Development of three-dimensional breast cancer cell culture drug resistance model / 生理学报

The aim of the present study was to develop three-dimensional (3D) culture model, a more pathologically relevant model, of human breast cancer for drug resistance study. MCF-7 cells were embedded within collagen gel to establish 3D culture model. Cellular morphology was observed using Carmine and HE staining. Cell proliferation was evaluated by CCK-8 assay, and cell activity was detected by Live/Dead staining kit. Drug sensitivities of the 3D culture to doxorubicin, carboplatin, 5-fluorouracil were assayed and compared with those of monolayer (2D) culture. In addition, the levels of drug resistance-related genes P-glycoprotein (P-gp), mrp2 mRNA expressions were detected by real time RT-PCR. Expression level of P-gp protein was detected by Western blot. The results showed that MCF-7 cells in 3D culture formed a number of cell aggregates, and most of them displayed good cell viability. The IC50 values of doxorubicin, carboplatin, 5-fluorouracil were all increased significantly in 3D culture compared with those in 2D culture. Moreover, compared with MCF-7 cells in 2D culture, the cells in 3D culture showed increased mRNA levels of P-gp and mrp2, as well as up-regulated protein expression of P-gp. These results suggest that in vitro collagen-embedded culture system of human breast cancer cells represents an improved pathologically relevant 3D microenvironment for breast cancer cells, providing a robust tool to explore the mechanism of drug resistance of cancer cells.

Treatment effect of Qi ming granule in preventing macular edema after phacoemulsification in diabetes / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the clinical therapeutic efficacy of the Qi ming granule for macular edema ( ME ) in diabetic patients after phacoemulsification. METHODS:In this was a prospective clinical comparison study, 57 diabetic patients ( 76 eyes ) who underwent phacoemulsification were recruited and divided into two groups:treatment group (34 eyes) and control group (42 eyes) . All the patients in treatment group were given oral administration Qi ming granule (4. 5g, tid) and vitamin C ( 0. 1g, tid ) for 6mo postoperatively, while vitamin C ( 0.1g, tid ) for the controls. General clinical examinations, including blood glucose and glycated hemoglobin, as well as comprehensive standardized ophthalmic examinations were performed. Optical coherence tomography ( OCT ) were used to detect macular edema incidence and measure central field retinal thickness. RESULTS: No significant difference was found in the levels of blood glucose, glycated hemoglobin, course of disease, and macular thickness between the two groups during the initial visits. At the 6th month, 2 eyes ( 6%) eyes had clinically apparent macular edema in treatment group, while 6 ( 14%) eyes had clinically apparent macular edema in control group (P=0. 285). The central subfield retinal thickness values were significantly lower in the treatment group ( 211. 76±41. 21μm ) than those in control group (278. 36±48. 94μm) (P CONCLUSION:Qi ming granule can significantly reduce the incidences of macular edema and suppresses increasing retinal thickening after phacoemulsification in patients with diabetes mellitus.

Comparison of parathyroid hormone (1-34) and elcatonin in postmenopausal women with osteoporosis: an 18-month randomized, multicenter controlled trial in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.</p><p><b>METHODS</b>A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded.</p><p><b>RESULTS</b>rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group.</p><p><b>CONCLUSIONS</b>rhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.</p>

Nosocomial spread of hospital-adapted CC17 vancomycin-resistant Enterococcus faecium in a tertiary-care hospital of Beijing, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The incidence of vancomycin-resistant enterococci (VRE) appeared to be increasing in China, but very few nosocomial outbreaks have been reported. Our hospital had experienced an outbreak of VRE since March 2008 to March 2009. The objective of this study was to analyze the molecular features of the isolates and the control measures used to eradicate a VRE outbreak in a tertiary institution in China.</p><p><b>METHODS</b>We characterized VRE isolates from 21 infected and 11 colonized inpatients from a single hospital by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST), the analysis of Tn1546-like elements and virulence genes detection. Infection control measures, including more environmental disinfection, screening for VRE colonization, contact precautions, education and strict antibiotic restriction, were implemented to control the outbreak.</p><p><b>RESULTS</b>During the outbreak, a total of 32 VRE strains were obtained. There were 21 strains found in Emergency Intensive Care Unit (EICU), 9 isolates from Geriatric Ward, and two from other units. All the isolates harbored the vanA gene, however, four of them exhibited the VanB phenotype. Meanwhile, MLST analysis revealed that all isolates belonged to clonal complex (CC) 17. With the infection-control measures, the epidemic was constrained in two units (EICU and Geriatric Ward). After March 2009, no further case infected with VRE was detected in the following one-year period.</p><p><b>CONCLUSION</b>The outbreak was controlled by continuous implementation of the infection control programme, and more rigorous infection control policy is needed.</p>

