摘要：Objective:The aim of this study was to identify biomarkers associated with immunity and prognosis in patients with cervical cancer.Materials and methods:Data from patients with cervical squamous cell carcinoma(CESC)were retrieved from the UCSC Xena database and subjected to analysis.Gene sets representing 22 types of immunocytes were acquired,and immunocytes relevant to prognosis were identified.Weighted gene co-expression network analysis(WGCNA)was utilized to identify gene modules associated with prognosis-related immunocytes and to construct immune-related gene markers.Differentially expressed genes were then screened,and the association between immune score and biological function of immune-related gene markers was analyzed.Furthermore,tissue samples from cervical cancer patients in Northeast China were collected to validate the expression of two genes using real-time PCR and immunohistochemistry.Results:This study identified 10 immunocytes significantly correlated with overall survival time in patients.Six gene modules were identified as significantly associated with prognosis-related immunocytes,with gene module 6 showing relevance to all prognosis-related immunocytes.Gene module 6 was related to all prognosis-related immunocytes.Moreover,two genes(including PLA2G2D and CHIT1)were found to be significantly associated with overall survival in cancer patients.Patients with CESC were classified into high and low immune score groups based on the median score of gene markers.Correlation analysis of the immune score and biological function was performed.Immunohistochemistry and real-time PCR results revealed high expression of CHIT1 and PLA2G2D in CESC tumor tissues.Conclusion:PLA2G2D and CHIT1 show promise as biomarkers for evaluating immune infiltration and prognosis in patients with cervical cancer.

摘要：Objective:The study aimed to explore the association between gut microbiota and anastomotic leakage(AL)after surgery in colorectal cancer(CRC)patients from a frigid zone,based on high-throughput sequencing.Methods:A total of 98 CRC patients admitted to the Second Affiliated Hospital of Harbin Medical University from July 2018 to February 2019,who met the inclusion criteria,were included.Among these,10 patients were diagnosed as AL.After propensity-score matching of baseline characteristics,10 patients from the anastomotic leakage group(AG)and 10 patients from the normal group(NG)were finally included in this study.Fecal samples were collected,and total DNA was extracted for high-throughput sequencing and bioinformatic analysis.Results:Alpha diversity analysis showed no significant difference between the two groups,while beta diversity analysis revealed significant differences in principal components.Differential microbiota were classified as Proteobacteria at the phylum level(P=0.021).At the genus level,the abundances of Streptococcus(P=0.045),Citrobacter(P=0.008)and Klebsiella(P=0.002)were significantly different between the two groups.LEfSe analysis indicated that these genera contributed most to the differences between the groups.Conclusion:The characteristics of the gut microbiota in the AG and NG were significantly different,and these differences might be associated with AL in CRC patients from frigid zones.

摘要：Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus (PDA) as to how and when to treat. We aimed to clarify this issue in very preterm infants (VPIs; < 32 weeks). Methods: This retrospective study included 1659 VPIs who were diagnosed with PDA according to echocardiographic examinations and cardiovascular dysfunction scoring system (the CVD scoring). The VPIs were classified into six groups (A1, A2, A3, B1, B2, and B3) based on CVD scores (A, < 3, and B, ≥ 3), and treatment with ibuprofen for PDA (1, conservational management; 2, early ibuprofen treatment; and 3, late ibuprofen treatment). Treatment was stopped when PDA was closed, CVD score was zero or PDA needed ligation. Results: VPIs with CVD scores < 3 had most PDA closure without surgery, and early ibuprofen treatment did not significantly affect PDA closure. VPIs with CVD scores ≥ 3 had some PDA closure after 2 courses of treatment, but closure rates decreased linearly with ibuprofen course (1st 75.2％, 2nd 62.3％, 3rd 50.0％, P < 0.0001), and early ibuprofen treatment (group B2) did not increase PDA closure compared to late ibuprofen treatment (group B3). In these same infants, the longer they were in CVD scores ≥ 3, the more the complications of preterm were increased (retinopathy of prematurity ROP 1st 16.5％, 2nd 23.8％, 3rd 29.6％, P = 0.016; bronchopulmonary dysplasia BPD 1st 15.5％, 2nd 26.7％, 3rd 33.8％, P < 0.0001; intraventricular hemorrhage IVH 1st 20.4％, 2nd 32.4％, 3rd 23.8％, P = 0.015). Conclusion: Ibuprofen is suggested for PDA closure when the PDA reopens or has developed into the stage when the CVD score ≥ 3.

