[Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV].

Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease （CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74 (0.34, 0.94)×109/L vs. 0.99 (0.71, 1.29)×109/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) µg/L vs. 0.11 (0.06,0.20) µg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m2 vs. 22.0 (20.0, 24.0) kg/m2，P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25.0 kg/m2, which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors （all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

Microangiopathy in diabetic polyneuropathy revisited.

OBJECTIVE: Microangiopathy is a major cause in diabetic polyneuropathy (DPN). This review examines evidence from both human and animal studies to elucidate the important microvascular factors in DPN. MATERIALS AND METHODS: This is a literature review of articles published on PubMed in English. RESULTS: There is an abundance of evidence linking endoneurial microvascular abnormalities to peripheral nerve dysfunction and pathology in patients with diabetes. These structural changes result in an abnormal diffusion barrier leading to endoneurial hypoxia. Furthermore, the functional changes of endoneurial microvessels characterized by reduced vasodilation and potentiated vasoconstriction also exacerbate the endoneurial hypoxia. Although reduced endoneurial blood flow has also been widely reported in established DPN, there is some evidence that blood flow may be elevated early in the course of the disease. Capillary dysfunction in DPN, which reduces the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow, may explain that the tissue may be hypoxic even in the context of normal or elevated nerve blood flow. The pathogenesis of painful DPN also remains unclear although neural hemodynamic changes have been demonstrated both in the peripheral and central nervous system, offering potential new insights for the treatments of this distressing condition. CONCLUSIONS: Compelling experimental and human work has highlighted the close association connection between endoneurial microangiopathy and diabetic polyneuropathy. Future investigations will need to investigate the role of microvascular factors both in the periphery and the central nervous system in the pathogenesis of painful DPN.

Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy: a randomized, open-label, prospective study (VISION).

AIMS: To compare the efficacy and safety of combination of vildagliptin and metformin therapy with metformin uptitration in Chinese patients with type 2 diabetes (T2DM) inadequately controlled with low-dose metformin. METHODS: In this 24-week prospective, randomized, multicentre, open-label study, patients with T2DM inadequately controlled with metformin ≤1000 mg daily were divided 1 : 1 : 1 : 1 into four prespecified subgroups based on age and body mass index (BMI). Patients in each subgroup were randomized 5 : 1 to receive either vildagliptin (50 mg twice daily) plus metformin [500 mg twice daily; vildagliptin and low-dose metformin (VLDM) group] or metformin uptitration [1000 mg twice daily; high-dose metformin (HDM) group]. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline at week 24. The key secondary endpoints included percentage of patients achieving target HbA1c without adverse gastrointestinal (GI) events and mean change in fasting plasma glucose (FPG) from baseline to week 24. RESULTS: A total of 3084 patients were randomized. HbA1c reduction of 0.54% at week 24 in the VLDM group was non-inferior and statistically superior compared with 0.40% in the HDM group (P < 0.0001). VLDM's non-inferiority to HDM was confirmed in the four subgroups and its superiority was shown for all subgroups (p < 0.05) except for the subgroup of patients aged <60 years with a BMI of ≥24 kg/m(2) . Compared with HDM, VLDM significantly increased the percentage of patients achieving HbA1c ≤6.5% and HbA1c ≤6.5% without GI events. FPG levels in the VLDM group were lower at week 24 numerically than in the HDM group. The two treatment arms had similar safety profiles. CONCLUSIONS: VLDM was non-inferior and statistically superior to HDM in glycaemic control in Chinese patients with T2DM inadequately controlled with low-dose metformin.

Effects of sex and age on chicken TBC1D1 gene mRNA expression.

The objective of this study was to investigate the effects of sex and slaughter age of chickens on fatty acid composition and TBC1D1 gene expression in 4 different tissues: breast muscle, thigh muscle, abdominal fat, and subcutaneous fat. Sixty Erlang mountainous chickens (hybrid SD02 x SD03) were raised under the same conditions and slaughtered at 8, 10, and 13 weeks of age. The results showed that the sex of the animal significantly affected the content of arachidic acid (C20:0), sinapic (C22:1), linoleic (C18:2n-6), eicosapentaenoic (C20:5n-3), and docosahexaenoic acids (C22:6n-3), whereas other fatty acid contents were not affected. Age had a significant effect on most monounsaturated fatty acids, except for octadecenoic acid (C18:1). TBC1D1 mRNA was abundant in all tissues at all 3 ages of slaughter. Cocks exhibited higher TBC1D1 mRNA levels than hens in the thigh muscle and abdominal fat at 10 and 13 weeks, respectively.

Oligonucleotide microarray analysis reveals dysregulation of energy-related metabolism in insulin-sensitive tissues of type 2 diabetes patients.

