1.Identification and drug sensitivity analysis of key molecular markers in mesenchymal cell-derived osteosarcoma
Haojun ZHANG ; Hongyi LI ; Hui ZHANG ; Haoran CHEN ; Lizhong ZHANG ; Jie GENG ; Chuandong HOU ; Qi YU ; Peifeng HE ; Jinpeng JIA ; Xuechun LU
Chinese Journal of Tissue Engineering Research 2025;29(7):1448-1456
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.
2.Short-term efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for the treatment of non-small cell lung cancer
Yixing LI ; Heng ZHAO ; Bohao LIU ; Jizhao WANG ; Yanpeng ZHANG ; Chendong GUO ; Chuchen ZHAO ; Kun FAN ; Hongyi WANG ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):369-374
Objective To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
3.Thoracic surgery perspective of comprehensive treatment of esophageal cancer with esophagus preserved
Ruiyang SUO ; Zhiyu WANG ; Runyi TAO ; Jinteng FENG ; Kun FAN ; Hongyi WANG ; Heng ZHAO ; Bohao LIU ; Yixing LI ; Yanpeng ZHANG ; Jia ZHANG ; Guangjian ZHANG ; Junke FU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(02):245-250
Surgery is a classic traditional method for the treatment of early-stage esophageal cancer, and it is also recognized as an effective first-choice method in the medical community. With the development of endoscopic technology, esophagus-preserving comprehensive treatment of esophageal cancer has almost the same or even better effects in some aspects in the treatment of early esophageal cancer than surgery. Many clinical guidelines have also recommended it as the first-choice treatment for early esophageal cancer. The room for surgical treatment of esophageal cancer has been further compressed. This article discusses the comprehensive treatment model of esophageal cancer from the perspective of thoracic surgery, aiming to find a new position of thoracic surgery in the treatment of esophageal cancer.
4.Treatment of Stage Ia Non-small Cell Lung Cancer in Patients: Comparison of Ablation and Sub-lobectomy.
Heng ZHAO ; Kun FAN ; Hongyi WANG ; Bohao LIU ; Yixing LI ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Lung Cancer 2021;24(9):613-622
BACKGROUND:
Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients' survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis.
METHODS:
Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures.
RESULTS:
The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P<0.05). In the univarlable analysis, the hazard ratio (HR) of sub-lobotomy group was 0.571 (95%CI: 0.455-0.717) compared with the ablation group. Patients treated with sub-lobectomy had a 0.571 times greater risk of adverse outcomes than those treated with ablation. In the multivariable analysis, the HR for sub-lobectomy group was 0.605 (95%CI: 0.477-0.766) compared with the ablation group. Patients treated with sub-lobectomy had a 0.605 time greater risk of adverse outcomes than those treated with ablation. The results suggested that the overall survival rate of patients with stage Ia NSCLC treated with sub-lobotomy was higher than that of patients treated with ablation.
CONCLUSIONS
This study suggests that there is a significant difference in overall survival of stage Ia NSCLC patients treated with ablation and with sub-lobotomy. Patients treated with sub-lobotomy for stage Ia NSCLC had higher overall survival than those treated with ablation.
5.Mechanism of microglia involved in the pathophysiology of brain white matter hyperintensity
Hongyi YU ; Zhongyi JIA ; Zhongling ZHANG
International Journal of Cerebrovascular Diseases 2021;29(6):467-470
As an important imaging marker of cerebral small vessel disease, white matter hyperintensity is closely associated with the clinical manifestations such as cognitive impairment, gait abnormalities, and urinary incontinence. Current studies have shown that the destruction of blood-brain barrier and inflammation response are the important pathophysiological mechanisms of white matter hyperintensity. As the most common immune cell in the inflammatory response of the central nervous system, microglia activation is the key to the occurrence and development of white matter hyperintensity. This article reviews the pathophysiological mechanisms of microglia involved in brain white matter hyperintensity.
