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.

Objectives:To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)—NP@Pt(Ⅳ) in ovarian cancer.Methods:Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)—Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment ( P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm 3, which was significantly lower than those in control group [(1 349±161) mm 3, P<0.001] and cisplatin group [(715±293) mm 3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion:Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

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 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.

Objective: This study aims to analyze factors associated with lymphovascular space invasion (LVSI) and evaluate the prognostic significance of LVSI in Chinese endometrioid endometrial cancer (EEC) patients. Methods: Five-hundred eighty-four EEC patients undergoing surgery in our center from 2006 to 2016 were selected for analysis. Univariate analysis and multivariate logistic regression were used to examine relevant factors of LVSI. To evaluate the prognostic role of LVSI, survival analyses were conducted. In survival analyses, both multivariate Cox regression and propensity score matching were used to control the confounders. Results: The incidence of LVSI was 12.16% (71/584). Diabetes history (p=0.021), lymph node metastasis (p=0.005), deep myometrial invasion (p<0.001) and negative PR expression (p=0.007) were independently associated with LVSI. Both Kaplan-Meier method and univariate Cox regressions showed LVSI negative and positive cases had similar tumor-specific survival (TSS) and disease-free survival (DFS). After adjusting for the influence of adjuvant therapy and other clinicopathological factors with multivariate Cox regressions, LVSI still could not bring additional survival risk to the patients (p=0.280 and p=0.650 for TSS and DFS, respectively). This result was verified by Kaplan-Meier survival analyses after propensity score matching (p=0.234 and p=0.765 for TSS and DFS, respectively). Conclusion LVSI does not significantly compromise the survival outcome of Chinese EEC patients.

Objective To study the surgery effect on early application of toe flap to repair thumb severe electric bum.Methods From July 2007 to October 2017,a total of 25 cases of thumb severe electric burn were repaired by thumb toe flap grafting.The function of the finger after operation was evaluated comprehensively,and the effect of 72 hours before and after the injury was compared.Results All the flaps survived and the finger function was excellent.The excellent and good rate of 25 cases was 72％.The excellent and good rate of 72 hours before and after injury were 85.7％ and 54.5％ respectively.5 cases had bad wound complications after operation.1 cases were operated within 72 hours after injury,and 4 cases were operated after 72 hours.Conclusions The early application of toe flap to repair severe electric bum thumb can maximize the recovery of function of the thumb.The earlier the operation,the fewer complications,the better the repair effect.

Objective To investigate the difference of vacuum sealing drainage (VSD) on the effect of one-stage skin graft and second-stage sugery after scar release.Methods A total of 42 patients who wanted to undergo scar release and skin graft was randomly divided to control group (n =21) and VSD treatment group (n =21).The control group implemented skin graft immdiately after scar release while VSD treatment group were treated with VSD for 3 days after scar release and then implemented skin graft.The rate of subcutaneous blood stasis and the survival rate of skin graft were observed at 7 days after skin graft.The condition of grafted skin contracture and hyperplasia after half a year was also observed.Results The incidcnce of subcutaneous blood stasis was significantly lower in the VSD group than that in the control group (P ＜ 0.05).The survival rate of skin grafts was significantly higher in the VSD group than that of the control group (P ＜ 0.05).The score of Vancouver scar was significantly lower in the VSD group than that in the control group (P ＜ 0.05).Conclusions VSD treatment of second-stage sugery after scar release can reduce the occurrence of subcutaneous blood stasis,promotc skin graft survival,reduce postoperative skin graft contracture and improve the prognosis of patients compared to one-stage skin graft.

OBJECTIVE To analyze trimethylation of genome-wide histone H3 lysine 4(H3K4met3) induced by silicon dioxide(SiO2)through chromatin immunoprecipitation linked to microarrays(ChIP-chip)in lung fibroblast(LF)of rats. METHODS A primary co-culture model of rat alveolar macrophages (AM)and LF in vitro. AM were exposed to 100 mg · L-1 free SiO2 for 24 h,before LF were collected and the phenotype of LF was determined after transdifferentiation by immunohistochemistry. ChIP-chip was used to profile the variations of trimethylation in H3K4 of lung fibroblasts in CpG island regions. ChIP-qPCR was used to validate the microarray results. The mRNA expression of nfib and kpna3 was analyzed by qRT-PCR. RESULTS Totally 1815 (518 increased and 1297 decreased) genes of H3K4met3 displayed significant differences in SiO2 100 mg·L-1 group compared with control group(Cy3/Cy5 value>2.0 or <0.5,NimbleScan V2.5 software). The results of ChIP-qPCR were quite consistent with those of microarray. CONCLUSION There are significant differences in methylation of genome-wide H3K4 between SiO2 100 mg·L-1 group and control group. These novel candidate genes may become potential biomarkers or new interfered targets.

