2011年 · 第124卷第02期

Phosphate plays a critical part in the regulation of cell metabolism,and phosphate homeostasis is closely regulated in normal humans.Chronic hypophosphatemia can cause abnormal mineralization of bone,increased alkaline phosphatase and,in the longer term,metabolic bone disease.Osteomalacia is the main metabolic bone disorder caused by chronic hypophosphatemia,which is characterized by inadequate or delayed mineralization of osteoid in mature cortical or spongy bone。

Abstract：Background The debate over the overall benefits of self-monitoring of blood glucose in type 2 diabetes patients is still continuing.We aimed to assess the difference in glycaemic control and coronary heart disease (CHD) risk levels of experimental type 2 diabetes patients provided with facilities for self-monitoring blood glucose and their counterparts without such facilities.Methods Sixty-one patients who had no prior experience in using glucometers were studied as intervention (n=30) and control (n=31) groups.The intervention group was trained in self-monitoring of blood glucose and documentation.Baseline blood glucose and fasting blood glucose were measured and the intervention patients were provided with glucometers and advised to self-monitor their fasting and postprandial blood glucose over six months.The 10-year CHD risk levels were determined with the United Kingdom Prospective Diabetes Study-derived risk engine calculator.Results The age and diabetes duration were similar in the two groups (P ＞0.05).The majority of the patients were unemployed or retired females with only a primary level education.After 3 months,the haemogolbin A1c (HbA1c) levels of the control patients remained unchanged ((7.8±0.3)% vs.(7.9±0.4)%,P ＞0.05) whereas the HbA1c levels of the intervention patients were significantly reduced from the baseline at three ((9.6±0.3)% vs.(7.8±0.3)%,P ＜0.001) and six ((9.2±0.4)% vs.(7.5±0.3)%,P ＜0.001) months.Interestingly,while the 10-year CHD risk level of the control group remained unchanged after three months,that of the intervention group was remarkably reduced at three and six months from the baseline level ((7.4±1.3)% vs.(4.5±0.9)%,P=0.056).Conclusion Self-monitoring of blood glucose in type 2 diabetes patients significantly improved glycaemic control and the CHD risk profile,suggesting that type 2 diabetes patients will potentially benefit from inclusion of glucose meters and testing strips in their health-care package。

Abstract：Background Both repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes.They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects.The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control,insulin secretion,and lipid profiles in type 2 diabetes patients.Methods A total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide.The standard mixed meal tolerance test was performed before and after the treatment.Plasma glucose (PG),insulin concentration,and lipid profiles were measured.The area under insulin concentration curve (AUCins) and the early-phase insulin secretion index (△I30/△G3o) were calculated.Results After the trial,fasting and postprandial PG and postprandial insulin improved significantly in both groups (P＜0.05).The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group.AUCins increased in both groups (P ＜0.05),but no significant difference was found between groups.△I30/△G30 increased in both groups (P ＜0.05),especially in the repaglinide group (P ＜0.05).Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points,while no significant change was observed in the gliclazide group.Conclusions Repaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion,while repaglinide had more effects on improvements in β-cell function and lipid metabolism。

Abstract：Background Tumor necrosis factor (TNF)-α plays an important role in mediating inflammatory state in obesity and related disorders.Lipopolysaccharides (LPS)-induced TNF-α factor (LITAF) is recently verified as a regulator of TNF-α and other inflammatory cytokines,and maybe act as a transcriptional factor.The aim of this study was to confirm the association between LITAF and obesity and insulin resistance.Methods Forty-seven subjects with a wide range of body mass index (BMI) were included.Subjects were divided intothree groups according to the criteria of normal weight,overweight and obese.Anthropometrics and metabolic profile were tested for all the subjects.Peripheral monocytes were isolated and purified.LITAF transcription was detected by real time PCR,and the protein expression in whole cell and nucleus extracts was detected by Western blotting analysis;transcriptional activity of LITAF was detected by ELISA like assay using a probe containing the DNA binding sequence of LITAF.Plasma TNF-α and interleukin (IL)-6 concentrations were determined with ELISA kit.Results The LITAF mRNA and protein expression in whole cell were higher in overweight (P ＜0.05) and obese group (P ＜0.05) compared with that in normal weight group.The LITAF protein expression in the nucleus and transcriptional activity could not be detected.LITAF protein expression was positively correlated with BMI (r=0.541,P ＜0.001),waist circumference (r=0.391,P=0.007),the homeostasis model assessment for insulin resistance (r=0.372,P=0.011) and fasting insulin levels (r=0.359,P=0.013).As a regulator of inflammatory cytokines,LITAF protein expression was positively correlated with plasma TNF-α (r=0.621,P=0.002) and IL-6 (r=0.407,P=0.039) concentration.Multiple variant regression analysis indicated that BMI (P=0.002) and waist circumference (P=0.017) were independent predictors of LITAF protein expression.Conclusions LITAF is associated with obesity and insulin resistance,as well as inflammatory cytokine secretion.The results indicate LITAF to be a new mediator between inflammation and the obesity related disorders。

