Quantitative magnetic susceptibility imaging sequence for intracranial inflammation in patients with optic neuromyelitis / 中国医师进修杂志

Objective:To identify the potential intracranial inflammation in neuromyelitis optica spectrum disorders(NMOSD) patients without supratentorial MRI lesions using quantitative susceptibility mapping (QSM).Methods:Seventy NMOSD patients and 35 age- and gender-matched healthy controls (NC) underwent QSM, 3D-T 1, diffusion MRI from Beijing Tiantan Hospital during June 2019 to June 2021. Susceptibility was compared among NMOSD patients with acute attack (ANMOSD), NMOSD patients in chronic phase (CNMOSD) and NC. The correlation between susceptibility in several brain regions and the cerebrospinal fluid levels of inflammatory makers were analyzed. Results:NMOSD patients showed different susceptibility in several brain regions including bilateral hippocampus, precuneus, right cuneus, putamen, superior parietal and inferior temporal ( P<0.001) and the posr-hoc showed it is higher than normal. Compared to CNMOSD patients, the ANMOSD patients showed increased susceptibility in the cuneus (0.009 ± 0.004 vs. 0.005 ± 0.004, P<0.05). There was significant positive correlations between susceptibility and CSF levels of sTREM2 which reflect the active of microglial cells ( r = 0.494, P<0.05). Conclusions:Despite the absence of supratentorial lesions on MRI, increased susceptibility suggests underlying inflammation in the cerebral cortex in both patients with ANMOSD and CNMOSD, and some of them are obviously related to inflammatory markers in CSF. QSM sequence can be used to explore the potential inflammation in NMOSD patients without obvious supratentorial lesions.

Construction of training program system for hospice care volunteers / 中国实用护理杂志

Objective:To construct the training program system for hospice care volunteers and provide reference for the training of hospice care volunteers in China.Methods:The training program system for hospice care volunteers was initially determined by using the method of literature analysis and investigation, and 16 experts were consulted by two rounds of letters using the method of expert inquiry from May to July 2022, and finally the training program system was established.Results:The effective recovery rate of the two rounds of expert consultation questionnaire was 100%, the expert authority coefficient was 0.88, and the Kendall coordination coefficient was 0.141, 0.131 (both P<0.05). The final training program system for hospice care volunteers contained 7 first-class indicators including training objectives, training objects, training contents, training methods, training hours, training resources and training evaluation, 27 second-class indicators and 92 third-class indicators. Conclusions:The training program system for hospice care volunteers constructed in this study has high reliability and scientificity, and has a good guiding role and reference value for the training of hospice care volunteers.

The therapeutic effect of Gansu tablet combined with entecavir on severe hepatitis B patients and its influence on their immune function / 公共卫生与预防医学

Objective To explore the therapeutic effect of Gansu tablets combined with entecavir on patients with severe hepatitis B and the effect on patients’ immune function. Methods A total of 108 cases of severe hepatitis B patients who were treated in our hospital from January 2018 to January 2019 were randomly divided into two groups: entecavir group and combination treatment group, 54 cases each. Entecavir group was treated with entecavir, and combination treatment group was treated with Gansu tablets and entecavir. The levels of AST, GGT, alt, FIB, APTT, Pt, GSH Px, LPO and MDA in serum were measured by enzyme-linked immunosorbent assay. T-lymphocyte subsets were measured by cell analyzer. The therapeutic effect and adverse reactions were compared between the two groups. Results The levels of AST, GGT and ALT in the combined treatment group were significantly lower than those in the entecavir group (P 0.05). Conclusion The use of Gansu tablets combined with entecavir in the treatment of severe hepatitis B patients was able to improve liver function, improve coagulation function, reduce oxidative stress injury, and improve the immune function of patients, demonstrating a potential clinical application value.

PCV13 (13-valent pneumococcal conjugate vaccine) containing capsular polysaccharides of Streptococ-cus pneumoniae serotypes 6A and 6B confers cross-protection against newly discovered serotypes 6C and 6D / 中华微生物学和免疫学杂志

Objective To investigate whether capsular polysaccharides of Streptococcus pneumoniae serotypes 6A and 6B contained in 13-valent pneumococcal conjugate vaccine ( PCV13 ) could induce cross- protective antibodies against newly discovered serotypes 6C and 6D and the differences between them. Methods New Zealand rabbits were radomly divided into three groups and respectively muscularly administrated with three doses of PCV13, PCV6A and PCV6B on days 0, 14 and 28. PCV6A and PCV6B were conjugates of capsular polysaccharides of serotypes 6A and 6B chemically coupled with diphtheria toxin mutant CRM197. Serum samples were collected on days 0 and 35. Enzyme-linked immunosorbent assay (ELISA) recommended by World Health Organization (WHO) was used to quantitatively measure serotype-specific antibodies to capsular polysaccharides of serotypes 6A, 6B, 6C and 6D. Opsonophagocytosis assay ( OPA) of WHO pneumococcal serology reference laboratory was used to determine antibody functional activities targeting serotypes 6A, 6B, 6C and 6D. Results Immunization rabbits with PCV13 induced the secretion of antibodies to capsular polysaccharides of serotypes 6A and 6B. These antibodies were able to not only cross-react with capsular polysaccharides of serotypes 6C and 6D but also recognize and bind to target Streptococcus pneumoniae serotypes 6A, 6B, 6C and 6D, resulting in the activation of complements and further phagocytosis of target bacteria by differentiated HL60 cells. Bactericid-al titers were largely even among these serotypes except for serotype 6D which was slightly lower. PCV6A could induce antibody against capsular polysaccharide of serotype 6A, which was able to cross-react with capsular pol-ysaccharides of serotypes 6B, 6C and 6D and showed higher bactericidal titers to serotypes 6A, 6B and 6C over serotype 6D. PCV6B could induce antibody against capsular polysaccharide of serotype 6B, which was able to cross-react with capsular polysaccharides of serotypes 6A, 6C and 6D and showed higher bactericidal titers to se-rotypes 6A, 6B and 6C over serotype 6D. Antibody concentrations and bactericidal titers specific to serotypes 6A, 6B, 6C and 6D were significantly increased following immunization with PCV13, PCV6A or PCV6B (P<0. 01). Conclusion PCV13 containing pneumococcal serotypes 6A and 6B induced antibodies against capsular polysaccharides of serotypes 6A and 6B in New Zealand rabbits, which were able to cross-react with capsular polysaccharides of serotypes 6C and 6D and provide cross-protection to bacteria of serotypes 6C and 6D. Both serotypes of 6A and 6B contained in PCV13 contributed to the induction of cross-protective antibodies, especially to serotype 6C.

