BACKGROUND AND OBJECTIVES: Dysregulation of histone deacetylase expression and enzymatic activity is associated with a number of diseases. It has been reported that protein levels of histone deacetylase (HDAC)1 and HDAC5 increase during human pulmonary hypertension, and that the enzymatic activity of HDAC6 is induced in a chronic hypertensive animal model. This study investigated the protein expression profiles of class I and II a/b HDACs in three systemic hypertension models. SUBJECTS AND METHODS: We used three different hypertensive animal models: (i) Wistar-Kyoto rats (n=8) and spontaneously hypertensive rats (SHR; n=8), (ii) mice infused with saline or angiotensin II to induce hypertension, via osmotic mini-pump for 2 weeks, and (iii) mice that were allowed to drink L-N(G)-nitro-L-arginine methyl ester (L-NAME) to induce hypertension. RESULTS: SHR showed high systolic, diastolic, and mean blood pressures. Similar increases in systolic blood pressure were observed in angiotensin II or L-NAME-induced hypertensive mice. In SHR, class IIa HDAC (HDAC4, 5, and 7) and class IIb HDAC (HDAC6 and 10) protein expression were significantly increased. In addition, a HDAC3 protein expression was induced in SHR. However, in L-NAME mice, class IIa HDAC protein levels (HDAC4, 5, 7, and 9) were significantly reduced. HDAC8 protein levels were significantly reduced both in angiotensin II mice and in SHR. CONCLUSION: These results indicate that dysregulation of class I and class II HDAC protein is closely associated with chronic hypertension.
Angiotensin II ; Animals* ; Blood Pressure ; Histone Deacetylases* ; Histones* ; Humans ; Hypertension ; Hypertension, Pulmonary ; Mice ; Models, Animal* ; NG-Nitroarginine Methyl Ester ; Rats ; Rats, Inbred SHR

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of tanshinone ⅡA(TSⅡA), salvianolic acid B(SAB) and ginsenoside Rg₁ (GRg₁) in rat plasma and brain tissues. Male healthy Sprague-Dawley(SD) rats were orally given single dose of Fufang Danshen preparation (TS ⅡA 60 mg•kg⁻¹, SAB 300 mg•kg⁻¹, GRg₁ 150 mg•kg⁻¹, borneol 300 mg•kg⁻¹), and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix WinNolin 6.1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range(r>0.992 2). Their mean recoveries were between 58.86% and 112.1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9.7%, and the accuracy(RE) ranged from -9.68% to 8.20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.58±0.081) h, (725.4±88.20) μg•L⁻¹, (2 101.3±124.85) μg•h•L⁻¹ and (3.66±0.05) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.29±0.21) h, (307.9±46.75) μg•L⁻¹, (537.4±88.24) μg•h•L⁻¹ and (2.08±0.11) h, respectively. For GRg₁, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.42±0.20) h, (460.38±154.60) μg•L⁻¹, (383.4±88.16) μg•h•L⁻¹ and (1.87±0.046) h, respectively. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the brain tissue were (0.75±0.22) h, (1.41±0.42) ng•g⁻¹, (4.34±2.48) ng•h•g⁻¹ and (4.00±1.90) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.08±0.20) h, (21.09±4.850) ng•g⁻¹, (14.83±3.160) ng•h•g⁻¹ and (0.99±0.08) h, respectively. For GRg₁, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (0.50±0.16) h, (130.96±54.220) ng•g⁻¹, (136.24±34.350) ng•h•g⁻¹ and (2.87±0.33) h, respectively. The developed method was successfully applied in pharmacokinetic studies on content of TS ⅡA, SAB and GRg₁ in rat plasma and brain tissues.

