[Progress in research of rash and fever syndrome surveillance and early warning].

Objective: To introduce the progress in research of rash and fever syndrome (RFS) surveillance and early warning both at home and abroad, and provide reference for surveillance and prevention of RFS in China. Methods: The keywords "fever" "rash" and "surveillance" and others were used for a literature retrieval by using China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and Web of Science. The languages of literatures were limited in Chinese and English. The key information of the literatures were collected and analyzed with Excel. Results: A total of 36 study papers (21 in Chinese and 15 in English) were included. The studies mainly focused on the pathogen surveillance of RFS (n=19). The pathogens included measles virus, varicella-zoster virus, rubella virus, enterovirus, human B19 virus, dengue virus, streptococcus group A, Salmonella typhi and Salmonella paratyphoid,human herpesvirus, mumps virus and adenovirus. Eight studies were about the surveillance in major events, such as sport game, World Expo and religious gathering, or sudden natural disasters, such as earthquake and tropical storm, during 2010-2015. Eight studies focused on case or epidemic surveillance, most of which were studies from other counties. The surveillance sites were medical institutions. RFS was diagnosed according to the International Classification of Diseases, 9th (ICD-9) and symptoms descripted in chief-complaint. Only one study in Mongolia conducted RFS epidemic prediction. The analysis methods of 36 papers included simple descriptive analysis, time-based early warning models (such as regression analysis, fixed threshold method, Hugh Hart control chart method and cumulative sum control chart method) and time series analysis method. Conclusions: In the future, RFS surveillance system should cover both known pathogens and emerging pathogens. Automatic surveillance using information capture and intelligent modelling can be applied to improve the sensitivity and specificity of RFS surveillance and early warning.

Circular ribonucleic acid circ-FADS2 promotes colorectal cancer cell proliferation and invasion by regulating miR-498/S100A16.

The aim of this study is to examine the role and functional mechanism of circ-FADS2 in colorectal cancer (CRC). The levels of expression of circ-FADS2 were detected in 48 patients with CRC and their paired normal tissue samples and cell lines (SW480, SW620, HCT116, HT29, and NCM460) using quantitative real-time polymerase chain reaction (qRT-PCR). Circ-FADS2 was then silenced in SW480 and HT29 cells using two small interfering ribonucleic acids. Themolecular mechanism of circ-FADS2 in CRC progression and migration was then examined by sponging miR-498 and promoting S100A16 expression. After this, the expression of miR-498 and S100A16 in CRC tissues was analyzed using a qRT-PCR. In results: circ-FADS2 was found to be significantly upregulated in CRC tissues, when compared with paired normal tissues. Higher circ-FADS2 expression was associated with advanced stages, lymphatic metastasis, and reduced overall survival (OS). In addition, silencing circ-FADS2 markedly inhibited the proliferation and invasion of CRC and increased the percentage of cancer cells in the G1 phase in vitro. Reducing circ-FADS2 decreased SW480 cell proliferation in vivo. By inhibiting miR-498 expression, circ-FADS2 promoted S100A16 expression leading to the activation of the AKT pathway, resulting in CRC progression. We conclude that Circ-FADS2 expression was upregulated in CRC tissues and cells and was found to be correlated with advanced cancer, metastasis, and poor OS. A study of the molecular mechanism suggests that a circ-FADS2/miR-498/S100A16/AKT signaling cascade may be a potential therapeutic target for the treatment of CRC.

[Effects of occupational exposure to aluminum on verbal function of workers].