Establishment of rabbit model for immunogenicity evaluation of pneumococcal conjugate vaccine / 中华微生物学和免疫学杂志

Objective To establish an animal model for evaluating immunogenicity of pneumococcal conjugate vaccine.Methods New Zealand rabbits were intramuscularly administrated with three doses of 13-valent pneumococcal conjugate vaccine (PCV13) with two weeks interval between each injection.Serum samples were collected at different time points before and after vaccination.Quantitative enzyme-linked immunosorbent assay (ELISA) and opsonophagocytosis assay (OPA) that were in conformity with the World Health Organization (WHO) standards were used to detect the concentrations of serotype-specific antibodies and their bactericidal activities.Results The concentrations (Geometric mean concentration, GMC) of serotype-specific antibodies in rabbit serum samples were well correlated with their bactericidal activities (Geometric mean titer, GMT) following vaccination.Moreover, the dynamic changes of GMC and GMT of the same serotype-specific antibody remained consistent as time went by.Conclusion Rabbit model can be used to analyze the immunogenicity of PCV13 vaccine with quantitative ELISA and OPA, which indicates that it is a suitable animal model for evaluating immunogenicity of pneumococcal conjugate vaccine.

The analysis of the glycometabolism in the non-catch-up growth children born small for gestational age / 国际儿科学杂志

Objective To investigate the insulin sensitivity in children born small for gestational age without catch-up growth.Methods We investigated 439 outpatients in pediatric department of the Third Hospital of Peking University with diagnosis of short stature from August 2008 to August 2016.Two groups were divided based on their diagnosis as born small for gestational age group(SGA)with 218 patients and idiopathic short stature group(ISS)with 221 patients.Fasting blood-glucose,fasting insulin,fasting insulin/fasting blood-glucose,islet beta-cell function(HOMA%),homeostasis model assessment-insulin resistance(HOMA-IR)were analyzed in two groups.Results Hierarchy based on age and sex in SGA and ISS.No significant difference was observed in preadolescent boys with fasting blood-glucose(4.7±0.6 vs 4.8±0.6,P=0.678),fasting insulin(5.1±4.0 vs 4.3±4.7,P=0.345),fasting insulin/fasting blood-glucose,HOMA%,HOMA-IR.No significant difference was observed in preadolescent girls with fasting blood-glucose(4.5±0.5 vs 4.6±0.5,P=0.828),fasting insulin(4.7±3.5 vs 4.5±3.3,P=0.603),fasting insulin/fasting blood-glucose,HOMA%,HOMA-IR.No significant difference was observed in adolescent boys with fasting insulin(5.9±4.3 vs 6.0±4.5,P=0.958),fasting blood-glucose(5.0±0.8 vs 4.9±0.5,P=0.176),fasting insulin/fasting blood-glucose,HOMA%,HOMA-IR.No significant difference was observed in adolescent girls with fasting blood-glucose(4.9±0.6 vs 4.8±0.4,P=0.141),fasting insulin(7.5±6.4 vs 7.4±8.6,P=0.448),fasting insulin/fasting blood-glucose,HOMA%,HOMA-IR.Conclusion The insulin sensitivity were in good condition in children born small for gestational age without catch-up growth.

Roles of phosphatidylinositol 3-kinase/protein kinase B signaling pathway in skeletal muscle, peroxisome proliferator-activated receptor γ and phosphatase and tension homologue deleted on chromosome 10 in regulating insulin sensitivity of rats with fetal growth restriction / 中华围产医学杂志

