[Optic atrophy in a patient with axonal Charcot-Marie-Tooth disease 2A2A due to MFN2 gene mutations].

A 27-year-old male patient had progressive vision loss in both eyes, which was mainly manifested by impaired ganglion cells in the macular area, accompanied by systemic muscle atrophy in limbs. A complete mitochondrial exon gene detection was performed. The final diagnosis was bilateral optic atrophy and axonal Charcot-Marie-Tooth disease 2A2A caused by mutations of the MFN2 gene. There has been no effective treatment. Applications of nutrients to restore the mitochondrial function may alleviate the clinical symptoms.

[The efficacy and safety of insulin degludec versus insulin glargine in insulin-naive subjects with type 2 diabetes: results of a Chinese cohort from a multinational randomized controlled trial].

Objective: To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM). Methods: This was a 26-week, randomized, open-label, parallel-group, treat-to-target trial in 560 Chinese subjects with T2DM (men/women: 274/263, mean age 56 years, mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2∶1 to once-daily IDeg (373 subjects) or IGlar(187 subjects), both in combination with metformin. The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks. Results: Mean HbA1c decreased from 8.2% in both groups to 6.9% in IDeg and 7.0% in IGlar, respectively. Estimated treatment difference (ETD) of IDeg-IGlar in change from baseline was -0.10% points (95%CI-0.25-0.05). The proportion of subjects achieving HbA1c<7.0% was 56.3%and 49.7% with IDeg and IGlar, respectively [estimated odds ratio of IDeg/IGlar: 1.26(95%CI 0.88-1.82)]. Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar, respectively [estimated rateratio of IDeg/IGlar 0.69(95%CI 0.46-1.03), and 0.43(95%CI 0.19-0.97)]. No differences in other safety parameters were found between the two groups. Conclusions: IDeg was non-inferior to IGlar in terms of glycaemic control, and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia. IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment. Clinical trail registration: Clinicaltrials.gov, NCT01849289.

[Clinical value of tumor size in the evaluation of adrenal incidentalomas].

Objective: To investigate the clinical value of tumor size in the evaluation of endocrinological and histological natures regarding adrenal incidentaloma (AI) patients. Methods: A total of 1 941 AI patients who were hospitalized in Department of Endocrinology, Chinese PLA General Hospital between January 1997 and December 2016 were retrospectively reviewed. The demographics of patients, imaging features, functional status and histological results were analyzed. Results: Of 1 941 patients, 984 (50.70%) were males, and 957 (49.30%) were females. The median age was 52 years old. Endocrine evaluation according to the mass size showed that the proportion of non-functional AI and primary aldosteronism (PA) was declined from 84.55% (558/660) to 27.95% (45/161) and from 6.82% (45/660) to 0, respectively. The highest frequency of subclinical Cushing's syndrome (SCS), PA and pheochromocytomas were observed in 2.1-4.0, ≤2.0 and 4.0-6.0 cm group, respectively. Histological results showed that in>6 cm group, the frequency of malignancy were sharply increased. Multivariate logistical regression analysis indicated tumor size had a significant association with the presence of malignancy (OR=1.043, 95% CI: 1.033-1.054, P<0.001). A mass size of 4.0 cm was of great value in distinguishing malignant tumors from the benign ones, with a sensitivity of 89.19%, and a specificity of 69.91%. Conclusion: Mass size was of great value in the endocrinological evaluation, as well as distinguishing malignant tumors from the benign ones in AI patients.

[Surgery versus conservative management for subclinical Cushing's syndrome in adrenal incidentalomas].

Objective: To determine the effect of the surgical and conservative approaches on the metabolic profiles in patients with subclinical Cushing's syndrome (SCS) in adrenal incidentalomas (AI). Methods: A hundred and thirty AI patients with SCS in Department of Endocrinology, PLA General Hospital between January 2008 and December 2016 were studied, surgery was performed in 88 patients (surgical group), and the rest received conservative approach (conservative group). The improvement/worsening of blood pressure, blood glucose, lipid profiles and body weight after a duration of >18 months follow-up were analyzed, respectively. Results: Baseline demographics, clinical characteristics were similar between surgical and conservative groups. In the surgical group, blood pressure, blood glucose, lipid profiles and body weight improved more frequently than that in conservative group (29.69% vs 3.12%, P=0.003; 10.94% vs 3.12%, P=0.262; 7.81% vs 3.12%, P=0.660; 39.06% vs 9.38%, P=0.004, respectively). In conservative group, blood pressure, blood glucose, lipid profiles and body weight worsened more frequently than that in surgical group (28.13% vs 0, P<0.001; 25.0% vs 0, P<0.001; 18.75% vs 0, P=0.003; 40.62% vs 20.31%, P=0.051, respectively). Logistic regression analysis indicated surgical treatment was associated with improvement of blood pressure (OR=10.687, 95%CI: 1.279-89.299) and weight loss (OR=5.541, 95%CI: 1.404-21.872) independently of gender, age, duration of follow-up, serum cortisol level after 1 mg-dexamethasone suppression test and the mass size. Conclusion: In AI patients with SCS, surgery was beneficial in the aspect of metabolic profiles.

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.

Life and death of human vascular endothelial cells by stimulation with free fatty acids through death receptors.

Diabetic individuals may have elevated levels of serum free fatty acids and may exhibit injury to the vascular endothelial cells. This study was undertaken to determine the relationship between various free fatty acids (FFAs) and vascular endothelial cell injury and the molecular mechanisms linking FFA-induced vascular endothelial cells injury or protection. We observed the survival of HUVECs exposed to different FFAs, and our results revealed that the effects of various FFAs on the cell survival of HUVECs were significantly different. Palmitic acid (PA) markedly decreased the HUVEC survival rate in a time- and dose-dependent manner, but arachidonic acid (AA) significantly increased the cell survival rate and could partially prevent cellular apoptosis induced by PA. Interestingly, PA and AA could activate the same target receptor, TNF-R1. PA induced the apoptosis of HUVECs by initiating the death pathway (TNF-R1/TRADD/caspases 8 pathway), whereas AA enhanced cell survival to protect vascular endothelial cells by activating the survival pathway (TNF-R1/RIP/NF-κB 50/NF-κB 65).

Hip fracture after first-ever stroke: a population-based study.

OBJECTIVES: The aim of this study is to estimate the risk of hip fracture after first-ever stroke, using a nationwide population-base data set and a retrospective cohort design. MATERIALS AND METHODS: The cohort study involved 18,413 patients surviving a first-ever stroke during the 12-year period from 1997 to 2008. Another 18,413 control subjects were randomly selected with adjustment for age, gender and enrolled year. Stroke type, duration between stroke and hip fracture, six comorbidities and five categories of medication prior to hip fracture were investigated. RESULTS: This study found that 788 (4.3%) subjects in the study group suffered from hip fracture, with a 4.2 years median time frame (interquartile range = 1.8-7.1). In the control group, 492 subjects (2.7%) suffered from hip fracture during a 4.8 years median time frame (interquartile range = 2.0-7.5). The relative risk of hip fracture for stroke was increased in the first four years (1.4-2.4) and gradually declined to the level of the general population. Cox regression analysis showed osteoporosis-related factors, including ageing, female and antidepressants, significantly increased hip fracture risk (hazard ratios 1.89, 1.57, 1.92). CONCLUSIONS: These findings imply that osteoporosis may play a major role in the occurrence of hip fracture in the first four years after a first-ever stroke. Early intervention to prevent bone loss should be regarded as an important part in stroke management, especially in older females, and should be sustained for four years at least. The benefit of antidepressants in stroke patients should be weighed against the increased risk of hip fracture.

Expression of aquaporin 1 and 4 in rats with acute hypoxic lung injury and its significance.

Aquaporin (AQP)-1 and AQP-4 expression in lung tissues of SD rats during high altitude hypoxic lung injury, and the relationship between AQP-1 and AQP-4 expression, and acute hypoxic lung injury was analyzed. Thirty six healthy SD rats were divided into hypoxia 1d, 2d, 3d, 5d, and 7d groups and control group (N = 6). Pathological changes in lung tissue were observed by hematoxylin and eosin staining; lung injury was scored, and ultrastructural changes in lung tissue were observed by transmission electron microscopy. Changes in moisture content in lung tissues were determined by analyzing the wet/dry weight ratio (W/D). Localization of AQP-1 and AQP-4 was determined by immunohistochemistry. AQP-1 and AQP-4 expression were detected by western blot. Lung W/D was lower in hypoxia groups than in control group, and the highest in 3d group (P < 0.05). Light microscopy revealed a thickening alveolar wall and outstretched and congestive alveolar wall in hypoxia group; electron microscopy revealed the presence of abnormal alveolar type II epithelial cells, cavitation in cytoplasm, microvillus-like protrusions, and a reduced lamellar body. AQP- 1 and AQP-4 were mainly distributed in the capillaries and lymphatic and alveolar epithelial cells and airway epithelial cells, respectively. AQP-1 protein expression was decreased (western blot) in hypoxia 1d group (the lowest in 3d group; P < 0.05); there were no significant changes about AQP- 4 expression. Therefore, AQP-1 may be involved in abnormal transport of liquid ALI and pathogenesis of lung edema. AQP-4 may not be involved in the formation of ALI lung edema.

Branches of NF-κb signaling pathway regulate hepatocyte proliferation in rat liver regeneration.

Previous studies have demonstrated that the nuclear factor κB (NF-κB) pathway is involved in promoting cell proliferation. To further explore the regulatory branches and their sequence in the NF-κB pathway in the promotion of hepatocyte proliferation at the transcriptional level during rat liver regeneration, Rat Genome 230 2.0 array was used to detect the expression changes of the isolated hepatocytes. We found that many genes involved in the NF-κB pathway (including 73 known genes and 19 homologous genes) and cell proliferation (including 484 genes and 104 homologous genes) were associated with liver regeneration. Expression profile function (Ep) was used to analyze the biological processes. It was revealed that the NF-κB pathway promoted hepatocyte proliferation through three branches. Several methods of integrated statistics were applied to extract and screen key genes in liver regeneration, and it indicated that eight genes may play a vital role in rat liver regeneration. To confirm the above predicted results, Ccnd1, Jun and Myc were analyzed using qRT-PCR, and the results were generally consistent with that of microarray data. It is concluded that 3 branches and 8 key genes involved in the NF-κB pathway regulate hepatocyte proliferation during rat liver regeneration.

Isolation and characterization of polymorphic microsatellite markers from Coilia ectenes.

Coilia ectenes (Jordan and Seale 1905) is an important anadromous species that is an important resource at risk of extinction because of over-fishing, pollution, and coastal construction. To evaluate the genetic diversity of C. ectenes for use in breeding programs, elite microsatellite-enriched libraries were constructed and novel microsatellite markers were developed, and applied to genetically detect wild populations. Out of 92 randomly selected and sequenced clones, 89 contained a CA or GA repeat motif. Twenty-two pairs of primers were designed to investigate the polymorphism and genetic structure of a wild population collected from the Yellow River estuary, China. It was found that 2 loci were monomorphic and 20 loci were polymorphic. The number of alleles per polymorphic loci ranged from 3 to 13, with an average of 7.9. The expected heterozygosity per locus ranged from 0.05 to 0.89, with an average of 0.68. The isolated polymorphic markers are expected to be of use in future genetic breeding programs for C. ectenes, and in the assessment of genetic variation within this species.