Relationship between hypertension and osteoporosis in elderly female with type 2 diabetes mellitus / 第二军医大学学报

Objective: To investigate the relationship of hypertension with osteoporosis (OP) and bone mineral density (BMD) in elderly type 2 diabetic women. Methods: A total of 179 elderly type 2 diabetic women were categorized into hypertension group(n=124)and non-hypertension group(n=55). Lumbar and hip BMD were measured by dual-energy X-ray absorptiometry. Prevalences of osteoporosis were compared between the two groups using Chi-square test, and BMD was compared using covariance analysis. The correlation between the osteoporosis and risk factors was analyzed using binary logistic regression method. Results: The prevalences of osteoporosis (total OP, lumber OP and hip OP) in non-hypertension group were higher than that of the hypertension group(P1=0.037, P1=0.042 and Ph=0.051, respectively). Lumbar and hip BMD in the hypertension group was higher than that in the non-hypertension group, and there were significant differences in L3 and L4 BMDs between the two groups (P3=0.040, P4=0.021); however, the difference disappeared after adjustment for body mass index (BMD). After adjustment for C peptide, the P value also increased, but not as obvious as after adjustment for BMI. Binary logistic regression analysis showed that OP was associated with age, BMI and osteocalcin, but not with hypertension. Conclusion: OP is associated with the age, BMI, and osteocalcin, but not with hypertension in elderly type 2 diabetic women.

Expression and clinical significance of syndecan-1 mRNA and HPA-1 mRNA in colorectal cancer detected with real-time fluorescent quantitative polymerase chain reaction / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Invasion and metastasis are the most common causes of mortality for patients with colorectal neoplasms, and blocking invasion and metastasis in a timely fashion has become a hot research focus. We investigated the expression of the messenger RNA of Syndecan-1 and HPA-1 in colorectal cancer, and their correlation with invasion and metastasis.</p><p><b>METHODS</b>Real-time fluorescent quantitative polymerase chain reaction (PCR) was used to detect the expression of Syndecan-1 and HPA-1 in specimens from 49 patients with colorectal cancer, 49 paired adjacent colorectal neoplasms (2 cm from the carcinoma), and 49 surgical margins of paired normal colorectal mucosa tissue (5 cm from the carcinoma), to analyze their correlation with clinicopathologic characteristics of colorectal neoplasm.</p><p><b>RESULTS</b>The expression of HPA-1 mRNA was significantly higher in colorectal cancer (40.56 +/- 11.75) than that in the paired adjacent colorectal neoplasms (18.28 +/- 11.33) and normal colorectal mucosa tissue (10.80 +/- 10.20) (all P < 0.001). The expression of HPA-1 mRNA was significantly higher in paired adjacent colorectal neoplasms than that in normal colorectal mucosa (P < 0.05). The expression of Syndecan-1 mRNA was significantly higher in normal colorectal mucosa (61.21 +/- 12.96) than in the paired adjacent mucosa (14.35 +/- 11.06) or colorectal cancer (10.12 +/- 8.58) (all P < 0.001). The expression of Syndecan-1 mRNA was significantly higher in the paired adjacent mucosa than that in colorectal cancer (P < 0.05). The decreased expression of Syndecan-1 mRNA and the increased expression of HPA-1 were closely associated with the degree of differentiation, the depth of infiltration, lymph node metastasis, vessel metastasis, and TNM staging of colorectal cancer (all P < 0.05). Spearman rank correlation analysis demonstrated a significant correlation between Syndecan-1 and HPA-1(r = -0.405, P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of Syndecan-1 mRNA was significantly highest in normal colorectal mucosa and the expression of HPA-1 mRNA was significantly highest in colorectal cancer. At the same time, the decreased expression of Syndecan-1 mRNA and the increased expression of HPA-1 mRNA can promote the invasion and metastasis of colorectal cancer. The determination of Syndecan-1 and HPA-1 may be of value in the treatment as well as in the prognosis of patients with colorectal cancer.</p>

