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Objective:To investigate whether radiotherapy should be delivered before the application of immune checkpoint inhibitor PD-1 in patients with advanced non-small cell lung cancer (NSCLC) and evaluate the effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor.Methods:Clinical data of patients with stage Ⅳ NSCLC who received immunotherapy in Henan Cancer Hospital from March 2015 to September 2019 were retrospectively analyzed. The baseline data of patients, the status of radiotherapy and immunotherapy and the pulmonary toxicity were collected. According to whether radiotherapy was given before PD-1 inhibitor application, all patients were divided into the previous radiotherapy and non-radiotherapy groups. Survival analysis was performed by Kaplan- Meier method. Results:A total of 90 patients were enrolled including 39 cases in the previous radiotherapy group and 51 cases in the non-radiotherapy group. The median follow-up time was 22.9 months. The median progression-free survival (mPFS) in the previous radiotherapy group was 7.5 months (95% CI 5.4-9.5 months), significantly longer compared with 4.1 months (95% CI 3.1-5.1 months) in the non-radiotherapy group ( P=0.003). The median overall survival (mOS) significantly differed between two groups[15.2 months (95% CI 12.3-18.1 months) vs. 9.3 months (95% CI 6.1-12.5 months)]( P=0.040). The incidence of pulmonary toxicity showed no significant difference between two groups ( P=0.154). Conclusions:Patients with stage Ⅳ NSCLC patients in the previous radiotherapy group obtain significantly better mPFS and mOS and similar pulmonary toxicity compared with their counterparts in the non-radiotherapy group. Nevertheless, the findings remain to be validated by subsequent investigations with larger sample size.
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Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.
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Objective:To investigate the effect and molecular mechanism of circ_0001955 on the radiosensitivity of prostate cancer DU145 cells.Methods:The si-con, si-circ_0001955, miR-con and miR-149 were transfected into DU145 cells and recorded as the si-con group, si-circ_0001955 group, miR-con group, miR-149 group. The miR-149 and pc-circ_0001955 were co-transfected into DU145 cells and recorded as the miR-149+ pc-circ_0001955 group. Untreated cells were used as the blank control (NC) group. Real-time quantitative PCR was employed to detect the expression levels of circ_0001955 and miR-149. MTT assay was performed to detect cell viability. Flow cytometry was carried out to detect cell apoptosis. Transwell chamber assay was conducted to observe cell migration and invasion. Western blot was performed to detect the expression levels of MMP-2, MMP-9, Cleaved caspase-3, Cleaved caspase-9 and γ-H 2AX proteins. Colony formation assay was employed to determine the cell radiosensitivity. Dual-luciferase reporter assay was conducted to verify the targeting relationship between circ_0001955 and miR-149. Results:The circ_0001955 was highly expressed, whereas the miR-149 was lowly expressed in prostate cancer DU145 cells. Silencing circ_0001955 or over-expressing miR-149 could decrease the cell viability, migration and invasion, down-regulate the expression levels of MMP-2 and MMP-9, up-regulate the expression levels of Cleaved caspase-3 and Cleaved caspase-9, and increase the apoptosis rate (all P<0.05). After 4 Gy dose irradiation, the expression level of γ-H 2AX was up-regulated, the cell survival fraction was decreased, and the sensitivity ratio was 1.38. circ_0001955 could targetedly regulate the expression level of miR-149. After simultaneous overexpression of circ_0001955 and miR-149, cell proliferation activity and the number of migrating and invading cells were increased, cell apoptosis rate was decreased, and cell survival fraction was increased, and the sensitivity ratio was calculated as 0.72. Conclusion:Silencing circ_0001955 can targetedly up-regulate the expression level of miR-149, which inhibits the proliferation, migration, and invasion, induces cell cycle arrest, induces cell apoptosis and increases the radiosensitivity of prostate cancer DU145 cells.