6.Anatomy of upper lung lobes of patients with small pulmonary nodules based on three-dimensional reconstruction of PC
Kun FAN ; Jinteng FENG ; Hongyi WANG ; Jia ZHANG ; Haiqi HE ; Zhuoqi JIA ; Xiaopeng WEN ; Qifei WU ; Junke FU ; Guangjian ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(9):557-561
Objective:The extensive development of anatomical pulnonary segmentectomy requires thoracic surgeons to be familiar with the anatomical variations of the lung segment. The purpose of this study is to analyze the anatomical patterns of the right upper lobe lung segment using three-dimensional reconstruction, and to count rare variant types.Methods:From October 2017 to March 2020, 101 patients with small pulmonary nodules who were undergo segmental resection in our center were subjected to preoperative three-dimensional reconstruction of the lung structure, and the reconstruction data was retained for the statistics and analysis of the anatomical structure in the right upper lung lobe.Results:The right upper lobe bronchus is the most common with three branches(77/101), followed by two branches(16/101) and four branches(7/101). The two branches(70/101) of the right upper lobe pulmonary artery are the most common, followed by single branch(19/101) and three branches(11/101). In rare cases, four branches(1/101 cases) can be seen. The two branches(63/101) of the right upper pulmonary vein were the most common, followed by three branches(32/101) and single branch(6/101). In addition, a total of 12 rare mutations were counted. There were 2 variants in the bronchus, totaling 2 cases; 4 rare variants in the pulmonary artery, 13 cases total; 6 rare variants in the pulmonary vein, 10 cases total.Conclusion:The lung anatomy is complex and has many variations. The surgeon should fully grasp the anatomical structure of the lung segment of the patient's operating area before surgery, the data in this article will be a valuable reference for thoracic surgeons to carry out the upper right lobe segmentectomy.
7.Human urinary kallidinogenase reduces cerebral ischemia-reperfusion injury through activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathway in rats
Yaowu WANG ; Hongyi ZHANG ; Chunli YIN ; Yehua JIA
Chinese Journal of Neuromedicine 2019;18(5):459-463
Objective To study the protective effect of human urinary kallidinogenase (HUK) on focal cerebral ischemia-reperfusion injury in rats via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Methods Eighty adult male SD rats were randomly divided into sham-operated group,model group,HUK group and LY294002 group (n=20).The rat focal cerebral ischemia-reperfusion models in the latter three groups were established by suture-occluded method;model group and HUK group were,respectively,injected with sterile saline or HUK 1.0 mL/kg via tail vein 3 h after reperfusion;rats in the LY294002 group accepted intraventricular injection of 10 nmol LY294002 before cerebral ischemia and caudal vein injection of 1.0 mL/kg HUK three h after reperfusion.Twenty-four h after reperfusion,Neurological Deficit Scale was performed,cerebral infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining,and protein expressions of Akt,phosphorylated (p)-Akt and Caspase-3 were assessed by Western blotting.Results As compared with those in the model group,the Neurological Deficit Scale scores were significantly lower,cerebral infarct volumes were significantly smaller,p-Akt expression was significantly increased,and Caspase-3 expression was significantly decreased in the HUK group (P<0.05).As compared with those in the HUK group,Neurological Deficit Scale scores were significantly higher,infarction volumes were significantly increased,p-Akt expression was significantly decreased,and Caspase-3 expression was significantly increased in the LY294002 group (P<0.05).Conclusion HUK has neuro-protective effect through up-regulating p-Akt expression in the PI3K/Akt signaling pathway and down-regulating Caspase-3 expression.
8.Development and verification of reference nucleic acid materials of H9N2 influenza viruses by real-time RT-PCR.
Jie SONG ; Cui LI ; Jing LI ; Shuang ZHANG ; Wenhui FAN ; Lirong LIU ; Hongyi JIA ; Aibi YU ; Ke HAO ; Chunyan NIU ; Jing WANG ; Qizu ZHAO ; Wenjun LIU
Chinese Journal of Biotechnology 2018;34(10):1579-1586
The HA gene of H9N2 influenza virus (A/chicken/Hunan/04.14 (H9N2)) was amplified and sequenced. The RNA was synthesized by in vitro transcription. The RNA transcription solutions were diluted to 10⁹ copies/μL using the RNA storage solution. The aliquoted RNA solutions were used to evaluate the homogeneity and stability. The results were determined by the average value obtained from four independent laboratories. Furthermore, the fluorescence quantitative RT-PCR method was also developed to verify the detection accuracy of clinical samples. The detection limit of this method is approximately 10 copies. Taken together, the RNA transcription solution established in our study can used as positive standard reference for rapid detection of H9N2 influenza virus.