A randomized, multicenter controlled trial to compare the efficacy of recombinant human parathyroid hormone (1-34) with elcatonin in postmenopausal women with osteoporosis in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique. rhPTH (1-34) is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.</p><p><b>METHODS</b>Two hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 microg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), as well as biochemical markers of bone turnover were measured. Adverse events were recorded.</p><p><b>RESULTS</b>rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months (2.38% vs 0.59%, P < 0.05; 5.51% vs 1.55%, P < 0.01), but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH (1-34) group than in the elcatonin group at 3 months and 6 months (serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%). Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events (67.0% vs 59.0%; 0 vs 0).</p><p><b>CONCLUSIONS</b>rhPTH (1-34) has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.</p>

Effect of multi-glycosides of tripterygii on latent autoimmune diabetes in adults in early stage / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of multi-glycosides of tripterygii (MT) on latent autoimmune diabetes of adults (LADA) in early stage.</p><p><b>METHODS</b>The diabetic patients were divided randomly into the control group treated with insulin alone and the treated group treated with insulin and MT. Levels of insulin, C-peptide, glutamic acid decarboxylase antibody (GADAb) and islet cell antibody (ICA) were detected and clinical features of the disease were observed.</p><p><b>RESULTS</b>There was no difference between the control group and the treated group in body mass index (BMI), the occurrence of diabetic keto-acidosis and the function of liver and kidney (P >0.05). After 6 months' treatment, the positive rate of GADAb and ICA decreased, plasma levels of fasting and 2 hrs post-prandial C-peptide and also 2 hrs post-prandial true insulin in the treated group increased (P <0.01), while all the above indexes improved more significantly after 1 year's treatment (P <0.01).</p><p><b>CONCLUSION</b>Compared treatment of insulin with multi-glycosides of tripterygii in early stage of LADA has better effects in relieving autoimmune injury and recovering function of pancreatic island than insulin alone.</p>

Effect of multiple micronutrients supplementation on anti-oxidative activity and oxidized DNA damage of lymphocytes in children / 中华流行病学杂志

<p><b>OBJECTIVE</b>To examine the effect of multiple micronutrients supplementation on anti-oxidative activity and decreasing oxidized DNA damage of lymphocytes in Chinese children.</p><p><b>METHODS</b>82 healthy children in a rural areas, aged 9-11 years, were selected and randomized allocated into group receiving supplements and control group with each of them 41. 24-hour dietary recall was used to collect data on daily nutrient intakes of the research subjects. The subjects in the supplement group were given vitamin A (VA) 600 microg, beta-carotene (beta-C) 1.0 mg, vitamin E (VE) 100 mg, vitamin C (VC) 300 mg and Na2SeO3(Se) 200 microg in a tablet on daily base while those in the control group took a same-sized color placebo tablet. The trial lasted 8 weeks. 5 ml blood samples from each subject were taken during 7 to 9 o'clock in the morning. DNA damage of lymphocytes and levels of plasma VA, VE, VC, beta-C, Se, malondialdehyde (MDA), activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were then analyzed twice before and after the 8-week of trial.</p><p><b>RESULTS</b>The low intakes of VA, VC and Se only accounted for 50.6%, 65.6% and 67.3% of their recommended nutrient intake (RNI) respectively. After the trial, levels of plasma beta-C, VA, VE, VC and Se in the supplemented group increased by 13.4%, 32.8%, 11.5%, 46.9% and 24.6% respectively, compared with the control group, indicating that nutritional status regarding antioxidant nutrients had largely been improved. GSH-Px activity had a significant increase in the supplement group than before the supplement and in the control group (P < 0.01). GSH-Px before the trial (the 100.4 U/ml) also showed significant increase after the trial (161.7 U/ml) (P < 0.01). However, the values of SOD and MDA significantly decreased after the trial. Analysis of DNA damage indicated that there was no significant difference in the intrinsic damage of DNA (P > 0.05). Significant decreases of oxidized DNA damage induced by 5 micromol/L, 10 micromol/L and 25 micromol/L H2O2 were found more in peripheral lymphocytes of the supplemented group, than in pre-supplement and the control group after the trial (P < 0.01).</p><p><b>CONCLUSION</b>Supplementation of multiple micronutrients could effectively increase the levels of beta-C, VA, VE, VC and Se in plasma, and GSH-Px activity. In the meantime, MDA and oxidized DNA damage induced by a low level H2O2 decreased significantly after the trial. The reason accounted for the decrease of SOD activity after the trial needs to be further studied.</p>

Effect of 1-deoxynojirimycin on high glucose-stimulating proliferation of rat mesangial cells / 中华内分泌代谢杂志

