[Analysis of clinical characteristics and risk factors of postoperative complications in infants with early-onset necrotizing enterocolitis after enterostomy].

Objective: To investigate the clinical characteristics of children with early-onset necrotizing enterocolitis (NEC) undergoing enterostomy and analyze the risk factors for postoperative complications. Methods: Retrospective analysis was conducted on the clinical data (perinatal conditions, clinical characteristics, clinical outcomes, etc.) of NEC patients who underwent enterostomy at Beijing Children's Hospital from May 2016 to May 2023. The patients were divided into two groups based on the age of onset: an early-onset enterostomy group (<14 days) and a late-onset enterostomy group (≥14 days). Furthermore, the children with NEC were categorized into complication group and non-complication group based on whether there were complications after enterostomy. The differences in clinical data between these groups were analyzed, and the clinical characteristics of children with early-onset NEC and enterostomy were summarized. Multivariate logistic regression model was employed to analyze the risk factors for postoperative complications in NEC children with enterostomy. Results: A total of 68 cases were enrolled, including 43 cases in the early-onset enterostomy group [26 males and 17 females, aged (6.5±3.0) days] and 25 cases in the late-onset enterostomy group [15 males and 10 females, aged (21.0±3.0) days]. There were 28 cases (17 males and 11 females), age [M (Q1, Q3)] 9 (5, 14) days in the complication group and 33 cases (22 males and 11 females), aged of 14 (6, 21) days in the non-complication group. Compared to the late-onset enterostomy group, the early-onset enterostomy group had significantly higher rates of intraventricular hemorrhage [30.2% (13/43) vs 8.0% (2/25)], hemodynamically significant patent ductus arteriosus [37.2% (16/43) vs 12.0% (3/25)], mechanical ventilation≥72 hours after birth [39.5% (17/43) vs 16.0% (4/25)], stage Ⅲ NEC [(69.8% (30/43) vs 40.0% (10/25)], extensive NEC [27.9% (12/43) vs 8.0% (2/25)], and short-term postoperative complications [56.8% (21/37) vs 29.2% (7/24)] (all P<0.05).Multivariate logistic regression model analysis revealed that residual length of proximal small intestine was a protective factor for postoperative complications after enterostomy in NEC infants (OR=0.764, 95%CI: 0.648-0.901, P=0.001), but stage Ⅲ NEC was a risk factor (OR=1.042, 95%CI: 1.004-5.585, P=0.017). Conclusions: The incidence of postoperative complications is high, and the prognosis is poor in children with early-onset NEC enterostomy. The residual length of proximal enterostomy is a protective factor for postoperative complications of NEC enterostomy, but stage Ⅲ NEC is a risk factor.

[Analysis of glucose changes in adults with type 1 diabetes mellitus within 1 year after using mobile APP decision support system].

Objective: To analyze the changes in glucose after using a decision support system (DSS) of a smartphone mobile application (APP) in adults with type 1 diabetes mellitus (T1DM). Methods: In the intervention study, the data (including general information at the time of registration) of adult T1DM patients enrolled in the Chinese T1DM Registration Management Project and registered with TangTangQuan® APP were collected. Within 1 year after registration, fasting blood glucose, pre-prandial and postprandial blood glucose at the three meals, blood glucose before bedtime and in nocturnal time were collected every 3 months. Frequencies of total recorded glucose values and proportion of different ranges of glycemia were also collected and analyzed, including the range between 3.9-7.8 mmol/L (Euglycemia), ranged below 3.9 mmol/L (Hypoglycemia) and range above 13.9 mmol/L (hyperglycemia). The patients were divided into 3 groups according to the daily use frequency of DSS (Low/Moderate/High frequency groups). The changes in point blood glucose, the proportion of hyperglycemia and hypoglycemia over time were compared among different groups, as well as the baseline characteristics and glucose characteristics of patients. Results: A total of 629 eligible T1DM patients were included, including 216 (34.3%) males and 413 (65.7%) females, aged (31.5±10.8) years, and disease duration [M(Q1, Q3)] of 1.2 (0.1, 7.4) years. There were 239, 189 and 201 patients in the low, moderate and high frequency groups, respectively. Significant differences were observed among the three groups in all timepoints of self-monitoring blood glucose except for the glucose before bedtime from 10 to 12 months after registration (all P values<0.05), and the glucose level at each point in the high frequency group was lower than that in the other two groups. In the first three months after registration, there was no difference in the proportion of hypoglycemia among the three groups (P>0.05). However, from 10 to 12 months after registration, the proportion [M(Q1, Q3)] of hypoglycemia [3.34% (0.85%, 7.40%), 3.00% (0.78%, 6.17%), 1.81% (0.37%, 4.69%)] (P=0.022) between groups (from low to high frequency groups) and hyperglycemia [4.04% (0, 12.16%), 1.88% (0, 7.80%), 0.81% (0, 3.87%)] (P=0.001) were significantly different. Conclusions: The DSS function of mobile APP is helpful to the glucose management of adult patients with T1DM within 1 year after registration. The average blood glucose in adults with T1DM decreased, and the proportions of hyperglycemia and hypoglycemia were also reduced.