Objective To investigate the roles of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and its regulatory protein peroxisome proliferator-activated receptor γ (PPAR γ) and phosphatase and tension homologue deleted on chromosome 10 (PTEN) in regulating insulin sensitivity in rats with fetal growth restriction (FGR).Methods Sixteen pregnant rats were randomly divided into two groups including FGR and control groups on the 12th day of pregnancy (eight in each group).The FGR group was given low protein diet (8％ of casein) and restriction diet to establish the neonatal rat model of FGR.All maternal rats after delivery and newborn rats after weaning on 21 days after born were fed with normal diet.Each time blood samples were collected from eight newborn rats of each group to measure levels of fasting plasma glucose (FPG) and fasting insulin(FINS) at the time points of 21 days,two and four months after birth.Then insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.Expression of PI3K,AKT,PPAR γγ,PTEN and glucose transporters 4 (GLUT4) in skeletal muscle at mRNA and protein levels were measured at 21 days,two and four months after birth with real time fluorescence polymerase chain reaction and Western blot,respectively.Relationships between the expression of key molecules of PI3K/AKT signaling pathway and insulin sensitivity were analyzed.T-test,and Pearson's correlation analysis were used for statistical analysis.Results (1) The average birth weight of newborn rats in the FGR group was lower than that of the control group [(4.37± 0.69) vs (7.03±0.55) g,t=-20.75,P＜0.05].The incidence of FGR in the FGR group was 93.33％ (70/75).(2) Compared with normal offspring,those in the FGR group showed significantly increased FPG [two months after birth:(5.53± 0.58) vs (7.49 ± 0.38) mmol/L,t=8.08;four months afterbirth:(6.35±0.66) vs (8.94±0.90) mmol/L,t=6.58],FINS [two months afterbirth:(9.18±0.66) vs (14.67± 1.90) mU/L,t=7.71;four months after birth:(33.08±2.76) vs (56.33±2.81) mU/L,t=16.71] and IR1 (two months after birth:2.25±0.31 vs 4.90±0.81,t=8.63;four months after birth:9.30±0.90 vs 22.44±3.10,t=1 1.51),but decreased ISI (two months after birth:0.020 ± 0.002 vs 0.009± 0.001,t=-10.1 4;four months after birth:0.005±0.000 vs 0.002 ±0.000,t=-14.91) at two and four months after birth (all P＜0.05).(3) Compared with normal offspring,those in the FGR group showed decreased expression of PI3K (21 days after birth:0.082±0.028 vs 0.019±0.004,t=-6.29;two months after birth:0.020±0.003 vs 0.010±0.005,t=-4.78;four months after birth:0.014±0.004 vs 0.003±0.001,t=-7.87) and GLUT4 (21 days after birth:0.132±0.057 vs 0.041 ±0.019,t=-4.32;two months after birth:0.183±0.084 vs 0.069±0.017,t=-3.74;four months after birth:0.248±0.069 vs 0.113±0.040,t=-4.74) at mRNA level at 21 days,two and four months after birth (all P＜0.05).Compared with normal offspring,decreased expression of PPAR γ (two months after birth:0.028±0.002 vs 0.012±0.005,t=-3.70;four months after birth:0.030±0.008 vs 0.012±0.005,t=-3.80) and increased expression of PTEN (two months after birth:0.020±0.004 vs 0.045±0.014,t=5.09;four months after birth:0.023±0.007 vs 0.034±0.009,t=2.57) at mRNA level were observed in offspring of the FGR group at two and four months after birth (all P＜0.05).(4) Compared with normal offspring,expression of PI3K protein (21 days after birth:0.22±0.01 vs 0.17±0.02,t=-6.62;two months after birth:0.27±0.03 vs 0.16±0.02,t=-7.25;four months after birth:0.18±0.01 vs 0.09±0.02,t=-9.79) and GLUT4 protein (21 days after birth:0.21 ±0.01 vs 0.03±0.01,t=-27.29;two months after birth:0.10±0.01 vs 0.06t±0.01,t=-3.90;four months after birth:0.13 ±0.01 vs 0.08± 0.02,t=-8.10) decreased in offspring in the FGR group at 21 days,two and four months after birth (all P＜0.05).Compared with normal offspring,those in the FGR group showed decreased expression of PPAR γ protein (two months after birth:0.10 ± 0.01 vs 0.07± 0.01,t =-7.29;four months after birth:0.09±0.01 vs 0.08±0.01,t=-2.83),but increased expression of PTEN at protein level (two months after birth:0.10±0.01 vs 0.15±0.02,t=6.01;four months after birth:0.09±±0.01 vs 0.13±0.02,t=5.51) at two and four months after birth (all P＜0.05).(5) The IRI levels in offsprings in the FGR group were negatively correlated with the expression of PI3K,GLUT4 and PPAR γ at protein level (two months after birth:r=-0.90,-0.92 and-0.79;four months after birth:r=-0.92,-0.75 and-0.73,all P＜0.05),but positively correlated with the expression of PTEN at protein level (r=0.87 and 0.86,both P＜0.05) at two and four months after birth.Conclusions The abnormal expression of the key molecules of PI3K/AKT signaling pathway precedes the decrease of insulin sensitivity in newborn rats with FGR and the expression regulatory protein PPAR γ and PTEN are also changed,suggesting that these molecules may induce the impairment of insulin sensitivity in rats with FGR and be involved in the development of insulin resistance.

Placental expression of CDKN1C imprinted gene and birth weight of appropriate and small for gestational age neonates / 中华围产医学杂志

Objective To investigate the relationship between the expression of imprinted gene CDKN1C in placenta and the birth weight of neonates.Methods Twenty-nine term small for gestational age (SGA) neonates admitted to Peking University Third Hospital from January 1,2014 to December 31,2014 were recruited,and 29 appropriate for gestational age (AGA) neonates with a difference of not more than one week in gestational age served as controls.Fresh placental tissue was collected and the expression of imprinted gene CDKN1C mRNA in the placenta were detected by real-time fluorescence quantitative-polymerase chain reaction,and its protein expression was estimated by Western-blot.Chi-square test,independent-sample t test,Pearson's correlation analysis were used for statistical analysis.Results The CDKN1C mRNA expression level in SGA was significantly higher than that in AGA (0.133± 0.059 vs 0.100±0.046,t=2.401,P=0.020),so was the CDKN1C protein expression (0.280±0.043 vs 0.190±0.041,t=8.410,P=0.000).The CDKN1C mRNA expression levels were negatively correlated with birth weight in both groups (SGA group,r=-0.587,P=0.001;AGA group,r=-0.569,P=0.001),and the correlation was slightly stronger in SGA (r2=0.344) than in AGA (r2=0.324).The CDKN1C protein expression levels of the two groups were negatively correlated with birth weight (SGA group,r=-0.579,P=0.001;AGA group,r=-0.497,P=0.006),the correlation being stronger in SGA group (r2=0.335) than in AGA group (r2=0.247).The CDKN1C mRNA and protein expression levels of the two groups were negatively correlated with birth weight for gender,especially in males [mRNA:r2=0.293(male)vs r2=0.185(female);protein:r2=0.730 (male) vs r2=0.601(female)].Neither CDKN1C mRNA nor protein expression level was correlated to the placenta weight (mRNA:SGA group,r=0.119,P=0.540;AGA group,r=-0.069,P=0.722;protein:SGA group,r=0.126,P=0.515;AGA group,r=-0.247,P=0.196).Conclusions The expressions of CDKN1C mRNA and protein may be related to birth weight of term SGA neonates,especially in male infants.

Effect of PDCA-based self-management intervention model on health behavior and medication adherence in aged patients with percutaneous coronary intervention / 中国实用护理杂志

Objective To explore the effects of PDCA-based self-management intervention model on health behavior and medication adherence in aged patients with percutaneous coronary intervention (PCI). Methods Totally 130 aged patients treated by PCI were randomly divided into the intervention group and the control group with 65 patients. The patients in the control group received routine health education, and the patients in the intervention group received PDCA-based self-management intervention model. All patients were investigated with Coronary Heart Disease Self-Management Behavior Scale (CSMS) and Health Promoting Lifestyle Profile (HPLP) and Medication Compliance Scale (MMAS-8) 3 months and 6 months after discharge. Results Six months after discharge, the score of self-management and healthy behavior and medication adherence were 96.98 ± 14.12, 131.86 ± 16.53, 7.18 ± 0.69 respectively in the intervention group, and the score of them were 86.04 ± 11.78, 105.33 ± 10.97, 5.69 ± 1.29 respectively in the control group, and the difference was statistically significant (t=10.981, 10.793, 7.438, P<0.05 or 0.01). Conclusions PDCA-based self-management intervention model is a patient-centered, problem-oriented, dynamic and interactive health education intervention. It may be helpful in improving PCI patients′ health behavior and medication adherence after discharge. And it may establish lasting self-management skills, and is worthy of application and promotion.

