BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Objective To investigate the mechanism of mitochondrial division regulating myocardi-al fatty acid oxidation in diabetic mice.Methods A total of 16 7-week-old male SPF C57BLKS/J diabetic mice were randomly divided into model group and mitochondrial division inhibitor 1(mdivi-1)intervention group(intervention group),with 8 mice in each group.Another 8 male SPF C57BLKS/J mice of the same age were fed adaptively for 1 week and served as control group.The changes in blood glucose and body mass were monitored in above groups.Echocardiography was conducted to detect LVEF and LVFS1 rate and E/A between early and late ventricular diastole.The pathological changes of myocardial tissue were observed by HE staining.The size,morpholo-gy and quantity of mitochondria were observed by TEM.Western blotting was used to detect the expression of mitochondrial dynamin-related protein 1(Drp1),peroxisome proliferator activated receptor α(PPARα),long chain acyl-CoA synthetase 4(ACSL4),carnitine palmitoyl transferase 1B(CPT1B),and fatty acid oxidation detection kit was conducted to determine the activity of fat-ty acid oxidation.Results Compared with the control group,the model group presented hyper-trophic cardiomyocytes and significantly larger cross-sectional diameter of cardiomyocytes(22.36±2.80 μm vs 12.71±1.78 μm,P＜0.01)than the control group.Mdivi-1 intervention resul-ted in greatly improved myocardial hypertrophy and obviously smaller cross-sectional diameter of cardiomyocytes(13.79±1.39 μm vs 22.36±2.8 μm,P＜0.01)when compared with the model group.The expression level of myocardial mitochondrial Drp1,number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocardial cyto-plasm were significantly higher,and the average mitochondrial area of myocardial tissue,the ex-pression of PPARα,ACSL4 and CPT1B in myocardial mitochondria,and fatty acid oxidation activ-ity were significantly lower in the model group than the control group(P＜0.01).After mdivi-1 intervention,the expression level of myocardial mitochondrial Drp1,the number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocar-dial mitochondria were notably lower,and the expression of PPARα,ACSL4 and CPT1B in myo-cardial mitochondria and fatty acid oxidation activity in myocardial tissue were significantly higher when compared with those in the model group(P＜0.05,P＜0.01).Conclusion In diabetic mice,increased myocardial mitochondrial division,decreased translocation of fatty acid oxidation regula-tory protein from cytoplasm to mitochondria,inhibited fatty acid oxidation,and myocardial injury are observed.Mdivi-1 intervention inhibits mitochondrial division,promotes fatty acid oxidation by increasing the translocation of fatty acid oxidation regulatory proteins to mitochondria,and thus improves cardiac function.

Objective To investigate the mechanism of mitochondrial division regulating myocardi-al fatty acid oxidation in diabetic mice.Methods A total of 16 7-week-old male SPF C57BLKS/J diabetic mice were randomly divided into model group and mitochondrial division inhibitor 1(mdivi-1)intervention group(intervention group),with 8 mice in each group.Another 8 male SPF C57BLKS/J mice of the same age were fed adaptively for 1 week and served as control group.The changes in blood glucose and body mass were monitored in above groups.Echocardiography was conducted to detect LVEF and LVFS1 rate and E/A between early and late ventricular diastole.The pathological changes of myocardial tissue were observed by HE staining.The size,morpholo-gy and quantity of mitochondria were observed by TEM.Western blotting was used to detect the expression of mitochondrial dynamin-related protein 1(Drp1),peroxisome proliferator activated receptor α(PPARα),long chain acyl-CoA synthetase 4(ACSL4),carnitine palmitoyl transferase 1B(CPT1B),and fatty acid oxidation detection kit was conducted to determine the activity of fat-ty acid oxidation.Results Compared with the control group,the model group presented hyper-trophic cardiomyocytes and significantly larger cross-sectional diameter of cardiomyocytes(22.36±2.80 μm vs 12.71±1.78 μm,P＜0.01)than the control group.Mdivi-1 intervention resul-ted in greatly improved myocardial hypertrophy and obviously smaller cross-sectional diameter of cardiomyocytes(13.79±1.39 μm vs 22.36±2.8 μm,P＜0.01)when compared with the model group.The expression level of myocardial mitochondrial Drp1,number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocardial cyto-plasm were significantly higher,and the average mitochondrial area of myocardial tissue,the ex-pression of PPARα,ACSL4 and CPT1B in myocardial mitochondria,and fatty acid oxidation activ-ity were significantly lower in the model group than the control group(P＜0.01).After mdivi-1 intervention,the expression level of myocardial mitochondrial Drp1,the number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocar-dial mitochondria were notably lower,and the expression of PPARα,ACSL4 and CPT1B in myo-cardial mitochondria and fatty acid oxidation activity in myocardial tissue were significantly higher when compared with those in the model group(P＜0.05,P＜0.01).Conclusion In diabetic mice,increased myocardial mitochondrial division,decreased translocation of fatty acid oxidation regula-tory protein from cytoplasm to mitochondria,inhibited fatty acid oxidation,and myocardial injury are observed.Mdivi-1 intervention inhibits mitochondrial division,promotes fatty acid oxidation by increasing the translocation of fatty acid oxidation regulatory proteins to mitochondria,and thus improves cardiac function.