Impaired insulin action within skeletal muscle, adipose tissue, and the liver is an important characteristic of type 2 diabetes (T2D). In order to identify common underlying defects in insulin-sensitive tissues that may be involved in the pathogenesis of T2D, the gene expression profiles of skeletal muscle, visceral adipose tissue, and liver from autopsy donors with or without T2D were examined using oligonucleotide microarrays and quantitative reverse transcriptase-PCR. Compared with controls, 691 genes were commonly dysregulated in these three insulin-sensitive tissues of humans with T2D. These co-expressed genes were enriched within the mitochondrion, with suggested involvement in energy metabolic processes such as glycolysis and gluconeogenesis, fatty acid beta oxidative, tricarboxylic acid cycle, and electron transport. Genes related to energy metabolism were mostly downregulated in diabetic skeletal muscle and visceral adipose tissue, while they were upregulated in the diabetic liver. This observed dysregulation in energy-related metabolism may be the underlying factor leading to the molecular mechanisms responsible for the insulin resistance of patients with T2D.

Pedobarography - a novel screening tool for diabetic peripheral neuropathy?

AIM: To investigate the diagnostic significance of foot plantar pressure distribution abnormalities in patients with diabetic peripheral neuropathy (DPN). PATIENTS AND METHODS: A total of 107 patients were divided into normal control (28 participants, 56 feet), non-DPN (56 patients, 112 feet), and DPN groups (23 patients, 46 feet). Foot plantar pressure was measured while patients walked at a constant speed over a flat floor using F-Scan pressure insoles. Recordings of six middle strides were averaged to evaluate the characteristics of foot plantar pressure distribution. RESULTS: Compared with the normal group, the time of contact (TOC) was longer in non-DPN (p < 0.05) and DPN groups (p < 0.01). The foot to floor force-time integral (FTI) was increased in DPN group (p < 0.01). The forefoot plantar force ratio increased in non-DPN and DPN patients (p < 0.05). Moreover, in DPN patients, the ratio of lateral foot plantar force increased (p < 0.05). The examination of the correlations between biomechanical parameters of the foot plantar and electrophysiological parameters of the lower limbs showed foot plantar biomechanical abnormalities correlated with abnormal sensory conduction of the sural nerve and motor conduction of the common peroneal nerve. Receiver operating characteristic (ROC) analysis showed the area under FTI curve was 0.714 (p < 0.001). CONCLUSIONS: The plantar pressure was shifted towards the side of the forefoot in DPN patients. The foot plantar biomechanical changes were closely correlated with lower limb paresthesia and contraction abnormalities of lower-limb extensor muscles. Foot plantar pressure measurement might be used as a screening tool for early diagnosis of DPN.

Association of two glyoxalase I gene polymorphisms with nephropathy and retinopathy in Type 2 diabetes.

BACKGROUND: Glyoxalase I (GLO1), which is the major enzyme that catalyzes the metabolism of methylglyoxal (MG), may play an important role in the pathogenesis of diabetic microvascular complications. AIM: To investigate whether the C-7T and A419C polymorphisms of the GLO1 gene are associated with nephropathy and retinopathy in Chinese Type 2 diabetic patients. SUBJECTS AND METHODS: A total of 364 Type 2 diabetic patients and 301 healthy controls were enroled in the study. Diabetic microvascular complications were determined by urinary albumin excretion measurements and ophthalmological examinations. Genetic analyses were performed using either Taqman PCR or direct sequencing. The effect of C-7T polymorphism on promoter activity was measured by reporter gene assays. RESULTS: The albumin/ creatinine ratio (ACR) and prevalence of nephropathy and retinopathy were significantly higher in diabetic patients with GLO1 -7CC genotype than in patients with -7CT and -7TT genotypes (p=0.02, p=0.02, and p=0.04, respectively). The - 7CC genotype is independently associated with ACR (ß=0.13, p=0.01) and the risk for retinopathy [odds ratio (OR): 2.30, 95% confidence interval (CI): 1.25-4.24, p<0.01]. The luciferase activity of the -7T promoter was higher than that of the -7C promoter (13.2±0.2 vs 11.7±0.8, p=0.04). No differences were found between ACR and the prevalence of nephropathy and retinopathy for A419C polymorphism in Type 2 diabetic patients. CONCLUSIONS: GLO1 C-7T polymorphism alters promoter activity and confers susceptibility to nephropathy and retinopathy to Type 2 diabetic patients.

The gene expression profiling of sporadic pheochromocytoma and novel full-length cDNAs cloning.

Pheochromocytoma is a chromaffin cell neoplasm that typically causes symptoms and signs of episodic catecholamine release. Pheochromocytoma can be divided into two types: familial and sporadic. The molecular mechanisms involved in familial pheochromocytoma have been unraveled, but the detailed molecular mechanism of sporadic pheochromocytoma remains unknown. The present study thus aimed at characterization of gene expression profiling of sporadic pheochromocytoma using expressed sequence tags (ESTs), and established a preliminary catalog of genes expressed in the tumor. In total, 4115 ESTs were generated from the tumor library. The gene expression profilings of the pheochromocytoma and the normal adrenal gland were compared, and 341 genes were identified to be significantly expressed differently between the two libraries. Interestingly, 16 known genes participating in cell division or apoptosis were notably differently expressed between the tumor and the normal adrenal gland. Twenty-four novel full-length cDNAs were cloned from the tumor library and five of them were significantly up-regulated in the tumor. Some of them may be involved in the tumorigenesis of pheochromocytoma. The sequence data of ESTs and novel full-length cDNAs described in this paper have been submitted to the GeneBank library.

Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.