Objective:To analyze the causal relationship between lifestyle-based factors and the occurrence and development of hepatobiliary malignancies by Mendelian randomization study method,and to provide the potential clinical evidence for the prevention and treatment of hepatobiliary malignancies.Methods:The data from large-scale,independent genome-wide association studies(GWAS)were selected,and seven-step inclusion criteria for the instrumental variable screening were set up.The exposure lifestyles included the percentage of carbohydrate intake,percentage of fat intake,percentage of protein intake in the diet,coffee intake,weekly alcohol consumption times,leisure electronic screen exposure time,moderate to vigorous intensity physical activity(MVPA)during leisure time,sedentary behavior at work,age at first smoking,daily smoking quantity,current smoking status,and past smoking status,totaling 12 phenotypes.The primary analysis method used was the random effect model of the inverse variance weighted(IVW)method,and the heterogeneity was detected by Cochrane's Q test and the horizontal pleiotropy was detected by MR-Egger intercept method.Results:The current smoking status was significantly positively correlated with the increasing risk of extrahepatic cholangiocarcinoma(OR=1.607,95%CI:1.113-2.322,P=0.011).Higher coffee intake was causally linked to a higher risk of liver cancer and intrahepatic cholangiocarcinoma(OR=1.000,95%CI:0.999-1.000,P=0.012).In the physical activity,more MVPA was associated with the lower risk of liver cancer and intrahepatic cholangiocarcinoma(OR=0.998,95%CI:0.996-0.999,P=0.002).The Cochrane's Q test results showed that there was mild heterogeneity between MVPA and extrahepatic cholangiocarcinoma(Q=18.354,P=0.049)as well as the percentage of protein intake and intraphepatic cholangiocarainoma(Q=12.715,P=0.026),and the MR-Egger intercept method results showed there was no horizontal pleiotropy.Conclusion:There is a causal relationship between current smoking status and extrahepatic cholangiocarcinoma,and there is a causal relationship between more MVPA and the lower risk of liver cancer and intrahepatic cholangiocarcinoma.Education on smoking and physical activity for the patients may offer potential benefits for the prevention of hepatobiliary malignancies.

【Objective】 To compare the results by minipool and individual NAT on blood samples with HBsAg detection S/CO value between 0.25-0.90 by ELISA, in order to re-evaluate the safety of NAT for such negative samples with high HBsAg S/CO value and provide references for the optimization of detection process. 【Methods】 A total of 30 blood samples which were non-reactive for HBsAg by ELISA twice and with the S/CO value of any reagent between 0.25-0.90 (defined as " high S/CO value negative" ) from our center from February to October 2020 were collected, and minipool test of 6 samples and individual test were performed in parallel. 11 samples which were negative by minipool tests but positive by individual test were submitted to repeated NAT minipool tests, and the results of each test were recorded and analyzed. 【Results】 The median S/CO values of the 30 samples by two ELISA reagents were 0.565 and 0.320, respectively, and the differences were statistically significant (P<0.01). The NAT yield of primary minipool and individual NAT was 13.33% (4/30) and 76.67% (23/30), respectively, and the differences were statistically significant (P<0.05). Eleven samples, minipool NAT negative but individual NAT positive, were subjected to repeated minipool NAT. One remained negative throughout the 10 times of repeated minipool NAT test, and 10 (90.91%) presented positive results at least once. The repeated positive rate was 5.88% (1 /17) -70.00% (7/10). The Ct value of NAT ranged 34.4-38.5 (median 36.76) in the primary minipool test, 29.6-42.8 (median 36.50) in the individual test, and 36.1-56.0 (median 37.75) in repeated minipool test afterwards. The Ct value was significantly different between repeated minipool tests and individual tests (P<0.01), but not between repeated minipool tests and primary ones (P> 0.05). 【Conclusion】 The NAT-yield of samples with high ELISA HBsAg S/CO value was high in individual test and low in minipool test, and the NAT-yield in minipool test could be improved by repetitive test. Therefore, the safety of NAT for samples with high HBsAg S/CO value should be re-evaluated as minipool test is dominant in blood stations. Individual NAT test is recommended for such samples currently as there is no any other more sensitive detection approaches.