[Related factors for microalbuminuria in adult type 1 diabetes patients of short disease duration].

Objective: To investigate related factors for microalbuminuria in adult type 1 diabetes (T1D) patients of short disease duration (less than 5 years), and provide evidence for prevention of early diabetic kidney disease in this population. Methods: All adult patients enrolled in the Guangdong T1D translational medicine study between 2011 and 2017 with a disease duration of less than 5 years were included in this analysis. At enrollment, patients' demographic and clinical data were documented, and blood and urine samples were collected for the measurements of blood lipids, glycated hemoglobin A1c and urine albuminuria. Insulin resistance was evaluated by estimated glucose disposal rate (eGDR). Patients were categorized into groups based on urine albumin creatitine ratio (UACR): normoalbuminuric group (UACR<30 mg/g) and microalbuminuric group (UACR≥30 mg/g). Stepwise multivariate linear regression analysis was used to analyze risk factors for microalbuminuria in adult T1D patients of short disease duration. Results: A total of 384 patients were included in this analysis, and 51.3% (197/384) of which was female. The onset age of patients was (24.6±12.5) years, with a disease duration of 2.1(0.6, 3.5) years, body mass index of (19.8±3.2) kg/m(2), waist hip ratio of 0.85±0.21, and glycated hemoglobin A1c of (9.8±3.3)% at enrollment. Microalbuminuria occurred in 62 patients (16.1%). Multivariate linear analysis showed that higher glycated hemoglobin A1c, higher systolic blood pressure and more severe insulin resistance were related factors for microalbuminuria (t=2.322, 2.868 and -2.373, respectively, all P<0.05). Conclusions: Microalbuminuria was not rare in adult T1D patients of short disease duration. Inadequate glycemic control and insulin resistance were independent related factors for microalbuminuria in this population.

[The effect of mobile application based interactive peer support on glycemic control in patients with type 1 diabetes mellitus].

Objective: To evaluate the effect of mobile application (APP) based interactive peer support on glycemic control in patients with type 1 diabetes mellitus (T1DM). Methods: The data of the present study were from the largest mobile APP platform for patients with T1DM in China, Tangtangquan. Patients with T1DM who has registered in the APP for at least 1 year and had completed data entry were recruited. According to the monthly interaction index during the first year of APP registration (including four indicators: praise, comment, posting and collection), the eligible patients were divided into the high-interaction group and the low-interaction group. The changes from baseline of self-blood glucose monitoring frequency (SMBG), glycosylated hemoglobin (HbA1c), incidence of hyperglycemia and incidence of hypoglycemia were compared between the two groups after one year of using the APP. Results: A total of 238 patients with T1DM with an age of (27±8) years were included. Among them, 77.3% (184/238) were female. The baseline SMBG [the low-interaction group (1.71±1.14) times/day vs. the high-interaction group (1.82±1.15) times/day] and HbA1c [the low-interaction group (6.72±0.99)% vs. the high-interaction group (6.76±1.04)%] were comparable between the two groups. After one year use of the APP, the frequency of SMBG in the high-interaction group was significantly higher than that in the low-interaction group [ΔSMBG (0.59+2.06) times/d vs. (0.08+1.69) times/d, t=4.280, P=0.04), and the reduction of HbA1c was more obvious in the high-interaction group [ΔHbA1c (-0.40+1.10)% vs. (-0.06+1.13)%, t=5.651, P=0.018] than in the lower-interaction group. The incidence of hyperglycemia in the high-interaction group was significantly lower than that in the low-interaction group [13.19(6.22,23.19)% vs. 17.69(10.56,30.49)%, Z=2.850, P=0.005]. There was no significant difference in the incidence of hypoglycemia between the two groups [4.62(2.14, 8.03)% vs. 4.83(2.06, 8.87)%, Z=1.276, P=0.204]. The correlation analysis showed that interaction index was significantly associated with the reduction of HbA1c and incidence of hyperglycemia. Conclusion: Participation in interactive peer education via mobile APP may be beneficent for glycemic control in patients with T1DM.

[Clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients].

Objective: To describe the clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients. Methods: Medical records of newly diagnosed diabetes onset with ketosis or ketoacidosis in the Third Affiliated Hospital of Sun Yat-sen University between January 2011 and August 2016 were reviewed. Patients aged 18 years or older were included, while other diseases that may cause urinary ketoacidosis and special types of diabetes were excluded. Patients were classified as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) or diabetes mellitus untyped based on discharged diagnosis, and groups were compared for differences in clinical profiles. Then the patient's medication, final diagnosis and outcome within 2 years of discharge were tracked through the inpatient and the outpatient medical record systems. Receiver operating characteristics (ROC) curves were analyzed to check the ability of clinical indicators such as onset age, body mass index (BMI) and C-peptide to discriminate T1DM from T2DM, and to find the best diagnostic cut-off points. Results: A total of 123 patients (88 males) were enrolled [with a mean age of (41.1±13.6) years old], with 37 patients (30.1%) diagnosed as T1DM, 60 patients (48.8%) diagnosed as T2DM and 26 patients (21.1%) diagnosed as Untyped. There was a statistically significant difference in onset age, BMI, blood pressure, blood gas pH and bicarbonate, blood lipids, fasting, 0.5 h and 2 h C-peptide level, any diabetic antibody and anti-glutamic acid decarboxylase antibody (GADA) positive rate, combined fatty liver ratio and family history among the three groups (all P<0.05). ROC curve analysis was performed on patients diagnosed with T1DM (n=36) and T2DM (n=87) after 2 years follow-up, and the area under the curve (AUC) of onset age, BMI, fasting C-peptide, 0.5 h and 2 h C-peptide was 0.735, 0.813, 0.855, 0.898, and 0.882, respectively. Conclusion: The ROC curve analysis indicates that C-peptide, onset age and BMI can provide effective diagnostic value, and the diagnostic value of C peptide is better than BMI and onset age.

[Awareness of preconceptional care and its related factors in women of child-bearing age with type 1 diabetes].

Objective: To investigate the awareness of preconception care among women of child-bearing age with type 1 diabetes (T1DM) and their self-management status, in order to provide evidence for establishment of management pathway for women with T1DM in pregnancy in China. Methods: This cross-sectional survey recruited female participants of child-bearing age from the cohort of Guangdong Type 1 Diabetes Translational Medicine Study conducted between June 2011 and December 2017. The participants were asked to fill out a questionnaire on the awareness of preconception care, their frequency of self-monitoring of blood glucose (SMBG) and other related variables. Chi-squared test or chi-squared test for trend was used in comparisons of categorical variables, and logistic regression analysis was performed to assess associated factors. Results: Totally, 441 women of child-bearing age with T1DM were investigated. The results show that their awareness of preconception care was poor (15.42%, 68/441). Higher educational level (χ(2trend)=3.990, P=0.046), experience of post-diabetes education evaluation (P<0.001), and better coverage of different modules in diabetes education (survival skills: χ(2)=7.525, P=0.004; basic knowledge: χ(2)=8.598, P=0.002; advanced knowledge: P<0.001) were associated with better awareness of preconception care. The average frequency of SMBG in these participants was 0.29 (0.14, 2.00) times per day, and only 8.5% (37/435) of them reached the frequency (≥4 times per day) recommended by guidelines. Moreover, 21.1% (92/435) of them hardly ever performed SMBG. Conclusion: Child-bearing age women with T1DM in Gunangdong had poor awareness of preconception care, with a much lower SMBG frequency than recommendation.

