Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.

Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

OBJECTIVE: To observe the therapeutic effect of different doses of dihydroartemisinin (DHA) on atopic dermatitis (AD) in mice and explore the mechanism. METHODS: Forty-two C57BL/6 mice were randomly divided into 7 groups ( RESULTS: Treatment with 25, 75, and 125 mg/kg DHA and dexamethasone all alleviated AD symptoms of mice, reduced the severity scores of skin lesions, and ameliorated pathological changes of the skin tissue. DHA at 125 mg/kg produced the most obvious therapeutic effect and significantly alleviated mast cell infiltration in the lesions as compared with the other treatment groups ( CONCLUSIONS DHA is effective for the treatment of AD in mice with an optimal dose of 125 mg/kg. The therapeutic effect of DHA is achieved probably through regulation of local immunity by inhibiting mast cell infiltration in the lesions.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Artemisinins ; Cytokines ; Dermatitis, Atopic/drug therapy* ; Immunoglobulin E ; Mast Cells ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Skin

Objective To evaluate the effect of remifentanil on the minimum alveolar concentration of sevoflurane required to blunt the adrenergic response(MACBAR)in the patients with hepatic dysfunction undergoing laparoscopic surgery.Methods The patients,aged 18-64 yr,with body mass index ＜ 30 kg/m2,undergoing elective laparoscopic hepatobiliary surgery,were selected.Patients with normal liver function were selected as control group(C group),and patients with liver dysfunction(Child-Pugh grade B)were selected as test group and divided into 3 subgroups by a random number table method: no remifen-tanil group(R0 group)and different target plasma concentrations of remifentanil groups(R1 group and R2 group).Anesthesia was induced by intravenously injecting propofol 2-3 mg/kg,remifentanil 2 μg/kg and cisatracurium 0.15 mg/kg.After endotracheal intubation,mechanical ventilation was performed.The end-tidal sevoflurane concentration was adjusted to the preset concentration in each group and maintained at the level for 20 min before the pneumoperitoneum was established.Anesthesia was maintained as follows:remifentanil was not used in C group and R0 group,and the target plasma concentration of remifentanil was 1 and 2 ng/ml in group R1 and group R2,respectively,and sevoflurane was inhaled.The MACBAR of sevoflurane was determined using the sequential method.The initial end-tidal sevoflurane concentrations were 5.0％,4.6％,2.6％and 2.4％in group C,group R0,group R1 and group R2,respectively.MAP and HR were recorded and blood samples were collected before and after pneumoperitoneum,and the plas-ma epinephrine and norepinephrine concentrations were measured by enzyme-linked immunosorbent assay,and the difference in MAP and HR before and after pneumoperitoneum was calculated.Results A total of 14 cases in group C,19 cases in group R0,19 cases in group R1 and 15 cases in group R2 completed the study.Compared with group C,the MACBAR of sevoflurane and plasma adrenergic concentration before and after pneumoperitoneum were significantly decreased(P＜0.05),and no significant change was found the other parameters in group R0(P>0.05).Compared with group R0,the MACBAR of sevoflurane was signifi-cantly decreased in group R1 and group R2,and HR before and after pneumoperitoneum and the difference were significantly decreased in group R2(P＜0.05).The MACBAR of sevoflurane was significantly lower in group R2 than in group R1(P＜0.05).Conclusion Remifentanil can decrease the MACBAR of sevoflurane and enhance the efficacy in inhibiting the stress responses in the patients with hepatic dysfunction undergo-ing laparoscopic surgery.

