Skin diseases in the Da Qing Diabetes Study: a cross-sectional study / 中华医学杂志(英文版)

BACKGROUND@#The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM.@*METHODS@#We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated.@*RESULTS@#In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01).@*CONCLUSIONS@#There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

Construction of Tn5 transposon insertion mutants of Ralstonia solanacearum isolated from Pogostemon cablin / 中国中药杂志

Ralstonia solanacearum strain PRS-84 used in this study was isolated from diseased Pogostemon cablin plants in our previous study.The competent cells of R.solanacearum strain PRS-84 were transformed by electroporation with Tn5 transposon and then were plated on TTC agar plates containing kanamycin to select for kanamycin-resistant colonies.The detection of kanamycin-resistant gene in kanamycin-resistant colonies was performed by PCR.Further,the flanking fragments of Tn5 transposon insertion site in the mutants were amplified by inverse PCR,and the flanking fragments were sequenced and analyzed.The results indicated that the kanamycin-resistant colonies were obtained in the transformation experiment of R.solanacearum strain PRS-84 by electroporation with Tn5 transposon.A specific band of approximately 700 bp was amplified by PCR from kanamycin-resistant colonies.The flanking sequences of Tn5 transposon insertion site in the transformants were obtained by inverse PCR.After sequencing and sequence analysis of Tn5 transposon insertion site in mutants,we preliminarily speculated that the Tn5 transposon inserted in the typ A gene,rec O gene and gid A gene in three mutants,respectively.A random mutagenesis system of R.solanacearum strain PRS-84 by electroporation with Tn5 transposon has been established,and the Tn5 insertion mutants have been obtained.This study might facilitate the creation of mutant library and the discovery of the virulence gene of R.solanacearum isolated from P.cablin.

Role of PI3K/Akt pathway in hypoxic-activated calcium sensing receptor mediated A549 cell metastasis / 中国药理学通报

Aim: To explore the role of PI3K/Akt signaling pathway in A549 and A549/DDP cells metastasis mediated by hypoxic-activated calcium sensing receptor (CaSR). Methods: The A549 and A549/DDP cells in the logarithmic growth stage were randomly divided into control, hypoxia, hypoxia + GdCl3 (CaSR agonist), hypoxia + NPS2143 (CaSR inhibitor) and hypoxia + LY294002 (PI3K inhibitor) + GdCl3 group. The protein levels of CaSR, MMP-2 and p-Akt were analyzed by Western blot in A549 and A549/DDP cells under different treatment conditions. The effects of different treatment factors on the ability of cell migration and invasion were measured by wound scratch assay and transwell migration assay. The effects of different treatment factors on the secretion of matrix metalloproteinase-2 (MMP-2) protein by A549 and A549/DDP cells was analyzed by ELISA. Results: Compared with control group, hypoxia increased the protein expression of CaSR, enhanced cell migration ability, increased MMP-2 protein expression in cells and culture medium, and promoted Akt protein phosphorylation in A549 and A549/DDP cells. NPS2143 reduced the effect of hypoxia, GdCl3 amplified the effect of hypoxia, and LY294002 inhibited effect of hypoxia and GdCl3. Conclusions: Hypoxic-activated CaSR promotes A549 cell metastasis, and its mechanism may involve PI3K/Akt pathway.

Fibronectin extra-domain B:biological characteristics and role in new targeted drugs development / 药学学报

Fibronectin extra-domain B (ED-B) has been a good target in new drug development, several relevant antibody drugs are in phase Ⅱ or Ⅲ clinical trials for metastatic melanoma, soft-tissue sarcoma and so on. Some data of phase Ⅱ clinical trials shows that ED-B antibody drugs (L19-IL2 and L19-TNF α) for melanoma are significantly superior to PD-1 antibody drugs. This article describes several aspects of ED-B, such as biological characteristics, the development of targeted drugs, and the potential therapeutic applications, including modifying protein drug structure, constructing fusion protein, expanding indications, developing companion diagnostics and individual treatments. We also discuss how to promote original innovation in drug discovery, which might help to find new development focus.