[Association of insulin resistance with dyslipidemia in adults with type 1 diabetes].

Objective: To investigate the relationship between insulin resistance (IR) and dyslipidemia in adults with type 1 diabetes (T1DM) and provide more insights on diabetes-related cardiovascular disease management. Methods: A cross-sectional study recruiting patients from Guangdong T1DM Translational Study cohort was conducted between 2011 and 2017. The patients aged ≥18 years, with a diabetes duration of ≥1 year were enrolled in the study. Plasma lipid profile data of eligible patients, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were collected and their relationships with insulin resistance were analyzed. IR in these adults with T1DM was estimated by glucose disposal rate (eGDR) calculated by a model published previously. Patients with eGDR lower than 25 percentiles were grouped as severe IR, otherwise non-severe IR. Results: In total, 499 eligible patients were studied, among which 274 were women (54.9%). The level of eGDR was 8.43 (6.11, 10.63) mg kg(-1) min(-1) and the overall incidence of lipid disorders was 65.3% (326/499) in the study population. The result showed that eGDR was correlated with TC, TG, HDL-C and LDL-C (r=-0.163, -0.303, 0.170 and -0.150, respectively, all P<0.05). After adjusting for gender, age and diabetes duration, eGDR was still associated with TG, TC and LDL-C (all P<0.05). Stepwise multiple linear regression analysis showed that gender (female), elevated TC and declined HDL-C were independent factors associated with the severity of IR (t=5.651, 5.823 and 2.908, respectively, all P<0.05). Conclusions: IR is associated with dyslipidemiain in adults with T1DM. Elevated TC and decreased HDL-C are independent associated factors for insulin resistance.

Pathogenic Nocardia cyriacigeorgica and Nocardia nova Evolve To Resist Trimethoprim-Sulfamethoxazole by both Expected and Unexpected Pathways.

Nocardia spp. are Gram-positive opportunistic pathogens that affect largely immunocompromised patients, leading to serious pulmonary or systemic infections. Combination therapy using the folate biosynthesis pathway inhibitors trimethoprim (TMP) and sulfamethoxazole (SMX) is commonly used as an antimicrobial therapy. Not surprisingly, as antibiotic therapies for nocardiosis can extend for many months, resistance to TMP-SMX has emerged. Using experimental evolution, we surveyed the genetic basis of adaptation to TMP-SMX across 8 strains of Nocardia nova and 2 strains of Nocardia cyriacigeorgica By employing both continuous experimental evolution to provide longitudinal information on the order of changes and characterization of resistant endpoint isolates, we observe changes that are consistent with modifications of two enzymes of the folate biosynthesis pathway: dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) (FolP), with the mutations often being clustered near the active site of the enzymes. While changes to DHFR and DHPS might be expected, we also noted that mutations in a previously undescribed homolog of DHPS (DHPS2 or FolP2) that was annotated as being "nonfunctional" were also sufficient to generate TMP-SMX resistance, which serves as a cautionary tale for the use of automated annotation by investigators and for the future discovery of drugs against this genus. Additionally, folP2 overlapped glucosyl-3-phosphoglycerate synthase. Remarkably, an adaptive frameshift mutation within the overlapping region resulted in a new in-frame fusion to the downstream gene to produce a potentially new bifunctional enzyme. How a single potentially bifunctional DHPS2 enzyme might confer resistance is unclear. However, it highlights the unexpected ways in which adaptive evolution finds novel solutions for selection.

RETRACTED: Modulation of macrophage phenotype through controlled release of interleukin-4 from gelatine coatings on titanium surfaces.

