BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

BACKGROUND:Steroid-induced femoral head necrosis is mostly caused by long-term and extensive use of hormones,but its specific pathogenesis is not yet clear and needs further study. OBJECTIVE:To screen out the differential miRNAs in osteoclast exosomes after the intervention of Panax notoginseng saponins,and on this basis,to further construct an osteogenic-related ferroptosis regulatory network to explore the potential mechanism and research direction of steroid-induced osteonecrosis of the femoral head. METHODS:MTT assay was used to detect the toxic effects of different concentrations of dexamethasone and different mass concentrations of Panax notoginseng saponins on Raw264.7 cell line.Tartrate resistant acid phosphatase staining and TUNEL assay were used to detect the effects of Panax notoginseng saponins on osteoclast inhibition and apoptosis.Exosomes were extracted from cultured osteoclasts with Panax notoginseng saponins intervention.Exosomes from different groups were sequenced to identify differentially expressed miRNAs.CytoScape 3.9.1 was used to construct and visualize the regulatory network between differentially expressed miRNAs and mRNAs.Candidate mRNAs were screened by GO analysis and KEGG analysis.Finally,the differential genes related to ferroptosis were screened out,and the regulatory network of ferroptosis-related genes was constructed. RESULTS AND CONCLUSION:(1)The concentration of dexamethasone(0.1 μmol/L)and Panax notoginseng saponins(1 736.85 μg/mL)suitable for intervention of Raw264.7 cells was determined by MTT assay.(2)Panax notoginseng saponins had an inhibitory effect on osteoclasts and could promote their apoptosis.(3)Totally 20 differentially expressed miRNAs were identified from osteoclast-derived exosome samples,and 11 differentially expressed miRNAs related to osteogenesis were predicted by target mRNAs.The regulatory networks of 4 up-regulated differentially expressed miRNAs corresponding to 155 down-regulated candidate mRNAs and 7 down-regulated differentially expressed miRNAs corresponding to 238 up-regulated candidate mRNAs were constructed.(4)Twenty-four genes related to ferroptosis were screened out from the differential genes.Finally,12 networks were constructed(miR-98-5p/PTGS2,miR-23b-3p/PTGS2,miR-425-5p/TFRC,miR-133a-3p/TFRC,miR-185-5p/TFRC,miR-23b-3p/NFE2L2,miR-23b-3p/LAMP2,miR-98-5p/LAMP2,miR-182-5p/LAMP2,miR-182-5p/TLR4,miR-23b-3p/ZFP36,and miR-182-5p/ZFP36).These results indicate that Panax notoginseng saponins may regulate osteoblast ferroptosis by regulating the expression of miRNAs derived from osteoclast exosomes,thus providing a new idea for the study of the mechanism of steroid-induced femoral head necrosis.

Objective:To evaluate the effect of terlipressin combined with dopamine on intraoperative renal perfusion and early postoperative renal function in patients undergoing living-donor kidney transplantation.Methods:In this prospective cohort study, 84 patients of either sex, aged 18-64 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, undergoing living-donor kidney transplantation at the First Affiliated Hospital of Zhengzhou University from September 2022 to July 2024, in whom dopamine was continuously infused during operation to maintain fluctuation in the mean arterial pressure within 10% of the baseline value, were selected and divided into dopamine group (group D, n=42) and dopamine+ terlipressin group (group DT, n=42) based on whether terlipressin was used during operation. Terlipressin was continuously infused at a constant rate even before induction in group DT. The renal artery resistance index, intraoperative urine output, urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and delayed postoperative transplanted renal function were recorded. Results:Compared with group D, the intraoperative renal vascular resistance index was significantly reduced, the intraoperative urine output was increased ( P<0.01), and no statistical change was found in the urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and incidence of delayed postoperative transplanted renal function in group DT ( P>0.05). Conclusions:Terlipressin combined with dopamine provides better efficacy than dopamine alone in improving intraoperative renal perfusion and exerts no effect on early postoperative renal function in patients undergoing living-donor kidney transplantation.

