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OBJECTIVE To sy stematically evaluate the relations hip between immune-related adverse events （irAEs） and efficacy of immune checkpoint inhibitors （ICIs） in the treatment of non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical application of ICIs and safety evaluation. METHODS PubMed，Embase，Cochrane Library ， Web of Science ，CNKI，Wanfang database ，VIP and CBM were searched to collect prospective or retrospective cohort studies on the correlation between irAEs and efficacy of ICIs in the treatment of NSCLC. The retrieval time was from the inception to June 30th，2021. After literature screening and data extraction ，Newcastle-Ottawa scale was used to evaluate the quality of included literatures. Meta-analysis and publication bias analysis were performed by using RevMan 5.3 software；Stata 15.0 software was used for sensitivity analysis. RESULTS A total of 7 957 patients were included in 31 studies. Meta-analysis showed that the objective response rate （ORR）[RR＝2.34，95％CI（1.98，2.76），P＜0.000 01]，progression-free survival （PFS）[HR＝0.49，95％CI （0.44，0.55），P＜0.000 01] and overall survival （OS）[HR＝0.45，95％CI（0.39，0.53），P＜0.000 01] of irAEs group as well as ORR[RR＝1.88，95％CI（1.57，2.25），P＜0.000 01]，PFS [HR ＝0.59，95％CI（0.50，0.69），P＜0.000 01] and OS [HR ＝0.58，95％CI （0.48，0.70），P＜0.000 01] of this group at 6th week were all significantly higher or longer than non irAEs group. According to organ specificity ，severity and quantity of irAEs，subgroup analysis showed that skin ，gastrointestinal and endocrine system ，mild irAEs（grade 1-2）and one or more than 2 kinds of irAEs were significantly correlated with the improvement of PFS and OS （P＜ 0.05），while liver and lung ，severe irAEs（≥ grade 3）were not significantly correlated with the improvement of PFS and com OS （P＞0.05）. Sensitivity analysis results showed that the results of the above-mentione d meta-analysis were relatively robust. The results of publication bias showed that there was may be some possibility of publication bias in this study. CONCLUSIONS For NSCLC patients treated with ICIS ，the occurrence of irAEs may be related to their good prognosis. The irAEs may be a predictor of the efficacy of ICIs.
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OBJECTIVE：To systematically evaluate the occurren ce of non-immune related adverse events （AEs）caused by immune checkpoint inhibitors （ICIs）alone or combined with routine chemotherapy in the treatment of non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical medication. METHODS ：Retrieved from PubMed ，Cochrane Library，Embase，CNKI，CBM，VIP and Wanfang database during the inception to Oct. 2020，randomized controlled trials （RCT） about ICIs alone or combined with routine chemotherapy （trial group ）versus routine chemotherapy or placebo combined with routine chemotherapy （control group ） were collected. After literature screening and data extraction ，the quality of included literatures were evaluated with bias risk evaluation tool recommended by Cochrane systematic evaluator manual 5.1.0. Meta-analysis was performed by using Rev Man 5.3 software and Stata 15.0 software. Sensitivity analysis was conducted with Stata 15.0 software. Inverted funnel plot and Egger ’s test were used to analyze publication bias. RESULTS ：A total of 20 RCTs were included ， involving 12 283 patients. Results of Meta-analysis showed that the incidence of all grades and s evere AEs ，anemia，neutropenia， vomiting and alopecia as well as the incidence of thrombocytopenia，nausea and peripheral neuropathy in all grades of trial group were all significantly lower than control com group（P＜0.05）. There was no statistical significance in the incidence of termination of treatment ， death， severe thrombocytopenia， severe nausea and severe peripheral neuropathy or all grades and severe diarrhea between 2 groups（P＞0.05）. Subgroup analysis showed that the incidence of all grade and total severe AEs ，the incidence of anemia ，neutropenia，thrombocytopenia，clinically relevant symptoms （except for severe diarrhea），termination of treatment and death of patients receiving ICIs alone in trial group were significantly lower than control group（P＜0.05）. The incidence of ermination of treatment and death ，the incidence of nausea ，vomiting，diarrhea and alopecia in all grade ，severe diarrhea of patients receiving ICIs and chemotherapy in trial group were all significantly higher than control group （P＜0.05）. Sensitivity analysis supported the above results. Analyze publication bias results showed that the possibility of publication bias in this study was small. CONCLUSIONS ：For NSCLC patients ，the safety of ICIs is better than that of routine chemotherapy or placebo combined with routine chemotherapy in the treatment-related AEs ，hematologic toxicity and clinically relevant symptoms ；however，the risks of treatment discontinuation ，AEs-induced deaths ，and all-grade nausea ，vomiting， diarrhea，alopecia and severe diarrhea will be increased in the ICIs combined with routine chemotherapy.
