Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Background@#Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. @*Methods@#Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. @*Results@#Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. @*Conclusion@#Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

Postprandial proximal gastric acid pocket and its association with gastroesophageal acid reflux in patients with short-segment Barrett's esophagus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett's esophagus (BE).@*METHODS@#Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out.@*RESULTS@#The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH.@*CONCLUSIONS@#In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.

Analysis of external quality control results of iodine deficiency disorders network laboratory in Ningxia from 2002 to 2011 / 中国地方病学杂志

Objective To analyze the examination results of external quality assessment (EQA),at all levels of iodine deficiency disorders (IDD) network laboratories in Ningxia Province and to further standardize and improve the laboratory,and to provide a reliable laboratory quality assurance for surveillance and control of IDD.Methods The examination results of EQA at all levels of IDD laboratories in Ningxia Province were statistically analyzed in accordance with the National Reference Laboratory (NRL) of IDD (2002-2011).Results Laboratory hardware equipment and technology at all levels met the testing requirements,and qualified rate of quality control increased year by year.Both of the response rate and qualification rate of urine iodine laboratories at provincial level were 100％ in the past decade.From 2005 on,the response rate of city laboratories had been 100％,and the qualification rate had been 100％ since 2007.The response rate and qualification rate of salt iodine laboratories at both the provincial level and the city level were 100％ in the past decade.The response rate of salt iodine laboratories at county level had been 100％ since 2004,and the qualification rate had been 100％ since 2009.Salt iodine and urinary iodine levels were fully qualified for the past three years at provincial,municipal and county levels.Conclusions All levels of IDD network laboratory in Ningxia Province runs good,EQA is fully qualified,and is able to provide a reliable laboratory quality assurance for surveillance and control of IDD.

Possible role of mast cells and neuropeptides in the recovery process of dextran sulfate sodium-induced colitis in rats / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To clarify the role of mast cells and neuropeptides substance P (SP), somatostatin (SS), and vasoactive intestinal peptide (VIP) in dextran sulfate sodium (DSS)-induced colitis in rats.</p><p><b>METHODS</b>Experimental colitis was induced in Sprague-Dawley rats (180-200 g, n=20) by oral ingestion of 4% (w/v) DSS in drinking water for 7 days. Control rats (n=5) drank water and were sacrificed on day 0. Mast cell number, histamine levels in whole blood and tissue, tissue levels of SP, SS and, VIP in the distal colon of the rats were measured on day 8, day 13, and day 18 of experimentation.</p><p><b>RESULTS</b>Oral administration of 4% DSS solution for 7 days resulted in surface epithelial loss and crypt loss in the distal colon. Mast cell count increased on day 8 (1.75±1.09/mm vs. 0.38±0.24/mm, P<0.05) and day 13 (1.55±1.01/mm vs. 0.38±0.24/mm, P<0.05) after DSS treatment. Whole blood histamine levels were increased on day 8 (266.93±35.62 ng/mL vs. 76.87±32.28 ng/mL, P<0.01) and gradually decreased by day 13 and day 18 after DSS treatment. Histamine levels in the distal colon were decreased on day 8 (1.77±0.65 ng/mg vs. 3.06±0.87 ng/mg, P<0.05) and recovered to control levels by day 13 after DSS treatment. SP level in the distal colon gradually increased and were raised significantly by day 13 (8777.14±3056.14 pg/mL vs. 4739.66±3299.81 pg/mL, P<0.05) after DSS treatment. SS and VIP levels in the distal colon were not changed.</p><p><b>CONCLUSIONS</b>Mast cell degranulation followed by histamine release may play an important role in the pathogenesis of colitis induced by DSS. SP may be a significant substance in the progression of inflammation and the recovery process of DSS-induced colitis.</p>

Family-based association study of a variable number of tandem repeat polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population.</p><p><b>METHODS</b>A total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis.</p><p><b>RESULTS</b>The repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481).</p><p><b>CONCLUSION</b>Our data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.</p>

Glycemic variability in insulin treated type 2 diabetes with well-controlled hemoglobin A1c and its response to further treatment with acarbose / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glycemic variability, an HbA1c-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus (T2DM) with HbA1c < 6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose.</p><p><b>METHODS</b>Eighty-six T2DM patients who used premixed insulin analogue (insulin aspart 30) twice daily and had HbA1c < 6.5% and 20 controlled subjects with normal glucose regulation (NGR) were monitored using the continuous glucose monitoring (CGM) system. The mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD) were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level < 3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups: low-MAGE group with MAGE < 3.4 mmol/L (L-MAGE) and high-MAGE group with MAGE ≥ 3.4 mmol/L (H-MAGE). H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system.</p><p><b>RESULTS</b>After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR (P < 0.01). Twenty-four percent (n = 11) in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% (n = 2) in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night (hypoglycemic events: 24% vs. 5%, χ(2) = 6.40, P < 0.01). MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value (r = -0.32 and 0.26, respectively, P < 0.05). After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased (40%, P < 0.01, and 15%, P < 0.05, respectively), but remained higher than in the subjects with NGR (P < 0.05); 2% (n = 1) had a total of 1 hypoglycemic event, incidence significantly decreased (2% vs. 24%, χ(2) = 9.61, P < 0.01).</p><p><b>CONCLUSIONS</b>CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbA1c in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.</p>