Parsimonious model for blood glucose level monitoring in type 2 diabetes patients / 生物医学与环境科学（英文）

To establish the parsimonious model for blood glucose monitoring in patients with type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and fifty-nine adult Chinese type 2 diabetes patients were randomized to receive rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood glucose levels were measured at 10 time points in a 24 h period before and after treatment, and the 24 h mean blood glucose levels were measured. Contribution of blood glucose levels to the mean blood glucose level and HbA1c was assessed by multiple regression analysis. The correlation coefficients of blood glucose level measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79, respectively, before and after treatment (P<0.0001). The multiple stepwise regression analysis showed that the blood glucose levels measured at 6 of the 10 time points could explain 95% and 97% of the changes in MBG before and after treatment. The three blood glucose levels, which were measured at fasting, 2 h after breakfast and before dinner, of the 10 time points could explain 84% and 86% of the changes in MBG before and after treatment, but could only explain 36% and 26% of the changes in HbA1c before and after treatment, and they had a poorer correlation with the HbA1c than with the 24 h MBG. The blood glucose levels measured at fasting, 2 h after breakfast and before dinner truly reflected the change 24 h blood glucose level, suggesting that they are appropriate for the self-monitoring of blood glucose levels in diabetes patients receiving oral anti-diabetes therapy.

A case of Klinefelter's syndrome with type 1 diabetes mellitus / 中华医学杂志(英文版)

Klinefelter’s syndrome (KS) is the most common sex chromosome disease in men. Classical features of the syndrome include a eunuchoidal body habitus, small testes and hypergonadotrophic hypogonadism. There has been an increased risk of diabetes mellitus and autoimmune disease for KS patients. This paper reports a case of KS in association with type 1 diabetes mellitus. The patient was a 21-year-old man, who has been confirmed by absolute insulin deficiency and positive IA-2 autoantibody. The hyperinsulinemic euglycemic clamp test indicated his insulin sensitivity in normal range, and his blood glucose was controlled well by the insulin therapy.

Increased myocardial expression of calcium-sensing receptor and apoptosis in a rat model of atherosclerosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of hyperlipidemia and atherosclerosis on rat myocardial expression of calcium-sensing receptor and apoptosis.</p><p><b>METHODS</b>The rat atherosclerosis model was induced by intraperitoneal injection of VD(3) (6 x 10(5) U/kg) and high cholesterol diet. Wistar rats were divided into two groups: (1) Control group; (2) AS group (n = 12 each). The expressions of CaSR, Bcl-2, Bax and caspase-3 were analyzed by Western blot and RT-PCR. Apoptotic cells were observed by TUNEL assay. The morphological changes of abdominal aorta and cardiac tissues were observed under optical and electro microscopes. The activity of LDH, CK, SOD and the content of MDA were assayed with ultraviolet spectrophotometer. The level of cTnT was detected by electrochemical immunofluorescence.</p><p><b>RESULTS</b>Compared with control group, the activity of LDH and CK, the content of MDA and cTnT, the apoptosis index, the expression of CaSR, Bax and caspase-3 were significantly increased, but the SOD activity and Bcl-2 expression were significantly decreased, the myocardial ultrastructure injury was significantly aggravated in the AS group (all P < 0.05).</p><p><b>CONCLUSION</b>Hyperlipidemia and atherosclerosis can up-regulate myocardial calcium-sensing receptor expression, promote myocardial apoptosis, aggravate oxidative stress and myocardial ischemia.</p>

Blood pressure reduction found in subjects after evolution of impaired glucose tolerance to normal glucose tolerance or diabetes——New information from The Da-Qing IGT and Diabetes Study / 中华内分泌代谢杂志