Abstract：Background An epidemiologic link between hepatitis C virus (HCV) and abnormal glycometabolism had been established.This study was designed to investigate the prevalence of type 2 diabetes rnellitus and insulin resistance,and to explore the relation between insulin resistance and hepatitis C virus genotype,serum hepatitis C virus-RNA level in chronic hepatitis C(CHC) patients.Methods Three hundred and fifty-nine consecutive patients (CHC,n=296;chronic hepatitis B (CHB),n=63) were evaluated.HCV genotyping was performed by restriction fragment method and serum hepatitis C virus-RNA quantified PCR for all CHC patients in the baseline serum.Fasting levels of insulin and glucose were measured in all patients and the homeostatic assessment of insulin resistance was calculated in the baseline serum.Results Type 2 diabetes mellitus was diagnosed in 15.5% of 296 CHC patients.Insulin resistance was present in 23.8% of the 235 nondiabetic CHC patients,in 23.1% of the 182 nondiabetic and noncirrhotic CHC patients,and associated with high serum HCV RNA level (OR: 1.754;95% CI:1.207-2.548,P=0.003) and age ＞40 years (OR.3.542;95% CI:1.257-9.978,P=0.017).Insulin resistance was less frequent in CHB than in matched CHC (7.9% vs.21.4%respectively,P ＜0.0001).Conclusion The incidence of insulin resistance in CHC was significantly higher than that in CHB patients,associated with high serum HCV RNA level and age ＞40 years。

Abstract：Background The assembled data from a population could provide information on health trends within the population.The aim of this research was to extract and know basic health information from an urban professional population in Beijing.Methods Data analysis was carried out in a population who underwent a routine medical check-up and aged ＞20 years,including 30 058 individuals.General information,data from physical examinations and blood samples were collected in the same method.The health status was separated into three groups by the criteria generated in this study,i.e.,people with common chronic diseases,people in a sub-clinic situation,and healthy people.The proportion of both common diseases suffered and health risk distribution of different age groups were also analyzed.Results The proportion of people with common chronic diseases,in the sub-clinic group and in the healthy group was 28.6%,67.8% and 3.6% respectively.There were significant differences in the health situation in different age groups.Hypertension was on the top of list of self-reported diseases.The proportion of chronic diseases increased significantly in people after 35 years of age.Meanwhile,the proportion of sub-clinic conditions was decreasing at the same rate.The complex risk factors to health in this population were metabolic disturbances (61.3%),risk for tumor (2.7%),abnormal results of morphological examination (8.2%) and abnormal results of lab tests of serum (27.8%).Conclusions Health information could be extracted from a complex data set from the heath check-ups of the general population.The information should be applied to support prevention and control chronic diseases as well as for directing intervention for patients with risk factors for disease。

