Poly(ADP-ribose) polymerase (PARP)-1 and PARP2 function as ADP-ribosylases involved in DNA repair. PARP1/2 is highly expressed in cancers and emerged as an attractive target for antitumor drug. In this study, we investigated the antitumor activity of a novel PARP1/2 inhibitor YHP-743 in vitro and in vivo. The results showed that YHP-743 had potent enzymatic inhibitory activity against PARP1 and PARP2 to down-regulate the PAR level. YHP-743 not only inhibited breast cancer cells with genes deficiency of homologous recombination repair, but also potentiated chemotherapy agent's cytotoxicity, such as temozolomide, topotecan, cisplatin and doxorubicin. YHP-743 elicited good antitumor activity in combination with temo-zolomide in vivo.

The aim of present study was to explore the effect of triptolide derivative LB-1 on imiquimod (IMQ) induced psoriasiform inflammation in BALB/c mice, and to investigate the immune mechanism of LB-1 in the prevention and treatment of psoriasis. In the present study, topical application of IMQ for seven days induced the psoriasiform inflammation in BALB/c mice. This is a promising mouse model of psoriasis for the natural immune reaction compared to those induced by xenograft, trangenic or gene knockout. psoriasis area and severity index (PASI) score, hematoxylin-eosin (HE) staining and flowcytometry were employed to investigate the changes of psoriasiform inflammation, histopathological response and percentage of T cells, respectively. The result showed that LB-1 significantly attenuated the psoriasiform inflammation. Com-pared with model group, PASI score were decreased in the LB-1 group. In the isolated immunocytes of spleen, LB-1 decreased percentage of CD8⁺ (P < 0.01) T cells and increased the ratio of CD4⁺/CD8⁺ T cells at the dosage of 2 mg·kg^-1 (P < 0.01), whereas LB-1 raised percentage of CD4⁺ T cells and CD3⁺ T cells at the dosage of 4 mg·kg^-1. In conclusion, the present study demonstrated that LB-1 attenuated psoriasiform inflammation induced by imiquimod in BALB/c mice. The mechanism of LB-1 action may be related to change percentage of CD4⁺ T, CD8⁺ T cells in the spleen. These results provide a basis for LB-1 or other triptolide derivative in the intervention of psoriasis in the future.

Objective To investigate the status quo of clinical engineering departments (CED) in Guangdong province, to find out the main problems and challenges, and to give some suggestions on promoting the development of clinical engineering. Methods Questionnaires were issued to directors or engineers in hospitals on department missions, staff composition, quality control and obstructive factors for discipline development. Statistical analysis was executed for the questionnaires. Results Only 53.19% of the CED operated independently. The daily CE practice in Guangdong hospitals included carrying out procurement, installation, maintenance and archiving. Only 28.0%of the hospitals had QC instruments. The education backgrounds were mainly restrained in undergraduate degree and junior college degree, accounting for 80.0%. Totally 39.0% of the clinical engineers majored in biomedical engineering. The personnel with primary or intermediate professional titles accounted for 61.96%. There was 0.68 engineer per 100 beds or 0.23 engineer per ten million Yuan medical equipment. The top 3 factors that hindered the development of CE were inadequacy of professional staff, low education level and absence of laws and regulations. Conclusion CED in Guangdong province drops behind the outstanding institutions in China, and has to be promoted with the efforts of supervision facilities and etc.

Poly (ADP-ribose) polymerase 1/2(PARP1/2) can catalyze the poly (ADP ribose) (PAR) substrate protein modification and play an important role in the regulation of DNA damage repair, cell death and transcriptional activity. The PARP inhibitor olaparib (AZD2281) can be used as a sensitizer of radiotherapy and chemotherapy in the cancer treatment. Through establishment of biological fluorescent labeled 4T1 ectopic breast tumor model, we found that olaparib exhibited a poor effect on 4T1 breast cancer alone. However, in the combination with Taxol, olaparib significantly increased the anti-tumor effect of Taxol, and reduced the PAR levels of the tumor tissues. Importantly, olaparib did not amplify the toxicity of chemotherapy drugs. This study suggests that olaparib is a representative of the PARP inhibitor that can enhance Taxol 's antitumor effect in the 4T1 ectopic breast tumor model, which sets the foundation for future study of the mechanism of olaparib action.

