Objective To investigate the dose of docetaxel appropriate for patients with metastatic castration-resistant prostate cancer and its affects to the prognosis.Methods A retrospective analysis was performed on the clinical data of 75 patients with metastatic castration-resistant prostate cancer admitted from March 2010 to July 2016 who received docetaxel combined with prednisone chemotherapy.The patients were divided into the low-dose group (n =43,docetaxel ＜ 65 mg/m2),the middle-dose group (n =21,docetaxel 65-70 mg/m2) and the high-dose group (n =11,docetaxel ＞ 70 mg/m2).The median age in the low-dose group,middle-dose group and high-dose group was 67 (53-80),66 (56-78) and 61 (47-76) years old,respectively.Among 75 patients with bone metastasis,2 patients had no evidence of bone metastasis in the low-dose group.The lymph node metastasis was found in 26,13 and 6 cases in each group,respectively.And visceral and other metastasis were founded in 11,4 and 2 cases,respectively.The Gleason score in the low-dose group was≤7 points in 15 cases,≥8 points in 22 cases and no score in 6 cases.The Gleason score inthe middle-dose group was ≤7 points in 4 cases,≥8 points in 13 cases and no score in 4 cases.The Gleason score in the high-dose group was ≤7 points in 3 cases,≥8 points in 5 cases and no score in 3 cases.The number of patients with pain in the low-dose group,middle-dose group and high-dose group was 36,12 and 9,respectively,there were no significant differences in the above indicators (P ＞ 0.05),except age,which showed relatively more aged patients in the low-dose group,(P =0.045).Kaplan-Meier method was used to compare the overall survival (OS),progression-free survival (PFS) and the incidence of ≥CTCAE-4 grade 3 adverse reactions between the two groups.The Cox regression model was adopted to analyzed the factors that might affect patient prognosis,including the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,age,dose of docetaxel and alkaline phosphatase (ALP).Kaplan-Meier method was used to analyze the effect of dose of docetaxel on the prognosis,and log-rank method was used to test the significance of the results.Results The median OS was respectively 24.1,18.5 and 23.5 months in the low-dose group,middle-dose group and high-dose group,respectively.The median PFS was 5.3 months in all three groups,which didn't show statistically significant differences.The incidence of grade 3/4 adverse reactions in the low-dose group,middle-dose group and high-dose group was 15 cases (34.9％),8 cases (38.1％) and 5 cases (45.5％) respectively.It showed an increasing trend,but no statistically significant difference.The single factors related to OS mainly include the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,there was no significant correlation with age,docetaxel dose,ALP and PSA value.Conclusions It is common to receive lower doses of docetaxel in clinical practice for patients with metastatic castration-resistant prostate cancer in China.The efficacy of low-dose docetaxel is similar to that of high doses (standard dosage).There was no significant correlation between the OS and the actual dose of docetaxel in the tolerable range.

Objective To evaluate the efficacy and safety of the modified docetaxel plus prednisone scheme for the metastatic castration resistant prostate cancer patients who got poor tolerance to chemotherapy.Method The clinical data of 50 metastatic castration resistant prostate cancer who received docetaxel + prednisone chemotherapy from March 2010 to October 2015 were analyzed retrospectively.23 cases received the modified DP regimen (modified group),27 cases received the standard DP regimen (standard group).The median age of the modified group and the standard group were 69 years (47-80 years) and 63 years (52-77 years) (P =0.005).There were 19 and 24 cases with pain in modified group and standard group respectively;10 and 19 cases with lymph node metastasis respectively;3 and 4 cases of visceral metastasis respectively;all of the 50 patients were complicated with bone metastasis.For the pathological Gleason score,there were 7 cases scored ≤7 points,13 cases scored ≥ 8 points and 3 cases unscored in the modified group;7 cases scored ≤7 points,15 cases scored ≥8 points and 5 cases unscored in standard group.There was no significant difference of the pain,metastasis,and Gleason score between the two groups (P ＞ 0.05).Progression free survival (PFS),overall survival (OS)and adverse events were analyzed using Kaplan-Meier curves,and the differences were assessed using the log-rank test.Results In the modified group and standard group,the median follow-up times were 11.0 months and 14.0 months respectively,the median chemotherapy cycles were 4.5 cycles and 5.0 cycles respectively;OS were 18.0 months and 27.5 months respectively (P =0.746).The PFS of the two groups were 6.0 months and 5.2 months,respectively (P =0.822).The PSA response were 13 cases and 17 cases in the modified group and standard group respectively (P =0.615),and the pain response were 8 cases and 7 cases (P =0.927),grade 3 to 4 adverse events were 3 cases and 14 cases (P =0.003).The main adverse events were blood toxicity,neutrophils,gastrointestinal reaction,edema,fatigue and oral mucositis etc.Conclusions Compared with the standard DP scheme,the modified DP scheme had no significant difference in OS,PFS,pain response rate and PSA response rate,while the incidence of grade 3 to 4 adverse events was significantly reduced.Modified DP scheme may be a better choice for patients with metastatic castration resistant prostate cancer who get poor tolerance to chemotherapy.

