The Roles of Deubiquitinases in Renal Cell Carcinoma / 生物化学与生物物理进展

Renal cell carcinoma (RCC) is the primary malignant neoplasm. The ubiquitin-proteasome system (UPS) is crucial to the control of protein level and regulation of physiological and pathological processes. Deubiquitinases (DUBs), key components of UPS, specifically removing ubiquitin chains from the target protein, have showed crucial roles for protein homeostasis and quality control by rigidly regulating the balance between ubiquitination and deubiquitination in normal physiology. Accumulating studies indicate that abnormal function DUBs is associated with the progression and metastasis of RCC. Depending on the substrates, some DUBs may suppress RCC while others promote. Herein, we review recent research advances in RCC-associated DUBs, describe their classification, functional roles, summarize the role and mechanisms of action of DUBs in RCC and discuss the potential of targeting DUBs for cancer treatment.

SPOP-mediated Non-degradative Ubiquitination / 中国生物化学与分子生物学报

Protein post-translational modification is a precondition guaranteeing normal exertion of protein functions. Ubiquitination is an important post-translational modification that maintains normal protein levels and activity. Numerous researches show that the E3 ubiquitin ligase speckle-type POZ protein (SPOP) displays mutations in many tumors and genetic diseases. Mainly concentrated in the MATH structural domain that recognizes substrates, these mutations influence the binding between SPOP and substrates, and further influence their protein levels, positioning and activities, thus disturbing the normal physiological functions. Wild-type SPOP binds the substrates, most of which enter the proteasome pathway for decomposition after being ubiquitinated by SPOP, but some substrates are also influenced functionally. Herein we review the ubiquitination types and functions of SPOP substrates, including the ubiquitin-proteasome system (UPS), structure, functions and molecular pathways of SPOP, and non-degradative ubiquitinated modification of SPOP. The emphasis will be laid on the molecular mechanisms of the signaling pathways mediated by the three non-degradative substrates of SPOP, that is, myeloid differentiation primary response gene 88 (MyD88)-mediated NF-κB pathway, X-chromosome silence signal pathway of histone macroH2A1 (macroH2A. 1 histone, macroH2A1), and inverted formin 2 (INF2)mediated chondriokinesis pathway, in inhibiting tumorigenesis and development. We expect to provide a new perspective for precise targeted therapies of tumors.

The impact of fasting blood glucose on the prognosis of non-diabetic patients undergoing primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction / 中国介入心脏病学杂志

Objective To investigate the impact of fasting blood glucose on the prognosis of non-diabetic patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). Methods We retrospectively recruited consecutive patients who underwent primary PCI in our hospital from February, 2003 to March, 2015. Patients with prior history of diabetes mellitus before the index hospitalization and those with newly diagnosed diabetes mellitus during the index hospitalization were excluded. The clinical and angiographic features, medical and interventional treatment, and 30-day outcomes were compared between patients with elevated fasting blood glucose (FBG) (>5.4 mmol/L) and those with normal FBG (≤5.4 mmol/L). Results A total of 721 patients were recruited with an age of(61.2 ± 12.8)years, of whom 601 (83.4 %) were male. As compared with patients with normal FBG,those with elevated FBG were more likely to be female(20.1 % vs.13.5 %, P=0.017),had faster heart rate on admission[(82.9 ± 17.2)bpm vs.(79.4 ± 16.7)bpm,P=0.006]and more use of intra-aortic balloon pump(3.8 % vs.1.3 %,P=0.034),and had higher rates of 30 day all-cause mortality(3.5 % vs.0.5 %,P=0.004),cardiac mortality(2.9 % vs.0.5 %,P=0.012)and heart failure(18.1 % vs. 7.4 %, P< 0.001). After adjusting baseline characteristics, FBG > 5.4 mmol/L was one of the independent predictors of 30-day all-cause mortality(HR 6.030,95 % CI 1.235-29.447,P=0.026).Other independent predictors of 30-day all-cause mortality included age(HR 1.059,95 % CI 1.002-1.120,P=0.044),heart rate on admission(HR 1.036,95 % CI 1.003-1.070,P=0.034),left descending artery as the culprit vessel(HR 6.427,95 % CI 1.389-29.728,P=0.017),and use of angiotensin converting enzyme inhibitor/angiotensin receptor blocker(HR 0.154,95 % CI 0.051-0.461,P=0.001).Conclusions In non-diabetic patients undergoing primary PCI for STEMI, elevated FBG was one of the independent predictors of 30-day all-cause mortality.