9.Clinical efficacy of preoperative SIB-IMRT for 26 cases of locally-advanced low rectal cancer
Qiteng LIU ; Linchun FENG ; Baoqing JIA ; Xiaohui DU ; Hongyi LIU ; Guanghai DAI ; Jing CHEN ; Yongqiang YANG ; Ke WEN ; Yunlai WANG ; Tao YANG ; Yuyan GAO
Chinese Journal of Radiation Oncology 2018;27(10):906-910
Objective To evaluate the feasibility and clinical efficacy of preoperative simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with neoadjuvant chemotherapy of capecitabine in patients with locally-advanced low rectal cancer.Methods Between 2015 and 2016,26 patients admitted to 301 Hospital who were diagnosed with locally-advanced low rectal cancer,which was located within 5 cm from the anal verge,were enrolled in this investigation.Dose fractionation pattern was delivered:58.75 Gy in 25 fractions (2.35 Gy/fraction) for rectal cancer and lymph node metastasis and 50 Gy in 25 fractions for the pelvic lymphatic drainage area and simultaneously combined with capecitabine chemotherapy (825 mg/m2,bid d 1-5 weekly).One cycle of capecitabine (1 250 mg/m2,twice daily,d 1-14)was given at one week after the completion of chemoradiotherapy (CRT).Total mesorectal excision (TME)was performed at 6 to 8 weeks after the completion of CRT.The primary endpoints included pathological complete response rate (ypCR) and sphincter-preserving rate.The secondary endpoints included acute toxicity,tumor downstaging rate and postoperative complications.Results Twenty-six patients successfully completed neoadjuvant CRT,25 of them underwent surgical resection and one patient failed to receive surgery due to pxrianal edema.Postoperative ypCR rate was 32% (8/25),the sphincter-preserving rate was 60% (15/25),the tumor downstaging rate was 92% (23/25) and the R0 resection rate was 100%.During the period of CRT,grade 1 and 2 adverse events occurred in 24 patients,grade 3 radiation dermatitis was noted in 2 cases.No ≥ grade 4 acute adverse event was observed.Postoperative complications included ureteral injury in one case and intestinal obstruction in one patient.Conclusions Preoperative SIB-IMRT combined with neoadjuvant chemotherapy of capecitabine is a feasible and safe treatment for patients with locallyadvanced low rectal cancer,which yields expected ypCR rate,R0 resection rate and sphincter-preserving rate.Nevertheless,the long-term clinical benefits remain to be elucidated.Clinical Trial Registry Chinese Clinical Trial Registry,registration number:ChiCTR-ONC-12002387.
10.Investigation and analysis of internal quality control on clinical chemistry, clinical immunology and clinical hematology of mutual recognition laboratories in 142 medical institutions in Beijing
Rui ZHOU ; Yanyan QIN ; Jian GUO ; Meiyi HE ; Yanmin YANG ; Rui ZHANG ; Shunli ZHANG ; Yuhong YUE ; Zhixin SONG ; Chunying WU ; Hongyi YIN ; Yufang LIANG ; Tingting JIA ; Qingtao WANG
Chinese Journal of Laboratory Medicine 2016;39(12):922-929
Objective To investigate the internal quality control ( IQC ) on clinical chemistry , clinical immunology and clinical hematology in mutual recognition laboratories in medical institutions in Beijing.Methods By means of questionnaire survey and on -site investigation, fresh frozen serum and whole blood samples with assigned values by reference method were measured to investigate the status of IQC on clinical chemistry , clinical immunology and clinical hematology in 142 mutual recognition laboratories in medical institutions of Beijing,and results were analyzed.Results 142 copies of questionnaireson clinical chemistry, clinical immunology and clinical hematology were send out and 120, 97, and 101 laboratories returned the questionnaires respectively .The information feedback rate was 84.5%, 68.3% and 71.1%respectively .All the questionnaires were effective .Questionnaires survey results showed that more than 50%laboratories set up quality control goals and the most of the goals were probability for error detection ( Ped) 95%, probability for false rejection(Pfr)5%;About 70% laboratories usecd the same quality control plan for different tests ;The most frequently used quality control rules are 12s/13s/22s.On-site investigation showed that ,take the results of clinical chemistry for example , based on the desirable biological variation and WS/T 403 -2012 , most of the tests can't meet the quality control goalsunder the existing quality controlcondition.Conclusion Clinical laboratories should consider their actual situations , assess their own qualitylevels that they can reach , set reasonable quality standards for themselves , and make appropriateindividualized quality control plan.

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