The diagnosis and treatment of prostate cancer are being improved due to the popularized screening of prostate specific antigen. Advanced prostate cancer, in spite of its response to androgen deprivation therapy, may finally develop into castration-resistant prostate cancer (CRPC) and shorten the overall survival of the patients. Many efforts have been made by worldwide researchers for new approaches to the management of CRPC, including new hormonal therapy, cytotoxic chemotherapy, immunotherapy, and bone metastasis-targeted therapy. This paper reviews the emerging agents undergoing clinical evaluation and drugs that have received approval for the treatment of CRPC in order to provide doctors and patients with more treatment options for CRPC and improve the overall survival rate and quality of life of the patients.
Androgen Antagonists ; Bone Neoplasms ; prevention & control ; Humans ; Immunotherapy ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; therapy ; Quality of Life

Objective To study critical hemophagocytic syndrome (HPS) or macrophage activation syndrome (MAS) presented with multiple organ dysfunction syndrome (MODS) in pediatric intensive care unit (PICU),including clinical features and outcomes In order to explore the effect of bedside continuous hemodialysis/hemofiltration (CBP) as adjuvant treatment for severe HPS/MAS.Methods A total of 19 children with HPS/MAS were hospitalized met the diagnostic criteria for HPS from January,2009 to December,2012.Twelve cases were treated with CBP by continuous venin-venin hemodialysis/hemofiltration (CVVHDF) or high-volume hemofiltration (HVHF) following conventional anti-inflammatory therapy.The replacement liquid dose was 50-75 ml/ (kg · h).The organs function were evaluated and laboratory biomarkers including blood 、electrolytes,ferritin changes were measured before and after CBP treatment.Results Ninteen cases of HPS were acute onset and developed to MODS rapidiy after admission to PICU.The main clinical features were the irregular fever or high fever,hepatosplenomegaly and significant liver damage,nervous system dysfunction and disseminated intravascular coagulation (DIC).Eight cases were death and mortality rate was 42.1％,and all death occurred in those aged less than 3 years old.The mortality rate were 25％ (3/12) and 71.4％ (5/7) in CBP group and non-CBP group respectively.After CBP for 6-24 hours,the fever returned to normal range and blood electrolytes improved.The serum ferritin,serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) reduced significantly.Serum creatinine (sCr),blood urea nitrogen (BUN) level improved.Four cases with acute respiratory distress syndrome (ARDS) improved and the ventilator parameters were downregulated.Conclusions Our findings indicate that HPS/MAS complicated with MODS is life threatening with high mortality rate.CBP therapy can lower the fever within a short time,correct electrolyte imbalance,stable circulatory function,improve the lung,liver,and brain function.It is suggested that CBP may be the potential effective therapy in severe HPS/MAS with MODS in children.

OBJECTIVESevere Epstein-Barr (EB) virus infection is potentially a devastating process that often leads to death encountered in pediatrics recently. Inappropriate control of EB virus replication may cause severe infection resulting in multiple organ dysfunction. However, little information is available on pulmonary complications associated with EB virus infection. The aim of the present study was to investigate severe EB virus (EBV) infection complicated with lung injury in pediatric intensive care unit (PICU), including clinical characteristics, laboratory or imaging feature and outcomes.

METHODA total of 45 children with severe EBV infection seen in PICU of Shanghai Children's Hospital between January 2011 and December 2014 were retrospectively reviewed. According to clinical characteristics and imaging feature, 45 children were divided into non-lung injury group (n =27), lung injury without pulmonary fibrosis group(n = 12) and pulmonary fibrosis group (n = 6).