Relevant factors of estrogen changes of myopia in adolescent females / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gender is one of the risk factors accounting for the high prevalence of adolescent myopia. Considerable research results have shown that myopia incidence of female is higher than that of male. This study aimed to analyze the correlation between ocular parameters and serum estrogen level and to investigate the vision changes along with estrogen change in menstrual cycle of adolescent females.</p><p><b>METHODS</b>A total of 120 young females aged between 15 and 16 years, diagnosed with myopia were recruited. Spherical lens, cylindrical lens, axis, interpupillary distance (IPD), and vision in each tested eye of the same subject were measured by automatic optometry and comprehensive optometry, with repetition of all measurements in the menstrual cycle of the 2 nd or 3 rd days, 14 th days, and 28 th days, respectively. Serum estradiol (E 2 ) levels were assayed by chemiluminescence immunoassay at the same three times points of the menstrual cycle mentioned above.</p><p><b>RESULTS</b>In young females with myopia, the spherical lens showed a statistically significant difference among all different time in menstrual cycle (all P < 0.0001). The cylindrical lens, axis, and IPD were changed significantly during the menstrual cycle (P < 0.05). The vision of the three different time points in menstrual cycle had a significant difference (χ2 = 6.35, P = 0.042). The vision during the 14 th and 28 th day was higher compared to that on the 2 nd or 3 rd days (P = 0.021). Serum E 2 levels were significantly different at different time points in menstrual cycle (P < 0.05). E 2 levels reached its maximum value on the 14 th day and the minimum value on the 2 nd or 3 rd day.</p><p><b>CONCLUSIONS</b>In adolescent females, the spherical lens and other related ocular parameters vary sensitively with different levels of E 2 in menstrual cycle. Vision in late menstrual stage is significantly higher than that in premenstrual stage.</p>

Synthesis and biological evaluation of 2-(3-butynoicamidophenyl) benzothiazole derivatives as antitumor agents / 药学学报

A series of 2-(3-butynoicamidophenyl)benzothiazole derivatives were synthesized starting from 4-fluoro-3-nitrobenzoic acid. Structures of all the synthesized compounds were confirmed by 1H NMR and HR-MS. Their antitumor activities against human tumor cells lines (HCT116, Mia-PaCa2, U87-MG, A549, NCI-H1975) were evaluated by MTT assay. The results revealed that most of the synthesized compounds showed potent activities against HCT116, Mia-PaCa2, U87-MG tumor cells lines. Particularly, compounds 14c and 14h exhibited better activity with IC50 values of 1 x 10(-8) mol x L(-1) against U87-MG and HCT116 respectively. The structure-activity relationship of compounds was also discussed preliminarily.

Changed accumulation of active ingredient in different localities and growth period of Hemsleya zhejiangensis (Cucurbitaceae) / 中国中药杂志

In this paper, the content of moisture, ethanol-soluble extractives, total saponins and polysaccharide of different tuber samples of Hemsleya zhejiangensis, from different localities, years and seasons, were detected based upon Chinese Pharmacopoeia 2010 version. The samples of roots, stems and leaves in summer were detected as well. The results are mainly as follows. (1)With tuber quality increasing, the content of total saponins increased and then decreased. The individual quality of tubers getting 594.06 g, the content of total saponins reached the peak. (2) The content of active ingredients in different localities was significantly different, and the population of Wuyanling had the maximum content of total saponins and polysaccharide. (3) The content of active ingredients revealed stability between the years 2012 and 2013, but the content of polysaccharide was significantly different. The content in 2012 was higher than that of 2013. (4) The content of active ingredients reached the peak in autumn, which was the best harvest season. (5) Among different component content detection of nutritional organs, tubers had the maximum content of ethanol-soluble extractives, total saponins and polysaccharide. Leaves also contained higher content of ethanol-soluble extractives and total saponins than roots and stems. All of these provide theoretical basis for plant, harvest and production of H. zhejiangensis, which is an endemic, rare, and endangered medicinal plants.

Clinical and coronary features of systemic lupus erythematosus patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVES</b>To observe the clinical and coronary features of patients with systemic lupus erythematosus (SLE) and coronary artery disease (CAD).</p><p><b>METHODS</b>Among 2877 SLE inpatients (age ≥ 18 years, male 363, female 2514) admitted in the Peking Union Medical College Hospital between January 1999 to October 2009, 33 patients [mean age (50.7 ± 12.8) years] were diagnosed with CAD and coronary angiogram was available in 20 out of these 33 patients. Clinical and coronary features of these patients were retrospectively reviewed.</p><p><b>RESULTS</b>The incidence of CAD was significantly higher in male SLE patients than in female patients [2.48% (9/363) vs. 0.95% (24/2514), P = 0.022]. Patients with secondary antiphospholipid syndrome were more likely to suffer from CAD [5.76% (8/139) vs. 0.91% (25/2738), P < 0.001]. Myocardial infarction was the major form of CAD (24/33). Coronary artery angiographic changes included coronary stenosis and occlusions, coronary aneurysms and acute thrombosis and multi-vessel lesions was found in 75.0% (15/20) patients with SLE and CAD.</p><p><b>CONCLUSIONS</b>Male SLE patients and patients with secondary antiphospholipid syndrome are at higher risk for CAD. Myocardial infarction and multi-vessel lesions are common in SLE patients with CAD.</p>

Long-term effects of drug-eluting stents versus bare metal stents on patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: outcomes of 3-year clinical follow-up / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The long-term safety and efficacy of drug-eluting stents (DES) versus bare metal stents (BMS) are unclear and controversial issues in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The purpose of this study was to compare the long-term outcome of STEMI patients undergoing primary PCI with DES versus BMS implantation.</p><p><b>METHODS</b>A total of 191 patients with acute STEMI undergoing PCI from Jan. 2005 to Dec. 2007 were enrolled. Patients received DES (n = 83) or BMS (n = 108) implantation in the infarction related artery according to physician's discretion. The primary outcome was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of death, myocardial infarction (MI), target vessel revascularization (TVR) and stent thrombosis. The difference of MACE was observed between DES and BMS groups.</p><p><b>RESULTS</b>The clinical follow-up duration was 3 years ((41.7 ± 16.1) months). MACE occurred in 20 patients during three years follow-up. Logistic regression analysis showed that the left ventricular ejection fraction (LVEF) was an independent predictor for MACE in the follow-up period (P = 0.0301). There was no significant difference in all-cause mortality (3.61% vs. 7.41%, P = 0.2647), the incidence of myocardial infarction (0 vs. 0.93%, P = 0.379) and stent thrombosis (1.20% vs. 1.85%, P = 0.727) between the DES group and BMS group. The incidence of MACE was significantly lower in the DES group compared to the BMS group (4.82% vs. 14.81%, P = 0.0253). The rate of TVR was also lower in the DES group (0 vs. 5.56%, P = 0.029). In the DES group, there was no significant difference in the incidence of MACE between sirolimus eluting stents (SES, n = 73) and paclitaxel-eluting stents (PES, n = 10) subgroups (2.74% vs. 20.00%, P > 0.05).</p><p><b>CONCLUSIONS</b>This finding suggested that drug-eluting stents significantly reduced the need for revascularization in patients with acute STEMI, without increasing the incidence of death or myocardial infarction. Use of DES significantly decreased the incidence of MACE compared with BMS during the 3-year follow-up.</p>

Design, synthesis and antitumor activity of sorafenib analogues containing 2-picolinylhydrazide moiety / 药学学报

A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2-3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.

Long-term outcome analysis of patients underwent percutaneous coronary intervention with prior ischemic stroke / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and long-term outcomes of patients underwent percutaneous coronary intervention (PCI) with prior ischemic stroke.</p><p><b>METHODS</b>A total of 2053 patients underwent PCI in Peking union medical college hospital from January 2003 to December 2007 were included in this analysis and patients were followed up to December 2009. End-point included all-cause mortality, cardiac death, stent thrombosis, target-lesion revascularization, myocardial infarction, re-cerebral infarction. Major bleeding events were recorded during follow-up.</p><p><b>RESULTS</b>There are 1945 coronary heart disease patients were followed up and 222 patients with prior ischemic stroke. Compared patients without prior ischemic stroke, patients with prior ischemic stroke were older (P = 0.000), had higher hypertension morbidity (P = 0.000), higher diabetes mellitus morbidity (P = 0.005), higher incidence of multi-vessels disease (P = 0.000). During the follow-up of (35.0 ± 19.6) months, cardiac death rate (8.5% vs. 3.9%, P = 0.002) and re-cerebral infarction rate (5.8% vs. 1.4%, P = 0.000) were higher in patients with prior ischemic stroke than patients without prior ischemic stroke. Dual antiplatelet therapy treatment time [(13.77 ± 11.33) months vs. (13.94 ± 11.33) months, P = 0.986] and major bleeding events (5.8% vs. 3.6%, P = 0.100) were similar between the two groups and cerebral hemorrhage rate (1.8% vs. 0.5%, P = 0.028) were higher in patients with prior ischemic stroke than patients without prior ischemic stroke.</p><p><b>CONCLUSION</b>Patients with prior ischemic stroke were associated with increased rate of risk factors, multiple coronary artery disease, cardiac death and re-cerebral infarction and higher cerebral hemorrhage rate during follow-up despite similar dual-anti platelet therapy time.</p>

Clinical and coronary angiographic features of patients with systemic vasculitis and coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical and coronary angiographic features of patients with systemic vasculitis and coronary artery disease.</p><p><b>METHOD</b>Fifteen patients (11 male) with systemic vasculitis and coronary artery diseases admitted to our hospital from January 1999 to October 2009 were reviewed.</p><p><b>RESULTS</b>There were 6 patients with Behcet's disease, 3 patients with Churg-Strauss syndrome, 2 patients with Takayasu arteritis, 1 patient with polyarteritis nodosa, 1 patient with microscopic polyangiitis, 1 patient with Wegner's granulomatosis and 1 patient with Kawasaki disease. Mean age of this cohort was (39.3 ± 11.9) years. Adverse coronary events occurred in 4 patients during the inactive phase of systemic vasculitis and in 9 patients during the active phase of systemic vasculitis. Twelve patients were hospitalized with acute myocardial infarction, 2 with angina pectoris and 1 with cardiac tamponade. There were 3 patients with acute left ventricular dysfunction and 3 patients with severe arrhythmias. Compared to patients in the inactive phase, patients in the active phase were younger [(32.4 ± 8.1) years vs. (47.0 ± 10.2) years], had less risk factors for atherosclerosis (1.2 ± 1.5 to 2.8 ± 1.7) and the time intervals between coronary artery disease and systemic vasculitis was shorter [0 - 7 years (average 1.6 years) to 3 - 30 years (average 17.7 years)]. Coronary angiography evidenced coronary stenosis or occlusions in 11 patients, coronary aneurysm and acute thrombosis in 1 patient, coronary aneurysms and occlusions in 1 patient and coronary spasm in 2 patients. LVEF measured by echocardiography was less than 50% in 8 patients.</p><p><b>CONCLUSION</b>Patients with various systemic vasculitis could develop severe coronary artery disease due to coronary stenosis/occlusion, aneurysma, thrombosis and coronary spasm.</p>

Clinical manifestations of premenopausal women with coronary arterial disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare clinical characteristics among premenopausal women with coronary arterial disease (CAD) with or without atherosclerosis (AS) and postmenopausal women with CAD.</p><p><b>METHODS</b>The clinical and coronary angiographic data, traditional risk factors (age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history) were compared among premenopause (Pre-M, n=42) and post-menopause (Post-M, n=172) women with CAD as well as Pre-M patients with non-AS CAD (non-AS CAD, n=8).</p><p><b>RESULTS</b>Compared with the Post-M patients with CAD, Pre-M CAD patients had significantly fewer traditional risk factors, such as hypertension, diabetes and hypercholesterolemia, significantly more acute coronary syndrome and fewer previous history of chest pain, significantly more single vessel lesion and lower Gessini score (all P < 0. 01). The logistic regression results showed that obesity is an independent risk factor for the development of CAD in premenopausal women (OR = 3. 655, 95% CI: 1. 5-11.59, P = 0.028). Hypertension (OR = 4.73, 95% CI: 0.991-22.589, P = 0.051) and hypercholesterolemia (OR = 4.68, 95% CI: 0.971-22.564, P = 0.055) might also contribute to the development of CAD in these patients. Clinical characteristics were similar between Pre-M and non-AS CAD patients (P > 0.05).</p><p><b>CONCLUSIONS</b>Pre-M CAD patients had less traditional risk factors and lower coronary lesion score compared to post-M CAD patients. Obesity is an independent risk factor for Pre-M CAD. Non-AS coronary artery disease is also an important reason for the development of coronary arterial events in premenopausal women.</p>

