Treating hyperglycaemia in a patient with maternally inherited diabetes and deafness with an inhibitor of dipeptidyl peptidase-4: a case report and two-year follow-up.

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder with diverse characteristics, which make early diagnosis difficult. We report a case of 32-year-old woman with diabetes who was admitted due to weight loss and poor glycemic control. She had a history of gestational diabetes at age 26. Pancreatic function was evaluated by oral glucose tolerance. An ophthalmologic examination detected conjunctivitis and refractive errors and hearing tests were normal. The patient had a family of diabetes. Then we tested the patient and her first-degree relatives with a confirmed genetic mutation at position 3243 in the tRNA. After two years of treatment with linagliptin, both glycated hemoglobin and pancreatic function have shown improvement to some extent. Although MIDD is a rare form of diabetes, due to distinctive management and associated comorbidities it is important to diagnose.

Prediction model for low bone mass mineral density in type 2 diabetes: an observational cross-sectional study.

PURPOSE: Considering the prevalence of type 2 diabetes (T2D), osteoporosis should be considered a serious complication. However, an effective tool for the assessment of low bone mass mineral density (BMD) in T2D patients is not currently available. Therefore, the aim of our study was to establish a simple-to-use risk assessment tool by exploring risk factors for low BMD in T2D patients. METHODS: This study included 436 patients with a low BMD and 381 patients with a normal BMD. Multiple logistic regression analysis was performed to evaluate risk factors for low BMD in T2D patients. A nomogram was then developed from these results. A receiver operating characteristic (ROC) curve, calibration plot, and goodness-of-fit test were used to validate the nomogram. The clinical utility of the nomogram was also assessed. RESULTS: Multivariate logistic regression indicated that age, sex, education, body mass index (BMI), fasting C-peptide, high-density cholesterol (HDL), alkaline phosphatase (ALP), estimated glomerular filtration rate (eGFR), and type I collagen carboxy terminal peptide (S-CTX) were independent predictors for low BMD in T2D patients. The nomogram was developed from these variables using both the unadjusted area under the curve (AUC) and the bootstrap-corrected AUC (0.828). Calibration plots and the goodness-of-fit test demonstrated that the nomogram was well calibrated. CONCLUSIONS: The nomogram-illustrated model can be used by clinicians to easily predict the risk of low BMD in T2D patients. Our study also revealed that common factors are independent predictors of low BMD risk. Our results provide a new strategy for the prediction, investigation, and facilitation of low BMD in T2D patients.

Transcriptome analysis of table grapes (Vitis vinifera L.) identified a gene network module associated with berry firmness.

Berry firmness is one of the main selection criteria for table grape breeding. However, the underlying genetic determinants and mechanisms involved in gene expression during berry development are still poorly understood. In this study, eighteen libraries sampled from Vitis vinifera L. cv. 'Red Globe' and 'Muscat Hamburg' at three developmental stages (preveraison, veraison and maturation) were analyzed by RNA sequencing (RNA-Seq). The firmness of 'Red Globe' was significantly higher than that of 'Muscat Hamburg' at the three developmental stages. In total, a set of 4,559 differentially expressed genes (DEGs) was identified between 'Red Globe' and 'Muscat Hamburg' in the preveraison (2,259), veraison (2030) and maturation stages (2682), including 302 transcription factors (TFs). Weighted gene coexpression network analysis (WGCNA) showed that 23 TFs were predicted to be highly correlated with fruit firmness and propectin content. In addition, the differential expression of the PE, PL, PG, ß-GAL, GATL, WAK, XTH and EXP genes might be the reason for the differences in firmness between 'Red Globe' and 'Muscat Hamburg'. The results will provide new information for analysis of grape berry firmness and softening.

The contribution of wall shear stress insult to the growth of small unruptured cerebral aneurysms in longitudinal 3D-TOF-MRA.