"Effects of asphyxia as a ""Second Hit"" on renal function in small for gestational age infants" / 中华围产医学杂志

ObjectiveTo investigate the effects of the asphyxia as a Second Hit on renal function during early stage after birth in small for gestational age (SGA) infants.MethodsThe infants who were hospitalized within 24 hours after birth in Peking University Third Hospital between January 2013 and March 2015 were retrospectively enrolled, and divided into different groups depending on gestational age and asphyxia history. There were 40 preterm non-asphyxia SGA infants and 80 controls who were preterm non-asphyxia appropriate for gestational age (AGA) infants; 11 preterm asphyxia SGA infants and an equal number of preterm asphyxia AGA infants as controls; 33 term non-asphyxia SGA infants and 33 term non-asphyxia AGA infants as controls; and four term asphyxia SGA infants and 13 term asphyxia AGA infants as controls. Blood urea nitrogen (BUN), serum creatinine (SCr), and estimate glomerular filtration rate (eGFR) were tested within 48 h after admission and the incidence of abnormal indexes was compared between groups byt-test and Fisher exact test.Results(1) Compared with preterm non-asphyxia AGA group, BUN level significantly decreased in preterm non-asphyxia SGA group [(3.99±1.69) vs (5.11±2.08) mmol/L,t=2.948, P=0.004]. Compared with term non-asphyxia AGA group, term non-asphyxia SGA group had higher SCr level [(72.03±10.29) vs (62.58±12.27)μmol/L,t=3.390,P=0.001] and lower eGFR level [(25.19±4.07) vs (33.99±8.75) ml/(min·1.73 m2),t=5.238,P=0.000]. (2) Compared with preterm non-asphyxia AGA infants, preterm asphyxia AGA infants had higher BUN [(6.96±3.09) vs (5.11±2.08) mmol/L,t=2.602,P=0.011] and SCr [(76.45±10.11) vs (66.70±13.18)μmol/L,t=2.357,P=0.021] and lower eGFR level [(15.86±2.31) vs (19.54±5.08) ml/(min·1.73 m2),t=2.361,P=0.020]. Compared with preterm non-asphyxia SGA group, there was a significant increase in BUN level [(6.70±3.37) vs (3.99±1.69) mmol/L,t=2.581,P=0.025] and decrease in eGFR level [(14.80±4.67) vs (18.66±5.03) ml/(min·1.73 m2),t=2.285,P=0.027] in preterm asphyxia SGA group. Changes in term infants were similar to preterm infants. (3) Compared with asphyxia AGA group, asphyxia SGA group showed a higher frequency of abnormal eGFR in term infants (4/4 vs 4/13, Fisher exact test,P=0.029). ConclusionsAsphyxia as a probable Second Hit can influence the renal function during early stage in both preterm and term infants, especially in SGA infants.

The impact of non-alcoholic fatty liver disease on islet function in type 2 diabetes / 中华内科杂志

Objective To analyze the influence of hepatosteatosis on pancreatic β-cell function in type 2 diabetes mellitus (T2DM).Methods A total of 213 subjects with T2DM from Metabolic Disease Hospital,Tianjin Medical University from January 2013 to December 2013 were included in the study.Non-alcoholic fatty liver disease (NAFLD) was diagnosed with abdominal ultrasonography.Patients were divided into two groups:T2DM with NAFLD and T2DM without NAFLD.ALT,AST,γ-glutamyltransferase,serum lipid,glycosylated hemoglobin A1 c (HbA1c),fructosamine,fasting glucose,insulin and 2 hours plasma glucose,insulin after 75g glucoseload were detected.The insulin resistance and β-cell function were assessed by HOMA-IR and HOMA-β.Results Among the 213 T2DM subjects,51％ (108 cases) were with NAFLD.The HOMA-IR [4.76 (2.83,7.21) vs 2.79 (1.76,4.37),P ＜ 0.05] and HOMA-β [49.18 (37.78,85.09) vs 29.50 (18.09,45.54),P ＜ 0.05] were significantly higher in T2DM with NAFLD than those in T2DM alone.Within subjects with T2DM and NAFLD,the HOMA-IR [6.28 (2.87,8.17) vs 2.95 (2.07,3.66) P ＜ 0.05] and HOMA-β [59.18 (37.78,85.09) vs 30.59 (28.56,34.49),P ＜ 0.05] levels were higher in subjects with normal liver function than those with abnormal liver function.Conclusions T2DM patients with NAFLD have severer insulin resistance than those without NAFLD.The β-cell function of those patients was compensatory increased,which was decreased in subjects with abnormal liver function.

Effects of folic acid and vitamin B12 on insulin resistance of fetal growth restriction rats / 中华围产医学杂志