Abstract：Background Use of neoadjuvant chemotherapy necessitates assessment of response to cytotoxic drugs.The aim of this research was to investigate the effectiveness of dynamic contrast-enhanced magnetic resonance imaging (MRI) for evaluating clinical responses to neoadjuvant chemotherapy in breast cancer patients.Methods We examined patients receiving neoadjuvant chemotherapy for primary breast cancer between October 2007and September 2008.Dynamic contrast-enhanced MRI was used to examine breast tumors prior to and after neoadjuvant chemotherapy.The MRI examination assessed tumors using Response Evaluation Criteria in Solid Tumors (RECIST).The Miller-Payne grading system was used as a histopathological examination to assess the effect of the treatment.We examined the relationship between the results of RECIST and histopathological criteria.In addition,we used time-signal intensity curves (MRI T-SI) to further evaluate the effects of neoadjuvant chemotherapy on tumor response.Results MRI examination of patients completing four three-week anthracycline-taxanes chemotherapy treatment revealed that no patients had complete responses (CR),58 patients had partial responses (PR),29 patients had stable disease (SD),and four with progressive disease (PD).The effectiveness of neoadjuvant chemotherapy (CR + PR) was 63.7% (58/91).The postoperative histopathological evaluations revealed the following:seven G5 (pCR) cases (7.7%),39G4 cases (42.9%),16 G3 cases (17.6%),23 G2 cases (25.3%),and six G1 cases (6.6%).The effectiveness (G5 + G4 +G3) was 68.1% (62/91).MRI T-SI standards classified 53 responding cases,29 stable cases,and nine progressing cases.These results indicated that the treatment was 58.2% effective (53/91) overall.Conclusions Dynamic contrast-enhanced MRI and histopathological standards were highly correlated.Importantly,MRI T-SI evaluation was found to be useful in assessing the clinical effectiveness of neoadjuvant chemotherapy。

Abstract：Background Although chemotherapy is one of the most important treatments of breast cancer,it is limited by significant inter-individuval variations in response and toxicity.The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs).It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms.The aim of this research was to examine the effects of genetic polymorphisms in CYP3A,GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.Methods One hundred and twenty patients with stage Ⅱ or Ⅲ invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m2 and CTX 600 mg/m2 every two weeks.The AJCC TNM staging system (sixth edition)was used to evaluate the pathological response of primary tumor and axillary lymph nodes.The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.Results Patients carrying GSTP1 105 lle/Val or 105 lle/lle genotype were more likely to have good response (OR,0.40;95% CI,0.16-0.96;P=0.024) and light toxicity (OR,0.35;95% Cl,0.13-0.78;P=0.006) than those carrying 105Val/Val genotypes.The response to the treatment was not correlated with estrogen receptor,progesterone receptor and Her2/neu status of tumors.No correlation was found between toxicity effect and patient's age,tumor staging,menopause status,and dose intensity of the drugs.Conclusion GSTP1 polymorphism was associatiated with the chemotherapy response or adverse effects of EPI and CTX regimens。

Abstract：Background Simultaneous pancreas-kidney transplantation (SPKT) frees the diabetic patient with end-stage nephropathy from dialysis and daily insulin injections.Herein,we review consecutive cases of SPKT with bladder drainage performed at our institution over an 8-year period.Methods The study population included 21 patients (16 males and 5 females) who underwent SPKT between September 2001 and September 2009.Seven patients had type-1 diabetes and 14 had type-2 diabetes.Nineteen patients were on dialysis at the time of transplantation.Donation after cardiac death donors were selected for SPKT.The mean human leukocyte antigen match was 2 (range 0-4).SPKT was always performed using bladder drainage and vascular anastomoses to the systemic circulation.Immunosuppressive treatment consisted of anti-lymphocyte globulin induction followed by tacrolimus,mycophenolate mofetil,and prednisone.Results The mean hospital stay was 45.43 days.After a mean follow-up of 39.4 months,survival rates for patient,kidney,and pancreas were 76.2%,76.2%,and 66.7% at 1 year;76.2%,59.3%,and 55.6% at 5 years;and 57.1%,39.5%,and 41.7% at 8 years,respectively.Major complications included anastomotic leaks,reflux pancreatitis,and rejection.Six patients died from septic shock (n=3),duodenal stump leak (1),cardiac arrest (1),or renal failure (1).Eight kidney grafts were lost due to acute rejection (n=2),chronic rejection (3),and death with a functioning graft (3).Pancreatic graft failure (9) was caused by thrombosis (n=1),rejection (2),duodenal stump leak (1),and death with a functioning graft (5).Concluslons SPKT is a valid therapeutic option for uremic diabetics although few hospitals in China can undertake SPKT。

