BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

OBJECTIVE: Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS: This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS: This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; 23(3): 282-288.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Retrospective Studies ; Aged ; Neutrophils ; COVID-19 Drug Treatment ; COVID-19/blood* ; Middle Aged ; Prognosis ; Lymphocytes ; Blood Platelets ; Platelet Count ; SARS-CoV-2 ; Aged, 80 and over ; Adult

Collagen, a vital matrix protein for various tissue and functions in animals, is widely applied in biomaterials. In type Ⅰ collagen, missense mutations of glycine (Gly) in the Gly-Xaa-Yaa triplet of the triple helix are a major cause of osteogenesis imperfecta (OI). Clinical manifestations exhibit marked heterogeneity, spanning a broad disease spectrum from mild skeletal fragility (Type Ⅰ) to severe limb deformities (Type Ⅲ) and perinatal lethal forms (Type Ⅱ). This study utilized recombinant collagen as a model to further elucidate whether Gly→Ala/Val mutations at the N-terminus of the integrin-binding sequence GFPGER affect collagen structure and function, and to explore the underlying mechanisms by which missense mutations impact the biological function of collagen. By introducing Ala and Val substitutions at seven Gly positions N-terminal to the GFPGER sequence, we systematically assessed the effects of these amino acid replacements on the triple-helical structure, thermal stability, integrin-binding ability, and cell adhesion of recombinant collagen. All constructs formed a stable triple-helix structure, with slightly compromised thermal stability. Gly→Val substitutions increased the susceptibility of recombinant collagen to trypsin, which suggested local conformational perturbations in the triple helix. In addition, Gly→Val substitutions significantly reduced the integrin-binding affinity and decreased HT1080 cell adhesion, with the effects stronger than Gly→Ala substitutions. Compared with Gly→Ala substitutions, substitution of Gly with the larger residue Val had enhanced negative effects on the structure and function of recombinant collagen. These findings provide new insights into the molecular mechanisms of osteogenesis imperfecta and offer theoretical references and experimental foundations for the design of collagen sequences and the development of collagen-based biomaterials.
Recombinant Proteins/biosynthesis* ; Glycine/genetics* ; Humans ; Osteogenesis Imperfecta/genetics* ; Integrins/metabolism* ; Collagen/metabolism* ; Collagen Type I/metabolism* ; Amino Acid Substitution ; Mutation ; Mutation, Missense

OBJECTIVES: The core pathology of osteoporosis lies in bone resorption exceeding bone formation; thus, promoting osteogenesis is a key therapeutic strategy. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) forms the biological basis of bone formation. Astragaloside IV (A-IV), a major active component of Astragalus membranaceus, is known to enhance osteogenesis, but its precise molecular mechanisms remain unclear. This study aims to investigate the effects of A-IV on the proliferation and osteogenic differentiation of BMSCs from osteoporotic rats and to elucidate its molecular mechanism through the regulation of microRNA-21 (miR-21) and Notch2 expression. METHODS: After 1 week of adaptive feeding, mature female SD rats were randomly divided into a sham-operated (Sham) group (n=4) and an ovariectomized (OVX) group (n=8) to establish an osteoporosis model. Twelve weeks after surgery, BMSCs were isolated from femoral bone marrow and cultured. Cells were divided into a S-BMSCs group (from Sham), an O-BMSCs group (from OVX), and an A-BMSCs group (from OVX-derived BMSCs treated with A-IV). S-BMSCs and O-BMSCs were induced for osteogenic differentiation using osteogenic induction medium, whereas A-BMSCs were treated with A-IV before induction. Flow cytometry was used to identify mesenchymal stem cell surface markers (CD29) and hematopoietic stem cell marker (CD34) to confirm BMSC characteristics. Cell proliferation was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Alizarin red staining was performed to quantify calcium nodule formation, and alkaline phosphatase (ALP) activity assays were used to evaluate osteogenic differentiation. Real-time reverse transcription PCR (real-time RT-PCR) was used to detect changes in osteogenic-related genes, runt-related transcription factor 2 (Runx2) and osteopontin (OPN), as well as miR-21 expression. Western blotting was performed to assess Runx2, OPN, and Notch2 protein expression. RESULTS: Flow cytometry confirmed that O-BMSCs retained the phenotypic characteristics of mesenchymal stem cells. A-IV significantly enhanced the proliferation of BMSCs from osteoporotic rats (P<0.05), increased ALP activity, and upregulated the mRNA and protein expression of Runx2 and OPN (P<0.05). Bioinformatic and experimental analyses demonstrated that miR-21 directly targeted Notch2. A-IV treatment increased miR-21 expression while suppressing Notch2 protein expression and inhibiting activation of the Notch signaling pathway (P<0.05). CONCLUSIONS Astragaloside IV promotes the osteogenic differentiation of BMSCs derived from osteoporotic rats by upregulating miR-21 expression and inhibiting the key Notch signaling protein Notch2, thereby relieving the Notch2-mediated suppression of osteogenesis.
Animals ; Triterpenes/pharmacology* ; Saponins/pharmacology* ; Osteogenesis/drug effects* ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Female ; Cell Differentiation/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Signal Transduction/drug effects* ; Osteoporosis/pathology* ; Rats ; Cells, Cultured ; Receptor, Notch2/metabolism* ; Receptors, Notch/metabolism* ; Ovariectomy ; Cell Proliferation/drug effects*

