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BACKGROUND@#Immune checkpoint inhibitor monotherapy is reported to have little effect in advanced non-small cell lung cancer (NSCLC) patients with driver oncogenes. However, recent studies have shown that some patients with driver genes are still benefit from combination immunotherapy after tyrosine kinase inhibitors (TKIs) drug resistance. The purpose of this study was to analyze the efficacy of posterior line immunotherapy in NSCLC patients with epidermal growth factor (EGFR) sensitive mutation, and to evaluate the value of immunotherapy in posterior line therapy in patients with advanced EGFR mutation.@*METHODS@#A total of 27 patients with EGFR mutation diagnosed in Beijing Chest Hospital, Capital Medical University from June 2018 to November 2020 were collected. After the progress of targeted therapy, they had received programmed cell death protein 1 (PD-1) checkpoint inhibitor combined with chemotherapy and anti-angiogenic drug therapy.@*RESULTS@#Of the 27 advanced NSCLC patients, 19 cases (70.4%) did not have T790M mutation. There were 8 cases (29.6%) with T790M point mutation. The total objective response rate (ORR) was 40.7%. Kaplan-Meier survival analysis showed that there was no statistically significant difference among different EGFR mutations (χ²=4.15, P=0.230). But progression-free survival (PFS) was significantly longer in patients without T790M mutation than in patients with T790M mutation (9.2 mon vs 3.3 mon, χ²=2.808, P=0.041), and the same trend was observed in patients with overall survival treated with the PD-1 inhibitor (12.2 mon vs 7.3 mon, χ²=3.22, P=0.062). ORR of patients without T790M was significantly better than that with T790M (52.63% vs 12.5%, P=0.045).@*CONCLUSIONS@#Patients with EGFR mutation can benefit from later-line combined immunotherapy. The patients with T790M mutation in the population of EGFR mutation had the worst effect of immunotherapy in the later line. Therefore, the follow-up treatment and whole-course management of these patients need to explore better treatment strategies to improve the benefit.
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BACKGROUND@#Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been widely used in the treatment of lung cancer. There are controversies in clinical practice for patients with advanced non-small cell lung cancer (NSCLC) and high programmed cell death-ligand 1 (PD-L1) expression receiving ICIs monotherapy or combination chemotherapy.@*METHODS@#This study retrospectively analyzed the clinical data of 49 patients with advanced NSCLC and high PD-L1 expression. Immunohistochemistry was performed with 22C3 antibody, and the expression level of PD-L1 was evaluated according to tumor proportion score (TPS). Objective response rate (ORR) and progression free survival (PFS) were compared by groups of different clinical characteristics.@*RESULTS@#ORR of monotherapy and combination therapy group was 47.1% (8/17) and 43.8% (14/32), respectively, without statistical difference (P=0.825). The median PFS of monotherapy and combination therapy group was 8.0 months and 6.8 months, respectively, without statistical difference (P=0.502). Statistical analysis of predictors of immunotherapy for the patients showed first-line immunotherapy had better ORR than subsequent immunotherapy (12/19, 63.2% vs 10/30, 33.3%, P=0.041), however no difference in PFS. And there were no differences in ORR or PFS among groups of age, gender, smoking status, performance status (PS), pathological type, tumor size and tumor-node-metastasis (TNM) stage.@*CONCLUSIONS@#The therapeutic effect is similar between ICIs monotherapy and combination chemotherapy for patients with advanced NSCLC and high PD-L1 expression. ORR of first-line immunotherapy was better in patients with advanced NSCLC and high PD-L1 expression. The optimal treatment for this population remains further prospective clinical studies.
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BACKGROUND@#Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring.@*METHODS@#The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy.@*RESULTS@#Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months.@*CONCLUSIONS@#The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.
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Objective:To investigate the predictive value of Graeb score for the outcome of high-grade aneurysmal subarachnoid hemorrhage (aSAH) patients with intraventricular hemorrhage (IVH).Methods:Consecutive high-grade aSAH patients with IVH admitted to the No. 1 People's Hospital of Jiujiang from January 2012 to March 2020 were enrolled retrospectively. High-grade aSAH was defined as grade Ⅳ to Ⅴ according to the World Federation of Neurological Surgeons (WFNS) scale. The outcome of patients was evaluated by the modified Rankin Scale (mRS) at 3 months after discharge. A score of ≤2 was defined as a good outcome and a score of >2 were defined as a poor outcome. Multivariate logistic regression model was used to evaluate the correlation between Graeb score and clinical outcome, and the receiver operating characteristic (ROC) curve was used to determine the predictive value of Graeb score for clinical outcome. Results:A total of 86 high-grade aSAH patients with IVH were enrolled. Aneurysm treatment: craniotomy clipping in 42 patients (48.8%), intravascular embolization in 21 (24.4%), and conservative treatment in 23 (26.7%). Twenty-nine patients (33.7%) had a good outcome and 57 (66.3%) had a poor outcome. Multivariate logistic regression analysis showed that the Graeb score >6 (odds ratio [ OR] 26.360, 95% confidence interval [ CI] 4.106-169.235; P<0.001), the modified Fisher grade 3-4 ( OR 11.674, 95% CI 1.540-88.512; P=0.017) and complicated with chronic hydrocephalus ( OR 21.236, 95% CI 2.883-156.431; P=0.003) were the independent risk factors for the poor outcome. ROC curve analysis showed that the area under the curve of the Graeb score predicting for poor outcome was 0.843 (95% CI 0.760-0.926; P<0.001), the best cut-off value was 6.5, and the corresponding sensitivity and specificity were 71.9% and 86.2%, respectively. Conclusion:The Graeb score is an independent influencing factor affecting the clinical outcome of high-grade aSAH patients with IVH. Graeb score >6.5 had higher predictive value for the poor outcome in such patients.
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Seventy patients with advanced non-small-cell lung cancer (NSCLC) aged 65 or above were treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib or gefitinib from February 2006 to September 2010. The efficacy and toxicities of treatment were retrospectively analyzed.The overall response rate and disease control rate were 31.4％ and 84.3％,respectively. Themedian progression-free survival time and median survival time were 8.0 months and 13.5 months,respectively(P ＜ 0.05 ). One-year survival rate was 54.3％. Response rate ( CR + PR) ( 42.9％ ) anddisease control rate (94.3％ )in female patients were superior to males (20.0％ and 74.3％ ) (P ＜ 0.05 ).Non-smoking and PS score ＜ 2 were good predictors for survival.The side effects were generally mild and mainly were skin rash and diarrhea.
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To obtain a recombinant human plasminogen (hPLG) with potential anti-platelet aggregation activity, we cloned the cDNA coding Pro544 to Asn791 of hPLG, a kringle-deficit derivative (hPLG-deltaK). The Pro559 in activation loop was then mutated into Asp559 to provide Arg-Gly-Asp (RGD) motif. The constructed pPICZalphaA-RGD-HPLG-deltaK plasmid was expressed in yeast Pichia pastoris GS115, which produced RGD-hPLG-deltaK about 0.160 g/L broth. After affinity chromatography, the purity of the recombinant protein reached above 90%. Western blotting test confirmed that it retained the immunological reaction capability as human PLG. Its urokinase activation rate in 24 hours and its fibrinolytic activity made no deference against native hPLG-deltaK (P=0.630, n=5). Importantly, after activation by urokinase, RGD-hPLG-deltaK showed a significantly higher platelet aggregation inhibition rate (Ri) (21.8% +/- 1.57%) than hPLG-deltaK (3.8% +/- 0.33%) (P=0.000, n=5). These results proved that we constructed an hPLG mutant with anti-platelet aggregation activity, which made a foundation for developing innovative thrombolytic drugs with multifunction.
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Humanos , Kringles , Genética , Oligopeptídeos , Genética , Pichia , Genética , Metabolismo , Plasminogênio , Genética , Inibidores da Agregação Plaquetária , Farmacologia , Mutação Puntual , Proteínas Recombinantes , Genética , FarmacologiaRESUMO
Objective To explore the effect of Electroacupuncture on anxiety mood and periaqueductal grey (PAG) β-endorphine expression in rats with morphine abstinence syndrome.Methods The model of heroin-addicted rat was firmly established by the subcutaneous injection of gradually-increased dosages of heroin. Rats were randomly divided into control group, herion-addict group, withdrawal group, electroacupuncture group.Anxiety mood of experimental rats were assessed by Elevated Plus Maze test. Expression of β-EP in PAG was detected by immunohistochemstry. The effect of electroacupuncture at bilateral zusanli and sanyinjiao on anxiety mood and expression of β-EP in PAG was observed in rats with herion abstinence symptom.Results The anxiety index in rats with herion abstinence symptom:the value of OT％,OE％and head-dips times was (12.5±4.3) ％, (17.1±6.7)％and (5.7±2.0) times respectively,lower than that in control group [ (26.8±8.7) ％,(32.4±6.0) ％ and (12.2±4.0) times respectively],there existed significant difference(The value of P was 0.003,0.018 and 0.003 respectively).Meanwhile,The expression of β-EP-positive neurons(206.1±23.1)was significantly higher than the control(186.2±15.3). There existed significant difference( P =0.041).Electroacupuncture could increase OT％,OE％,head-dips times[(26.5±8.7)％、(31.8±7.7)％ and (9.9±3.1) times respectively] in rats with herion abstinence symptom,which comparied with control group were not statistically distinctive(The value of P was 0.920,0.816 and 0.122 respectively).The expression of β-EP(185.3±11.4)in PAG increased, which comparied with control group(186.2±15.3)were not statistically distinctive( P =0.891).Conclusion Electroacupuncture could inhibit the abstinence syndrome effectively.And there is obvious promotion of β-EP expression in PAG. This is probably one of underlying mechanisms for electroacupuncture improving withdrawal symptoms.
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@#Objective To analyze the related factors of congestive heart failure (CHF) in elderly female patients. Methods 39 female patients aged over 60-year-old with chronic CHF were divided into two groups according to the cardiac functional grading. Historical features and data were compared between two groups by single factor and multifactorial regression analysis.Results There were differences between two groups in hemoglobin concentration, serum creatinine, incidence of chronic kidney disease and anemia (P<0.01), but no obvious difference between two groups in morbidity of hypertension and diabetes. And it was n by multifactorial regression analysis showed that hemoglobin concentration, serum creatinine, incidence of chronic kidney disease and anemia could not be in regression equation. Conclusion The hemoglobin concentration, serum creatinine, incidence of chronic kidney disease and anemia may associated with degree of congestive heart failure.
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<p><b>BACKGROUND</b>Matrix metalloproteinase-9 (MMP-9), endostatin (ES) and vascular endothelial growth factor (VEGF) are important angiogenic regulators for many neoplasms. The aim of this study is to judge clinical and prognostic values of detection of serum MMP-9, ES and VEGF in patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Serum levels of MMP-9, ES and VEGF were detected in 92 patients with NSCLC, 50 patients with pulmonary benign disease and 52 healthy controls by ELISA method.</p><p><b>RESULTS</b>The serum levels of MMP-9, ES and VEGF in NSCLC patients were significantly higher than those in patients with pulmonary benign disease and healthy controls (P=0.000, P=0.000, P=0.000). The sensitivity and specificity of serum MMP-9 was 92.51% and 79.10% with a cutoff value of 117.17 μg/L, 88.32% and 74.25% for ES with a cutoff value of 100.31 μg/L, and 83.40% and 75.63% for VEGF with a cutoff value of 380.32 ng/L. Serum MMP-9 and ES levels were significant prognostic factors for lung cancer patients (P=0.0145, P=0.008). The change of serum MMP-9 level after chemotherapy was a useful indicator of prognosis for NSCLC patients (P=0.0322).</p><p><b>CONCLUSIONS</b>The serum levels of MMP-9, ES and VEGF are significantly increased in patients with NSCLC. They might be used as prognostic parameters in patients with NSCLC.</p>
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Objective:To investigate learning burnout of undergraduates and its relationship with health-related hardiness.Methods:408 undergraduates were investigated with Undergraduate Learning Burnout Scale and Health-Related Hardiness Scale.Results:Boys scores were significantly higher than those of girls in behavior inadequacy, reduced personal accomplishment and general burnout;significant differences were found between grades in emotion turndown and majors in emotion turndown, reduced personal accomplishment and general burnout.Health-related hardiness has a sig-nificant negative correlation with learning burnout.The results of regression analysis found that control and commitment were the effective precursors.Conclusion:Health-related hardiness has a significant influence on undergraduates' learning burnout.
