Incidence and mortality trends in oral and oropharyngeal cancers in China, 2005-2013.

BACKGROUND: Oral and oropharyngeal cancers are among the most common cancers globally. This study aimed to assess the incidence and mortality trends of oral and oropharyngeal cancers in China between 2005 and 2013. METHODS: Estimates of national trends of oral and oropharyngeal cancers were based on the data from Chinese Cancer Registry Annual Reports. The crude incidence rates of oral and oropharyngeal cancers between 2015 and 2035 were evaluated. The age-standardized rate was based on the world standard population. RESULTS: It was estimated that 285,857 new cases and 132,698 deaths were related to oral and oropharyngeal cancers in China between 2005 and 2013, with mouth and tongue cancers being the most frequently diagnosed and the leading causes of death among all oral and oropharyngeal cancers. The incidence rates of oral and oropharyngeal cancer fluctuated from 1.69 to 1.89 per 100,000 person-years, and the mortality rate showed an increasing trend, ranging from 0.77 and 0.84 per 100,000 person-years. Males were more susceptible than females to oral and oropharyngeal cancers. The incidence and mortality rates of oral and oropharyngeal cancers were significantly higher in urban regions. The crude incidence rates of oral cancers are projected to increase from 2.26 to 3.21 per 100,000 person-years over the next 20 years in China. CONCLUSION: The incidence of oral and oropharyngeal cancers fluctuated, whereas the mortality rate showed an upward trend from 2005 to 2013. A heavier burden from oral and oropharyngeal cancers is predicted in the next two decades in China.

Development of a facescan 3D facial reconstruction technology method for quantitative evaluation of cheilitis granulomatosa.

We explored the applicability of Facescan three-dimensional (3D) facial reconstruction technology for adjunctive diagnosis and therapeutic evaluation of cheilitis granulomatosa (CG) in 33 patients with CG and 29 healthy controls at the Dept. of Oral Medicine, Peking University, School and Hospital of Stomatology (PKUSS), from January 2015 to May 2016. The Facescan structured-light 3D facial reconstruction scanner was used to scan the scope of lips in both groups, in order to acquire 3D morphological data of the lips. The lengths of six characteristic line segments were measured from the 3D lip model of the two groups, and the acquired data were compared. The results showed that the distance between the labiale superius and labiale inferius, and the lengths of the upper and lower vermilion borders showed significant differences between the CG and control groups, by using the 3D lip model. Thus, Facescan 3D facial reconstruction technology showed good reproducibility in the evaluation of lip swelling in CG patients, and it can be used to analyse the degree of lip swelling and evaluate the therapeutic efficacy of different treatments for CG.

Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells.

BACKGROUNDS: Autophagy is an important process in the pathogenesis of diabetes and plays a critical role in maintaining cellular homeostasis. However, the autophagic response and its mechanism in diabetic vascular endothelium remain unclear. METHODS AND RESULTS: We studied high-glucose-induced renin-angiotensin system (RAS)-mitochondrial damage and its effect on endothelial cells. With regard to therapeutics, we investigated the beneficial effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) against high-glucose-induced endothelial responses. High glucose activated RAS, enhanced mitochondrial damage and increased senescence, apoptosis and autophagic-responses in endothelial cells, and these effects were mimicked by using angiotensin II (Ang). The use of an ACEI or ARB, however, inhibited the negative effects of high glucose. Direct mitochondrial injury caused by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) resulted in similar negative effects of high glucose or Ang and abrogated the protective effects of an ACEI or ARB. Additionally, by impairing autophagy, high-glucose-induced senescence and apoptosis were accelerated and the ACEI- or ARB-mediated beneficial effects were abolished. Furthermore, increases in FragEL™ DNA Fragmentation (TUNEL)-positive cells, ß-galactosidase activation and the expression of autophagic biomarkers were revealed in diabetic patients and rats, and the treatment with an ACEI or ARB decreased these responses. CONCLUSIONS: These data suggest that autophagy protects against senescence and apoptosis via RAS-mitochondria in high-glucose-induced endothelial cells.

Inhibition of farnesyl pyrophosphate synthase prevents norepinephrine-induced fibrotic responses in vascular smooth muscle cells from spontaneously hypertensive rats.

Both norepinephrine (NE) and connective tissue growth factor (CTGF) contribute to vascular fibrosis during hypertension. Recent studies indicate that farnesyl pyrophosphate synthase (FPPS) plays an important role in cardiac remodeling in hypertension. However, the role of FPPS in NE-induced fibrotic responses and related molecular mechanisms is unknown. Vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were stimulated with NE. The fibrotic responses were assessed by measuring CTGF, hydroxyproline (hyp), and α-1 procollagen I levels using Western blot, a hydroxyproline test kit, and real-time quantitative PCR assays, respectively. Ras activity was determined by a pull-down assay using a Ras activation assay kit and detected by Western blot. NE dose-dependently increased fibrosis in SHR-VSMCs, and this increase was significantly reduced by ibandronate, an inhibitor of FPPS. The addition of farnesol, but not geranylgeraniol, partially reversed the inhibitory effects of ibandronate. Furthermore, the anti-fibrotic effects of ibandronate could be mimicked by FTI-276 but not by GGTI-286. A pull-down assay showed that ibandronate reduced the NE-induced Ras activation. Moreover, ibandronate inhibited the NE-induced activation of p38, JNK, and ERK1/2. Only SB203580 (specific inhibitor of p38) diminished the NE-induced CTGF production. These results demonstrated that inhibiting FPPS prevents NE-induced fibrotic responses in SHR-VSMCs and that the Ras kinase and p38 pathways were the underlying mechanisms involved in this process.

The elevated serum S100A8/A9 during acute myocardial infarction is not of cardiac myocyte origin.

Overproduction of circulating S100A8/A9 occurs in patients following acute myocardial infarction (AMI). It remains unclear whether ischemia insult per se induces S100A8 and S100A9 expression in cardiac myocytes or even whether the cardiac myocytes participate as a source of these proteins. In this study, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction were used to test samples obtained from isolated spontaneously hypertensive rat hearts and Wistar-Kyoto rat hearts subjected to global normothermic ischemia and from neonatal Wistar rat cardiac myocytes undergoing hypoxia. Ischemia did not increase the expression of S100A8 and S100A9 proteins and mRNA in the myocardium either from the spontaneously hypertensive rat hearts or the Wistar-Kyoto rat hearts. In addition, the levels of S100A8 and S100A9 proteins were unchanged in the neonatal rat cardiac myocytes undergoing hypoxia. However, both ischemia and hypoxia activated NF-kappaB in ischemic myocardium and in hypoxic cardiac cells in a time-dependent manner. The results suggest that the increased serum S100A8/A9 concentrations following AMI were not of cardiac myocyte origin.

Systemic evaluation of platelet and leukocyte activation and interaction in a rat model of pulmonary arterial hypertension.

OBJECTIVES: Thrombosis and inflammation are associated with the pathogenesis of pulmonary arterial hypertension (PAH). However, there are no solid data supporting the involvement of platelet and leukocyte activation and interaction in PAH. The present study thus investigated the activation and interaction of circulating platelets and leukocytes in a rat model of monocrotaline (MCT)-induced pulmonary hypertension. METHODS: Mean pulmonary arterial pressure (mPAP) was monitored in rats (n = 24) before and 2, 3 and 7 weeks after MCT (60 mg/kg)injection. In parallel, activation of circulating platelets and leukocytes and platelet-leukocyte aggregates were measured by whole-blood flow cytometry. RESULTS: Two weeks after MCT injection, mPAP had increased significantly, i.e. from 11.25 ± 0.92 mm Hg at baseline to 15.71 ± 1.66 mm Hg (p < 0.05), and it had increased even further at week 7 (26.83 ± 3.29 mm Hg; p < 0.01). Fibrinogen binding of circulating platelets had increased from the basal level of 1.45 ± 0.61 to 4.08 ± 1.59% 3 weeks after MCT injection (p < 0.01). Platelet responsiveness to ADP was also significantly enhanced. CD11b expression of circulating neutrophils was elevated; i.e. mean fluorescence intensity increased from 1.67 ± 0.38 before MCT injection to 2.37 ± 0.31 3 weeks after MCT injection (p < 0.01), and N-formyl-methionyl-leucyl-phenylalanine (1 × 10⁻7M) stimulation induced more marked elevation of neutrophil CD11b expression in MCT-treated animals. Circulating platelet-neutrophil aggregates were already increased 2 weeks after MCT treatment (14.93 ± 4.22%; p < 0.01) compared to baseline (6.01 ± 2.91%) and remained elevated at 3 weeks (15.19 ± 4.78%; p < 0.01). CONCLUSIONS: MCT-induced PAH in rats is associated with increased platelet and leukocyte activation and platelet-leukocyte interaction in vivo, which may play an important role in the pathogenesis of PAH.

Proteasome inhibitor MG132 suppresses number and function of endothelial progenitor cells: involvement of nitric oxide synthase inhibition.

The aim of this study was to determine whether proteasome inhibitor MG132 treatment has any effect on endothelial progenitor cells (EPCs). Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation. EPCs were identified as adherent cells double positive for DiLDL-up-take and lectin binding by direct fluorescent demonstrated under a laser scanning confocal microscope. After 7 days in culture, EPCs were stimulated with proteasome inhibitor MG132 in series of final concentrations of 20, 50, 100, 200 nmol/l for 12, 24, 48 h. Cell proliferation and apoptosis were determined, respectively, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V/propidium iodide binding assay. Colony-forming capacity was performed by colony assay. EPCs adhesion and migration were assayed with adhesion assay and transwell migration assay, respectively. The expression of endothelial nitric oxide synthase (eNOS) was assayed by Western blot analysis, while nitric oxide (NO) generation was detected using the Griess method. It was found that proteasome inhibitor MG132 decreased the number of EPCs and EPC colonies, increased EPC apoptosis, decreased EPC proliferative, adhesive, migration capacity and eNOS/NO production in a concentration- and time-dependent manner. These data indicate that proteasome inhibitor MG132 suppresses the number and function of EPCs, and these actions may involve decreased eNOS/NO production in the EPCs.

Cyclophosphamide protects against myocardial ischemia/reperfusion injury in rats: one of the therapeutic targets is high sensitivity C-reactive protein.

OBJECTIVE: Cyclophosphamide has a role of decreasing high-sensitivity C-reactive protein in the treatment of autoimmune disorders. The effect of cyclophosphasmide on high-sensitivity C-reactive protein was investigated in myocardial ischemia/reperfusion rat. METHODS: Open-chest rats were submitted to 30 minutes of ischemia and followed for 3, 12, or 24 hours of reperfusion. All 72 rats survived and were divided into sham, ischemia/reperfusion (I/R) and cyclophosphamide groups, and each group included 3 time-point subgroups (3, 12, and 24 hours; n = 8 for each subgroup). Cyclophosphamide (0.75 g/m(2)) or saline was intraperitoneally administrated in the cyclophosphamide or I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure, left ventricular end-diastolic pressure, and maximum rate of rise or fall of left ventricular pressure. In the end, blood was collected for detection of high-sensitivity C-reactive protein, and hearts were harvested for histopathologic assessment and infarct size determination. RESULTS: Compared with the I/R group, rats treated with cyclophosphamide showed a significant recovery in myocardial function with improved left ventricular systolic pressure (88.27 +/- 3.78 vs 68.62 +/- 3.78 mm Hg at 3 hours, 92.04 +/- 3.77 vs 63.74 +/- 4.87 mm Hg at 12 hours, and 90.41 +/- 3.98 vs 64.21 +/- 4.88 mm Hg at 24 hours; P < .05, respectively). Left ventricular end-diastolic pressure and maximum rate of rise or fall of left ventricular pressure also had similar trends. Infarct size was reduced (26.1% +/- 0.4% vs 40.4% +/- 0.4% at 3 hours, 21.6% +/- 0.4% vs 49.9% +/- 0.4% at 12 hours, and 21.6% +/- 0.4% vs 40.0% +/- 0.4% at 24 hours; P < .01, respectively). Histopathologic damage score was attenuated (1.83 +/- 0.14 vs 2.17 +/- 0.14 at 3 hours, 2.33 +/- 0.14 vs 3.17 +/- 0.14 at 12 hours, and 2.83 +/- 0.14 vs 3.83 +/- 0.14 at 24 hours; P < .01, respectively). Plasma high-sensitivity C-reactive protein concentration was significantly reduced (29.28 +/- 0.51 vs 32.26 +/- 0.51 ng/mL at 3 hours, 29.06 +/- 0.50 vs 31.8 +/- 0.51 ng/mL at 12 hours, and 28.61 +/- 0.51 vs 31.86 +/- 0.51 ng/mL at 24 h; P < .01, respectively). CONCLUSION: Cyclophosphamide protects myocardial ischemia/reperfusion injury in the rat with a decrease in plasma concentration of high-sensitivity C-reactive protein.

[Quantitative and functional changes of circulating endothelial progenitor cells in dogs with dehydromonocrotaline-induced pulmonary artery hypertension].

OBJECTIVE: To determine the quantitive and functional changes of circulating endothelial progenitor cells (EPCs) in dogs with dehydromonocrotaline-induced pulmonary artery hypertension (PAH). METHODS: Dehydromonocrotaline was injected into the canine right ventricle to induce pulmonary hypertension. Circulating EPCs were enumerated as AC+(113), KDR+ cells by fluorescence-activated cell sorter using counting beads, and the number and activity of EPCs after in vitro expansion were determined by acLDL uptake/lectin staining assay and in vitro tubule forming assay. RESULTS: Nine of the 10 beagles survived after dehydromonocrotaline injection. Six weeks later, mean pulmonary artery pressure increased from (11.3 +/- 2.0) mm Hg (1 mm Hg = 0.133 kPa) to (20.2 +/- 1.6) mm Hg (t =10.307, P < 0.01), and the AC+(133) and KDR+ cells decreased from (632.8 +/- 42.8) cells/ml to (206.1 +/- 26.8) cells/ml (t = 25.361, P < 0.01). UEA- I and DiLDL positive cells deceased from (41 +/- 6) EPCs/ x 200 field to (22 +/- 6) EPCs/ x 200 field (t = 6.510, P < 0.01). In addition, in vasculogenesis assay, PAH EPCs formed less quantitative (11.2 +/- 2.8 vs 21.1 +/- 2.8 tubules/ x 200 field, respectively, t = 7. 583, P <0. 01) and less qualitive tubules than baseline EPCs. CONCLUSION: The number and vessel forming ability of EPCs are impaired in this canine model of dehydromonocrotaline-induced pulmonary hypertension.

[Contribution of circulating platelet and leukocyte activation to primary pulmonary hypertension in rats].

OBJECTIVE: To evaluate the contribution of platelet and leukocyte activation in pathogenesis primary pulmonary hypertension (PPH). METHODS: Pulmonary hypertension was induced by subcutaneous injection of 2% monocrotaline (MCT) in male Prague-Dawley (SD) rats. Blood samples were collected at the third week after MCT injection, and flow cytometry was used to determine the fibrinogen-binding platelet, CD11b expression on leukocyte and platelet-leukocyte aggregation. RESULT: Three weeks after MCT injection, rats exhibited higher right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure(mPAP), as compared with controls. MCT induced vascular remodeling characterized by vascular medial wall thickening in pulmonary muscular arteries. The ratio of platelets fibrinogen binding was increased in rats 3 weeks after MCT injection than that of control group[(4.08 +/-1.59)% compared with (1.45 +/- 0.61)%, P<0.01]. CD11b expression in monocytes and neutrophils, but not in lymphocytes was increased significantly 3 weeks after MCT injection (P <0.01). Platelet-neutrophil aggregations increased in MCT injected rats as compared with controls (P <0.01). CONCLUSION: Rats of PPH model demonstrate enhanced circulating platelet and leukocyte activation, which may contribute to the pathogenesis of PPH.

