Because of the overbearing low temperature, cold areas increase the morbidity and mortality of chronic non-communicable diseases (chronic diseases) in exposed populations. With the growth of the aging population and the superposition of lifestyle risk factors, the number of people with chronic diseases in cold areas is climbing, and the family and social burdens are rising. These health-threatening circumstances in the cold areas render the general practitioners to face serious challenges and difficulties in the community management of chronic diseases. This paper summarizes the current situation of chronic disease management in cold areas and explores the relevant management models so as to provide a useful reference for regional health construction, graded diagnosis and treatment, and prevention and control of chronic diseases in China.

Thrombotic diseases are the leading causes of death worldwide, especially in cold climates. Traditional Chinese medicine (TCM)-based therapies have gained increasing popularity worldwide, but also raised some concerns about its efficacy, safety profile and exact mechanisms. TCM has been traditionally used in the management of thrombosis and convincingly proven effective in modifying thrombosis progression, particularly the platelet function, coagulation system and fibrinolytic system. This review article focuses on TCM regulation of thrombosis with brief discussion on the fundamental aspects and relevant background information for better understanding of the subject. In addition to its antithrombotic effects, we will dive insight into the cellular and molecular mechanisms of TCM as pharmacological regulators of platelet aggregation, coagulation, and fibrinolysis. With increasing awareness and understanding of the benefits and potentials of TCM, TCM products will in no doubt gain its broader applications in the treatment of thrombosis and associated disorders, which in turn will deepen our understanding of its pharmacological and molecular mechanisms. Finally, current review provides a perspective view on the future directions to TCM research on thrombosis.

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.

Hypertension is the most common cardiovascular condition in clinical practice and a major risk factor for stroke and cardiovascular events. There are more than 270 million hypertension patients in China, and the prevalence of hypertension in the high-latitude cold areas is significantly higher than in the low-latitude warm areas. The unique epidemiological characteristics and risk factors of hypertension in the cold regions of China urge for establishment of the prevention and control system for targeted and more effective management of the condition.

Objective: Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results: Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1°C), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1°C). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion: TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

With the global population aging, especially in China, the prevention and management of osteoporotic fragility fractures has become increasingly important. Bone mineral density (BMD) is an important index of osteoporotic fracture risk, which has become aroutine measurement inclinical practice and thus formed the cornerstone in monitoring treatment efficacy of osteoporosis. In the past 30 years, several pharmacologic therapies have been developed to increase BMD and reduce osteoporotic fractures, especially vertebral fractures. However, the management of nonvertebral fractures and hip fractures remains challenging as low BMD is only one of the multi-factors for these conditions. Hip fractures mainly result from a fall and its incidence is higher in the frigid zone due to low temperature affecting neuromuscular function and high latitude with less sunlight, the conditions rendering less active vitamin D conversion, apart from increased falling. In this paper, we focus on two therapeutic strategies targeting both skeletal and non-skeletal factors, that is, Tai Chi (TC) exercise for improving balance and "kidney-tonifying" traditional Chinese medicine (TCM) against muscle atrophy. TC is a mind-body exercise that has the potential as an effective and safe intervention for preventing fall-related fractures in the elderly. This makes it a promising and feasible physical activity for the elderly in frigid zone to prevent osteoporotic fractures. Several TCM formula popular in northeast of China within frigid zone are also introduced. They are reportedly effective in maintaining or improving BMD and muscle strength with the potential of reducing osteoporotic fracture. However, more rationally designed vigorous basic investigations and prospective clinical trials are highly desired to validate and consolidate the preliminary observations in the future.

In recent years, cryotherapy has gained increasing acceptance as a treatment for prostate cancer, offering complementary therapeutic benefits when combined with radical surgery and radiotherapy. Despite the potential for surgical complications, it stands as a safe and viable therapeutic modality. Cryotherapy provides an efficient approach for elderly patients, especially those with compromised physical conditions and individuals experiencing recurrence after initial treatment. It has shown promise in extending survival periods and improving the overall quality of life for these patients. This article aims to comprehensively examine the developmental trajectory, surgical techniques, indications, therapeutic outcomes, and potential complications associated within prostate cancer treatment.

Osteoarthritis is a common chronic irreversible joint disease characterized by degenerative changes of articular cartilage and secondary hyper osteogeny. Knee osteoarthritis(KOA) affects not only the articular cartilage, but also the entire joint, including subchondral bone, joint capsule, synovial membrane, meniscus, ligaments, periarticular muscles, and tendons. The primary aim of treatment is to relieve symptoms, delay joint degeneration, and maximally maintain patient's quality of life. There are many risk factors contributing to the development of KOA, including climate. This review will discuss the relationship between climate in cold region and KOA and the possibility of modifying risk factors such as the environment for the prevention and treatment of KOA.

Cardiovascular diseases (CVDs) have been the top-ranked cause of human death in the world for years, according to the World Health Organization. Accumulating evidence from epidemiological data supports the view that the risk of CVDs is higher in northern China than in southern area. There is no doubt that living environment has become a crucial factor contributing to the occurrence and progression of CVDs in northern region. However, there have not been any clinical guidelines for the prevention strategy of environment-related CVDs, especially for cold exposure. Thus, there is an urgent need for better understanding of the clinical characteristics and underlying mechanisms of cold-induced CVDs in order to formulate and implement proper and effective measures for minimizing the risk of CVDs for people residing in low-temperature area. Cold exposure, air pollution, lack of sunlight and irrational diet are believed to be crucial factors responsible for environment-related CVDs, and preventive measures might be carried out accordingly to decrease the high risk of CVDs in northern China.