RESULTIn totally 45 cases of severe EBV infection, 21 (46.7%) were male and 24 (53. 3%) were female, mean age was 2. 4 years; 18 cases were complicated with lung injury, including 8 male and 10 female, median age was 31. 2 months. All of 18 cases presented with fever and cough, 15 of them exhibited dyspnea,12 cases were complicated with gasping, and 6 cases with ARDS. Eight cases accepted mechanical ventilation for acute respiratory distress; 6 cases who developed pulmonary fibrosis had tachypnea, refractory hypoxemia and hypercapnia, severe pulmonary air leak. The average EBV-DNA level in peripheral blood was 4. 42 x 10(6) copies/ml (range: 3. 25 x 10(3) - 6.59 x 10(7) copies/ml). Anti-EBV antibodies were positive in 41 cases, 18 cases were positive (+) for VCA-IgM, 15 cases were VCA-IgG and EA-IgG (+), 8 cases VCA-IgM and VCA-IgG (+). The radiographic findings revealed pulmonary interstitial infiltrates in all 18 cases with lung injury, 4 cases with segmental consolidation and 2 cases showed pleural effusions. HRCT scanning found EBV associated fibrosis including multifocal patches and diffuse ground-glass attenuation in both lungs, reticular opacities and honeycombing changes were observed 4 weeks after illness onset. There were significant differences in respiratory failure, PICU stay (days), Pediatric risk of mortality III (PRISM III) and pediatric clinical illness score(PCIS), serum TNF-α, EBV-DNA levels, percentage of NK cells and CD4+/CD8+ T cell ratio among non-lung injury group, lung injury without pulmonary fibrosis group and pulmonary fibrosis group (X2 =27. 12, F = 85. 23, 78. 23, 88. 68, 323. 80, 7. 35, χ2 = 6. 71, 12. 15; all P < 0. 05). COX regression analysis revealed that EBV-DNA and serum TNF-α levels were correlated with pulmonary fibrosis significantly (OR = 3. 92, P = 0. 04; OR = 5. 95, P = 0. 01). The patients with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) had higher incidence of pulmonary fibrosis compared with non-EB-HLH (70% vs. 13%, χ2 = 4. 82, P = 0. 03). Of 18 cases, 8 cases died, including 3 cases with pulmonary fibrosis. The surviving cases with pulmonary fibrosis needed longer additional oxygen. Chest HRCT imaging of 3 cases with pulmonary fibrosis was improved at 6 months and oxygen therapy was discontinued at 18 months after discharge.

CONCLUSIONEB virus infection complicated with lung injury had higher incidence of respiratory failure, pulmonary fibrosis with a fatal outcome. EBV-DNA and serum TNF-α level were found to be statistically significant indicators of pulmonary fibrosis. Pulmonary fibrosis associated with severe EB virus infection may be reversible.

Antibodies, Viral ; blood ; CD4-CD8 Ratio ; Child, Preschool ; China ; DNA, Viral ; blood ; Epstein-Barr Virus Infections ; pathology ; Female ; Herpesvirus 4, Human ; Humans ; Intensive Care Units, Pediatric ; Killer Cells, Natural ; Lung Injury ; virology ; Lymphohistiocytosis, Hemophagocytic ; pathology ; virology ; Male ; Pulmonary Fibrosis ; pathology ; virology ; Retrospective Studies ; Tumor Necrosis Factor-alpha ; blood

Objective To investigate the effects of early hemofiltration combined with traditional Chinese medicine on nasal feeding on severe acute pancreatitis (SAP) patients. Methods Seventy four patients were divided into traditional Chinese medicine group (group A, 35 cases) and traditional Chinese medicine+hemofiltration group (group B, 39 cases). In group A, patients were given a serious of procedure including fasting, gastrointestinal decompression, fluid resuscitation, inhi-bition of pancreatic secretion, antibiotic prophylaxis, parenteral nutrition and traditional Chinese medicine on nasal feeding;In group B, patients received continuous veno-venous hemofiltration treatment(also called Continuous Renal Replacement Therapy,CRRT) in addition to the procedures receiving by group A. On admission and the first, 3rd, 7th days post-treatment, the scores of acute physiology and chronic health evaluation (APACHEⅡ), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8) levels were recorded. Length of hospital stay, local and systematic complications, surgical inter-vention, mortality and hospitalization expenses were compared between two groups. Results On admission, no statistical significance was seen in the hematocrit, white blood cell count, lactic acid dehydrogenase, blood urea nitrogen, blood glu-cose, APACHEⅡscore, Ranson’s score and classification of etiology between these two groups (P>0.05). But APACHEⅡ, TNF-α, IL-6, IL-8 were decreased significantly in group B than in group A, after the first, 3rd, 7th days post-treatment (P＜0.05). Compared with group A, the length of hospital stay, local complications, systemic complications, surgical interven-tion, mortality and hospitalization expense were lower in group B. Conclusion Traditional Chinese medicine on nasal feed-ing combined with early hemofiltration could effectively reduce complications, incidence of organ dysfunction and could im-prove the prognosis of SAP patients.