Objective To investigate the feasibility of using low-dose prostate CT perfusion (pCTP)on a third-generation dual-source CT. Methods Nine patients with elevated prostate-specific antigen underwent pCTP before having prostate biopsy. We measured the blood flow (BF),blood volume (BV),mean transit time (MTT),permeability surface (PS),and time to peak(TTP)of both lesions and normal prostate tissue. The effective dose (ED)was calculated. Results Of the 9 cases,6 were prostate cancers and 3 were prostate hyperplasia with chronic inflammation. The average ED of the 9 pCTPs was (3.5±0.3)mSv. The BF (t=4.64,P<0.001),BV (t=3.27,P<0.001),and PS (t=3.58,P=0.004)of prostate cancer were significantly higher than those of normal prostate tissue and TTP (t=-1.26,P<0.001)of prostate cancer was significantly lower than that of normal prostate tissue. BF (t=3.96,P=0.001)and PS (t=2.91,P=0.021)of prostate hyperplasia with chronic inflammation were also significantly higher and TTP (t=-1.19,P<0.001)was significantly lower than those of normal prostate tissue. TTP of prostate cancer was significantly lower than that of prostate hyperplasia with chronic inflammation (t=-2.56,P=0.049). Conclusion sLow-dose pCTP is feasible on third-generation dual-source CT. The BF,PS,and TTP differ among prostate cancer,prostate hyperplasia with chronic inflammation,and normal prostate tissue.
Blood Volume ; Feasibility Studies ; Humans ; Male ; Prostatic Neoplasms ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

Objective To explore the feasibility of reducing radiation dose of CT colonography (CTC) while preserving image quality using the third-generation dual-source CT at 70 kV tube voltage with advanced modeled iterative reconstruction (ADMIRE). Methods This prospective study consecutively included 53 patients. All patients underwent CTC at 120 kV in supine position with filtered back projection reconstruction and at 70 kV in prone position with ADMIRE with the same scan range. Radiation dose and image quality were compared between these two protocols. Results CT dose index volume,dose-length product,and effective dose of 70 kV were (1.47±0.23)mGy,(68.85±13.82)mGy·cm,and (1.03±0.21)mSv,respectively,which were significantly lower than 120 kV mode [(2.96±0.61)mGy (t=25.356,P=0.000),(136.97±32.77)mGy·cm (t=22.246,P=0.000),and (2.05±0.49)mSv (t=22.293,P=0.000)]. Signal to noise ratio of 70 kV with ADMIRE was 3.60±0.58,which was obviously higher than that of 120 kV as 2.34±0.47 (t=-18.036,P=0.000). Noise of 70 kV with ADMIRE was (11.81±1.93)HU,which was obviously lower than that of 120 kV as (14.39±2.57)HU (t=7.856,P=0.000). The κ value of two radiologists' overall subjective image score was 0.843 (P=0.000). For 2D images,the noise score of 70 kV with ADMIRE was significantly lower (Z=325.000,P=0.000) and the overall image quality was significantly higher (Z=78.000,P=0.001) compared with 120 kV;however,the sharpness had no significant difference. All scores ranged from 4 to 5. For 3D virtual endoscopy,the overall image quality of 70 kV with ADMIRE and 120 kV was not significantly different (Z=4.000,P=0.059),and all scores ranged from 4 to 5. Conclusion CTC at 70 kV tube voltage combined with ADMIRE can remarkably reduce the radiation dose while maintaining imaging quality than 120 kV at third-generation dual-source CT.
Colon ; diagnostic imaging ; Colonography, Computed Tomographic ; methods ; Humans ; Prone Position ; Prospective Studies ; Radiation Dosage ; Radiographic Image Interpretation, Computer-Assisted ; Radionuclide Imaging ; Signal-To-Noise Ratio

Objective To evaluate the feasibility of a low-dose one-stop-shop cardiac CT imaging protocol with third-generation dual-source CT (DSCT). Methods Totally 23 coronary artery disease (CAD) patients were prospectively enrolled between March to September in 2016. All patients underwent an ATP stress dynamic myocardial perfusion imaging (MPI) (data acquired prospectively ECG-triggered during end systole by table shuttle mode in 32 seconds) at 70 kV combined with prospectively ECG-triggered high-pitch coronary artery angiography (CCTA) on a third-generation DSCT system. Myocardial blood flow (MBF) was quantified and compared between perfusion normal and abnormal myocardial segments based on AHA-17-segment model. CCTA images were evaluated qualitatively based on SCCT-18-segment model and the effective dose(ED) was calculated. In patients with subsequent catheter coronary angiography (CCA) as reference,the diagnosis performance of MPI (for per-vessel ≥50% and ≥70% stenosis) and CCTA (for≥50% stenosis) were assessed. Results Of 23 patients who had completed the examination of ATP stress MPI plus CCTA,12 patients received follow-up CCA. At ATP stress MPI,77 segments (19.7%) in 13 patients (56.5%) had perfusion abnormalities. The MBF values of hypo-perfused myocardial segments decreased significantly compared with normal segments [(93±22)ml/(100 ml·min) vs. (147±27)ml/(100 ml·min);t=15.978,P=0.000]. At CCTA,93.9% (308/328) of the coronary segments had diagnostic image quality. With CCA as the reference standard,the per-vessel and per-segment sensitivity,specificity,and accuracy of CCTA for stenosis≥50% were 94.1%,93.5%,and 93.7% and 90.9%,97.8%,and 96.8%,and the per-vessel sensitivity,specificity and accuracy of ATP stress MPI for stenosis≥50% and ≥70% were 68.7%,100%,and 89.5% and 91.7%,100%,and 97.9%. The total ED of MPI and CCTA was (3.9±1.3) mSv [MPI:(3.5±1.2) mSv,CCTA:(0.3±0.1) mSv]. Conclusion The third-generation DSCT stress dynamic MPI at 70 kV combined with prospectively ECG-triggered high-pitch CCTA is a feasible and reliable tool for clinical diagnosis,with remarkably reduced radiation dose.
Computed Tomography Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Heart ; diagnostic imaging ; Humans ; Myocardial Perfusion Imaging ; Prospective Studies ; Radiation Dosage ; Sensitivity and Specificity

OBJECTIVETo investigate the changes in the range of motion (ROM) and stress of the intervertebral disc and facet joint of the adjacent segments following anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) using finite element analysis.

METHODSA three-dimensional finite element model of the lower cervical vertebrae was constructed and validated by comparing the ROM of the finite element model against the published data. After the validation of successful modeling, finite element models of ACDF and ACCF were constructed. The ROM and the stress of the intervertebral disc and facet joint of the adjacent segments were compared between the intact lower cervical vertebrae and the cervical vertebrae after ACDF and ACCF.

RESULTSThe ROM of the finite element model was consistent with the published data. The total ROM and the ROM of the fusion segments with ACDF and ACCF were significantly decreased compared with the intact cervical vertebrae. In the adjacent segments following ACDF and ACCF, the ROM the adjacent segments and the stress peak of the intervertebral disc and facet joint all increased obviously compared with those of intact cervical vertebrae.

CONCLUSIONAfter fusion surgeries, the total ROM of the cervical vertebrae decreases and the ROM of the adjacent segment increases. The stress peak of the intervertebral disc and facet joint of the adjacent segments also increases to significantly alter the physiological characteristics of the intact cervical vertebrae.

Esophagustype cervical spondylosis is easily misdiagnosed or missed diagnosed for its lower incidence. The pathological basis manily concerned with compression of osteophyte for esophageal and tracheal wall and local inflammatory reaction. The diagnosis of disease is generally not difficult. Especially dynamic esophagogram could not only show degree of cervical degeneration and osteophyte shape, but also could clearly observe location and degree of osteophytosis indenting esophageal and tracheal. Recently, the treatment of esophagustype cervical spondylosis has been the focus of attention. It is generally believed that conservative treatment could alleviate disease but could not cure it. More and more scholars tend to treat disease by surgical resection of osteophyte to relieve compression for esophagus, and clinical symptoms could obviously improved. However, long-term follow up is lack, and further follow-up effect is lack of powerful support, anddifferent treatment methods and surgical procedures are lack of comparative research.

OBJECTIVETo assess the detection of maternal serum alpha fetoprotein (MSAFP) and free beta-HCG levels of second trimester for screening of fetal gastroschisis and omphalocele.