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

Objective:To clarify the genetic associations between obesity, diabetes, smoking, non-alcoholic fatty liver disease, acute and chronic pancreatitis, and pancreatic cancer risk.Methods:Summary data from genome-wide association studies (GWAS) of individuals of European descent were used. Obesity, alcohol consumption, diabetes, and acute and chronic pancreatitis data for the UK population were obtained from the GWAS catalog, while alcohol consumption, non-alcoholic fatty liver disease, occasional smoking, and regular smoking data were obtained from the UK biobank. Pancreatic cancer-related data for the Finnish population were sourced from the latest R11 version of the Finnish database. Two-sample Mendelian randomization (MR) analysis was conducted on the associations between the aforementioned risk factors and pancreatic cancer using five MR methods, primarily inverse variance weighting. The robustness of the results was assessed through Q heterogeneity tests, pleiotropy tests, MR-PRESSO analysis, and reverse MR analysis.Results:Obesity showed a significant positive association with pancreatic cancer risk ( OR=1.407, 95% CI: 1.100-1.714, P=0.030), and the results were robust based on Q heterogeneity tests, pleiotropy tests, MR-PRESSO, and reverse MR analysis (all P>0.05). However, no significant associations were found between pancreatic cancer risk and alcohol consumption ( P=0.330), heavy drinking ( P=0.382), type 1 diabetes ( P=0.674), type 2 diabetes ( P=0.825), occasional smoking ( P=0.607), regular smoking ( P=0.758), non-alcoholic fatty liver disease ( P=0.287), acute pancreatitis ( P=0.336), or chronic pancreatitis ( P=0.545). Conclusion:This study further confirms the strong genetic association between obesity and increased pancreatic cancer risk.

This report evaluates the preliminary outcomes of a "six-in-one" integrated cough and asthma center developed under a dual-contract physician model at the Changfeng Community Health Service Center in Putuo District, Shanghai. By combining the efforts of family doctors and medical specialists, the center integrated six core functions-clinical treatment, prevention, nursing, rehabilitation, pharmacy, and nutrition-into a seamless management system covering screening, diagnosis, therapy, and follow-up. Supported by specialist guidance and teaching clinics, the model significantly enhanced comprehensive respiratory disease management capabilities within the community setting. The initiative not only improved patient health outcomes but also strengthened multidisciplinary collaboration and resource efficiency, offering a replicable example for improving chronic disease management in primary care through integrated and coordinated service delivery.

Recently, the number of artificial intelligence methods used to develop clinical risk prediction models has rapidly increased. To ensure the value of clinical prediction model research, researchers must report the research content transparently, completely, and accurately. Updated Guidance for Reporting Clinical Prediction Models that Use Regression or Machine Learning Methods (TRIPOD+AI) was released in 2024 and covers a checklist of 27 major items. It aims to promote the complete reporting of global clinical prediction model research and facilitate research evaluation, model evaluation, and model implementation. This article interprets and compares aspects such as the formulation process, checklist content, applicable scenarios, and advantages of TRIPOD+AI, as well as the original Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklist. It also analyzes an example of predicting the depression of elderly patients using artificial intelligence methods, providing references for researchers to standardize the reporting of clinical prediction models.

Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Objective Based on the transcriptome data of Scolopendra subspinipes mutilans L.Koch,SSR primers were designed and developed to evaluate the genetic diversity and analyze the population structure of the germplasm resources of S.mutilans,which can provide a theoretical basis for the development and utilization of the germplasm resources of S.mutilans.Methods We collected 301 samples of S.mutilans from major production areas,and analyzed the population genetic diversity and population structure of the germplasm resources of S.mutilans using 18 pairs of highly polymorphic SSR primers after screening.Results A total of 142 alleles were amplified by 18 primer pairs across all samples,with an average of 7.89 alleles amplified per locus.The mean of observed heterozygosity(HO)of the 18 populations was 0.39,the mean of expected heterozygosity(HE)was 0.46,the mean of polymorphism information content(PIC)was 0.41,the mean of Nei's gene diversity index(H)was 0.46,and the mean of Shannon information index(I)was 0.81.The results showed that the wild resources of S.mutilans collected in this study had a high level of genetic diversity,Four populations in Anhui and Zhejiang had higher genetic diversity than populations in Hubei.Molecular analysis of variance(AMOVA)of the population showed that most of the genetic variation in the materials of this study mainly occurred within populations.The STRUCTURE analysis of germplasm resources showed that all germplasm could be divided into four populations.Conclusion This study showed that the natural population of S.mutilans possesses high genetic diversity with high genetic variation and is better adapted to changes in the environment.Our results provided a research basis for the rational utilization of the germplasm resources of S.mutilans and the selection and breeding of superior varieties.