Objective: To explore the effect of occupational aluminum (Al) exposure on workers' overall cognitive level and speech function. Methods: In July 2019, by using cluster sampling method, the group of 232 exposed to Al from an Al plant in Shanxi Province were selected as the exposed group, and the group of 228 not exposed to Al were selected as the control group. The blood Al concentration was determined by inductively coupled plasma mass spectrometry (ICP-MAS) . The exposed group was divided into high exposure group and low exposure group according to the median (M) concentration of Al in serum. The general cognitive function and speech function were evaluated with the Montreal Cognitive Assessment Scale (MoCA) , and the differences in the general cognitive function and speech function between the groups were compared, and non-conditional logistic regression was used to analyze the possible influencing factors of mild cognitive impairment (MCI) . Results: There were significant differences in age, working age, education and drinking status between Al exposed group and control group (P<0.05) . The total MoCA score, animal naming tese (ANT) score and category fluency repetition (CFT) score in Al exposure group were lower than control group and the differences were statistically significant (P<0.05) . The full rate of ANT was lower than that of CFT in Al exposure group (P<0.05) . The total MoCA score, ANT score and CFT score in the high exposure group were significantly lower than those in the control group (P<0.05) . The score of MoCA, ANT and CFT in high exposure group were lower than those in low exposure group between the level of serum aluminum>60 µg/L group and ≤60 µg/L group (P<0.05) . Logistic regression analysis showed that working age, serun Al concentration, ANT score, CFT score and SR score were the possible influencing factors of MCI in occupational Al exposure workers (P<0.05) . Conclusion: Occupational Al exposure can lead to impaired speech function of workers, the higher the ANT score, CFT score and SR score, the lower working age and serum Al concentration, the lower risk of MCI.

[Study on warfarin medication checklist for improving patient compliance].

This study explored whether clinical pharmacists can improve patients' medication compliance with the use of warfarin medication checklist and the correlation between them. A total of 147 inpatients discharged from Shanghai Tongren Hospital with warfarin from July 2018 to September 2019 were randomly divided into the control group and the intervention group by random number table, including 75 in the control group and 72 in the intervention group. There were no statistically significant differences in gender, age, marital status, drinking history, smoking history, department distribution, type of thromboembolic disease, comorbidity and combined medication between the two groups (P>0.05). The control group received routine warfarin medication education at discharge, while the intervention group received clinical pharmacist's assessment of bleeding risk and targeted medication education using warfarin medication checklist at discharge. The monitoring time and value of the international normalized ratio (INR) between the two groups during hospitalization and within 6 months after discharge were recorded, as well as warfarin-related adverse events. The Morisky Medication Adherence Scale was used to evaluate the medication compliance of patients in the two groups. Spearman correlation analysis was used to study the relationship between warfarin compliance and variables in the warfarin medication checklist. The intervention group had better follow-up regularity than the control group (χ²=34.3, P<0.001), and the medication compliance in the intervention group was better than that in the control group (χ²=38.6, P<0.001). There were significant correlations between warfarin compliance and duration of warfarin therapy (R=-0.275, P=0.027), number of comorbidities (R=-0.335, P=0.004), bleeding risk (R=-0.433, P<0.001). In conclusion, using warfarin medication checklist can improve patients' medication compliance. Patients' medication compliance was significantly negatively correlated with duration of warfarin therapy, number of comorbidities and bleeding risk. Clinical pharmaceutical care can improve the medication compliance of patients with warfarin, so as to improve the medication results, which may be helpful for the drug treatment of patients with chronic diseases.

[Conversion of serum anti-Schistosoma japonicum antibodies detected by immunological tests following treatment with praziquantel: a meta-analysis].

OBJECTIVE: To evaluate the conversion of serum antibodies against Schistosoma japonicum in humans and livestock detected by immunological tests following treatment with praziquantel. METHODS: The studies pertaining to serological tests of schistosomiasis japonica published from 1991 to 2020 were retrieved in electronic databases, including Chinese National Knowledge Infrastructure, WanFang Data, PubMed and ScienceDirect. Data were extracted from included studies. The publication bias was assessed with funnel plots using the software RevMan version 5.3, and the conversion of antibodies against S. japonicum was evaluated through meta-analysis. RESULTS: A total of 40 publications were included in the final meta-analysis, consisting of 33 Chinese publications and 7 English publications, and all immunological tests were performed with indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA). Pooled analysis showed that the negative rates of serum anti-S. japonicum antibody were 45.36% [95% confidential interval (CI): (43.96%, 46.76%)] and 20.83% [95% CI: (19.69%, 21.97%)] detected by ELISA and IHA within 6 months post praziquantel treatment, 62.95% [95% CI: (61.59%, 64.31%)] and 55.61% [95% CI: (54.21%, 57.01%)] within 6 to 12 months after treatment and 85.92% [95% CI: (84.94%, 86.90%)] and 86.90% [95% CI: (85.95%, 87.85%)] over 12 months after treatment, respectively. CONCLUSIONS: The negative rate of the serum anti-S. japonicum antibody by IHA and ELISA increased with the time of post-treatment with praziquantel. The overall negative rates of anti-S. japonicum antibody detected by IHA and ELISA are low within 12 months post praziquantel treatment. However, a high negative rate of anti-S. japonicum antibody is detected if there is no new contact with infested water after 12 months of praziquantel treatment.