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Objective:To explore the application of endoscopic narrow-band imaging(NBI) in the early diagnosis of throat malignant tumors.Methods:From January 2014 to December 2019, 512 patients with suspected benign or malignant diseases of the throat in the First People's Hospital of Wenling were selected, and all patients were performed white light endoscopy and NBI endoscopy.The biopsies were taken for pathological examination.The histopathological results were seemed as gold standard for diagnosis.Results:NBI endoscopy was superior to white light endoscope in terms of microvascular morphology and lesion outline(χ 2=457.497, 293.209, all P<0.05). The diagnostic coincidence rate, sensitivity and negative coincidence rate of NBI endoscope for malignant tumors were higher than those of white light endoscope(χ 2=10.131, 6.197, 4.084, all P<0.05). The sensitivity of NBI endoscope type Ⅰ-Ⅱ in the diagnosis of benign lesions was 90.65%, and the specificity was 96.88%.The sensitivity and specificity of NBI endoscope type Ⅲ-Ⅳ in the diagnosis of mild-moderate dysplasia were 80.99% and 97.52%, respectively.The sensitivity and specificity of NBI endoscopy type Va in the diagnosis of severe atypical hyperplasia were 15.18% and 98.54%, respectively.The sensitivity and specificity of NBI endoscope Va-c in the diagnosis of invasive cancer were 93.24% and 96.93%, respectively. Conclusion:Compared with white light endoscope, NBI endoscope can more clearly show the outline of lesions and submucosal blood vessels, and can more accurately diagnose malignant tumors in the throat, especially can more recognized the pre-cancerous lesions and early malignant tumors.It has important clinical application value in early diagnosis of malignant tumor in the throat.
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<p><b>OBJECTIVE</b>To investigate the expression of metastasis-associated in colon cancer-1 (MACC-1) mediated by siRNA, and to study the effects of its downregulation on cell proliferation, cell cycle and invasion ability of cervical cancer SiHa cells.</p><p><b>METHODS</b>MACC-1 siRNA and control siRNA were transfected into cervical cancer SiHa cells, and the expression of MACC-1 protein after transfection with MACC-1 siRNA was detected by Western blotting. The changes of cell proliferation, cell cycle and invasion ability of the SiHa cells were determined by CCK-8 kit, flow cytometry and Boyden chamber assay. The expressions of cell cycle- and invasion-related proteins were analyzed by Western blotting.</p><p><b>RESULTS</b>Compared with the untreated group (0.317 ± 0.023) and control siRNA group (0.309 ± 0.021), the expression of MACC-1 protein was downregulated in the MACC1 siRNA group (0.041 ± 0.006) (P < 0.05), and its downregulation significantly suppressed the cell proliferation, altered the cell cycle distribution and reduced the cell invasion ability of the SiHa cells (P < 0.05). Compared with the untreated group (0.217 ± 0.025 and 0.215 ± 0.024) and the control siRNA group (0.222 ± 0.023 and 0.207 ± 0.027), the expression of cyclin D1 and Cdk2 proteins were significantly decreased in the MACC1 siRNA group (0.076 ± 0.010 and 0.039 ± 0.007) (P < 0.05). Compared with the untreated group (0.099 ± 0.007) and control siRNA group (0.105 ± 0.012), the expression of p21 protein was significantly increased in the MACC1 siRNA group (0.676 ± 0.044) (P < 0.05). The downregulation of MACC-1 expression also evoked a decrease of expressions of MMP-2 and MMP-9 proteins and an increase of E-cadherin protein expression (P < 0.05).</p><p><b>CONCLUSIONS</b>MACC-1 downregulation-mediated inhibition of proliferation and decreased invasion ability of tumor cells may be closely associated with the alterations of expressions of cell cycle- and invasion-related proteins.</p>