OBJECTIVE: Aneurysm growth is a risk factor for rupture, however the detailed mechanism remains unclear. The present study was performed to identify whether hemodynamic insult could prompt small unruptured aneurysms to grow. METHODS: Six pairs of unruptured small (<5 mm) cerebral aneurysms from patients followed with longitudinally three-dimensional MR imaging were selected and divided into an angiographic confirmed enlarged group (with >50% volume increase; n = 6) and an angiographic stable group (with ±10% volume changes; n = 6). Patient-specific computational fluid dynamic models were created and run under pulsatile flow conditions. Reverse reconstruction technique was used to simulate the status of before aneurysm generation. Relevant hemodynamic variables were calculated and compared between the two groups. RESULTS: In the enlarged group, wall shear stress (WSS) decreased from aneurysm neck to dome, whereas WSS at the aneurysm neck (58.68 ± 34.45 Pa) and body (52.68 ± 46.37 Pa) was significantly higher than the stable group (neck: 36.83 ± 18.20 Pa and body: 30.77 ± 18.85 Pa) (P < .05). WSS decreased at the neck, body, and dome and flow patent became stable after aneurysm growth (P < .05). Reverse reconstruction revealed an elevated WSS at the site of aneurysm formation compared with other sites in the parent artery, and WSS at the formation site significantly decreased after aneurysm growth and further enlargement (P < .05). CONCLUSION: Local elevated WSS to the arterial wall contributed to cerebral aneurysm generation, whereas turbulent flow patterns and elevated WSS at the aneurysm neck and body worked together to result in further growth of small aneurysms.

LncRNA IUR downregulates ZEB1 by upregulating miR-200 to inhibit prostate carcinoma.

We in this study investigated the role of imatinib-upregulated lncRNA (IUR) in prostate carcinoma (PC). We observed that IUR was downregulated in PC, and its expression levels decreased with the increase of clinical stages. In PC tissues, microRNA (miR)-200 was positively, while ZEB1 was inversely correlated with IUR. In PC cells, IUR and miR-200 overexpression mediated the downregulated ZEB1. IUR overexpression mediated the upregulation of miR-200, while IUR expression was not significantly affected by miR-200 overexpression. Cell invasion and migration analysis showed that IUR and miR-200 overexpression resulted in decreased invasion and migration rates. ZEB1 overexpression played an opposite role and attenuated the effects of IUR and miR-200 overexpression. Therefore, IUR can downregulate ZEB1 by upregulating miR-200 to inhibit PC cell invasion and migration.

Aneurysm outflow angle at MRA as discriminant for accurate diagnosis and differentiation between small sidewall cerebral aneurysms and infundibula.

OBJECTIVE: To evaluate whether the aneurysm outflow angle (OA) at MR angiography (MRA) might serve as discriminant for accurate diagnosis of, and differentiation between, small sidewall cerebral aneurysms (SCAs) and infundibula. METHODS: Between June 2007 and July 2015, 426 consecutive patients with SCAs completed both an MRA and DSA examination. Of these, 156 patients with small SCAs and 52 patients with infundibula were included in this study. A patient with an OA ≥90° was defined as having a SCA, while those with OA <90° were defined as having an infundibulum. RESULTS: DSA identified 172 SCAs in 156 patients and 55 infundibula in 52 patients. The average OA on MRA was 102.96°±13.36° (range 60°-151°) in 172 SCAs of 156 patients. An OA of ≥90° was seen for 159 (92.4%) small SCAs in 147 patients, while an OA of <90° was observed for 13 SCAs. The average OA on MRA was 69.05°±14.26° (range 35-107°) in 55 infundibula of 52 patients. An OA of ≥90° was seen in one patient with one infundibulum; while an OA of <90° was observed for 54 infundibula (98.2%) in 51 patients. The average OA in SCAs (n=172) was greater than the average OA in infundibula (n=55; 102.96° vs 69.05°, p<0.001). CONCLUSIONS: The OA at MRA could serve as discriminant for accurate diagnosis of, and differentiation between, small SCAs and infundibula.

Sidewall cerebral aneurysms: effect of an outflow angle-assisted approach on diagnosis.

BACKGROUND: The ability to diagnose sidewall cerebral aneurysms (SCAs) on an angle measurement basis may be useful in clinical practice. A study was undertaken to evaluate the effect of an outflow angle (OA)-assisted approach. METHODS: MR angiography (MRA) images of 438 patients with suspected SCAs and other cerebrovascular diseases were separately evaluated using the subjective approach and the OA approach. The approaches were then exchanged for confirmation of unclear cases. An OA of ≥90° was considered to represent SCA positivity. The accuracy, sensitivity, and specificity of the OA-assisted approach were determined using patient-based, aneurysm-based, and size-based evaluations. RESULTS: Digital subtraction angiography (DSA) detected 301 SCAs in 267 patients and no SCAs in 171. An OA of ≥90° was observed for 271 aneurysms in 244 patients (true positives); the OA approach misinterpreted OA as <90° for 29 aneurysms in 29 patients (false negatives) and missed one aneurysm. The subjective approach detected 309 SCAs in 273 patients. This approach misdiagnosed 10 patients (false positives) and missed two aneurysms in two patients (false negatives). The OA-assisted approach detected 300 SCAs in 267 patients and no SCAs in 171, overlooking one aneurysm. Patient-based evaluation yielded high accuracy, sensitivity, specificity, and positive and negative predictive values for the OA-assisted approach. CONCLUSIONS: The OA-assisted approach for SCA diagnosis effectively reduced the false-positive rate obtained with the subjective approach with high accuracy, sensitivity, and specificity, suggesting that MRA based on this approach can be a reliable alternative to DSA in SCA screening and diagnosis.

Effects of Exenatide on Metabolic Changes, Sexual Hormones, Inflammatory Cytokines, Adipokines, and Weight Change in a DHEA-Treated Rat Model.

Insulin resistance and hyperandrogenism are the main features of polycystic ovarian syndrome (PCOS). Low-grade inflammation is also involved in PCOS. This study was performed to evaluate the effect of exenatide on metabolic changes, sexual hormones, inflammatory cytokines, adipokines, and weight changes in a dehydroepiandrosterone (DHEA)-treated rat model. After the model was produced by daily subcutaneous injections of DHEA, rats were given metformin (265 mg/kg), exenatide (10 µg/kg), and saline (1 mL). One group served as a control group. Blood samples and ovarian tissues were removed and prepared for biochemical and hormonal analyses. Exenatide significantly reduced body weight and insulin, testosterone, interleukin 6 (IL-6), PEDF, and visfatin levels. Exenatide also ameliorated changes in ovarian morphology, as evidenced by decreased numbers of cystic follicles and various follicles and elevated numbers of granular cell layers. The effects observed with exenatide were comparable to those observed with metformin. This study has provided evidence that exenatide may be efficient in the treatment of PCOS.

The association of fish consumption with bladder cancer risk: a meta-analysis.

BACKGROUND: The association between fish consumption and risk of bladder cancer has not been established yet. The results from epidemiological studies are inconsistent. METHODS: We conducted a meta-analysis of cohort and case-control studies on the relationship between fish intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of relative risk associated to the highest versus the lowest category of fish intake using random effect models. Heterogeneity among studies was examined using Q and I2 statistics. Publication bias was assessed using the Begg's funnel plot. RESULTS: Five cohort and 9 case-control studies were eligible for inclusion. The combined relative risk showed that fish consumption was negatively, but not significantly, associated with a decreased risk of bladder cancer (relative risk, 0.86; 95% confidence interval, 0.61-1.12). In subgroup analyses, there was no evidence that study design, geographical region, case sample size, or exposure assessment substantially influenced the estimate of effects. CONCLUSION: The overall current literature on fish consumption and the risk of bladder cancer suggested no association. Because of the limited number of studies, further well-designed prospective studies are needed to explore the effect of fish on bladder cancer.

[Effects of fructus schisandrae on the function of the pituitary-testis axis and carbohydrate metabolism in rats undergoing experimental navigation and high-intensity exercise].

OBJECTIVE: To investigate the influence of fructus schisandrae (FS) on the function of the pituitary-testis axis and carbohydrate metabolism in male rats undergoing experimental navigation and strenuous exercise. METHODS: Thirty-four SD rats were randomly allocated into three groups, quiescent control (A), stress control (B) and FS (C). Those in Groups B and C received 10 days of Benford's high-intensity training, followed by 7 days of intragastric administration of normal saline and FS, respectively. Blood samples were immediately obtained at the end of the experiment for the measurement of the levels of serum testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu) by radioimmunoassay. The pituitary gland and testis tissues were also collected for the observation of their ultrastructures under the electron microscope. RESULTS: Group A showed a significantly lower Glu level and a higher T level than B ([5.22 +/- 2.13] mmol/L versus [9.41 +/- 2.56] mmol/L, and [0.61 +/- 0.68] ng/ml versus [0.10 +/- 0.15] ng/ml, P < 0.01), but there was no significant difference in the CORT level between the two groups ([4.67 +/- 1.19] ng/ml versus [7.25 +/- 6.20] ng/ml, P > 0.05). Compared with Group B, both the Glu and CORT levels were remarkably decreased in Group C ([5.09 +/- 1.64] mmol/L and [3.55 +/- 3.52] ng/ml, P < 0.05 and P < 0.01), but the T level showed no significant change ([0.11 +/- 0.12] ng/ml, P > 0.05). And there were no significant differences in the serum LH level among the three groups (P > 0.05). Ultrastructural pathology showed a significant reduction of secretory granules in the pituitary cells in Group B as compared with A, and a markedly increased number of granules in the cytoplasm in Group C in comparison with B. Such changes as mitochondrial swelling, increase of electron density and decrease or disappearance of mitochondrial cristae were also found in the Leydig cells of Group B. No significant differences were observed in the testicular cells between Groups and C. CONCLUSION: Experimental navigation and high-intensity training significantly suppress the function of the pituitary-testis axis in rats. Intragastric administration of fructus schisandrae can protect the pituitary-testis axis and reduce the blood Glu level in the stressed rats.

Glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) metabolism computational network analysis between chimpanzee and human left cerebrum.

We identified significantly higher expression of the genes glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) from human left cerebrums versus chimpanzees. Yet the distinct low- and high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism networks between chimpanzee and human left cerebrum remain to be elucidated. Here, we constructed low- and high-expression activated and inhibited upstream and downstream AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network between chimpanzee and human left cerebrum in GEO data set by gene regulatory network inference method based on linear programming and decomposition procedure, under covering AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 pathway and matching metabolism enrichment analysis by CapitalBio MAS 3.0 integration of public databases, including Gene Ontology, KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, etc. Our results show that the AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network has more activated and less inhibited molecules in chimpanzee, but less activated and more inhibited in the human left cerebrum. We inferred stronger carbohydrate, glutathione and proteoglycan metabolism, ATPase activity, but weaker base excision repair, arachidonic acid and drug metabolism as a result of inducing cell growth in low-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of chimpanzee left cerebrum; whereas stronger lipid metabolism, amino acid catabolism, DNA repair but weaker inflammatory response, cell proliferation, glutathione and carbohydrate metabolism as a result of inducing cell differentiation in high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of human left cerebrum. Our inferences are consistent with recent reports and computational activation and inhibition gene number patterns, respectively.

Survivin (BIRC5) cell cycle computational network in human no-tumor hepatitis/cirrhosis and hepatocellular carcinoma transformation.

