BACKGROUND: Osteoporosis is a genetic disease associated with many enes. To date, the genes that regulate bone mass are incompletely defined.OBJECTIVE: To investigate the relationship between polymorphisms of steoprotegerin (OPG) gene promoter with bone mineral density (BMD) in remenopausal and postmenopausal women.DESIGN: Prospective study.SETTING: Peking Union Medical College Hospital.PARTICIPANTS: In July 2002, 495 Han nationality women selected from Peking Union Medical College Hospital were non-related volunteers and gave their informed consent prior to the study, which included 306 premenopausal women aged 20-39 years, 189 postmenopausal women aged 50-84 years.METHODS: ① BMD measurement: BMD was measured at the Lumbar Spine and Femoral Neck, trochanter, Ward's triangle by dual-energy X-ray absorptiometry. ② Genotyping: Whole blood genome DNA was extracted by QIAGEN DNA extraction kit. The PCR product and the result of endonuclease digest were confirmed by sequencing (Bioasia Biotechnology,Shanghai, China). The impact of the polymorphisms on BMD was also investigated using multiple Logistic regression.MAIN OUTCOME MEASURES: ① Distribution of OPG genotypes and the relationship with BMD. ② Association between OPG polymorphisms and osteoporosis.RESULTS: All 495 subjects were involved in the final analysis. ① These polymorphisms were in Hardy-Weinberg equilibrium (χ2= 0.056 -0.222, P＞ 0.05). The frequencies of genotypes of these subjects were as follows: AA (70.1%), AG (26.9 %), GG (3.0 %) for 163A→G polymorphism; TT (71.3 %), TG (25.9 %), GG (2.8 %) for 245T→G polymorphism. BMD was lower in premenopausal women with GG +AG genotype than AA genotype for 163A→G polymorphism, so did GG+TG genotype than TT genotype for 245T→G polymorphism. But there was no significant difference. BMD was lower in postmenopausal women with AG+GG genotype than AA genotype for 163A→G polymorphism at Lumbar Spine 2-4, Femoral Neck, Ward's triangle and Trochanter (P ＜ 0.05). For 245T→G polymorphism, BMD of postmenopausal women with TG+GG genotype was lower at Femoral Neck,Ward's triangle and Trochanter than TT genotype (P ＜ 0.05). For 245T→G polymorphism, BMD of postmenopausal women with TG+GG genotype was lower at Femoral Neck, Ward's triangle, and Trochanter than TT genotype (P ＜ 0.05). ② Age, weight, height, years since menopause, and 163A→G/245T→G genotypes were sewed as covariates. AG+GG genotype was contributed to low BMD at Lumbar Spine 2-4 and Ward's triangle (OR =2.045, OR=2.956, P ＜ 0.05, 95% CI 1.05-6.7). TG+GG genotype was risk factor for osteoporosis at Lumbar Spine 2-4, Ward's triangle,and Trochanter (OR=2.059, OR=2.859, OR=2.123, P ＜ 0.05, 95% CI 1.04-6.5).CONCLUSION: BMD was lower in postmenopausal women with the variant G allele for 163A→G and 245T→G polymorphisms at Femoral Neck,Ward's triangle, and Trochanter. The variant allele G may associate with lower BMD in postmenopausal women.

OBJECTIVETo evaluate the role of Jiangzhi Xiaoban Tablet (JXT) in improving heartfunction of coronary heart disease (CHD) patients by tissue Doppler imaging (TDI) and speckle trackingimaging (STI) technology.

METHODSRecruited were 60 inpatients with confirmed CHD by coronary angiography at First Affiliated Hospital, Hunan University of Traditional Chinese Medicine from October 2013to November 2014. They were assigned to the treatment group (group A) and the control group (groupB) according to random digit table, 30 cases in each group. Patients in group A took JXT, 0.45 g/tablet,4 tablets each time, 3 times per day, while those in group B took Simvastatin Tablet, 20 mg/tablet, 1 tablet each time, once per evening. The therapeutic course for all was 8 weeks. The long axis view of theheart of 18 segments STI Peak strain LS and TDI peak systolic Sa parameters were performed in all patients before and after treatment.

RESULTSBefore treatment segments of STI strain LS and TDI longitudinal peak systolic peak Sa were not statistically different between the two groups (P > 0.05). Each segment of STI peak longitudinal strain LS and TDI peak systolic Sa in the two groups were higher after treatment than before treatment (P < 0.05). After treatment each segment of STI parameters of LS and eachTDI segment parameters of Sa were significantly lower in group B than in group A (P < 0.01).

CONCLUSIONJXT could improve heart function of CHD patients to different degrees, and its curative effect was betterthan that of routine Western medicine (Simvastatin Tablets) treatment.

Coronary Artery Disease ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Echocardiography, Doppler ; Heart ; drug effects ; Humans ; Simvastatin ; therapeutic use ; Tablets

OBJECTIVEQingkailing injection (QKLI), Jinnaduo injection (JNDI), Shuxuetong injection (SXTI), Shenmai injection (SMI) and Kangai injection (KAI) are widely used in China. To predict the herb-drug interactions in clinical application, they were evaluated for their in vitro inhibition effect on CYP3A in rat liver microsomes.

METHODThe rat liver microsomes were incubated with different doses of 5 kinds of traditional Chinese medicine injections (TCMIs) in the present of testosterone, a specific substrate of CYP3A. 6beta-hydroxytestosterone, the metabolite of testosterone, was monitored by HPLC to compare the inhibition effect of 5 TCMIs on CYP3A in rat liver microsomes. Ketoconazole was used as a positive control.

RESULT10% QKLI reduced the formation of 6beta-hydroxytestosterone by approximately 93.0%, which is more significant than other four TCMIs. The half maximal inhibitory concentration (IC50) and the enzyme-inhibitor constant K(i) were 1.0% and 0.7% respectively.

CONCLUSIONQKLI showed much stronger inhibition activity against CYP3A, comparing to other 4 TCMIs. The results revealed that QKLI may be involved in herb-drug interactions by inhibition of CYP3A.

Animals ; Cytochrome P-450 CYP3A Inhibitors ; Injections ; Male ; Medicine, Chinese Traditional ; Microsomes, Liver ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

0.05).Conclusion The distribution of G990R CASR genotype in PHPT patients is different from healthy women,and R allele is higher in PHPT group.Among PHPT patients,A986S and G990R polymorphisms are associated with serum calcium and ICa levels.Patients with S or G allele have lower levels of serum calcium and ICa.A986S genotype is also associated with serum PTH level and patients with S allele have relatively lower level of PTH.

Objective To evaluate the relationship between p38mitogen-activated protein kinase (p38MAPK) signaling pathway and calcium over-loading during oxygen-glucose deprivation and restoration (OGD/R) in cardiomyocytes of rats.Methods Cardiomyocytes obtained from Sprague-Dawley rats,aged 1-3 days,were cultured and divided into 3 groups (n =27 each) using a random number table method:control group (group C),group OGD/R and p38MAPK inhibitor SB203580 group (group SB).The cells were subjected to OGD for 6 h followed by restoration of O2-glucose supply for 2 h.Ceils were incubated for 1 h with 10 μmol/L SB203580 in group SB.At 2 h of restoration of O2-glucose supply,cell morphology was observed under an inverted microscope,cell viability was measured by the CCK-8 method,the release of lactate dehydrogenase (LDH) in the supernatant was determined by 2,4-dinitrobenzene chromogenic method,intracellular calcium concentration was determined by flow cytometry,and the expression of phosphorylated p38MAPK (p-p38MAPK) and p38MAPK was detected using Western blot.The LDH release rate and p-p38MAPK/p38MAPK ratio were calculated.Results Compared with group C,the LDH release rate,intracellular calcium concentration and p-p38MAPK/p38MAPK were significantly increased,and the cell viability was markedly decreased in group OGD/R and group SB (P＜0.05).Compared with OGD/R group,the LDH release rate,intracellular calcium concentration and p-p38MAPK/p38MAPK ratio were significantly decreased,the cell viability was increased (P＜0.05),the cell morphology was nearly normal,and the number of cells was increased in group SB.Conclusion p38MAPK signaling pathway can mediate calcium overload after being activated and is involved in the pathophysiological mechanism of OGD/R in cardiomyocytes of rats.

OBJECTIVETo explore the relationship between waist-to-hip ratio (WHR) and insulin resistance(IR) in non-diabetic normal-weight individuals and investigate how this association differs between male and femalesubjects.

METHODSFrom June to October, 2012, we performed a cross-sectional survey among 2142 community-based non-diabetic Chinese participants, who were divided into 4 groups according to the gender-specific quartiles of WHR. Homeostatic model assessment of insulin resistance (HOMA-IR), calculated as the product of fasting plasma glucose (mmol/L) and fasting insulin (mU/L) divided by 22.5, was used as the indicator of insulin resistance. Logistic regression models were used to explore the association of WHR with IR in these subjects.

RESULTSIn the unadjusted model, WHR was significantly associated with IR in women (OR=6.60, 95%CI: 2.86-15.26, P<0.001); the association was still significant (OR=3.28, 95%CI: 1.34-8.04, P=0.009) after adjustment for the potential confounders including the history of hypertension, coronary heartdisease, current smoker, physical inactivity, and body mass index.

CONCLUSIONWHR is independently associated with IR in non-diabetic Chinese women with normal body weight.

OBJECTIVETo discuss the technique details of subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) to improve technical success in the treatment of chronic total occlusions (CTO) diseases in lower extremity when there is failure to reenter the distal true lumen.

METHODSBetween May 2009 and Aug 2010, 15 patients underwent endovascular recanalization with SAFARI technique. There were 8 male and 7 female patients with a mean age of 74.9 years. There were 3 patients with severe claudication (Rutherford category 3) and 12 patients with critical limb ischemia (Rutherford category 4 to 6). The clinical and follow-up data of these patients were analyzed retrospectively.

RESULTSFourteen patients were treated with SAFARI technique successfully. The technique success rates were 93.3%. The mean ankle brachial index increased from 0.39 to 0.83.Symptoms were relieved in 86.6% patients, Ulcer were healed in 93.3%patients.

CONCLUSIONSSAFARI technique is a safe and effective method in treating CTO diseases, when it is failure to renter the distal true lumen with subintimal angioplasty technique.

Aged ; Aged, 80 and over ; Angioplasty, Balloon ; methods ; Arterial Occlusive Diseases ; surgery ; Female ; Follow-Up Studies ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Retrospective Studies

Objective To study the effect of aqueous extract from Araliae Echinocaulis Radicis et Cortex (AEAE) on expression of TGF-β/BMPs signaling pathway in osteoblasts.Methods The fracture model of rat was established and randomly divided into model group,AEAE low,middle and high dose (3.6,1.8,0.9 g/kg) group.After ig administration for 7 d,the blood was taken from abdominal aorta and the serum was separated.The rats primary osteoblasts were cultured and qualified after alkaline phosphatase staining and alizarin red staining.The osteoblasts were cultured continuously for 48 h in animal serum of the corresponding group.The contents of BMP-2,TGF-β,Smad-1 and Smad-2 were detected by qRT-PCR and Western blotting method.Results Compared with model group,the mRNA level ofBMP-2,TGF-β and Smad-1 in AEAE low,middle and high dose group,Smad-2 mRNA level in middle and high dose group,and the protein level of BMP-2,TGF-β,Smad-1 and Smad-2 in low,middle and high dose groupwere significantly higher than those in model group (P＜0.05 and 0.01).Conclusion AEAE can promote the proliferation ofosteoblasts by up-regulating the expression of BMP-2,TGF-β,Smad-1 and Smad-2 in TGF-β/BMPs signaling pathway.