Pro-inflammatory phenotype (M1) macrophages initiate angiogenesis, while their prolonged activation can induce chronic inflammation. Anti-inflammatory phenotype (M2) macrophages promote vessel maturation and tissue regeneration. Biomaterials which can promote M2 polarisation after appropriate inflammation should enhance angiogenesis and wound healing. Herein, Interleukin-4 (IL-4), an anti-inflammatory cytokine, was adsorbed onto a titanium surface. Then, a genipin cross-linked gelatine hydrogel was coated onto the surface to delay IL-4 release. The cross-linking degree of the hydrogel was modulated by the different amount of genipin to control release of IL-4. When 0.7 wt% (weight %) genipin was used as a cross-linker, the sample (GG07-I) released less IL-4 within the first several days, followed by a sustained release time to 14 d. Meanwhile, the release rate of IL-4 in GG07-I reached a peak between 3 d and 7 d. In culture with macrophages in vitro, GG07-I and GG07 exhibited good cytocompatibility. The phenotypical switch of macrophages stimulated by the samples was determined by FACS, ELISA and PCR. Macrophages cultured with GG07-I, GG07 and PT were firstly activated to the M1 phenotype by interferon-gamma (IFN-γ). Then, due to the release of IL-4 in 5 to 7 d, GG07-I enhanced CD206, increased the secretion and gene expression of M2 marker, such as interleukin-10 (IL-10), arginase-1 (ARG-1) and platelet derived growth factor-BB (PDGF- BB). GG07-I prompted the switch from M1 to M2 phenotype. Those appropriate secretion of cytokines would benefit both vascularisation and osseointegration. Thus, the biomaterial directing inflammatory reaction has good prospects for clinical treatments.

[Glycemic control and its associated factors in children and adolescents with type 1 diabetes mellitus].

Objective: To explore the factors associated with glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). Methods: Subjects were enrolled from the Guangdong Type 1 Diabetes Translational Medicine Study between June 2011 and August 2017. Patients with T1DM aged less than 18 years and treated with CSII for at least 6 months were included. Demographic data and clinical information on self-monitoring of blood glucose (SMBG), glycosylated hemoglobin (HbA1c) and insulin treatment were collected. Participants were categorized based on HbA1c levels as sufficient control group (HbA1c<7.5% ) and insufficient control group ( HbA1c≥7.5%). A multivariate logistic regression model was used to examine the factors associated with glycemic control. Results: A total of 142 participants (76 females, 66 males) with a median age of 13.0 (9.9, 15.0) years and a median disease duration of 3.0 (1.6, 5.0) years were enrolled. HbA1c was (8.2±2.0)% and 41.55%(59/142) of patients achieved the target for HbA1c. The frequency of SMBG was 5.0 (2.0, 8.0) and 3.0 (1.0, 4.0) tests per day (P<0.001), and the frequency of hypoglycemia was 2.0 (0.8, 4.0) and 1.0 (0, 2.0) times per week (P=0.003) in sufficient control group and insufficient control group, respectively. Sufficient glycemic control (HbA1c <7.5%) was associated with the frequency of SMBG (OR=1.238, 95% CI: 1.088-1.409, P=0.001). Conclusion: A higher frequency of SMBG is one of the key factors to achieve sufficient glycemic control among children and adolescents with T1DM treated with CSII.

Differential increments of basal glucagon-like-1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter-individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes.

AIM: To elucidate the effects of rs2289669, an intron variant of the SLC47A1 gene, on glucose response to metformin in Chinese people with newly diagnosed Type 2 diabetes. METHODS: Rs2289669 was genotyped, using Sequenom, in 291 participants receiving 48 weeks of metformin monotherapy. The changes in HbA1c were compared among rs2289669 genotypes, and associations with rs2289669 were evaluated using linear regression analysis. RESULTS: We found that, compared with participants with a homozygous G allele, those carrying the minor A allele had significantly greater HbA1c reduction and greater increases in basal glucagon-like peptide-1 concentration. Regression analysis showed that there was a significant association between rs2289669 and the glucose response to metformin after adjusting for confounding factors, except for changes in basal glucagon-like peptide-1, for which an association was not observed. CONCLUSIONS: Our findings suggest that rs2289669 might help predict the glycaemic response to metformin in Chinese people newly diagnosed with Type 2 diabetes, and that differential increases in basal glucagon-like peptide-1 concentration among rs2289669 genotypes might be associated with inter-individual response to metformin.

A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes.

AIMS: To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. METHODS: The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse-coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). RESULTS: Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs -0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). CONCLUSIONS: Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364).

[Value of CT imaging in the differentiation of gastric leiomyomas from gastric stromal tumors].

