Background Psoriasis is a disease caused by genetics and immune system dysfunction, affecting the skin and joints. Toll-like receptors (TLRs) play an important role in triggering the innate immune response and controlling adaptive immunity. The role of TLR2 in the progression of psoriasis is not well understood. Methods A case-control study was conducted on a northern Chinese Han population, consisting of psoriasis patients and healthy control subjects. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls. Results Four TLR2 SNPs (rs11938228, rs4696480, rs3804099, rs5743699) were genotyped and found to be in linkage disequilibrium. The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model. The haplotypes ATTC and ATCC were found to be protective against psoriasis. Conclusion Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

The concept of Traditional Chinese Medicine (TCM) emphasizes the intrinsic connection between human beings and nature, positing that the human body undergoes distinct physiological changes in response to various natural environments. Cold, as a primary external factor in cold areas, necessitates the body's autonomous adaptation to uphold optimal living conditions. The repercussions of cold on the body are both far-reaching and profound, with metabolic equilibrium adjustments playing a pivotal role. This article, rooted in the TCM principle of Yin-Yang balance, delves into the metabolic intricacies and adaptive responses to the human body in cold environments. The effects manifest in heat-producing tissues, systemic substance consumption, the blood substance concentrations, liver function, and metabolic rhythms. The article subsequently presents TCM recommendations for maintaining health in cold climates. It concludes by advocating the exploration of metabolic homeostasis changes as a key avenue for investigating the metabolic traits s of populations in cold regions. We posit that such insights will enhance comprehension of the metabolic shifts in cold region populations and advance the evolution of regional medicine.

Bladder cancer (BC) ranks as the tenth most common cancer globally. Histopathologically, BC is broadly categorized into urothelial and non-urothelial BC. Urothelial carcinoma represents over 90% of BC in most regions worldwide. The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer (NMIBC) is transurethral resection of bladder tumors (TURBT). Currently, the standard of care for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy. Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue. This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney, prostate gland, lung, liver, and breast, and is particularly effective for unresectable tumors, offering less trauma, quick recovery, good tolerability, and symptom control. However, cryoablation has its limitations. Over the past few years, cryoablation therapy has emerged as a new method for treating early BC. This treatment is minimally invasive, precise, and offers quick recovery, providing patients with a new treatment option. Although randomized studies are still limited, increasing evidence suggests its potential application in bladder cancer combined with transurethral resection (TURBT) or medication. Cryoablation is not standard therapy for bladder cancer. Treatment decisions should be discussed by a multidisciplinary team of urologists, oncologists, and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.

Cold stimulation has been shown to regulate glucose, lipid, and amino acid metabolism, while also increasing heat production and energy expenditure in the body. Disordered energy metabolism is a key factor in the onset and progression of chronic metabolic conditiones such as diabetes, obesity, and cardiovascular disease. Recent research has unveiled the myriad pathways through which cold stimulation affects human energy metabolism. This article provides an overview of how cold stimulation affects energy metabolism across the three major metabolic pathways. Furthermore, it explores the implications and potential therapeutic applications of cold stimulation in the prevention and treatment of various metabolic diseases.

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.

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.

Background and objective Commonly plaguing in the frigid zone of the world, vitamin D deficiency, as indicated by low levels of 25-hydroxyvitamin D, exacerbated inflammatory responses and impaired endothelial function. Leukoaraiosis (LA) is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses. This study aimed to investigate the impact of vitamin D on the severity of LA. Methods Patients with LA were categorized based on 3.0 T brain MRI findings into mild (N = 43), moderate (N = 40), or severe groups (N = 29) using the Fazekas scale (scoring 1-6). A control group consisting of 41 healthy individuals was included. Serum fibrinogen C, homocysteine, plasma 25-hydroxyvitamin D, and intercellular cell adhesion molecule-1 (ICAM-1) levels were measured using ELISA. Results All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group, with a more pronounced decrease observed as LA severity increased. Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA (P < 0.05) according to Multiple logistic regression analysis. Additionally, a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1. Conclusion Disease severity positively correlated with levels of the inflammatory marker ICAM-1, worsening as plasma 25-hydroxyvitamin D concentration decreased. Low 25-hydroxyvitamin D emerged as an independent risk factor for LA, potentially exacerbating the inflammatory response. These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.

