[Study on F9 gene expression downregulation and its clinical value in hepatocellular carcinoma].

Objective: To analyze the expression levels of the F9 gene and F9 protein in hepatocellular carcinoma by combining multiple gene chip data, real-time fluorescence quantitative PCR (RT qPCR), and immunohistochemistry. Additionally, explore their correlation with the occurrence and development of hepatocellular carcinoma, as well as with various clinical indicators and prognosis. Methods: The mRNA microarray dataset from the GEO database was analyzed to identify the F9 gene with significant expression differences associated with hepatocellular carcinoma. Liver cancer and adjacent tissues were collected from 18 cases of hepatocellular carcinoma. RT-qPCR method was used to detect the F9 gene expression level. Immunohistochemistry was used to detect the F9 protein level. Combined with the TCGA database information, the correlation between F9 gene expression level and prognostic and clinicopathological parameters was analyzed. The biological function of F9 co-expressed genes associated with hepatocellular carcinoma was analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Statistical analysis was performed using Graphpad Prism software. Results: Meta-analysis results showed that the expression of the F9 gene was lower in HCC tissues than in non-cancerous tissues. Immunohistochemistry results were basically consistent with those of RT-qPCR. The data obtained from TCGA showed that the F9 gene had lower expression values in stages III-IV, T3-T4, and patients with vascular invasion. A total of 127 genes were selected for bioinformatics analysis as co-expressed genes of F9, which were highly enriched in redox processes and metabolic pathways. Conclusion: This study validates that the F9 gene and F9 protein are lower in HCC. The down-regulation of the F9 gene predicts adverse outcomes, which may provide a new therapeutic target for HCC.

[Risk factors analysis of acute kidney injury in patients with exertional heatstroke].

Objective: To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) . Methods: In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ(2) test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results: At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant (P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine (r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion: AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.

Population Structure and Genetic Diversity of Fungi Causing Rice Seedling Blight in Northeast China Based on Microsatellite Markers.

Rice seedling blight, which is caused by diverse pathogenic microorganisms, occurs worldwide and is the most important seedling disease affecting rice production in Northeast China. To further characterize the population structure and genetic diversity of the fungi responsible for rice seedling blight in Northeast China, 225 fungal strains were isolated from diseased rice seedlings collected from various rice-producing areas. The isolated strains included Fusarium oxysporum (48.0%), F. verticillioides (11.6%), F. tricinctum (8.0%), F. redolens (6.7%), F. equiseti (6.2%), F. solani (6.2%), Rhizoctonia solani (6.7%), Alternaria alternata (4.0%), and Curvularia coatesiae (2.7%). F. oxysporum was the dominant fungal species causing rice seedling blight, with most isolates exhibiting moderate pathogenicity. Moreover, to our knowledge, this is the first study to identify A. alternata and C. coatesiae as causal agents of rice seedling blight in Northeast China. None of the F. oxysporum isolates were sensitive to 10 µg/ml of carbendazim, implying that carbendazim is ineffective for controlling rice seedling blight in Northeast China. The F. oxysporum isolates were divided into nine groups based on a simple sequence repeat analysis involving 14 primer pairs. In addition, an analysis of molecular variance revealed a significant correlation between the F. oxysporum population and geographical location, which had a significant effect on the differentiation of the dominant isolate population. The results of this study provide insights into the genetic diversity of F. oxysporum strains causing rice seedling blight and may be useful for selecting isolates to screen for disease-resistant rice varieties, evaluating fungicide efficacy, and developing effective disease management strategies.

[Different anesthesia management in preterm infants undergoing surgeries for retinopathy of prematurity: A retrospective study].