Abstract：Background Targeted therapy for erectile dysfunction (ED) involves fewer screening tests and provides a variety of treatment choices for patients.Although the advantage of targeted therapy in diagnosis and therapy for ED has been recognized,the rational mode for oriented ED therapy has not been established.This study aimed to investigate targeted diagnosis and therapy for ED.Methods A total of 198 patients with ED were included in the study.After intracavernosal vasoactive agent injection was given,color Doppler flow imaging was performed and penile rigidity was classified as Schramek grade 5 (10 minutes duration),grade 4 (10 minutes duration),grade 3 and grade 2,defining four patient groups as group Ⅴ (143 cases),group Ⅳ (23 cases),group Ⅲ (18 cases),and group Ⅱ (14 cases).Appropriate and acceptable treatment was recommended to patients according to erection grade.Results In 198 patients with ED,the peak systolic velocity,end diastolic velocity,and resistance index in the cavemosal artery and dorsal artery and the flow velocity in the deep dorsal vein were not significantly different before injection (P ＞0.05).After injection,peak systolic velocity,end diastolic velocity,and resistance index in the cavernosal artery were different among the four groups (P＜0.05).Between each two groups,the difference in resistance index was significant (P ＜0.05).The statistical differences in other indexes were not significant (P ＞0.05).Selective targeted therapy based on erection grade by color Doppler flow imaging improved the clinical satisfaction rate to 91.91% (182/198).Conclusions Based on the routine diagnosis of ED,blood flow indexes in the cavernosal artery are measured by color Doppler flow imaging following minimally invasive intercavernosal injection,which is combined with the Schramek grade of erection.The most appropriate and acceptable treatment is recommended according to the different groups,which improves the clinical satisfaction of treatment for ED and is an ideal model of targeted diagnosis and treatment。

Abstract：Background Previous clinical and basic research of axial lumbar interbody fusion (AxiaLIF) all focused on the L5/S1.However,there is no data on the feasibility of this approach for the fusion of both L4/5 and L5/S1.This study aimed to explore whether transsacral axial interbody fusion is a candidate for the fusion of both L4/5 and L5/S1.Methods The subjects (n=40) underwent lumbosacral magnetic resonance imaging (MRI).The median sagittal MRI images were analyzed and five measurement markers were defined as follows:the center of the L4/5 disc (A),the center of the L5/S1 disc (B),the anterior margin of the S1/2 space (C),the sacrococcygeal junction (D),and the coccygeal tip (E).The measurement markers were connected each other to produce nine lines (AB,AC,AD,AE,BC,BD,BE,CD and CE) as the reference lines for surgical approaches.The distance between each reference line and the anterior and posterior margins of the L4,L5 and S1 vertebral bodies were measured to determine the safety of the respective approaches.Results Twenty subjects were capable of finding one reference line to fuse both L4/5 and L5/S1 via transsacral axial interbody fusion approach.The surgical approach reference line was AE or CE line.In the other 20 subjects,it was failed to find a reference line which met the safety criteria for fusing both L4/5 and L5/S1.Conclusions About half of subjects were capable of finding a suitable AxiaLIF reference line to fuse both L4/5 and L5/S1.In some subjects,it was difficult to find a suitable AxiaLIF reference line to fuse both L4/5 and L5/S1。

