BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Brain metastases are the most common intracranial tumors, and their incidence is increasing with the improvement of systemic treatments and survival rates. Optimal treatment usually requires a multidisciplinary approach, including radiotherapy, surgical resection, chemotherapy, targeted therapy, and immunotherapy. Stereotactic radiotherapy, compared to whole-brain radiotherapy, offers improved local control rates and reduced risk of neurocognitive impairment, and has become a new standard option for the treatment of brain metastases. Additionally, the widespread use of targeted and immune therapies in brain metastases has significantly improved the survival of some patients. This article reviews and integrates recent literature on the treatment of brain metastases and analyzes the role of stereotactic radiotherapy in comprehensive treatment, aiming to provide a reference for the selection of clinical treatment plans.

Background With urbanization and residential space expansion, ecological environment and human health issues have become hot social topics. Forest health, as a way of seeking health in nature, has begun to receive public attention in the context of the gradually increasing sub-healthy population and various psychological and physical diseases at a young age. Objective To systematically evaluate the effects of forest therapy on selected physical and mental health indicators. Methods Relevant research literature was retrieved from domestic and international databases (China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Service System, Web of Science, ScienceDirect, PubMed, Embase, and Cochrane Library), with a time range from database establishment to January 31, 2023. Relevant data were extracted for meta-analysis to explore the relationship between forest therapy and selected psychological and physiological indicators. Results A total of 85 articles were included, and the meta-analysis results showed that better scores of Profile of Mood States, Positive and Negative Affect Scale, Beck Depression Inventory, and State Trait Anxiety Scale were found in the forest group than those in the urban group (P<0.05); the levels of systolic blood pressure, diastolic blood pressure, heart rate, sympathetic nerve indicator [ln (LF/HF)], salivary cortisol, and serum inflammatory factors were lower in the forest group than in the urban group, while parasympathetic nerve indicator [ln (HF)] level was higher in the forest group than in the urban group (P<0.05). The results of subgroup analysis showed that the changes in heart rate (SMD=−1.62, 95%CI: −2.41, −0.82), ln (HF) (SMD=1.29, 95%CI: 0.73, 1.85), ln (LF/HF) (SMD=−1.49, 95%CI: −2.13, −0.86), and salivary cortisol (SMD=−0.53, 95%CI: −0.81, −0.25) were more significant when the duration of forest therapy was ≤ 0.5 h, the recovery effect on emotional state was better in the >0.5~3 h group (such as tension SMD=−2.40, 95%CI: −3.21, 1.59), and the reduction effects on systolic blood pressure (SMD=−0.53, 95%CI: −1.03, −0.03) and diastolic blood pressure (SMD=−0.42, 95%CI: −0.88, 0.04) were better in the >3 h group. Seated meditation showed better recovery effects on multiple indicators of Profile of Mood States (such as fatigue SMD=−2.26, 95%CI: −3.07, −1.45), while walking showed better recovery effects on physiological indicators such as blood pressure (systolic blood pressure SMD=−0.57, 95%CI: −1.07, −0.06; diastolic blood pressure SMD=−0.72, 95%CI: −1.36, −0.07) and heart rate (SMD=−1.51, 95%CI: −2.38, -0.64). Except for blood pressure, the health benefits of forest therapy in the younger age group were generally better than those in the middle-aged and elderly group. Conclusion Relaxed and comfortable psychological feeling is reported when practicing forest therapy; it can lower blood pressure and heart rate, regulate the autonomic nervous system; it can also reduce the release of stress hormones and lower serum levels of inflammatory factors, exerting an auxiliary recovery effect on cardiovascular and immune system disorders. At the same time, the therapy duration, form, and age of the subjects have a certain impact on the effects of forest therapy practice.