[The impact of occupational aluminum exposure on workers' overall cognitive function and various cognitive fields].

Objective: To evaluate the effects of occupational aluminum exposure on workers' overall cognitive function and cognitive fields. Methods: From July to August 2019, using the method of cluster sampling, 101 and 117 workers were selected from the electrolytic aluminum workshop of an aluminum plant in a region and the maintenance workshop of a plant in the same region. The venous blood of the subjects was collected, the plasma was extracted, and the blood aluminum concentration was measured by ICP-MS. According to the blood aluminum concentration and type of work, 93 workers who were lower than the median blood aluminum concentration and in the maintenance workshop of a factory were divided into low aluminum exposure group, and 85 workers who were higher than the median blood aluminum concentration and in the electrolytic aluminum workshop of an aluminum factory were divided into high aluminum exposure group. The basic information of the respondents, was collected through the employee physical examination form. The overall cognitive function of workers was evaluated by Beijing Montreal Cognitive Assessment Scale (MoCA) . Multiple linear regression analysis and logistic regression analysis were used for multiple statistical analysis. Results: Compared with the low aluminum exposure group (25.42±1.808) , the total score of MoCA in the high aluminum exposure group (23.84±2.919) was significantly lower, and the scores of visual space, executive function, abstract and delayed recall were significantly lower (P<0.05) . Linear regression analysis showed that the total score of MoCA, visual space and executive function, naming and delayed recall were negatively correlated with blood aluminum concentration (ß=-0.018、-0.008、-0.003、-0.008, P<0.05) .MOCA total score, visual space and executive function, attention, language, abstraction, orientation were positively correlated with educational level (ß=0.853、0.310、0.216、0.171、0.412、0.122, P<0.05) . Logistic regression analysis showed that adjusting for age, smoking, drinking and education, blood aluminum was a risk factor for mild cognitive impairment (OR=1.017, P<0.05) ; Education level was the protective factor of mild cognitive impairment (OR=0.419, P<0.05) . Conclusion: Occupational aluminum exposure can affect the overall cognitive function of workers, and occupational aluminum exposure increases the risk of MCI.

MiR-20a suppresses proliferation and facilitates apoptosis of breast cancer cells via the MTOR signaling pathway.

OBJECTIVE: The paper aimed to explore the role of micro ribonucleic acid (miR)-20a in regulating the proliferation and apoptosis of breast cancer cells. MATERIALS AND METHODS: The expression of miR-20a in breast cancer cells was analyzed via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry were employed to analyze the proliferation and apoptosis of cells. Thereafter, the target proteins of miR-20a were predicted using TargetScan, a website for miRNA target gene prediction, and the interaction between miR-20a and the target genes was detected through the Luciferase reporter gene assay, qRT-PCR assay, and Western blotting. Finally, the miR-20a inhibitor and target gene expression plasmids were co-transfected for rescue experiment to study whether the target genes participate in the inhibitory effect of miR-20a on the proliferation of breast cancer cells. RESULTS: It was found that the expression of miR-20a was upregulated in breast cancer cell lines. Silencing miR-20a expression inhibited the proliferation and promoted the apoptosis of breast cancer cell. Besides, it was demonstrated that late endosomal/lysosomal adaptor, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) activator 3 (LAMTOR3) were a direct target of miR-20a. The knockdown of LAMTOR3 expression repressed the influence of miR-20a on the proliferation of breast cancer cells. CONCLUSIONS: MiR-20a targets LAMTOR3 gene to regulate the mTOR signaling pathway, thereby suppressing the proliferation and facilitating the apoptosis of breast cancer cells. It suggests that miR-20a exerts a carcinogenic effect in breast cancer, which may be a potential target for the treatment of breast cancer.

Objective response of first-line chemotherapy of triple-negative breast cancer translates into survival benefit: an analysis in an independent, prospective clinical trial and a real-world setting.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p<0.001) together with Eastern Cooperative Oncology Group (ECOG) performance status, disease-free survival, number of metastatic organ sites and platinum-based chemotherapy used as first-line chemotherapy were observed to be independent prognostic factors for progression-free survival (PFS), and OR (OR vs non-OR, HR, 0.602, p=0.002) together with ECOG score, disease-free survival, number of metastatic organ sites and previous anthracycline and/or taxane treatment were observed to be independent predictive factors for OS in the training cohort. These predictors were confirmed in the validation cohort. For OR and non-OR group, median OS was 23.72 and 13.83 months in the training cohort (HR, 0.637, p=0.002), and 21.95 and 13.80 months in the validation cohort (HR, 0.608, p<0.001), respectively. By adding OR in the OS predictors, the concordance index (C-index) improved from 0.622 to 0.645 in the training cohort and 0.653 to 0.675 in the validation cohort. PFS and OS of mTNBC can be predicted by OR status with any regimen of first-line chemotherapy in an independent prospective clinical trial and a real-world setting. Therefore, TNBC, not like other subtypes of breast cancer, may be in need of combination chemotherapy or intense chemotherapy to achieve a high response rate for survival.

MiR-566 protects the malignant progression of breast cancer by negatively regulating WNT6.

OBJECTIVE: To elucidate the relationship between microRNA-566 (miR-566) and prognosis in breast cancer (BC) and to clarify the influences of miR-566 and WNT6 in its locus region on BC progression. PATIENTS AND METHODS: MiR-566 and WNT6 levels in 44 pairs of BC samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of miR-566 on clinical features and prognosis in BC patients were analyzed. According to the differential expressions of miR-566 in the tested BC cell lines, MDA-MB-231 and MCF-7 cells were selected for generating miR-566 knockdown and overexpression models, respectively. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assays were conducted to explore the role of miR-566 in BC cell functions. Besides, the regulatory interaction between miR-566 and its downstream gene WNT6 was assessed by performing Dual-Luciferase reporter assay. Finally, the co-regulation of miR-566 and WNT6 in BC cell functions was examined. RESULTS: MiR-566 was downregulated in BC tissues. BC patients with a low expression level of miR-566 were prone to suffering a large tumor size, advanced tumor grade, high incidence of lymphatic metastasis and poor prognosis. Overexpression of miR-566 weakened proliferative and migratory abilities in MCF-7 cells, whereas knockdown of miR-566 produced the opposite results in MDA-MB-231 cells. WNT6 was the target gene binding to miR-566, and they displayed a negative expression correlation in BC tissues. Regulatory effects of miR-566 on BC progression could be reversed by WNT6. CONCLUSIONS: MiR-566 is closely related to tumor size, tumor grade, lymphatic metastasis and prognosis in BC. It protects the malignant progression of BC by negatively regulating WNT6.

[Comparison of short-term and long-term efficacy between robot-assisted and thoracoscopy-laparoscopy-assisted radical esophageal cancer surgery].