Background Cataracts are the leading cause of reversible blindness worldwide. Diabetic cataract (DC), a prevalent complication of diabetes mellitus, is characterized by its high occurrence, rapid progression, and severe impact. The prevalence of diabetes varies greatly between the northern and southern regions, with higher rates observed among northern residents. DC-induced lens opacity is mainly attributed to oxidative stress. However, it remains unclear whether ferroptosis, a form of regulated cell death, occurs in crystalline epithelial cells during the pathogenesis, which may represent a novel mechanism contributing to DC. Methods Transmission electron microscopy, quantitative assays for iron levels and reactive oxygen species (ROS), real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, and immunohistochemistry were used to detect ferroptosis. Gene editing techniques were utilized to study the regulatory relationships among lipocalin 2 (LCN2), glutathione peroxidase 4 (GPX4), and ferritin heavy chain (FTH). Local knockdown of the LCN2 gene in B-3 cells and the eyes of Sprague Dawley (SD) rats was performed to verify and further explore the role and regulatory mechanisms of LCN2 in DC-associated ferroptosis. Results An in vitro model using high glucose levels and an in vivo model with streptozotocin-induced diabetes in SD rats were successfully established. Ferroptosis was observed in both in vitro and in vivo experiments. LCN2 protein was normally expressed in human and rat lens epithelial cells, but its expression significantly increased during ferroptosis. The ferroptosis inhibitor, ferrostatin-1 (Fer-1) effectively inhibited ferroptosis and reduced LCN2 protein expression. Notably, local knockdown of LCN2 via gene editing protected lens epithelial cells from ferroptosis in vitro and slowed the progression of DC in SD rats in vivo. Conclusion Our findings underscore the significant role of ferroptosis in the pathogenesis of DC, suggesting that selectively targeting LCN2 activation and enhancing ferroptosis resistance may offer a novel therapeutic approach for treating DC.

Background and objective In northern China's cold regions, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) exceeds 50%, significantly higher than the national and global rates. MASLD is an important risk factor for cardiovascular and cerebrovascular diseases, including coronary heart disease, stroke, and tumors, with no specific therapeutic drugs currently available. The ethanol extract of cassia seed (CSEE) has shown promise in lowering blood lipids and improving hepatic steatosis, but its mechanism in treating MASLD remains underexplored. This study aims to investigate the therapeutic effects and mechanisms of CSEE. Methods MASLD models were established in male Wistar rats and golden hamsters using a high fat diet (HFD). CSEE (10, 50, 250 mg/kg) was administered via gavage for six weeks. Serum levels of total cholesterol (TC), triglyceride (TG), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as liver TC and TG, were measured using biochemical kits. Histopathological changes in the liver were evaluated using Oil Red O staining, Hematoxylin-eosin (H&E) staining, and transmission electron microscopy (TEM). HepG2 cell viability was assessed using the cell counting kit-8 (CCK8) and Calcein-AM/PI staining. Network pharmacology was used to analyze drug-disease targets, and western blotting was used to confirm these predictions. Results CSEE treatment significantly reduced serum levels of TC, TG, LDL-C, ALT, and AST, and improved liver weight, liver index, and hepatic lipid deposition in rats and golden hamsters. In addition, CSEE alleviated free fatty acid (FFA)-induced lipid deposition in HepG2 cells. Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK, p-ACC, PPARα, CPT1A, PI3K P110 and p-AKT, while decreasing the protein levels of SREBP1, FASN, C/EBPα, and PPARγ, thus improving hepatic lipid metabolism and reducing lipid deposition. The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro. Conclusion CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK, PPARα, and PI3K/AKT signaling pathways.