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Objective:To evaluate the therapeutic effects and prognostic factors of neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.Methods:The clinical data of a total of 148 patients with locally advanced esophageal squamous cell carcinoma enrolled in the Affiliated Cancer Hospital of Zhengzhou University from 2007 to 2017 were retrospectively analyzed. The patients received 5-Fu/Cisplatin or Paclitaxel/Cisplatin for chemotherapies. The total treatment dose for the radiotherapy was delivered at 36-40Gy under conventional fractionation. Kaplan-Meier method was used to calculate survival rates, and Log-rank test and Cox model were performed for univariate analysis and multivariate analysis, respectively.Results:The overall survival (OS) rates of 1-, 3-and 5-year were 74%, 51% and 51%, respectively, with a median survival time (MST) of 72.4 months. The carcinoma/disease-free survival (DFS) rates for 1, 3, 5 years were 60%, 51%, 45%, respectively, with a median time of 60.1 months. The 1-, 3-and 5-year OS rates of the pCR group were 86%, 70%, 70%, the ones of which in the non-pCR group were 70%, 44%, 43%, respectively ( P=0.002). The 1-, 3-and 5-year DFS rates were 76%, 71%, 68% for the pCR group, and 53%, 43%, 37% for the non-pCR group, respectively ( P=0.002). In pN(-) group and pN(+ ) group, the 1-, 3-and 5-year OS rates were 83%, 56%, 55% and 50%, 38%, 38%( P=0.004), respectively. Further, the 1-, 3-and 5-year DFS rates were 66%, 56%, 51% for the pN(-) group, and 43%, 38%, 31% for the pN(+ ) group ( P=0.006), respectively. Multivariate analysis revealed that pCR and pN status were independent prognostic factors for OS and DFS ( P=0.012, 0.011 and P=0.025, 0.033). Conclusion:Neoadjuvant chemoradiotherapy demonstrated significant therapeutic effects in the treatment of locally advanced esophageal squamous cell carcinoma, while pCR and pN status served as independent prognostic factors.
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Objective To determine the treatment outcome of nimotuzumab in combination with neoadjuvant concurrent chemoradiotherapy followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC).Methods A total of 23 ESCC patients were enrolled.The preoperative strategies consisted of nimotuzumab (200 mg per week in week 1-5),concurrent chemotherapy by paclitaxel (45 mg/m2 per week in week 2-5) and cisplatin (20 mg/m2 per week in week 2-5) and radiotherapy by a total dose of 40 Gy (2.0 Gy/d,5 days per week in week 2-5).Esophagectomy was performed 4 weeks after the completion of preoperative therapies.Results All of the 23 patients enrolled completed the planned combined therapy method,and 22 patients underwent final surgery.The clinical response rate of nimotuzumab in combination with preoperative chemoradiotherapy was 96%.The most frequent Grade 1/2 toxicities observed were gastrointestinal reaction,bone marrow suppression,and esophagitis.The rate of radical resection was 100%,and the pathological complete response rate was 41%.The incidence rate of postoperative pulmonary infection,anastomotic leak,hoarseness,and arrhythmia were 14%,9%,4%,and 4%,respectively.No perioperative deaths occurred in our study.The 1-,3-,and 5-year overall survival (OS) rate for all the patients were 86%,52% and 52%,respectively.The median survival time (MST) was 28.9 months.Postoperative pathologic results showed 15 patients with lymph node negative and 7 patients with lymph node positive.the 1-,3-,and 5-year OS for pN0 group were 100%,62% and 62%,versus 57%,29% and 29% for pN+ group (P=0.033).The MST for pNo group was 42.6 months versus 14.2 months for pN + group.Conclusions The regimen of nimotuzumab in combination with preoperative concurrent chemoradiotherapy followed by surgery is safe and effective for locally advanced ESCC.Patients with lymph node negative after surgery have significantly improved long-term survival.
