Study on the Biological Function of Abemecilib in Inhibiting the Proliferation, Invasion and Migration of Small Cell Lung Cancer with High c-Myc Expression / 中国肺癌杂志

BACKGROUND@#Small cell lung cancer (SCLC) with high c-Myc expression is prone to relapse and metastasis, leading to extremely low survival rate. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib plays a key role in the treatment of tumors, but the effects and mechanisms on SCLC remain unclear. This study was to analyze the effect and molecular mechanism of Abemaciclib in inhibiting proliferation, migration and invasion of SCLC with high c-Myc expression, with a view to expanding a new direction for reducing the recurrence and metastasis.@*METHODS@#Proteins interacting with CDK4/6 were predicted using the STRING database. The expressions of CDK4/6 and c-Myc in 31 cases of SCLC cancer tissues and paired adjacent normal tissues were analyzed by immunohistochemistry. The effects of Abemaciclib on the proliferation, invasion and migration of SCLC were detected by CCK-8, colony formation assay, Transwell and migration assay. Western blot was used to detect the expressions of CDK4/6 and related transcription factors. Flow cytometry was used to analyze the effects of Abemaciclib on the cell cycle and checkpoint of SCLC.@*RESULTS@#The expression of CDK4/6 was associated with c-Myc by STRING protein interaction network. c-Myc can directly modalize achaete-scute complex homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1) and Yes-associated protein 1 (YAP1). Moreover, CDK4 and c-Myc regulate the expression of programmed cell death ligand 1 (PD-L1). Immunohistochemistry showed that the expressions of CDK4/6 and c-Myc in cancer tissues were higher than those in adjacent tissues(P<0.0001). CCK-8, colony formation assay, Transwell and migration assay verified that Abemaciclib could effectively inhibit the proliferation, invasion and migration of SBC-2 and H446OE(P<0.0001). Western blot analysis further showed that Abemaciclib not only inhibited CDK4 (P<0.05) and CDK6 (P<0.05), but also affected c-Myc (P<0.05), ASCL1 (P<0.05), NEUROD1 (P<0.05) and YAP1 (P<0.05), which are related to SCLC invasion and metastasis. Flow cytometry showed that Abemaciclib not only inhibited the cell cycle progression of SCLC cells (P<0.0001), but also significantly increased PD-L1 expression on SBC-2 (P<0.01) and H446OE (P<0.001).@*CONCLUSIONS@#Abemaciclib significantly inhibits the proliferation, invasion, migration and cell cycle progression of SCLC by inhibiting the expressions of CDK4/6, c-Myc, ASCL1, YAP1 and NEUROD1. Abemaciclib can also increase the expression of PD-L1 in SCLC.

Association between phenolic compound exposure and dyslipidemia in the population / 环境与职业医学

Background Phenolic compounds may adversely affect human health, but the current relevant studies are mostly limited to the impact of single phenolic compound exposure on human health, and there is still a lack of studies on the population-based association between combined exposure to multiple common phenolic compounds and dyslipidemia. Objective To explore the association of phenolic compound combined exposure and dyslipidemia based on principal component analysis-random forest (PCA-RF) strategy. Methods The data were from the National Health and Nutrition Examination Survey (2013–2016). A total of 1301 adult residents aged ≥ 20 years with complete information on demographics and lifestyle, urine phenol concentrations (bisphenol A, bisphenol F, bisphenol S, triclocarban, benzophenone, and triclosan), and serum concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were included in this study. The concentrations of six urinary phenolic compounds were determined by solid phase extraction coupled with high performance liquid chromatography and tandem mass spectrometry, and the lipid indicators were determined by enzymatic methods. Principal component analysis combined with random forest model was used for model construction. First, principal component analysis was performed on 18 original variables including 6 phenolic compounds and 12 basic characteristic indicators, and then random forest model was established with dyslipidemia and its four evaluation indicators as dependent variables and the extracted principal components as independent variables, respectively. Results The PCA-RF analysis showed that bisphenol A, bisphenol F, and benzophenone may be important factors for dyslipidemia in the study subjects; bisphenol A, bisphenol F, and triclosan may be important factors for TC level in the study subjects; bisphenol A, bisphenol F, triclocarban, and benzophenone may be important factors for TG level in the study subjects; bisphenol A may be an important factor for LDL-C level in the study subjects; bisphenol F and benzophenone may be important factors for HDL-C level in the study subjects. Conclusion Phenolic compound exposure may be an important risk factor for the development of dyslipidemia. PCA-RF strategy can be effectively used to explore the association between phenolic compound exposure and dyslipidemia in the population.

Research Progress on the Mechanism and Clinical Data of Cereblon in Reversing the Resistance of Lung Cancer to PD-1 Antibody by T cells / 中国肺癌杂志

Programmed cell death receptor 1 (PD-1) is a membrance-spanning protein mostly expressed in the T cell, and combines with programmed cell death ligand 1 (PD-L1) in the targeting cell. When binding to the ligand on tumor cells, PD-1 as an immunosuppressive molecule, can inhibit the immune function of T cells, thus tumor immune escape. For example, depletion of peripheral effector T cell and accelerate the transformation of effector T cells into regulator T cells. To solve this problem, PD-1 antibody is used to bind to PD-1 on T cells to inhibit the interaction between PD-1 on the T cells and PD-L1 on the tumor cells so that it can restore the function of T cells to kill tumor cell. PD-1 antibodies, such as Nivolumab and Pembrolizumb, are approved as a first-line treatment for advanced non-small cell lung cell cancer. However, due to the interaction of tumor cells, T cells and cytokines, some patients developed drug resistance which reduces the efficacy of immunotherapy. Hence, how to overcome resistance has become a urgent problem. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex and the only known molecular receptor of immunoregulatory drugs, has been found to reverse PD-1 antibody resistance by binding to CRBN regulatory agents (CMS), exert T cell immune function by regulating proliferation, activation and metabolism of T cell. In this paper, the mechanism of down-regulation of T cells leading to resistance of PD-1 antibody in lung cancer, the mechanism of CRBN regulating T cells, and research progress of CRBN regulator in the treatment of lung cancer were reviewed.
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Analysis on the epidemiological features of human brucellosis in northern and southern areas of China, 2015-2016 / 中华流行病学杂志

Objective To analyze the epidemiological characteristics of human brucellosis in northern and southern areas of China,and to develop national strategies for brucellosis prevention and control.Methods Individual data on human brucellosis was collected from the National Notifiable Infectious Disease Reporting Information System to describe the situation of brucellosis in China during 2015-2016.Epidemiological features of the disease in northem and southern areas of China were analyzed.Results A total of 104 125 cases were reported in mainland China during 2015-2016,with an average incidence rate as 3.81/100 000.The overall incidence rate from the northem provinces was 7.77/100 000 in 2016,a 18.6％ decrease from 2015 (9.55/100 000),whereas the incidence rate in the southern provinces was 0.27/100 000 in 2016,with an increase of 28.6％ than 0.21/100 000 in 2015.90.0％ of the newly infected counties mainly distributed in southern China.As for the locations of reporting cases,most of them were in the same counties in the northern areas (52.3％) while most cases in the southern areas (59.6％) were imported from other counties.The median age of the cases was 48 (IQR:38-58) years,with male-to-female ratios as 2.7 ∶ 1 in the north and 2.2 ∶ 1 in the south.Majority of the cases were occupation-related,from both the northern (86.8％) and southern (62.7％) areas.Human brucellosis occurred every month throughout the year but with an obvious seasonal increase between March and July.Conclusions Different epidemiological features of human brucellosis appeared in both northern and southern areas of China.The disease was seen endemic in the northem and dispersal in the southem provinces.Appropriate strategies for brucellosis prevention and control should be developed,according to the different epidemiological characteristics in the northcm or southcm areas.