OBJECTIVE: To evaluate the effect of different anesthesia management on clinical outcomes in former prematurely born infants undergoing surgeries for retinopathy of prematurity (ROP). METHODS: In this retrospective study, electronic medical record database was searched for all former prematurely born infants (gestational age < 37 weeks and post conceptual age < 60 weeks) who received ROP surgery under inhalational general anesthesia between November 2016 and October 2018. The patients were divided into two groups based on anesthesia management: laryngeal mask airway (LMA) insertion without intravenous muscle relaxant injection and with pressure support ventilation (LMA group) or airway secured with endotracheal tube (ETT) with intravenous muscle relaxant injection and pressure controlled ventilation (ETT group). Primary outcomes included perioperative adverse events and complications. Extubation time and length of stay after surgery were also recorded. RESULTS: Sixty eight preterm infants in the LMA group and 100 preterm infants in the ETT group were included. The incidence of adverse events during surgery (including airway management change and desaturation) was similar in LMA group and ETT group (4.4% vs. 1.0%, P =0.364). During the early recovery period after surgery, the incidence of difficult extubation (extubation time >30 min) was significantly lower in LMA group compared with ETT group (4.4% vs.15.0%, RR=0.262, 95%CI:0.073－0.942, P=0.029). The incidence of respiratory events was similar between the two groups (20.6% vs. 27.0%, P =0.342). However, the incidence of apnea was significantly lower in the LMA group than in the ETT group (5.9% vs.19.0%, RR=0.266, 95%CI: 0.086－0.822, P =0.015). No significant difference was observed between the LMA group and ETT group in incidences of cardiovascular events (0% vs. 1.0%, P =1.000) and unplanned admission to neonatal intensive care unit (5.9% vs. 7.0%, P=0.774). No airway spasm, re-intubation, aspiration or regurgitation was observed during early recovery. During late recovery after returning to ward, the incidence of adverse events was also similar between the two groups (0% vs. 2.0%, P =0.241). The median (IQR) extubation time was 6 (5, 10) min in LMA group and 10 (6, 19) min in ETT group (P < 0.001). The median length of stay after surgery was significantly shortened in LMA group compared with ETT group [20 (17, 22) hours vs. 22 (17, 68) hours, P =0.002]. CONCLUSION: Compared with endotracheal intubation with intravenous muscle relaxant injection, laryngeal mask airway insertion without muscle relaxant could achieve an early extubation, and reduce the incidence of apnea during early recovery period in former prematurely born infants undergoing ROP surgery.

[A birth cohort study of the association between prenatal serum bisphenol A concentration and infant neurobehavior development].

Objective: To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant. Methods: Participants were from the Ma'anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants' neurobehavioral development. Results: A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants' neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M (P25,P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant's development of social behavior [ß (95%CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with ß (95%CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion: BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.

[Application value of urinary IGFBP7 and TIMP-2 in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis].

Objective: To investigate the application value of new urinary biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue matrix metalloproteinase inhibitor-2 (TIMP-2) in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis. Methods: 45 newly hospitalized cases with decompensated hepatitis B virus-related liver cirrhosis were selected. Among them, 19 cases were combined with AKI on admission (cirrhosis-AKI group), 26 cases without AKI (cirrhosis-non-AKI group), and 12 healthy cases (normal control group). First-morning urine samples were collected and IGFBP7 and TIMP-2 were detected by enzyme-linked immunosorbent assay (ELISA). Urinary IGFBP7 and serum creatinine (SCr) were dynamically monitored after hospitalization in cirrhosis-non-AKI group. Normally distributed measurement data were compared by t-test, and non-normally distributed measurement data were compared by rank sum test. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic accuracy of the indicators. Results: Urinary IGFBP7, IGFBP7 with TIMP-2 (IGFBP7×TIMP-2) in cirrhosis-AKI group (n = 19) were equally higher than that of the cirrhosis-non-AKI group (P < 0.05). Urinary IGFBP7, TIMP-2 and IGFBP7×TIMP-2 in cirrhosis-AKI group or cirrhosis-non-AKI group were significantly higher than those of the normal control group (P < 0.01). The AUC of urinary IGFBP7 and urinary IGFBP7×TIMP-2 for diagnosis of AKI were 0.703 (95% CI 0.547-0.860) and 0.700 (95% CI 0.541-0.859), respectively. In the liver cirrhosis-non-AKI group (n = 26), 5 cases of AKI were newly diagnosed according to the changes in SCr during hospitalization (progressive group). Urinary IGFBP7 was significantly increased 2 days before the diagnosis of AKI. The concentration of urinary IGFBP7 at admission in the progressive group (n = 5) was higher than that of the non-progressive group (n = 21) (P < 0.05). Conclusion: Urinary IGFBP7 and TIMP-2 concentrations were significantly increased in patients with decompensated hepatitis B virus-related liver cirrhosis. When AKI occurred, urinary IGFBP7 and IGFBP7×TIMP-2 was further increased. Urinary IGFBP7 is valuable for early AKI diagnosis, and may play a role in predicting AKI occurrence.