METHODSClinical data of 622 639 pregnant women from 5 prenatal screening centers in Hangzhou during October 2007 and September 2016 were analyzed retrospectively. Thirty cases of gastroschisis and 30 cases of omphalocele diagnosed by ultrasonography and postmortem findings were enrolled in the study and 116 cases of pregnant women with normal fetal development during the same period were selected as control group. The cut-off value and area under ROC curve (AUC) of MSAFP and free β-hCG for diagnosis of fetal gastroschisis and omphalocel were analyzed.

RESULTSMSAFP levels of women with fetal gastroschisis and omphalocele were 4.41 (0.88-11.69) MOM and 2.31 (0.72-23.20) MOM, which were significantly higher than that of control group[0.98 (0.41-2.26) MOM, all<0.01]. Free β-hCG level of women with fetal gastroschisis was 1.25 (0.35-19.94) MOM, which was significantly higher than that of control group[0.86 (0.17-6.11) MOM,<0.05). But there were no significant difference in free β-hCG between fetal omphalocele group[1.03(0.21-8.95)]and control group (>0.05). The AUCs of MSAFP for diagnosis of gastroschisis and omphalocele were 0.897 (95%:0.822-0.972) and 0.852(95%:0.762-0.942), respectively (all<0.01). Taking 1.655 MOM as the cut-off value of MSAFP for abdominal wall defects (gastroschisis and omphalocele), the sensitivity was 68.30%, specificity was 99.60% and Youden index was 0.649.

CONCLUSIONSMSAFP of second trimester is a better biomarker than free β-hCG in screening abdominal wall defects.

OBJECTIVETo determine whether additional Chinese medicine (CM) could prolong survival and improve the quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC) compared with Western medicine (WM) alone.

METHODSThis was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage III-IV NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network (NCCN) guidelines. In the integrative medicine (IM) group, individualized CM (Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months.

RESULTSThe median survival was 16.60 months in the IM group and 13.13 months in the WM group (P<0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group (P<0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course (P<0.05).

CONCLUSIONSAdditional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio- and chemotherapy may be attenuated as CM is used in combination with conventional treatments.

OBJECTIVETo study the effects of allicin on cardiac function and underlying mechanism in rat model of myocardial infarction (MI).

METHODSNinety-four Wistar rats were randomly assigned to 6 groups (n=14-16 per group): sham control group [underwent thoracotomy without left anterior descending (LAD) occlusion and only received an injection of the same amount of citrate buffer], MI control group (subjected to LAD occlusion and only received an injection of same amount of citrate buffer), positive control group (subjected to LAD occlusion and received an injection of diltiazem hydrochloride at the dose of 1.5 mg/kg), and MI + allicin groups (subjected to LAD occlusion and received an injection of allicin at the doses of 1.2, 1.8, and 3.6 mg/kg). All of the drugs were administered intraperitoneally daily for 21 days. The infarct area was measured by myocardial staining. Hematoxylin-eosin staining was used to observe the pathological changes. Cardiac function parameters were assessed by echocardiography. The myocardial apoptotic index was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. The expression of Bax and Bcl-2 were detected by quantificational real-time polymerase chain reaction and Western blot.

RESULTSTreatment with allicin could attenuate the myocardial infarct area (P<0.05) and relieve the changes of the myocardium. The left ventricular anterior wall diastolic and systolic thicknesses were increased in the allicin-treated groups (P<0.05), while there was no signifificant difference in the left ventricular posterior wall diastolic and systolic thickness (P>0.05). The left ventricular internal diameter in systole, ejection fraction, fractional shortening, and stroke volume were dramatically elevated in allicin-treated rats (P<0.05). Allicin dose-dependently reduced creatine kinase and lactate dehydrogenase levels (P<0.05). The myocardial apoptotic index was also markedly lowered, and Bax expression was signifificantly decreased, whereas Bcl-2 expression exhibited an opposite trend in allicin-treated rats (P<0.05).

CONCLUSIONAllicin appears to exert a cardioprotective effect that may be linked to blocking Bcl-2/Bax signaling pathway-denpendent apoptosis, further improving cardiac function.