Objective: To evaluate the effect of remifentanil on the minimum alveolar concentration of sevoflurane required to blunt the adrenergic response (MAC_BAR) in the patients with hepatic dysfunction undergoing laparoscopic surgery. Methods: The patients, aged 18-64 yr, with body mass index < 30 kg/m², undergoing elective laparoscopic hepatobiliary surgery, were selected.Patients with normal liver function were selected as control group (C group), and patients with liver dysfunction (Child-Pugh grade B) were selected as test group and divided into 3 subgroups by a random number table method: no remifentanil group (R₀ group) and different target plasma concentrations of remifentanil groups (R₁ group and R₂ group). Anesthesia was induced by intravenously injecting propofol 2-3 mg/kg, remifentanil 2 μg/kg and cisatracurium 0.15 mg/kg.After endotracheal intubation, mechanical ventilation was performed.The end-tidal sevoflurane concentration was adjusted to the preset concentration in each group and maintained at the level for 20 min before the pneumoperitoneum was established.Anesthesia was maintained as follows: remifentanil was not used in C group and R₀ group, and the target plasma concentration of remifentanil was 1 and 2 ng/ml in group R₁ and group R₂, respectively, and sevoflurane was inhaled.The MAC_BAR of sevoflurane was determined using the sequential method.The initial end-tidal sevoflurane concentrations were 5.0%, 4.6%, 2.6% and 2.4% in group C, group R₀, group R₁ and group R₂, respectively.MAP and HR were recorded and blood samples were collected before and after pneumoperitoneum, and the plasma epinephrine and norepinephrine concentrations were measured by enzyme-linked immunosorbent assay, and the difference in MAP and HR before and after pneumoperitoneum was calculated. Results: A total of 14 cases in group C, 19 cases in group R₀, 19 cases in group R₁ and 15 cases in group R₂ completed the study.Compared with group C, the MAC_BAR of sevoflurane and plasma adrenergic concentration before and after pneumoperitoneum were significantly decreased (P<0.05), and no significant change was found the other parameters in group R₀ (P>0.05). Compared with group R₀, the MAC_BAR of sevoflurane was significantly decreased in group R₁ and group R₂, and HR before and after pneumoperitoneum and the difference were significantly decreased in group R₂(P<0.05). The MAC_BAR of sevoflurane was significantly lower in group R₂ than in group R₁ (P<0.05). Conclusion Remifentanil can decrease the MAC_BAR of sevoflurane and enhance the efficacy in inhibiting the stress responses in the patients with hepatic dysfunction undergoing laparoscopic surgery.

Objective To conduct a prospective phase Ⅱ clinical study to explore the distribution of CYP2D6 gene polymorphism in Chinese population and its relationship with the metabolism of tamoxifen in early-stage hormonal receptor-positive breast cancer. Methods CYP2D6 genotype was tested by Sanger sequencing using the ABI 3500 Genetic Analyzer. Plasma concentrations of tamoxifen and endoxifen were measured using the HPLC-MS/MS(API 2000)assay. We downloaded the data of CYP2D6 allele from the CPIP database. Results In Chi-nese patients,the most common alleles were CYP2D6*1,*2,and *10;the predominant diplotypes were *1/*10 (38.3%)and*10/*10(18.8%). The distribution of metabolic phenotype,plasma concentration of endoxifen,and endoxifen:tamoxifen plasma concentration ratio were inconsistent between the normal metabolic phenotype(EM) and the intermediate phenotype(IM)under different CYP2D6 activity prediction criteria.The differences in the ratios and endoxifen plasma concentrations were statistically significant between the three groups by cluster analysis. Conclusions The CYP2D6 genotype distribution in Chinese population is different from that in the Western popu-lation. There is considerable variation of serum endoxifen concentration in Chinese breast cancer patients possess-ing the phenotype previously known as the intermediate active metabolizers of CYP2D6. Therefore,in the current era of precision medicine,the standard CYP2D6 genotype-phenotype classification system cannot properly stratify the Chinese population with different levels of endoxifen plasma concentration.

Objective To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults.Methods The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults.Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine,could be contacted and were sero-negative before primary vaccination.All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine.The blood samples were collected before booster dose vaccination and 28 days after the immunization.Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus.Results The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml,respectively,and the sero-protection rates were 94.7％ and 65.0％,respectively.After the vaccination of the booster dose,the sero-protection rates in both groups were 100.0％,and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml,respectively.Conclusion The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination.However,the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group.Significant increases of GMC levels were observed in both groups after one booster dose vaccination.

Objective:To investigate the activation of peripheral basophils from patients with rheumatoid arthritis ( RA) and its mechanisms. Methods:The activation markers including CD203c and the proportion of IL-4 positive rate of peripheral basophils from RA patients and healthy controls were detected by flow cytometry. Serum levels of IgE in RA patients and healthy controls were detected by electrochemilu minescence immunoassay. Basophils were negatively isolated and co-cultured with or without purified IgE,anti-IgE as positive control,then,the expression of CD203c and propotion of IL-4 positive basophils were detected by flow cytometry. Results:The expression of CD203c and IL-4 positive rate of basophils from RA patients were higher than that of healthy controls (P<0. 05). Serum levels of IgE in RA were higher than that of healthy controls (P<0. 05). After co-cultured with isolated IgE from RA patients,basophils negatively isolated from healthy controls were activated,and higher expression of CD203c and proportion of IL-4 (P<0.05). Conclusion:Basophil activation is related with development of RA,and its activation is mainly mediated by IgE. Targeting basophil and its activation pathway would be expected to provide new strategies for the treatment of RA.