[A multicenter clinical analysis of short-term efficacy of laparoscopic radical resection of hilar cholangiocarcinoma].

Objective: To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China. Methods: Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People's Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A(1) (116 cases), and the center with less than 10 cases was set as group A(2) (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results: All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced (Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ(2)=4.341, 0.007; P=0.037, 0.047) .Compared with group A(2), the operation time in group A(1) was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A(1) was lower than that in group A(2) (χ(2)=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant (P<0.05) . Conclusions: The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

[Application of the Virtual Reality-Pattern Visual Evoked Potential in Forensic Visual Acuity Evaluation].

ABSTRACT: Objective To explore a kind of visual evoked potential test equipment and method that is more suitable for the application of forensic clinical visual acuity evaluation. Methods Thirty-four volunteers （68 eyes） were selected, including 15 males and 19 females, aged between 20 and 40 years. Test lenses were placed before the tested eyes of volunteers to induce refractive myopia with insert method, and the diopter lenses were adjusted so that the visual acuity level of one eye of volunteers was above 0.8, and the visual acuity of the other eye was at moderate damage level （<0.3 and ≥0.1）. The tests were carried out under the binocular simultaneous asynchronous stimulation mode （hereinafter referred to as "binocular mode"） and monocular separate stimulation mode （hereinafter referred to as "monocular mode"） of virtual reality-pattern visual evoked potential （VR-PVEP）, and the amplitude of PVEP of volunteers under the two modes was compared at four spatial frequencies of 8×8, 16×16, 24×24 and 32×32. Results The differences in the amplitude of P100 wave between monocular and binocular modes at 8×8 spatial frequency had no statistical significance and the differences in amplitude of P100 wave between monocular and binocular modes at 16×16, 24×24, and 32×32 spatial frequencies had statistical significance （P<0.05）. The amplitude of the same eye in monocular mode was higher than that in binocular mode. Through correlation analysis, it was found that the amplitude of P100 wave in monocular mode was moderately correlated with amplitude of P100 wave in binocular mode. Conclusion In forensic identification practice, VR-PVEP is helpful for overcoming the disturbance of poor fixation, and to increase the reliability of PVEP evaluation results. It can greatly shorten the detection time of PVEP and improve work efficiency.

[Comparison of different critical care scoring systems in prognosis evaluation of heat stroke].

Objective: To evaluate the prognostic value of different critical care scoring systems in 28-day survival rate of patients with heat stroke. Methods: A retrospective analysis was conducted on the clinical data of 71 patients with heat stroke admitted to the department of emergency medicine of Beijing Luhe Hospital. Capital Medical University from July 2015 to September 2018. The general information and the worst values of vital signs and related pathophysiological indicators within 24 hours were collected and the sequential organ failure assessment (SOFA) , multiple organ dysfunction (MODS) , simplified acute physiological scoreⅡ (SAPS Ⅱ) and acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) were calculated. The patients were divided into the survival group (n=45) and the non-survival group (n=26) according to 28-day prognosis, and the clinical data and scores of the two groups were compared.The ROC curve was drawn to analyze the evaluation value of each scoring system on the survival rate of patients at 28-day. Kaplan-Meier method was used to plot the survival curve of patients. Results: There were no significant differences in age, sex, vital signs and laboratory parameters between two groups (P>0.05) . In non-survival patients, SOFA, SAPS Ⅱ, APACHE Ⅱ scores were significantly elevated in the survival group (P<0.05) . ROC curve analysis showed that the area under ROC curve (AUC) of SOFA score for predicting 28-day survival rate was the highest, which was significantly higher than the APACHE Ⅱ, SAPS Ⅱ, MODS score. When the best cut-off value of SOFA score was 9.0, the sensitivity was 84.6%, and the specificity was 71.1%. Kaplan-Meier survival analysis showed that 28-day survival rate after hospital discharge in patients with SOFA score<9 (n=27) was significantly higher than that in patients with SOFA score ≥9.0 (χ(2)=1.0, P<0.01) . Conclusion: SOFA, APACHE Ⅱ, SAPS Ⅱ on admission have been proved to have good prognostic ability to predict 28-day prognosis in heat stroke patients. Among them, SOFA score system has more accurate prediction value.

