OBJECTIVETo study the relationship between SNP rs17401966 at the KIF1B gene and the genetic susceptibility to Hepatocellular carcinoma (HCC).

METHODSAll study objects were recruited from two Grade A hospitals of Amoy from January 2011 to October 2014.They were surveyed in individual matching case-control study. Accepting criterias in the cases: HCC was first diagnosed based on diagnostic basis during the investigations, over 18 years old, present addresses were as same as surveyed areas in the district (county) level range, no past history of cancers; Exclusion criterias: patients with other liver diseases. The tumor patients without HCC, patients with autoimmune hepatitis or toxic hepatitis, patients who refused to be investigated or too ill to be investigated. Accepting criterias in the controls: the control who passed the physical examination matched the case in ages (no more than 3 years old), sex, health screening in the same hospital over the same period and district (county); Exclusion criterias: people with liver disease or any history of cancers. This study consisted of 376 HCC patients and 403 controls, 5 ml morning fasting venous blood of all subjects were obtained to isolate cells and distribute genotype. The differences in general information between cases and controls were tested by χ² test and t-test. The association between SNP rs17401966 and the risk of developing HCC were assessed by using the multiple factors logistic regression.

RESULTSThe mean age and standard deviation for case and control groups were (61.7 ± 12.8) years and (60.6 ± 12.7) years (t = 1.15, P = 0.251), respectively. The proportion of family history of cancer [28.7% (108/376)] and the HBsAg positive rate [26.9 % (101/376)] in case group were higher than these in control group [15.9% (64/403), 2.7% (11/403)] (χ² = 18.65, 92.02, P < 0.001). In HBsAg carriers, GG genotype genetic susceptibility to HCC is 0.12 (0.02-0.75) times for AA genotype, and G allele susceptibility to HCC is 0.38 (0.15-0.98) times for A allelc. In HBsAg negative group, it showed no statistical significance in the relationship between SNP rs17401966 and susceptibility to HCC, and compared with the A allele, the risk for HCC of G allele is 0.79 (0.62-1.01).

CONCLUSIONThe results demonstrated that the presence of the GG genotype, the GA genotype and the G allele at rs17401966 of the KIF1B gene might decrease the risk for HCC.

Aged ; Alleles ; Carcinoma, Hepatocellular ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kinesin ; Liver Neoplasms ; Middle Aged ; Polymorphism, Single Nucleotide

Objective To study the relationship between SNP rs17401966 at the KIF1B gene and the genetic susceptibility to Hepatocellular carcinoma(HCC).Methods All study objects were recruited from two Grade A hospitals of Amoy from January 2011 to October 2014.They were surveyed in individual matching case-control study . Accepting criterias in the cases:HCC was first diagnosed based on diagnostic basis during the investigations, over 18 years old, present addresses were as same as surveyed areas in the district (county) level range, no past history of cancers;Exclusion criterias:patients with other liver diseases. The tumor patients without HCC, patients with autoimmune hepatitis or toxic hepatitis, patients who refused to be investigated or too ill to be investigated. Accepting criterias in the controls:the control who passed the physical examination matched the case in ages (no more than 3 years old) ,sex , health screening in the same hospital over the same period and district (county);Exclusion criterias: people with liver disease or any history of cancers. This study consisted of 376 HCC patients and 403 controls, 5 ml morning fasting venous blood of all subjects were obtained to isolate cells and distribute genotype. The differences in general information between cases and controls were tested by χ2 test and t-test. The association between SNP rs17401966 and the risk of developing HCC were assessed by using the multiple factors logistic regression. Results The mean age and standard deviation for case and control groups were (61.7 ± 12.8) years and (60.6 ± 12.7) years(t=1.15,P=0.251), respectively. The proportion of family history of cancer[28.7%(108/376)]and the HBsAg positive rate [26.9%(101/376)] in case group were higher than these in control group [15.9%(64/403),2.7%(11/403)](χ2=18.65,92.02,P<0.001). In HBsAg carriers, GG genotype genetic susceptibility to HCC is 0.12(0.02-0.75)times for AA genotype, and G allele susceptibility to HCC is 0.38 (0.15-0.98) times for A allelc. In HBsAg negative group,it showed no statistical significance in the relationship between SNP rs17401966 and susceptibility to HCC,and compared with the A allele,the risk for HCC of G allele is 0.79(0.62-1.01).Conclusion The results demonstrated that the presence of the GG genotype,the GA genotype and the G allele at rs17401966 of the KIF1B gene might decrease the risk for HCC.

