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.

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.

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.

Climate is one of the environmental conditions on which people live. Climate conditions impact every aspect of people's daily life and production activities, even the survival of humankind. In recent years, human activities have adversely changed the climate. The emergence of global warming and extreme weather has prompted people to pay attention to the impact of climate on life. The adverse climate issues include reduced quality of air and food, facilitated spread of diseases and increased mortality of the population. Being more orientated to climate changes in the past, research has been less alerted to the negative impacts that climate changes could bring to human health. This could be ascribed to that after living in a region for a long time, the human body has "adapted" to climate. And after adaptation, routine health outcomes such as disease incidence and hospitalization rate become less obvious, making the habitants blind from the undesirable impacts of climate on the health status. This review article summarizes the impacts of cold climate on human development, including maternal/fetal factors, lifestyle factors, etc., and delineates the relationship between cold climate and human health.

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 40 μg/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.

Cryotherapy is a minimally invasive treatment. With increasing rate of breast cancer detection, ablation therapy has become an alternative approach for the treatment of this pathology due to its advantages of minimally invasive, fewer complications, good efficacy, and repeatability. Preclinical and clinical studies of cryotherapy for breast cancer published through December 2022 were identified through a literature search using PubMed, ClinicalTrials.gov, and CNKI. This article reviews the progress of cryoablation in the treatment of breast cancer.

Objective: Studies have shown that both short-term and long-term cold exposures disturb the biological process. The aim of the present study is to investigate the effects of intermittent cold exposure on proteomic profiles in the hypothalamus and pituitary of female Sprague-Dawley (SD) rats. Materials and methods: The rats were exposed to -10°C in a cabin for 4 h per day, and the treatment lasted for 14 days. The comparative label-free LC-MS/MS analysis was performed to investigate the changes of proteomic profiles in the hypothalamus and pituitary. ELISA analysis was used to validate the expression of differential proteins. Results: 22 differential proteins in the hypothalamus and 75 differential proteins in the pituitary were identified by the label-free proteomic analysis. Gene ontology annotation and enrichment analysis indicated that cold exposure disrupted protein phosphorylation, filopodium assembly, intracellular protein transport, peripheral nervous system neuron axonogenesis, spinal cord development, Golgi organization, positive regulation of pseudopodium assembly, and cell-cell adhesion. Three proteins (Cdc42, Ptprs, and Setd7) were down-regulated in the cold exposure group. Conclusion: The results indicate that intermittent cold exposure alters the proteomic profiles of hypothalamus and pituitary in female rats.

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 (I_hERG). 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.

Background: Myocardial infarctions (MI) is a major threat to human health especially in people exposed to cold environment. The polarization of macrophages towards different functional phenotypes (M1 macrophages and M2 macrophages) is closely related to MI repairment. The growth differentiation factor 11 (GDF11) has been reported to play a momentous role in inflammatory associated diseases. In this study, we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI. Methods: In vivo, the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery (LAD), and mice were randomly divided into the sham group, MI group, and MI+GDF11 group. The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography, triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue. In vitro, based on the RAW264.7 cell line, the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR, Western blot, and flow cytometry. Results: We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice. And GDF11 supplementation can improve the cardiac function. Moreover, GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice. Furthermore, the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance. At the cellular level, application of GDF11 could inhibit the expression of M1 macrophage (classically activated macrophage) markers iNOS, interleukin (IL)-1β, and IL-6 in a dose-dependent manner. In contrast, GDF11 significantly increased the level of M2 macrophage markers including IL-10, CD206, arginase 1 (Arg1), and vascular endothelial growth factor (VEGF). Interestingly, GDF11 could promote M1 macrophages polarizing to M2 macrophages. At the molecular level, GDF11 significantly down-regulated the Notch1 signaling pathway, the activation of which has been demonstrated to promote M1 polarization in macrophages. Conclusions: GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is incurable chronic disease which kills 3.3 million each year worldwide. Number of global cases of COPD is steadily rising alongside with life expectancy, disproportionally hitting middle-income countries like Russia and China, in such conditions, new approaches to the COPD management are desperately needed. DNA microarray technology is a powerful genomic tool that has the potential to uncover underlying COPD biological alteration and brings up revolutionized treatment option to clinicians. We executed systematic review studies of studies published in last 10 years regarding DNA microarray application in COPD management, with complacence to PRISMA criteria and using PubMed and Medline data bases as data source. Out of 920 identified papers, 39 were included in the final analysis. We concluded that Genome-wide expression profiling using DNA microarray technology has great potential in enhancing COPD management. Current studied proofed this method is reliable and possesses many potential applications such as individual at risk of COPD development recognition, early diagnosis of disease, COPD phenotype identification, exacerbation prediction, personalized treatment optioning and prospect of oncogenesis evaluation in patients with COPD. Despite all the proofed benefits of this technology, researchers are still in the early stage of exploring it’s potential. Therefore, large clinical trials are still needed to set up standard for DNA microarray techniques usage implementation in COPD management guidelines, subsequently giving opportunity to clinicians for controlling or even eliminating COPD entirely.