Population structure and genetic diversity of Setosphaeria turcica from corn in Heilongjiang province, China.

AIM: The aims of this study were to identify races and mating types of Setosphaeria turcica causing northern corn leaf blight in Heilongjiang province of China and analyse the genetic diversity of S. turcica isolates using SSR markers. METHODS AND RESULTS: Based on gene-for-gene interactions, 13 races of S. turcica (races 0, 1, 2, 3, 12, 13, 23, 123, N, 1N, 12N, 3N and 23N) were isolated from infected corn plants in Heilongjiang province. Races 0 and 1 were the predominant races, and race 23N was identified for the first time in the region. Using two pairs of specific primers, three mating types, 'a', 'Aa' and 'A', were identified, with 'a' being the predominant mating type. SSR markers were used to analyse genetic diversity of 60 S. turcica isolates. Five SSR primers were polymorphic, which resulted in 45 reproducible bands with 2-15 bands for each primer. Cluster analysis separated the isolates into five groups at a similarity coefficient of 0·84. Analysis of molecular variance showed that there was significant correlation between SSR groups and mating type of the isolates. No significant correlation was found between SSR groups and physiological races or geographical location of the isolates. CONCLUSIONS: The work reported that races 0 and 1 were the predominant races, and race 23N was identified for the first time in Heilongjiang province with 'a' being the predominant mating type. There was significant correlation between SSR groups and mating type of S. turcica isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide information on population structure and genetic diversity of S. turcica causing Northern corn leaf blight, which will facilitate the development of effective disease management programs.

[Changes in natural killer cell subsets marked with CD27 and CD11b for HBV carrier mice].

Objective: To evaluate the changes in natural killer cell subsets marked with CD27 and CD11b for HBV carrier mice. Methods: The pAAV-HBVl.2 plasmid was injected into the tail vein of C57BL/6 mice by hydrodynamic injection method to construct HBV-carrier model group and empty vector as the control group. Liver function and virological examination at different time points were used to judge the construction of HBV- plasmid carrier animal model. Flow cytometry was used to detect the frequency of NK cells and CD11b combined with CD27 NK cell subsets in spleen and liver. GraphPad Prism software was used for statistical analysis. Results: HBV-carrier mouse model was successfully constructed. There were no statistically significant difference in NK cell frequencies between spleen and liver of HBV carrier mice (P> 0.05), compared to control group. NK cells were divided into four subsets with in combination to CD27 and CD11b: CD11b(+)CD27(-)(CD11b(+)SP), CD11b(+)CD27(+)(DP), CD11b(-)CD27(+)(CD27(+)SP) and CD11b-CD27-(DN). Furthermore, the spleen of HBV-carrier mice had no statistically significant difference (P> 0.05) with the frequency of the four NK-cell subsets. The frequency of DN NK cell subsets was significantly increased in the liver of HBV carrier mice than control group (P< 0.001); however, the frequency of CD11b(+)SP cell subsets was significantly decreased (P < 0.05).There were no statistical significance in the frequency comparison between NK subgroups of DP and CD27(+)SP NK cell subsets (P> 0.05). Conclusion: HBV-carrier mice with abnormal distribution of hepatic NK cell subsets significantly increased and decreased the frequency of DN NK cell subsets and CD11b(+)SP cell subsets.

[The relationship of maternal and umbilical cord blood zinc level associated with newborn birth weight: a birth cohort study].

