Increased Two-Hour Post-Load Plasma Glucose Fluctuation Corresponds with Worse Clinical Prognoses among Acute Ischemic Stroke Patients without a History of Diabetes Mellitus.

INTRODUCTION: This study aimed to evaluate the relationship between 2-h post-load minus fasting plasma glucose (2hPG-FPG) and 1-year clinical outcomes, such as death, stroke recurrence, and modified Rankin Scale (mRS) ≥2-3 among acute ischemic stroke (AIS) patients without diabetes mellitus (DM) history. METHODS: 1,214 AIS patients without DM history, obtained from ACROSS-China, were divided into 4 quartiles, based on 2hPG-FPG measurements obtained 14 days post-admission. Four models were constructed using multivariate Cox and logistic regression analyses, based on the inclusion of age, gender, trial of ORG 10172 in acute stroke treatment, NIH Stroke Scale scores (model 1), plus 10 other clinical parameters (model 2), plus newly diagnosed DM (NDDM) post-admission (model 3), plus 2hPG and FPG (model 4). Associations found from those 4 models between 2hPG-FPG and 1-year clinical outcomes were confirmed via stratification, multiplicative interaction, sensitivity, and restricted cubic spline analyses. RESULTS: The highest quartile of 2hPG-FPG, after adjusting for variables, such as stroke severity (model 2), was independently associated with death, stroke recurrence, and mRS ≥2-3 (odds ratio [OR] = 3.95, 2.96, 4.15, and 4.83, respectively, all p < 0.0001). Increased 2hPG-FPG remained independently associated with mRS ≥2-3 in models 3-4, as well as increased mRS ≥2 under stratification analyses among both non-NDDM and NDDM patients. CONCLUSION: 2hPG-FPG is a relatively specific indicator of poorer 1-year clinical prognoses among AIS patients, independent of NDDM, 2hPG, and FPG post-hospital admission. Therefore, the oral glucose tolerance test could be a useful approach for detecting a higher likelihood for developing poorer prognoses among patients without DM history.

Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer.

BACKGROUND: The amino acid transporter SLC6A14, which transports 18 of the 20 proteinogenic amino acids, is too low to be detected in healthy normal tissues but is significantly increased in some solid cancers. However, little is known about the roles of SLC6A14 in colorectal cancer (CRC). METHODS: The mRNA and protein levels of SLC6A14 were detected using TCGA database, real-time polymerase chain reaction, western blot, and tissue microarrays, respectively. Amino acids concentration was determined by LC-MS/MS. Cell proliferation and apoptosis were determined using MTT assay and flow cytometry. Transwell invasion assay and wound healing assay were employed to analyze cell migration and invasion. The protein levels of Akt-mTOR signaling pathway and MMPs proteins were detected by western blot. RESULTS: Both of the mRNA and protein levels of SLC6A14 were upregulated in CRC tissues, and the protein levels of SLC6A14 were closely related to the tumor cells differentiation: the higher the expression of SLC6A14 was, the poorer the differentiation of the tumor cells was. Further knockdown SLC6A14 with siRNA or treatment with α-MT in CRC cell lines reduced cell proliferation and migration in vitro and inhibited xenograft tumor growth in vivo. Mechanistically, SLC6A14 was demonstrated to regulate the expression and phosphorylation of Akt-mTOR, which mediates the promoting tumor growth function of SLC6A14. Blockade of SLC6A14 with α-MT inhibited the activation of mTOR signaling. CONCLUSION: SLC6A14 was upregulated in CRC and could promote tumor progression by activating the Akt-mTOR signaling pathway, which may serve as an effective molecular target for the treatment of CRC.

Elevation of EIF4G1 promotes non-small cell lung cancer progression by activating mTOR signalling.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), as the key component of the transcription initiation factor complex EIF4F, is significantly upregulated in multiple solid tumours, including lung cancer. However, the function and mechanism of EIF4G1 in the regulation of non-small-cell lung cancer (NSCLC) remain unclear. Here, using the clinical samples and the comprehensive survival analysis platforms Kaplan-Meier plotter, we observed aberrant upregulation of EIF4G1 in NSCLC tissues; furthermore, high expression of EIF4G1 showed association with low differentiation of lung cancer cells and poor overall survival in NSCLC patients. Non-small-cell lung cancer cell line A549 and H1703 stably infected with EIF4G1 shRNA were used to determine the function of EIF4G1 in regulating cell proliferation and tumorigenesis in vitro and in vivo. The results demonstrated that EIF4G1 promoted the G1/S transition of the cell cycle and tumour cell proliferation in non-small cell lung cancer. Mechanistically, EIF4G1 was found to regulate the expression and phosphorylation of mTOR (Ser2448), which mediates the tumorigenesis-promoting function of EIF4G1. The inhibition of mTOR attenuated the EIF4G1-induced development and progression of tumours. These findings demonstrated that EIF4G1 is a new potential molecular target for the clinical treatment of non-small cell lung cancer.

Does the medical insurance system play a real role in reducing catastrophic economic burden in elderly patients with cardiovascular disease in China? Implication for accurately targeting vulnerable characteristics.

BACKGROUND: The vulnerability of cardiovascular disease (CVD) patients' health abilities, combined with the severity of the disease and the overlapping risk factors, leads such people to bear the economic burden of the disease due to the medical services. We estimated the economic burden of CVD and identified the weak link in the design of the medical insurance. METHODS: Data from 5610 middle-aged and elderly with CVD were drawn from the 2015 wave of "China Health and Retirement Longitudinal Study" (CHARLS). The recommended method of the "World Health Organization" (WHO) was adopted to calculate "catastrophic health expenditure" (CHE), "impoverishment by medical expenses" (IME), and applied the treatment-effect model to analyze the determinants of CHE. RESULTS: The incidence of CHE was 19.9% for the elderly families with CVD members, which was 3.6% higher than for uninsured families (16.3%). Families with CVD combined with > 3 other chronic diseases (38.88%) were the riskiest factor for the high CHE in the new rural cooperative medical system (NCMS). Moreover, families with members > 75 years old (33.33%), having two chronic disease (30.74%), and families having disabled members (33.33%), hospitalization members (32.41%) were identified as the high risky determinants for the high CHE in NCMS. CONCLUSIONS: Elderly with physical vulnerabilities were more prone to CHE. The medical insurance only reduced barriers to accessing health resources for elderly with CVD; however it lacked the policy inclination for high-utilization populations, and had poorly accurate identification of the vulnerable characteristics of CVD, which in turn affects the economic protection ability of the medical insurance. The dispersion between the multiple medical security schemes leads to the existence of blind spots in the economic risk protection of individuals and families.

Does the medical insurance system really achieved the effect of poverty alleviation for the middle-aged and elderly people in China? Characteristics of vulnerable groups and failure links.

BACKGROUND: We examined the physiological, household, and spatial agglomeration characteristics of the health poverty population in China. We identified weak links that affect the implementation of the medical insurance and further improve its effectiveness for health poverty alleviation. METHODS: A national representative sample from the China Health and Retirement Longitudinal Study (CHARLS) was analyzed. The WHO recommended method was adopted to calculate catastrophic health expenditure (CHE) and impoverishment by medical expenses (IME). We created a binary indicator for IME as the outcome variable and applied the treatment-effect model to analyze the determinants of IME. RESULTS: The incidence of IME was 7.2% of the overall population, compared to 20.3% of the sample households trapped in CHE. The incidence of IME enrolled in insurance schemes was 7.4% higher than that of uninsured families (4.8%). Economic level, living area, family size, age of household head, having hospitalized members, and participating in insurance were statistically significant for the occurrence of IME. CONCLUSIONS: The original poverty-promoting policies has not reached the maximum point of convergence with China's current demand for health. The overlapped health vulnerabilities exacerbated the risk of poverty among the elderly and households with high health needs and utilization. In addition, the medical insurance schemes have proven to be insufficient for protection against economic burden of poor households. So, special health needs, age, and household capacity to pay should be comprehensively considered while strengthening the connection between the disease insurance scheme with supplementary insurance.

Regulation of Insulin Resistance by Multiple MiRNAs via Targeting the GLUT4 Signalling Pathway.

BACKGROUND/AIMS: Type 2 Diabetes Mellitus (T2DM) is characterized by insulin resistance (IR), but the underlying molecular mechanisms are incompletely understood. MicroRNAs (miRNAs) have been demonstrated to participate in the signalling pathways relevant to glucose metabolism in IR. The purpose of this study was to test whether the multiple-target anti-miRNA antisense oligonucleotides (MTg-AMO) technology, an innovative miRNA knockdown strategy, can be used to interfere with multiple miRNAs that play critical roles in regulating IR. METHODS: An MTg-AMO carrying the antisense sequences targeting miR-106b, miR-27a and miR-30d was constructed (MTg-AMO106b/27a/30d). Protein levels were determined by Western blot analysis, and transcript levels were detected by real-time RT-PCR (qRT-PCR). Insulin resistance was analysed with glucose consumption and glucose uptake assays. RESULTS: We found that the protein level of glucose transporter 4 (GLUT4), Mitogen-activated protein kinase 14 (MAPK 14), Phosphatidylinositol 3-kinase regulatory subunit beta (PI3K regulatory subunit beta) and mRNA level of Slc2a4 (encode GLUT4), Mapk14 (encode MAPK 14) and Pik3r2 (encode PI3K regulatory subunit beta) were all significantly down-regulated in the skeletal muscle of diabetic rats and in insulin-resistant L6 cells. Overexpression of miR-106b, miR-27a and miR-30d in L6 cells decreased glucose consumption and glucose uptake, and reduced the expression of GLUT4, MAPK 14 and PI3K regulatory subunit beta. Conversely, silencing of endogenous miR-106b, miR-27a and miR-30d in insulin-resistant L6 cells enhanced glucose consumption and glucose uptake, and increased the expression of GLUT4, MAPK 14 and PI3K regulatory subunit beta. MTg-AMO106b/27a/30d up-regulated the protein levels of GLUT4, MAPK 14 and PI3K regulatory subunit beta, enhanced glucose consumption and glucose uptake. CONCLUSION: Our data suggested that miR-106b, miR-27a and miR-30d play crucial roles in the regulation of glucose metabolism by targeting the GLUT4 signalling pathway in L6 cells. Moreover, MTg-AMO106b/27a/30d offers more potent effects than regular singular AMOs.

Potent anti-inflammatory responses: Role of hydrogen in IL-1α dominated early phase systemic inflammation.

Introduction: It has been proven that hydrogen has obvious anti-inflammatory effects in animal experiments and clinical practice. However, the early dynamic process of the inflammatory response caused by lipopolysaccharide (LPS) and the anti-inflammatory effect of hydrogen has not been definitively reported. Methods: Inflammation in male C57/BL6J mice or RAW264.7 cells was induced with LPS, for which hydrogen was immediately administered until samples were taken. Pathological changes in lung tissue were assessed using hematoxylin and eosin (HE) staining. Levels of inflammatory factors in serum were determined using liquid protein chip. The mRNA levels of chemotactic factors in lung tissues, leukocytes, and peritoneal macrophages were measured by qRT-PCR. The expression levels of IL-1α and HIF-1α were measured by immunocytochemistry. Results: Hydrogen alleviated LPS-induced inflammatory infiltration in the lung tissues of mice. Among the 23 inflammatory factors screened, LPS-induced upregulation of IL-1α etc. was significantly inhibited by hydrogen within 1 hour. The mRNA expression of MCP-1, MIP-1α, G-CSF, and RANTES was inhibited obviously by hydrogen at 0.5 and 1 h in mouse peritoneal macrophages. In addition, hydrogen significantly blocked LPS or H2O2-induced upregulation of HIF-1α, and IL-1α in 0.5 h in RAW264.7 cells. Discussion: The results suggested that hydrogen is potentially inhibitive against inflammation by inhibiting HIF-1α and IL-1α release at early occurrence. The target of the inhibitive LPS-induced-inflammatory action of hydrogen is chemokines in macrophages in the peritoneal cavity. This study provides direct experimental evidence for quickly controlling inflammation with the translational application of a hydrogen-assisted protocol.

Li3Bi/LiF/Li2O derived from mechanical rolling of Li metal with BiOF nanoplates as stable filler for dendrite-free Li metal batteries.

Li is attractive anode for next-generation high-energy batteries. The high chemical activity, dendrite growth, and huge volume fluctuation of Li hinder its practical application. In this work, a Li-BiOF composite anode (LBOF) is obtained by combining Li metal with BiOF nanoplates through facile folding and mechanical cold rolling. Further, Li3Bi/LiF/Li2O filler is formed by the in-situ reactions of BiOF with contacted Li. In the filler, the Li3Bi, with high ionic conductivity and a lithiophilic nature, provides a mutually permeable channel for Li+ diffusion. The low surface diffusion energy barrier of Li3Bi and LiF can further promote the uniform deposition of Li. The conductive lithiophilic filler can reduce the local current density and provide a spatial limitation to the deposited Li. Consequently, the symmetrical LBOF||LBOF cell can cycle stably at 1 mA cm-2 for over 1300 h. Additionally, the surface of LBOF is flat with suppressed dendrite formation and free of dead Li accumulation, and the change in electrode volume is significantly alleviated. Furthermore, the LBOF||LiFePO4 full battery can maintain a stable cycle of more than 200 times with high capacity retention of 88.7% in a corrosive ester-based electrolyte. This simple mechanical approach is compatible with the current industrial route and is inspiring to solve the long-standing lithium-dendrite problem.

Non-insulin-based insulin resistance indexes in predicting severity for coronary artery disease.

BACKGROUND: Triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) are considered simple and reliable indicators of insulin resistance (IR). Although they have been associated with coronary artery disease (CAD), evidence supporting this is limited. Here, this is the first study to demonstrate the relationship between TyG-BMI index and CAD severity. The performance of the four non-insulin-based IR indexes in predicting CAD severity was explored. METHODS: We retrospectively analyzed 485 CAD patients between August 2020 and August 2021 in China, who were assigned into single- and multi-vessel CAD groups according to the coronary angiography (CAG) results. All patients were stratified into groups based on the tertiles of the TyG index, TyG-BMI index, TG/HDL-C ratio, and METS-IR. RESULTS: Patients in the multi-vessel CAD group had significantly higher TyG index, TyG-BMI index, TG/HDL-C ratio and METS-IR than those in the single-vessel CAD group. After adjusting for confounding factors, these four indicators were significantly associated with the risk of multi-vessel CAD. Notably, the highest tertile of TyG index, TyG-BMI index, TG/HDL-C ratio and METS-IR were significantly associated with the risk of multi-vessel CAD compared to participants in the lowest tertile. We also constructed receiver operating characteristic (ROC) curve, to assess CAD severity. The area under the curve (AUC) of the ROC plots was 0.673 (95% CI 0.620-0.726; P < 0.001) for TyG index, while those for the TyG-BMI index, TG/HDL-C ratio, and METS-IR were 0.704 (95% CI 0.652-0.755; P < 0.001), 0.652 (95% CI 0.597-0.708; P < 0.001), and 0.726 (95% CI 0.677-0.775; P < 0.001), respectively. CONCLUSIONS: TyG-BMI index is not only significantly associated with CAD severity, but is also an independent risk factor for multi-vessel CAD. The TyG index, TyG-BMI index, TG/HDL-C ratio, and METS-IR could be valuable predictors of CAD severity. Among the four non-insulin-based IR indexes, METS-IR had the highest predictive value, followed by TyG-BMI index.

The mediation and interaction of depressive symptoms in activities of daily living and active aging in rural elderly: A cross-sectional survey.

Background: Compared with urban areas, old adults in rural areas have limited access to medical and health resources in China. Active of daily living ability (ADL) decline and depressive symptoms are common in rural older adults. In particular, the depressive symptoms of the elderly in rural areas are often ignored. Thus, it is difficult to realize high-level active aging at the individual level. In order to explore the effects of ADL and depressive symptoms on the active aging of rural elderly, we conducted a survey and analyzed the mediation and interaction effects of depressive symptoms of ADL on active aging. Methods: From July to November 2019, a cross-sectional study of 945 elderly rural individuals was conducted in three townships in Xiangtan County, China. Active aging, ADL, and depressive symptoms were assessed using the positive aging questionnaire (PAEQ), ADL scale, and depression in old age scale (DIA-S), respectively. PROCESS macro program model 4 and logistic regression were used to explore the mediation and interaction between ADL and depressive symptoms on active aging. Results: The proportions of rural elderly with an active aging level were 23.5% (well above average), 50.9% (above average), 24.1% (below average), 1.5% (well below average), respectively. The rates of ADL decline and depressive symptoms were 44.7 and 19.7%, respectively. Mediated effect analysis showed that the relationship between ADL and active aging could be partly mediated by depressive symptoms (ab = -0.2382, boot SE = 0.0437), and the 95% confidence interval was [-0.3311, -0.1584]. The mediating effect proportion of the total effect was 30.7%. Logistic regression showed that ADL and depressive symptoms have an interactive additive effect on active aging. The relative excess risk of interaction (RERI), the attributable proportion due to interaction (API), and the synergy index (SI) scores were 13.109, 0.621, and 2.871, respectively. Older adults with ADL decline and depressive symptoms had higher (OR = 21.115) odds of well-below-average active aging compared with older adults with ADL decline (OR = 3.258) or only depressive symptoms (OR = 5.749). Conclusion: The findings suggest that the association between ADL and active aging is persistent and partly mediated by depressive symptoms, and comorbid depressive symptoms and ADL decline have an additive effect on active aging. Maintaining independence is an important factor for realizing active aging. However, for the rural elderly with ADL decline and low-level active aging, we can promote the realization of high-level active aging at the individual level through the prevention and treatment of depressive symptoms based on multidisciplinary care.

Cationic amino acid transporter-1 (CAT-1) promotes fibroblast-like synoviocyte proliferation and cytokine secretion by taking up L-arginine in rheumatoid arthritis.

BACKGROUND: Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA. METHODS: The concentrations of amino acids and cytokines in the synovial fluid of RA (n = 9) and osteoarthritis (OA, n = 9) were detected by LC-MS/MS and CBA assay, respectively. The mRNA and protein expression of cationic amino acid transporter-1 (CAT-1) were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion, and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo. RESULTS: L-rginine was upregulated in the synovial fluid of RA patients and was positively correlated with the elevation of the cytokines IL-1ß, IL-6, and IL-8. Further examination demonstrated that CAT-1 was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration, and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice. CONCLUSION: CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.

Tunable Photocontrolled Motions of Anil-Poly(ethylene terephthalate) Systems through Excited-State Intramolecular Proton Transfer and Trans-Cis Isomerization.

With the combination of excited-state intramolecular proton transfer and trans-cis isomerization as microscopic molecular motions under light stimulus, multiple photodeformable processes are achieved in anil-poly(ethylene terephthalate) systems, including simple bending, dancing butterflies, and switches. The doping films can realize light-driven contraction as large as 70% and bending angle of about 141°, upon a simple stretching process. The internal mechanism is confirmed by transient absorption spectra, and the relationship between molecular structure and photocontrolled motion is investigated by theoretical calculations and crystal analysis. This work provides a convenient approach by utilizing anils to fabricate reversible actuations with desirable geometries, greatly contributing to the applications and manufacturing of soft robots and related research.

The medical insurance system's weakness to provide economic protection for vulnerable citizens in China: A five-year longitudinal study.

OBJECTIVES: Little is known about the magnitude of catastrophic health expenditure (CHE) attributable to critical disease, especially in the middle-aged and elderly population. This research aimed to exploring the key aspects of how the health insurance fails to protect the middle-aged and elderly against CHE in the past five years. And propose corresponding measures to improve. METHODS: Data were obtained from the 2011 to 2015 China Health and Retirement Longitudinal Study. The method was adapted from WHO to calculate the catastrophic health expenditure (CHE) and impoverishment by medical expense (IME), and use Generalized Linear Mixed Models (GLMMs) to comprehensively analyze the risk factors that cause middle-aged and elderly people to fall into CHE. RESULTS: The incidence of CHE of China's middle-aged and elderly population has been rose in the five years from 2011 (10.5 %) to 2013 (17.5 %) to 2015 (19.7 %). The CHE of richest families was almost 6 times from 2011 to 2015. Urban Employee Medical Insurance Scheme, the incidence of CHE was up 10 percentage from 2011 to 2015. According to the GLMMs, families have inpatient cares as the most important factor to CHE. The incidence of CHE increased by 2.25 times compared with those who did not use inpatient services. CONCLUSIONS: The health system needs to control the irrational growth of health expenses and reduce residents' overuse of health services. Government should take supplementary measures to comprehensively strengthen the advantages of health insurance. Raise residents' awareness of health care, enhance citizens' physical fitness, and avoid unnecessary waste of health resources.

Construction of Glycometabolism- and Hormone-Related lncRNA-Mediated Feedforward Loop Networks Reveals Global Patterns of lncRNAs and Drug Repurposing in Gestational Diabetes.

Gestational diabetes mellitus (GDM) is a condition associated with the onset of abnormal glucose tolerance during pregnancy. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and genes can form lncRNA-mediated feedforward loops (lnc-FFLs), which are functional network motifs that regulate a wide range of biological processes and diseases. However, lnc-FFL network motifs have not been systematically investigated in GDM, and their role in the disease remains largely unknown. In the present study, a global lnc-FFL network was constructed and analyzed. Glycometabolism- and hormone-related lnc-FFL networks were extracted from the global network. An integrated algorithm was designed to identify dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. The patterns of dysregulated lnc-FFLs in GDM were complex. Moreover, there were strong associations between dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM. Core modules were extracted from the dysregulated lnc-FFL networks in GDM and showed specific and essential functions. In addition, dysregulated lnc-FFLs could combine with ceRNAs and form more complex modules, which could play novel roles in GDM. Notably, we discovered that the dysregulated lnc-FFLs were enriched in the thyroid hormone signaling pathway. Some drug-repurposing candidates, such as hormonal drugs, could be identified based on lnc-FFLs in GDM. In summary, the present study highlighted the effect of dysregulated glycometabolism- and hormone-related lnc-FFLs in GDM and revealed their potential for the discovery of novel biomarkers and therapeutic targets for GDM.

Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation.

BACKGROUND: Both beta-cell dysfunction and decreased insulin sensitivity are involved in the pathogenesis of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), while their relative contribution in the progression to type 2 diabetes still remains controversial. The aim of the present study is to clarify this process in Chinese subjects by using cross-sectional method. METHODS: 2,975 Chinese subjects were classified into: normal glucose tolerance (NGT), impaired glucose regulations (IGR), and diabetes mellitus (DM) based on oral glucose tolerance test (OGTT). The IGR group was sub-classified as isolated IFG, isolated IGT and combined glucose intolerance (CGI). The DM group was sub-classified as normal fasting plasma glucose and 2-hour hyperglycemia (N0D2), fasting hyperglycemia and normal 2-hour plasma glucose (D0N2), and both fasting and 2-hour hyperglycemia (D0D2). RESULTS: As far as insulinogenic index (IGI) was concerned, there was no difference between IFG and IGT in either gender, however, HOMA2-B% (homeostasis model assessment for beta-cell function) of IGT was higher than that of IFG and CGI in both male and female (P < 0.05). In the diabetic sub-groups, IGI of N0D2 was higher than that of D0N2, and both deteriorated compared with those of IGT and IFG, respectively. HOMA2-B% of N0D2 was still higher than that of D0N2 and D0D2. No significant difference was detected in OGIS and HOMA2-S% (homeostasis model assessment for insulin sensitivity) between IFG and IGT, and this was the case between N0D2 and D0N2. OGIS and HOMA-IR of IGR sub-groups were not different from those of their diabetic counterparts. CONCLUSION: Failure of beta-cell function might be the main reason for both IGT and IFG developing into diabetes instead of aggravated insulin resistance.