摘要：Familial amyloidotic polyneuropathy (FAP) is a type of systemic amyloidosis characterized by peripheral and autonomic neuropathy. Although FAP is a typical autosomal dominant disorder caused by a point mutation in the TTR gene, the average age at onset varies significantly among different countries. This discrepancy clearly suggests that a combination of intrinsic factors as well as extrinsic (environmental) factors shapes the development of FAP. However, these factors are diffcult to analyze in humans, because detailed pathologic tissue analysis is only possible at autopsy. Thus, mouse models have been produced and used to disentangle these factors. This review covers the mouse models produced thus far and how these models are applied to analyze intrinsic and extrinsic factors involved in disease development and to test drug effcacy.

摘要：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.

摘要：Since the first outbreak of the coronavirus disease (COVID-19) in the winter of 2019, this pandemic has resulted in significant global social and economic disruption, as well as global public health and medical crises[1]. Climate, weather conditions, and even latitude have now been acknowledged to be directly associated with COVID-19 outbreaks[2-4]. It was reported that 60％ of the confirmed cases of COVID-19 occurred in areas where the air temperature ranged from 5℃ to 15℃[4]. These earlier research results strongly implied that the COVID-19 pandemic might spread cyclically and outbreaks might recur in large cities in the mid-latitudes (for example, the northern part of China) in autumn 2020[4], which has now been confirmed by the third wave of the pandemic. With quarantines and other restrictive legislations and control measures being put in action to contain the spread of the disease[5], the pandemic has also manifested additional obstacles in the treatment of other diseases. For example, a median dose delay of 14 (6-20) days was found in patients who received one cycle of gastric chemotherapy in our department from the first outbreak till the spring festival of 2020 (n = 79).

摘要：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.

摘要：Objective: It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine (VM) patients, and to explain the potential pathological effects of these biomarkers. The hypothesis of VM being a variant of migraine was examined. Methods: A total of 32 VM patients, 35 migraine patients, and 30 healthy control subjects (HC) were selected for this cross-sectional study. Detailed statistics on demographic data, clinical manifestations, calcitonin gene-related peptide (CGRP) and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions. Receptor operating characteristic (ROC) curve and area under the curve (AUC) were analyzed for biomarkers. The risk factors of VM and migraine were determined through univariate and multivariate analyses. Results: Compared with HC, serum CGRP levels (p(VM) = 0.012, p(Migraine) = 0.028) increased and Mg2+ levels (p(VM) < 0.001, p(Migraine) < 0.001) deceased in VM patients and migraine patients. In multiple logistic regression, VM was correlated with CGRP [odds ratio (OR) = 1.07; 95％ confidence interval (CI), 1.02-1.12; P = 0.01] and Mg2+ [odds ratio (OR) = 0.03; 95％ CI, 0.07-0.15; P < 0.001)]. Migraine was correlated with CGRP [odds ratio (OR) = 1.07; 95％ CI, 1.02-1.12; P = 0.01] and Mg2+ [odd ratio (OR = 0.01; 95％ CI, 0-0.02; P <0.001)]. Mg2+ discriminated good differentiation between VM and migraine groups, with AUC of 0.649 (95％ CI, 0.518 to 0.780). The optimal threshold for Mg2+ to diagnose VM was 0.805. Conclusions: This study demonstrated that CGRP and Mg2+ may be promising laboratory indicators to discriminate HC from VM/migraine, while Mg2+ may be uded as a discriminator between VM and migraine.

摘要：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 hypothermia-induced 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.

摘要：It is my great pleasure and distinct honor to be named Editor-in-Chief of Frigid Zone Medicine,a high-quality,open access,medical journal in the English language,sponsored by the Heilongjiang Health Commission under the supervision of the Heilongjiang Health Development Research Center.