Abstract：Background Thymidylate synthase (TS) is a key regulatory enzyme for de novo DNA synthesis.TS activity is also an important determinant of the response to chemotherapy with fluoropyrimidine prodrugs,and its expression may be affected by gene polymorphisms.In this study,we investigated the associations between polymorphisms of the TS gene and its protein expression,and the implications on the efficacy of 5-fluorouracil (5-FU) in pancreatic cancer cells.Methods Genotypes based on the 28-bp TS tandem repeat for pancreatic cell lines were determined by electrophoretic analysis of PCR products.A single nucleotide polymorphism (SNP) at nucleotide 12 of the second 28-bp repeat of the 3R allele was determined by nucleotide sequencing.The chemosensitivity of pancreatic carcinoma cells to 5-FU in vitro was evaluated using Cell Counting Kit-8 (CCK-8).TS protein expression was analyzed by Western blotting.Results Seven pancreatic carcinoma cell lines had different genotypes in terms of the 28-bp TS tandem repeat,as follows:homozygous 2R/2R (T3M4 and BxPC-3 cells),heterozygous 2R/3R (AsPC-1,Capan-1,and SU86.86),and homozygous 3R/3R (PANC-1 and COLO357).The optical density ratio of genotypes 3R/3R,2R/2R and 2R/3R was 1.393±0.374,0.568±0.032 and 0.561±0.056,respectively.Cells with the 2R/3R or 3R/3R genotypes were further analyzed for the G to C SNP at nucleotide 12 of the second 28-bp repeat of the 3R allele,yielding heterozygous 2R/3Rc (AsPC-1,Capan-1,and SU86.86),homozygous 3Rg/3Rg (COLO357) and homozygous 3Rc/3Rc (PANC-1).The optical density ratio of homozygous 3Rg/3Rg cells and homozygous 3Rc/3Rc cells was 1.723±0.062 and 1.063±0.134,respectively,and this difference was statistically significant (P ＜0.05).Cells with the 2R/2R and 2R/3R genotypes of TS were hypersensitive to 5-FU in vitro as compared with those with the 3R/3R cells.Conclusions Polymorphisms in the TS gene influenced its protein expression and affected sensitivity of 5-FU in seven pancreatic cancer cell lines.Cells with the 3R/3R genotype had higher TS protein expression than the 2R/2R or 2R/3R genotypes.Cells of the 3R/3R genotype with high TS protein expression were shown lower 5-FU sensitivity than cells with the 2R/2R or 2R/3R genotypes.These data warrant large-scale clinical studies to assess the role of polymorphisms in the TS gene on its protein expression and chemosensitivity to 5-FU in pancreatic cancer。

Abstract：Background Capsular contracture has become the most common complication associated with breast implant.Transforming growth factor-beta (TGF-β) is well known for a prominent role in fibrotic diseases.Due to the critical role of TGF-β in pathogenesis of capsular formation,we utilized thermosensitive C/GP hydrogel to controlled release of TGF-β receptor kinase inhibitor (SD208) and investigated their effects on capsular contracture.Methods In vitro degradation and drug release of C/GP hydrogel were performed.Twenty-four rabbits underwent subpanniculus implantation with 30 ml smooth silicone implants and were randomly divided into four groups as fellows:Group 1 received saline solution;Group 2 received SD208;Group 3 received SD208-C/GP;Group 4 received C/GP.At 8 weeks,the samples of capsular tissues were analyzed by hematoxylin and eosin and immunohistological staining.The mRNA expression of collagen Ⅲ and TGF-β1 was detected by RT-PCR assay.Results C/GP hydrogel could be applied as an ideal drug delivery vehicle which supported the controlled release of SD208.SD208-C/GP treatment showed a significant reduction in capsule thickness with fewer vessels.The histological findings confirmed that the lower amounts of inflammatory cells and fibroblasts infiltrate in SD208-C/GP group.In contrast,typical capsules with more vessel predominance were developed in control group.We did not observe the same inhibitory effect of SD208 or C/GP treatment on capsular contracture.Moreover,SD208-C/GP therapy yielded an evident down-regulation of collagen Ⅲ and TGF-β1 mRNA expression.Conclusions This study demonstrated that controlled release of TGF-β receptor kinase inhibitor from thermosensitive C/GP hydrogel could significantly prevent capsule formation after mammary implants。

Abstract：Left ventricular diverticulum is a rare congenital anomaly of which the incidence was reported to be 0.26%.Diverticula are usually localized near the apex and most often involve the inferior or anterior parietal walls of the left ventricle.In this report,we describe a rare case of congenital isolated left ventricular apical diverticulum,which was tako-tsubo-like in systole,"dumbbell-like" the whole left ventricle,diagnosed by angiography and magnetic resonance imaging。

In the early 20th century,the prominent medical educator William Osler (Figure 1) correctly pointed out that medical practice is disadvantaged by "the lack of historical insight,the rift between science and humanity,and the alienation of technology advancement and humanitarianism".Even today,these three issues continue to hinder the development and innovation of modern medicine。