The effect of 1-deoxynojirimycin(DNJ)on the proliferation of rat mesangial cells was observed and its mechanism was explored.The results showed that DNJ significantly inhibited the proliferation of rat mesangial cells induced by high glucose in time-and dose-dependent manners.DNJ significantly decreased expressions of?-smooth muscle action(?-SMA),integrin?1 mRNA and protein and focal adhesion kinase (FAK)protein stimulated by high glucose in rat mesangial cells(P

Total flavonoids of Herba Epimedii increases Cbfal expression in bone of ovariectomized rats / 中华内分泌代谢杂志

Objective To investigate the effect of total flavonoids of Herba Epimodii (HEF) on the expression of core binding factor?1 (Cbfal) in the bone of ovariectomized rats.Methods Fifty-four female SD rats were allocated into 6 groups (9 in each): sham operation group,ovariectomized (OVX) group,OVX followed by three kinds of HEF doses(40,80 and 160 mg?kg~(-1)?d~(-1))and nilestriol (0.1 mg?kg~(-1)?week~(-1))for 12 weeks respectively.Bone mineral density (BMD) of whole body was determined by DEXA.The levels of osteocalcin (BGP) and estradiol (E_2) in serum were measured by radioimmunologic method.All rats were then sacrificed,and total RNA were directly isolated from the skull.Relative quantification of Cbfal mRNA expression was detected by real time quantitative PCR.Results Serum E_2 and BMD of whole body in the OVX group were lower than those in sham group significantly after 12 weeks (both P0.05).Relative quantification of Cbfal mRNA expression in the OVX group was significantly lower than that in sham group after 12 weeks (P

Regulating effect of 17?-estradiol on osteoprotegerin and osteoclast differentiation factor expressions in osteoblasts from newborn rats / 中华内分泌代谢杂志

Osteoblasts (OB) isolated from newborn SD rats were cultured in vitro.After treatment with different concentrations of 17?-estradiol (10~(-11)-10~(-6)mol/L),the mRNA expressions of osteoprotegerin (OPG) and osteoclast differentiation factor (ODF) in OB were measured by RT-PCR.17?-estradiol increased the expression of OPG in OB with the maximal effect at the concentration of 10~(-8) mol/L.No significant difference was observed in the expression of ODF in OB with different concentrations of 17?-estradiol.The therapeutic effect of estrogen on osteoporosis appears to be related to the enhanced OPG expression in OB at physiological concentration of estrogen.

Effects of total flavonoids of Herba Epimedii on the metabolism of typeⅠcollagen and the expression of cathepsin K in the bone of ovariectomized rats / 中华内分泌代谢杂志

Objective To investigate the effects of total flavonoids of Herba Epimedii(HEF)on the metabolism of typeⅠcollagen and the expression of cathepsin K in the bone of ovariectomized(OVX)rats. Methods Fifty-four female SD rats were allocated into 6 groups;OVX group,sham operation group,OVX rats followed by three doses of HEF(40,80 and 160 mg?kg~(-1)?d~(-1))and nilestriol(0.1 mg?kg~(-1)?d~(-1))for 12 weeks respectively.Bone mineral density(BMD)of whole body was determined by dual-energy X-ray absoptiometry.The level of cross-linked N-telopeptide of typeⅠcollagen(NTx)in the urine were determined by ELISA.The amounts of typeⅠcollagen protein and cathepsin K protein in bone tissue were detected by immunohistochemical method and Western blotting.Results Compared with OVX group,the total BMD values in the HEF treated groups were increased(all P＜0.05),and the expression levels of typeⅠcollagen in three HEF treated groups rose significantly in a dose-dependent manner after 12 week,and simultaneously,both the expression of cathepsin K in bone and the level of NTx/Cr were reduced markedly(P＜0.05),being most significant(P＜0.01)in the group treated with the highest dose of HEF(160 mg?kg~(-1)?d~(-1)).Conclusion HEF seems to be able to elevate BMD and improve bone quality of rats via promoting synthesis and inhibiting proteolysis and absorption of typeⅠcollagen in the bone.

Efficacy of?-lipoic acid in treating diabetic peripheral neuropathy / 中华内分泌代谢杂志

Forty type 2 diabetic patients with diabetic peripheral neuropathy (DPN) were assigned to two groups and treated respectively with?-lipoic acid or mecobalamin for 2 weeks.The results suggested that?-lipoic acid could accelerate the nerve conduction velocity and decrease the plasma level of endothelin and C reactive protein as well as microalbuminceria with a effect similar to mecobalamin therapy on DPN.