Objective: To analyze the longitudinal change of serum total cholesterol concentration in 733 rural residents in Shanxi province. Methods: Based on the residents of five rural areas in Shanxi province who participated in China nutrition and health survey in 2002, a follow-up survey was conducted in 2015. Fasting venous blood of the participants was collected and serum TC concentration was tested by cholesterol oxidase method. Results: Of 733 participants, 332 were male and 401 were female. In 2002 baseline survey, the age of the participants was (42.6±9.5) years old, 76.2% of male and 83.8% of female had junior middle school education or below. Proportion of smoking were 65.7% and 1.2%, drinking were 26.8% and 4.0%, obesity were 6.3% and 12.0%, and central obesity were 27.1% and 31.9%, respectively in male and female. The follow-up age of participants in 2015 was (55.8±9.5) years old, proportion of smoking changed to 48.2% and 1.5%, drinking were 49.7% and 3.0%, obesity increased to 11.8% and 18.2% and central obesity increased to 41.6% and 53.6%, respectively in male and female. The overall serum TC level increased from (3.82±0.89) mmol/L to (4.72±0.97) mmol/L with an average increase of 27.2%, which increased from (3.84±0.94) mmol/L to (4.54±0.93) mmol/L in male with an average increase of 22.7%, and increased from (3.81±0.84) mmol/L to (4.86±0.98) mmol/L in female with an average increase of 30.9%. The serum TC levels in 18-, 30-, 40-, and 50-59 years old group increased from (3.42±0.83), (3.72±0.77), (3.90±0.83) and (4.00±1.03) mmol/L to (4.38±1.01), (4.79±0.92), (4.73±0.99) and (4.76±0.96) mmol/L, with average increase range of 31.4%, 32.1%, 25.2% and 22.6%, respectively. The mean serum TC levels between two years all had statistically significant difference among groups of gender, age, education, marital status, family history of cardiovascular disease, smoking, drinking, BMI and waist circumference after paired t-test and ANOVA analysis (P<0.01). Conclusion The longitudinal serum TC level of rural residents in Shanxi province increased rapidly.

Objective To investigate the influence of depression on glycemic control in the patients with type 2 diabetes mellitus(T2DM).Methods The Zung self-rating depression scale(SDS) was used to assess depression.A total of 276 cases of T2DM were divided into the group A(SDS standard score ≥53 points) and B(SDS standard score ＜53points).The levels of HbA1c,FPG,HOMA-IR,etc.were compared between the two groups,and the influencing factors of glycemic control in T2DM patients were analyzed.Results In the patients with T2DM,the SDS standard score was correlated with HbA1c(r=0.26,P＜0.05).The multivariate regression analysis showed that the SDS standard score was still correlated with HbA1c (β =0.30,t =5.1,P＜ 0.05).The HbA1c level in the group A was higher than that in the group B(t=3.685,P＜0.05);after correcting the factors of sex,age and education,the HbA1c level in the group A was still higher than that in the group B(F=47.8,P＜0.05).Conclusion The depression mood is adverse to glycemic control in T2DM patients.