Objective To investigate the blood pressure change in relation to the evolution of impaired glucose tolerance (IGT). Methods From 1986 to 1992, 334 subjects with IGT were randomized to placebo, diet, exercise and diet plus exercise intervention groups. No anti-hypertension drug was given to these enrolled subjects. Blood pressure was measured at the beginning and the end of the six-year prospective study. In this analysis these subjects were stratified to seven subgroups based on 2 h plasma glucose (2hPG) level during OGTT at the end of the study: < 7.8,7.8~8.8,8.9~9.9,10.0~11.0,11.1~13.8,13.9~16.6 and≥16.7mmol/L. Blood pressure changes in relation to the evolution of glucose tolerance in these subgroups were compared by least square mean procedure. Results Changes of systolic blood pressure (SBP) in average in these seven groups were -2.4,0.6,7.7,4.3,1.7,-2.9and-6.9mm Hg (1mm Hg=0.133kPa), and changes of diastolic blood pressure (DBP) were-3.2,3.0,3.3,1.7,-0.7,-1.3 and-3.7mm Hg respectively after controlling for age, sex, BMI at baseline and Δ BMI during the follow-up period. In those subjects with IGT evolved into normal glucose tolerance (NGT) or diabetes, reductions in SBP and DBP were significantly greater than those who retained IGT with 2hPG between 8.9-9.9mmol/L (all P < 0.05 ). In 264 out of the 334 subjects with IGT and blood pressure≥130/80mm Hg at baseline, blood pressure changed more strikingly: changes of SBP in these groups were-5.2,-2.6,5.2,2.3,-2.3,-4.2,-7.6mm Hg, and DBP were -5.0, -3.7,1.5, -2.9, -4.3, - 4.0 and-6.0mm Hg respectively after the adjustment of age, sex, BMI, BMI variation. The reductions of SBP and DBP in subjects whose status of IGT was converted to NGT or diabetes were significantly greater than those with retained IGT and 2hPG between 8.9-9.9mmol/L. Conclusion Blood pressure is increased in the subjects with IGT who retained in the IGT group during the six-year follow-up period in Da-Qing Study. On the contrary, subjects with IGT evolved into NGT or diabetes demonstrate significant reduction of blood pressure.

Prevalence and risk factors of peripheral arterial disease in diabetic patients over 50 years old in China / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the prevalence of peripheral arterial disease (PAD) in China type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD.</p><p><b>METHODS</b>In total 1,397 type 2 diabetic patients aged 50 years and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in 15 Class III Grade A hospitals in 7 major cities of China.</p><p><b>RESULTS</b>Mean patient age was 63.7 +/- 8.2 years and mean duration of diabetes mellitus was 9.39 +/- 7.4 years. Two hundreds and seventy-two (19.47%) patients were diagnosed as PAD by ABI < 0.9, 122 (18.37%) in male and 150 (20.46%) in female. PAD patients had a significantly longer duration of diabetes mellitus, higher hemoglobin A1c, and a significantly lower mean body mass index than non-PAD ones. Aging, smoking, and systolic blood pressure were found to be positively related with the prevalence of PAD. In terms of lipid profiles, no variable was found to relate with PAD. Notably, baPWV showed as the same significant guiding index for PAD, almost matched with ABI.</p><p><b>CONCLUSIONS</b>PAD is a common complication in China type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for diabetic patients with high risk factors.</p>

Study on the distribution and risk factors of hypertension among children: a cohort study / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the association between hypertension and the tendency of change among children,so as to lay a foundation for the prevention and control of hypertension.</p><p><b>METHODS</b>Based on findings from the prevalence survey that carried out in September 1999 in Daqing of Heilongjiang province. New admission children were selected as subjects to conduct a five-year cohort study. All the subjects were interviewed with questionnaires and their blood specimens were collected for biochemical analysis. All data were analyzed using SPSS 10.0 software. Results The prevalence of hypertension among 447 children was found 2.01% at the baseline study but increased to 5.37% in the fifth year. During a five year period, the systolic pressure level among children increased from (100.65 +/- 11.62)mmHg (1 mm Hg = 0.133 kPa) to (106.67 +/- 9.29) mm Hg,while the diastolic pressure level was from (66.27 +/- 11.31) mm Hg to (70.28 +/- 7.98) mm Hg and showed significant difference between boys and girls. There were association between hypertension and family history, body mass index (BMI), triglyceride, insulin, insulin resistance index while insulin sensitivity index and family history, BMI and insulin sensitivity index appeared to be the important factors. Children under this study were divided to 'with family history or without' and then every group was divided to 'with over weight-obesity or normal'. Obesity and insulin sensitivity seemed the key risk factors on hypertension. Descent of insulin sensitivity was an independent risk factor.</p><p><b>CONCLUSION</b>The level of blood tension among children in Daqing city was higher than that from the national data. The present study confirmed that over-weight,obesity, heredity and insulin resistance were the risk factors of hypertension while insulin resistance was related to hypertension. The interaction of these risk factors was independent or correlated to each other.</p>

