwell assays and tumor growth xenograft model. Moreover, the effects of the combined treatment on the expression of phosphorylated (p)-STAT3, as well as epithelial mesenchymal transition (EMT) and apoptosis related proteins of cells were evaluated by western blot analysis. Results: It was identified that cryptotanshinone inhibited the viability of both HepG2 and Huh7 cells in a dose- and time-dependent manner, and decreased p-STAT3 expression rather than total STAT3 expression at a concentration of 40 μmol/L. In the sorafenib-resistant cells, sorafenib in combination with cryptotanshinone markedly inhibited cell viability, invasion and migration compared with sorafenib alone. In contrast, increased p-STAT3 level by colivelin led to the inhibition of the synergistic effect of cryptotanshinone and sorafenib not only on cell viability, but also on EMT and apoptosis, suggesting that cryptotanshinone and sorafenib may act by downregulating STAT3 signaling. Further, the inhibition of carcinogenicity effect was also verified in xenografted tumor models. Conclusion: The present results indicated that cryptotanshinone could synergize with sorafenib to inhibit the proliferative, invasive, and migratory abilities of sorafenib-resistant cells by downregulating STAT3 signaling.

摘要：Objective: Present study aimed to explore the effects of intermittent cold-exposure (ICE) on culprit plaque morphology in patients with ST-segment elevation myocardial infarction (STEMI) in frigid zone.Methods: Totally 848 STEMI patients with plaque rupture (N = 637) or plaque erosion (N = 211) were enrolled consecutively according to optical coherence tomography imaging. Data on the changes of outdoor air temperature corresponding to 24 solar terms were collected. Patients were divided into different groups according to 24 solar terms and the number of days with indoor central heating. Imaging data were measured and analyzed qualitatively and quantitatively. Statistical analysis was conducted to elucidate the possible association of the STEMI patients of different groups with plaque morphology of culprit vessel with alterations of ambient temperature. Results: The incidence of both plaque rupture and plaque erosion presented trough in summer. The incidence of plaque rupture reached a peak value in early winter when outdoor air temperature dropped below 0℃ and declined with supply of central heating. Persistent cold exposure in early winter was positively and significantly associated with plaque rupture. The incidence of plaque erosion presented a peak in severe winter with outdoor air temperature dropping below -20℃ and steady supply of central heating. ICE in severe winter was positively and significantly associated with plaque with intact intima, especially in aged male or current smoking patients. The positive correlation of cold exposure with lipid size in culprit plaque in winter weakened with central heating. Conclusion: ICE resulted from switching staying in between outdoor cold environment and indoor warm temperature with central heating in severe winter changed culprit plaque morphology in STEMI. Plaque rupture decreased whereas plaque erosion increased impacted by ICE. The effect of ICE on the transformation of plaque morphology might be explained by reduced lipid deposition.

摘要：Objective: To evaluate the inflammatory pattern and the interferon (IFN) -γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods: We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results: Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r =-0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion: In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.

摘要：Hibernation is an adaptive behavior for some small animals to survive cold winter. Hibernating mammals usually down-regulate their body temperature from ～37℃ to only a few degrees. During the evolution, mammalian hibernators have inherited unique strategies to survive extreme conditions that may lead to disease or death in humans and other non-hibernators. Hibernating mammals can not only tolerant deep hypothermia, hypoxia and anoxia, but also protect them against osteoporosis, muscle atrophy, heart arrhythmia and ischemia-reperfusion injury. Finding the molecular and regulatory mechanisms underlying these adaptations will provide novel ideas for treating related human diseases.

摘要：1 Cold stress reshapes the immune status The winter of 2019 marked history with the advent of the COVID-19 Coronavirus pandemic; Cross-country skiers are more susceptible to asthmatic symptoms than their peers in warmer places[1].

摘要：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.

