[The effect and mechanism of transient continuous subcutaneous insulin infusion therapy on beta cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetes].

OBJECTIVES: To explore the effect of transient continuous subcutaneous insulin infusion (CSII) on ß cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetic patients and its potential mechanism. METHODS: Ten patients with newly diagnosed type 2 diabetes mellitus (T2DM) accepted CSII for two weeks. Intravenous glucose tolerance test (IVGTT) and hyperinsulinemia euglycemia clamp test were performed before and after CSII. Serum soluble E-selectin (sE-selectin) was used to evaluate the injury of vascular endothelial cell, while serum high sensitivity C reactive protein (hsCRP) and soluble CD14 (sCD14) were both used to assess inflammatory condition. RESULTS: (1) Compared with those before treatment, the blood glucose levels of IVGTT, the area under the curve of the blood glucose, glycosylated hemoglobin, TC and LDL-C in the patients were decreased after CSII (P < 0.05 or 0.01). (2) Compared with those before treatment, the insulin levels of IVGTT (except the fasting insulin), the area under the curve of insulin and acute insulin response were all increased after CSII (P < 0.05 or 0.01). (3) Compared with that before treatment, the glucose infusion ratio in the clamp test [(3.46 ± 1.66) mg x kg⁻¹ x min⁻¹ increased to (7.14 ± 2.37) mg x kg⁻¹ x min⁻¹] and HOMA-beta elevated, while HOMA-IR declined (P < 0.05 or 0.01 in all). (4) Compared with those before treatment, the levels of serum sE-selectin, sCD14 and hsCRP were decreased (P < 0.01, except for hsCRP). CONCLUSION: Transient intensive insulin therapy in patients with newly diagnosed T2DM is useful to restore beta cell function, attenuate insulin resistance, repair vascular endothelial injury and improve the disorder of blood sugar and lipid. The mechanism may be related with the inhibition of inflammation in patients.

Bone mineral density and its relationship with body mass index in postmenopausal women with type 2 diabetes mellitus in mainland China.

Bone mineral density (BMD) and its association with body mass index (BMI) are uncertain in postmenopausal women with type 2 diabetes mellitus (T2DM) in mainland China. This study was performed to assess this association including 1,042 postmenopausal women with T2DM and 919 non-diabetic control subjects. Bone mineral density of the posteroanterior spine and of the left hip was measured by use of dual-energy X-ray absorptiometry. Diabetic participants were divided into three groups according to BMI, i.e. low BMI (DML < 18.5 kg/m(2)), intermediate BMI (DMM 18.5-24.9 kg/m(2)), and high BMI (DMH >or= 25 kg/m(2)). The BMD values of diabetic subjects between groups exhibited a significant gradient difference, with DML < DMM < DMH. On the fitting curves, where BMD in various skeletal regions varied with age, BMDs of DML were approximately 15% lower than those of DMM, and those of DMM were approximately 10% lower than those of DMH. For prevalence and risks of osteoporosis a gradient difference was observed among diabetic groups, DML > DMM approximately control > DMH. The osteoporosis risk was higher for the hip than for the lumbar spine, especially in DML. This study indicated that postmenopausal women with T2DM had higher BMD and lower osteoporosis risk in the lumbar spine, and that lower BMI was an indicator of osteoporosis in mainland China.

[Herceptin plus adjuvant chemotherapy for the prognosis of patients with human epithelial growth factor receptor 2 positive early-stage breast cancer: a meta-analysis].

OBJECTIVE: To evaluate the effect of herceptin(trastuzumab) plus adjuvant chemotherapy on the prognosis of patients with human epithelial growth factor receptor 2 (HER2) positive early-stage breast cancer by Meta-analysis. METHODS: Search all of randomized clinical trials (RCTs) on herceptin plus adjuvant chemotherapy for HER2 positive early-stage breast cancer in MEDLINE, EMBase, Cochrane library, Clinical Trails, ASCO Conference data, CHKD, Wanfang Database, VIP information, scholar.google.com and SIGLE. A Meta-analysis was carried out by collecting information based on the inclusion and exclusion criteria from all papers available. RESULTS: The Meta-analysis included 4 trials. A total of 9116 patients were included in the analysis(4555 in the study group and 4561 in the control group). There were statistical differences between the study group(herceptin plus adjuvant chemotherapy) and the control group(adjuvant chemotherapy) in the disease-free survival rate [relative risk(RR)=1.08, 95% CI, 1.06-1.09, P<0.001], the overall survival rate(RR=1.01, 95% CI, 1.01-1.02, P=0.0003), the distant recurrence rate(RR=0.49, 95% CI, 0.42-0.57, P<0.001), and the cardiac events rate (RR=3.93,95% CI, 1.03-15.06, P=0.05). CONCLUSION: Herceptin plus adjuvant chemotherapy can improve the disease-free survival rate and the overall survival rate, decrease distant recurrence rate of patients with HER2 positive early-stage breast cancer, but may cause heart toxicity, especially when combined with anthracycline (doxorubicin).