Changes of mast cells and gut hormones in rats with TNBS-induced ulcerative colitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of mast cells and gut hormones and their interactions in TNBS-induced ulcerative colitis.</p><p><b>METHODS</b>Rat models of ulcerative colitis were established by a single intracolonic injection of 100 mg/kg TNBS (in 0.3 ml 50% ethanol). At 0, 6, 11, 16, 21 days after TNBS injection, the rats were sacrificed to determine the count of the mast cells. Histamine level in the whole blood, and the levels of histamine, substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SS) in the distal colons were measured by fluorimetry or radioimmune assay. Immunofluorescence double staining was used to observe the relationship of the mast cells with SP, VIP, and SS positive nerve fibers.</p><p><b>RESULTS</b>On day 6 after TNBS injection, obvious ulcers occurred in the distal colon of the rats with significantly increased histamine level in the whole blood (P<0.05) but significantly decreased colonic histamine levels (P<0.05). The histamine levels in the whole blood and distal colon gradually recovered the normal levels. The mast cells significantly increased on day 16 (P<0.05) and maintained the high level till day 21. The distribution of mast cells was altered after TNBS injection, and the cells were found to aggregate in the myenteric region. SP levels in the distal colon significantly increased on day 11 (P<0.05) and maintained the high level till day 21. Immunofluorescence double staining revealed numerous mast cells close to the SP- and VIP-positive nerve fibers at different time points after TNBS injection. VIP positivity and the number of VIP-positive nerve fibers in the myenteric region were markedly increased, but no mast cells were observed in association with SP- and VIP-positive nerve fibers. The distribution of MC was not found to associate with the SS-positive nerve fibers.</p><p><b>CONCLUSION</b>The mast cells and histamine released by them, as well as parasecretion of SP and VIP, participate in tissue damage by TNBS-induced colitis. Bidirectional neuroimmunomodulation of the mast cells, SP and VIP have important effect on the development of TNBS-induced colitis.</p>

Clinical analysis of completion pneumonectomy for pulmonary disease / 中华外科杂志

<p><b>OBJECTIVE</b>Completion pneumonectomy (CP) is widely known to be associated with a high morbidity and mortality. However, in certain instances, CP offers the only chance for a cure. Now to explore the indications, prevention and management of complications as well as late outcomes of CP.</p><p><b>METHODS</b>During a period of 21 years from January 1985 to August 2006, 24 patients received CP, representing 2.3% of 1026 patients who had undergone pneumonectomy in the same period. There were 17 right and 7 left CPs done in 20 male and 4 female patients with an average age of 58 years (range from 42 to 67 years). Lung malignancy accounted for 22 of these cases in which the indication included local recurrence in 18, second primary tumors in 2 and primary malignancies that developed after right upper lobectomies for pulmonary tuberculoma and pulmonary cyst respectively in 2 cases. Benign disease was progression or recurrence of bronchiectasis in 2 cases. Before CP, 17 patients had had a lobectomy, 5 a bilobectomy, 1 sleeve lobectomy and 1 wedge resection. There were 16 of 20 lung cancer patients receiving postoperative chemotherapy and 3 with positive residues having radiotherapy. The mean interval between the two procedures was 65 months for the whole group (5.5-360) and 32 months for lung cancer patients (5.5-120). They all underwent CP, included sleeve CP in 1 patient.</p><p><b>RESULTS</b>For all patients, the previous thoracotomy incision was reopened and maneuvers such as rib resection, intrapericardial blood vessel ligation, division of the bronchus first, local application of glues and hemostatic agents, and bronchial reinforcement were routinely used. Intrapericardial route was used in 10 patients (41.7%). Two patients had right pulmonary artery injured. The operation lasted 4-7 hours, with blood loss of 300 to 3000 ml. Overall respectability, morbidity and hospital mortality were 95.8%, 29.2% and 4.2%. No intraoperative deaths occurred. There was 1 early postoperative death after 40 days from adult respiratory distress syndrome. There was no occurrence of bronchopleural fistula, and the 25% associated morbidity rate was a result of bleeding necessitating reexploration in 1 case, chronic empyema in 1 case, arrhythmia in 1 case, anemia in 1 case and fever of unknown reason in 2 cases. Actuarial 1-, 3-, 5-year survival rates from the time of completion pneumonectomy for patients with lung cancer were 77.3%, 50.0% and 29.4%. And 1-, 3-, 5-year survival rates for patients with recurrent lung cancer were 72.2%, 47.1% and 29.4%.</p><p><b>CONCLUSIONS</b>CP can be performed with an acceptable operative mortality and morbidity rate in selected patients. For patients with local recurrence, first and second primary bronchogenic carcinoma as well as benign pulmonary disease, treatment should be surgical when a less invasive procedure is not available and the patients are in good health. In addition, patients undergoing CP have a reasonable prospect for long-term survival.</p>