Objective To observe the protective effect of hydroxysafflor yellow A(HSYA) on anoxia/reoxygenation (A/R) injury of neonatal primary cardiomyocytes, and its relationship with phosphoinositide 3-kinase/protein ki-nase B/glycogen synthase kinase 3β(PI3K/Akt/GSK3β) signaling pathway. Methods Primary cardiomyocytes of neonatal rats were isolated from the rats and incubated for 48 hours. The cells were adhered to each other and then divided into five groups:control group (Con group), anoxia/reoxygenation group (A/R group),HSYA treatment group(A/R+H group),PI3K inhibitor (LY294002)treatment group(A/R+L group)and HSYA+LY294002 treat-ment group (A/R+H+L group),then to collect the supernatant fluid of each group to measure LDH.The flow cy-tometry was used to measure the apoptotic cells. The protein levels of Bcl-2,Bax,Akt,p-Akt (Ser473),GSK3β, p-GSK3β (Ser9) were evalated by Western blot. Results A/R increased LDH release,the apoptosis rate (P<0.001),and the expression of pro-apoptotic protein Bax (P <0.001) with the decrease of anti-apoptotic protein Bcl-2,p-Akt(Ser473), p-GSK3β(Ser9)(P<0.001) as compared with the control group. HSYA treatment de-creased LDH release,the apoptosis rate (P<0.001),and the expression of Bax (P<0.001) and increase the ex-pression of Bcl-2,p-Akt(Ser473),p-GSK3β(Ser9)(P<0.001). Compared with the A/R+H group,the expres-sion of Bax was increased (P<0.001),while the expression of Bcl-2, p-Akt(Ser473), p-GSK3β(Ser9)was de-creased (P<0.001) in the A/R+H+L group. Conclusions HSYA protects rats'cardiomyocytes from anoxia/reoxy-genation injury by regulating PI3K/Akt/GSK3β signaling pathway.

The main purpose of this paper is to explore the applicability of multivariate multilevel models for bioequivalence evaluation. Using an example of a 4×4 cross-over test design in evaluating bioequivalence of homemade and imported rosiglitazone maleate tablets,this paper illustrated the multivariate-model-based method for partitioning total variances of In (AUC) and In (C_(max)) in the framework of multilevel models. It examined the feasibility of multivariate multilevel models in directly evaluating average bioequivalence (ABE),population bioequivalence (PBE) and individual bioequivalenc (IBE). Taking into account the correlation between In (AUC) and In (C_(max)) of rosiglitazone maleate tablets,the proposed models suggested no statistical difference between the two effect measures in their ABE bioequivalence via joint tests,whilst a contradictive conclusion was derived based on univariate multilevel models. Furthermore,the PBE and IBE for both In (AUG) and In(C_(max)) of the two types of tablets were assessed with no statistical difference based on estimates of variance components from the proposed models. Multivariate multilevel models could be used to analyze bioequivalence of multiple effect measures simultaneously and they provided a new way of statistical analysis to evaluate bioequivalence.

BACKGROUND: Chinese medicine is effective for preventing and treating glucocorticoid-induced osteoporosis, however, the underlying mechanism remains unclear. DKK1, an inhibitor of Wnt/β-catenin signaling pathway, can be up-regulated by glucocorticoid. Thereafter, DKK1 is an important target in the prevention and treatment of osteoporosis. OBJECTIVE: To explore the regulatory effect of Zuogui pill on DKK1 in the prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: Eighteen three-month-old female Sprague-Dawley rats were randomly divided into three groups: control group, model group and Zuogui pill group. Rats in the model and Zuogui pill groups received the subcutaneous injection of dexamethasone to establish the model of glucocorticoid-induced osteoporosis. The Zuogui pill group rats were administrated Zuogui pill extracts, and the control rats were given the same volume of normal saline. At 1 month after modeling, the lumbar vertebrae were removed to test the bone mass and microstructures by micro-CT scanning. The biomechanical properties were detected by compression test. The mRNA expression levels of DKK1, Runx2 and CTSK were determined by Qpcr. The serum alkaline phosphatase activity was tested. RESULTS AND CONCLUSION: Compared with the control group, in the model group, the volumetric bone mineral density, trabecular bone volume fraction, trabecular number, and trabecular thickness were significantly decreased (P ＜ 0.05), the trabecular separation and structure model index were significantly increased (P ＜ 0.05). The serum alkaline phosphatase activity was on a decline. The mRNA expression level of DKK1 showed a significant up-regulation (P ＜ 0.05). The mRNA expression level of Runx2 showed a down-regulated trend while mRNA expression level of CTSK showed an up-regulated trend. Compared with the model group, the Zuogui pill group showed significantly enhanced volumetric bone mineral density, trabecular bone volume fraction, and trabecular number (P ＜ 0.05); the structure model index was significantly decreased (P ＜ 0.05); the trabecular separation was reduced; the serum alkaline phosphatase activity was enhanced; the mRNA expression level of DKK1 showed a significant down-regulation (P ＜ 0.05); the mRNA expression level of Runx2 showed an up-regulated trend while mRNA expression level of CTSK showed a down-regulated trend. The vertebral compressive strength in the Zuogui pill group was significantly higher than that in the model group (P＜0.05). In summary, Zuogui pill prevents and treats glucocorticoid-induced osteoporosis possibly through the down-regulation of mRNA expression of DKK1.

OBJECTIVETo investigate the relationship between p53 codon 72 polymorphism and susceptibility to keloid in a southern Chinese population.

METHODSThe p53 genotypes were determined by polymerase chain reaction-reverse dot blot (PCR-RDB) and DNA direct sequencing in 45 patients with keloid and 60 unrelated healthy controls.

RESULTSThe frequency of the p53 Pro allele among keloid patients was significantly higher than that among healthy controls (chi2 = 4.485, P = 0.034). The Pro/Arg and Arg/Arg genotype distribution among keloid patients was not significantly different from that among healthy controls (chi2 = 0.949, 1.346; P = 0.330, 0.246, respectively). However, the Pro/Pro genotype frequency among keloid patients was significantly higher than that among healthy controls (chi2 = 4.375, P = 0.036). The p53 Pro/Pro genotype significantly increased the risk for developing keloid, compared to the combination of Pro/Arg and Arg/Arg genotypes,with the odds ratio (OR) of 2.400 (95%CI: 1.048-5.498).

CONCLUSIONSDetermination of the p53 codon 72 genotype may be used as a stratification marker to predicate high-risk individuals for keloid.

Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; China ; epidemiology ; Codon ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Keloid ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

BACKGROUNDAlthough previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.

METHODSA total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m(2) of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m(2)2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0.

RESULTSThe median age of groups 1 to 4 was 61, 62, 56, and 60 years, respectively. Most patients were in stages II/III of MM and the most common subtype was IgG. The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% (13/18), 73.8% (48/65), 78.8% (26/33) and 78.0% (32/41) (P = 0.91), including a complete response rate of 22.2% (4/18), 20.0% (13/65), 33.3% (11/33) and 29.3% (12/41) (P = 0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P > 0.05). The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups (P > 0.05) except that peripheral neuropathy was reported more frequently in group 3 (36.3%) than in group 2 (13.8%, P < 0.05) and group 4 (14.6%, P < 0.05).

CONCLUSIONSThe combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China.