Compensated hyperinsulinemia based on selective insulin resistance predicts elevation of blood pressure in non-diabetic adults / 中国医学科学院学报

<p><b>OBJECTIVES</b>To investigate if hyperinsulinemia or insulin resistance could predict the elevation of blood pressure in non-diabetic adults.</p><p><b>METHODS</b>One hundred and seventy non-diabetic adults (NGT 107, IGT 63) were included based on the screen by OGTT in 1986. Height, weight, blood pressure were measured. Plasma glucose and insulin concentration at 0.60 and 120 min during OGTT were determined at baseline. All the subjects were followed for six years with blood pressure and plasma glucose examined at the end of the study. Subjects worsening to diabetes were excluded. Insulin area under-curve (INSAUC) and insulin sensitivity index [IAI = (1/FINS x FPG)] were calculated. Stepwise regression analysis was performed to evaluate the effects of INSAUC and insulin sensitivity to the elevation of blood pressure.</p><p><b>RESULTS</b>Both SBP and DBP levels at the end of the study were increased with increased INSAUC baseline. The SBP were (119.5 +/- 2.3), (122.1 +/- 2.5), (129.4 +/- 2.4) and (128.3 +/- 2.6) mmHg, and the DBP were (78.6 +/- 1.6), (79.7 +/- 1.7), (85.2 +/- 1.4) and (84.0 +/- 1.0) mmHg from the lowest to the highest quartiles of INSAUC respectively. Pearson correlation analysis showed Age, SBP, DBP, BMI, FINS, INS1h, INSAUC at baseline were positively correlated to blood pressure levels at the end of the study. After the adjustment of Age, sex, BMI, smoking, PG2 h and blood pressure at baseline, the INSAUC was significantly correlated to blood pressure six years later, while the insulin sensitivity index was not.</p><p><b>CONCLUSION</b>The compensated hyperinsulinemia based on selective insulin resistance rather than insulin resistance to glucose per se could predict the elevation of blood pressure in nondiabetic adults.</p>

Time-dependent changes of astrocytes and CD31-marked microvessels in human cerebral infarction / 中华老年医学杂志

Objective To observe the time-dependent changes of astrocytes and microvessels in the ischemic core and surrounding areas.Methods Glial fibrillary acidic protein (GFAP)was measured by HE,and CD31 by immunohistochemistry as markers in post-mortem specimens from ten patients,who died of cerebral infarction.Results Each section of the infarcted brains was divided into four areas (the area 0-3).GFAP expressed a little in area 0 and 1,increased in a time-dependent manner in area 2 and 3;CD31 die not expressed in area 0,expressed a little in the area 1,and increased in area 2 and 3 continuously.Conclusions The proliferation of astrocytes and microvessels may play a significant role in the process of restoration after cerebral infarction.

Predictors of long-term remission induced by short-term intensive insulin treatment in type 2 diabetic patients / 中华内分泌代谢杂志

Objective To investigate the predictors of long-term remission of type 2 diabetes induced by short-term intensive insulin treatment.Methods Fifty-four cases of diabetes mellitus with the duration of illness less than 5 years received an intensive insulin treatment for 2 weeks.The standard meal test and intravenous glucose tolerance test were performed at the baseline and 24 h after treatment completion respectively.Long-term remission meant that the diabetic patients should maintain the target glyeaemic control without any hypoglyeaemie agent within one year.Results The remission rate was 57.4% (31/54) overall,and even reached to 80.6% (29/36) in patients with the duration of illness less than 6 months,whereas,the remission rate was only 11.1% (2/18) in those with the duration of illness more than 12 months.In another view,the remission rate was significantly higher in the patients with fasting plasma glucose (FPG) level of less than 7 mmol/L (78.8%,26/ 33) 24 h after intensive treatment than those with FPG level of more than 7 mmol/L (23.8%,5/21,P