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.

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 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.

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.

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

OBJECTIVEThe ability of oral bacteria to adhere to tooth surface is associated with their pathogenicity. The objective of this study was to compare the ability of 4 strains of periodontal pathogens attaching to collagen-treated hydroxyapatite (C-HA) beads in order to evaluate the ability of the main periodontal pathogens to form the biofilm on root surface.

METHODSThe binding amount and binding percentage of 4 strains to C-HA were measured and compared by 3H-labeled binding assay. 4 strains of periodontal pathogens were Fusobacterium nucleatum (F. nucleatum) ATCC 10953, Porphyrin gingivalis (P. gingivalis) ATCC 33277, Prevotella intermedia (P. intermedia) ATCC 25611 and Hemophilic actinomycetemcomitans (H. actinomycetemcomitans) ATCC 29523.

RESULTSThe differences of the percentage of relative adherence between F. nucleatum ATCC 10953 and P. gingivalis ATCC 33277, as well as between H. actinomycetemcomitans ATCC 29523 and P. intermedia ATCC 25611 could not be observed. However, the percentage of relative adherence of F. nucleatum ATCC 10953 and P. gingivalis ATCC 33277 was higher than that of P. intermedia ATCC 25611 and H. actinomycetemcomitans ATCC 29523 (P<0.001), no matter cultured 24 h or 48 h. No significant difference of the percentage of the relative adherence of each stain between 24 h and 48 h cultured time could be found.

CONCLUSIONF. nucleatum and P. gingivalis exhibited strong binding ability to C-HA. Their adherence to root surface may play an important role in their local aggregation, biofilm formation during the development and recurrence of the periodontitis.

Aggregatibacter actinomycetemcomitans ; Bacteria ; Collagen ; Durapatite ; Fusobacterium nucleatum ; Humans ; Periodontitis ; Porphyromonas gingivalis ; Prevotella intermedia

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

OBJECTIVETo observe the therapeutic effect of moxibustion and exercise comprehensive scheme intervention for children with short stature of deficience of the kidney essence.

METHODSTwenty four cases of children in 12 to 14 years old were selected, 12 male and 12 female, they were treated with comprehensive therapy of exercise therapy and moxibustion. Running and jumping were selected as main exercise therapy, it became a suitable exercise amount when the heart rate reach to 150 to 170 times per minute, thrice each week, 35 to 45 minutes each time. After exercises they were treated with moxibustion, Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Dazhu (BL 11), Xuanzhong (GB 39), Geshu (BL 17) etc. were selected. After treatment for half a year, the changes of the body height, body weight, bone age(BA), growth hormone (GH), testosterone (T) and estradiol (E2) were compared before and after treatment.

RESULTSThe body height and bone age of the boys and girls were significantly higher than those before treatment (all P<0.05), the growth of body height was more than 4 cm, the growth of bone age was more than 0.5 years old in half a year; the testosterone of all children was significantly increased (all P<0.05), and there were no significant differences in body weight, GH and E2 compared to those before treatment (all P>0.05).

CONCLUSIONMoxbustion and exercise comprehensive scheme can effectively improve the children with short stature of deficience of the kidney essence, the mechanism is related to the improving of the testosterone level.

Adolescent ; Body Height ; Child ; Estradiol ; metabolism ; Exercise Therapy ; Female ; Growth Disorders ; metabolism ; physiopathology ; therapy ; Human Growth Hormone ; metabolism ; Humans ; Kidney ; physiopathology ; Male ; Moxibustion ; Testosterone ; metabolism ; Treatment Outcome

BACKGROUNDInvasive fungal infections have constituted an increasingly important cause of morbidity and mortality in immunocompromised patients. In this study, a surveillance project was conducted in three different intensive care units of two large tertiary hospitals in China.

METHODSA one-year surveillance project was conducted in two tertiary hospitals which located in northern China and southwest China respectively. Air, surfaces and tap water were sampled twice a month in a central intensive care unit, a bone marrow transplant unit, a neurosurgery intensive care unit and a live transplant department. Environmental conditions such as humidity, temperature and events taking place, for example the present of the visitors, healthcare staff and cleaning crew were also recorded at the time of sampling.

RESULTSThe air fungal load was 91.94 cfu/m(3) and 71.02 cfu/m(3) in the southwest China hospital and the northern China hospital respectively. The five most prevalent fungi collected from air and surfaces were Penicillium spp., Cladospcrium spp., Alternaria spp., Aspergillus spp. and Saccharomyces spp. in the southwest China hospital, meanwhile Penicillium spp., Fusarium spp., Aspergillus spp., Alternaria spp. and Cladospcrium spp. in the northern China hospital. The least contaminated department was intensive care units, and the heaviest contaminated department was neurosurgery intensive care unit. Seventy-three percent of all surfaces examined in the northern China hospital and eighty-six percent in the southwest China hospital yielded fungi. Fifty-four percent of water samples from the northern China hospital and forty-nine percent from the southwest China hospital yielded fungi.

CONCLUSIONSThese findings suggested that the fungus exist in the environment of the hospital including air, surface and water. Air and surface fungal load fluctuated over the year. Air fungal load was lower in winter and higher in summer and autumn, but seldom exceeded acceptable level. The higher values were created during May to August in the northern China hospital and May to June and September to October in the southwest China hospital. A correlation between air fungal load and humidity, as well as personnel was observed.

Air Microbiology ; China ; Environmental Monitoring ; methods ; Fungi ; isolation & purification ; Hospitals ; Intensive Care Units ; Water Microbiology