Objective: To explore the safety and short-term and long-term efficacy of robot-assisted radical esophageal cancer surgery. Methods: A prospective randomized controlled trial was conducted. Patients who were preoperatively diagnosed as stage 0-IIIB esophageal squamous cell carcinoma and suitable for minimally invasive surgery in our hospital from January 1, 2014 to June 30, 2018 were prospectively enrolled. Those of age ≥75 years having received preoperative neoadjuvant therapy, contradicted to anesthesia or operation due to severe complications, with history of thoracotomy or laparotomy, with concurrent malignant tumors, without complete informations or refusing to participate in this study were excluded. Participants were randomly divided into the thoracoscopy-laparoscopy group and the robot group using a random number table in ratio of 1:1. Preoperative clinicopathological data, surgical data and postoperative outcomes were recorded. The patients were followed up mainly by telephone. Follow-up endpoint was recurrence of esophageal cancer and death. Kaplan-Meier method was used to estimate survival rate. The survival difference between the two groups was analyzed using the log-rank test. Results: According to above criteria, a total of 192 esophageal cancer patients were enrolled finally, including 144 males and 48 females with mean age of (61.9±8.6) years. The robot group had 94 cases, including 72 males and 22 females with mean age of (61.3±8.2) years, and the thoracoscopy-laparoscopy group had 98 cases, including 72 males and 26 females with mean age of (62.4±9.1) years. There were no significant differences in baseline data between the two groups (all P>0.05). Operation was abandoned in one case in each group due to extensive pleural cavity metastasis and one case in each group was converted to thoracotomy. The success rate of operation was 97.9% (92/94) in the robot group and 98.0% (96/98) in the thoracoscopy-laparoscopy group (χ(2)=0.002, P=0.996). The number of lymph nodes dissected in the robot group was significantly higher than that in the thoracoscopy-laparoscopy group (29.2±12.5 vs. 22.8±13.3, t=3.433, P=0.001), while there were no significant differences in operative time, intraoperative blood loss, R0 resection rate, postoperative 30-day mortality, postoperative hospital stay, ICU stay, time to withdrawal of chest drainage tube, ICU readmission, and postoperative morbidity of complications between the two groups (all P>0.05). The median follow-up time was 21 (3 to 57) months. During the follow-up, 3 cases and 4 cases were lost, and 2 cases and 3 cases died of other diseases in the robot group and in the thoracoscopy-laparoscopy group respectively. Recurrence occurred in 39 cases during follow-up, including 14 recurrences in the robotic group with 1- and 3-year recurrence-free survival rates of 92.4% and 87.6% respectively and the median recurrence time of 15 (9 to 42) months. There were 25 recurrences in the thoracoscopy-laparoscopy group with 1- and 3-year recurrence-free survival rates of 81.7% and 67.9% respectively and the median recurrence time of 9 (3 to 42) months. There was significant difference in recurrence-free survival between the two groups (χ(2)=4.193, P=0.041). Conclusions: The robotic surgical system has good oncology effect and surgical safety in the radical operation of esophageal cancer, which deserves further research and promotion.

[Analysis of epidemiological characteristics of report cases of rotavirus diarrhea in children under 5 years old in China, 2005-2018].

Objective: To analyze the epidemiological characteristics of rotavirus in children under 5 years old in China (excluding China Hong Kong, Macau and Taiwan data, the same below) from 2005 to 2018. Method: Data on other infectious diarrhea in the country from 2005 to 2018 were downloaded from the National Notifiable Disease Report System was to build a database for report cases of rotavirus diarrhea in children under 5 years of age, and descriptive epidemiological methods were used to analyze the data. Result: In 2005-2018, a total of 820 588 cases of rotavirus infection in children under 5 years old were reported nationwide, with male 500 944 cases, and with an average annual incidence of 63.7/100 000. The reported incidence showed a fluctuating upward trend increased from 8.4/100 000 to 178.1/100 000. The number of reporting provinces increased from 17 to 30. The reported incidence showed a peak of season from November to following February. The reported cases of rotavirus diarrhea in children under 5 months of age was 13.1%(107 845 cases), and the high-incidence age ranged from 6 months to 2 years old, accounting for 70.3% (576 874 cases), with a peak of 11-13 months (163 947 cases). The top three provinces (cities) reporting the incidence rate were Zhejiang (535.2/100 000), Guangdong (334.3/100 000) and Beijing (317.3/100 000), the provinces with the low reported case rates were Shanxi (0.9/100 000), Heilongjiang (1.6/100 000) and Liaoning (2.5/100 000), but there was no case reported in Tibet; The report cases of south region (745 526 cases) were 9.9 times north region (74 935 cases).The cases of rotavirus infection and other diarrhea pathogens were detected simultaneously accounted for 1.8% (15 030 cases) and mainly were positive for rotavirus and adenovirus (90.1%, 13 544 cases). Conclusion: The rate of rotavirus infection in children has increased rapidly since the age of 6 months, and 84.4% of the reported cases were infants before the age of 2 years.

[Platelet derived growth factor-BB regulates phenotype transformation of pulmonary artery smooth muscle cells via SIRT3 affecting glycolytic pathway].