Objective To investigate the metabolic changes and the metabolites distribution of different hippocampal regions (head,body and tail)in patients with Alzheimer’s disease (AD)using 1 H-MRS for early diagnosis.Methods The hippocampal multivoxel 1H-MRS at 3.0 T was scanned in 30 patients with AD and other 30 normal cognitive elders (NC)as contrast.The data obtained were processed at a workstation.The hippocampus was divided into 3 parts (head,body and tail),and the ratios of N-acetylaspartate (NAA)/creatine (Cr),myoinositol (MI)/Cr and MI/NAA were calculated respectively.The metabolite ratios and distribution changes were compared between group AD and NC.Results Compared with the group NC,the NAA/Cr in group AD in bilateral hippocampal body and tail was decreased,whereas the MI/Cr and MI/NAA in bilateral body and tail,MI/NAA in left head were opposite (P<0.01).In group NC,the NAA/Cr was gradually decreased from the bilateral hippocampal heads to tails (P<0.01),however,the MI/NAA was opposite (P<0.01).No distribution differences in every metabolic ratios of bilateral hippocam-pus were found in AD group (P>0.05).Conclusion Metabolic changes and disappearance of the normal distribution in different hippocampal regions detected by 1 H-MRS provide helpful clues for early diagnosis of the AD.

Objective To evaluate the value of noninvasive monitoring of pulmonary arterial pressure in the children with severe pneumonia and respiratory failure.Methods A prospective study was adopted to investigate 69 patients who suffered from severe pneumonia and respiratory failure in Pediatric Intensive Care Unit in Shanghai Children's Hospital from June 2013 to December 2013 were involved in this study,except for heart disease.The pulmonary arterial pressure (PAP) and cardiac function were monitored by using bedside color doppler ultrasound cardiogram,such as PAP,cardiac index (CI),left ventricle ejection fraction(LEFT),and heart early diastolic filling velocity maximum/heart late diastolic filling velocity maximum (E/A ratio).They were divided into 2 groups according to PAP,one group as pulmonary arterial pressure normal group,the other group as pulmonary arterial hypertension(PAH) group,and the impact of the PAP on the prognosis and mechanical ventilation was assessed.Milrinone[0.5 μg/(kg · min)] were given the patients who were combined with pulmonary hypertension,and the PAP and cardiac function before using Milrinone and 24 h,48 h and 72 h after giving medicine was observed.Results Among 69 cases,40 cases were male and 29 cases were female,age ranging from 2 months to 12 years old,and the weight range was (14.3 ± 8.9) kg.The pediatric critical illness score(PICS) was 70.5 ± 9.6,and the pediatric risk of score m ortality Ⅲ was 13.5 ± 5.0.Among 69 cases,46 cases had pulmonary arterial hypertension,38 cases of them experienced mechanical ventilation,and 9 cases died.Among 23 cases who had no pulmonary arterial hypertension,only 8 cases experienced mechanical ventilation.There was a significant difference in the mechanical ventilation rate and mortality between two groups(x2 =15.78,P ＜0.0l ; x2 =5.18,P ＜ 0.05).The mechanical ventilation time was longer in pulmonary arterial hypertension group (t =3.89,P ＜0.01).PAP was (58.23 ±5.44) mmHg(1 mmHg =0.133 kPa),(49.10 ±4.69) mmHg,(42.53 ±4.54)mmHg and(35.63 ±4.78) mmHg respectively before and after using Milrinone 24 h,48 h and 72 h in 46 cases with pulmonary arterial hypertension,and the pressure decreased significantly after using medicine (F =67.11,P ＜ 0.01).There was no significant difference in CI,LVEF and E/A(all P ＞0.05).However,9 cases of them did not show any response to Milrinone,and in the end they couldn't live without mechanical ventilation,they died.Conclusions Noninvasive pulmonary arterial pressure monitoring could be beneficial in judging patient's condition and assessing prognosis of children with severe pneumonia and respiratory failure,and milrinone could decrease PAP.