Objective To explore the effect of miR-1-3p on the malignant biological behavior of human esophageal squamous cell carcinoma cells and the potential mechanisms.Methods The Gene Expression Omnibus(GEO)database was analyzed to screen differentially expressed miRNAs in esophageal squamous cell carcinoma(ESCC).qRT-PCR was used to detect the expression of miR-1-3p in human ESCC cell lines(KYSE30,KYSE150,KYSE410,KYSE510,and Eca109)and normal esophageal epithelial cell line HET-1A.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of miR-1-3p on the proliferation,migration,invasion,and apoptosis of ESCC cells.Bioinformatics tool was used to predict the target genes of miR-1-3p.A Kaplan-Meier survival curve was drawn to analyze the correlation between STC2 expression and overall survival of patients in the ESCC cohort of the TCGA database.Fluorescence in situ hybridization was performed to verify the subcellular location of miR-1-3p in ESCC cells,and dual-luciferase reporter gene assay was performed to validate the regulation of miR-1-3p on stanniocalcin 2(STC2).RNA immunoprecipitation assays were used to detect the binding of miR-1-3p and STC2.Western blot assay was performed to determine the effect of miR-1-3p on the expression of STC2 and endoplasmic reticulum stress pathway-related proteins,including p-PERK,p-eIF2α,and ATF4.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of STC2 overexpression and knockdown on the proliferation,migration,invasion,and apoptosis of ESCC cells.Results The expression of miR-1-3p was lower in ESCC cell lines than in HET-1A cells(all P<0.05).The transfection of miR-1-3p mimic decreased the proliferation,invasion,and migration of ESCC cells(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.001).Bioinformatics tool showed that STC2 was a target gene of miR-1-3p.The expression of STC2 in ESCC tissues was higher than that in normal esophageal epithelial tissues in the ESCC cohort of TCGA database and was negatively correlated with prognosis(all P<0.05).miR-1-3p was located in the cytoplasm and can directly bind to STC2 mRNA.The transfection of miR-1-3p mimic downregulated the expression of STC2,p-PERK,p-eIF2α,and ATF4(all P<0.05).The overexpression of STC2 promoted the proliferation,invasion,and migration(all P<0.05)and inhibited the apoptosis of ESCC cells(all P<0.05).Knockdown of STC2 inhibited the proliferation,invasion,and migration(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.05).Conclusion miR-1-3p inhibits the malignant biological behavior and promotes the apoptosis of esophageal squamous cell carcinoma cells by regulating STC2 possibly by suppressing the endoplasmic reticulum stress.

Objective:A genome-wide molecular characterization of FJ21351116, a strain of G3P[8]-E2 2021 collected in Fujian, China, was performed.Methods:Whole genome sequencing of FJ21351116 was performed using a high-sensitivity group A rotavirus whole genome sequencing method. Genomic characteriza-tion of the virus was assessed by nucleic acid sequence analysis using MEGA 11.0, Geneious 9.0.2 and DNASTAR software. Neutralization epitopes of VP7 and VP4 (VP8*) were analyzed using BioEdit v. 7.0.9.0 and PyMOL v. 2.5.2.Results:In this study, FJ21351116 was shown to be a G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype, and the result of phylogenetic tree showed that the VP7, VP4, VP3, and NSP2-NSP5 genes of the FJ21351116 strain were related to the equine-like DS-1-like G3P[8] genes that have been detected in Japan in recent years. VP6, VP1, VP2, and NSP1 genes are closely related to G2P[4] in most countries, especially in Singapore, suggesting that this strain was formed by genetic reassortment during the evolution of equine-like G3P[8] and G2P[4]. Evolutionary relationships between the VP7/VP4 genes of FJ21351116 and Rotarix and RotaTeq vaccines suggest that the multiple mutations in both VP7 and VP4 (VP8*) neutralizing antigenic epitopes and vaccine amino acid sites. It is hypothesized that the Rotarix and RotaTeq vaccines may be less effective against equine DS-1-like G3P[8] RVA, and the sequence differences with Rotarix are higher than those with RotaTeq.Conclusions:In this study, we found a rare case of DS-1-like G3P [8] RVA strain in China. Currently, horse-like DS-1-like G3P [8] RVA is relatively rare in China and may be poorly protected by vaccine strains, emphasizing the importance of continuous monitoring of RVA strains and the development of efficient and full-coverage RVA vaccines.

Osteosarcoma is a common primary malignant bone tumor in adolescents and children,characterized by a high recurrence rate and metastasis,making its treatment extremely challenging.Traditional treatment modalities,including surgery,radiation therapy,and chemotherapy,can alleviate symptoms to some extent,but improving long-term survival rates remains a pressing issue.With the continuous development of immunotherapy,breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years,providing new perspectives and strategies for osteosarcoma treatment.Currently,immunotherapy strategies include tumor vaccines,targeted cytokines,immune checkpoint inhibition,adoptive cell therapy,combination therapy,etc.,significantly enhancing patient immune responses from the aspects of boosting immunity,overcoming immune tolerance,and preventing immune evasion,thereby effectively improving the patients'survival rates and prognosis.This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma.By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods,it is hopeful to provide more effective strategies for personalized treatment,contributing to the improvement of the patients' survival rates and prognosis.