Objective To Establish a loop-mediated isothermal amplification(LAMP)assay for detection of Salmonella in fecal samples of tree shrews, and report the result of preliminary application of this method. Methods LAMP primers were designed and synthesized according to the conserved sequence of Salmonella specific gene invA (invasive protein gene A). To optimize the reaction time and temperature by setting 10 reaction times(24 to 42 min)and temperature(57℃ to 66℃)and tested its specificity and sensitivity. At the same time, a conventional PCR test was performed to verify and compare with the LAMP assay. 91 fecal samples of wild-derived tree shrews were detected by the LAMP assay. Results The experimental condition was confirmed as 62℃ and 34 min. The sensitivity of Salmonella was 3.36×101CFU/mL, which was 10 to 100 times higher than that of conventional PCR assay. In 10 kinds of intestinal bacteria for LAMP amplification,Salmonella enteritidis and Salmonella paratyphi B were positive,the others were negative. Among the 91 samples of tree shrew fecal samples detected by the LAMP assay, the positive detection rate was 20.88%. The LAMP assay can be completed within 40 min, the result can be observed and judged visually by color changes. Conclusions The LAMP assay established in this study is convenient,rapid,sensitive and specific. It can be used as a rapid measure for large-scale detection of Salmonella in feces of tree shrews.

Objective To establish a quick and accurate method for detection of tree shrew adenovirus(TAV) using TaqMan real-time fluorescence quantitative PCR. Methods Based on the published TAV genome sequence, a 3' conserved sequence was used to design specific probe primers. A standard curve was prepared using a recombinant plasmid containing the target gene fragment. A real-time fluorescence quantitative PCR method was established for detecting TAV based on TaqMan probe. Results The detection method was specific and was not cross-reactive with other common pathogens. The detection limit of the method was 3.7 copies/μL,showing a high sensitivity. The correlation coefficient was 0.998, and the efficiency was 95.7%. The amplification result showed a fine linear relationship,and the repeatability test effect was good. Conclusions The TAV real-time quantitative PCR detection method based on TaqMan probe has been successfully established. It has high sensitivity and reproducibility and can be applied to early detection of TAV infection.

Parkinson's disease(PD)is a progressive neurodegenerative disorder, with an etiology that is now considered to be due to interaction between genetic and environmental factors. Typical PD features include loss of dopaminergic neurons in the nigrostriatal region, with typical motor traits of PD associated with dopamine deficiency. Animal models have contributed to determining PD etiology and pathogenesis,as well as testing new therapeutic schedules and novel drug research. Rodents, tree shrews, primates, and other animal models of PD have been established by different method. These models each have their own advantages and limitations, showing different clinical features and pathological mechanisms to those in humans. Therefore, the appropriate model for scientific research must be carefully considered. This article reviews the main neurotoxic and transgenic models of PD.

Objective To determine the median effective dose(ED50)of etomidate inhibiting responses to endotracheal intubation when combined with dexmedetomidine in the patients with obstructive jaundice. Methods American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients with obstructive jaundice,aged 45-63 yr,with body mass index of 18-30kg/m2,scheduled for elective operations under general anesthesia,were divided into control group(group C)and dexmedetomidine group(group D)using a random number table. At 15min before induction of anesthesia,normal saline 0.1 ml/kg was infused intravenously in group C,and dexmedetomidine 0.4 μg/kg was infused intravenously in group D. Anesthesia was induced with midazolam 0.05 mg/kg,fentanyl 4 μg/kg,etomidate and cisatracurium 0.15 mg/kg. The ED50 of etomidate was determined using Dixon′s up-and-down method. Etomidate was injected intravenously at the initial dose of 0.2 mg/kg in the first patient in each group. Each time the dose increased/decreased in the next patient according to whether or not the increase in mean arterial pressure and/or heart rate ≥ 20% of the baseline value within 3min after endotracheal intubation. The ratio between the two successive doses was 1.1. The number of patients in whom inhibition was effective or ineffective was recorded,and the ED50 and 95% confidence interval of etomidate inhibiting responses to intubation were calculated using Probit analysis. Results The ED50 (95% confidence interval)of etomidate inhibiting responses to intubation was 0.185(0.162-0.201)mg/kg in group C,the ED50(95% confidence interval)of etomidate inhibiting responses to intubation was 0.129(0.093-0.143)mg/kg in group D,and there was significant difference between the two groups(P<0.05).Conclusion When combined with dexmedetomidine,the ED50 of etomidate inhibiting responses to endotracheal intubation is 0.129 mg/kg in the patients with obstructive jaundice.

Objective To determine the effect of different doses vitamin D supplementation to the change of bone metabolism in 6 months after Roux-en-Y gastric bypass ( RYGB) .Methods The change of body weight and body mass index ( BMI ) in 36 patients in 6 months after RYGB WAS analyzed.Then,the effect of low-dose (n=11,400 IU/day) and high-dose (n=12,1 600 IU/day) vitamin D to the serum calcium,25-hydroxyvitamin D and bone density were observed ,and 15 patients as control .Results In 6 months after RYGB,the body weight and BMI were decreased ,and the differences were statistical significance (P<0.05).The serum calcium,25-hydroxyvitamin D and bone density were increased in high-dose group,and the differences were statistical significance (P<0.05).Conclusion High-dose (1 600 IU/day) vitamin D supplementation is effective to the bone loss of patients undergoing RYGB .