OBJECTIVES: To detect the changes of microbial community functional diversity of corpses with different postmortem interval （PMI） and to evaluate forensic application value for estimating PMI. METHODS: The cultivation of microbial community from the anal swabs of a Sus scrofa and a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Microplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial community on the decomposed corpse under natural environment were also observed. RESULTS: The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples became relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components （accumulative contribution ratio >90%）.The carbon source tsquare-analysis showed that N-acetyl-D-glucosamine and L-serine were the dominant carbon sources for estimating the PMI （0=240 h） of the Sus scrofa and human corpse. CONCLUSIONS The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI.
Biodiversity ; Cadaver ; Carbon ; Humans ; Postmortem Changes ; Principal Component Analysis ; Soil Microbiology ; Time Factors

OBJECTIVETo investigate the applications of percutaneous screw fixation for the treatment of pelvic fractures and its related surgical considerations.

METHODSFrom June 2010 to June 2012,19 patients with pelvic fractures were treated with percutaneous hollow screws. There were 13 males and 6 females, with an average age of 41 years (ranged from 22 to 58 years). Fractures were caused by traffic accidents in 11 cases, by falling down from high place in 8 cases. Based on the Tile classification, there were 15 cases of Tile C type and 4 case of Tile B type. The indexes such as screw inserting time, intraoperative blood loss, complications, functional recovery and reduction conditions were observed. Fixation methods included sacroiliac screws, cannulated screw fixation of the pubic ramus and cannulated screw fixation of the pubic symphysis separation.

RESULTSAnatomical reduction achieved in 7 cases, satisfactory reduction 11 cases, and unsatisfactory reduction 1 case. Union time of fracture union ranged from 8 to 12 weeks (mean 10 weeks). Wound infection,ununion of fracture and nerve injuries were not found. According to the Majeed standards, 12 patients obtained an excellent results, 6 good and 1 fair.

CONCLUSIONPercutaneous screw fixation for the treatment of pelvic fractures under fluoroscopy has several advantages such as less trauma, less blood loss, fewer rates of complications, reliable fixation and no blood transfusion, which can reconstruct the stability of the pelvic ring, but it needs adequate preoperative preparation and high requirements for the surgeon.

Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; diagnostic imaging ; surgery ; Humans ; Male ; Middle Aged ; Pelvic Bones ; diagnostic imaging ; injuries ; surgery ; Radiography ; Young Adult

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

OBJECTIVETo study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China.

METHODSA cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria.

RESULTSThe age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions.

CONCLUSIONUsing both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.

Adult ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; epidemiology ; Middle Aged ; Obesity ; epidemiology ; Prevalence ; Risk Assessment ; Risk Factors ; Waist Circumference

OBJECTIVETo improve the awareness of acute coronary artery thrombosis in Kawasaki disease (KD).

METHODSix KD patients with acute coronary artery thrombosis (Jan. 2004 to Jan. 2013) were studied retrospectively. The basic information, clinical manifestations, laboratory data, echocardiography and electrocardiography (ECG), method and consequence of thrombolytic therapy were analyzed.

RESULTThe mean age of patients with coronary artery thrombosis (5 males and 1 female) was (17.2 ± 11.3) months.Five cases had thrombosis in left coronary artery (LCA), and four cases had thrombosis in aneurysm of left anterior descending artery (LAD). One case had thrombosis in both left and right coronary artery (RCA).One case died. Maximum thrombus was about 1.60 cm × 0.80 cm, locating in LAD. The diameter of LCA and RCA was (0.44 ± 0.07) cm and (0.45 ± 0.07) cm. Two patients showed abnormal ECG. Case 3 showed ST segment depression in lead V5. Case 6 showed myocardial infarction.In acute phase of KD, three patients received treatment with intravenous immunoglobin (IVIG), five patients were treated with aspirin.In sub-acute and convalescent phase of KD, all patients were treated with low-dose aspirin.Warfarin and dipyridamole were applied in 5 patients. All cases were treated with thrombolytic therapy using urokinase and/or heparin. After thrombolytic therapy, echocardiography showed thrombolysis in four cases and no change in one.One patient died of myocardial infarction.

CONCLUSIONMost of acute coronary thrombosis in KD occurred in LAD. KD patients with coronary artery thrombosis are at risk of sudden death due to myocardial infarction.

Acute Disease ; Anticoagulants ; administration & dosage ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Child, Preschool ; Coronary Aneurysm ; diagnosis ; drug therapy ; etiology ; Coronary Thrombosis ; diagnosis ; drug therapy ; etiology ; Echocardiography ; Electrocardiography ; Female ; Fibrinolytic Agents ; administration & dosage ; therapeutic use ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; therapeutic use ; Infant ; Infant, Newborn ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; drug therapy ; Myocardial Infarction ; diagnosis ; etiology ; mortality ; Retrospective Studies

BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.

METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.

RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.

CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology