Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

Objective:To investigate the epidemiological characteristics for family clusters of COVID-19 in Zhejiang Province.Methods:The data including cases information of asymptomatic infected cases of family clusters of COVID-19 in Zhejiang Province were collected from Public Health Emergencies Reporting System of China Center for Disease Control and Prevention. Calculate the case number of subsequent cases, index cases, asymptomatic infected cases, exposure cases, and then, compute family secondary attack rate (SIR) and serial interval.Results:A total of 389 cases comprised 149 family index cases and 240 subsequent cases. The clinical symptoms between family index cases and subsequent cases (exclude asymptomatic infected cases ) were similar, fever was the most common symptoms in the two groups 115 (77.18%) and 110（48.67%）respectively, the cases with diarrhea symptoms accounted for the least proportion, which were 7 (4.70%) and 6 (2.65%) respectively. The serial interval between the family index cases and the subsequent cases [ M ( P25, P75)] was 4.00 (2.00, 6.00) days. Family secondary attack rate for subsequent cases was 34.43%, subsequent cases aged between 14 and 60 have the highest SIR (43.42%) compared with other two age groups, the difference was statistically ( P<0.001); the family SIR of the spouses of the family index cases is 68.57%, and are higher than that of parents (29.03%), children (25.00%) and other family members (24.21%), the difference was also statistically ( P<0.001). Conclusion:2019 novel coronavirus has shorter serial interval and higher family SIR, the SIR of spouses is higher than other family members.

Objective:To investigate the epidemiological characteristics for family clusters of COVID-19 in Zhejiang Province.Methods:The data including cases information of asymptomatic infected cases of family clusters of COVID-19 in Zhejiang Province were collected from Public Health Emergencies Reporting System of China Center for Disease Control and Prevention. Calculate the case number of subsequent cases, index cases, asymptomatic infected cases, exposure cases, and then, compute family secondary attack rate (SIR) and serial interval.Results:A total of 389 cases comprised 149 family index cases and 240 subsequent cases. The clinical symptoms between family index cases and subsequent cases (exclude asymptomatic infected cases ) were similar, fever was the most common symptoms in the two groups 115 (77.18%) and 110（48.67%）respectively, the cases with diarrhea symptoms accounted for the least proportion, which were 7 (4.70%) and 6 (2.65%) respectively. The serial interval between the family index cases and the subsequent cases [ M ( P25, P75)] was 4.00 (2.00, 6.00) days. Family secondary attack rate for subsequent cases was 34.43%, subsequent cases aged between 14 and 60 have the highest SIR (43.42%) compared with other two age groups, the difference was statistically ( P<0.001); the family SIR of the spouses of the family index cases is 68.57%, and are higher than that of parents (29.03%), children (25.00%) and other family members (24.21%), the difference was also statistically ( P<0.001). Conclusion:2019 novel coronavirus has shorter serial interval and higher family SIR, the SIR of spouses is higher than other family members.

Objective: Previous cross-sectional studies suggested that elevated levels of total cholesterol content of erythrocyte membrane (CEM) could significantly increase the risk of acute coronary syndrome (ACS). The purpose of the present study was to assess the predictive value of baseline CEM levels for the risk of clinical endpoint events in patients with ACS through prospective follow-up studies. Methods: This study is a prospective follow-up study, which consisted of 859 patients with first ACS (698 patients with unstable angina pectoris and 161 patients with acute myocardial infarction), diagnosed and hospitalized in the First and Second Affiliated Hospital of Anhui Medical University. The routine blood lipid levels and CEM were measured. Patients were divided into two groups according to the median of baseline CEM: CEM≤131.56 μg/mg group (n=430) and CEM>131.56 μg/mg group (n=429). Patients were followed up at 6 months interval. The clinical endpoints were nonfatal myocardial infarction, nonfatal stroke, all-cause mortality, all-cause mortality, heart failure requiring hospitalization, and coronary artery revascularization. Kaplan-Meier curve analysis and Cox proportional hazard model were used to analyze the impact of elevated CEM on the occurrence of clinical end-point events. HR values and 95%CI of each variable were obtained. Cox regression analysis of all-cause mortality was performed according to whether patients had risk factors for coronary heart disease (hypertension, diabetes, smoking and elevated LDL-C) and whether they were treated with PCI. Results: The follow-up time was 1 640 (1 380, 2 189) days. Cox analysis after adjustment showed that an elevated baseline of CEM (>131.56 μg/mg) was associated with an increased risk of all-cause mortality (HR=1.690, 95%CI 1.041-2.742, P=0.034), but had no significant predictive effect on the other clinical endpoints. Subgroup analysis showed that elevated baseline CEM levels in ACS patients with LDL-C>1.8 mmol/L (HR=1.687, 95%CI 1.026-2.774, P=0.039), receiving in-hospital PCI (HR=2.365, 95%CI 1.054-5.307, P=0.037), or male (HR=1.794, 95%CI 1.010-3.186, P=0.046) were associated with an increased risk of all-cause mortality. Conclusion The results showed that elevated CEM levels can increase the risk of all-cause mortality in ACS patients.