Objective: To investigate whether platelet-derived growth factor-BB (PDGF-BB) can regulate phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) via SIRT3 affecting glycolytic pathway. Methods: The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into 3 groups by using 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway: normal control group, PDGF-BB group(30 ng/ml) and PDGF-BB (30 ng/ml)+2-DG (10 mmol/L) group. In lentivirus-mediated overexpression assay, cells were divided into control group, PDGF-BB group(30 ng/ml), PDGF-BB+deacetylase sirtuin-3 (SIRT3) overexpression group and PDGF-BB+empty vector group. The expression levels of phenotype related index such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), calponin, vimentin were detected by qRT-PCR and Western blot. Meanwhile, the expression of α-SMA was detected by cellular immunofluorescence staining. EDU staining was used to detect the proliferation of PASMCs. The expression of SIRT3 was detected by Western blot. The expressions of glucose transporter 1 and aerobic glycolytic enzymes were detected by qRT-PCR and Western blot in lentivirus-mediated overexpression assay. Results: (1) PDGF-BB affects PASMCs phenotypic transformation through glycolytic pathway: compared with normal control group, PDGF-BB significantly decreased the expressions of contractile phenotype markers such as α-SMA, SM-MHC, calponin mRNA and protein (all P<0.05), but it increased the expressions of the synthetic phenotype marker vimentin mRNA and protein (both P<0.05). Cellular immunofluorescence assay showed that PDGF-BB significantly decreased the number of α-SMA positive cells, while 2-DG reversed the process. (2) PDGF-BB promoted cell proliferation through glycolytic pathway: the proliferation of PASMCs was significantly higher in PDGF-BB group than in control group (P<0.05), and which could be significantly reduced by 2-DG (P<0.05). (3) PDGF-BB inhibited the expression of SIRT3 protein in PASMCs: the expression of SIRT3 protein in PDGF-BB group was lower than that in control group (P<0.05). (4) PDGF-BB affected glycolytic pathway through SIRT3:compared with the control group, PDGF-BB significantly increased the expression levels of glucose transporter 1 (Glut1), hexokinase 2 (HK2) and 6-phosphfructo-2-kinase 3 (PFKFB3) mRNA (all P<0.05), which was reserved by over-expression of SIRT3. There were no significant difference in mRNA expression levels between PDGF-BB group and PDGF-BB+empty vector group (P>0.05).Compared with the control group, PDGF-BB significantly increased the expression levels of Glut1, HK2 and PFKFB3 protein(all P<0.05), which was reserved by over-expression of SIRT3. There were no significant differences in protein expression levels between PDGF-BB group and PDGF-BB+empty vector group (all P>0.05). Conclusion: PDGF-BB regulates phenotypic transformation of PASMCs via SIRT3 affecting glycolytic pathway.

Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

Long noncoding RNA UCA1 promotes cell proliferation, migration and invasion of human leukemia cells via sponging miR-126.

OBJECTIVE: Acute myeloid leukemia (AML) is a bone marrow malignancy. Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) plays an important role in several cancers. However, the role of lncRNA UCA1 in AML remained unclear. MATERIALS AND METHODS: LncRNA UCA1 expressions in different cell lines were determined by RT-PCR. In human myelogenous leukemia (ML) cell lines K562 and HL60, effects of lncRNA UCA1 knockdown on cell viability, migration, invasion, and apoptosis were assessed, respectively. Binding effects between lncRNA UCA1 and microRNA (miR)-126, and between miR-126 and RAC1 3'UTR were detected by RT-PCR and luciferase activity assay. Involvements of miR-126 and RAC1 in lncRNA UCA1-mediated cell bioactivities were assessed. RESULTS: We found that lncRNA UCA1 was upregulated in ML cell lines. Knockdown of lncRNA UCA1 inhibited cell viability, migration, invasion, and prompted apoptosis of ML cells in vitro. LncRNA UCA1 could bind with miR-126 and downregulate miR-126 expression. Simultaneously, the anti-growth and anti-metastasis actions of lncRNA UCA1 knockdown on ML cells were reversed by miR-126 suppression. RAC1 was a target gene of miR-126, and the anti-ML actions of miR-126 were abolished by RAC1 overexpression. Moreover, PI3K/AKT and JAK/STAT signaling pathways were blocked by miR-126 overexpression while were activated by RAC1 overexpression. CONCLUSIONS: Taken together, this study elucidates a novel UCA1-miR-126-RAC1 regulatory network in ML cells, which may provide the feasibility for use lncRNA-based therapy in AML treatment.

[Interaction between transcriptional factor E26 transformation specific 1 and peroxiredoxin 1 in nicotine-induced oral precancerous lesion cells].

