[摘 要] 尽管以PD-1/PD-L1抑制剂为基础的免疫治疗显著提升了肺癌患者的生存期，但耐药问题依然严峻。本文阐述了免疫治疗耐药的定义、发生机制及预测模型，介绍了针对耐药的治疗策略，包括免疫治疗继续应用、再挑战、寡转移背景下的局部治疗联合全身免疫治疗、广泛进展后的联合治疗等。此外，还探讨了新型治疗手段如过继性细胞疗法、抗体偶联药物、双特异性抗体和肿瘤疫苗等在克服耐药中的应用前景。同时，总结了肺癌免疫治疗的挑战与发展方向，强调了持续研究、创新治疗策略以及跨学科合作的重要性。为未来肺癌治疗的个体化、精准化和高效化提供新思路与研究方向。

Objective:To predict the efficacy and safety of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections using Bayesian network meta analysis.Methods:Databases including PubMed, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database were searched for literatures from January 1990 to May 2018 with the key words of ( "intraabdominal infections" [MeSH Terms]) AND ( "Cephalosporins*" [MeSH Terms]) AND ( "randomized controlled trial" [MeSH Terms]),腹腔感染,继发性腹膜炎,腹腔脓肿,头孢. The randomized controlled trials (RCTs) about comparison of efficacy and safety between cephalosporins antibiotics combined with metronidazole versus other antibiotics for intra-abdominal infections were received and included. Experimental group included patients who received cephalosporins antibiotics combined with metronidazole for intra-abdominal infections, and control group included patients who received other antibiotics for intra-abdominal infections. The primary outcomes were the clinical cure rates, microbial clearance rate and incidence of serious adverse drug reactions. R 3.6.2 software random Bayesian model was used for meta analysis. The Markov Chain Monte Carlo was used for direct evaluation and indirect prediction. The tracing method, density plotting and leverage figure method were used to evaluate the model convergence and stability. No closed loop formed between intervention measures, so there was no need to evaluate consistency.Results:(1) Document retrieval: a total of 18 available RCTs were enrolled. There were 6 792 patients, including 3 402 in the experimental group, 3 390 in the control group. (2) Results of Bayesian network meta analysis. ① The clinical cure rates of the third generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole [ odds ratio ( OR)=0.46, 0.61, 95% confidence interval( CI) as 0.26-0.81, 0.38-0.97, P<0.05]. There was no significant difference in the clinical cure rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=1.03, 95% CI as 0.59-1.80, P>0.05). ② The microbial clearance rates of the fifth generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole ( OR=0.84, 0.41, 95% CI as 0.73-0.98, 0.23-0.74, P<0.05). There was no significant difference in the microbial clearance rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=0.76, 95% CI as 0.27-1.80, P>0.05). ③ The incidence of serious adverse drug reactions was significantly lower for the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins antibiotics+ cetronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, quinolones+ metronidazole, and tigecycline than for quinolones ( OR=0.13, 0.13, 0.14, 0.13, 0.15, 0.13, 95% CI as 0.03-0.50, 0.02-0.98, 0.02-0.75, 0.02-0.59, 0.02-0.78, 0.02-0.57, P<0.05). Compared with carbapenems, the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole had no significant difference in the incidence of serious adverse drug reactions ( OR=0.96, 1.00, 1.10, 95% CI as 0.52-1.60, 0.31-3.50, 0.49-2.30, P>0.05). (3) Ranking of the efficacy and safety. ① The ranking list for clinical cure rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, synthetic penicillins, the second generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 51.73%, 35.72%, 22.57%, 31.37%, 24.98%, 32.82%, 34.69%, 29.05%, 72.36%, respectively. ② The ranking list for microbial clearance rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, the second generation cephalosporins+ metronidazole, synthetic penicillins, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 89.62%, 77.01%, 38.60%, 20.94%, 26.26%, 26.39%, 22.22%, 20.19%, 62.55%, respectively. ③ The ranking list for incidence of serious adverse drug reactions of different therapeutic regimens showed from high to low as quinolones, quinolones+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, the fourth generation cephalosporins+ metronidazole. The corresponding ranking probabilities of above regimens were 96.21%, 30.46%, 21.09%, 25.27%, 27.26%, 19.45%, 31.69%, respectively. Conclusion:In the treatment of middle- and low-risk intra-abdominal infections, it is recommended to empirically use cephalosporins+ metronidazole instead of carbapenems.

Objective:To investigate the risk factors of portal vein system thrombosis (PVST) after portoazygous devascularization in patients with portal hypertension.Methods:Clinical data of 215 patients with portal hypertension treated by splenectomy at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi′an Jiaotong University from Jan 2012 to Dec 2017 were retrospectively analyzed. Univariate analysis of variance and Logistic regression were used to analyze the clinical risk factors that may lead to PVST.Results:The incidence of PVST was 43.7%(94/215). Univariate analysis of variance showed that the diameter of portal vein, the diameter of splenic vein, the thickness of spleen, laparoscopic or open surgery, and postoperative platelet count were correlated with postoperative PVST (all P<0.05). Logistic regression analysis showed that splenic vein diameter ( OR=3.137, 95% CI 1.391-7.076, P=0.006), splenic thickness ( OR=3.065, 95% CI 1.418-6.626, P=0.004) and postoperative platelet count ( OR=7.446, 95% CI 3.057-18.137, P=0.000) were independent risk factors for PVST in patients with portal hypertension. Conclusion:Postoperative PVST in patients with portal hypertension are more likely to develope when preoperative splenic vein ≥11 mm, splenic thickness ≥60 mm and platelet count ≥300×10 9/L on the 7th day after operation.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective:To explore the current situation of recognition, need and execution towards medical standards among nurses, and to analyze the correlations among them.Methods:In May 2018, this study selected four areas, east, central section, west and northeast of China, according to the regional division criteria of National Bureau of Statistics of China by multistage stratified sampling. Totals of 31 provinces or municipalities directly under the Central Government were extracted; three provinces were from the northeast including Heilongjiang, Jilin, Liaoning Province; 6 to 10 provinces were randomly selected from the west. A number of nurses from 10 to 20 hospitals were randomly selected as subjects in every province or municipality directly under the Central Government. The Medical-related Standards Questionnaire designed by Medical Standard Department, Medical Management Service Guidance Center, National Health Commission of the People's Republic of China, was used to investigate the situation of recognition, execution and propagation of nurses towards two medical standards in China. The survey adopted the way of on-the-spot questionnaire combined with the online questionnaire.Results:A total of 4 439 questionnaires were sent out and 4 084 valid questionnaires were collected with 92.0% for the vail recovery rate. Among 4 084 nurses, the scores of the recognition, need and execution towards medical standards were (4.10±0.75) , (4.34±0.83) and (4.33±0.83) respectively. The recognition rate, need degree and execution rate of nurses towards published standards within the scope profession were 82.0% (3 350/4 084) , 94.7% (3 868/4 084) and 84.1% (3 436/4 084) respectively. Pearson correlation analysis showed that the recognition of nursing towards standards had positive correlations with the need ( r=0.393, P<0.01) and execution ( r=0.401, P<0.01) with statistical differences; the need had a positive correlation with the execution with a statistical difference ( r=0.217, P<0.01) . Multiple hierarchical regression analysis showed that the recognition (β=0.391, P<0.01) and need (β=0.219, P<0.01) of nursing towards standards had predictive roles on execution after controlling demographic variables with statistical differences. Conclusions:In China, nurses have high levels of recognition, need and execution towards standards. The positive propagation and implementation can promote the positive cognition and attitude which help nurses to perform the standard.

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.