Analysis on the epidemiological features of human brucellosis in northern and southern areas of China, 2015-2016 / 中华流行病学杂志

Objective To analyze the epidemiological characteristics of human brucellosis in northern and southern areas of China,and to develop national strategies for brucellosis prevention and control.Methods Individual data on human brucellosis was collected from the National Notifiable Infectious Disease Reporting Information System to describe the situation of brucellosis in China during 2015-2016.Epidemiological features of the disease in northem and southern areas of China were analyzed.Results A total of 104 125 cases were reported in mainland China during 2015-2016,with an average incidence rate as 3.81/100 000.The overall incidence rate from the northem provinces was 7.77/100 000 in 2016,a 18.6％ decrease from 2015 (9.55/100 000),whereas the incidence rate in the southern provinces was 0.27/100 000 in 2016,with an increase of 28.6％ than 0.21/100 000 in 2015.90.0％ of the newly infected counties mainly distributed in southern China.As for the locations of reporting cases,most of them were in the same counties in the northern areas (52.3％) while most cases in the southern areas (59.6％) were imported from other counties.The median age of the cases was 48 (IQR:38-58) years,with male-to-female ratios as 2.7 ∶ 1 in the north and 2.2 ∶ 1 in the south.Majority of the cases were occupation-related,from both the northern (86.8％) and southern (62.7％) areas.Human brucellosis occurred every month throughout the year but with an obvious seasonal increase between March and July.Conclusions Different epidemiological features of human brucellosis appeared in both northern and southern areas of China.The disease was seen endemic in the northem and dispersal in the southem provinces.Appropriate strategies for brucellosis prevention and control should be developed,according to the different epidemiological characteristics in the northcm or southcm areas.

Choledochoduodenal fistula in Mainland China: a review of epidemiology, etiology, diagnosis and management

PURPOSE: Choledochoduodenal fistula (CDF) is an extremely rare condition even in the most populous nations. However, diagnostic tools are inadequate for the young surgeon to be made aware of such a rare condition before surgery. Hence, basic understanding of the epidemiology, etiology, and management for this unusual but discoverable condition are necessary and essential. METHODS: The exclusive case reports of CDF, which were published from 1983 to 2014 concerning mainland Chinese people, were performed to review the epidemiology, etiology, and management. RESULTS: A total of 728 cases were incorporated into this review among 48 papers. More than half of the CDF cases were female (416) with an average age of 57.3 years. CDF was usually caused by cholelithiasis (573 of 728). Epigastric pain (589 of 728) and cholangitis (395 of 728) were the most common symptoms of CDF. CDF was usually detected and confirmed by endoscopic retrograde cholangiopancreatography (ERCP) (475 of 728) in Mainland China. The fistulas larger than 1 cm (82 of 654) were recommended for surgical biliary reconstruction. Fistulas between 0.5 cm and 1.0 cm (467 of 654) which were followed frequently by cholangitis attacks also required surgery; the rest were recommended to have stone removal and/or the application of an effective biliary drainage. Fistulas less than 0.5 cm (105 of 654) were usually received conservative therapy. CONCLUSION: CDF should be considered in differential diagnosis of recurrent epigastric pain and cholangitis. A possible ERCP should be arranged to investigate carefully. Depending on the size of fistula and clinical presentation, different programs for CDF are indicated, ranging from drug therapy to choledochojejunostomy.