Objective: To investigate the interaction between nuclear transcriptional factor E26 transformation specific 1 (Ets1) and peroxiredoxin 1 (Prx1) in nicotine-induced oral precancerous lesion cells. Methods: Human oral precancerous lesion dysplastic oral keratinocyte (DOK) cells were cultured and divided into nicotine group, control group, knockdown group and knockdown control group. The nicotine group, knockdown group and knockdown control group were treated with 1 µmol/L nicotine for 7 days while the control group was untreated. Western blotting, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) were performed to detect Prx1 and Ets1 protein expression, Prx1 and Ets1 protein interaction, combined activity of Ets1 with PRDX1 gene promoter region in nicotine group and control group DOK cells. In nicotine group, DOK cells were transfected with siRNA or lentivirus to knockdown Ets1 and Prx1 expression. Prx1 and Ets1 protein expression was examined by Western blotting. Results: Nicotine increased the expression of Prx1 and Ets1 protein in DOK cells. The relative expression of Prx1 and Ets1 was 0.71±0.02, 0.12±0.01 in nicotine group and 0.53±0.06, 0.01±0.01 in control group (P=0.009, P=0.000). Co-IP showed that Prx1 could form protein complex with Ets1. The expression of Prx1 and Ets1 complex protein was increased in nicotine group. ChIP revealed that nicotine upregulated the combination of transcriptional factor Ets1 with PRDX1 gene promoter region, and the enrichment fold was 80.9±19.7 in nicotine group and 13.8±1.2 in control group (P=0.004). Ets1 and Prx1 protein expression was knocked down. The relative expression of Ets1 and Prx1 was 0.60±0.06, 0.48±0.03 in knockdown group and 0.83±0.08, 0.80±0.06 in knockdown control group (P=0.016, P=0.002). Ets1 knockdown suppressed the expression of Prx1 (P=0.002). Conversely, Prx1 knockdown also inhibited the expression of Ets1 significantly (P=0.000). Conclusions: In oral precancerous lesion cells, Ets1 directly regulates Prx1 expression and nicotine might promote the development of oral precancerous lesion by magnifying the positive feedback signal pathway between Ets1 and Prx1.

[The prevalence and related factors of HBV infection among adults in Mianyang].

Objective: To analyze the prevalence and related factors of HBV infection among people aged 18 years old and above in Mianyang city. Methods: A total of 260 950 residents, living in Mianyang city more than 6 months, aging 18 years old and above were employed by multi-stage random sampling method from November 2014 to September 2015. Questionnaire survey was conducted on participants using a self-designed questionnaire, including general demographic characteristics, family history of Hepatitis B, history of Hepatitis B vaccination and history of present illness, etc. 5ml blood was collected from all participants, and the blood samples were detected for HBsAg by enzyme-linked immunosorbent assay (ELISA). The multivariate unconditional logistic regression was performed to identify the related factors of positive HBsAg. Results: Among the 260 950 subjects, 113 184 were males (43.37%), 147 766 were females (56.63%), and the average age was (47.68±17.36) years old. The positive rate of HBsAg was 6.10%(15 822 cases). Subjects who were 25-34 years old (OR=1.23), 35-44 years old (OR=1.26), 45-54 years old (OR=1.23), and 55-64 years old (OR=1.34) were more likely to be HBsAg positive,65 years and older (OR=0.88) were less likely to be, compared with subjects aging 18-24 years old; males were more likely to be HBsAg positive compared with females (OR=1.35); people living in Fucheng district were more likely to be HBsAg positive compared with who living in Jiangyou district(OR=1.91); married people were more likely to be HBsAg positive compared with unmarried ones (OR=1.36); medical staff were less likely to be HBsAg positive compared with non-medical staff (OR=0.61); subjects with a surgery history were more likely to HBsAg positive compared with who without (OR=1.13); subjects with trauma history were more likely to HBsAg positive compared with who without (OR=1.13); people with history of Hepatitis B were more likely to HBsAg positive compared with who without (OR=4.21); people with Hepatitis B vaccination history were less likely to be HBsAg positive compared with who without (OR=0.48); all the P values above were less than 0.05. Conclusion: The positive rate of HBsAg among adults in Mianyang city was very high, and we should pay more attention to people aging between 25 and 64 years old, male, medical staff, with surgery history, trauma history, and a family history of Hepatitis B and Hepatitis B vaccination history.