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<p><b>BACKGROUND</b>Uroacitides is a group of cell differentiation inducers, which is purified from fresh human urine. Preclinical studies of Uroacitides have showed that cancer cells could be induced to differentiate, and the growth of cancer cells could be inhibited by Uroacitides. The aim of this study is to compare the efficacy and toxicity between Uroacitides combined with NP regimen and NP alone in treatment of advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Forty-two cases of advanced NSCLC were randomized into Uroacitides+NP and NP groups. NP group: NVB 25mg/m² on days 1 and 8, DDP 75mg/m² on day 1. Uroacitides combined with NP group: Uroacitides of 300mL was given through subclavian catheter daily for 7 days prior to the NP chemotherapy, then concurrently with NP regimen for 2 cycles, except the days of administration of chemotherapy.</p><p><b>RESULTS</b>In the Uroacitides+NP group, the overall response rate was 44.4%, and 20.0% in the NP group (P > 0.05). The median survival time was 9 months in the Uroacitides+NP group and 6 months in the NP group (P=0.0287). The main toxicities were myelosuppression, gastrointestinal reaction and alopecia, and there was no significant difference in incidences of toxicities between the two groups (P > 0.05).</p><p><b>CONCLUSIONS</b>Uroacitides combined with NP regimen shows a good curative effect and low toxicity, and may significantly prolong the median survival time for advanced NSCLC.</p>
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<p><b>BACKGROUND</b>To evaluate the efficacy, side-effects, median survival duration and survival rate of vinorelbine (NVB) combined with cisplatin (DDP) in the treatment of non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 220 patients with inoperable NSCLC received NVB and DDP combined chemotherapy: NVB 25-30 mg/(m²*d) on days 1 and 5 (or 8), DDP 60-80 mg/(m²*d) on day 2. The schedule was repeated every 28 days. The efficacy and side-effects were analysed and followed-up after at least two cycles of chemotherapy.</p><p><b>RESULTS</b>The overall response rate (CR+PR) was 30.9% (68/220). The response rate was 31.3% (51/163) in initial treatment group, and 29.8% (17/57) in retreatment group. The median survival duration was 8.3 months. The 1-, 2- and 3-year survival rates were 39.23%, 19.31% and 6.32%, respectively. The main side-effects were myelosuppression and digestive tract reactions.</p><p><b>CONCLUSIONS</b>Vinorelbine plus cisplatin is an effective and well-tolerated regimen for non small cell lung cancer and myelosuppression is its dose-limiting toxicity.</p>
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<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of Serratia marcescens (S311) vaccine in the treatment of malignant pleural effusion.</p><p><b>METHODS</b>Thirty-four patients with malignant pleural effusion were given S311 as intrapleural injection with a dose of 10(9) U (0.32 mg) on D 1, 8 and 15, and observed for four weeks.</p><p><b>RESULTS</b>The overall response rate (CR + PR) was 97.1% (CR in 12 patients and PR in 21 patients). The systemic toxicity was mild, including fever (82.4%), pleuritic pain (50.7%), nansea (26.5%), dyspnea (17.5%) and chills (5.9%).</p><p><b>CONCLUSION</b>Serratia marcescens vaccine is effective for malignant pleural effusion, with tolerable toxic effects. Further study is warranted.</p>
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Bacterianas , Alergia e Imunologia , Usos Terapêuticos , Dor no Peito , Relação Dose-Resposta a Droga , Febre , Derrame Pleural , Tratamento Farmacológico , Alergia e Imunologia , Serratia marcescens , Alergia e Imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Objective: To determine the sinapine in Semen Raphani(Laifuzi) from different places by measns of RP HPLC. Method: The column empolyed was Alltima Phenyl Collumn(250?4.6mm,5?m). The mobile phase was acetonitrile 0.08 mol/LKH 2PO 4(15∶85). The flow rate was 1.0mL/min and detection was effected at 326nm results. Conclusion: The results show the method is accurate, rapid and reproducible. We found it has marked discrepancy in the content of Semen Raphani(Lai Fuzi) from different places.