Objective:To investigate the effect of tumor deposits on the prognosis and lymph node staging in patients with gastric cancer.Methods:The clinicopathological data of 907 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from Jan to Dec 2016 were retrospectively analyzed. According to the pathological diagnosis, the patients were divided into tumor deposits positive group (121 cases) and tumor deposits negative group (786 cases), and the relationship between tumor deposits and clinicopathological features and prognosis was analyzed.Results:Tumor deposits were found in 121 patients among 907 cases. Univariate analysis showed that tumor deposits were correlated with pT stage, pN stage, pTNM stage, tumor diameter, nerve invasion and vascular invasion (all P<0.05). Multivariate analysis showed that pT stage ( P<0.001), pN stage ( P=0.002), pTNM stage ( P=0.001), tumor diameter ( P=0.033),nerve invasion ( P=0.017), vascular invasion ( P=0.011) were the independent influencing factors of positive tumor deposits. The prognosis of patients with tumor deposits was worse than those without ( χ2=77.869, P<0.001). By univariate analysis, age, tumor location, size, pT stage, pN stage, pTNM stage, tumor thrombus, nerve invasion, tumor deposits and number affected prognosis (all P<0.05). Multivariate analysis showed that age, pT stage, pN stage, pTNM stage, nerve invasion, vascular invasion and the number of tumor deposits were independent prognostic factors (all P<0.05). By stratified analysis tumor deposits were found to have statistical difference in N0~N3a stage (all P<0.05). Conclusion:Tumor deposits is an independent risk factor affecting the prognosis of gastric cancer patients.

Objective:To explore the expression of long non-coding RNA (lncRNA) HAGLR in breast cancer and its effect on the prognosis of breast cancer, and to construct a competitive endogenous RNA (ceRNA) network.Methods:The Atlas of Genetics and Cytogenetics in Oncology and Haematology website was used to search for HAGLR chromosome gene mapping and transcript expression. The lnclocater website was used to predict the subcellular localization of HAGLR, and the differential expression of HAGLR in breast cancer tissues and adjacent tissues was analyzed by using lnCAR database. The patients in lnCAR database were divided into HAGLR high expression group and HAGLR low expression according to HAGLR expression. The Kaplan-Meier method was used to analyze the overall survival (OS) and metastasis-free survival, which was verified by using UCSC Xena database. lnCAR database was used to search the co-expressed genes of HAGLR. The top 200 co-expressed genes were submitted to the Metascape website for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, and protein interaction network (PPI) was constructed. Starbase, a bioinformatics online analysis website, was used to predict HAGLR targeting mircoRNA (miRNA) and mRNA that directly encoded proteins. ceRNA network of HAGLR was constructed with Cytoscape3.8 software.Results:HAGLR gene was localized in 2q31.1 and mainly distributed in cytoplasm. The expression level of HAGLR in breast cancer tissues was higher than that in adjacent tissues, and the difference was statistically significant ( P < 0.001). lnCAR database and UCSC Xena database analysis showed that OS in HAGLR high expression group was worse than that in HAGLR low expression group (all P < 0.01). lnCAR database, the metastasis-free survival in HAGLR high expression group was worse than that in HAGLR low expression group ( P = 0.030). Among the top 200 HAGLR co-expressed genes, 129 genes were negatively correlated with HAGLR and 71 genes were positively correlated with HAGLR. KEGG pathway analysis showed that HAGLR was related to metabolic pathways, MAPK signaling pathway, JAK-STAT signaling pathway and cancer pathway. GO annotation analysis showed that HAGLR was mainly enriched in cell cycle, centromeric complex assembly, mitotic progression, protein kinase binding, kinase activity regulation, cell response to DNA damage stimulation and other functions. hsa-miR-130b-3p, hsa-miR-1245b-5p, hsa-miR-182b-5p, hsa-miR-512-3p, hsa-miR-302b-3p, hsa-miR-185b-5p, hsa-miR-106b-5p were HAGLR targeting miRNA. Conclusions:HAGLR is highly expressed in breast cancer tissues, and it may be a biomarker for predicting the prognosis of breast cancer.