Objective: To study serum zinc level in pregnancy and umbilical cord blood and their association with newborn birth weight. Methods: Pregnant women accepting obstetric examination in Ma'anshan Maternal and Child Care Center were recruited from May 2013 to September 2014. The follow up was conducted during their first, second and third trimesters of pregnancy and the self-designed questionnaire was used to collect information of social and demographic characteristics. Blood samples in the first, second pregnancy period and umbilical cord blood samples were collected and serum concentrations of zinc were assayed. 3 239 mother-infant entered the final analysis. We divided serum zinc level into low (P(75)) groups according to their exposure concentrations at each trimesters. Non-conditional multivariate logistic regression model was conducted to evaluate the association between serum zinc level in first, second trimesters of pregnancy and umbilical cord blood with small for gestational age (SGA) and large for gestational age (LGA). Results: Serum zinc level in P(50) (P(25)-P(75)) during the first, second trimesters and cord blood were 1 016.18 (907.09-1 145.60), 813.36 (732.47-897.89) and 903.44 (808.71-1 015.64) µg/L, respectively. The prevalence of zinc deficiency during the first, second trimesters and cord blood were 1.5% (44/2 957), 15.9% (492/3 087) and 6.5% (176/2 707), respectively. The prevalence of total SGA and LGA were 9.7% (313/3 239) and 16.5% (536/3 239), respectively. Compared to high-level serum zinc group, the risk of SGA (OR (95%CI) in low-level serum zinc group during first trimesters was 1.51 (1.05-2.19)). Serum zinc level among second pregnancy period and umbilical cord blood had no statistically significant effect on SGA and LGA (both P values >0.05). Conclusion: Zinc nutritional status of pregnant women in Ma'anshan city was at a good level. The low serum zinc level in first trimester increased the risk of SGA.

[Association between the internal exposure levels of phthalates and executive function of preschool children].

Objective: To investigate the association between the internal exposure levels of phthalic acid esters (PAEs) and executive function (EF) of preschool children. Methods: Between October 2008 and October 2010, pregnant women who accepted pregnancy health care services in four municipal medical and health institutions in Ma'anshan city, Anhui Province, were recruited as study objects. A total of 5 084 pregnant women and 4 669 singleton live births were enrolled in this cohort. The follow-up study was conducted from April 2014 to April 2015. A total of 3 725 data-completed preschool children aged 3 to 6 years older entered in this study. The method of analysis seven metabolites of phthalates in urine was high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and divided objects into low (P(0)-P(24)), medium (P(25)-P(74)) and high (P(75)-P(100)) groups according to their exposure concentrations. To investigate the executive function of preschool children, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the etiology association between the phthalate metabolites levels and preschool children's executive function. Results: In this study, 53.6% (1 997/3 725) of preschoolers were boys, children's age was (51.5±5.6) months. The detection rates of seven phthalate esters were: mono-n-methyl phthalate (MMP) was 99.89% (3 721/3 725); mono-ethyl phthalate (MEP) was 99.97% (3 724/3 725); mono-benzyl phthalate (MBzP) was 69.10% (2 574/3 725); mono-butyl phthalate (MBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 100.00% and mono-ethylhexyl phthalate (MEHP) was 99.95% (3 723/3 725). The median concentrations of the seven phthalate metabolites were: 17.71, 15.36, 0.07, 155.24, 10.73, 14.67, 3.59 µg/L, respectively. The median concentrations corrected by urinary creatinine were 29.65, 26.65, 0.12, 257.73, 17.94, 24.80, 6.27 µg/g Cr, respectively. The P(25) and P(7)5 concentration of the total PAEs metabolites corrected by urinary creatinine were 1.20 µmol/g Cr and 3.04 µmol/g Cr. After adjusted the relevant demographic information: children sex, children age in month, maternal age, parental education levels, household exposure to secondhand smoke and whether the child is the only child as confounds, multivariate logistic regression model showed that the risk of inhibitory self-control index (ISCI) dysplasia in MEHHP high concentration group and MEOHP high concentration group were 1.71 and 1.54 times (OR=1.71, 95% CI: 1.11-2.62; OR=1.54, 95% CI: 1.01-2.34) than in low concentration group. The risk of ISCI dysplasia in total PAEs metabolites high concentration group was 1.55 times (OR=1.55, 95% CI: 1.00-2.38) than in low concentration group. Conclusion: Phthalates exposure may damage the executive function of preschool children.