Objective To investigate the effects of Furong-Tongmai capsules on the expressions of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) in the sciatic nerve in diabetic rats.Methods A total of 50 rats were randomly divided into the normal control group,model group,and low-,medium-,and high-dose of Furong-Tongmai groups,10 rats in each group.Diabetes mellitus in rats were induced by intraperitoneal streptozotocin injection (60 mg/kg).The rats in the low-,medium-,and high-dose of Furong-Tongmai groups were intragastric administrated with Furong-Tongmai suspension 0.7,1.4 and 2.8 g/kg daily for 8 weeks,respectively.The rots in the normal control group and model group were intragastric administrated with equal-volume normal saline daily for 8 weeks.The expression levels of IL-1 and TNF-α in the sciatic nerve were detected with immunohistochemistry staining.Results The expression levels of IL-1 (1.43％ ± 0.17％ vs.0.21％ ± 0.09％;P＜0.05) and TNF-α (1.98％ ± 0.12％ vs.0.35％ ± 0.03％;P＜0.05) in the model group were significantly increased than those in the normal control group.The expression levels of IL-1 (0.54％ ± 0.14％,0.51％ ± 0.13％ vs.1.43％ ± 0.17％;all P＜0.05) and TNF-α (0.57％ ± 0.17％,0.49％ ± 0.15％ vs.1.98％ ± 0.12％;all P＜0.05) in the medium-,and high-dose of Furong-Tongmai groups were significantly decreased than those in the model group and low-dose of Furong-Tongmai group (1.08％ ± 0.18％ in IL-1,1.11％ ± 0.09％ in TNF-α;all P＜0.05).Conclusion Furong-Tongmai capsules can reduce the expressions of IL-1 and TNF-α in sciatic nerve in diabetic rats.

Objective To compare the application effect between the method of cassette automatic blood analyzer and the method of traditional serological .Methods Using the method of cassette automatic blood analyzer and the method of traditional serological , respectively ,the samples of blood donors in Dongguan from October 1 ,2013 to April 30 ,2014 were performed irregular antibody screening .The positive samples of screening were identified by using antiglobulin method ,and the irregular antibodies of blood do‐nors were analyzed .Results There were 95 positive cases of irregular antibody by the method of cassette automatic blood analyzer , and the detection rate was 0 .208% .There were 16 positive cases of irregular antibody by the method of traditional serological ,the detection rate was 0 .035% ,and there was statistical significance in differences (P< 0 .05) .The positive coincidence rate of the method of cassette automatic blood analyzer was 56 .547% ,higher than the rate of the method of traditional serological which was 28 .571 % (P<0 .05) .The positive rate of irregular antibody was 2 .242% in RhD‐negative blood donors ,higher than the rate in RhD‐positive blood donors which was 0 .198% (P<0 .05) .Conclusion The positive rate of irregular antibody in blood donors i‐dentified by using the method of cassette automatic blood analyzer is higher than the rate identified by using the method of tradition‐al serological .The irregular antibody screening should be performed for RhD‐negative blood donors .The types of irregular antibody in blood donors are mainly the types of IgM which are no clinical significance .

OBJECTIVETo detect structural changes in the brain in fetuses with agenesis of the corpus callosum (ACC) and holoprosencephaly (HPE) in the first trimester.

METHODSThe ultrasound data were analyzed retrospectively in 620 normal singleton fetuses between 11 and 13(+6) gestational weeks, 5 fetuses diagnosed to have ACC, and 13 fetuses with HPE. The midbrain diameter (MD) and falx diameter (FD) were measured and their ratio (MD/FD) was calculated for comparative analysis.

RESULTSNo significant difference was found in the MD, FD, and MD/FD ratio between fetuses with ACC and HPE (P>0.05). Compared to the normal fetuses, all the fetuses with ACC and HPE showed significantly increased mean MD and MD/FD ratio (P<0.05); 4 (80%) fetuses with ACC and 11 (84.6%) with HPE had a reduced FD. All the fetuses with ACC and HPE had MD/FD ratios greater than 1, which were below 1 in all the normal fetuses.

CONCLUSIONIn the first trimester, fetuses with ACC and HPE have measurable abnormalities in the midbrain and falx area of the brain, and these changes, represented by abnormal midsagittal MD, FD and their ratio, can be of value in detecting ACC or HPE in fetuses in the first trimester.

Agenesis of Corpus Callosum ; diagnosis ; Corpus Callosum ; diagnostic imaging ; Female ; Fetus ; Gestational Age ; Humans ; Pregnancy ; Pregnancy Trimester, First ; Retrospective Studies ; Ultrasonography, Prenatal