摘要：Objective: China was the first country suffering from the SARS-CoV-2 pandemic and one of the countries with stringent mother-neonate isolation measure implemented. Now increasing evidence suggests that coronavirus disease 2019 (COVID-19) should not be taken as an indication for formula feeding or isolation of the infant from the mother.Methods: We conducted a retrospective cohort study in 44 hospitals from 14 provinces in China to investigate the management of neonates whose mothers have confirmed or suspected COVID-19. In addition, 65 members of Chinese Neonatologist Association (CNA) were invited to give their comments and suggestions on the clinical management guidelines for high-risk neonates. Results: There were 121 neonates born to 118 mothers suspected with COVID-19 including 42 mothers with SARS-CoV-2 positive results and 76 mothers with SARS-CoV-2 negative results. All neonates were born by caesarean section, isolated from their mothers immediately after birth and were formula-fed. Five neonates were positive for SARSCoV-2 at initial testing between 36 and 46 h after birth. Regarding the confusion on the clinical management guidelines, 58.78％ of the newborns were put into isolation, 32.22％ were subject to PCR tests, and 5.16％ and 2.75％ received breastfeeding and vaccination, respectively. Conclusion: The clinical symptoms of neonates born to mothers with confirmed SARS-CoV-2 were mild, though five neonates might have been infected in utero or during delivery. Given the favorable outcomes of neonates born to COVID-confirmed mothers, full isolation may not be warranted. Rather, separation of the mother and her newborn should be assessed on a case-by-case basis, considering local facilities and risk factors for adverse outcomes, such as prematurity and fetal distress.

摘要：Growing evidence has shown that exposure to low ambient temperature poses a huge challenge to human health globally. Actually, cold stress is closely associated with a higher incidence of cardiovascular morbidity and mortality in winter or in cold regions. Cellular and molecular mechanisms underlying cardiovascular complications in response to cold exposure have yet to be fully clarified. Considering that cold exposure is an important risk of cardiovascular complications, it is necessary to clarify the molecular mechanism of cold stress-induced cardiovascular diseases and to develop effective intervention strategies. Hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO) are well-known gasotransmitters that are endogenously produced in many biological systems. Accumulating studies have demonstrated that these gasotransmitters play a critical role in a wide spectrum of physiological and/or pathophysiological processes by regulating numerous signaling pathways. These gas signal molecules are emerging as important players in cardiovascular homeostasis, and disruption of these gasotransmitters is critically implicated in cardiovascular anomalies, such as hypertension, atherosclerosis, myocardial ischemia, heart failure, and stroke. Also, evidence is emerging that H2S, NO, and CO may be involved in the pathologies of cold stress-induced cardiovascular ailments. In this review, we aim to highlight and discuss the recent advances towards the development of gasotransmitters-based therapeutics for cold stress-related cardiovascular pathogenesis. We believe that the effects of H2S, NO, and CO on cardiovascular regulation under cold environment will attract tremendous interest in the near future as they serve as novel regulators of cardiovascular biology in cold environment.

摘要：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.

摘要：Introduction:Bioactive secondary metabolites from the microbes living in frigid,toxic or other extreme environments are emerging as a new medicinal resource.Here,we report the discovery of new antidiabetic and anti-inflammatory compounds with novel structures from endophytic fungi hosted toxic medicinal plant.Methods:The endophytic fungus isolated from toxic plants was fermented and extracted.The obtained extracts were purified with preparative HPLC to yield pure compounds.The purified compounds were examined by PTP1b inhibition and NO inhibition assays to evaluate their bioactivities.Results:One new tridepsides(Compound 1),one new benzeneacetic acid derivative(Compound 3)and five known compounds(Compounds 2 and 4-7)were isolated from the ethyl acetate extract of Colletotrichum gloeosporioides,an endophytic fungus obtained from a toxic medicinal plant Tylophora ovata.Their structures were determined by spectroscopic data(1D and 2D NMR,HRESIMS)analyses.Compound 2 showed significant inhibitory activity against PTP1 b with an IC50 value of 0.84 μM.Compounds 2 and 3 exhibited moderate inhibitory activities against the NO(nitric oxide)release in LPS-induced RAW 264.7 cells at 10 pM with percent inhibition of 39％and 33％,respectively.Conclusion:The Compound 2 has potent PTP1b inhibitory effect indicating its antidiabetic potential and thus might be considered a lead compound for antidiabetic drug development.

