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Objective:To screen the key exosomal long non-coding RNAs (lncRNAs) molecules that cause nasopharyngeal carcinoma cells to develop chemoradiotherapy resistance.Methods:In vitro, a model of concurrent chemoradiotherapy for human nasopharyngeal carcinoma cells was constructed, and the continuous shock method of high-dose concurrent chemoradiotherapy was used to induce the establishment of chemoradiotherapy-resistant nasopharyngeal carcinoma cell lines, and its resistance formation was verified. Exosomes produced by chemoradiotherapy-resistant cell lines and respective mother cell lines for nasopharyngeal carcinoma were extracted and identified. Finally, biochip technology was used to detect the differential expression levels of exosomal lncRNAs. Results:After 10 repeated treatments of concurrent chemoradiotherapy, CNE-1 CRR and CNE-2 CRR were successfully obtained. Compared with the mother cell lines, CNE-1 CRR and CNE-2 CRR had a tendency to transform from epithelial to interstitial morphology, and the number of cell clones was higher, and the values of average lethal dose (D 0), quasi-threshould dose (D q), survival fraction after 2 Gy irradiation (SF 2) and cell survival rate were higher. Nasopharyngeal carcinoma cells were detected by PCR chip of exosomal lncRNAs. Compared with their respective mother cell lines, 18 lncRNAs in CNE-1 CRR exosomes were significantly up-regulated and 31 lncRNAs were significantly down-regulated, and 15 lncRNAs were significantly up-regulated and 38 lncRNAs were significantly down-regulated in CNE-2 CRR exosomes. CNE-1 CRR also had similar expression profiles to CNE-2 CRR. Conclusion:There are significantly up-regulated and down-regulated lncRNAs in the exosomes of CNE-1 CRR and CNE-2 CRR.
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OBJECTIVE To compare the safety of polysaccharide iron complex and ferrous sulfate in the treatment of anemia during pregnancy. METHODS Retrieved from Cochrane Library， PubMed， Embase， SinoMed， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about polysaccharide iron complex （trial group） versus ferrous sulfate （control group） in the treatment of anemia during pregnancy were collected from the inception to May 20th， 2022. After literature screening， data extraction and quality evaluation， meta-analysis， sensitivity analysis and publication bias analysis were conducted with RevMan 5.3 software. RESULTS A total of 13 RCTs were included， with a total of 1 318 patients. Results of meta-analysis showed that the total incidence of adverse drug reactions （ADR） [RR＝0.11， 95%CI （0.06， 0.18）， P＜0 000 01]， gastrointestinal adverse reactions [RR＝0.08， 95%CI （0.05， 0.12）， P＜0.000 01]， anorexia and nausea [RR＝0.21， 95%CI （0.09， 0.54）， P＝ 0.001]， abdominal pain [RR＝0.18， 95%CI （0.04， 0.78）， P＝0.02]， diarrhea [RR＝0.18， 95%CI （0.04， 0.79）， P＝0.02]， vomiting [RR＝0.24， 95%CI （0.06， 0.89）， P＝0.03] and gingival melanosis [RR＝0.09， 95%CI （0.03， 0.28）， P＜0.000 1] in the trial group were all significantly lower than the control group. The results of sensitivity analysis showed that the conclusions obtained in this study were relatively robust. The results of publication bias analysis indicated that there was a high possibility of publication bias in this study. CONCLUSIONS The polysaccharide iron complex is safer than ferrous sulfate for treatment of anemia during pregnancy.
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Objective:It introduced the application of bayesian network in real-world data and the implementation of Tetrad software, so as to provide methodological application reference for medical researchers.Methods:Real-world data for diabetes diagnosis had been taken as an example. UCI machine learning database Pima-Indian-diabetes data set was used as case data, Bayesian network ratiocination was carried out according to the construction order of bayesian network of Tetrad software.Results:When the screening age was over 30 years old, impaired glucose tolerance, abnormal serum insulin two hours after meal, body weight index and family genetic index were large, the probability of diabetes onset from 34.99% to 83.33%.Conclusions:The bayesian network realized by Tetrad software provides a powerful tool for causal inference of real-world data, and promoted the objective and quantitative interpretation of the dependence between variables.
