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.

Objective By screening and passaging G0 generation Wistar rats,we obtained hypoxia-sensitive and hypoxia-tolerant G1 generation rats,and then the differences in hypoxia sensitivity among these rats were preliminarily explored.Methods 200 Wistar rats(half male and half female)were selected as G0 generation and placed in a controlled oxygen concentration system.The hypoxia tolerance time,which refers to the time from placement to near death,was recorded for the G0 generation rats at an oxygen volume fraction of 3％.30 rats(half male and half female)with the shortest hypoxia tolerance time were selected for mating and passage to obtain G1 generation hypoxia-sensitive rats.Similarly,30 rats(half male and half female)with the longest hypoxia tolerance time were selected for mating and passage to obtain G1 generation hypoxia-tolerant rats.An additional 24 standard Wistar rats were randomly divided into two groups:a control group and a model group,with 12 rats in each group(half male and half female).The control group was kept in a normoxic environment,while the model group,along with the G1 generation hypoxia-sensitive rats(G1 sensitive group)and G1 generation hypoxia-tolerant rats(G1 tolerant group),were placed in a hypobaric hypoxia chamber(simulating an altitude of 5 000 m).After 12 hours,various indicators,including blood gas,complete blood count,blood biochemistry,pathological sections,and hypoxia-related genes were detected or observed to compare the differences in hypoxia sensitivity among the 4 groups.Results Compared with the G0 generation standard rats,the hypoxia tolerance time of G1 generation rats was significantly prolonged(P＜0.01).Compared with the model group,the oxygen saturation(SatO2)in G1 tolerant group was significantly higher(P＜0.05).In the G1 sensitive group,the levels of white blood cell(WBC)count,neutrophil(NEUT)count,hemoglobin(HGB)concentration,hematocrit(HCT),red blood cell distribution width(RDW),platelet(PLT),and creatinine(Cr)significantly increased(P＜0.05 or P＜0.01),while actual bicarbonate(AB)content significantly decreased(P＜0.05),and the brain and lung coefficients were significantly elevated(P＜0.05).In addition,pathological section results showed that the brain and lung tissues in the model group,G1 sensitive group,and G1 tolerant group all suffered from significant damage,with no evident differences in the gene expression levels of hypoxia-inducible factor-1 α(HIF-1α)and vascular endothelial growth factor A(VEG FA)in brain tissues amongthe three groups(P＞0.05).Conclusion Compared with standard rats,G1 generation hypoxia-sensitive/tolerant rats exhibit good signs of hypoxia sensitivity/tolerance traits,but further screening and passage are still needed to purify them.

Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Ulcerative colitis is characterized by the alternation of recurrence and remission of mucosal inflammation.Both its diagnosis and efficacy evaluation require the combination of clinical,laboratory examination,endoscopy,and histology.Therefore,evaluation scales are important for ulcerative colitis.Many different scales have been developed to accompany the escalation of therapeutic goals from clinical remission and mucosal healing to histological remission.This article summarized the current commonly used scales from multiple perspectives,including clinical evaluation,endoscopic evaluation,histological evaluation,and patient-reported assessment,which aimed to help clinical practitioners understand the advantages and disadvantages of different scales more comprehensively and choose more appropriate assessment method.