摘要：Background: Periapical endodontic surgery (PES) for root amputation and tooth replacement by immediate implant placement are two possible treatment options for bone lesions in the root apex of a tooth that has previously undergone endodontic treatment. Treatment methods are performed when the effectiveness of orthograde canal revision is questionable or when such treatment cannot be performed. The effectiveness of these methods varies from study to study.Objective: clinical evaluation of the efficacy of periapical endodontic surgery for root amputation and immediate implant placement with simultaneous tooth extraction in the proximate and long-term treatment. Materials and methods: The study included 183 patients between the ages of 24 and 63. Patients were divided into 2 groups; group I - endodontic surgery was performed to resect the apex of the tooth root (108 patients) and group Ⅱ- an operation to install an implant with simultaneous tooth extraction (75 patients). In group I, in 36 cases, PES was performed in the area of the first molars and premolars, and 72 cases in the area of incisors and canines. In group Ⅱ, 75 patients received 231 implants. Results: In all 108 patients of group I in the postoperative period and within 1 month, the wounds healed without complications. In none of the 36 operated premolars and molars, there was no definitive elimination of the radiographic bone loss (Rude grade 2 and 3) after 12 months. In the area of incisors and canines, complete healing was observed only in 37.5％ of cases (I class according to Rud). In group Ⅱ, out of 184 implants installed immediately after tooth extraction, one was removed one month after implantation. In other cases, all implants were successfully integrated with the subsequent fabrication of prosthetic construction. Conclusion:The complex "implant (installed in the socket of the tooth immediately after its removal) - bone - soft tissues - prosthetic construction" is stable over time in terms of functional and aesthetic parameters, preservation of bone tissue, and mucous membrane.

摘要：The corona virus disease 2019 (COVID-19) pandemic has created a global health and economic crisis. Our studies uncovered that in addition to respiratory symptoms, liver damage is also common in COVID-19 patients; however, the cause of liver damage has not been fully elucidated. In this article, we summarize the clinical manifestations and pathological features of COVID-19 reported in published relevant studies and delineate the etiology and pathogenesis of COVID-19-related liver injury. We speculate that cold stimulation may be associated with COVID-19-related liver injury, which should be considered in clinical decision-making and treatment of COVID-19 in cold regions.

摘要：Background: Patients with coronavirus disease 2019 (COVID-19) have high resource utilization. Identifying the causes of severe COVID-19 is helpful for early intervention to reduce the consumption of medical resources. Methods: We included 103 patients with COVID-19 in this single-center observational study. To evaluate the incidence, predictors, and effects of COVID-19, we analyzed demographic information, laboratory results, comorbidities, and vital signs as factors for association with severe COVID-19. Results: The incidence of severe COVID-19 was 16.5％ and the percent poor outcome (including mortality, entering in ICU or transferred to a superior hospital) was 6.8％. The majority of severe COVID-19 patients had abnormal electrocardiogram (ECG) (82.35％), hypertension (76.47％) and other cardiac diseases (58.82％). Multivariate logistic regression was used to determine the predictors of severe illness. Abnormal body mass index (BMI) and ECG (P < 0.05) were independent predictors of severe COVID-19. ECG abnormality was associated with increased odds of poor outcome (area under the receiver operating characteristic curves [AUC], 0.793; P = 0.010) and severe COVID-19 (AUC, 0.807; P < 0.0001). Overweight was also associated with increased odds of poor outcome (AUC, 0.728; P = 0.045) and severe illness COVID-19 (AUC, 0.816; P < 0.0001). Conclusion: Overweight and electrophysiological disorders on admission are important predictors of prognosis of patients with COVID-19.

摘要：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.

摘要：Diabetes mellitus (DM) is a progressive metabolic disease characterized by chronic hyperglycemia and caused by different degree of pancreatic islet dysfunction and/or insulin resistance (IR). Long course DM can lead to a variety of macrovascular and microvascular complications which involve artery vessels, heart, kidney, retina, nervous system, etc. In recent years, DM has attracted more and more attention due to its high morbidity and mortality. In addition to achieve effective glycemic control, prevention of complications has also been considered a priority for type 2 diabetes mellitus (T2DM) management. Herein, we provide a comprehensive overview on the pharmacotherapeutics for T2DM and perspectives on the future directions of basic and translational research on anti-diabetic therapy and pharmatheutical development of new drugs. Keywords

摘要：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.