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Two new flavanoids fissistiganoids A and B (

Two novel aporphine-derived alkaloids, aporaloids A and B (1 and 2), together with eight known biogenetically related alkaloids (3−10), two known isoquinoline alkaloids (3 and 4), and six known aporphinoid alkaloids (5–10) were isolated from the stems of Fissistigma glaucescens. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1 and 2 represent the rare example of a six-membered lactone ring aporphine-derived alkaloids from natural products. The inhibitory activities of all compounds against four cancer cell lines were evaluated. Aporaloids A and B (1 and 2) showed broad spectrum cytotoxic activities.

One new norsesquiterpene polyalone A (1), and one new natural product 9-keto-cyclocolorenone (2), along with three known analogues (3–5) were isolated from the roots of Polyalthia laui. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. All compounds were evaluated for their cytotoxic activities and antibacterial activities.

BACKGROUND Fecal calprotectin (FC) levels have been extensively reported to correlate with clinical and endoscopic activities in Crohn's disease (CD); however, the utility of FC levels in the postoperative setting remains to be determined. Using meta-analysis, we aimed to evaluate the utility of FC as a noninvasive marker of recurrence in patients with CD who had undergone previous surgical resection. METHODS An electronic search using keywords related to CD and FC was performed in multiple electronic resources from 1966 to March 2014. The extracted data were pooled using a hierarchical summary receiver operating curve model. RESULTS Ten articles met the inclusion criteria, and methodological quality was determined in detail for each study. The 10 studies presented FC levels in 613 postoperative CD patients. The pooled sensitivity and specificity values for assessing suspected endoscopic recurrence were 0.82 (95% confidence interval (CI), 0.73-0.89, 8 studies, n = 391) and 0.61 (95% CI, 0.51-0.71), respectively. The overall positive and negative likelihood ratios were 2.11 (95% CI, 1.68-2.66) and 0.29 (95% CI, 0.197-0.44), respectively. The pooled sensitivity and specificity values for evaluating clinical relapse were 0.59 (95% CI, 0.47-0.71; 3 studies, n = 183) and 0.88 (95% CI, 0.80-0.93), respectively. The overall positive and negative likelihood ratios were 5.10 and 0.47, respectively. CONCLUSIONS As a simple and noninvasive marker, FC is useful in evaluating recurrence of postoperative patients with CD.

Thiopurines (TPs) are effective in reducing clinical and endoscopic recurrence in postoperative patients with Crohn's disease (CD). However, whether TPs could prevent surgical recurrence (SR) remains unknown. We aimed to explore whether TPs could prevent SR and identify risk factors associated with SR.This was a retrospective cohort study of 246 postoperative patients with CD. Cox proportional hazard model was used to identify risk factors for SR. Patients were stratified according to the presence of risk factors.A total of 50 (20.3%) patients suffered SR after a mean follow up of 54.3±46.4 months. Multivariable analysis showed independent risk factors for SR were penetrating disease behavior (HR 8.628; 95% CI 1.573-47.341; P = 0.01), ileocolonic disease location (HR 2.597; 95% CI 1.047-6.445; P = 0.04) and isolated upper gastrointestinal disease (UGID) location (HR 5.082; 95% CI 1.496-17.267; P = 0.009). However, use of TPs after surgery significantly reduced the risk of SR (HR 0.120; 95% CI 0.063-0.231; P 0.001). When stratifying patients according to risk factors, there was no statistical difference of SR between patients treated or not by TPs (P = 0.08) in low-risk group (n = 46). However, in high risk group (n = 200), patients with TPs use had a lower risk of SR than those without TPs (HR 0.093; 95% CI 0.048-0.178; P 0.001).Penetrating disease behavior and ileocolonic/isolated (UGID) location were associated with SR in CD patients. TPs use was beneficial in decreasing risk for SR in CD patients at high risk.

In an effort to identify novel, small molecules which can affect the proliferation of lung cancer cells, F-01A, a polyether antibiotic isolated from the fermentation broth of Streptomyces was tested.F-01A was tested for its antitumor properties on the lung cancer cell line SPC-A-1, at six doses (0.1, 0.5, 1, 2.5, and 5 μmol·L(-1)), using various cellular assays. Cell viability was measured by the MTT assay, Hochest 33258 was used to study nuclear morphology; DNA ladder and the loss of mitochondrial membrane potential were also evaluated.F-01A induces apoptosis against SPC-A-1 cells in a dose-dependent manner. The IC50 is 0.65 μmol·L(-1), and the inhibition at 5 μmol·L(-1) is 87.89%. Further, JC-1 staining indicates F-01A could induce the loss of mitochondrial membrane potential, and the DNA fragment is evident.Mechanistic analysis showed that F-01A induced apoptosis of cancer cells probably in the mitochondrial pathway. The antitumor actions of F-01A involve activation of the apoptotic pathway against SPC-A-1 cells, and it may be valuable for further drug development.