Objective To explore the clinical characteristics and prognostic factors of primary gastric lymphoma.Methods Clinical data of 78 primary gastric lymphoma patients treated between September 2012 and January 2017 in our hospital were analyzed retrospectively.Results 1-year and 3-year survival rate were 86％ and 68％ respectively.Univariate analysis showed that the four factors including the level of serum lactate dehydrogenase (x2 =35.088,P =0.000),Musshoff stage (x2 =29.930,P =0.000),pathology types (x2 =6.077,P =0.014),IPI score (x2 =21.337,P =0.000) were associated with the prognosis.Multivariate analysis showed that Musshoff stage was an independent risk factor for the prognosis when stage Ⅰ,stage Ⅱ (OR =1.075,95％ CI:0.060-19.107,P =0.961) were compared with stageⅢ (OR =11.994,95％ CI:1.042-138.083,P =0.046),or stage Ⅳ (OR =13.165,95％ CI:1.476-117.417,P =0.021).Conclusions Musshoff stage is an independent factor for the prognosis,surgical treatment can not prolong survival and chemotherapy is the therapy of choice.

Objective To optimize the treatment plan for dermatitis medicamentosa in a patient with abnormal liver function associated with infection.Methods The culprit medication for drug eruption was identified by reviewing the patient′s liver and kidney function, routine blood count, therapeutic drugs, allergic history, by analyzing the characteristics of the compounding medication, combined with literature search on drug eruption diagnosis and treatments.Following the antihistamines and glucocorticoid use guidelines, the treatment plan was optimized by selecting appropriate antihistamines and glucocorticoids based on their metabolism and excretion pathway.Results The rash was poorly controlled after clinical pharmacist′s initial recommendation to use chlorpheniramine (intramuscular injection) and cetirizine (oral).The clinical pharmacist further suggested dexamethasone intravenous drip.The patient recovered well with the combination therapy of antihistamines and glucocorticoid.Conclusion When drug eruption occurred, clinical pharmacists should evaluate patient′s disease and medications comprehensively, provide timely and accurate pharmaceutical care to patients.

OBJECTIVETo explore the feature of primary light chain amyloidosis patients treated with high-dose melphalan with auto peripheral blood stem cell transplantation (auto-PBSCT) and bortezomib plus dexamethasone (VD).

METHODSThirty-eight patients diagnosed from September 2004 to September 2012 were analyzed retrospectively, including 15 cases received auto-PBSCT, 23 cases exposed with VD.

RESULTSThe median follow-up duration for the patients was 34 months (range, 1-112 months), including auto-PBSCT group of 38 months (range, 5-112 months) and VD group of 31 months (range, 1-108 months). The organ response rate in all the patients was 39.5% (15/38), and the organ response rate between these two groups has no significant difference [33.3% (5/15) vs 43.5% (10/23), P=0.532]. However, the median time of organ response was significant difference [6 (3-10) months vs 3 (1-6) months, respectively (P=0.032)]. The 3-year overall survival (OS) rates in the two groups were 72.0% and 66.9%, and their average survival were 84.7 months and 75.9 months, respectively (P=0.683). In the patients with auto-PBSCT, the occurrence of III-IV grade of bone marrow suppression (P<0.001), fever (P<0.001), nausea and infection (P=0.006) were obviously higher than those with VD, but there was no statistically significant difference in pulmonary infection (P=0.069) and bloodstream infection (P=0.059).

CONCLUSIONSThe preliminary results have presented that primary light chain amyloidosis patients treated with auto-PBSCT or VD had similar organ response rate and survival. However, more adverse events occurred in the group of auto-PBSCT.

Amyloidosis ; therapy ; Bortezomib ; therapeutic use ; Dexamethasone ; therapeutic use ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Melphalan ; therapeutic use ; Myeloablative Agonists ; therapeutic use ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies

Humans ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; classification ; complications ; Receptors, Antigen, T-Cell, gamma-delta ; beta-Thalassemia ; complications

Humans ; Multiple Myeloma ; Paresis