Background and Objective Some patients continue to experience major adverse cardiovascular and cerebrovascular events (MACCE) after percutaneous coronary intervention (PCI) in frigid places. Indexes of inflammation and nutrition alone were shown to predict outcomes in patients with PCI. However, the clinical predictive value of mixed indicators is unclear. This study aimed to assess the predictive value of the albumin/neutrophil/lymphocyte ratio (NLR) on the long-term prognosis of patients with coronary heart disease (CHD) following percutaneous coronary intervention (PCI). Methods A total of 608 post-PCI CHD patients were categorized into low- and high-index groups based on the optimal cut-off values for albumin and NLR. The primary outcome was a composite endpoint comprising all-cause mortality and major adverse cerebrovascular events. The secondary outcome was the comparison of the predictive efficiency of the new nutritional index, albumin/NLR, with that of albumin or NLR alone. Results Over the five-year follow-up period, 45 patients experienced the composite endpoint. The incidence of endpoint events was significantly higher in the low-index group (12%) compared to the high-index group (4.9%). Receiver operating characteristic (ROC) curve analysis revealed that the albumin/NLR index had a larger area under the curve (AUC: 0.655) than albumin (AUC: 0.621) or NLR (AUC: 0.646), indicating superior predictive efficiency. The prognostic nutritional index had an AUC of 0.644, further supporting the enhanced predictive value of the albumin/NLR index over individual nutritional and inflammatory markers. Conclusion The albumin/neutrophil/lymphocyte ratio is independently associated with the long-term prognosis of CHD patients post-PCI and demonstrates superior predictive efficiency compared to individual nutritional and inflammatory markers.

Objective Cold regions exhibit a high prevalence of cardiovascular disease, particularly acute myocardial infarction (AMI), which is one of the leading causes of death associated with cardiovascular conditions. Cardiovascular disease is closely linked to the abnormal expression of long non-coding RNA (lncRNA). This study investigates whether circulating levels of lncRNA cardiac conduction regulatory RNA (CCRR) could serve as a biomarker for AMI. Materials and methods We measured circulating CCRR from whole blood samples collected from 68 AMI patients and 69 non-AMI subjects. An AMI model was established using C57BL/6 mice. Quantitative reverse transcription PCR (qRT-PCR) was used to assess CCRR expression. Exosomes were isolated from cardiomyocytes, and their characteristics were evaluated using electron microscope and nanoparticle tracking analysis. The exosome inhibitor GW4869 was employed to examine the effect of exosomal CCRR on cardiac function using echocardiography. Protein expression was detected using Western blot and immunofluorescence staining. Results The circulating level of CCRR was significantly higher in AMI patients (1.93 ± 0.13) than in nonAMI subjects (1.00 ± 0.05, P < 0.001). The area under the ROC curve (AUC) of circulating CCRR was 0.821. Similar changes in circulating CCRR levels were consistently observed in an AMI mouse model. Exosomal CCRR derived from hypoxia-induced cardiomyocytes and cardiac tissue after AMI were increased, a change that was reversed by GW4869. Additionally, CCRR-overexpressing exosomes improved cardiac function in AMI. Conclusion Circulating lncRNA CCRR is a potential predictor of AMI. Exosomal CCRR plays a role in the communication between the heart and other organs through circulation.

Objective The objective of this study was to assess seasonal changes in dietary and nutrient intake of residents (18-75 years old) in Northeast China during summer and winter, and to explore the associations between fatty acids, phytosterols, and the prevalence of obesity-related chronic diseases, particularly obesity, hyperlipidemia, and NAFLD. Methods A total of 4773 participants from the Internet-based Dietary Questionnaire for Chinese (IDQC) were included in this study. Dietary intake information was collected using a validated food frequency questionnaire. Student's t-test or Mann-Whitney U-test was used to analyze continuous variables, while Chi-squared tests were used to compare categorical variables. Multivariable logistic regression was employed to assess the relationship between fatty acids, phytosterols, and obesity-related chronic diseases. Results The mean consumption of legumes, vegetables, fruits, nuts, dairy products, fish, condiments, energy, protein, fat, and carbohydrate differed significantly between summer and winter (P < 0.05). Significant inverse associations were found between both fatty acids and phytosterols and obesity-related chronic diseases in multivariate adjusted models. Summer polyunsaturated fatty acid (PUFA) intake was negatively associated with the prevalence of hyperlipidemia (Q4, OR, 0.515; 95%CI, 0.283-0.921; P < 0.05) and non-alcoholic fatty liver disease (NAFLD) (Q4, OR, 0.331; 95%CI, 0.176-0.599; P < 0.001). Phytosterols intake was negatively associated with the prevalence of obesity (Q4, OR, 0.603; 95%CI, 0.414-0.873; P < 0.05), hyperlipidemia (Q4, OR, 0.420; 95%CI, 0.233-0.731; P < 0.001), and NAFLD (Q4, OR, 0.206; 95%CI, 0.111-0.360; P < 0.001) during the summer. Conclusion Higher PUFA intake was associated with a lower prevalence of obesity, hyperlipidemia, and NAFLD. Phytosterol intake was inversely associated with the prevalence of hyperlipidemia and NAFLD. These findings suggest that the associations between PUFA and phytosterols and the prevalence of obesity-related chronic diseases may be influenced by seasonal differences in food intake.