Objective: To explore the application value of CT imaging in differentiating gastric stromal tumors (GST) from gastric leiomyomas (GLMs). Methods: CT images of patients with GST (n=65) or GLMs (n=13, maximum diameter of tumor ≤5 cm) proved by surgery and pathology were retrospectively analyzed. The tumor size, location, contour, growth pattern, degree and pattern of enhancement, calcification, necrosis, surface ulceration, lymph nodes, and patient clinical data were evaluated by two independent reviewers. Receiver operating characteristic (ROC) curves were employed to assess the measurement and calculation parameters in the differentiation of GST and GLMs. Results: Between the GST and GLMs groups, there was no statistically significant difference in the contour, growth pattern, calcification, surface ulceration, and patient's sex (P>0.05). CT values of in plain scans, degree of enhancement in arterial phase (DE1), size, location and pattern of enhancement were found to be different between GST and GLMs (P<0.05). When the cutoff value of the maximum tumor diameter was 3.2 cm, the area under ROC curve, sensitivity and specificity were 0.707, 92.3%(12/13) and 60.6%(40/66), respectively. When the cutoff value of age was 59 years, the area under ROC curve, sensitivity and specificity were 0.773, 92.3% (12/13) and 46.2% (30/65), respectively. Taking the cutoff value of 10.9 HU as the degree of enhancement in arterial phase (DE1), the area under ROC curve, sensitivity and specificity were 0.774, 84.6% (11/13) and 77.3% (51/66), respectively. Using a cutoff value of 30.3 HU, the sensitivity, specificity, and the area under ROC curve were 84.6% (11/13), 65.2% (43/66), and 0.731, respectively. Conclusions: CT examination in addition to clinical data can be very helpful for the differential diagnosis of GLMs from GSTs in maximum diameter ≤5 cm.

[Effect of two different acellular lung matrices on α-SMA expression in A549 cells].

Objective: To explore the effect of acellular normal and fibrotic lung matrices on alpha smooth muscle actin (α-SMA) expression in human lung adenocarcinoma cell line A549. Methods: Twenty adult SD rats were randomly divided into normal group and idiopathic pulmonary fibrosis(IPF)group (n=10 each). The pulmonary fibrosis was induced by Bleomycin. Normal and fibrotic decellularized lungs were made, then sections with 500 µm thick were cut by a standard Vibratome. None scaffold was set as control group. A549 cells were seeded dropwise into different slices (normal and fibrotic scaffolds), and cultured for one week in vitro. The expression of α-SMA was measured by immunofluorescence staining and quantitative real time polymerase chain reaction (qRT-PCR). Results: In control group, the expression of α-SMA protein was positive in A549 cells by immunofluorescence staining. However, it expressed weakly both in normal and fibrotic scaffold group, and the fluorescence intensity in fibrotic scaffold group was significant lower than that in normal group (P<0.05). The relative expression amount of α-SMA mRNA in normal and fibrotic scaffold group were (0.70±0.11) and (0.55±0.12), which were significant lower than that of control group (1.28±0.21) (P<0.05). Moreover, the relative expression of α-SMA mRNA in fibrotic scaffold group was decreased compared to that in normal scaffold group (P<0.05). Conclusions: Acellular normal and fibrotic lung scaffold can downregulate the expression of α-SMA in human lung adenocarcinoma cell line A549. It may inhibit the movement of A549 cells in acellular normal and fibrotic lung matrices, especially in acellular fibrotic lung scaffold.

[Association between SORCS1 rs1416406 and therapeutic effect of exenatide].