While osteoporosis is a chronic disease caused by multiple factors, it is also a risk factor for fractures. At present, numerous risk factors for osteoporosis and secondary fractures have been identified, including sunlight, physical fitness, gender, age, trauma, dietary habits, tobacco, alcohol, drugs, air quality, and genetics. Despite that factors such as long winters, short daylight hours, less daily physical activity, air pollution, low calcium and high salt diet, and sedentary lifestyle could negatively impact the bones of residents in the alpine regions of northern China, the direct effect of low-temperature stimulation on bone growth and development remains unclear. In this study, by reviewing current research progress related to osteoporosis and fracture risk in northern China, we proposed appropriate preventive measures for different risk factors to reduce the occurrence of osteoporosis and fracture in cold areas of northern China.

Among the vast resources of traditional Chinese medicine (TCM) herbal species, only a handful of Chinese herbs are growing in frigid regions or extreme environment but they have a unique property. The most recognizable TCM herb falling in this category is Panax ginseng, which is widely considered the representative tonic herb with oceans of beneficial effects on human health. In this article, we will introduce several typical Chinese herbal medicines with beneficial effects aiming to arouse broader attention from the scientific community to expand the exploration and exploitation on this for their potential applications to meet the increasingly demanding medical needs.

Eukaryotes and microbiota produce H₂S, using the same substrates and enzymes which constitute the reverse-trans-sulfuration and transsulfuration pathways. The homeostasis of gut microbiota impacts on the structural and functional integrity of gut epithelial barrier. Microbiota also serve as signalling sources to inform the host of the metabolism and functional changes. Microbiota dysbiosis negatively affect human health, contributing to diseases like obesity, diabetes, inflammatory bowel diseases, and asthma. Not by coincidence, these pathological conditions are also closely related to the abnormal metabolism and function of H₂S signalling.H₂S serves as a bacterial signal to the host and the host-produced H₂S impacts on the population and size of microbiota. These bi-directional interactions become especially important for the digestion and utilization of sulfur amino acid in diet. Dietary restriction of sulfur amino acid increases the endogenous production of H₂S by the host and consequently offers many health benefits. It, on the other hand, decreases the nutritional supply to the microbiota, which could be remedied by the co-application of prebiotics and probiotics. It is strategically sound to target the expression of H₂S-producing enzymes in different organs to slow aging processes in our body and promote better health.

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.

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.

Acute liver injury (ALI) is characterized by apoptosis, inflammation, and oxidative stress, and pathogenic mechanism of ALI is poorly understood. Apoptosis-stimulating of p53 protein 1 (ASPP1) is involved in environmental responses, tumor growth, and NF-_KB activity, which is of critical importance to ALI. However, the role of ASPP1 in ALI remains largely unexplored. The current study aimed to determine the role of ASPP1 in ALI induced by CCl4 and the underlying mechanism. ASPP1 expression was detected in wild type (WT) mice with ALI induced by CCl4. The function of ASPP1 in ALI induced by CCl4 was investigated using conventional knockout ASPP1 mice. ASPP1 expression significantly increased in ALI mice at 24 hours after CCl4 injection. Deletion of ASSP1 ameliorated apoptosis, inflammation, and necrosis in ALI relative to WT mice. In addition, deficiency of ASPP1 improved liver flood flow as well as ALT and AST levels. The levels of phosphorylated p65 and phosphorylated IκBα were lower in ASPP1-/- mice than in WT mice with ALI. These results implicate that deletion of ASPP1 may act via inhibition of the NF-кB pathway and protect mice from ALI, which may be a new potential therapeutic target for the treatment of ALI.

Cold exposure increases the risk of adverse events related to cardiovascular causes, especially in the elderly. In this review, we focus on recent findings concerning the impact of aging on the regulatory mechanisms of cold-induced cardiovascular responses. In response to cold exposure, the initial physiological thermoregulation in healthy young persons, such as cutaneous vasoconstriction to reduce heat loss, is attenuated in older individuals, resulting in a reduced ability of the older persons to maintain body temperature in cold environment. Impaired sympathetic skin response, reduced noradrenergic neurotransmitter synthesis, insufficient noradrenergic transmitters, and altered downstream signaling pathways inside the vascular smooth muscle may be among the underlying mechanisms for the maladaptive vasoconstrictive response to cold stress in the elderly. The increase in blood pressure during cold exposure in young persons may be further augmented in aging adults, due to greater central arterial stiffness or diminished baroreflex sensitivity with aging. Cold stress raises myocardial oxygen demand caused by increased afterload in both young and old adults. The elderly cannot adjust to meet the increased oxygen demand due to reduced left ventricular compliance and coronary blood flow with advancing age, rendering the elderly more susceptible to hypothermiainduced cardiovascular complications from cold-related diseases. These age-associated thermoregulatory impairments may further worsen patients' health risk with existing cardiovascular diseases such as hypertension, coronary artery disease, and heart failure. We searched PubMed for papers related to cold stress and its relationship with aging, and selected the most relevant publications for discussion.