[Isolation of differentially expressed genes in human osteoblast-like osteosarcoma cell line induced with 17beta-estradiol].

OBJECTIVE: To obtain a serial differentially expressed cDNA fragments from human osteoblast-like osteosarcoma MG-63 cells induced with 17beta-estradiol and to find some estrogen-responsive genes. METHODS: Optimized cDNA representational difference analysis (RDA) was performed to isolate up-regulated expressed sequences between cDNA from MG-63 cell line treated with and without 17beta-estradiol. The sources of up-regulated expressed cDNA fragments were proved by Southern blot. The fragments were cloned into the pGEM-T easy vector and a cDNA library was prepared in E. coli JM109 cells. The cDNA library was plated on LB/Amp(+)/X-gal/IPTG plates and white colonies were picked up and individually grown in LB/Amp(+) medium in 96-well plates. After PCR, colonies were individually blotted onto a Hybond N membrane. Membranes were hybridized with alpha-(32)P-labeled subtracted or unsubtracted tester cDNA. Clones showing a strong hybridization signal with the forward-subtracted probes compared with the reverse-subtracted ones were selected for DNA sequencing, BLAST and Northern blot analysis after release of the pGEM-T easy insert with EcoR I. RESULTS: Five up-regulated expressed fragments were isolated in the fourth subtraction hybridization using cDNA from MG-63 cells induced with 17beta-estradiol as tester amplicon and cDNA from untreated MG-63 cells as driver amplicon by cDNA RDA. These fragments were proved to be really coming from tester amplicon and down-regulated expressed in the untreated cell by Southern blotting. We obtained more than 600 cDNA clones with positive insert from MG-63 cells line induced with 17beta-estradiol and about 120 differentially expressed clones through dot blotting. Twenty clones were sequenced and we got 15 gene sequences. One of them was proved to be differentially expressed through Northern blotting. CONCLUSIONS: cDNA RDA is one of the most effective methods which can isolate differentially expressed genes and we can screen differentially expressed genes rapidly through cDNA RDA combined with cDNA arrays. Some genes of human osteoblast-like osteosarcoma MG-63 cell line showed up-regulated expression after induction by 17beta-estradiol.

The effect of low dose nylestriol-levonorgestrel replacement therapy on bone mineral density in women with postmenopausal osteoporosis.

OBJECTIVE: Recently our studies have shown that nylestriol in combination with levonorgestrel prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in retinoic acid (RA) induced osteoporotic rats. In addition to the animal experiments, we evaluate the effect of Compound Nylestriol Tablet (CNT) on bone mineral density (BMD) in women with postmenopausal osteoporosis. Compound Nylestriol Tablet, which contains 0.5 mg of nylestriol (cyclopentylethinyl estriol) and 0.15 mg of levonorgestrel per tablet, was authorized as a new anti-osteoporotic agent for clinical trial in postmenopausal osteoporosis. METHODS: One year's clinical observation was performed in 191 eligible patients who were randomly divided into two groups (A and B). In group A, 119 patients were treated for one year with CNT (one tablet per week) and in group B, 72 patients with placebo. Bone mineral density of lumbar antero-posterior spine (L1-L4), lateral spine, total hip and total forearm positions including radius+ulna at the ultra distal areas, mid areas, and one-third areas, were measured before and after treatment. Biochemical parameters and effects of CNT on uterus, and breast were observed. RESULTS: We found that patients treated with CNT had a significant decrease of bone loss in total forearm, including radius+ulna at the ultra distal, mid, and 1/3 areas compared with control subjects (all P < 0.05). An improved BMD tendency could be seen at the lumbar spine. There were no differences in the observed biochemical variables. No side-effects on uterus, or mammary glands observed. None of the patients had uterine bleeding or vertebral fractures during one year's CNT treatment. CONCLUSION: These data suggested that CNT is effective, safe and convenient in treating postmenopausal osteoporosis.

Age-related bone mineral density, accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in chinese women.

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward's triangle [Ward's]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination ( R(2)) of the fitting curve were 0.398 to 0.612 ( p = 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20-24 years at Troc and Ward's, and the latest at the age of 40-44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward's (-66.2%) and the lowest at RU1/3 of the distal forearm (-31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 +/- 0.4% in those 30-39, 4.6 +/- 4.4% in those 40-49, 23.9 +/- 13.3% in those 50-59, 56.3 +/- 20.3% in those 60-69, 71.8 +/- 16.7% in those 70-79 and 83.2 +/- 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6-11.1% at the age of 40-49 and 36.5-40.6% at the age of 50-59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5-3.7% at the age of 40-49 and and 3.9-21.7% at the age of 50-59 years at the other skeletal sites (AP, FN, Troc, Ward's, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites ( p<0.001) at the age of 40-59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured.