Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.

ObjectiveTo observe the effects of bone marrow stromal cells (BMSCs) on vessel endothelial cells proliferation and microvessel formation in vitro.MethodsBMSCs and brain vessel endothelial cells were separated from adult and divided into co-culture group of BMSCs and endothelial cells, medium group of BMSCs, comparison group. Endothelial cells proliferation and microvessel formation were observed. ResultsEndothelial cells were promoted to proliferate and formate the microvessel in medium group and co-culture group. And the effect was prominence in co-culture group.ConclusionBMSCs can promote the proliferation and microvessel formation of endothelial cells.

Objective To examine the expression of recombinant cytolethal distending toxin(CDT)produced by Actinobacillus actinomycetemcomitans(Aa).Methods CDT encoding gene cdtABC was amplified by PCR.Through TA clone and restriction endonuclease digestion,gene cdtABC and vector pQE60 were ligated to form pQE60-cdtABC expression system which transformed into competent cells.Protein expression was induced by IPTG and examined by SDS-PAGE and Western-blotting.Results Random colony PCR of pQE60-cdtABC transformed cells demonstrated that all strains contained cdtABC gene.The DNA sequence was blast with cdtABC gene from GenBank and 99%homology was obtained.SDS-PAGE and Western-blotting confirmed that recombinant CDT was obtained.Conclusions CDT protein expression system was reconstructed and recombinant protein was obtained.

OBJECTIVETo explore the role of Xuebijing Injection (XBJI) in inhibiting inflammatory factors associated with anoxia/reoxygenation myocardial inflammatory response of rats.

METHODSTotally 36 healthy male Sprague-Dawley rats, 280 ± 30 g were randomly divided into six groups, i.e., the normal control group (N group), the balanced perfusion group (BP group),the model group (M group),the low dose XBJI group (XBJI(L) group), the middle dose XBJI group (XBJI(M) group),and the high dose XBJI group (XBJI(H) group), 6 in each group. The myocardial anoxia/reoxygenation rat model was established by Langendorff isolated heart perfusion. The concentration of TNF-α in the myocardial tissue was detected by ELISA. The expression of nuclear factor kappa B p65 (NF-κB p65) protein and Toll like receptor 4 (TLR4) protein were detected using Western blot. The expression of NF-κB p65 mRNA and TLR4 mRNA was detected by RT-PCR. Ultrastructural changes of anoxia-reoxygenation rats' heart muscle were observed under transmission electron microscope.

RESULTSCompared with the M group,the TNF-α concentration, expression levels of NF-κB p65 protein and mRNA, TLR4 protein and mRNA decreased to various degrees in the XBJI(L) group, the XBJI(M) group, and the XBJI(H) group. The TNF-α expression level decreased most significantly in the XBJI(L), group (P < 0.01), while other indices decreased most obviously in the XBJI(M) group (P < 0.01, P < 0.05). Expression levels of NF-κB p65 and TLR4 protein were obviously lower in the XBJI(M) group than in the XBJI(L) group (P < 0.05). There was no statistical difference in other indices among the three XBJI groups (P > 0.05). Myocardial fibers were loose and broken with disappearance of transverse striation, and mitochondrial cristae was dissolved and severely damaged in the M group. The aforesaid condition was improved after treated by XBJI, with the most obvious effect obtained in the XBJI(M) group.

CONCLUSIONSDifferent doses of XBJI could attenuate inflammatory reactions after myocardial anoxia/reoxygenation rats' heart muscle through inhibiting TLR4-NF-κB-TNF-α signal transduction pathway. The best effect could be obtained by 4 mL/100 mL XBJI.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Hypoxia ; Male ; Myocardium ; metabolism ; Myocytes, Cardiac ; NF-kappa B ; metabolism ; Oxygen ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha ; metabolism

Objective To evaluate the possible interactions among different impact factors possibly affecting the treatment efficacy of 131I in Graves′ disease (GD). Methods Six hundred and thirty two GD patients that had been treated by 131I, with or without antithyroid drugs (ATD), were included in this study. The impact factors were pre-defined as age (x1), sex (x2), mass of thyroid (x3), course of disease (x4), initial symptom (x5), condition of disease (x6), ATD treatment duration (x7), effective half life time (x8), maximum 131I uptake rate (x9), total dose of 131I (x10), dose of 131I per gram of thyroid (x11), TRAb (x12), TSI (x13), TgAb (x14), and thyroid microsomal antibody(TMAb) level(x15). Interactions among different impact factors were studied by t-test, χ2 test and multi-variant logistic regression. Results Age, mass of thyroid, ATD treatment duration, maximum 131I uptake rate, dose of 131I per gram of thyroid tissue and TSI level were identified as independent impact factors affecting the 131I treatment efficacy on GD (χ2=6.908, t=-4.063, χ2=13.558, t=-2.553, t=4.528, χ2=9.716, all P<0.05) by uni-variant and multi-variate analyses. Loglinear and general linear model analyses showed that there existed multiple multiplicative and additive interactions among the factors of age, mass of thyroid, ATD treatment duration and maximum 131I uptake rate (likelihood χ2=8.176, P>0.05; F=2.928, 1.992, 2.629, 2.215, all P<0.05), which indicated that the treatment efficacy with co-existing multiple factors was not equal to simple summation of single factors. Conclusions The interactions among multiple factors can cause indi-rect effect on 131I treatment, which might guide the prescription of 131I dosage for GD treatment.

OBJECTIVETo observe the thoracic aorta features in patients with bicuspid aortic valve (BAV) with echocardiography.

METHODSWe retrospectively analyzed the echocardiographic features and clinical manifestations in 273 patients with BAV detected from 1991-04 to 2006-02.

RESULTS(1) Aortic dimensions of the anulus, the sinuses of valsalva, the sinotubular junction, the ascending aorta at the level of its largest diameter of 31 patients with functionally normal BAV were significantly increased compared that in control subjects (P < 0.01 to P < 0.001) while the dimension of the descending aorta posterior to the left atrium was similar between the two groups (P > 0.05). (2) There is no relation between the vulval positions of BAV and aortic dimensions (P > 0.05). (3) The dimensions of the annulus as well as the sinuses of valsalva were negatively related to the aortic valve gradient, and the dimension of the annulus, the sinuses of valsalva and sinotubular junction were positively related to the degree of aortic regurgitation in 273 patients with BAV (all P < 0.05).

CONCLUSIONOur results show there is a hemodynamic independent thoracic aortic dilation in patients with functionally normal BAV. Gradient and aortic regurgitation are related to the dimension of the annulus, the sinuses of valsalva and sinotubular junction in patients with BAV.

Adult ; Aorta, Thoracic ; diagnostic imaging ; Aortic Valve ; abnormalities ; Female ; Heart Defects, Congenital ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Ultrasonography

OBJECTIVETo evaluate the effect of short-term intensive therapy on blood glucose control, BETA-cell function, and blood lipid levels in newly diagnosed type 2 diabetic patients.

METHODSOut-patients with newly diagnosed type 2 diabetic patients were enrolled for intensive treatment with sulfonylureas and metformin for 12 weeks, and the therapeutic effect was evaluated.

RESULTSAfter the intensive treatment, FPG, 2 hPG, and HbA1c decreased significantly (P<0.01); HOMA-IR decreased and HOMA-B increased significantly (P<0.01), and TG, CHOL, LDL decreased significantly (P<0.01) after the treatment.

CONCLUSIONShort-term intensive treatment with glimepiride combined with metformin is safe and effective in newly diagnosed type 2 diabetic patients with HbA1c>9%.

Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Male ; Metformin ; therapeutic use ; Sulfonylurea Compounds ; therapeutic use ; Treatment Outcome

The clinical data of one patient with autoimmune polyendocrinopathy syndrome type I were collected. PCR-DNA direct bidirectional sequencing was applied for mutation screening of 14 exons in autoimmune regulator (AIRE) gene in the patient and her parents. A total of 50 unrelated healthy controls were selected and tested. The bioinformatic methods were used to predict the possible impact of the mutations on the structure and function of the AIRE protein. The results of sequencing showed that heterozygous mutation c.622G>T (p.G208W) in exon 5 of the AIRE gene was detected in the patient and was a novel mutation, which had not been reported in the HGMD database and latest articles. This mutation was not detected in the 50 unrelated normal controls. The novel mutation of c.622G>T (p.G208W) in AIRE gene might play an important role in the pathogenesis of this case of autoimmune polyendocrinopathy syndrome type I.
Adolescent ; Adult ; Amino Acid Sequence ; Base Sequence ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pedigree ; Polyendocrinopathies, Autoimmune ; genetics ; Sequence Alignment ; Transcription Factors ; chemistry ; genetics ; Young Adult

OBJECTIVEPorphyromonas gingivalis (P. gingivalis) is considered to be major putative periodontal pathogens. The purpose of the study was to evaluate P. gingivalis and clinical effects of scaling and root planning (SRP) in 20 subjects after 3 months.

