BACKGROUND: Preactivation of peripheral blood mononuclear cells (PBMCS) is one of the most important eerly events and facilitating factor for the formation of atherosclerosis. Tanshinone is a lipolytic component extracted from traditional Chinese medicine of denshen, it has definite anti-atherosclerotic effect.OBJECTTVE: To analyze whether PBMCS preactivation existed at early essential hypertension, and investigate the effects of tanshinone on inhibiting the PBMCS activation cultured in vitro by detecting the adhesion and excretory activities of PBMCS.DESTGN: A case-controlled analysis.SETTING: Department of Emergency and Research Room of Traditional Chinese Medicine, Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.PARTTCTPANTS: Thirty patients with untreated essential hypertension or with withdrawal from antihypertensives for at least 2 weeks were selected from the Department of Cardiology, Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology from January 2003 to October 2004, including 16 males and 14 females, aged (44.6±7.4) years, body mass index of (26.2±4.5) kg/m2, average disease course of (38.5±16.9) months.Informed contents were obtained from all the subjects. Their hypertension was grade Ⅰ-Ⅱ according to the diagnostic standards for hypertension by WHO/ISH in 1999. Secondary hypertension, organic heart disease, hyperglyceridemia,diabetes mellitus, liver and kidney dysfunction, heart, brain, kidney, vessel and other target damaged induced by infection and other clinical conditions and hypertension were excluded by history, physical examination and assistant examination.Another 30 healthy physical examinees with normal blood pressure were enrolled as the normal control group. Human umbilical vein endothelial cells (Species Reserving Center of Wuhan University); Tanshinone injection (Yaan Sanjiu Pharmaceutical, Co., Ltd., batch number: 020724);METHODS: ① Venous blood samples (4.0-5.0 mL) were drawn from all the subjects, and mononuclear cells were separated by means of Ficoll-Hypaque density gradient centrifugation and plastic adhesion, then incubated at 37 ℃ for 40-60 minutes, and the adherent cells were the PBMCS. These cells (viability ＞ 95%, Trypan blue staining) had the characteristics of mononuclear cells (Wright staining). The newly separated adherent PBMCS were resuspended, and then inoculated to the 24-well plate (4×107 L-1). There were 3 wells for each sample: the first was for basic excretion, the second for angiotensin Ⅱ stimulation, and the third for tanshinone pretreatment. The PBMCS were co-incubated with tanshinone for 30 minutes before angiotensin Ⅱ stimulation. The terminal concentration was 1×10-8 mol/L and 1×10-8 g/L for angiotensin Ⅱ andtanshinone respectively, and that of PBMCS was 2×107 L-1. The cells were cultured in the incubator (CO2 of 0.05 in volume fraction) at 37 ℃ for 24 hours, then the supernatant and cell ingredients were collected respectively. ② The PBMCS suspension was preparedl, and the cellular density was adjusted to 2.5×109 L-1. The human umbilical vein endothelial cells were cultured on the 24-well plate with M199 medium containing fetal bovine serum (0.1 in volume fraction), and spread to monolayer after the cells entered the logarithm phase. Each well was added with PBMCS suspension (100 μL), incubated at 37 ℃ for 2 and 4 hours respectively. The unadherent cells were removed, and the adherent ones were counted after fixed with 20 g/L glutaral, 40 visual sights were counted for each well under high power microscope, and the average value was used. ③ The double-antibody sandwich enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in supernatant of PBMCS, and the expressions of their mRNA.MATN OUTCOME MEASURES: ① Changes of PBMCS adhesion activity; ② Concentrations of cytokines and their mRNA expressions in supernatant of PBMCS.RESULTS: ① At 2 and 4 hours of inoculation, the numbers of PBMCS adhered to endothelial cells under basic conditions were similar between the hypertension group and normal control group (t =1.153-1.577, P ＞ 0.05); After angiotensin Ⅱ stimulation, the adherent cells were obviously more in the hypertension group than in the normal control group (t =3.842-4.536, P ＜ 0.01); The numbers of the adherent cells were decreased to the same levels after tanshinone pretreatment (t =0.855-1.702, P ＞ 0.05). ②Under basic state, the concentrations of TNF-α, IL-1β and IL-6 in supernatant were all lower in both groups (t =0.981-1.829, P ＞ 0.05); The concentrations of the cytokines after angiotensin Ⅱ stimulation were obviously higher in the hypertension group than in the normal control group (t = 2.442, 5.075, P ＜ 0.01,0.01, 0.05); The concentrations of the cytokines after tanshinone pretreatment were all decreased to different extent, and there were no significant differences (t =1.227-1.940, P ＞ 0.05). Similar changes were observed in the mRNA expressions of the cytokines in PBMCS in the two groups.CONCLUSTON: ① The number of PBMCS adhered to endothelial cells, the concentrations and mRNA expressions of the cytokines under basic state in patients with essential hypertension were at the levels of normal subjects, and they were significantly increased after angiotensin Ⅱ stimulation, suggesting that the PBMCS were at preactivation at early essential hypertension. ② Tanshinone could decrease the adhesion and excretory activities of PBMCS in patients with essential hypertension to the normal levels, it is proved that tanshinone can inhibit the further activation of the preactivated PBMCS, and can prevent the occurrence of atherosclerosis to some extent.

Androgen is an anabolic steroid composed of 19 carbon atoms. As a sex hormone, it has far-ranging effects on many sites within the body, including bone metabolism. Androgen has important effects on bone development and homeostasis. It has been proved that the androgen receptor (AR) expresses in bone cells, which indicates that androgen has direct effects on bone cells. Furthermore there is convincing evidence that aromatization to estrogen is an important way of mediating the action of testosterone. Androgen not only plays an important role in gaining the peak bone mass and maintaining the bone mass, but also has a close correlation with aging-related bone loss.
Androgens ; physiology ; Animals ; Bone Density ; physiology ; Bone and Bones ; physiology ; Female ; Humans ; Male ; Osteoblasts ; physiology ; Osteoclasts ; physiology ; Osteoporosis ; physiopathology ; Rats ; Receptors, Androgen ; physiology

OBJECTIVETo explore the clinical application value of Provider-Initiated HIV Testing and Counseling (PITC) by analyzing the positive rate of HIV tests for people in need of PITC and that of routine HIV tests.

METHODSWe retrospectively analyzed the demographic and epidemiologic data about the patients seeking PITC services or undergoing routine HIV tests in Nanjing Drum Tower Hospital between January and December 2013.

RESULTSThe positive rate of initial HIV screening was 1.98% in the PITC group and 0.24% in the routine test group, while that of confirmed HIV was 0. 40% in the former and 0.07% in the latter, both with statistically significant differences between the two groups (P < 0.01). The positive rate of HIV was markedly higher in males than in females, particularly in the PITC group.

CONCLUSIONPITC has a high clinical value in HIV detection for targeted subjects and therefore deserves general application in dermatology.

Counseling ; Dermatology ; Female ; HIV Seropositivity ; diagnosis ; epidemiology ; Humans ; Male ; Mass Screening ; methods ; Retrospective Studies ; Sex Factors

Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum concentrations data from 260 patients including 177 males and 83 females were collected separately from two centers. A one-compartment model was used to describe this sparse data. No significant difference was observed between two center datasets by introducing SID covariate. The final model was as CL= (θ (base0+ θ(max) x(1 -e(-θ(Age)(Age/72) and V = θ x θ (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the most significant covariate in the final model. Typical values of clearance (CL) and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76 L, respectively. Internal model validation by Bootstrap and NPDE were performed to evaluate the robustness and prediction of the final model. The median and 95% confidence intervals for the final model parameters were based on 1000 Bootstraps. External model evaluation was conducted using an independent dataset that consisted of 34 patients to predict model performance. Pharmacodynamic assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated by clearance based on the above population model. The results indicate that the conventional dosing regimen probably being suboptimal concentrations in aged patients. The approach via population pharmacokinetic of VAN combined with the relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational dose for attaining efficacy.
Aged ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Models, Biological ; Nonlinear Dynamics ; Vancomycin ; pharmacokinetics