Objective:To investigate the differential expression of brain-expressed X-linked (BEX) family genes in pan-cancer and its value in diagnosis and prognosis of pan-cancer.Methods:RNA sequencing (RNA-seq) data, survival data, immune subtypes, the stem cell scores based on RNA and DNA methylation of 33 different tumors from The Cancer Genome Atlas (TCGA) database were downloaded from the online database of University of California, Santa Cruz (UCSC Xena) on April 10, 2022. The limma package of R software (V.4.2.0) was used to analyze the expression of BEX family genes in the TCGA database. The differential expression of BEX family genes in pan-cancer tissues and normal tissues was compared by using Wilcox test. Pan-cancer patients were divided into high expression group and low expression group according to the median expression level of BEX family genes; Kaplan-Meier survival analysis was used to evaluate the relationship between the expression of BEX family genes and the overall survival (OS) of patients; Cox proportional risk model was used to analyze the effect of the expression of BEX family genes on OS in pan-cancer patients and then the forest map was drawn. The correlation of the expression of BEX family genes with tumor microenviroment and tumor stem cells in pan-cancer patients was analyzed based on the correlation index Cor value. Spearman correlation analysis was used to analyze the correlation between the expression of BEX family genes and tumor microenviroment and cancer stem cell index in gastric cancer tissues. The RNA-seq of different tumor cell lines and drug sensitivity data download from the CellMiner database were used to analyze the correlation between the expression of BEX family genes and drug sensitivity. The correlation of pan-cancer and gastric cancer immune subtypes with the expression of BEX family genes was analyzed by using Kruskal test.Results:BEX3 was highly expressed in pan-cancer tissues in TCGA database, BEX2 and BEX4 were moderately expressed in pan-cancer tissues, and BEX1 and BEX5 were relatively low expressed in pan-cancer tissues. The expressions of BEX2, BEX3 and BEX4 were the highest in cholangiocarcinoma, the expression of BEX5 was the highest in endometrial neoplasms, and the expression of BEX1 was the highest in invasive breast cancer. Compared with normal tissue samples, the expressions of BEX family genes were up-regulated or down-regulated in various cancers (all P < 0.05). Survival analysis showed that the expressions of BEX family genes were associated with the OS of various cancers. Some tumor patients with high expressions of BEX1, BEX3, BEX4 and BEX5 had better OS compared with those with low expressions, and the differences were statistically significant (all P < 0.05). Other patients with high expression of BEX family genes had worse OS compared with those with low expressions, and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that the high expression of BEX1 for stomach neoplasms; the high expression of BEX2 for acute myeloid leukemia, thymoma and endometrial neoplasms; the expression high of BEX3 for squamous cell carcinoma of head and neck,sarcoma, stomach neoplasms and endometrial neoplasms; the high expression of BEX4 for rectal adenocarcinoma, stomach neoplasms and endometrial neoplasms; the high expression of BEX5 for renal suspicious cell carcinoma and thymoma were risk factors for OS (all P < 0.05).The expression of BEX family genes was negatively correlated with the stromal score of most cancers (all P < 0.05), and positively correlated with the stem cell score (all P < 0.05). The expression of BEX family genes was negatively correlated with cancer stem cell index of gastric cancer ( P < 0.05), and was positively correlated with matrix score and estimated total score (all P < 0.05). Among different tumor cell lines in CellMiner database, BEX family genes were closely related to drug resistance of vemurafenib (Cor = -0.368, P = 0.004), Kahalide f (Cor = -0.391, P = 0.002), O-6-benzylguanine (Cor = -0.375, P = 0.003) and other drugs. All genes in the BEX family were related to the immune subtypes of pan-cancer and were highly expressed in C5 subtype (all P < 0.05).For gastric cancer, all genes showed high expression in the C3 subtype (all P < 0.05), except BEX5 ( P = 0.24). Conclusions:The expression of BEX family genes is closely related to the prognosis of pan-cancer patients, and has an impact on the tumor microenvironment, cancer stem cells and drug sensitivity. BEX family genes may be potential biomarkers for diagnosis and prognosis of pan-cancer.

Objective:To explore the application of PDCA (plan, do, check, act) cycle theory in the teaching of eight-year clinical medical students for the course of Laboratory Diagnostics.Methods:From September 2021 to November 2022, the students majoring in clinical medicine of eight-year system who were studying the course of Laboratory Diagnostics at Peking Union Medical College were selected as the research objects. The teaching reform of the course of Laboratory Diagnostics was carried out according to the four stages of PDCA cycle theory, and the teaching effect was evaluated by the final examination results and questionnaire survey scores of the students.Results:The score of theoretical examination of eight-year students in 2018 was (86.7±4.68) points, which was higher than that of students in 2017 [(83.3±3.89) points], and the difference was statistically significant ( P<0.05). The questionnaire survey results of the two groups of students showed that the rating of experimental course was higher than that of theoretical course ( P<0.05). After the teaching reform based on PDCA cycle theory, the questionnaire survey scores of theoretical course [(3.83±0.25) points vs (2.94±0.28) points] and experimental course [(4.13±0.09) points vs (3.32±0.12) points] in students of 2018 were higher than those of 2017 (all P<0.001). Conclusion:PDCA cycle theory provides new methods and ideas for teaching management, which helps to improve the performance of clinical medical students of eight-year system and their recognition of the course.