Background: Taxus cuspidata S. et Z. is a precious species of frigid zone plant belonging to the Taxaceae family, which possesses anticancer, anti-inflammatory, hypoglycemic, and antibacterial pharmacological properties. While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities, whether Taxus cuspidata S. et Z. has skin-protective actions against injuries remained unknown. This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition, oxidation, inflammation, and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage. Methods: Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis method. Antioxidant capacity was evaluated by measuring superoxide dismutase (SOD) concentration and glutathione (GSH) content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay kit. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4 (GPX4). Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in mice. In a mouse model of skin allergy induced by 4-aminopyridine (4-AP), allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay (ELISA) kits. Two proinflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by qRT-PCR. Hematoxylin and eosin (HE) staining was conducted to assess the degree of skin lesion. Results: All three Taxus extracts including Taxus chinensis essential oil, Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals, of which Taxus chinensis essential oil produced the greatest effect. In contrast, the three Taxus extracts elevated SOD and GSH levels in the skin tissues, and the highest increase was seen with Taxus chinensis essential oil. Three Taxus extracts, especially Taxus chinensis essential oil, effectively reduce the rate of ear and paw swelling. All three Taxus extracts reduced the number of body licks, the levels of TNF-α and IL-1β, and the histamine content in tissue homogenates of mice and alleviated skin damage. Consistently, Taxus chinensis essential oil yielded the greatest magnitude of decreases. Conclusion: While all three Taxus extracts possessed the anti-skin melanin deposition, oxidation, and allergy properties, Taxus chinensis essential oil produced the superior effects.

Objective: Clinical manifestation of the inflammatory process in its relation to biochemical markers (total cysteine [Cys], cysteine-glycine [CysGly], glutathione [GSH], glutamate-cysteine [Glu-Cys], homocysteine [Hcy], the ratio of reduced to oxidized glutathione [GSH/GSSG], the ratio of reduced to oxidized cysteine [CySH/CySS], malondialdehyde-oxidized low-density lipoproteins [MDA-oxLDL]) has been studied in patients with coronavirus disease 2019 (COVID-19). Material and methods: 48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research. The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6 (IL-6). Results: All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6 (by 54.6%). There was no comorbidity in patients with mild COVID-19 (nasopharyngitis symptoms) and in healthy control subjects. 50% of patients with lung damage had accompanying diseases. Alterations of aminoethyl metabolism were detected in COVID-19 patients: as reflected by the decreased levels of Cys, CysGly, and Glu-Cys and the increased levels of GSH as compared to the control group. Conclusion: Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation, specifically MDA-oxLDL.

Kashin-Beck disease (KBD) is an endemic osteoarthropathy. Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer, long frost period, and large temperature differences between day and night. In particular, KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns. Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas. Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather. The epidemiological characteristics of KBD include agricultural area, early age of onset, gender equality, family aggregation, regional differences, and annual fluctuations. A series of preventive measures have been successfully taken in the past decades. National surveillance data indicate that the annual incidence of KBD is gradually declining.

Developmental disorders (DDs) are a kind of chronic maladies, which can cause serious irreversible detriment to children’s physical and mental health. It is predominantly regulated by the interaction of environment and heredity. Cold regions are mainly located in the high latitudes of China. Their living environment is characterized by frequent cold wave, huge temperature difference, severe air pollution, high calorie diet, less exercise, smoking, drinking, etc. In recent years, substantial advances have been made in studies of the correlation between the living environment features in cold regions and the DDs. Accordingly, this article reviews the impact of the peculiar living environment of cold regions on DDs, with a view to provide fresh prevention strategies for reducing the morbidity of DDs in China cold regions by ameliorating living environment.

The gut microflora is a combination of all microbes in intestine and their microenvironment, and its change can sensitively reflect the relevant response of the body to external environment and remarkably affect body's metabolism as well. Recent studies have found that cold exposure affects the body's gut microflora, which can lead to changes in the body's metabolism of glucose and lipid. This review summarizes recent research on the effects of cold exposure on gut microbes and metabolism of glucose and lipid, aiming to provide some new ideas on the approaches and measures for the prevention and treatment of diabetes and obesity.