Objective To investigate whether intensive atorvastatin treatment in patients after percutaneous coro-nary intervention ( PCI) could decrease the effect of contrast medium on kidney function and the incidence of con-trast-induced acute kidney injury( CI-AKI) . Methods A total of 128 patients with PCI were randomly divided into two groups:the enhanced treatment group (n=64) and the control group(n=64). The enhanced treatment group received 80 mg atorvastatin at 12~24 h before PCI and 24,48 h after PCI. The control group was given 20 mg ator-vastatin respectively before and after PCI. The primary end point was the incidence of CI-AKI. Serum creatinine (Scr), cystatin C, glomerular filtration rate(eGFR), urinary albumin and urinary β-2 microglobulin levels were observed at 24 h before PCI and 24, 48, 72 h after PCI. Results In the enhanced treatment group 3. 1 % (n=2) of patients developed CI-AKI versus 4. 7 % (n=3) in the control group, without statistical difference (P=1.00). There was no significant difference between two groups in postoperative Scr, cystatin C, eGFR, urinary al-bumin, urinary β-2 microglobulin and creatine kinase(CK). Three days after the operation, alanine aminotrans-ferase ( ALT) elevated in two groups, and aspartate aminotransferase ( AST) increased in the enhanced treatment group (P<0. 05), but they were all in the normal range. Conclusion There has been no significant difference in decreasing the incidence of CI-AKI and the damage of contrast medium on renal function between the enhanced treatment group and the control group before PCI.

Objective To investigate the predictive value of mild renal insufficiency on the endpoint events in patients with acute coronary syndrome (ACS).Methods A total of 552 patients with ACS were enrolled in the present study.According to the levels of estimated glomerular filtration rate (eGFR),patients were divided into two groups,normal renal function (eGFR≥90 ml · min-1 · 1.73 m-2) and mild renal insufficiency (60≤eGFR ＜90 ml · min-1 · 1.73 m-2).The primary and secondary events were collected and analyzed through the present prospective follow-up study.Results The patients in mild renal insufficiency group had a higher incidence of the primary endpoint events than normal renal function group [31 cases (12.6％) vs 15 cases (4.9％),P =0.001].There was no difference of the secondary endpoint events incidence in the two groups.The incidence rate of all-cause mortality [8.9％ (22 cases) vs 2.2％ (7 cases),P ＜0.001] and cardiac death [6.5％ (16 cases) vs 1.3％ (4 cases),P =0.001] was higher in mild renal insufficiency group,but there was no statistical difference of incidence rate of no fatal stroke and myocardial infarction in the two groups.The results of COX regression analysis showed that the incidence of primary endpoint events in patients with mild renal dysfunction was 2.265 folds (95％ CI 1.076-4.771,P=0.031) of patients with normal renal function.Further analysis indicated that the predictive value of mild renal insufficiency was only for all-cause mortality (HR 3.118,95％ CI 1.197-8.125,P =0.020),not for heart failure and revascularization.According to the Kaplan-Meier curves results,the incidences of the primary endpoint events (P =0.004) and all-cause mortality (P =0.001) were higher in mild renal insufficiency group than in normal renal function group.Conclusion Mild renal insufficiency has important predictive value for primary endpoint events in patients with ACS.

Objective To determine the in vitro antifungal effects of closantel against Candida albicans.Methods A microdilution method was used to determine the minimum inhibitory concentration (MIC)of fluconazole alone and in combination with closantel against Candida albicans standard strain CAF-2.Ten strains of Candida albicans were cultured in RPMI-1640 liquid culture containing 10％ calf serum with or without the presence of closantel at 16 mg/L,followed by the observation of hypha formation.Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were performed to observe the ultrastructure of Candida albicans CAF-2 strain after exposure to closantel at 16 mg/L for 24 hours.Results Closantel could inhibit the growth of Candida albicans,and enhance the antifungal effect of fluconazole against Candida albicans in vitro.The percentage of Candida albicans forming hypha was 91.2％ ± 3.9％ in untreated Candida albicans,significantly higher than that in closantel-treated Candida albicans (29.8％ ± 5.1％,t =30.24,P ＜ 0.05).As TEM showed,closantel-treated Candida albicans gave a round,oval or pleomorphic appearance,with an irregular budding from the cell surface.Further more,the electron dense layer in the outer layer of cell wall was absent or unevenly distributed,the transparent layer was irregularly thickened,some cell membrane was locally disrupted or collapsed,and intracellular vacuoles increased after closantel treatment.Scanning microscopy revealed a rough surface,sparse and irregular budding of Candida albicans after treatment with closantel.Conclusion Closantel exhibits a promising anti-Candida albicans property in vitro.

Objective To explore the correlation between coronary lesions and homocysteine and the plasma homocysteine changes before and after coronary intervention treatment.Methods By the transmission immune method than turbidity,respectively,89 patients with acute coronary syndrome test group and 28 coronary artery of the normal group Hcy level and 70 routine coronary stents after implantation of Hcy level.Results Acute coronary syndrome group of Hcy content was significantly higher than normal coronary artery (P ＜ 0.01 ).Coronary lesions impact Hcy level,its significant difference( P ＜ 0.01 ).And coronary intervention before and after treatment Hcy no significant differences( P ＞0.05 ).Conclusion High homocysteine is cardiovascular disease of a new and important independent risk factors.Hcy close relations with ACS,positively related,testing their level of change,and can be effectively reaction to the development process of the ACS and prognosis,prevention and treatment for clinical ACS provide reliable basis.Coronary intervention treatment can reduce Hcy whether level and role of blood vessels,is yet to be studied further.