Metabolic characteristics of subjects with normal glucose tolerance and 1-h hyperglycaemia.

OBJECTIVE: Nondiabetic subjects with a 1-h plasma glucose >or= 11.1 mmol/l during an oral glucose tolerance test (OGTT) drew our attention to their somewhat confusing status and relative frequency among Chinese patients. The aim of this study was to clarify the metabolic characteristics of these subjects. DESIGN AND PATIENTS: A total of 2549 Chinese subjects were included in this study. Based on results of OGTT, these subjects were classified into three groups: normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes mellitus (DM). Then, according to the level of 1-h plasma glucose, the NGT and IGR groups were subclassified, respectively, as: NGT without 1-h hyperglycaemia (NGTN), NGT with hyperglycaemia at 1 h (NGT1H), IGR without 1-h hyperglycaemia (IGRN), and IGR with hyperglycaemia at 1 h (IGR1H). RESULTS: After adjustments for age and gender, the insulinogenic index (IGI) of NGT1H and IGR1H was found to be lower than for those with NGTN and of IGRN, respectively (P < 0.05). No statistical differences, however, were found in oral glucose insulin sensitivity (OGIS) between either of the 1-h hyperglycaemic groups or of the corresponding NGTN or IGRN groups. Homeostasis model assessment for beta-cell function (HOMA-B) of NGT1H was lower than that of NGTN (P < 0.05), while IGRN and IGR1H showed no difference. No differences in homeostasis model assessment for insulin resistance (HOMA-IR) were found among NGTN, NGT1H, IGRN and IGR1H groups. The levels of triglycerides (TG) were not significantly different among NGT1H, IGRN and IGR1H, while TG in these groups were significantly higher than in NGTN (P < 0.05). LDL-C was significantly higher and HDL significantly lower in NGT1H than in all other groups (P < 0.05).The IGR group was also subclassified as: isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined glucose intolerance (CGI). The IGI of the NGT1H group was similar to the IGI that of combined glucose intolerance group but lower than those of IFG and IGT (P < 0.05).The OGIS of the NGT1H group was the highest among all groups (P < 0.05). HOMA-B of IGT and NGT1H were higher than that of IFG (P < 0.05). There was no difference among all groups in HOMA-IR. Plasma lipid levels were not significantly different between NGT1H and any other group. CONCLUSIONS: Chinese NGT subjects with a 1-h plasma glucose >/= 11.1 mmol/l are characterized by metabolic abnormalities, which may be caused by the impairment of early insulin release rather than aggravated insulin resistance.

Troglitazone acutely activates AMP-activated protein kinase and inhibits insulin secretion from beta cells.

Changes in AMP-activated protein kinase (AMPK) activity contribute to the regulation of insulin secretion. Troglitazone has been shown to lower serum insulin levels and protect beta cell function. The aim of the present study was to examine the effects of troglitazone on AMPK activity and insulin secretion in beta cells. Isolated rat islets and MIN6 cells were treated for a short (1 h) or a long time (20 h) with troglitazone. One-hour troglitazone treatment activated AMPK and inhibited both glucose-stimulated insulin secretion (GSIS) and the response of insulin secretion to combined stimuli of glucose and palmitate. Long (20 h) treatment with troglitazone caused a sustained phosphorylation of AMPK and acetyl-CoA carboxylase, and increased GSIS after withdrawal of the drug. This study provided evidence that troglitazone activated AMPK in beta cells. In addition to the insulin-sensitizing effects in peripheral tissues, troglitazone also directly inhibits insulin hypersecretion by the elevated glucose and fatty acids, and thus protects beta cells from glucolipotoxicity.

Canine distemper viral infection threatens the giant panda population in China.