Objective To investigta e the efficayc of bedside plasma exchange( PE) combined con-tinuous veno-venous hemodiafiltration ( CVVHDF ) in childer n with critical hemo lty ic uremic syndrome ( HUS) .Method s Eight patients with HUS from Pediatric Intensive Care Unit of Shanghai Ch ildren′s Hos-pitalw ere included in the present stuyd .The seveir ty of children was gar ded accordni g to peid atric critiac l ill-ness soc re and pediatric riks ofs core mortalityⅢ.Four of them received continuuo s blood purification treat-me nt.Meanwhile,the clinical manifestation and outcom e of HUS weer analyzed.Results Eight children with HUS weer ni itially trae ted with diuretic and blood transfusion for 12-24 hours.Four ac ses who deteriora-ted aggressively were ep rofr med PE and CVVHDF.Plasauto iQ21 and Prisma flex wereu sed with Pir sma TPE 2000 membrna e plasma separator and AN69 M60 membrane filter respectively.All the 4 patients with critical HUS survived after bedside continuous blood purification treatment.Clinical symptoms and serum bio-chemistry were improved sing ificantly as follows.The average levels of serum creatinine and lactate dehydro-genase decreased obviously(318μmol/L vs.162μmol/L;1 963 U/L vs.407 U/L,respectively).In addi-tion,platelet count increased significantly(40 ×109/L vs.97 ×109/L) .Eventually,symptoms disappeared in these 4 patients.Conclusion The combined therapy of PE and CVVHDF in HUS could stabilize fluid acid-base equilibrium,prevent hemolysis and improve the renal function.

OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles

Objective To analyze the patterns of cortical atrophy of the two subtypes of frontotemporal lobar degeneration (FTLD ),behavioural-vsriant frontotemporal dementia (bvFTD ) and primary progressive aphasia (PPA).And to compare them with that of Alzheimer disease (AD) to provide an objective basis for early diagnosis and differential diagnosis.MethodsA total of 83 patients were enrolled in this study and there were 30 patients with cognitively normal controls (CN),30 with AD and 23 with FTLD (10 with bvFTD,13 with PPA).Philips 3.0 T TX scanner and 8 channel head coil was employed.Three dimensional turbo fast echo(3D-TFE)T1WI sequence with high resolution was used to collect the volume data of gray matter.3D-TFE T1 WI images were normalized and segmented into gray matter map for statistical analysis by SPM 8 and VBM 8.The false discovery rate (FDR) was adopted in P value adjustment,P ＜ 0.001,and the cluster size was set at 5.The full width at half maximum (FWHM ) was set at 4 mm for the smoothing.Paired t test was used for statistics.ResultsIn bvFTD,PPA and AD groups,there were diffuse regions with reduced volume in cerebral cortex and subcortical structures (such as the hippocampus,the amygdala,the caudate nuclei,et al).The most obvious atrophic region in bvFTD and PPA group was found in the frontotemporal.Compared with AD,gray matter atrophy in bvFTD was found in brain regions including bilateral temporal lobes,bilateral superior temporal pole gyri,bilateral middle temporal pole gyri,right fusiform gyrus and bilateral frontal lobes.Among them,temporal and frontal lobes atrophy had obvious right partial lateralizing,with 14 301 voxels in right temporal lobe and 5105 in left (t =-5.03,P＜0.05).The number of atrophy voxels in right and left frontal lobe were 1344 and 125 (t =3.45,P ＜0.05).The left temporooccipital lobe atrophy was more obvious than the right in PPA,with 15 637 voxels in left and 10 723 in right ( t =- 2.65,P ＜ 0.05 ).ConclusionsThere are different brain gray matter atrophy patterns in bvFD,PPA and AD.Among them,bvFTD has asymmetric right frontal and temporal lobe atrophy,which may be related to characteristic personality changes.On the other hand,the asymmetric atrophy in left temporooccipital lobe may be responsible for the aphasis of patients with PPA.

A phytochemical investigation on the aerial parts of a Tibetan medicine Meconopsis horridula, by solvent extraction, repeated chromatographies on silica gel, Sephadex LH-20, and preparative TLC techniques, led to the isolation of 9 compounds. By spectroscopic analysis and comparison of its 1H and 13C-NMR data with those in literatures, their structures were identified as oleracein E(1), N-( trans-p-coumaroyl) tyramine (2), chrysoeriol (3), apigenin (4), hydnocarpin (5), p-coumaric acid glucosyl ester (6), stigmast-5-ene-3beta-ylformate (7), 3beta-hydroxy-7alpha-ethoxy-24beta-ethylcholest-5-ene (8), and beta-sitosterol (9), respectively, among which compounds 6-8 were isolated from the genus for the first time,and 1,3 were isolated from the species for the first time. A MTT method was applied to evaluate the cytotoxic activity of compounds 14 against the human hepatocellular liver carcinoma cell line (HepG2), and compound 1 showed significant cytotoxicity against HepG2,with its inhibitory rate of 52.2% at 10 micromol x L(-1).
Medicine, Tibetan Traditional ; Molecular Structure ; Papaveraceae ; chemistry ; Plant Extracts ; chemistry ; Spectrometry, Mass, Electrospray Ionization