Five new clerodane diterpenoids, polylauiester A (1), (4→2)-abeo-2,13-diformyl-cleroda-2,12E-dien-14-oic acid (2) and polylauiamides B-D (3-5), together with 11 known clerodane diterpenoids (6-16), were isolated from the roots of Polyalthia laui. Among them, polylauiester A (1) represents the first example of a novel norclerodane diterpenoid only containing 17 carbon atoms on the carbon skeleton, and polylauiamide B (3) is an unusual diterpenoid with a p-substituted benzene ring as a substituent. Their structures were elucidated by extensive spectroscopic methods, and the relative configuration of polylauiamide B (3) was further confirmed by the single crystal X-ray diffraction method. Biological evaluation of new compounds against human Hela, MCF-7 and A549 human cancer cell lines showed that all compounds displayed weak cytotoxicities against various human cancer cell lines in the range of IC50 at 25.01-39.31μM.

Duchenne muscular dystrophy is the most prevalent inheritable muscle disease. Transplantation of autologous stem cells with gene direction is an ideal therapeutic approach for the disease. The current study aimed to investigate the restoration of myofibers in mdx mice after mdx bone marrow-derived mesenchymal stem cell (mMSC) transplantation with human microdystrophin delivery. Possible mechanisms of action were also studied. In our research, mMSCs were successfully transduced by retrovirus carrying a functional human microdystrophin gene. Transplantation of transduced mMSCs enabled persistent dystrophin restoration in the skeletal muscle of mdx mice up to the 12th week after transplantation. Simultaneous coexpression of human microdystrophin and desmin showed that implanted mMSCs are capable of long-term survival as muscle satellite cells.

Two new succinimide-containing derivatives, cladosporitins A (1) and B (2), were isolated from the fermentation cultures of the mangrove-derived fungus Cladosporium sp. HNWSW-1, along with a new pyrone, clapone (3), as well as the previously reported talaroconvolutin A (4) and anthraquinone (5). The structures of the isolated compounds were elucidated by 1D, 2D NMR, and HRMS spectral analysis. Compound 2 showed cytotoxicity against BEL-7042, K562 and SGC-7901 cell lines with IC50 values of 29.4 &plusmn, 0.35 &mu, M, 25.6 &plusmn, 0.47 &mu, M, and 41.7 &plusmn, 0.71 &mu, M, respectively, whereas compound 4 exhibited cytotoxicity against Hela and BEL-7042 cell lines with IC50 values of 14.9 &plusmn, 0.21 &mu, M and 26.7 &plusmn, 1.1 &mu, M, respectively. In addition, compounds 4 and 5 displayed inhibitory activity against &alpha, glycosidase, with IC50 values of 78.2 &plusmn, 2.1 &mu, M and 49.3 &plusmn, 10.6 &mu, M, respectively.

Pathogen–host interaction plays an essential role in pathogenicity. In this study, we investigated transcriptomes of one Streptococcus pneumoniae TIGR4-derived unencapsulated strain upon exposure to THP-1 human macrophage-like cells for 0.5 h, 1 h and 3 h, respectively. Expression of most genes was up-regulated and the changes of selected genes were validated by qRT-PCR. To characterize the functions of the identified genes, one locus of genes (SP1057–SP1063) was deleted in TIGR4 by insertion replacement mutagenesis. Compared to the wild-type strain, the constructed mutant exhibited lower binding and internalization activities to the THP-1 macrophages at early incubation time periods (0.5 h and/or 1 h) but not at 3 h. However, no change was observed in the intracellular survival assays. These data indicate that the SP1057–SP1063 locus is involved in the early stage of interaction with host macrophages. Further sequence and PCR analyses suggest that the SP1057–SP1063 locus was acquired by lateral transfer.

To identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X).Based on clinical symptoms and inheritance pattern, linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently, sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR). Potential mutations were detected by direct DNA sequencing. All patients were also analyzed for the trait of thalassemia.Linkage analysis indicated the candidate gene to be ATRX. Subsequently, a homozygous missense mutation c.736CT (p.R246C) was found in exon 9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736CT (p.R246C) was also identified in the patient's mother and grandmother. Similar mutations were not detected in other members of the family. Alpha thalassemia was detected in the proband and another patient, whose genotypes were determined as -α(3.7)/αα and --(sea)/αα, respectively.Missense mutation of c.736CT in ATRX gene is a mutation hotspot, and p.R246C may disturb the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the disease in this family.

To explore the characteristics of DNA mutations underlying Duchenne muscular dystrophy and provide prenatal diagnosis.Multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) were applied for analyzing DMD gene mutations in 388 unrelated Chinese patients and 53 fetuses.Respectively, 230 and 43 subjects were found to harbor a deletion (59.28%) or duplication (11.08%). Two deletion hotspots were identified, which have located at exons 45-54 and exons 3-19. Duplications were mainly detected at exons 2-43. Point mutations were identified in 29.64% of patients. Fifty three fetuses were prenatal diagnosed, among which 18 were identified as patients.Frequencies of DMD gene deletions and duplications in China are similar to global data. Prenatal diagnosis can help to reduce births of DMD patients.