Objective A comparative study was conducted on rapid high-altitude models established in SD rats under two hypoxic stress modes,namely,a high-altitude field and simulated high-altitude environment,to evaluate the reliability of the simulated high-altitude test chamber.Methods SD rats were placed in a simulated rapid high-altitude animal experimental chamber(4000 m)or rapid high-altitude field laboratory(4010 m)to establish a rapid high-altitude rat model.After 24 or 72 h of exposure,physiological and pathological indicators related to high-altitude changes were collected and measured,mainly routine blood parameters,blood biochemistry,blood gas,oxidative damage indicators(superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)),and inflammation indicators(interleukin 1β(IL-1 β),interferon-γ(IFN-γ),monocyte chemotactic protein 1(MCP-1)and interleukin 6(IL-6)),and pathological tissue analysis and hypoxia sensitive gene(hypoxia inducible factor-1α(Hif-1α)and vascular endothelial growth factor A(Vegfa))testing were performed.Finally,differential analysis was conducted on the result to obtain a differential evaluation report.Results At the same altitude,both high-altitude field and simulated high-altitude exposure for 72 h caused significant lung and brain damage.Under the same exposure time,the routine blood parameter,blood biochemistry,and blood gas result for the rats were similar.There were no significant differences in the detection of inflammation indicators(IL-6,IL-1β,MCP-1,and IFN-y),oxidative damage indicators(MDA,SOD,and GSH),or hypoxia-sensitive gene expression(Hif-1α and Vegfa)in the brain.However,partial pressure of carbon dioxide(PaCO2)and base excess(BE)were significantly higher in the simulated-72 h group than the other treatment group.The lung hypoxia-sensitive genes(Hif-1α and Vegfa)in the simulated-72 h group showed no significant expression difference with control group,and the brain coefficient of the high-altitude field treatment group was significantly higher than that of the simulated high-altitude treatment group.These result indicate that there may be slight differences between models prepared in high-altitude field and simulated high-altitude environments.Conclusions The simulated high-altitude animal experimental chamber can successfully establish a rapid high-altitude animal model.The simulated altitude can be appropriately increased on the basis of 4000 m.If an altitude of 4000 meters is used,the exposure time should be greater than 24 h but slightly shorter than 72 h.The simulated high-altitude experimental module has good reliability,but it is advisable to use plateaus for on-site experiments as much as possible,if conditions permit.

Alzheimer''s disease (AD) has brought to us huge medical and economic burdens, and so discovery of its therapeutic drugs is of great significance.In this paper, we utilized knowledge graph embedding (KGE) models to explore drug repurposing for AD on the publicly available drug repurposing knowledge graph (DRKG).Specifically, we applied four KGE models, namely TransE, DistMult, ComplEx, and RotatE, to learn the embedding vectors of entities and relations on DRKG.By using three classical knowledge graph evaluation metrics, we then evaluated and compared the performance of these models as well as the quality of the learned embedded vectors.Based on our results, we selected the RotatE model for link prediction and identified 16 drugs that might be repurposed for the treatment of AD.Previous studies have confirmed the potential therapeutic effects of 12 drugs against AD, i.e., glutathione, haloperidol, capsaicin, quercetin, estradiol, glucose, disulfire, adenosine, paroxetine, paclitaxel, glybride and amitriptyline.Our study demonstrates that drug repurposing based on KGE may provide new ideas and methods for AD drug discovery.Moreover, the RotatE model effectively integrates multi-source information of DRKG, enabling promising AD drug repurposing.The source code of this paper is available at https://github.com/LuYF-Lemon-love/AD-KGE.

Objective:To compare and analyze the efficacy and safety of intraoperative radiotherapy (IORT) combined with conventional therapy (surgery combined with radiochemotherapy) and conventional therapy alone for pancreatic cancer.Methods:Literature review was conducted from PubMed, Cochrane Library, Web of Science, Embase, Chongqing VIP, CNKI, Wanfang Data and China Biomedical Literature Service System (SinoMed). The literatures that met the inclusion criteria were screened and the data were extracted. Meta-analysis was carried out by RevMan 5.4 software.Results:A total of 11 studies consisting of 813 patients were included. According to the combined results, compared with conventional therapy, IORT combined with conventional therapy could improve the overall survival rate of pancreatic cancer ( HR=0.66, 95% CI=0.54-0.81, Z=4.03, P<0.001), and did not increase the treatment-related side effects ( OR=1.00, 95% CI=0.69-1.46, Z=0.01, P=0.99), but failed to bring benefit to the local control rate ( HR=0.56, 95% CI=0.31-1.01, Z=1.93, P=0.05). Conclusions:The overall survival rate in the IORT combined with conventional therapy group is significantly better than that in the conventional therapy group. No significant difference is found in the treatment-related adverse reactions between two groups. IORT combined with conventional therapy is worthy of clinical application.