Objective: To study the relationship between SORCS1 gene rs1416406 and efficiency of exenatide. Methods: Between August 2010 and August 2012, a hundred and one newly diagnosed patients with type 2 diabetes mellitus (T2DM) were from CONFIDENCE study covering 25 university-affiliated hospitals in 13 provinces of China. All patients received exenatide treatment for 48 weeks. Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), body mass index (BMI), oral glucose tolerance test (OGTT) glucose and insulin levels were measured before and after therapy. ß-cell function was assessed by fasting proinsulin/insulin (PI/I), disposition index (DI) and acute insulin response (AIR). SORCS1 gene rs1416406 was genotyped by improved multiple ligase detection reaction. The relationship between rs1416406 and the glucose-lowering effect as well as ß-cell function improvement of exenatide was analyzed by multiple linear regression. Results: There were statistically significant differences of HbA1c, FPG, 2 h plasma glucose (2 h PG), ß-cell function (PI/I, DI and AIR) and changes of PI/I in three genotypes (GG, GA, AA) of rs1416406 between baseline and 48-week therapy of exenatide (all P<0.05). No statistically significant difference was found in changes of HbA1c, FPG, 2 h PG, DI, AIR except for PI/I, after stratifying by genotypes of rs1416406. Multiple linear regression analysis showed rs1416406 was significantly associated with the PI/I change (P<0.05) after adjustment of age, sex, baseline BMI, HbA1c and PI/I. Conclusion: SORCS1 gene rs1416406 was associated with the PI/I improvement induced by exenatide. Patients carrying GG genotype had greater reduction in PI/I after exenatide treatment as compared with those carrying allele A. The results suggests that the newly diagnosed T2DM patients with GG genotype might obtain more benefit from the early treatment of exenatide .

[Insulin dose analysis during pregnancy in type 1 diabetic patients treated with insulin pump therapy].

Objective: To analyze the insulin dose of type 1 diabetic patients who treated with insulin pump therapy during pregnancy in order to explore the features of these patients' insulin requirement during gestation. Methods: A total of 12 well-controlled type 1 diabetic women patients who were treated with insulin pump therapy before and during gestation without any adverse pregnancy outcomes from June 2011 to December 2014 were selected from Guangdong Type 1 Diabetes Translational Medicine Study and included in the study. Demographic data, hemoglobin A1c (HbA1c) before pregnancy and before delivery, insulin dose, hypoglycemia episodes and pregnancy outcomes were collected to analyze the insulin dose of preconception, the 1(st,) the 2(nd) and the 3(rd) trimester to analyze the requirement of insulin before and throughout pregnancy. Results: Subjects were (26.9±2.6) years old, with a diabetes duration of (6.6±4.4) years. HbA1c were (5.8±0.5)% before conception. The preconception total daily insulin dose, basal rate, bolus and bolus proportion were (0.60±0.18)U/kg, (0.28±0.10)U/kg, (0.32±0.13)U/kg and (54.8±12.9)%, respectively. Both of the insulin dose indexes mentioned above changed significantly in different trimesters compared with that in preconception (P value was <0.001, 0.034, <0.001 and <0.001, respectively). The total daily insulin dose, bolus and bolus proportion kept increasing during pregnancy. In the 1(st,) the 2(nd) and the 3(rd) trimester, the total daily insulin dose rose by 0.2%, 45.4% and 72.7%, respectively, the bolus rose by 8.0%, 72.2% and 106.8%, respectively, and the bolus proportion rose by 8.0%, 16.8% and 19.0%, respectively. While the basal rate decreased by 9.0% in the 1(st) trimester and rose by 14.1% and 32.9% in the 2(nd) and 3(rd) trimester, respectively. Conclusions: In well-controlled pregnant women with type 1 diabetes mellitus, insulin requirement increased throughout pregnancy. Most of the increased insulin requirement was attributed to the bolus instead of the basal rate. When titrating the dose of insulin for the pregnant women complicated with type 1 diabetes mellitus, the physicians should consider their features of insulin requirement so as to optimize the glycemic control.

[Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism].

Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg-1·d-1 exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group. Additional 6 mice were also selected as control group. Body weight, fasting blood glucose were recorded. Serum triglyceride (TG), total cholesterol (TC), insulin and skeletal muscle triglyceride levels were measured by enzyme-linked immunosobent assay (ELISA). Oil red O staining was used for morphologic changes of frozen sections from skeletal muscle. The protein levels of lipid metabolic pathway mediated by AMP-activated protein kinase (AMPK) and insulin signailing pathway were determined by Western blot. Results: Compared with mice in HFD group, exendin-4 significantly decreased body weight[(37.68±1.80) vs (46.03±5.00) g, P<0.025], fasting blood glucose[(5.40±0.33) vs (7.65±1.92) mmol/L, P<0.025], serum TG[(37.78±7.14) vs (80.76±34.22) mg/dl, P<0.025], TC[(180.13±18.75) vs (217.57±22.52) mg/dl, P<0.025], insulin[(0.58±0.01) vs (1.67±1.23) ng/ml, P<0.025]and skeletal muscle TG levels[(9.84±1.08) vs (19.35±7.44) mg/g, P<0.025]of obese mice. Oil red O staining revealed that exendin-4 alleviated the accumulation of larger lipid droplets in skeletal muscle. The protein expressions of lipolysis and lipid oxidation mediated by AMPK and insulin signailing pathway were up-regulated, and the protein expressions of lipogenesis mediated by AMPK were down-regulated after intervention of exendin-4. Conclusion: Exendin-4 reduces lipid deposition and insulin resistance in skeletal muscle of HFD-induced obese mice via activating AMPK and up-regulating insulin signailing pathway.

