Prevalence, risk factors and clinical correlates of glucose disturbances in a large sample of Han Chinese patients with first-episode drug-naïve major depressive disorder.

Glucose disturbances are a common comorbidity of major depressive disorder (MDD) patients and have been extensively studied in the past. However, few studies have explored glucose disturbances in first-episode drug-naïve (FEDN) MDD patients. The purpose of this study was to examine the prevalence and risk factors of glucose disturbances in FEDN MDD patients to understand the relationship between MDD and glucose disturbances in the acute early phase and provide important implications for therapeutic interventions. Using a cross-sectional design, we recruited a total of 1718 MDD patients. We collected their socio-demographic information, clinical data, and blood glucose indicators.17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, psychotic symptoms, respectively. The prevalence of glucose disturbances in FEDN MDD patients was 13.6%. Depression, anxiety and psychotic symptoms, body mass index (BMI) levels and suicide attempts rates were higher in the group with glucose disorders than in the group without glucose disorders among patients with first-episode drug-naive MDD. Correlation analysis showed that glucose disturbances were associated with HAMD score, HAMA score, BMI, psychotic symptoms and suicide attempts. Furthermore, binary logistic regression showed that HAMD score and suicide attempts were independently associated with glucose disturbances in MDD patients. Our findings suggest that the prevalence of comorbid glucose disturbances is very high in FEDN MDD patients. Moreover, more severe depressive symptoms and higher suicide attempts are correlated with glucose disturbances in MDD FEDN patients in the early stage.

Clinical Characteristics and Outcomes of Chinese Patients with Premature Acute Coronary Syndrome.

This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

Valve implantation for successful sealing of a balloon predilatation-induced annular rupture during transcatheter aortic valve replacement.

Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR.

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy.

Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

Metformin promotes microglial cells to facilitate myelin debris clearance and accelerate nerve repairment after spinal cord injury.

Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg-1·d-1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.

Annular and supra-annular structure assessments for transcatheter aortic valve replacement in patients with bicuspid aortic stenosis.

The clinical use indications for transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) have expanded from patients at high surgical risk to those at low risk based on the results of multiple large-scale randomized trials. However, patients with bicuspid AS have traditionally been excluded from clinical trials due to their unfavorable morphological characteristics. Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, occurring in 1% to 2% of the total population and affects more than 20% of octogenarians undergoing isolated aortic valve replacement for AS. In recent years, TAVR in patients with bicuspid AS has been the focus of research, especially with respect to the standard of prosthesis size selection. Annulus-based prosthesis size selection using computed tomography (CT) is the standard sizing strategy for tricuspid AS, but no standard sizing for bicuspid AS has been developed thus far. According to Western TAVR experiences, transcatheter heart valve (THV) size selection for BAV patients should be based on the annular structure assessment by CT measurement, whereas Chinese experiences favor adopting the supra-annulus structure assessment for THV size selection. This article will review annular and supra-annular sizing for prosthesis size selection in patients with bicuspid AS before TAVR and discuss which has more favorable clinical outcomes.

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

Long-term amlodipine-based combination therapy attenuates seasonal variation of blood pressure in hypertensive patients.

Objectives: This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. Methods: The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for three years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. Results: In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, P < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Conclusions: Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.

Effect of transient scrotal hyperthermia on human sperm: an iTRAQ-based proteomic analysis.

BACKGROUND: Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. METHODS: Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. CONCLUSIONS: The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

Genetic and morphological divergence among three closely related Phrynocephalus species (Agamidae).

BACKGROUND: The Qinghai-Tibetan Plateau (QTP) is the world's highest and largest plateau, but the role of its uplift in the evolution of species or biotas still remains poorly known. Toad-headed lizards of the reproductively bimodal genus Phrynocephalus are a clade of agamids, with all viviparous species restricted to the QTP and adjacent regions. The eastern part of the range of the viviparous taxa is occupied by three closely related but taxonomically controversial species, P. guinanensis, P. putjatia and P. vlangalii. Here, we combined genetic (mitochondrial ND4 gene and nine microsatellite loci), morphological (11 mensural and 11 meristic variables), and ecological (nine climatic variables) data to explore possible scenarios that may explain the discordance between genetic and morphological patterns, and to test whether morphological divergence is associated with local adaptation. RESULTS: We found weak genetic differentiation but pronounced morphological divergence, especially between P. guinanensis and P. vlangalii. Genetically, the species boundary was not so clear between any species pair. Morphologically, the species boundary was clear between P. guinanensis and P. vlangalii but not between other two species pairs. Body size and scale characters accounted best for morphological divergence between species. Morphological divergence was related to habitat types that differ climatically. CONCLUSIONS: Our study provides evidence for genetic and morphological divergence among the three closely related viviparous species of Phrynocephalus lizards, and supports the idea that natural selection in spatially heterogeneous environments can lead to population divergence even in the presence of gene flow. Our study supports the hypothesis that the evolutionary divergence between viviparous Phrynocephalus species was a consequence of environmental change after the uplift of the QTP.