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Objective To determine the feasibility and toxicity of the addition of cetuximab to paclitaxel,cisplatin,and concurrent intensity modulated radiation therapy (IMRT) for patients with esophageal squamous cell carcinoma (ESCC).Methods Nineteen patients with stage Ⅰ to Ⅲ ESCC,without distant organ metastases,were eligible.All patients received cetuximab,an initial dose of 400 mg/m2 in the first week followed by weekly injection of 250 mg/m2,paclitaxel 45 mg/m2 and cisplatin 20 mg/m2 weekly for 7 weeks with IMRT of 59.4 Gy/33 fractions.Results Two patients discontinued because of severe adverse events.Seventeen patients completed the planned treatment protocol.Of whom,12 patients achieved completeremission.The objective response rate was 100%.A median follow-up time was 29.3 months.The 1-year overall survival and recurrence-free survival rate was 100% and 82%,respectively.Main toxicities including myelosuppression,esophagitis and skin rash happened in 19 patients.Grade ≥2 neutropenia,esophagitis and skin toxicity noted rates was 89%,84% and 58%,respectively.Local recurrence was found in two patients.Neck lymph node and lung metastasis found in one patient.Conclusions Cetuximab,when combined with paclitaxel,cisplatin and IMRT,is efficient and safe for esophageal squamous cell carcinoma,Further clinical study is needed.
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ObjectiveTo analyze the characterstics of phenotype and genotype of multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) by molecular line probe assay and liquid culture with MGIT960.MethodsGenoType MTBDR Kits were used for identifying the types of the first-line and second-line antituberculosis drug resistant genes partly and BD MGIT960 was used for detecting the chug susceptibility.Results( 1 ) Out of 94 MDR-TB strains,the rate of drug resistant to EMB,AMK,OFX and MFX by BD MGIT960 assay were 36.2%,17.0%,54.3% and 55.3%,respectively.Among these isolates,13 were extensively drug resistant tuberculosis (XDR-TB).(2) Compared with MGIT960,the concordance rate of GenoType MTBDRplus was 86.2% and 95.7% respectively.Taking MGIT960 results as reference,the sensitivity of GenoType MTBDRsl detecting the susceptibility of EMB,AMK,OFX and MFX to 94 isolates were 47.1%,81.3%,94.1%,94.2%,respectively.The specificity were 75.0%,98.7%,90.7%,92.9%,respectively.(3) Among the rpoB mutation categories,S531L accounts for most.MTB resistant to IFN caused by the mutation of katG chiefly and the S315T1 was in the majority.The gyrA mutation sites located at the ninety-fourth codon most.Out of 94 strains,23 were mixed with 2 kindsof Mycobacterium tuberculosis at least and 7 were undetectable mutations.Conclusion Among the M/XDR-TB,the strains resistant to INH,RFP,AMK,OFX and MFX were caused most by the mutation of katG,rpoB,rrs and gyrA,respectively.The relationship between EMB and embB was not so clear relatively.As a fast detecting drug susceptibility test kit,GenoType MTBDR possess good sensitivity and specificity.So,it could be as an assistant method to guide the therapy on clinic.
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Objective To set up a method of rapid culture,drug susceptibility testing and identification for Mycobacterium Tuberculosis.Methods Using the method by ourselves made and examined the standard strains and clinical strains of mycobacterium,research to the culture, the drug susceptibility testing and the identification of group in mycobacterium by this method compared with the method of Lowenstein-Jensen (L-J) method. To make sure the characteristic identification of group in mycobacterium.Results Detection time of culture of this method was 19.13 d earlier than that of L-J method. The positive rate of the method was higher than that of the L-J method. The applied concentration of each drug was: INH:0.1 ?g/ml, RFP:1 ?g/ml, EB:2 ?g/ml, AMK:2 ?g/ml、LVFX:2 ?g/ml、PNB 200 ?g/ml、TCH 2.5 ?g/ml respectively. The report time of the method was 7~10 d. It was 18~21 d shorter than that of the L-J method (28 days).Conclusion The method shortened significantly the report time of culture、drug susceptibility testing and identification of group in mycobacterium. The rate of positive was raised.This method was economic, practical and suitable to expansion and application in the substrata units.
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Objective: To optimize the extraction process for Semen Strychni and Ephedra Sinica in Jiufen Powder. Methods: To determine the content of strychnine, brucine and ephedrine in extract solution by orthogonal design and TLC. Results: The volume of solvent and the number of times of extration have notable effect for extraction. The best conditions are 10 times of the herb quantity of water, extract three times, 1 hour per time.