[Association between early pregnancy bisphenol A exposure and sleep problems among preschool children].

Objective: To analyze the association between maternal bisphenol A exposure during early pregnancy and sleep problems among preschool children. Methods: Research subjects were from one of the sub-cohorts(Ma'anshan Cohort) of the China-Anhui Birth Cohort Study (C-ABCS) in Ma'anshan city. The basic situation of pregnant women and sleep information of preschool children were investigated. We selected preschool children whose mother's maternal serum bisphenol A concentrations of the first trimester had been already detected between December 2012 to Januray 2014. 1 259 pairs of mothers and children were included. The concentrations of bisphenol A exposure during early pregnancy were divided into low, medium and high exposure groups according to 25(th) percentile (P(25)) and 75(th) percentile (P(75)) levels. Multivariate multinomial logistic regression model was used to analyze the association between maternal bisphenol A exposure during early pregnancy and sleep-related problems in preschool children. Results: The P(50) (P(25)-P(75)) of serum bisphenol A exposure level during early pregnancy was 0.231 (0.106-0.512) ng/ml. The sleep-related problems scores of 1 259 preschool children were (16.43±3.82) points. The occasional sleep-related problems were detected about 47.8% (602 cases) and frequent sleep-related problems were detected about 18.3% (230 cases). After the adjustment of the confounding factors such as children's gender, age, BMI, sleep position (lying down, sleeping on one's back), the length of time to sleep and the length of sleep at night, in comparison with bisphenol A low exposure group, the OR (95%CI) value of preschool children with occasional sleep-related problems in maternal bisphenol A high exposure group during early pregnancy was 1.44 (1.01-2.06). After the gender stratification, the results showed that in comparison with bisphenol A low exposure group, the OR (95%CI) value of preschool girls with occasional sleep-related problems in maternal bisphenol A medium and high exposure group during early pregnancy were 1.61 (1.05-2.46) and 2.40 (1.42-4.04), respectively. The OR (95%CI) value of preschool girls with frequent sleep-related problems in maternal bisphenol A high exposure group during early pregnancy was 2.64 (1.34-5.17). However, in boys, there was no statistically significant association between maternal bisphenol A exposure during early pregnancy and sleep-related problems (P>0.05). Conclusion: Maternal bisphenol A exposure during early pregnancy might be related to sleep-related problems in preschool children.

[Potential application of sofosbuvir-based treatment for chronic hepatitis C in China].

Chronic hepatitis C (CHC) has a prevalence rate of 0.43% in China and approximately 10 million chronically infected people are in urgent need of treatment. Since the beginning of 2013, pan-genotypic sofosbuvir (SOF) with its potent antiviral activity, minimal drug resistance, less drug-drug interactions and good safety has created a new era in HCV treatment. Its combination with ribavirin, in single tablet regimen with either ledipasvir or velpatasvir has been widely used in about 1.6 million patients worldwide. Furthermore, SOF-based therapy is proven to be effective and safe in serious or terminal illness such as decompensated cirrhosis, liver or kidney transplantation, HIV or HBV co-infections, bleeding disorders, intravenous drug users, adolescents, and elderly. Therefore, SOF-based regimens would fill the unmet medical needs of our patients with HCV.

[Reduced frequency of natural killer cell on siglec-7(+) is associated with progression of hepatitis B virus-related cirrhosis].