[Insulin regimes and impact on glycemic control in patients with type 1 diabetes].

Objective: To describe the insulin regimens and their associations with glycemic control and to explore factors associated with intensive insulin therapy. Methods: Patients with type 1 diabetes (T1DM) were recruited from Guangdong Type 1 Diabetes Mellitus Translational Medicine Study which was conducted in 16 centers in Guangdong province. The demographic and clinical data were collected. Patients were grouped according to different insulin regimens: insulin pump (R1), basal insulin plus regular insulin or short-acting insulin (R2), insulin injection 1-3 times per day (R3). Distribution of insulin regimens and the relationships between insulin regimens and hemoglobin A1c (HbA1c) were described. Multivariate logistic regression was used to identify factors associated with intensive insulin therapy. Results: A total of 1 421 patients with the age of 27.8 (19.4, 38.3) years and a duration of T1DM of 3.3 (0.5, 7.1) years were recruited. There was 12.3% of patients in R1 (n=175), 35.5% in R2 (n=504), and 52.2% in R3 (n=742), respectively. HbA1c was 8.0 (6.8, 9.3)%, 8.9 (7.1, 11.8)%, and 9.2 (7.5, 11.4)% in R1, R2, R3, respectively, and it was associated with insulin regimens (P<0.001). HbA1c target rate was 32.3%, 21.1%, 17.8% in R1, R2, R3, respectively (P=0.002). Older age (OR=1.01, P=0.027), higher education level (college or above) (OR=1.56, P=0.003), and higher household income (>30 000 yuan per year per person)(OR=1.45, P=0.009) were associated with intensive insulin therapy in adult patients. Conclusions: The study suggested that insulin therapy need to be optimized in patients with T1DM. The optimization of insulin regimens and diabetes education may be helpful for improvement of glycemic control.

Transient hypoxia reprograms differentiating adipocytes for enhanced insulin sensitivity and triglyceride accumulation.

OBJECTIVES: To investigate the impact of transient (2-4 h) hypoxia on metabolic reprogramming of adipocytes. METHODS: The impact of transient hypoxia on metabolic reprogramming was investigated in 3T3-L1 cells before and after differentiation. Glucose uptake, fatty acid oxidation, lipolysis and mitochondria were examined to determine the hypoxia effects. Preadipocytes were exposed to transient hypoxia (4 h day(-1)) in the course of differentiation. Insulin sensitivity and triglyceride (TG) accumulation was examined in the cells at the end of differentiation to determine the reprogramming effects. AMP-activated protein kinase (AMPK) activity and gene expression were determined by quantitative reverse transcriptase-PCR and western blotting in search for mechanism of the reprogramming. RESULTS: In acute response to hypoxia, adipocytes exhibited an increase in insulin-dependent and -independent glucose uptake. Fatty acid ß-oxidation and pyruvate dehydrogenase activity were decreased. Multiple exposures of differentiating adipocytes to transient hypoxia enhanced insulin signaling, TG accumulation and expression of antioxidant genes in differentiated adipocytes in the absence of hypoxia. The metabolic memory was associated with elevated AMPK activity and gene expression (GLUT1, PGC-1α, PPARγ, SREBP, NRF-1, ESRRα, LPL). The enhanced insulin sensitivity was blocked by an AMPK inhibitor. CONCLUSIONS: Repeated exposure of differentiating adipocytes to transient hypoxia is able to reprogram the cells for increased TG accumulation and enhanced insulin sensitivity. The metabolic alterations were observed in postdifferentiated cells under normoxia. The reprogramming involves AMPK activation and gene expression in the metabolic pathways in cytosol and mitochondria.