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Objective To investigate the relation between TMB and the efficiency of PD-1/PD-L1 inhibitors treatment for non-small-cell lung cancer. Methods Studies were searched from PubMed, Embase, Cochrane Library database, Chinese Biomedical Literature Database and Wanfang Database up to March 25, 2020. RevMan 5.3 software and STATA15.0 were used for analysis. Results Twelve literatures were involved, including 1209 patients. TMB significantly improved PFS (HR=0.54, 95%CI: 0.42-0.70, P < 0.001) but reduced the ORR (OR=4.41, 95%CI: 2.54-7.63, P < 0.001) of NSCLC patients treated with PD-1/PD-L1 inhibitors. The subgroup analyses showed that the predictive value of TMB was significant in non-small cell lung cancer treated by PD-1/PD-L1 inhibitors combined with anti-CTLA-4 therapy or chemotherapy. No significant publication bias was observed by the Begg's test and Egger's test. Conclusion High tumor mutation burden may predict the improved PFS of non-small cell lung cancer by PD-1/PD-L1 inhibitors treatment, but its predictive value for OS, ORR and long-term survival need more exploration.
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Objective:To investigate the expression of Pyruvate dehydrogenase kinase 1(PDK1), phosphorylated Pyruvate dehydrogenase (p-PDH) and Pyruvate kinase isozyme type M2 (PKM2) based on Warburg effect pathway in cervical cancer tissues, and explore the roles of these molecules on prognosis and recurrence after postoperative radiation.Methods:The expressions of PDK1, p-PDH and PKM2 in primary tissues of 102 patients with cervical cancer were detected by immunohistochemistry, including 63 patients receiving postoperative radiation. The expression of the three molecules on prognosis and the efficacy of postoperative radiation on cervical cancer were analyzed separately and corporately.The level of mRNA were verified by using the 300 patients from GEO database. Kaplan-Meier method and COX proportional hazards regression model were used for univariate and multivariate analysis.Results:High expression of PDK1 and all the three indicators (PDK1 high/p-PDH high/PKM2 high) were positively correlated with pelvic lymphnode metastasis ( χ2=10.890, 7.407, P<0.05). PDK1 high/p-PDH high/PKM2 high, Federation International of Gynecology and Obstetrics (FIGO) staging, pelvic lymph node metastasis and postoperative radiation could affect the overall survival (OS) and disease-free survival (DFS) ( P<0.05). Multivariate analysis showed that PDK1 high /PDH high/PKM2 high, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS( P<0.05). The verification result of the GEO dataset showed that PDK1 high/PDH high/PKM2 high was the risk factor for DFS( P<0.05). Pathological type, pelvic lymph node metastasis and PDK1 high/p-PDH high/PKM2 high could affect the DFS of those patients with postoperative radiation ( P<0.05). In addition, the multivariate analysis showed that pathological type and PDK1 high /p-PDH high/PKM2 high were the independent prognosis factors for DFS( P<0.05). Conclusions:The patients of PDK1 high /p-PDH high/PKM2 high phenotype have poor prognosis and DFS with postoperative radiation, which may be a high-risk group with poor prognosis and high recurrence rate after postoperative radiotherapy of stageⅠ-Ⅱ B cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer.
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Objective :To evaluate therapeutic effect of allisartan isoproxil tablet on carotid atherosclerosis (CAS) le‐sion in patients with mild to moderate essential hypertension (EH).Methods :A total of 120 patients with mild to moderate EH complicated CAS treated in our hospital were enrolled .They were randomly divided into valsartan group (n＝60 ,received valsartan 80mg／d) and allisartan isoproxil group (n＝60 ,received allisartan isoproxil tablet 240mg／d) ,both groups received measure by carotid vascular ultrasound before treatment ,24 weeks and 48 weeks af‐ter treatment and its result were compared between two groups .Results :Compared with before treatment ,there were significant reductions in IMT ,size ,thickness and number of carotid atherosclerotic plaques on 24 weeks and 48 weeks after treatment in two groups ,and above indexes of 48 weeks were significantly lower than those of 24 weeks , P＜0.05 or ＜0.01. The decreased value of IMT in allisartan isoproxil group was significantly higher than that of valsartan group ,and there were no significant difference between two groups in time point of size ,thickness and number of carotid atherosclerotic plaques , P＞0.05 all.Conclusion :Therapeutic effect of two drugs on size ,thick‐ness and number of carotid atherosclerotic plaques are similar ;but therapeutic effect of allisartan isoproxil tablet on IMT is significantly better than that of valsartan .
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OBJECTIVE:To investigate the constraint mechanism on excessive medical behavior of doctors in Chinese medical market. METHODS:Under certain assumptions(suppose the hospital and the doctor's demands are consistent,the government and the patient's demands are consistent,etc),mixed game method(game theory)was used to analyze Nash equilibrium between government and doctors,between patients and doctors.The qualitative analysis was performed for these constraints based on the re-ality. RESULTS&CONCLUSIONS:The strict punishing mechanism and the choice right to doctor of patients and public satisfac-tion with the government can achieve the Nash equilibrium of game and effectively inhibit excessive medical behavior. The govern-ment should create a competitive environment to enhance the right of patients to select doctor and improve the relevant legal system on the basis of promoting incentive compatibility among all parties so as to strengthen the implementation of supervision. At the same time,the government should establish credit archives of the doctor to form effective reputation incentive mechanism to doc-tors,and proactively explore the patients participation mechanism based on reducing the cost of patient participation.