Objective: To explore the relationship between sialic-acid-binding immunoglobulin-like lectin 7 (Siglec-7) expressed on NK cells and hepatitis B virus-related cirrhosis. Methods: Peripheral venous blood samples were collected from 23 healthy controls and 31 patients with hepatitis B virus-related cirrhosis (Child-Pugh A, n = 7; Child-Pugh B, n = 12; Child-Pugh C, n = 12). Peripheral blood mononuclear cells (PBMCs) were obtained by using Ficoll-Hypaque density gradient centrifugation and the expression of Siglec-7 and NK cells phenotype and their subpopulations were detected by flow cytometry. Comparisons between various groups were performed using t -test, one-way analysis of variance (ANOVA), and correlations between variables were analyzed using Pearson's-correlation coefficient. Results: (1) There was no significant difference in the percentage of NK cells and in their subpopulations with HBV-related cirrhosis and healthy controls. (2) Siglec-7 expression on NK cells in patients with HBV-related cirrhosis(62.44±13.45%)was significantly down-regulated than that to healthy controls(75.39±12.19%)while the frequency of Siglec-7(+) NK cells were negatively correlated with Child-Pugh score. (3) Subpopulation analysis showed that Siglec-7 expression on CD56(bright)CD16(-)NK cells(66.99±15.93%)was significantly lower than CD56(dim)CD16(+)NK cells(76.54±13.9%) in HBV-related cirrhosis. However, the expression of Siglec-7 in healthy controls showed no difference in these two NK cell subsets. (4) Phenotypic analysis showed that Siglec-7(+) NK cells express higher levels of activating receptor CD16, CD38, NKp46 and lower levels of inhibitory receptor CD158b. Indeed, the frequency of CD16 and CD38 on Siglec-7(+) NK cells in HBV-related cirrhosis was lower than that in healthy controls. Conclusion: The disease progression in patients with hepatitis B virus-related cirrhosis is associated to decreased frequencies of Siglec-7(+)NK cells.

[Functional effects of killer cell lectin-like receptor subfamily G member 1 on natural killer cells in chronic hepatitis B infection].

Objective: To study the functional effects of killer cell lectin-like receptor subfamily G member 1 (KLRG1) expression on natural killer cells (NK cell) in chronic hepatitis B virus infection (HBV). Methods: Peripheral blood mononuclear cells (PBMC) were extracted from 120 patients with chronic hepatitis B virus infection and 19 healthy persons. The frequency of NK cells and KLRG1+ NK cells in peripheral blood was detected by flow cytometry. Interferon-γ levels secreted by NK cells were detected in peripheral blood. Statistical analysis of experimental data was performed using GraphPad Prism 6.03 software. Results: The frequency of NK cells in HBV-infected group (16.92% ± 7.9%) was not significantly different from that in healthy controls (10.57% ± 6.5%). The frequency of KLRG1+NK cells in HBV-infected group was significantly higher (49.43% ± 21.2%) than that to healthy control group (31.60% ± 17.9%), (t = 7.347 6, P < 0.001). IFN-γ secretion of KLRG1 + NK cells in HBV-infected patients (2.59% ± 1.0%) were significantly lower than healthy controls (5.96% ± 2.4%), (P = 0.009). Conclusion: HBV infection can increase the expression of KLRG1 in NK cells and further reduce the secretion of IFN-γ in NK cells, which may be an important cause for chronic HBV infection.

[Analysis on the performance evaluation of the Global Fund Malaria Programme in China from 2003 to 2013].