Objective To study the relationship between SNP rs17401966 at the KIF1B gene and the genetic susceptibility to Hepatocellular carcinoma(HCC).Methods All study objects were recruited from two Grade A hospitals of Amoy from January 2011 to October 2014.They were surveyed in individual matching case-control study . Accepting criterias in the cases:HCC was first diagnosed based on diagnostic basis during the investigations, over 18 years old, present addresses were as same as surveyed areas in the district (county) level range, no past history of cancers;Exclusion criterias:patients with other liver diseases. The tumor patients without HCC, patients with autoimmune hepatitis or toxic hepatitis, patients who refused to be investigated or too ill to be investigated. Accepting criterias in the controls:the control who passed the physical examination matched the case in ages (no more than 3 years old) ,sex , health screening in the same hospital over the same period and district (county);Exclusion criterias: people with liver disease or any history of cancers. This study consisted of 376 HCC patients and 403 controls, 5 ml morning fasting venous blood of all subjects were obtained to isolate cells and distribute genotype. The differences in general information between cases and controls were tested by χ2 test and t-test. The association between SNP rs17401966 and the risk of developing HCC were assessed by using the multiple factors logistic regression. Results The mean age and standard deviation for case and control groups were (61.7 ± 12.8) years and (60.6 ± 12.7) years(t=1.15,P=0.251), respectively. The proportion of family history of cancer[28.7%(108/376)]and the HBsAg positive rate [26.9%(101/376)] in case group were higher than these in control group [15.9%(64/403),2.7%(11/403)](χ2=18.65,92.02,P<0.001). In HBsAg carriers, GG genotype genetic susceptibility to HCC is 0.12(0.02-0.75)times for AA genotype, and G allele susceptibility to HCC is 0.38 (0.15-0.98) times for A allelc. In HBsAg negative group,it showed no statistical significance in the relationship between SNP rs17401966 and susceptibility to HCC,and compared with the A allele,the risk for HCC of G allele is 0.79(0.62-1.01).Conclusion The results demonstrated that the presence of the GG genotype,the GA genotype and the G allele at rs17401966 of the KIF1B gene might decrease the risk for HCC.

Objective To analyze the pathogenic features and risk factors of hospital-acquired pneumonia in patients with acute spontaneous intracerebral hemorrhage (sICH) in intensive care unit (ICU).Methods The clinical data of 110 patients with sICH admitted in ICU during January 2015 and February 2017 were collected.Patients were divided into hospital-acquired pneumonia group (HAP group,n =66) and non-HAP group (n =44).Multivariate Logistic regression was used to study the risk factors of HAP,and pathogen distribution and drug susceptibility were analyzed.Results Multivariate Logistic regression demonstrated that long-term mechanical ventilation (OR =1.028,95％ CI 1.012-1.044,P ＜ 0.01),lower score of glasgow coma scale (GCS) (OR =1.550,95％ CI 1.148-2.093,P ＜ 0.01),prolonged hospital stay (OR =1.131,95％ CI 1.046-1.224,P ＜0.01) and underlying diseases more than two forms (OR =9.793,95％ CI 1.012-1.044,P ＜ 0.01) were the independent risk factors of HAP,while high plasma albumin level was protective factor for HAP (OR =0.897,95％ CI O.811-0.992,P ＜ 0.05).One hundred and eighty-three bacterial strains were isolated from 66 patients,the top 4 pathogens were Acinetobacter baumannii (28.96％,53/183),Klebsiella pneumonia (15.85％,29/183),Pseudomonas aeruginosa (13.11％,24/183) and Staphylococcus aureus (12.02％,22/183).Acinetobacter baumannii,Klebsiella pneumoniae and Pseudomonas aeruginosa were highly resistant to the majority of antibiotics,some of which even reached 100％.Staphylococcus aureus showed high resistance to macrolides,fluoroquinolones and β-lactam antibiotics.Conclusions There is high incidence of HAP in patients with sICH,and the pathogenic bacteria are mainly gram-negative bacteria.Effective prevention and treatment measures should be taken to reduce the incidence of HAP for patients with sICH in ICU.

[Objective]To investigate the effect and mechanism of Shuxuetong and its main component hirudin on the apoptosis of cerebellar granule neurons(CGNs)in Sprague-Dawley(SD)rats.[Methods]CGNs incubated in vitro for 7 days were divided into survival control group or 25 K group(cultured in medium containing 25 mmol/L KCL)and apopto-sis group or 5 K group(cultured in medium containing 5 mmol/L KCL).CGNs were separately treated with proportionally diluted and different concentrations of Shuxuetong(1/50,1/40,1/30,1/20 and 1/10)and the corresponding different con-centrations of hirudin(2,2.5,3.34,5 and 10 U/mL).Hoechst staining was performed to analyze the apoptosis.Western blot was used to detect the expression levels of Cleaved Caspase-3,Bim and VEGF.[Results]Hoechst staining showed that 5 K group had a higher apoptosis rate than 25 K group.In 25 K group,there was no significant change in the apoptosis rate between neurons treated with different concentrations of Shuxuetong and hirudin,but significant changes was found in 5 K group and the higher the concentration,the lower the apoptosis rate.Western blot results revealed that,compared with control neurons in 5 K group,Shuxuetong injection and hirudin treatments resulted in a decrease of Cleaved Caspase-3 and Bim expression,but an increase of VEGF protein.[Conclusions]Shuxuetong and its main component hirudin inhibits the apoptosis of CGNs through suppressing proapoptotic BH3-only protein Bim.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*