BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters，such as R.E.N.A.L.，PADUA，C-Index，which are used to guide the clinical selection of surgical modalities，and predict perioperative complications and prognosis. In this paper，various scoring systems are grouped into three major categories according to their functions：prediction of surgical complexity，prediction of complications，and prediction of prognosis. The contents，characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists，enhance their surgical decision-making ability，and improve the clinical outcomes.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

MiR-138-5p is a microRNA that plays an important regulatory role in the pathogenesis of osteoarthritis.MiR-138-5p regulates various biological processes,including inflammation,cell apoptosis and proliferation,and matrix degradation in osteoarthritis,by modulating signaling pathways including nuclear factor-κB,Wnt/β-catenin,and phosphoinositide 3-kinase/AKT.This review summarizes the research progress regarding the mechanism of miR-138-5p in osteoarthritis.

Objective:To observe the clinical efficacy of auricular needle-embedding therapy for treating primary insomnia. Methods:A total of 63 patients were randomly divided into a conventional acupuncture group and an auricular needle-embedding group.The conventional acupuncture group received acupuncture at meridian points,while the auricular needle-embedding group received acupuncture at auricular points.Treatments were given once a day for 6 consecutive days,followed by a 1-day break,as a course of treatment.Both groups were treated for 2 courses.Before treatment,and after 1 course and 2 courses of treatment,the Pittsburgh sleep quality index(PSQI)score was assessed,and the efficacy was evaluated. Results:The cured and markedly effective rate and total effective rate of the auricular needle-embedding group were higher than those of the conventional acupuncture group,but there was no significant difference between the two groups(P>0.05).After 1 course of treatment,the PSQI global score and the scores of subjective sleep quality,sleep latency,sleep duration,habitual sleep efficiency,and daytime dysfunction of both groups decreased compared with those before treatment(P<0.01);there was no statistical significance in comparing the PSQI global score and individual component scores between the two groups(P>0.05).After 2 courses of treatment,the PSQI global score and the scores of sleep latency and habitual sleep efficiency of the auricular needle-embedding group decreased compared with those after 1 course of treatment(P<0.01 or P<0.05),while only the score of sleep latency of the conventional acupuncture group decreased compared with that after 1 course of treatment(P<0.05);the PSQI global score and the scores of subjective sleep quality and sleep latency of the auricular needle-embedding group were lower than those of the conventional acupuncture group(P<0.05). Conclusion:Both therapies can improve insomnia.Compared to conventional acupuncture,auricular needle-embedding therapy demonstrates a therapeutic advantage in improving sleep latency and sleep quality,making it worthy of clinical promotion.

Objective This study aimed to clarify the anti-influenza virus activity of Bingyanqing(BYQ),as well as to explore the mechanism of BYQ in treating influenza through network pharmacology and experimental verification.Methods The impact of BYQ on mortality,lung index,and viral load in an influenza mouse model was detected.We collected the ingredients and targets of BYQ formula by searching databases including TCMSP,Swiss Target Prediction and consulting the literature.The"ingredients-common target"network for anti-influenza effect of BYQ was constructed using Cytoscape software.The protein-protein interaction(PPI)network was constructed using the STRING database and Cytoscape software,and the core targets were screened.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for common targets.The effect of BYQ on reducing influenza-induced oxidative damage,the expression of antioxidant and pro-oxidant enzyme,P65 phosphorylation and nuclear factor E2-related factor 2(Nrf2)nuclear translocation in vivo were investigated.Results BYQ significantly reduced mortality,lung index,pulmonary viral load and lung injury in a mouse model of influenza.We obtained one hundred and ninety-three of BYQ active compounds,which corresponded to three hundred and thirty-eight targets.There are 180 influenza-related targets among them.Nine targets,including IκBα kinase α(CHUK),IκBα kinase γ(IKBKG),NF-κB p65(RELA),tumor necrosis factor(TNF)and interleukin 6(IL6),were identified as potential core targets.GO analysis indicated that BYQ is involved in several biological functions,including antibacterial and antioxidant stress responses.KEGG analysis revealed the involvement of several viral and immune-related pathways for BYQ in treating influenza,including herpes simplex virus,influenza A virus,TNFα and toll-like receptor pathways.In vivo studies showed that high-dose BYQ significantly reduced pulmonary malondialdehyde(MDA)levels(P＜0.01)and increased total superoxide dismutase(SOD)activity(P＜0.001)in a mouse mode of influenza compared to oseltamivir phosphate.The treatment group with the combination of BYQ&oseltamivir phosphate had lower levels of NADPH oxidase 2(NOX2)and 4(NOX4)(P＜0.001),and higher levels of catalase(CAT)and glutathione peroxidase 4(GPX4)(P＜0.001)in the lungs than oseltamivir phosphate group.The combined treatment group showed more significant Nrf2 nuclear translocation(P＜0.05)than the oseltamivir phosphate group.However,there was no significant difference in P65 phosphorylation levels between the combination treatment group and the oseltamivir phosphate group(P＜0.05),but P65 phosphorylation levels in both groups were lower than in the model group(P＜0.05).Conclusion BYQ exhibits significant anti-influenza virus activity,manifests a dual effect by inhibiting the synthesis of pro-oxidant enzymes and promoting the antioxidant system,thereby alleviates the oxidative stress damage caused by influenza.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

Objective:To identify and improve the weakness in different clinical practice teaching hospital,and enhance the quality of practical teaching.Methods:A total of 291 trainees majoring in clinical medicine in grade 2016 in a medical college in Shenyang who practiced in different clinical teaching hospitals and participated in the objective structured clinical examination(OSCE)were enrolled.The OSCE scores was analyzed with one way ANOVA and Kruskal-Wallis statistic methods to identify the weakness in clinical practice teaching and improve the teaching quality.Results:In the standardized patient consultation and physical examination results,the passing rate and average score of H hospital was the lowest.The average score of trainees in H hospital was statistically significant compared to that in A,B,F,G,K,and L hospitals(P＜0.01).In terms of skill operation scores,H hospital had the lowest pass rate and average score.The average score of interns in H hospital was statistically significant compared to that in A,D,E,F,G,I,J,K hospitals(P＜0.01).In the interpretation of auxiliary examination results,the passing rate and average score of H hospital was the lowest.The average score of interns in A and H hospital was significantly different from that of B and J hospitals(P＜0.01).Conclusions:There are great differences in the practice effect of students in different clinical teaching hospitals.Medical colleges and universities should strengthen the management of clinical teaching hospitals to ensure the homogeneity of clinical practice teaching quality.