The identity of higher-order neurons and circuits playing an associative role to control renal function is notwell understood.We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3~ days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice.PRV-614 infected neurons were detected in a number of mesencephalic (e.g.central amygdala nucleus),telencephalic regions and motor cortex.These divisions included the preoptic area (POA),dorsomedial hypothalamus (DMH),lateral hypothalamus,arcuate nucleus (Arc),suprachiasmatic nucleus (SCN),periventricular hypothalamus (PeH),and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN).PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH,Arc,SCN,PeH,PVN,the anterodorsal and medial POA.A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic.PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin.These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

ObjectiveTo study the role and mechanism of low-dose aspirin with IFN-α in inhibiting growth and metastasis of hepatocellular carcinoma (HCC).MethodsMHCC97L cells were cultured and a metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude (nu/nu) mice.After administration of different doses of Aspirin and IFN-α for 40 days,the mice bearing xenografts in liver were killed,and the tumor volume and lung metastasis were evaluated.Cell proliferation and MMP-2 activity were measured by MTT and gelatin zymography,respectively.The expressions of VEGF and MMP-2 were measured by western blot and ELISA.ResultsCompared to the control group,there were no significant differences in the high-dose Aspirin [45 mg/(kg · d)] treated group regarding tumor volume [(1.89 ±0.88) cm3 vs (3.12±0.85) cm3,P＞0.05] and incidence of lung metastases (58.3％ vs 66.7％,P＞0.05),but the tumor volume and incidence of lung metastasis were significantly inhibited in the highdose IFN-α group [1.5 × 107/(kg · d)],the high-dose IFN-α combined with high-dose Aspirin group,and the low-dose IFN-α [7.5 × 106 / (kg · d) ] combined with low-dose Aspirin [15 mg/(kg · d] group (P＜0.05).2 mmol/L Aspirin did not inhibit the proliferation of MHCC97 cells (P＞0.05),but inhibited the activities and expressions of MMP-2 and VEGF.Low-dose IFN-α combined with low-dose Aspirin significantly decreased the expressions of MMP-2 and VEGF in nude mice (P＜0.05).ConclusionLow-dose Aspirin combined with low-dose IFN-α significantly inhibited the growth and metastasis of HCC through suppressing the expressions of MMP-2 and VEGF.

Objective To detect the ascites CD64 index of patients with decompensated cirrhosis ,and explore the value in the di-agnosis of spontaneous bacterial peritonitis (SBP) .Methods Decompensated cirrhosis with ascites patients were divided into non-SBP group ,SBP suspected group and SBP diagnosed group .Two control groups were composed of patients with ascites culture pos-itive and non-SPB group .SBP suspected group were further grouped according to abdominal pain and the percentage of peripheral blood neutrophils .The CD64 index was detected by flow cytometry .Compared the difference of ascites CD64 index after treatment , and analyzed diagnosis performance of procalcitonin in human peripheral blood and ascites white blood cell count of SBP .Results The level of the ascites CD64 index was significantly higher in SBP diagnosed group (179 .39 ± 65 .56)and SBP suspected group (115 .49 ± 58 .42)than that of non-SBP group(26 .88 ± 26 .05)(P<0 .01) .The differences of the ascites CD64 index between SBP suspected associated with abdominal pain group and SBP suspected associated with painless group was not statistically significant (P>0 .05) .The level of the ascites CD64 index in SBP suspected with percentage of peripheral blood neutrophils elevated group was increased significantly than non-elevated group(P<0 .05) .CD64 index level in effective treatment group was significantly lower than the ineffective treatment group(P<0 .01) .The area of the ascites CD64 index under the curve was greater than procalcitonin in human peripheral blood and ascites WBC count ,and had a higher sensitivity and specificity .Conclusion The detection process of the ascites CD64 index is fast and with less influential factors ,which provides a new choice for the clinical diagnosis of SBP .