We evaluated exposure to canine distemper virus (CDV) in eight wild giant pandas (Ailuropoda melanoleuca) and 125 unvaccinated domestic dogs living in and around Foping National Nature Reserve (FNNR), China. Seventy-two percent of unvaccinated domestic dogs (mixed breed) had neutralizing antibodies for CDV due to exposure to the disease. The eight wild giant pandas were naïve to CDV and carried no positive antibody titer. RT-PCR assays for hemagglutinin (H) gene confirmed the presence of CDV in 31 clinically ill dogs from several areas near FNNR. Genomic sequence analysis showed that the 21 canine CDV were highly homologous to each other and belonged to the Asian-1 genotype. They showed high homology with the GP01 strain sequenced from a fatally infected giant panda, suggesting cross-species infection. Observational and GPS tracking data revealed home range overlap in pandas and dogs around FNNR. This study shows that CDV is endemic in domestic dogs near FNNR and that cross-species CDV infection threatens the wild giant panda population.

[Analysis of clinicopathologic features and morphogenesis of carcinoid tumorlets in the lung with bronchiectasis].

OBJECTIVE: To describe the clinicopathologic features and immunophenotypes of carcinoid tumorlets in the lung with bronchiectasis, and to study the morphogenesis of these tiny tumors. METHODS: The histopathologic characteristics of 3 bronchiectasis cases with carcinoid tumorlets, 11 bronchiectasis and 2 normal lungs were studied. Specific markers of the tiny tumors and the number of neuroendocrine cells (NECs) in the airway mucosa were immunohistochemically detected by EnVision method. RESULTS: The tumorlets in the lungs presented as multi-focal nodules and most were displayed only under microscopy. These cells were arranged in clusters and foci of fascicles which were situated in the surrounding bronchial wall and bronchioles adjacent to bronchiectatic lesion, or in the scar tissues. The tiny tumors were consisted of short fusiform cells and small ovoid cells. Their nuclei were circular, oval or long fusiform and the cells were strongly argyrophilic on Grimelius staining. Intensive positive immunostaining for calcitonin, chromogranin A, NSE and gastrin were detected. Weak positive for CK, EMA, S-100 and focal positive for HC, ACTH, 5-HT were also observed. Proliferative NECs in airway mucosa adjacent to the tiny tumors increased significantly in number, compared with those in the airway mucosa of bronchiectasis without tumorlets and normal lungs (P < 0.001, respectively). CONCLUSIONS: The clinicopathologic features and immunophenotypes of carcinoid tumorlets resemble carcinoid tumors. They are the early stage of carcinoid development. Their development may be related to the chronic pulmonary damage resulting in hypoxia and stimulating the proliferation of NECs. These pulmonary carcinoid tumorlets can be used as a model to study the tumorigenesis of carcinoid carcinoma of the lung.

Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue.

We previously showed that L-arginine (Arg) accumulates in colorectal cancer tissues. The aim of this study was to investigate the mechanism by which Arg accumulates and determine its biological significance. The concentration of Arg and Citrulline (Cit) in sera and tumor tissues from colorectal cancer (CRC) patients was analyzed by high-performance liquid chromatography (HPLC). The expression of Arg transporters was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis of tissue microarray. We also transfected the colon cancer cell line HCT-116 with siRNA specific for the Arg transporter CAT-1 and measured the induction of apoptosis by flow cytometry and cell proliferation by MTT assay. Consistent with our previous results, serum Arg and Cit concentrations in colorectal cancer patients were significantly lower than those in normal volunteers, while Arg and Cit concentrations in colorectal cancer tissues were significantly higher than in matched adjacent normal colon tissues. Quantitative RT-PCR showed that the CAT-1 gene was highly overexpressed in 70.5% of colorectal cancer tissue samples relative to adjacent normal colon tissues in all 122 patients with colorectal cancer. Immunohistochemical analysis of tissue microarray confirmed that the expression of CAT-1 was higher in all 25 colorectal cancer tissues tested. CAT-1 siRNA significantly induced apoptosis of HCT-116 cells and subsequently inhibited cell growth by 20-50%. Our findings indicate that accumulation of L-Arg and Cit and cell growth in colorectal cancer tissues is associated with over-expression of the Arg transporter gene CAT-1. Our results may be useful for the development of molecular diagnostic tools and targeted therapy for colorectal cancer.