Objective: To analyze the performance of the 5 Global Fund Malaria Programmes in China from 2003 to 2013. Methods: All of the proposals, summaries, progress reports, survey reports, Monitoring& Evaluation reports, and performance rating reports of the 5 Global Fund Malaria Programmes in China and the epidemic data of program areas were collected for statistical analysis from 2012 to 2014. Symposiums were held with relevant experts from national and provincial Centers for Disease Control and Prevention, program managers and staffs from national and provincial Global Fund Malaria Programme offices. The completion of the relevant programme indicators (including the general grant information such as program areas, beneficiaries and funding; the implementation of malaria control measures; the performance of malaria control measures; the malaria incidence in the program areas; the prevalence of malaria parasites; and program management and performance evaluation) were analyzed, and the results: of the symposiums were summarized. Results The implementation period of the 5 Global Fund Malaria Programs were as follows: Round 1 from 2003 to 2008, Round 5 from 2006 to 2010, Round 6 from 2007 to 2012, Round 10 from 2012 to 2013, and National Strategy Application (NSA) from 2010 to 2012. Under the support of all the Global Fund Malaria Programs, a total of 11 936 726 fever cases received microscopic tests, 1 485 915 confirmed and suspected malaria cases were treated, 1 579 773 Long Lasting Insecticide-treated Nets were distributed, 3 414 633 regular nets were treated by insecticide, 40 298 284 primary and middle school students received health education on malaria control. Compared with the baseline value, the completion rates of each indicator increased after the implementation of the programs. The growth value ranged from 12.83% to 83.11%, among which the biggest growth was the value of the indicator'Percentage of households with at least one LLIN/ITN in target areas', and it increased from 9.2% (baseline value of 2006) to 92.31% (value of 2012). The malaria incidence in program areas has dropped significantly year by year, the annual reported malaria incidence in Yunnan and Hainan provinces decreased from 1 950/100 000, 3 850/100 000 in 2002 to 3.31/100 000, 0.15/100 000 in 2012, the P. falciparum malaria incidence in target counties in Hainan province decreased from 90.6/100 000 in 2002 to 0/100 000 in 2012. As from the implementation of NSA grant in 2010 to 2012, the annual reported malaria incidence in 92% of the 75 Type 1 counties was less than 1 per 10 000, 60.00% of Type 1 counties and 98.69% of the 687 Type 2 counties reported zero locally transmitted malaria cases. The Global Fund Secretariat had conducted a total of 37 performance evaluations, of which 9 have been rated as A1, 4 rated as A2, 19 rated as B1 and 5 rated as B1. Conclusions: The Global Fund Malaria Program in China has been closely integrated with the goal and task of National Malaria Control Program, reducing malaria burden in target areas, and pushing Chinese malaria control efforts to move from control to elimination.

Siglec-7 Defines a Highly Functional Natural Killer Cell Subset and Inhibits Cell-Mediated Activities.

Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is an inhibitory receptor expressed on natural killer (NK) cells. In this study, we investigated the relationship between Siglec-7 expression and NK cell functions. Siglec-7 was highly expressed on NK cells and was preferentially expressed by mature NK cells from peripheral blood of healthy adults. Siglec-7(+) NK cells displayed higher levels of activating receptors CD38, CD16, DNAM1, NKp30 and NKp46, but lower levels of inhibitory receptors such as NKG2A and CD158b, compared with Siglec-7(-) NK cells. Functional tests showed that Siglec-7(+) NK cells displayed more CD107a degranulation and IFN-γ production than Siglec-7(-) NK cells. Siglec-7 inhibited NK cell functions when interacting with specific antibodies. These data suggest that Siglec-7 defines a highly functional NK cell subset and suppresses NK cell-mediated functions when cross-linked with specific antibodies.

CARMA3 regulates the invasion, migration, and apoptosis of non-small cell lung cancer cells by activating NF-кB and suppressing the P38 MAPK signaling pathway.

In our previous study, CARMA3 overexpression in lung cancer cells promoted cell proliferation and invasion; however, the mechanism underlying the role of CARMA3 in cancer cell invasion remained unclear. In the present study, knockdown of CARMA3 in A549 and H1299 cells suppressed cell invasion and migration, and downregulated matrix metalloprotease 9 expression at the protein and mRNA levels, as shown by Western blotting and real-time PCR. CARMA3 knockdown increased cell apoptosis, as shown by flow cytometry, increased the mRNA and protein expression levels of Bax and Caspase3, and downregulated Bcl-2 in A549 and H1299 cells. Phosphorylated P38 levels increased and NF-кB activation decreased following knockdown of CARMA3. SB203580, a P38 MAPK inhibitor, activated NF-кB, increased cell migration, and inhibited cell apoptosis after knockdown of CARMA3 compared to knockdown of CARMA3 without SB203580. These findings indicate that CARMA3 may suppress the activation of the P38 MAPK signaling pathway to regulate invasion, migration and apoptosis of lung cancer cells by activating NF-кB (P65) in the nucleus.