Objective To evaluate the prognosis and management of recurrent primary clear cell carcinoma of liver (PCCCL).Methods 214 patients with PCCCL treated by curative resection from January 1996 to March 2006 were retrospectively studied.Tumour recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results Of 99 patients who developed recurrences,28 developed early recurrence while 71 developed late recurrence.The patients with recurrences were treated with re-resection (n=33),percutaneous ethanol injection (PEI,n=7),radiofrequency ablation (RFA,n=10),transcatheter arterial chemoembolization (TACE,n =27),systemic chemotherapy (n=1),Chinese medicine (n=1),and conservative management (n=20).The re-resection rate was higher in the late than in the early recurrence group (P=0.04).In this study,reresection,PEI,and RFA were considered as curative therapies.There was no significant difference in the overall survival (OS) for patients who received these different curative therapeutic procedures (P=0.68).The 1,3-,and 5-year OS of patients with recurrences who were treated with curative treatment were comparable to those patients who did not develop recurrences (100％,86.0％,63.5％ vs 85.2％,72.2％,64.3％,P=0.71).The 1-,3-,and 5-year OS of patients who received TACE for recurrences were 100％,66.7％,and 44.4％ respectively.The results were poorer than patients who received curative treatment for recurrences (P=0.03),but were better than those who received conservative management after recurrences (80.0 ％,25.0 ％,and 10.0 ％,P＜ 0.01).Conclusions Reresection,PEI and RFA are optimal curative methods for recurrent PCCCL.TACE plays an important role in the management of patients with recurrent PCCCL who cannot be treated with curative methods.

Objective To investigate the mechanism of pseudomonasaeruginosa mannose sensitive hamemagglutination vaccine (PA-MSHA) in inducing apoptosis in hepatocellular carcinoma (HCC).MethodsA metastatic model of human hepatocellular carcinoma (HCC) was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were randomly divided into three groups:control group,PA-MSHA intraperitoneal administration group,and PA-MSHA subcutaneous administration group.The agent was administered every day after the third day post-tumor implantation.At the end of the sixth week,the mice were killed.Serum levels of TNF-α,IL-4,IL-6 and IFN-γ were measured by ELISA and the activities of caspase 3,caspase 8 and caspase 9 in the tumor samples were tested by spectrophotometric method.Fas/FasL expressions were evaluated by Western blotting.ResultsSerum TNF-α levels in the control group,PA-MSHA subcutaneous administration group and PA-MSHA intraperitoneal administration group were 25.24±3.22 pg/ml,25.50±4.55 pg/ml(P＞0.05) and 34.22±2.42 pg/ml (P＜0.01),respectively,while there were no significant differences in serum IL-4,IL-6 and IFN-γ among these three groups(P＞0.01).Compared with the control group,the activities of caspase 3,caspase 8 and caspase 9 in tumors in the intraperitoneal administration group increased by 4.1,2.3 and 1.9 fold(P＜0.01),respectively,and Fas/FasL expressions were significantly elevated in the intraperitoneal administration group and subcutaneous administration group.ConclusionWhen given intraperitoneally,PA-MSHA can induce apoptosis in HCC by promoting the secretion of TNF-α and expression of Fas/FasL,thereby inhibiting HCC growth and metastasis.

Objective To investigate the role and mechanism of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma (HCC).Methods Metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were killed after radiation and the residual tumors were resected and reimplanted into the liver of normal nude mice.At the end of sixth week,the mice were killed and the histopathological features,tumor volume,intrahepatic and lung metastasis were evaluated.Expression of epithelial-mesenchymal transition (EMT) related genes including N-cadherin,Vimentin,SIP1 and TMPRSS4 were measured by Western blotting and RT-PCR.Results The tumor volume and frequency of lung metastasis of control group was 2.25±0.52 cm3 and 66.7％,respectively.Compared to control group,tumor diameter (1.61±0.51 cm3,P＜0.05) and lung metastasis (12.5％,P＜0.05) were significantly inhibited 2 days after radiation.Whereas,30 days after radiation,tumor growth recovered (2.60±0.61 cm3,P＞0.05) and lung metastasis was enhanced (100％,P＜0.05).There were no intrahepatic metastasis in the control group and in the group of reimplantation of HCC 2 days after radiation,while the tumors from those 30 days after radiation showed enhanced intrahepatic metastasis (18 ± 8.05,P＜ 0.01 ),with overexpression of SIP1,N-cadherin,Vimentin and TMPRSS4,and reduced expression of E-cadherin.Conclusion The metastasis potential of residual HCC after radiation was first inhibited and then promoted.Overexpression of TMPRSS4 plays a critical role in radiation induced long-term metastasis of HCC by facilitating EMT.