Objective:To investigate the transcriptomic mechanisms and clinical efficacy of D-CAG regimen for the treatment of acute myeloid leukemia (AML) after failure to initial induction of remission.Methods:The transcriptome data of AML cells before and after the use of dexitabine before August 28, 2021 was searched in Gene Expression Omnibus (GEO) database with "decitabine" as the search term. The R language package was used for differential expression analysis and Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis of the data. Protein-protein interaction network (PPI) analysis was conducted on the STRING online analysis website. The accurate treatment prediction platform designed based on logistic omics theory (EpiMed) was used to make drug-disease-target correlation analysis. The clinical data of 18 AML patients treated with D-CAG regimen after failure to induction of remission with standard anthracycline and cytarabine regimen ("3+7" regimen) in the 305th Hospital of Chinese PLA from October 8, 2015 to July 9, 2018 were searched and analyzed, and the curative effect was evaluated. The effects of the dose and duration of each drug on the efficacy were analyzed.Results:The transcriptome data of AML cells before and after the use of decitabine in GSE40442 dataset of the GPL5188 platform were finally selected, updated on July 10, 2014. A total of 366 differentially expressed genes were screened, including 201 up-regulated genes and 165 down-regulated genes. The differential genes were mainly related to cell cycle regulation, bone marrow leukocyte migration and differentiation, transcriptional regulation, bone marrow hematopoiesis and other signaling pathways. Ten core genes such as ANXA5, IL-10, THBS1, TLR4, JUN and CXCL12 were screened by PPI analysis. Drug-disease-target analysis showed that dexitabine had a potential therapeutic effect on various blood diseases such as diffuse large B-cell lymphoma, thrombocytopenia, T-cell acute lymphocytic leukemia, aplastic anemia, and AML. Of the 18 patients, after initial induction of remission, 7 (38.8%) patients achieved partial remission (PR), and 11 (61.2%) patients had no response (NR); after one cycle of re-induction remission therapy, 9 patients had complete remission (CR), 5 patients had PR, 4 patients had NR, and the overall response rate (ORR) was 77.8% (14/18). Compared with patients with NR, the CR rate was higher in patients with PR after initial induction therapy, which were 85.7% (6/7) and 27.3% (3/11), and the difference was statistically significant ( χ2=5.84, P = 0.025). The median duration of cytarabine in CR patients was longer than that in NR patients [10 d (7-14 d) vs. 5 d (2-8 d), Z = 3.89, P = 0.002] and the median ratio of the number of bone marrow blast cells to the duration cytarabine was lower in CR patients than that in NR patients [2.29 (0.89-9.10) vs. 8.10 (3.00-38.50), Z = -2.19, P = 0.006]; the median dose of cytarabine in CR patients was lower than NR patients, which were 50 mg·m -2·d -1 (30-150 mg·m -2·d -1) and 100 mg·m -2·d -1 (50-500 mg·m -2·d -1), and the difference was not statistically significant ( Z = -1.80, P = 0.074). Conclusions:AML patients with PR after initial induction and failure to initial induction of remission may be more likely to achieve CR after the treatment of D-CAG regimen, and this change may be related to the epigenetic regulation of decitabine.

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

The clinical data of patients with chlamydia psitsiti pneumonia confirmed by metagenomic next-generation sequencing (mNGS) who were admitted to the Huizhou Municipal Central Hospital from January 2020 to November 2021 were retrospectively analyzed. Among 21 patients, the serum creatine kinase (CK) was elevated in 10 cases, and 5 cases was complicated with rhabdomyolysis (RM). The symptoms of patients with Chlamydia psittaci pneumonia-induced RM were severe, including high fever, dyspnoea, headache and myalgia; 2 case were complicated by acute kidney injury (AKI) and neurological symptoms. Laboratory testing showed a marked increase in CK, myoglobin (Mb), high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and D-dimer levels in all 5 patients. The chest CT revealed large areas of pulmonary consolidation, ground-glass opacity in 1 case and a small amount of pleural effusion in 2 cases. One patient died from multiple organ failure, and the other 4 patients were discharged with considerable improvement. Patients with psittacosis pneumonia are prone to developing rhabdomyolysis, early detection and early treatment can effectively improve the prognosis of patients.