摘要：The management of chronic kidney disease (CKD) patients in cold areas is an important task in the daily practice of primary medical and health institutions. An important way to reduce the burden of CKD is to achieve early identification of and implement timely intervention on the relevant risk factors. Studies have shown that diet, alcohol, tobacco, air, sedentary and other factors in cold areas have negative impacts on human kidneys; yet, our current understanding of the effect of cold stimulation on CKD remains blurry. This paper introduces the research progress of risk factors related to CKD in cold areas and analytically summarizes the pathogenesis of CKD caused by cold stimulation, aiming to provide a reference work for the prevention, screening, evaluation, and management of CKD in cold areas.

摘要：Objective: Myocardial infarction (MI) remains the leading cause of morbidity and mortality due partly to the limited regenerative capacity of cardiomyocytes to replace cardiomyocyte lost due to apoptosis. Inhibiting cardiomyocyte apoptosis is recognized as an effective therapeutic approach for MI. MicroRNAs (miRNAs, miRs), which regulate target genes at the post-transcriptional level, play a significant role in the regulation of cardiovascular diseases such as MI. MicroRNA-135b (miR-135b) has a protective effect on cardiomyocytes. However, the role of miR-135b in cardiomyocyte apoptosis in infarct myocardium needs further clarification. Methods: We generated α-MHC-miR-135b transgenic mice to investigate the role of miR-135b in myocardial injury after MI. MiR-135b mimic and negative control (NC) were transfected into H2O2-induced cardiomyocytes to evaluate the effect of overexpression of miR-135b on the levels of reactive oxygen species (ROS) and apoptosis. Results: Our results showed that overexpression of miR-135b had protective effect on cardiomyocyte injury both in vivo and in vitro. MiR-135b inhibited cardiomyocyte apoptosis and ROS generation, downregulated pro-apoptosis proteins (cleaved-caspase-3 and Bax), and increased anti-apoptosis protein (Bcl-2). Moreover, miR-135b showed an inhibitory effect on apoptosis-related protein target transient receptor potential vanilloid-type 4 (TRPV4) cation channel. Conclusion: MiR-135b might be considered a new molecular target for potential replacement therapy as antiapoptotic cardioprotection in the setting of MI.

摘要：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.

摘要：Extreme weather events and climate change have witnessed a substantial increase in recent years,leading to heightened concerns.The rise in abnormal ambient temperatures,both in intensity and frequency,directly and indirectly impacts cardiovascular health.While the impact of high ambient temperatures on cardiovascular response is a common concern in the context of global warming,the significance of low temperatures cannot be overlooked.The challenges posed by low temperatures contribute to increased cardiovascular morbidity and mortality,posing a significant threat to global public health.This review aims to provide an overview of the relationship between low ambient temperature and cardiovascular health,encompassing the burden of cardiovascular outcomes and underlying mechanisms.Additionally,the review explores strategies for cold adaptation and cardioprotection.We posit that to optimize cold adaptation strategies,future research should delve deeper into the underlying mechanisms of cardiovascular health in response to low ambient temperature exposure.

摘要：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.

摘要：Growing evidence demonstrate that cold stimulation as a nonpharmacological strategy can be applied to prevent the development of ageing. However, the optimal ambient temperature to mammals and the mechanism for low temperature to extend lifespan remain poorly understood. In this editorial, we highlight the data presented by Hyun et al. suggesting that a beneficial role of moderate cold temperature in reducing disease-related aggregation thereby age-related deteriorations[1].

摘要：1 The ever-growing crisis imposed by Omicron The global corona virus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for more than 3 years and resulted in about 657 million infections and 6.6 million deaths as of date 05 January, 2023 ( The latest variant of concern (VoC), Omicron, is leading a new wave of infections globally[1]. Although small molecule inhibitors are emerging to show antiviral activities for SARS-CoV-2[2-3], only limited drugs have been approved (e.g., remdesivir and baricitinib). Vaccination remains the preferred protection method, however, extra vaccine dose is often required to effectively neutralize Omicron[4];especially for the continuous evolution SARS-CoV-2 variants by constant mutations, escape from neutralizing antibodies is still a major concern that challenges the effectiveness of existing vaccines[5]. This global public health crisis urgently demands developing effective antibodies against the Omicron.