Objective To evaluate the clinical efficacy of combining arthroscopic patellar denervation with microfracture in the treatment of patellofemoral arthritis under cold weather conditions. Methods A total of 134 patients with patellofemoral arthritis who underwent treatment between June 2019 and June 2021 were included in this study. Patients were randomly divided into two groups: the control group, which received standard arthroscopic debridement and conventional therapy, and the study group, which underwent additional peripatellar denervation and microfracture procedures. Clinical outcomes, including Tegner scores, hospital for special surgery (HSS) scores, and treatment-related adverse events, were evaluated and compared between the two groups. Results The study group achieved a significantly higher excellent treatment rate (95.52%, 64/67) compared to the control group. Posttreatment Tegner scores (5.48 ± 1.86) and HSS scores (86.37 ± 11.25) were also significantly better in the study group than in the control group. Furthermore, the incidence of adverse reactions was lower in the study group (4.48%, 3/67), with statistically significant differences observed (P < 0.05). Conclusion Arthroscopic patellar denervation combined with microfracture markedly improves clinical outcomes, including Tegner and HSS scores, in the treatment of patellofemoral arthritis, particularly under cold weather conditions. The procedure is effective and safe, supporting its broader clinical application.

Objective Heilongjiang Province is part of the northern cold areas of China, where gastric cancer is one of the most common gastrointestinal malignancies. Peritoneal metastases (PM) are the leading cause of mortality among patients. This study conducted bioinformatics and basic research on the gene ANXA2 (Annexin A2), which may influence the prognosis of patients. Methods Genome sequencing was performed on patients from Heilongjiang to identify potential genes impacting survival time. The function of ANXA2 in gastric cancer was analyzed using multiple bioinformatics databases, focusing on its pathways and mechanisms. ANXA2-knockout gastric cancer cell lines were constructed, and in vitro assays, including CCK-8, flow cytometry, scratch, and Transwell experiments, were conducted. A nude mouse tumorigenesis model was also developed to analyze in vivo effects. Results ANXA2 was found to be expressed at higher levels in gastric cancer tissue than in normal gastric tissue, and its mRNA levels were associated with short overall survival (OS). Enrichment analysis indicated that ANXA2 is primarily localized on the cell membrane and primarily influences the PI3K-AKT signaling pathway. Cytological experiments demonstrated that knockdown of ANXA2 suppresses the growth and migration of gastric carcinoma cells, an effect that was also observed in vivo. Conclusion ANXA2 is essential for gastric cancer growth and may represent a potential risk factor affecting the survival probability of patients in cold regions.

Background Cold exposure is linked to numerous diseases, yet the changes in key genes and pathways in mice under cold exposure remain unexplored. Understanding these alterations could offer insights into the mechanisms of cold resistance and contribute valuable ideas for treating cold-related diseases. Methods The dataset GSE148361 was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on DEGs. The STRING (Search Tool for the Retrieval of Interacting Genes) database was used to construct a protein-protein interaction (PPI) network. Additionally, gene set enrichment analysis (GSEA) was conducted to identify pathways associated with key genes. miRNAs and upstream transcription factors (TFs) were predicted using the miRNet database. Results A total of 208 DEGs were identified, with 137 upregulated and 71 downregulated. In biological processes, DEGs were enriched in nucleotide and purine-containing compound metabolism. For cellular components, DEGs were involved in condensed chromosomes and mitochondrial protein complexes. In molecular functions, proton transmembrane transporter activity was enriched. KEGG pathway analysis showed significant enrichment in biosynthesis of unsaturated fatty acids, fatty acids, and pyruvate metabolism. From the PPI network, 12 hub genes were identified using MCODE. Four hub genes (Col3a1, fi203, Rtp4, Vcan) demonstrated similar trends in a validation set (GSE110420) and were significantly differentially expressed. GSEA analysis indicated that these four genes were enriched in pathways such as ECM-receptor interaction and cytokinecytokine receptor interaction. The hub gene network included 93 miRNAs and one TF. Conclusion This study identified four hub genes as potential diagnostic biomarkers for cold exposure, providing insights for further research on the effects of cold on gene expression and disease.