Objective To explore the effects of folic acid and vitamin B12 supplement in maternal lactation on insulin resistance in fetal growth restriction (FGR) in rat offspring.Methods Eighteen Sprague-Dawley female rats and male rats were used.Pregnant rats were randomly divided into two groups at 12 days:normal-protein group (NP,n=6) and low-protein group (LP,n=12).The were 84 FGR newborn pups in LP group (93.3％,84/90).Forty-eight FGR newborn pups were randomly selected and divided into two groups (24 in each group):intervention group and non-intervention group.The intervention group was fed with high folate and vitamin B12 in the diet;and non-intervention group and NP group were fed normal diet.All of the newborn pups were weaned at 21 days after birth and then fed with normal diet.At days 21,60 and 120 d after birth,eight pups were randomly selected from each group and fasting plasma glucose (FPG),fasting insulin (FINS),blood diglyceride (TG) and cholesterol (TC) were measured.The insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.Variance and Student-Newman-Keuls tests were used for statistical analysis.Results (1) The incidence of FGR:Birth weight of LP offspring [(4.44±0.58) g] was significantly lower than that of NP ones [(7.03±0.56) g] (t=15.75,P ＜ 0.05).(2) FPG and FINS:at day 21 after birth,FPG of the non-intervention group,intervention group and NP group was (4.8±0.3),(4.8±0.4) and (4.6±0.3) mmol/L (F=0.57),respectively;FINS was (4.2± 0.2),(4.5 ±0.4) and (4.3 ±0.1) mU/L (F=0.31),respectively;and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,FPG of the three groups was (7.5±0.4),(6.9± 1.0) and (5.5±0.6) mmol/L (F=17.14);FINS was (14.7± 1.9),(10.7± 1.0) and (9.2± 0.7) mU/L (F=38.34),respectively.At day 120,FPG was (8.9±0.9),(8.0±0.8) and (6.4±0.7) mmol/L (F=21.60);FINS was (56.3±2.8),(38.2±2.5) and (33.1 ±2.8) mU/L (F=164.46).FPG and FINS were highest in the non-intervention group,and lowest in NP group,with significant differences among the three groups of pups (all P ＜ 0.05).(3) IRI and ISI:at day 21,IRI of the non-intervention group,intervention group and the control group was 0.9±0.1,0.9±0.1 and 0.9±0.2 (F=0.49);ISI was-(3.0±0.7),-(3.0±0.1) and-(3.0±0.3) (F=0.69);and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,IRI of the three groups was 4.9±0.8,3.3±0.3 and 2.2±0.3 (F=49.48);ISI was-(4.7±0.2),-(4.3±0.1) and-(3.9±0.1) (F=63.47).At day 120,IRI of the three groups was 22.4±3.1,13.6±2.0 and 9.3±0.9 (F=75.15);ISI was -(6.2 ± 0.1),-(5.7 ± 0.1) and-(5.3 ± 0.1) (F=104.42);and there were significant differences among the three groups (all P ＜ 0.05).(4) TC and TG:at day 21,TC of the non-intervention group,intervention group and the control group was (2.0±0.1),(2.0±0.1) and (2.0±0.1) mmol/L (F=0.10);TG was (0.75±0.1),(0.77±0.1) and (0.74±0.1) mmol/L (F=0.33);and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,TC of the three groups was (2.3 ± 0.1),(2.2 ± 0.1) and (2.0± 0.2) mmol/L (F=8.34);TG was (1.5 ± 0.2),(1.2±0.1) and (1.0±0.2) mmol/L (F=17.93).At day 120,TC was (2.4±0.2),(2.2±0.1) and (2.1 ±0.1) mmol/L (F=6.12);TG was (1.7±0.5),(1.2±0.3) and (l.0±0.1) mmol/L (F=9.80).The TC and TG were highest in the non-intervention group and the lowest in the control group;and there were significant differences among the three groups (all P ＜ 0.05).Conclusion Supplementing folic acid and vitamin B12 in maternal lactation can improve in some extent insulin resistance in FGR rats,but not sufficient enough to completely repair glucose and lipid metabolism.

Decreased insulin sensitivity in rat hepatocytes with intrauterine growth retardation and establishment of insulin resistance cell model in vitro / 北京大学学报(医学版)

Objective:To explore the hepatocyte insulin sensitivity of intrauterine growth retardation ( IUGR) rats and establish an insulin resistance cell model in vitro.Methods: An IUGR animal model was established by protein malnutrition during the mother pregnancy .On 60 d and 90 d after birth , the offspring rats were fasted for 12 hours and then their angular vein blood was collected to measure the fasting plasma glucose and fasting serum insulin level , then the insulin resistance index ( HOMA-IR) and insulin sensitivity index ( ISI) were calculated .The insulin sensitivity was evaluated by HOMA-IR and ISI.Primary hepatocytes from each group were respectively isolated by two-step perfusion with collage-nase and were defined as normal hepatocytes group and IUGR hepatocytes group .The normal hepatocyte group was divided into two groups: control group and insulin induction group .Insulin induction group was established by primary cultures of normal hepatocyte incubated with varying dilutions of insulin . CCK-8 was used to detect the viability of the cultured hepatocytes .Glucose oxidase-peroxidase method kit was used to measure glucose consumption of the hepatocytes .Results:HOMA-IR was significantly higher in IUGR rats than in the normal rats at the age of 60 days ( t=-17 .02 , P<0 .05 ) and 90 days ( t=-12.52, P<0.05).ISI was significantly lower than in the normal rats aged 60 days (t=5.61, P<0.05) and 90 days (t=12.42, P<0.05).There were no significant differences in hepatocyte viability among the control group , IUGR group and insulin induction group after incubation of 48 h on day 60 (F=1.34, P=0.29) and day 90 (F=0.22, P=0.81).The glucose consumption of the IUGR group and insulin induction group were significantly decreased compared with the control group on day 60 ( F=9.28, P=0.002) and day 90 (F=56.60, P<0.001), while there was no significant difference be-tween the IUGR group and insulin induction group (P=0.08, P=0.10).Conclusion:The insulin sen-sitivity of hepatocytes of IUGR rats decreased from adolescence to adulthood .High-dilution insulin may induce insulin resistance cell model in vitro.

Characteristics of polymorphism in promoter region of insulin-like growth factor-1 gene in 561 neonates / 中华围产医学杂志