Survivin (BIRC5) relationship with tumor is presented in several papers. However, how the molecular network and interpretation concerning BIRC5 cell cycle between no-tumor hepatitis/cirrhosis and hepatocellular carcinoma (HCC) remains to be elucidated. Here, we constructed and analyzed significant higher expression gene BIRC5 activated and inhibited cell cycle network from HCC versus no-tumor hepatitis/cirrhosis patients (viral infection HCV or HBV) in GEO Dataset by combination of gene regulatory network inference method based on linear programming and decomposition procedure with the CapitalBio MAS 3.0 software based on the integration of public databases including Gene Ontology, KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, etc. Compared the same and different activated and inhibited BIRC5 network with GO analysis between no-tumor hepatitis/cirrhosis and HCC, our result showed BIRC5 cell cycle network weaker transcription factor activity in both no-tumor hepatitis/cirrhosis and HCC (1); stronger nucleus protein binding but weaker cytoplasm protein binding in no-tumor hepatitis/cirrhosis (2); stronger cytoplasm protein phosphatase binding but weaker ubiquitin-protein ligase activity in HCC (3). Therefore, we inferred BIRC5 cell cycle module less transcription from RNA polymerase II promoter in both no-tumor hepatitis/cirrhosis and HCC (4). We deduced BIRC5 cell cycle module different from more mitosis but less complex-dependent proteasomal ubiquitin-dependent protein catabolism as a result increasing cell division and cell numbers in no-tumor hepatitis/cirrhosis to more protein amino acid autophosphorylation but less negative regulation of ubiquitin ligase activity during mitotic cell cycle as a result increasing growth and cell volume in HCC (5).

MYBPC1 computational phosphoprotein network construction and analysis between frontal cortex of HIV encephalitis (HIVE) and HIVE-control patients.

MYBPC1 computational phosphoprotein network construction and analysis of frontal cortex of HIV encephalitis (HIVE) was very useful to identify novel markers and potential targets for prognosis and therapy. Based on integrated gene regulatory network infer method by linear programming and a decomposition procedure with analysis of the significant function cluster using kappa statistics and fuzzy heuristic clustering from the database for annotation, visualization, and integrated discovery, we identified and constructed significant molecule MYBPC1 phosphoprotein network from 12 frontal cortex of HIVEcontrol patients and 16 HIVE in the same GEO Dataset GDS1726. Our result verified MYBPC1 phosphoprotein module only in the upstream of frontal cortex of HIVEcontrol patients (CREB5, MAPKAPK3 inhibition), whereas in the upstream of frontal cortex of HIVE (CREB5, ZC3HAV1 activation; ROR1 inhibition) and downstream (MAPKAPK3 activation; CFDP1, PDCD4, RBBP6 inhibition). Importantly, we determined that MYBPC1 phosphoprotein cluster of HIVE was involved in signal transduction, transferase, post-translational protein modification, developmental process and glycoprotein (only in HIVE terms), the condition was vital to inflammation and cognition impairment of HIVE. Our result demonstrated that common terms in both HIVE-control patients and HIVE included phosphoprotein, organelle, response to stimulus, nucleic acid binding, primary metabolic process, and biological regulation, and these terms were more relative to inflammation and cognition impairment, therefore, we deduced the stronger MYBPC1 phosphoprotein network in HIVE. It would be necessary of the stronger MYBPC1 phosphoprotein function to inflammation and cognition impairment of HIVE.

[Effects of Panax notoginseng saponins on immune-neuroendocrine network of SD rats in experimental navigation and intensive exercise].