OBJECTIVE: To study the effect and outcome of Boari bladder flap plasty surgery for the treatment of kidney-sparing strategy for patients with middle and lower ureteral carcinoma. METHODS: Database at the department of urology in the Second Xiangya Hospital from 2002-2007 was screened and all cases of primary solitary lower ureteral carcinoma treated with Boari bladder flap plasty surgery or radical nephroureterectomy were collected. We performed a retrospective review of the clinical data including sex, age, smoking history, tumor site, size, stage, grade, bladder recurrence, renal function et al and evaluated survival rate. The Cox proportional hazards regression model was build to analyze the correlation between each variable and survival time. RESULTS: Thirty nine patients in total were enrolled, including 16 cases underwent Boari bladder flap plasty surgery and 23 cases underwent radical nephroureterectomy. The median follow-up time was 53 months (range 10-84 months). During the follow-up time, 18 patients died, including 6 patients treated with Boari bladder flap plasty surgery and 12 patients treated with radical nephroureterectomy. The estimated bladder recurrence-free survival rate and cancer-specific survival rate at 5 years were 63% vs 59% and 73.8% vs 73.5%, respectively (P>0.05). The survival rate at 5 years and the overall survival rate were 61% vs 57 % and 64.8% vs 58.1% respectively in the 2 groups (P>0.05). There was no significant difference in renal function before surgery between the two groups [creatinine clearance 57 (32-104 ) mL/ min vs 55 (30-102) mL/ min, P>0.05]. Patients underwent Boari bladder flap plasty showed better renal function than patients underwent radical nephroureterectomy [creatinine clearance 55 (35-102) mL/ min vs 43 (30-89) mL/min, P<0.05]. In multivariate Cox regression analysis, the tumor size, pT stage, tumor cell grade and the estimated glomerular filtration rate level were independent factors that affected the overall survival rate of the patients (P<0.05). The tumor size, pT stage and tumor cell grade were positively correlated to the survival time, and the estimated glomerular filtration rate was negatively correlated to the survival time. CONCLUSION Boari bladder flap plasty surgery could be used to treat lower ureteral carcinoma. Compared with radical nephroureterectomy, Boari bladder flap plasty surgery has equal survival rate and shows superior postoperative renal function.
Carcinoma ; surgery ; Humans ; Kidney ; Neoplasm Recurrence, Local ; Nephrectomy ; Postoperative Period ; Proportional Hazards Models ; Retrospective Studies ; Surgical Flaps ; Survival Rate ; Ureter ; pathology ; Ureteral Neoplasms ; surgery ; Urinary Bladder ; surgery ; Urologic Surgical Procedures ; methods

OBJECTIVETo evaluate the clinical results of tube gastrostomy in radical cystectomy and ileal conduit.

METHODSWe retrospectively analyzed the data of 98 patients undergoing radical cystectomy and ileal conduit between March 2007 and February 2010. According to postoperative gastrointestinal decompression methods, the patients were divided into nasogastric decompression group (n=50) and tube gastrostomy group (n=48), and the gastrointestinal recovery time, surgical complications and hospital stay were compared between them.

RESULTSNo statistical difference was found in gastrointestinal recovery time, hospital stay, or surgical complications between the two groups, but the incidence of pulmonary infection was significantly lower in tube gastrostomy group than in nasogastric decompression group (P<0.05).

CONCLUSIONTube gastrostomy is an easy, safe and effective means for gastric decompression after radical cystectomy with ileal conduit, especially suitable for elderly patients and those with potential pulmonary disorder.

Aged ; Aged, 80 and over ; Cystectomy ; Decompression, Surgical ; methods ; Female ; Gastrostomy ; Humans ; Male ; Middle Aged ; Postoperative Period ; Retrospective Studies ; Urinary Diversion