Objective To investigate polymorphism in the promoter region of insulin-like growth factor-1(IGF-1) gene.Methods Five hundred and sixty-one neonates admitted to Peking University Third Hospital from June 1st,2010 to June 30th,2012 were recruited into the study.Gender,gestational age,birth weight and birth length were collected.Heel blood samples were collected on 3-5 days after birth.DNA was extracted to analyze the polymorphism in the promoter region of IGF-1 gene.Chi-square test,independent-sample t-test,analysis of variance and HardyWeinberg equilibrium were performed.Results Among the 561 neonates,413 were full term,and 148 were preterm; 92 were large for gestational age (LGA),433 were appropriate for gestional age (AGA),and 36 were small for gestional age (SGA).Seven different alleles and 23 genotypes in the promoter region of IGF-1 gene were identified in the population.The seven alleles were 188,190,192,194,196,198 and 200 bp respectively.The three most common genotypes were 190-192 bp,192-196 bp and 192-192 bp,whose frequencies were 23.2％ (130/561),15.0％ (84/561) and 12.8％(72/561).There were no significant differences of cytosine-adenosine (CA)19/CA19,CA19/CAno19and CAno19/CAno19 genotypes between full term and preterm infants [11.4％ (47/413) vs 16.9％(25/148),55.9％ (231/413) vs 50.7％ (75/148) and 32.7％ (135/413) vs 32.4％ (48/148)respectively,x2=2.96,1.21 and 0.00,all P＞0.05].There was no difference in the gestional age among infants with CA19/CA19,CA19/CAno19 and CAno19/CAno19 genotypes [(37.1±2.9),(37.6±3.1) and (37.4±3.1) weeks respectively,F=0.54,P=0.58].The frequency of CA19/CA19 in SGA neonates was higher than that in LGA and AGA neonates [25.0％ (9/36) vs 7.6％(7/92) and 12.9％ (56/433),x2 =7.01,P=0.03],but there were no differences in the frequency of CA19/CAno19 and CAno19/CAno19 among LGA,AGA and SGA neonates (CA19/CAno19:x2 =1.13,P=0.57; CAno19/CAno19:x2 =0.58,P=0.75).Conclusions Polymorphism exists in the promoter region of IGF-1 gene.The gestational age is not associated with the frequency of CA19 allele.

Moxifloxacin-based triple therapy combined with rebamipide for Helicobacter pylori eradication in type 2 diabetic patients / 中华全科医师杂志

Objective To evaluate the efficacy of moxifloxacin-based triple therapy combined with rebamipide for Helicobacter pylori (Hp) eradication in type 2 diabetic patients.Methods Two-hundred age and sex matched type 2 diabetic patients with Hp infection and accompanied by gastrointestinal symptoms were assigned into rebamipide group (n =100) and placebo group (n =100).Both groups received moxifloxacin-based triple therapy for 10 d to eradicate Hp.Rebamipide was administrated in rebamipide group and placebo was administrated in placebo group for 30 d.All patients proceeded 14C-urea breath test (14C-UBT) hefore and 7-8 weeks after eradication therapy.The blood sugar indices,gastrointestinal symptom scores and Hp eradication rates were measured and compared.Those who had gained successful Hp eradication in both groups proceeded 14 C-UBT again 12 months after eradication therapy,and the re-infection rates of both groups were compared.Results There were no significant differences in the average fasting glucose,postprandial glucose and HbAlc levels between the rebamipide group and the placebo group before and after therapy (P ＞ 0.05),the gastrointestinal symptoms of the rebamipide group were improved more markedly than those of the placebo group after therapy (Rome Ⅲ Criteria,2.1 ± 0.9 vs.4.4 ± 0.7,P ＜ 0.01).The Hp eradication rate with both intention-to-treat (ITT) and per protocol (PP) analysis of the rebamipide group were higher than that of the placebo group [86.0％ (86/100) vs.73.0％ (73/100),P ＜ 0.05 and 92.5％ (86/93) vs.76.8％ (73/95),P ＜ 0.01].The re-infection rates with both ITT and PP analysis of those who had successful eradication in rebamipide group were lower than that in placebo group [19.8％ (17/86) vs.35.6％ (26/73),P＜0.05and20.5％ (17/83) vs.36.6％ (26/71),P＜0.05].Conclusions Moxifloxacin-based triple therapy combined with rebamipide has a more beneficial effect on Hp related symptoms,a higher Hp eradication rate and a lower Hp re-infection rate for type 2 diabetic patients.

Liver phosphatidylinosital 3-kinase/protein kinase B pathway is involved in the decrease of insulin sensitivity in rats with fetal growth restriction / 中华围产医学杂志

Objective To investigate the effect of liver phosphatidylinosital 3-kinase/protein kinase B (PI3-K/AKT) pathway on the decrease of insulin sensitivity in fetal growth restriction (FGR) rats.Methods Twenty pregnant female rats were randomly divided into two groups one day after conception:normal-protein group and low protein group (n=10,respectively).Rats in low-protein group was given low protein diet (8.00％ protein) during pregnancy to build FGR model,while normal-protein group was given normal protein diet (20.00％ protein).On day 3,7,14,30,60 and 90 after birth,fasting blood samples of 8 male FGR offsprings from low-protein group and 8 normal offsprings from normal-protein group were collected to measure fasting plasma glucose and insulin level.Then insulin resistance index and insulin sensitivity index were calculated to determine insulin sensitivity.On day 7,14,30,60 and 90 after birth,liver tissue of 8 male FGR and normal offsprings were collected,insulin receptor substrate 1,2 (IRS1/IRS2)and glucose transporter 4 (GLUT4) mRNA expression were measured by real-time fluorescence polymerase chain reaction and the protein expressions of IRS1,PI3-K (subunit p110β),and AKT and phosphorylated AKT (pAKT) were measured by Western blot.The relationships between the expression changes of key molecules of PI3-K/AKT pathway and insulin sensitivity were analyzed by correlation and multiple linear regression method.Results (1) Mean birth weight of baby rats in low-protein group was significantly lower than that of normal-protein group [(4.92±0.36) g vs (6.43±0.59) g,t=14.73,P＜0.05].The incidence of FGR in low-protein group was 88.2％ (97/110); and for male offsprings,it was 94.1 ％ (48/51).(2) Compared to normal offsprings,fasting plasma glucose levels of male FGR offsprings were significantly higher from the age of 60 days to 90 days.Insulin levels and insulin resistance index were significantly higher and insulin sensitivity index was lower from the age of 30 days to 90 days,P＜0.05 respectively.(3) Compared to normal offsprings,IRS1 (0.45 ± 0.02 vs 0.68± 0.03,t=16.633,P＜0.05) and IRS2 mRNA (0.34±0.10 vs 0.70±0.19,t=4.864,P＜0.05) expressions in FGR offsprings were lower from day 7 after birth to day 90 (0.48±0.03 vs 0.59±0.05,t=5.237,P＜0.05; 0.49±0.20 vs 0.70±0.11,t=2.253,P＜0.05).There were no differences in expressions of GIUT4 mRNA and AKT protein between two groups (P＞ 0.05).IRS1,PI3-K and pAKT protein expressions of FGR offsprings decreased significantly from day 14 (0.22±0.05 vs 0.52±0.11,t=7.024,P＜0.05; 0.46±0.03 vs 0.97±0.08,t=17.508,P＜0.05; 0.62±0.10 vs 0.89±0.08,t=6.100,P＜0.05) to day 90 (1.11±0.08 vs 1.32±0.14,t=3.714,P＜0.05; 0.63±0.07 vs 1.00±0.19,t=5.206,P＜0.05;0.28±0.03 vs 0.45±0.10,t=4.880,P＜0.05).(4) The pAKT protein expression level of FGR rats was positively correlated with insulin sensitivity index (r=0.704,P＜0.05) ; while negatively correlated to the level of fasting plasma glucose (r=-0.609,P＜0.05),fasting insulin (r=-0.561,P＜0.05) and insulin resistance index (r =0.577,P＜ 0.05).Conclusions The changes of some key molecules' expressions of PI3-K/AKT pathway in liver might be involved in the insulin resistance in FGR rats.