METHODSTwenty periodontitis patients were selected. The mean age was (44.33 +/- 13.86) years old. Clinical assessments of probing depth (PD), clinical attachment loss (CAL) and bleeding on probing (BOP) were made prior to SRP and at 3 months post-therapy. Subgingival plaque samples were taken at each visit and analyzed using TaqMan real-time polymerase chain reaction for the presence and levels of P. gingivalis. The quantification for P. gingivalis was also performed with the help of the species-specific primers/probes and the serial dilution of the plasmid standards.

RESULTSMean probing depth, mean clinical attachment loss and bleeding on probing showed significant reduction at 3 months (P<0.001). The prevalence and level of P. gingivalis were significantly reduced after SRP (P<0.001). A positive correlation was found between the numbers of P. gingivalis and PD at baseline (P<0.001). There were no correlation between the initial level of P. gingivalis at baseline and the clinical improvement after therapy. But the number of P. gingivalis at responding sites was more decreased than non-responding sites after SRP (P<0.05).

CONCLUSIONSRP produced a good clinical improvement. The prevalence and level of P. gingivalis were significantly reduced after SRP. The effect of SRP may be determined by the degree of P. gingivalis is decreased. The real-time polymerase chain reaction can be used to evaluate the effect of periodontal therapy.

Adult ; Dental Plaque ; Dental Plaque Index ; Dental Scaling ; Female ; Humans ; Male ; Middle Aged ; Periodontal Attachment Loss ; Periodontal Pocket ; Periodontitis ; Porphyromonas gingivalis ; Root Planing

BACKGROUNDInside out transobturator vaginal tape (TVT-O) and tension-free vaginal tape (TVT) are predominant surgical treatments for female stress urinary incontinence. This meta-analysis evaluated the complications and cure rates of TVT-O versus TVT.

METHODSA comprehensive literature search was conducted according to the Cochrane Collaboration methodology to identify randomized controlled clinical trials with no language restriction. Two authors independently assessed papers for eligibility and methodological quality. Estimates were measured by relative risk with 95% confidence intervals. Outcome measures were objective cure, subjective cure and complications. Quality rating for each outcome of the meta-analysis and recommendations were performed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

RESULTSTwenty randomized controlled trials met the inclusion criteria, and a pooled estimate of effectiveness and complications was made. Relative risks with 95% confidence intervals for pooled effects under the fixed effects model were: 0.20 (0.09 - 0.45), for bladder injury, 0.37 (0.16 - 0.86) for hematoma, and 2.35 (1.57 - 3.51) for postoperative pain, suggesting an 80% risk reduction of bladder injury, 63% risk reduction of hematoma, and a 1.35% risk elevation for postoperative pain with TVT-O. There was no significant difference between complications of urinary tract infection 1.14 (0.78 - 1.65), lower urinary tract symptoms 1.60 (0.67 - 3.79), recatheterization 0.93 (0.59 - 1.44), and tape erosion 0.90 (0.48 - 1.67), total objective cure rate 1.06 (0.39 - 2.84) and for the subjective cure rate 0.98 (0.93 - 1.04). The quality rating for each outcome and recommendations was high for objective cure, bladder injury, hematoma, lower urinary tract symptoms, and tape erosion and moderate for subjective cure, pain, and urinary tract infection.

CONCLUSIONSTVT-O is associated with a reduced risk of bladder injury and hematoma and an elevated risk of postoperative pain. Other complications, including tape erosion, urinary tract infection, lower urinary tract symptoms, and recatheterization, are similar to those of TVT.

Female ; Humans ; Randomized Controlled Trials as Topic ; Suburethral Slings ; Treatment Outcome ; Urinary Incontinence, Stress ; surgery ; Vagina ; surgery