Objective: To investigate the effects of domestic bivalirudin on plasma intercellular adhesion molecular-1 (ICAM-1) during percutaneous coronary intervention (PCI).Methods: Sixty PCI candidates were randomly divided into heparin group (n =30) and bivalirudin group (n =30).They were respectively treated with intravenous heparin and domestic bivalirudin as the anticoagulants during PCI.ICAM-1 in blood was measured before PCI and in 2h, 1d and 7d after PCI, respectively.Results: In heparin group, ICAM-1 level decreased significantly in 2 h after the intravenous injection when compared with that before the injection and that in bivalirudin group at the same time point (P＜0.05).No significant differences in ICAM-1 level were found on the 1st and 7th day after PCI in the two groups when compared with that before the administration (P＞0.05).Mild bleeding occurred in three patients receiving heparin and one patient receiving bivalirudin,but there was no significant difference after PCI.Conclusion: Compared with bivalivudin, heparin has a short inhibitory effect on the expression of ICAM-1 during PCI.It is beneficial to the patients with kidney disease or stroke during PCI.

OBJECTIVE:To investigate the effects of loading-dose rosuvastain before early percutaneous coronary intervention (PCI) on reperfusion arrhythmias in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI).METHODS:A total of 136 patients with NSTEMI were randomly divided into loading-dose group (68 cases) and control group (68 cases).Both groups who were not given anti-platelet drugs were given loading-dose of Aspirin enteric-coated tablets 300 mg+Clopidogrel sulfate tablets 600 mg immediately after admission.The patients who were given aspirin regularly were given loading-dose of Clopidogrel sulfate tablets 600 mg only once after admission.The patients who were given clopidogrel regularly were given loading-dose of Aspirin enteric-coated tablets 300 mg only once.Those received PCI 12-24 h after medication.After PCI,they took Aspirin enteric-coated tablets 100 mg for life+Clopidogrel bisulfate tablets 75 mg at least 12 months.Loading-dose group was given loading-dose of Rosuvastatin calcium tablets 20 mg orally,12 h before surgery.All patients began to take Rosuvastatin calcium tablets 10 mg,once a day,since the night after the operation.Coronary angiography and the occurrence of reperfusion arrhythmia were observed in 2 groups.The levels of CK-MB and cTnT,major adverse cardiovascular events (MACE) were observed before and after surgery.RESULTS:There was no statistical significance in the number of diseased vessels,culprit vessels,the degree of culprit vessels stenosis or the incidence of MACE between 2 groups (P＞ 0.05).The incidence of reperfusion arrhythmia in loading-dose group was significantly lower than control group,with statistical significance (P＜0.01).There was no statistical significance in the degree of culprit vessels stenosis between 2 groups (P＞0.05).Before surgery,there was no statistical significance in the levels of CK-MB or cTnT between 2 groups (P＞0.05).After surgery,the levels of CK-MB and cTnT in 2 groups were significantly higher than before surgery,but the loading-dose group was significantly lower than the control group,with statistical significance (P＜0.01).CONCLUSIONS:Preoperative loading-dose of rosuvastatin before PCI can reduce the incidence of reperfusion arrhythmias in NSTEMI patients.

Objective To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). Methods A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. Results ① There were no significant differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score among groups. ② Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. ③ Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). ④ Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). ⑤ The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). Conclusions Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients. Trial registration Registration of clinical trials in China, ChiCTR-IPR-15006644.

OBJECTIVE:To evaluate the effects of loading-dose rosuvastatin on vascular endothelial function in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS) after early interventional therapy. METHODS:Totally of 128 NSTE-ACS patients underwent early interventional therapy were randomly divided into conventional dose group (63 cases) and loading dose group(65 cases). Before operation,all patients were given Clopidogrel sulfate tablets 300 mg and Aspirin enteric-coat-ed tablets 100 mg;on this basis,conventional dose group was given Rosuvastatin calcium tablets 10 mg orally;loading dose group was given Rosuvastatin calcium tablets 20 mg orally. After PCI,both groups were given Rosuvastatin calcium tablets 10 mg orally, qd,and Aspirin enteric-coated tablets(100 mg/d)and Clopidogrel sulfate tablets(75 mg/d),for consecutive 3 months. The blood samples were collected before surgery,8 h and 24 h after surgery. The serum levels of CK-MB,cTn T,hs-CRP,ET and NO were detected. The occurrence of major adverse cardiovascular events was recorded within 3 months after surgery. RESULTS:Compared with before surgery,the serum levels of CK-MB,cTn T,hs-CRP and ET were increased significantly 8 h and 24 h after surgery, while the level of NO was decreased,with statistical significance (P<0.05). However,the change range of loading dose group was lesser than that of conventional dose group,with statistical significance(P<0.05). There was no statistical significance in the incidence of adverse cardiovascular events between 2 groups(P>0.05). CONCLUSIONS:For NSTE-ACS patients underwent ear-ly interventional therapy,loading dose of rosuvastatin can protect the patients and inhibit the injury of vascular endothelial cell in-duced by the surgery.

BACKGROUNDGastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH.

METHODSAll 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups.

RESULTSThe incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower.

CONCLUSIONGastrodin could prevent steroid-induced ONFH by anti-apoptosis.

Animals ; Apoptosis ; drug effects ; Benzyl Alcohols ; therapeutic use ; Femur Head Necrosis ; drug therapy ; prevention & control ; Glucosides ; therapeutic use ; Lipopolysaccharides ; pharmacology ; Male ; Rats ; Rats, Wistar ; Steroids ; pharmacology

Quite a few orthopedics experts have fabricated some novel bone scaffolds with nanotechnology and have carried out some researches on nano-biological effects. The study of the biological effects about nano-biomaterials can facilitate the understanding of the interaction between the biomaterials and the organism, and provide research ideas and direction to construct new biomaterials with physiological function. To better understand the interaction of nano biomaterials with protein, cells and bio-security, this review presents recent advances of biological effects about nano scaffold for bone tissue engineering.
Biocompatible Materials ; metabolism ; Bone Substitutes ; Bone and Bones ; Humans ; Nanostructures ; Nanotechnology ; Surface Properties ; Tissue Engineering ; methods ; Tissue Scaffolds

BACKGROUND: Cytoskeleton is a carrier of cell growth, and its pore caliber is one of the most important factors to affect the curative effect of tissue engineered spinal cord.OBJECTIVE: To explore the optimal pore size of poly lactic-co-glycotic acid (PLGA) scaffolds for tissue engineered spinal cord by in vitro culture of neural stem ceils (NSCs) and various pore sizes of PLGA scaffolds.METHODS: 50 μL (cell number 10~(10)/L)NSCs suspension at passage 1 was separately seeded on 200-300 pm, 400-500 μm PLGA stant for 7 days. Two sorts of tissue engineered spinal cord were constructed in vitro. Thirty rat models of spinal cord injury were established, and then assigned to 3 groups. The detect sites of these models were filled with above-mentioned spinal cord immediately, but the blank control was not treated with any material. The cells growth and proliferation implanted on PLGA were observed by phase contrast microscope and scanning electron microscope. Relative number of NSCs in two tissue engineered spinal cords was measured by MTT assay. The effects of transplantation with tissue engineered spinal cord were evaluated by the BBB scala.RESULTS AND CONCLUSION: Neural stem cells implanted on different pore size scaffolds were seen growing by phase contrast microscope and scanning electron microscope, with good histocompatibility. After 7-day coculture, absorbance was similar between 200-300 pm PLGA and 400-500 pm PLGA groups (P > 0.05). These indicated that the pore size had no effects on NSC number. At week 4 following transplantation, in the blank control group, neural function was recovered to different degrees in the 200-300 μm PLGA and 400-500 μm PLGA groups. BBB motor functional score was significantly increased (P < 0.05). The pore size of 200-300 μm utilized in fabriceting tissue engineered spinal cord has the best transplantation effect as compared to others.

Objective The purpose of this study is to determine whether atrial expression of hepatocyte growth factor (HGF), connective tissue growth factor (CTGF) and transforming growth factor-beta1 (TGF-13,) is altered in patients with rheumatic heart disease (RHD) and chronic atrial fibrillation (AF).Methods Atrial tissue was obtained from the right atrial appendage during heart surgery from 35 patients. In 27 patients with rheumatic heart disease, 8 patients had no history of AF, and 19 had chronic persistent AF (≥6 months cAF). Other 8 patients with congenital heart disease had no history of AF were the control group.The mRNA expression of HGF, CTGF, TGF-β1, collagen Ⅰ and collagen Ⅲ was measured by the real-time fluorescence quota polymerase chain reaction (real time PCR). The fibrosis of right atrial appendage was detected by HE and Masson staining. Results The amount of CTGF, TGF-β1, collagen Ⅰ and collagen Ⅲ was significantly increased in patients with sinus rhythm compared with the control group (P<0.05) and further increased in patients with chronic AF compared with patients with sinus rhythm (P<0.05). The amount of HGF was significantly decreased in patients with chronic AF compared with patients with sinus rhythm and the control group (P<0.05). But the difference of the latter two groups was not statistically significant.Correlation analysis demonstrated that the mRNA expression of collagen Ⅰ , collagen Ⅲ, TGF-β1, and CTGF in right atrial appendage of RHD and AF was positively correlated with the left atrial diameter and the area of myocardial fibrosis. Conclusion In human atrium with RHD, the mRNA expression of collagen Ⅰ , collagen Ⅲ, CTGF and TGF-β1, is up-regulated. HGF has anti-fibrosis function and the down-regulation of its mRNA expression in patients with RHD may be an important factor in the initiation or maintenance of AF.