DNA methylation of peroxisome proliferator-activated receptor γ promoter region and down-regulation of its mRNA expression in liver decrease insulin sensitivity of fetal growth restricted rats / 中华围产医学杂志

Objective To explore the effect of methylation of peroxisome proliferator-activated receptor γ(PPARy) gene promoter in liver and its mRNA expression changes on decreasing of insulin sensitivity in fetal growth restriction (FGR) rats.Methods Twenty pregnant rats were randomly divided into two groups on their first day of pregnancy:normal-protein group (NP) and low-protein group (LP),ten in each.During pregnancy the LP group rats were fed with low-protein diet (8.00％ protein),while the NP group rats were fed with normal-protein diet (20.00％ protein).The offspring rats were fed with standard feed after 21 days of birth.Male offsprings in NP group were as control offsprings,and male FGR offsprings in LP group ware as FGR offsprings.At day 3,7,14,30,60 and 90,fasting blood of offsprings was collected to measure fasting plasma glucose (FPG) and fasting insulin(FINS).Then insulin resistance index of homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.At day 7 and 90,liver tissue of male offsprings was collected to extract DNA and total RNA.The methylation level of PPARγ gene promoter and its mRNA expression were detected by methylation specific-polymerase chain reaction (MS-PCR) and reverse transcription-RCR,respectively.The relationships between methylation of PPARγ gene promoter and mRNA expression and insulin sensitivity were analyzed by Pearson correlation and nonparametric test method.Results (1) The mean offspring birth-weight of LP group was (4.92±0.36) g,which was lower than that [(6.43±0.59) g] of control group (t=14.73,P＜0.05).In LP group,the incidence of FGR offspring was 88.2％ (97/110) and the FGR incidence of male ones was 94.1％ (48/51).(2) At day 90,compared with control offsprings,FPG [(8.95±1.83) mmol/L vs (6.21±1.14) mmol/L,t=-3.291,P＜0.05],FINS [(59.57±9.89) mU/Lvs (36.10±7.32) mU/L,t=-4.916,P＜0.05] and HOMA-IR (0.967±0.297 vs 0.410±0.135,t=-4.472,P＜0.05) of FGR offsprings were significantly higher; while ISI of FGR offspring was lower than that of control offsprings (-3.043±0.294 vs -2.172±0.354,t=4.774,P＜0.05).(3) There was no significant difference in methylation degree of PPARγ gene promoter in liver between FGR and control offsprings at day 7 (0/8 vs 2/8,Fisher exact test,P＞0.05).The methylation degree of PPARγ gene promoter in liver in FGR offsprings was significantly higher than that of control offsprings at day 90 (8/8 vs 2/8,Fisher exact test,P＜0.05).Compared with control offsprings,PPARγ gene mRNA expression level of FGR offsprings decreased significantly at day 90 (4.3.07±7.51 vs 146.72± 40.66,t=7.09,P＜0.05).mRNA expression of PPARγ gene was the lowest in exhaustive methylation offsprings (27.2± 1.6),and then in partial methylation ones (47.3±33.0),the highest in no methylation ones (144.6 ± 21.2) (P＜0.05).(4) The correlation analysis showed that PPARγ mRNA expression level negatively correlated to the level of FPG (r=-0.819),FINS (r=-0.906) and HOMA-IR (r=-0.860),P＜0.05 respectively; but positively correlated to ISI level (r=0.947,P＜0.05).Conclusions Hypermethylation in promoter region of PPARγ gene might inhibit gene transcription,and be involved in the occurrence of insulin resistance in FGR rats.

Efficacy of nateglinide combined with metformin in patients with newly diagnosed drug-na(i)ve type 2 diabetes / 中华全科医师杂志

Objective To compare efficacy of nateglinide or acarbose combined with metformin in patients with newly diagnosed type 2 diabetes.Methods Ninety-six patients with newly diagnosed type 2 diabetes in Metabolic Diseases Hospital of Tianjin Medical University,were randomly to receive nateglinide combined with metformin (group A,n =46) or acarbose combined with metformin (group B,n =42) for four months.Drug dose was adjusted every two weeks.Before and after treatment,oral glucose tolerance test and insulin release test were performed to observe changes of their glucose tolerance,homeostasis model assessment for insulin resistance (HOMA-IR) ,insulin secretion function of β-cells and glucose disposition index (DI) in the two groups.Results After four-month treatment,six patients restored to normal glucose tolerance and 13 patients returned to impaired glucose tolerance (IGT) in group A and 12 patients restored to IGT in group B.Their HOMA-IR was markedly improved compared with baseline in both groups,decreased to 7.1 ± 1.3 from 8.6 ± 1.2 in group A and to 6.9 ± 1.7 from 8.6 ± 1.7 in group B ( P ＜ 0.05 ).Compared with group B,early insulin secretion ( LN△I30/△G30 ) obviously improved in group A [( 1.9 ±0.8) vs.(1.6±0.6) mU/mmol] (P＜0.05) and DI also increased (1.05±0.25 vs.0.89±0.21,P＜0.05 ).Conclusions Nateglinide combined with metformin can obviously restore early insulin secretion and improve insulin resistance in patients with newly diagnosed type 2 diabetes,thus facilitate restoration of their glucose tolerance.