OBJECTIVE: The present study aims to study the influences experimental navigation and intensive exercise on immune-neuroendocrine network of the male rats and the effects of PNS to this influence. METHOD: Thirty 6-week Sprague-Dawley male rats (SD rats) were randomly located into three groups: Quiescent control (QC) group, training control (TC) group and Panax notoginseng saponins (PNS) group. Rats from QC group were not given any stimuli, and samples were taken after 7-day intragastric administration of saline. Rats from TC group underwent 10-day run training of increasing load on treadmill and received 7-day intragastric administration of saline. PNS group were subjected to the same procedure of run training as group TC, and received intragastric administration of PNS at the dose of 0.2 g x kg(-1). Blood samples were immediately obtained at the end of the tests to determine the serum levels of corticosterone (Cort), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), Neuropeptide Y (NPY) and interleukin-1beta (IL-1beta), interleukin-6 (IL-6) by RIA. Expressions of Pituitary ACTH, NPY were observed use the immunohistochemistry method and correlation analyses conducted. And the ultrastructural changes of the pituitaries and the adrenal cortex cells were examined by electron microscope meanwhile. RESULT: The serum beta-EP and Cort levels in TC group were significantly increased compared to the QC group; whereas Expression levels of pituitary ACTH, NPY were markedly higher after experimental navigation and intensive exercise. In Group PNS, the plasma Cort, ACTH and NPY levels decreased significantly compared to Group TC. Meanwhile we found expression levels of pituitary ACTH, NPY also lower than group TC. There was no significant difference about the ultrastructure of anterior pituitary and adrenal cortex of QC and PNS group. However, a obvious change of ultrastructure occurred to TC group rats. CONCLUSION: These results suggest that immune-neuroendocrine network function of rats were confused by negative psychological stresses and intensive exercise. PNS therapy may exert regulation effects to the network.

[Salidroside protects the hypothalamic-pituitary-gonad axis of male rats undergoing negative psychological stress in experimental navigation and intensive exercise].

OBJECTIVE: To study the effects of salidroside on the function and ultramicro-pathological change of the hypothalamic-pituitary-gonadal (HPG) axis of male rats in experimental navigation and intensive exercise. METHODS: Six-week SD rats were randomized into 3 groups: non-stress control (NC, n = 10), training control (TC, n = 12) and salidroside treatment (ST, n = 12) group. Blood samples were collected from the NC rats that did not receive any stimulus after a 7-day intragastric administration of saline. The TC rats underwent a 10-day running training with increasing load on the treadmill followed by a 7-day intragastric administration of saline. The ST rats were subjected to the same process of running training as the TC group and received intragastric administration of salidroside. Then blood samples were immediately obtained and the levels of testosterone (T), corticosterone (CORT), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) measured by radioimmunoassay. The testis histopathology was observed by HE staining, and the ultrastructural changes of the pituitaries and testes investigated by electron microscopy. RESULTS: The serum T level was significantly lower in the TC than in the NC group, but showed no significant difference between the ST and NC groups. HE staining revealed no significant difference in testis histopathology among the 3 groups. Ultramicro-pathology showed that the secretory granules of the pituitary cells were significantly reduced in the TC rats compared with the NC ones; the number of the granules significantly increased in the ST group compared with the TC rats; and mitochondrial swelling, increase of electron density and decrease/disappearance of mitochondrial cristae were observed in the Leydig cells of the TC rats. But no significant differences were found in the testicular cells between the ST and NC groups. CONCLUSION: Negative psychological stress and intensive exercise can significantly suppress the function of the HPG axis in rats. Salidroside therapy has protective effect on the HPG axis.

[Effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in rats undergoing experimental chronic psychological stress, navigation and strenuous exercise].

OBJECTIVE: To investigate the effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in male rats undergoing experimental chronic psychological stress, navigation and strenuous exercise. METHODS: Thirty-four SD rats were randomly allocated into a non-stress group (Group A), a stress control group (Group B) and a schisandra group (Group C). The latter two groups received 10 days of Benford's high-intensity training, followed by 3 hours of wearing floating with psychological stress and another 3 hours of running at the speed of 26.7 m/min. Then blood samples were immediately obtained for the measurement of the levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu). Meanwhile the adrenal gland was excised and its cortex ultrastructure observed under the electron microscope. RESULTS: The Glu level was increased while the T level decreased significantly in Group B as compared with Group A. The CORT level remained unchanged in Group B. Both the Glu and CORT levels were significantly reduced in Group C in comparison with B. However, no significant differences were found in serum LH levels among the three groups. And electron microscopy revealed a reduction of lipid droplets and apoptosis of the adrenal cortex cells in Group B as compared with C. CONCLUSION: Schisandra can reduce the levels of CORT and Glu and protect the structure of the adrenal cortex.