The regulative effects of polydatin on toll-like receptor 4 signal transduction pathway in lung ischemia/reperfusion injury in rabbits / 中国应用生理学杂志

<p><b>AIM</b>To investigate protective effects of polydatin(PD) during lung ischemia/reperfusion in rabbits and its potential mechanisms.</p><p><b>METHODS</b>Rabbit lung model of ischemia/reperfusion (I/R) injury was constituted in vivo. Thirty rabbits were divided into groups randomly: Control (C), I/R, PD group, respectively. Endotoxin (ET) in plasma was analyzed by End-point Chromogenic Assay, the expression of Toll-like receptor 4 (TLR4) mRNA, nuclear factor (NF)-kappaBp65 mRNA, intracellular adhesion molecule-1 (ICAM-1) mRNA were measured by RT-PCR, the morphological changes of lung tissue were observed with hematoxylin-eosin (HE) staining.</p><p><b>RESULTS</b>There was no significant difference in ET concentration of plasma between groups (all of P > 0.05). The expression of TLR-4 mRNA, NF-kappaBp65 mRNA and ICAM-1mRNA in I/R group were significantly increased as compared to C group and PD group, while those expressions in PD group were evidently higher than those in C group (all of P < 0.01). Light microscope showed that the lung pathological injuries in PD group were obviously alleviated as compared to I/R group.</p><p><b>CONCLUSION</b>PD might have a protective effect on lung ischemia/reperfusion injury by down-regulating TLR4 and NF-kappaB expression, then inhibiting the release of mediators of inflammation as ICAM-1.</p>

Quality of life survey on patients with chronic rhinosinusitis by using Chinese version of the 22-item sinonasal outcome test (SNOT-22) / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the health-related quality of life (QOL) status of patients with chronic rhinosinusitis.</p><p><b>METHODS</b>Sixty four patients with chronic rhinosinusitis and twenty healthy volunteers were enrolled, and their QOL scores were assessed by using SF-36 questionnaire (Chinese version) and SNOT-22 questionnaire translated into Chinese.</p><p><b>RESULTS</b>The feasibility, reliability, validity, and responsibility of Chinese version of SNOT-22 questionnaire all passed the test. It showed that by Chinese version of SNOT-22 questionnaire the most five important items affecting health status were nasal obstruction, runny nose, loss of smell or taste, dizziness and post-nasal discharge respectively. The coefficient of correlation was 0. 233 between the SNOT-22 questionnaire and the Lund-MacKay CT score of patients with chronic rhinosinusitis.</p><p><b>CONCLUSIONS</b>Chinese version of SNOT-22 questionnaire can effectively assess the QOL status of patients with chronic rhinosinusitis. It showed less correlation between the SNOT-22 questionnaire and the Lund-MacKay CT score of patients with chronic rhinosinusitis.</p>

Side branch occlusion rate at sites of overlapping sirolimus- or paclitaxel-eluting stents for treating long coronary lesions / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare side branch occlusion rate at sites of overlapping sirolimus- or paclitaxel-eluting stents in treating long coronary lesions.</p><p><b>METHODS</b>We retrospectively reviewed the PCI CD and medical records of PCI 141 patients with at least one stent overlapping for long coronary lesion in our institute from January 2004 to October 2007. The side branches occlusion was documented and analyzed.</p><p><b>RESULTS</b>The study population were consisted of 141 patients that there were 115 man, and 26 women, who got 297 stents. There were 154 side branch vessels been observed. Side branch occlusion rate was 24.6% in Cypher group and 31.6% in TAXUS (P > 0.05), side branch TIMI flow decrease rate on overlapping region was 26.3% in Cypher group and 68.4% in TAXUS group (P > 0.05). A logistic regression model analysis show that the significant risk factors for side branch occlusion is the diameter and ostial occlusion of side branch.</p><p><b>CONCLUSION</b>Side branch occlusion rate and TIMI flow decrease rate were similar on overlapping region in patients treated with Cypher or TAXUS stents for long coronary lesions. The significant predictors for side branch TIMI flow decrease are the diameter and ostial occlusion of side branch.</p>