Objective:To evaluate the effect of terlipressin combined with dopamine on intraoperative renal perfusion and early postoperative renal function in patients undergoing living-donor kidney transplantation.Methods:In this prospective cohort study, 84 patients of either sex, aged 18-64 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, undergoing living-donor kidney transplantation at the First Affiliated Hospital of Zhengzhou University from September 2022 to July 2024, in whom dopamine was continuously infused during operation to maintain fluctuation in the mean arterial pressure within 10% of the baseline value, were selected and divided into dopamine group (group D, n=42) and dopamine+ terlipressin group (group DT, n=42) based on whether terlipressin was used during operation. Terlipressin was continuously infused at a constant rate even before induction in group DT. The renal artery resistance index, intraoperative urine output, urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and delayed postoperative transplanted renal function were recorded. Results:Compared with group D, the intraoperative renal vascular resistance index was significantly reduced, the intraoperative urine output was increased ( P<0.01), and no statistical change was found in the urine output within 24 h after surgery, concentration of creatinine within 7 days after surgery, glomerular filtration rate and incidence of delayed postoperative transplanted renal function in group DT ( P>0.05). Conclusions:Terlipressin combined with dopamine provides better efficacy than dopamine alone in improving intraoperative renal perfusion and exerts no effect on early postoperative renal function in patients undergoing living-donor kidney transplantation.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective To evaluate the effect of preoperative metabolic syndrome on early function of renal allografts in allogeneic kidney transplant recipients.Methods Clinical data of 117 kidney transplant recipients were retrospectively analyzed.According to the renal allograft function,they were divided into the delayed graft function(DGF)group(n=29)and non-DGF group(n=88).Relevant risk factors of DGF in recipients undergoing allogeneic kidney transplantation were assessed by univariate and multivariate regression analyses.The effect of preoperative metabolic syndrome on early function of renal allografts was analyzed.Results Among 117 kidney transplant recipients,47 cases were complicated with preoperative metabolic syndrome,and 29 cases developed postoperative DGF.In the DGF group,83％of the recipients were complicated with preoperative metabolic syndrome,higher than 74％in the non-DGF group(P＜0.05).Univariate analysis showed that the body mass index(BMI)and terminal serum creatinine(Scr)level of the donors,and BMI,blood glucose level,triglyceride level and the proportion of preoperative metabolic syndrome of the recipients in the DGF group were higher than those in the non-DGF group(all P＜0.05).Multivariate logistic regression analysis revealed that high Scr levels of the donors,high hemoglobin levels of the recipients and preoperative metabolic syndrome of the recipients were the independent risk factors for DGF after kidney transplantation(all P＜0.05).Conclusions Preoperative metabolic syndrome is an independent risk factor for DGF in allogeneic kidney transplant recipients.Corresponding measures should be taken to lower the incidence of DGF and other metabolic complications.

Objective: To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients. Methods: From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed. Results: A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Conclusion The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.

BACKGROUND:It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis,but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis. OBJECTIVE:To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis. METHODS:The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis.The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model.Consensus clustering algorithm,single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes.Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database,a medical ontology information retrieval platform. RESULTS AND CONCLUSION:Based on the four PANoptosis key genes(CASP1,CASP10,MEFV,and TNF),the diagnostic markers of osteoporosis were determined,and the risk prediction model was constructed and verified.Osteoporosis was divided into two different PANoptosis subtypes(clusters A,B and gene clusters A,B),and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A,respectively.Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.

Objective:To assess the efficacy of Tamsulosin monotherapy for overactive bladder(OAB)symptoms in benign prostatic hyperplasia(BPH)patients with the prostate volume(PV)<40 ml, and to analyze related factors affecting the efficacy.Methods:300 BPH patients with OAB were enrolled, with an average age of(66.9±7.7)years and the PV<40 ml.Smoking, drinking and other living habits were investigated.Data on the Overactive Bladder Symptom Score(OABSS), International Prostate Symptom Score(IPSS)and Quality of Life Scale(QOLS)were collected before and after 4 weeks of treatment with Tamsulosin 0.2 mg QN.The maximum urine flow rate(Qmax)and bladder residual urine volume(PVR)were measured before and after treatment.OBASS was used as the main assessment parameter to analyze the correlation of efficacy with age, lifestyle, pre-treatment symptom scores, PV, Qmax and PVR.Results:257 patients completed the study, and 169 patients were treated effectively, with an overall effectiveness rate of 65.8%.The effectiveness rates of the mild, moderate and severe OAB groups were 83.6%, 62.4% and 38.5%, respectively, with statistical significance( χ2=13.037, P=0.001).3 patients showed adverse drug reactions, including 2 patients with mild dizziness and 1 patient with nausea.The baseline OABSS score, the proportion of smoking patients and the proportion of drinking patients in the effectively treated OAB group were significantly lower than those in the ineffectively treated group.Multivariate analysis showed that baseline OABSS score( OR=0.735, P<0.001)and smoking( OR=2.111, P=0.029)were correlated with tamsulosin's efficacy in treating BPH patients with OAB with PV<40 ml. Conclusions:The effectiveness rate of Tamsulosin for the treatment of BPH patients with mild OAB with PV<40 ml is high.The baseline OABSS score and smoking are factors affecting the efficacy of Tamsulosin on OAB symptoms in these patients.