Antineoplastic Agents ; administration & dosage ; Antineoplastic Agents, Hormonal ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; China ; Dexamethasone ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Neoplasm Recurrence, Local ; Prospective Studies ; Pyrazines ; administration & dosage

Objective To explore the effects of bisoprolol adding to the conventional therapy on neuroendocrine hormones in patients with heart failure with preserved left ventricular ejection fraction ( HFPEF ) .Methods Fifty-one patients with HFPEF were randomly assigned into two groups: control group ( n =25 ) and trial group ( n =26 ).The control group was treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonist and aldosterone receptor antagonists, diuretics and other drugs combination therapy.The trial group was the control group plus bisoprolol 5 -10 mg · d-1 .Each group was two weeks.The levels of brain natriuretic peptide ( BNP ) , atrial natriuretic peptide ( ANP ) , leptin, chromogranin A ( CGA ) , interleukin -6 ( IL-6 ) , thromboxane B2 ( TXB2 ) , tumor necrosis factor -α( TNF-α) , endothelin ( ET ) , hypersensitive C-reactive protein ( hs-CRP) were observed fourteen days before and after the treatments, and the incidence rate of adverse drug reactions.Results The total efficiency of the trial group was 88.46%significantly higher than 60.00%in the control group(P<0.05).The levels of plasma BNP, ANP, leptin, CGA, ET, hs-CRP were significantly decreased in the trial group ( P<0.05 ) after treatment.The levels of plasma BNP, ANP, Leptin, CGA, hs-CRP were significantly decreased in the control group ( P<0.05) after treatment.The levels of BNP, leptin, CGA, ET, hs-CRP lower in trial group than in the control group ( P<0.05 ).The incidence rate of adverse drug reactions were not statistical difference between the two groups ( P>0.05).Conclusion Bisoprolol adding to the convertional therapy can significantly improve the heart function of patients with HFPEF and can lead to more decrease of BNP, leptin, CGA, ET, hs -CRP than the conventional therapy.

Objective To prepare monoclonal antibodies (McAbs) against VP1 capsid protein of Enterovims 71. Methods Two peptides, SP55 and SPT0, containing amino acid 163-177 and 208-222 of VP1, were synthesized respectively. Immunized BALB/c mice with the synthetic peptides to estabhsh the hybridoma cell strains secreting specific McAb to VP1. After the specific McAbs were prepared, identified and analyzed the titer by indirect ELISA assay. The positive clones were selected and their neutralization titer were determined by neutralization test. Results Two high titered anti-VP1 antibodies secreted by the hybfidoma cells showed good neutralization reaction with enterovirus 71 on RD cells, and the neutralization titer were 1:8 and 1 : 16 respectively. Conclusion Two high titered anti-VP1 antibodies, with good neutralization activity, secreted by the hybridoma cells, which lays the foundation for further study.

Objective Obtain the hepatitis C virus high purified subunit fusion protein and detect its immunogenicity.Methods With the vector of pET-11d,fusion protein was expressed in Escherichia coli BL21(DE3) after induced by IPTG.The protein was then purified by DEAE negative ion exchange chromatography and Ni2+ affinity chromatography.Western Blot analysis was used to detect the antigenicity of the fusion protein.At the same time,the sera were collected and prepared from the immunized experimental animals in order to investigate the immunogenicity of the protein by EIA.Results High purified hepatitis C virus subunit fusion protein was obtained successfully.The EIA indicated that the fusion protein could elicit specific antibodies in the animals with very high titers.Conclusion The hepatitis C virus subunit fusion protein expressed in prokaryotic system was proved to have strong immunogenicity.It could provide some helpful and useful information to the hepatitis C virus prophylactic and therapeutic vaccine development.

Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m2(0.7-1.0 mg/m2) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m2 (0.7-1.0 mg/m2)of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2％ (13/18), 73.8％ (48/65), 78.8％ (26/33) and 78.0％ (32/41) (P=0.91), including a complete response rate of 22.2％ (4/18), 20.0％ (13/65), 33.3％ (11/33) and 29.3％ (12/41) (P=0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P ＞0.05). The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups (P ＞0.05) except that peripheral neuropathy was reported more frequently in group 3 (36.3％) than in group 2 (13.8％, P ＜0.05) and group 4 (14.6％, P＜O.05).Conclusions The combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China.

OBJECTIVETo analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSThis is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.

RESULTSThe objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05).

CONCLUSIONSCompared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Disease-Free Survival ; Double-Blind Method ; Endostatins ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Prospective Studies ; Quality of Life ; Remission Induction