[Effects of angiotensin converting enzyme inhibitor on the expression of angiotensin converting enzyme 2 in atrium of patients with atrial fibrillation].

OBJECTIVE: To investigate the expression of angiotensin converting enzyme 2 (ACE2) and the changes treated with angiotensin converting enzyme inhibitor (ACEI), and its signal transduction pathway. METHODS: Atrial tissues were obtained from 47 patients with RHD undergoing cardiac surgery. The mRNA of ACE2 and ACE were semi-qualified by RT-PCR and normalized to the gene beta-actin. Western blot analysis was employed to examine the expressions of ACE2, ACE, ERK1/2 and phosphorylated ERK (pERK1/2). The atrial tissue angiotensin II (Ang II) content was determined by radioimmunoassay detection. RESULTS: The expression of ACE2 was significantly decreased (P < 0.05), the expression of ACE and pERK1/2 were significantly increased (P < 0.05), and the level of atrial tissue Ang II was significantly increased in patients with chronic atrial fibrillation group (CAF) compared with sinus rhythm group (SR) (P < 0.05). Compared with CAF patients treated without ACEI, the expression of ACE2 significantly increased (P < 0.01), and the relative activity of ERK1/2 significantly decreased (P < 0.05), whereas the expression of ACE and the level of atrial tissue Ang II remained unchanged in CAF patients treated with ACEI. CONCLUSIONS: The study suggested that the dysequilibrium of ACE/ACE2 might play an important role in the process of atrial fibrillation, which may be related to the activation of ERK1/2 pathway. The clinical effect of long-term treatment of ACEI maybe associated with elevated ACE2 expression but not ACE expression.

Pulmonary vein activation in atrial fibrillation and sinus rhythm.

AIMS: The purpose of this study was to determine the relationship between pulmonary vein (PV) electrical activation during atrial fibrillation (AF) and after cardioversion into sinus rhythm. METHODS AND RESULTS: Electrograms were recorded using a circular mapping catheter during AF and after cardioversion in 53 PVs from 41 patients. Two activation patterns were observed in AF. Group 1 had fixed, consistent, uniform activation sequences most (>70%) of the recording time. Group 2 had no fixed activation sequence. In Group 1, a constant single activation sequence pattern was seen in 22 PVs (Group 1a). The earliest PV activation sites were the same during AF and after cardioversion to sinus rhythm in 17 (77%) PVs from Group 1a. Fourteen of these 17 (82%) cases also had a common site of electrogram polarity reversal. In Group 2, a relationship between PV activation before and after cardioversion was not found. Segmental radio frequency (RF) ablation was performed during sinus rhythm after cardioversion. There was no difference in the number of atriovenous breakthroughs between the two groups (1.9+/-0.7 vs. 2.0+/-0.6 breakthroughs, P=NS). PV disconnection was achieved in all PVs with a mean RF duration of 13.5+/-4.5 min per vein in Group 1 and 14.0+/-4.9 min per vein in Group 2 (P=NS). CONCLUSION: A uniform PV electrogram pattern recorded during AF usually predicts the activation sequence and/or the polarity reversal sites during sinus rhythm. This pattern does not necessarily suggest a single atriovenous breakthrough point.

Homocysteine stimulates nuclear factor kappaB activity and interleukin-6 expression in rat vascular smooth muscle cells.