Analysis of epidemiological features of human rabies in China, 2012 / 中华流行病学杂志

Objective To analyze epidemiological characteristics and trends of rabies and explore control and prevention measures based on the rabies surveillance data of 2012 in China.Methods Data of 2012 from China' s infectious disease surveillance reporting and management system and sentinel surveillance systems in 6 provinces were used,for a retrospective analysis in descriptive epidemiological methods.Results 1 425 cases were reported in 731 counties of 27 provinces in 2012 and 1 361 deaths were reported due to rabies,with the rabies incidence rate and mortality rate of 0.11/100 000 and 0.10/100 000 respectively,decreasing by 26.0％ and 27.9％ respectively from 2011.Rabies epidemic was mainly found in southern regions,followed by middle and eastern regions in China.49.6％ of total rabies cases were found in Guangxi,Guangdong,Hunan,Guizhou,and Henan province,which were the top five provinces.The rabies cases were mainly peasants,students and scattered children,accounting for 70.9％,8.3％ and 5.8％ of total cases respectively.The male-female ratio in rabies cases was 2.6:1.In 2012,294 epidemiological questionnaires were collected,revealing that 92.1％ of the exposure was caused by dogs and 6.8％ by cats.The median of latent period was 70 days.62.4％ of the cases were exposed in upper limb,and only 6.9％ of such cases were vaccinated after exposure while the proportion of passive immunity biological vaccination was 2.9％ for cases with exposure of category Ⅲ.Surveillance data from PEP (post-exposure prophylaxis) clinics showed that 81.7％ of the visitors were hurt by dogs and the exposure categories Ⅰ,Ⅱ and Ⅲ accounted for 7.0％,50.5％ and 42.5％ respectively.The proportion of of the exposure categories varied by PEP surveillance clinics.Conclusion Despite continuing decrease of rabies cases in China in 2012,the number of counties (districts) affected failed relatively slow,with a tendency of rabies spreading to the western and northern regions in China.There were more rabies cases in rural areas than urban ones,and children and elderly people constitute the high-risk population.Animal reservoir of rabies was still dogs as before.Poor PEP and insufficient use of vaccination and passive immunity preparations were main causes for onset of human rabies.

Epidemiological analysis on severe fever with thrombocytopenia syndrome under the national surveillance data from 2011 to 2014, China / 中华流行病学杂志

Objective To analyze the epidemiological features and surveillance management programs on severe fever with thrombocytopenia syndrome (SFTS) in China from 2011 to 2014.Methods The analysis of epidemiological characteristics and surveillance management programs was based on the annual reporting data collected from the National Disease Reporting Information System while the description of cluster incidents was based on those reports collected from the Public Health Emergency Information Management System (PHEIMS).Association between age groups and fatality rate was tested under the Cochran-Armitage Trend Test.The difference of fatality rates between differing groups was analyzed,using the chi-square test,with statistical significance on α=0.05.Results Between 2011 and 2014,5 352 suspected,probable and lab-confirmed cases of SFTS were reported in 23 provinces,of which 16 provinces reported 2 750 lab-confirmed cases with a fatality of 7.9％,accounting for 51.4％ of all the cases,nation-wide.Henan,Shandong,Hubei,Anhui,Liaoning,Zhejiang and Jiangsu reported 99.3％ of those lab-confirmed cases.The period between April and October appeared the epidemic season,with its peak from May to July.Most cases were farmers,accounted for 88.3％ of the lab-confirmed cases.People at the age between 50-74 occupied 67.6％ of all the cases.Fatality of the disease continually increased from 3.7％ in the age group 40-44 to 13.5％ in the age group older than 80.Fatality rates appeared statistically different between the groups with or without misdiagnosis,with OR as 3.06 (95％CI:1.61-5.90).Secondary cases of the cluster incidents were most likely to result from contacting the blood of the index cases.Conclusion Number of reported SFTS cases showed a rising trend in China.Henan,Hubei,Anhui,Shandong and Liaoning provinces appeared at high risk of the disease.Geographical distribution of the SFTS cases' seemed highly sporadic,with May to July being the peak season.Farmers and elderly were considered as high risk population.Occasionally,cluster incidents might be seen,as the result of contacting the blood of cases or corpses.Being at older age and misdiagnosis seemed to be risk factors for fatality.