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Objective:To discuss the constraint mechanism of moral hazard from the supply side in the medical market of China.Methods:It analyzed the effectiveness of government regulation and of the influencing factors of the doctors and patients expected profits through the establishment 4 stage dynamic game model involved the doctors,patients and the government as the subject.Results:In the case of other conditions unchanged,the effective probability of government regulation would increase with the increase of profits made by excessive medical treatment,but would decrease with the increase of doctor's punishment cost and the increase of doctor's reputation value.Given the reasonable probability about medical treatment,the doctor's expected profits would increase with the increase of the value of a reasonable medical gain and doctor's reputation increase.The prospective profits of patients would increase as the doctor's profits increased,but decrease with the over-increased medical treatment.Conclusion:The effective restraint mechanism of moral hazard from the supply side of public hospitals in China included relax the price control,improve the market value of medical services,form effective doctor reputation incentive mechanism,reduce government supervision costs and improve government regulation on the basis of promoting incentive compatibility.
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OBJECTIVE:To investigate the constraint mechanism on excessive medical behavior of doctors in Chinese medical market. METHODS:Under certain assumptions(suppose the hospital and the doctor's demands are consistent,the government and the patient's demands are consistent,etc),mixed game method(game theory)was used to analyze Nash equilibrium between government and doctors,between patients and doctors.The qualitative analysis was performed for these constraints based on the re-ality. RESULTS&CONCLUSIONS:The strict punishing mechanism and the choice right to doctor of patients and public satisfac-tion with the government can achieve the Nash equilibrium of game and effectively inhibit excessive medical behavior. The govern-ment should create a competitive environment to enhance the right of patients to select doctor and improve the relevant legal system on the basis of promoting incentive compatibility among all parties so as to strengthen the implementation of supervision. At the same time,the government should establish credit archives of the doctor to form effective reputation incentive mechanism to doc-tors,and proactively explore the patients participation mechanism based on reducing the cost of patient participation.
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OBJECTIVE:To study the preventive and therapeutic effects of Xinmaitong tablets on model rats with atherosclero-sis (AS) and corresponding mechanism. METHODS:48 rats were randomized into normal group,model group,positive group (simvastatin tablets,2 mg/kg)and the groups of high,medium and low-dose(500,250,125 mg/kg)Xingmaitong tablets,with 8 rats in each group. The rats in all groups except for the normal group were fed high fat diets and given vitamin D3 ip for the estab-lishment of AS model. Meanwhile,the rats in the drug administration groups were given corresponding drugs ig,while those in the normal group and the model group were given normal saline ig,once a day,for 10 consecutive weeks. The levels of cholesterol (TC),triacylglycerol(TG),nitric oxide(NO)and endothelin 1(ET-1)in serum were determined. The pathological change of the aorta tissue was observed under the light microscope,and the size of the aortic atherosclerotic plaque and intima thickness were measured. RESULTS:Compared to the normal group,the rats in the model group had significantly higher levels of TC,TG and ET-1 in serum,a markedly larger aortic atherosclerotic plaque,remarkably thicker intima and much lower level of NO(P<0.01);and obvious aortic atherosclerotic plaque formation was found. Compared to the model group,the above-mentioned indexes of the rats in all drug groups all improved obviously (P<0.05 or P<0.01),except that the decrease in TC in serum of the rats in the group of low-dose Xinmaitong tablets was not significant,which were positively correlated with dose;and the aortic lesion in drug groups was found to be improved. CONCLUSIONS:Xinmaitong tablets have certain preventive and therapeutic effect on the model rats with AS by a mechanism which may be related to the reduction in lipid deposition and the size of an atherosclerotic plaque,the improvement in NO/ET balance and the alleviation of an endothelial injury.
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RNA interference(RNAi)is a process by which introduced small interfering RNA(siRNA)can cause the specific degradation of mRNA with identical sequences. The human herpes simplex virus type 1(HSV-1)RR is composed of two distinct homodimeric subunits encoded by UL39 and UL40, respectively. In this study, we applied siRNAs targeting the UL39 and UL40 genes of HSV-1. We showed that synthetic siRNA silenced effectively and specifically UL39 and UL40 mRNA expression and inhibited HSV-1 replication. Our work offers new possibilities for RNAi as a genetic tool for inhibition of HSV-1 replication.