Dynamic changes of insulin sensitivity in rats with fetal growth restriction / 中华围产医学杂志

Objective To investigate the regular pattern of dynamic changes of insulin sensitivity in fetal growth restriction (FGR) rats. Methods Twenty pregnant female rats were randomly divided into two groups as normal-protein group (NP) and low-protein group (LP), which respectively received normal protein diet (20% protein) and low protein diet (8% protein) during pregnancy. Weights of newborns were measured within 6 hours after birth, and the LP offspring whose birth weights were at least 2 standard deviations below the mean of NP offspring (≤2 standard deviations) were defined as FGR rats. At day 3, 7, 14, 30, 60 and 90 after birth, rats were fasted for 12 hours and then angular vein blood was collected to measure fasting plasma glucose (FPG) and fasting serum insulin (FINS) level. At 90 days of age, intraperitoneal glucose tolerance test (IPGTT)was performed; and blood triglyceride ( TG ), low-density lipoprotein cholesterol ( LDL-C ),high-density lipoprotein cholesterol (HDL-C) and glycosylated hemoglobin Alc (HbAlc) were measured. Insulin sensitivity was evaluated by FINS, insulin resistance index (HOMA-IR), insulin sensitivity index (ISI) and IPGTT. Results (1) Birth weights of LP offspring [(4. 92 ± 0. 36) g]were significantly lower than those of NP ones [(6. 43 ± 0. 59) g] (t = 14. 73, P＜0. 05). The incidence of FGR in LP was 88. 2% ; and for the male and female rats, the FGR rate was 94. 1% and 83. 1%, respectively. (2) FPG levels in the male FGR rats were significantly higher than in the NP from the age of 60 days [(9.38 ± 1.57) mmol/L vs (5. 58 ± 1.24) mmol/L] to 90 days [(8. 95 ±1.83) mmol/L vs (6. 21± 1.14) mmol/L] (t=-3. 291, P＜0. 05), while FPG levels in female FGR rats increased significantly only at 90 days of age [(9. 08±1.65) mmol/L vs (6.73±0. 67) mmol/L](t=-3. 226,P＜0. 05). FINS levels were significantly higher in FGR rats than in the NP from the age of 30 days (male FGR rats) or 60 days (female FGR rats) to 90 days (P＜0. 05, respectively).Similarly, HOMA-IR was significantly higher in FGR rats than in the NP at the age of 30 days (male FGR rats) or 60 days (female FGR rats) to 90 days (P＜0. 05, respectively). ISI in male FGR rats showed a reduction in comparison with the NP from the age of 30 to 90 days, while as to the female FGR rats it was significantly lower than in the NP only at 60 days of age and continued to 90 days (P＜0. 05, respectively). IPGTT showed that after injection of glucose, blood glucose at all four points (from 0 min to 120 min) in both male and female FGR rats were higher than that in the NP (P＜0. 05). (3) No significant difference was observed in TG, LDL-C and HDL-C at 90 days of age between the FGR rats and NP ones, while HbA1c in the male FGR rats was significantly higher than that in the NP [(7. 03±0. 54) % vs (4. 37±0. 64)%,t= -8. 028, P＜0. 05]. Conclusions FGR rats are able to maintain glucose balance and normal insulin levels during their earlier age, while insulin sensitivity decreased from adolescence to adulthood. The change of insulin sensitivity is different between male and female FGR rats, and male FGR rats are more likely to develop insulin resistance.

Effects of pregnancy complicated with diabetes on insulin sensitivity of offspring during their early childhood / 中华围产医学杂志

Objective To investigate the effects of pregnancy complicated with diabetes on the insulin sensitivity of offspring during their early childhood. Methods Offspring of diabetic mothers(ODM) and of non-diabetic mothers(ONDM) aged 1 month to 24 months were recruited into this prospective cohort study and followed up for two years. Body weight and body length were measured at 2, 4, 6, 8, 10, 12, 18 and 24 months of age respectively, and body mass index (BMI) were calculated. Fasting plasma glucose and fasting serum insulin levels were measured on the following-up day at 6, 12 and 24 months of age and insulin sensitivity index (ISI) was calculated. Homeostasis model assessment was used to calculate the insulin resistance (HOMA-IR). Insulin sensitivity was evaluated by fasting serum insulin, ISI and HOMA-IR. The difference of insulin sensitivity between ODM and ONDM group were examined by analysis of covariance adjusted by gender, gestational age,birth weight and BMI. Results Six hundred and five babies including ninety ODM and five hundred and eleven ONDM met the inclusion criteria. There were no differences in gender, gestational age,birth-weight/height between the two groups(P＞0. 05). ODM were heavier and higher than ONDM at each measure point during early childhood, but there were statistical differences at the age of 2, 4 and 6 months only (P＜0. 05). And the BMI at age of 2 and 4 months of ODM were higher than those of ONDM(P＜0.05). The number of baby who accepted the measurement of fasting plasma glucose and fasting serum insulin levels at 6, 12 and 24 months of age was 276 cases, 273 cases and 56 cases respectively. The fasting serum insulin of ODM (logarithmically transformed) were 0. 95±0. 30,0. 89±0. 34 and 0. 90±0. 27, which were higher than those of ONDM (0. 70±0. 45, 0. 73±0. 35 and 0. 67±0. 30) (t=9. 58, 5.01 and 6. 11, P＜0.05); HOMA-IR (logarithmically transformed) were 0. 34±0. 33, 0. 27±0. 36 and 0. 27±0. 31, which were higher than those of ONDM also(0.08±0. 46,0. 10±0. 36 and 0. 03 ± 0.33) (t= 9. 55, 4. 79 and 5. 06, P＜0.05); ISI(natural logarithmically transformed) were -3.87±0. 75, -3.73±0. 81 and -3. 73±0. 71, which were lower than those of ONDM(-3.29±1.05, -3.35±0.84 and -3.18±0. 77) (t=9.20, 4. 90 and 5.06, P＜0.05).There were differences in feeding characteristics of ODM between insulin sensitive subgroup [40. 9%(9/22) breast-feeding] and insulin insensitive subgroup [16.67 % (12/72) breast-feeding] (x2 = 7.02,P=0. 03). Conclusions Pregnancy complicated with diabetes has adverse effects on the offspring insulin sensitivity during their early childhood, and affects the early growth and development of them.Breast-feeding might decrease insulin resistance in babies.