Prevalence and clinical characteristics of renovascular hypertension associated with fibromuscular dysplasia in China.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics of renal artery fibromuscular dysplasia (FMD) in patients in China and identify the cure rate of hypertension after angioplasty. METHODS: Consecutive hypertensive patients with renal artery stenosis caused by FMD who underwent catheter-based angiography, and were followed at two Chinese referral centres, were retrospectively analysed. All patients underwent a detailed investigation, including demographic characteristics, clinical characteristics, biochemical sampling, Doppler ultrasonography of carotid arteries, magnetic resonance angiography (MRA) of the intracranial artery, and CTA or MRA of the abdominal artery and catheter-based renal angiography. Patients were routinely followed up at 1 month, 6 months and every year after the procedure. RESULTS: Among 245 study participants, with a mean diagnosed age of 26.9 ±â€Š9.9 years, 137 (55.9%) were women, and 38 (15.5%) were children. All patients were diagnosed with hypertension at a mean age of 23.4 ±â€Š8.4 years. There were 73.5% focal and 15.2% multivessel cases. Aneurysms, arterial dissections and total occlusions were found in 21.6, 4.1 and 12.2% of patients, respectively. Patients with multifocal FMD were older (26.0 vs. 23.7 years, P  = 0.021) and more often female (70.8 vs. 50.6%, P  = 0.004). Among children with renal FMD, 55.2% were men, and 86.8% were focal. After a median follow-up of 7.0 years, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.7 vs. 55.8%, P  = 0.032). CONCLUSION: In a cohort of mostly young Chinese patients, the prevalence of hypertension associated with renal FMD is similar in both sexes. Focal FMDs were more frequent than the multifocal ones and, after angioplasty, were associated with a worse blood pressure outcome.

Hyperthermia promotes degradation of the acute promyelocytic leukemia driver oncoprotein ZBTB16/RARα.

The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents. However, mild hyperthermia (42 °C) rapidly destabilized the ZBTB16/RARα fusion protein expressed in HeLa, 293T, and OCI-AML3 cells, followed by robust ubiquitination and proteasomal degradation. In contrast, hyperthermia did not affect the normal (i.e., unfused) ZBTB16 and RARα proteins, suggesting a specific thermal sensitivity of the ZBTB16/RARα fusion protein. Importantly, we found that the destabilization of ZBTB16/RARα was the initial step for oncogenic fusion protein degradation by hyperthermia, which could be blocked by deletion of nuclear receptor corepressor (NCoR) binding sites or knockdown of NCoRs. Furthermore, SIAH2 was identified as the E3 ligase participating in hyperthermia-induced ubiquitination of ZBTB16/RARα. In short, these results demonstrate that hyperthermia could effectively destabilize and subsequently degrade the ZBTB16/RARα fusion protein in an NCoR-dependent manner, suggesting a thermal-based therapeutic strategy that may improve the outcome in refractory ZBTB16/RARα-driven APL patients in the clinic.

The prevalence of masked hypertension in relation to cigarette smoking in a Chinese male population.

BACKGROUND: Smokers may smoke cigarettes during ambulatory or home blood pressure (BP) monitoring but not clinic measurement. We investigated the prevalence of masked hypertension in relation to cigarette smoking in Chinese outpatients enrolled in a multicenter registry. METHODS: Our study included 1646 men [494 (30.0%) current smokers]. We defined masked hypertension as a normal clinic SBP/DBP (<140/90 mmHg) and elevated daytime (≥135/85 mmHg) or night-time (≥120/70 mmHg) ambulatory or morning or evening home SBP/DBP (≥135/85 mmHg). RESULTS: In all men, multiple logistic regression showed that current cigarette smoking was significantly associated with daytime [prevalence 18.7%, odds ratio (OR) 1.69, 95% confidence interval 1.27-2.25, P = 0.0003] but not night-time (prevalence 27.1%, P = 0.32) ambulatory masked hypertension and associated with evening (prevalence 14.6%, OR 1.81, confidence interval 1.33-2.47, P = 0.0002) but not morning (prevalence 17.6%, P = 0.29) home masked hypertension. The associations were more pronounced for heavy smoking (≥20 cigarettes/day) relative to never smoking for both masked daytime ambulatory (OR 1.97, P = 0.001) and evening home hypertension (OR 2.40, P < 0.0001) or in patients over 55 years of age (P for interaction in relation to daytime ambulatory masked hypertension = 0.005). In men with clinic normotension (n = 742), the associations were also significant (P < 0.01), particularly in those with a normal to high-normal clinic BP (n = 619, P < 0.04). CONCLUSION: Cigarette smoking was associated with increased odds of masked daytime ambulatory and evening home hypertension, especially in heavy smoking or older men.

SIRT1 acts as a potential tumor suppressor in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in oral cancer, however, the mechanism underlying OSCC tumorigenesis is unknown. SIRT1, has been considered a prominent tumor-suppressing/promoting gene in various solid tumors, although the precise role of SIRT1 in OSCC progression remains unknown. METHODS: SIRT1 expression was assessed in surgically resected specimens from patients with OSCC for histopathologic factors. SIRT1 levels in OSCC were determined, SIRT1 overexpression was achieved on transfecting OSCC cells with a SIRT1-containing plasmid, followed by evaluation of proliferative ability and invasiveness of these cells. RESULTS: SIRT1 levels were significantly lower in patients with OSCC than in controls (p < 0.05). Moreover, SIRT1 levels in patients with OSCC were significantly associated with the lymphovascular permeation but not with the sex, age, stage and location. Furthermore, SIRT1 overexpression inhibited proliferation and invasion in OSCC cells. CONCLUSION: The present results suggest that SIRT1 is a potential tumor suppressor in OSCC.

Identification of essential amino acid changes in paired domain evolution using a novel combination of evolutionary analysis and in vitro and in vivo studies.

Pax genes are defined by the presence of a paired box that encodes a DNA-binding domain of 128 amino acids. They are involved in the development of the central nervous system, organogenesis, and oncogenesis. The known Pax genes are divided into five groups within two supergroups. By means of a novel combination of evolutionary analysis, in vitro binding assays and in vivo functional analyses, we have identified the key residues that determine the differing DNA-binding properties of the two supergroups and of the Pax-2, 5, 8 and Pax-6 subgroups within supergroup I. The differences in binding properties between the two supergroups are largely caused by amino acid changes at residues 20 and 121 of the paired domain. Although the paired domains of the Pax-2, 5, 8 and the Pax-6 group differ by >19 amino acids, their distinct DNA-binding properties are determined almost completely by a single amino acid change. Thus, a small number of amino acid changes can account in large part for the divergence in binding properties among the known paired domains. Our approach for selecting candidate sites responsible for the functional divergence between genes should also be useful for studying other gene families.