It has been reported that chronic inflammation of the vessel wall is a hallmark of atherosclerosis. Interleukin-6 (IL-6) is regarded as an important modulator of inflammatory events occurring during all stages of atherogenesis. Although many factors that induce IL-6 expression have been identified, the effect of homocysteine (Hcy) on the expression of IL-6 in atherogenesis and the underlying mechanisms are not entirely clear. The objective of the present study was to investigate the role of Hcy in IL-6 expression in rat aorta vascular smooth muscle cells (VSMCs). After VSMCs were incubated with Hcy for various time periods, enzyme-linked immunosorbent assay (ELISA) and semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) were performed to measure the expression of IL-6. Electrophoretic mobility shift assay (EMSA) was used to examine nuclear factor kappaB (NF-kappaB) activity. Hcy (0.01-0.25 mmol/l) significantly increased the expression of IL-6 mRNA and protein in rat VSMCs. The increase in IL-6 expression was associated with the activation of NF-kappaB. Pyrrolidine dithiocarbamate (PDTC) suppressed Hcy-induced IL-6 release, a finding compatible with involvement of reactive oxygen species as second messengers in cytokine production mediated by Hcy. The present study has clearly demonstrated the ability of Hcy to elicit an inflammatory response in rat VSMCs by stimulation of IL-6 production and activation of NF-kappaB. Inflammation activation on vessel walls by elevation of Hcy may contribute to the pathogenesis of atherosclerosis.

[Efficacy and safety of azosemide in patients with edema and ascites].

OBJECTIVE: To assess the efficacy and safety of azosemide in patients with edema and ascites. METHODS: A multicentral, randomized, double-blind, controlled clinical trial was applied. All 223 patients (cardiac edema 92, hepatogenic edema 63, renal edema 68) were randomized to azoesmide and furosemide group, and all patients were treated for 2 weeks. Patients with cardiac or renal edema took azosemide (30 mg/d) or furosemide (20 mg/d); patients with hepatogenic edema took azosemide (60 mg/d) or furosemide (40 mg/d). The dosage were adjusted to azosemide 60 mg/d (cardiac, renal edema), 90 mg (hepatogeic edema); or furosemide 40 mg/d (cardiac, renal edema), 60 mg (hepatogeic edema), if diuretic effects were not obtained at the end of third day. RESULTS: At the end of the study, the weight changes were (2.87+/-3.10) kg and (2.81 +/-2.84) kg; the total effective rate of edema lessen was 89.19% and 89.81%; the total effective rate of heart function improvement was 64.44% and 66.66%; the 24 h urine output increased (321.85 +/-669.52) ml and (273.80 +/-645.72) ml for azosemide and furosemide, respectively. The total effective rate of ascites lessen (tested by B-ultrasound) was 89.28% and 86.66%; abdominal girth decreased (5.20 +/-3.58) cm and (5.03 +/-3.74) cm for azosemide and furosemide, respectively. The adverse event rate was 23.01% in azosemide group and 21.01% in furosemide group; the main adverse effects were hypokalemia, hyperuricemia, hypertriglyceridemia and thirsty. CONCLUSION: Azosemide could effectively lessen edema, improve heart function and decrease ascitesûit is well tolerated and is particularly useful for the diuretic treatment.

[Early impairment of renal function in chronic heart failure and its clinical significance].

OBJECTIVE: To observe the changes of the microproteinuria (MA) and the relationship in patients with chronic heart failure (CHF). METHODS: Routine urine protein, blood creatinine and urea nitrogen and MA, immunoglobulin G (UIgG), retinal-binding protein (URbp) and beta-2-microglobulin (Ubeta(2)-MG) were measured and analyzed in 25 patients with CHF, 22 patients with cardiovascular diseases but compensated heart function s and 20 normal volunteers. RESULTS: The levels of Ualb and UIgG in the CHF group were significantly higher than those in the normal group and compensated heart function group [(7.49 +/- 10.47) mg/mmolCr vs (1.19 +/- 0.85) mg/mmolCr and (1.63 +/- 1.62) mg/mmolCr; (0.82 +/- 1.47) mg/mmolCr vs (0.27 +/- 0.15) mg/mmolCr and (0.40 +/- 0.49) mg/mmolCr; P < 0.01; P < 0.05; respectively] and they were negatively correlated with left ventricular ejection fraction (r = -0.31, r = -0.40, P < 0.01). There were no significant difference of URbp and Ubeta(2)-MG among the above three groups. CONCLUSIONS: There is early abnormality of renal function in CHF patients without primary renal disorder and the abnormality was featured by impaired glomerular filtration function. The more severe the heart failure, the more significant the renal function impairment.