The present study aims to investigate health-related quality of life (HRQOL) in disease-free survivors after radical surgery for mid-low rectal cancer.A retrospective cross-sectional study was performed in patients with rectal cancer who underwent primary surgery between August 2002 and February 2011 by use of the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires (n = 330). The impact of clinical characteristics on HRQoL were assessed and compared by univariate and multivariate regression analyses.Two hundred and four effective responses were received. Patients with stoma were more impaired in HRQoL than those without stoma, especially in the field of social psychology, such as emotional function (M(50) = 91.67, U = 2668.5, P = 0.026), social function (M(50) = 83.33, U = 2095.5, P0.001), financial difficulties (M(50) = 0, U = 2240.5, P0.001) and body image (M(50) = 88.89, U = 2507.0, P = 0.013). Only in the constipation scale (M(50) = 14.29, U = 2376.0, P = 0.001), nonstoma patients had a better score. The analysis in different types of surgical procedure paralleled those of stoma. Patients with complication had a poorer function in some symptom scales such as dyspnoea (M(50) = 0, U = 1505.0, P0.001), gastro-intestinal symptom (M(50) = 6.67, U = 1766.0, P = 0.034) and financial difficulties (M(50) = 33.33, U = 1795.5, P = 0.044), and in some functioning scales such as emotional function (M(50) = 83.33, U = 1608.5, P = 0.009), cognitive function (M(50) = 66.67, U = 1612.5, P = 0.010) and body image (M(50) = 66.67, U = 1617.0, P = 0.012). In our study, HRQoL after rectal cancer surgery improved with time. Our multivariate analysis displayed that stoma and postoperative time were the most significant characteristics. Variables associated with worse financial status were less postoperative months, occurrence of complications and presence of stoma.Different scales of HRQoL in patients of China after curative surgery for mid-low rectal cancer are significantly influenced by different clinical characteristics.

To study the chemical constituents, antimicrobial activity and antitumor activity of the essential oil from Zanthoxylum avicennae.The essential oil from the leaves of Zanthoxylum avicennae was extracted by steam distillation. The components of the essential oil were separated and identified by GC-MS.72 components were identified and accounted for 98.15% of the all peak area. The essential oil exhibited strong antitumor activity against K-562 human tumor cell lines with IC50 of 1.76 microg/mL. It also exhibited moderate antimicrobial activity against three bacteria.The essential oil of Zanthoxylum avicennae contains various active constituents. This result provides scientific reference for the pharmacological further research of Zanthoxylum avicennae.

To explore the correlation between genotypes and phenotypes in Chinese patients with pseudohypertrophic muscular dystrophy.Patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) were diagnosed clinically. Multiplex ligation-dependent probe amplification (MLPA) were performed to detect potential DMD gene mutations. The results were analyzed statistically.Among 280 patients, 238(85.0%) were diagnosed with DMD, 35(12.50%) were diagnosed with BMD and 7(2.5%) were diagnosed with intermediate muscular dystrophin (IMD). Among these, 252(92.31%) were in-frame mutations, and 21(7.69%) were out-of-frame mutations. Twelve patients with DMD have carried in-frame mutations, 9 with BMD have carried frame-shift mutations, and 7 IMD patients have carried frame-shift mutation.Most of the genotypes and phenotypes of DMD have complied with the reading-frame hypothesis. Patients with BMD with frame-shift mutations may facilitate understanding of the pathogenesis of DMD, and provide a theoretical basis for clinical therapy.

Few clinical studies or randomized clinical trial results have reported the impact of fast track surgery on postoperative insulin sensitivity. This study aimed to investigate the effects of fast track surgery on postoperative insulin sensitivity in patients undergoing elective open colorectal resection.Controlled, randomized clinical trial was conducted from November 2008 to January 2009 with one-month post-discharge follow-up. Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups: a fast track group (35 cases) and a conventional care group (35 cases). All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters (complication rates, return of gastrointestinal function and postoperative length of stay), stress index and insulin sensitivity were evaluated in both groups perioperatively.Sixty-two patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. Our findings revealed a significantly faster recovery of postoperative insulin sensitivity on postoperative day 7 in the fast-track group than that in the conventional care group. We also found a significantly shorter length of postoperative stay and a significantly faster return of gastrointestinal function in patients undergoing fast-track rehabilitation.Fast track surgery accelerates the recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.

To explore the effects of fast-track surgery on postoperative humoral immune function in patients undergoing elective colorectal resection.Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into fast-track group (n = 35) and conventional care group (n = 35). The clinical parameters and markers of humeral immune function were evaluated in both groups postoperatively.Sixty-two patients finally completed the study, including 32 in the fast-track group and 30 in the conventional care group. There was a significantly faster recovery of postoperative humoral immunity: blood levels of globulin (24.1 ± 2.4 vs 22.1 ± 3.3 g/L, P = 0.025), immunoglobulin G (10.79 ± 2.39 vs 8.66 ± 2.09 g/L, P = 0.007) and complement 4 (0.24 ± 0.09 vs 0.17 ± 0.05 g/L, P = 0.035) at Day 3 postoperation were higher in the fast-track group than in the conventional care group. And there was also a significantly shorter length of postoperative stay (6.0 ± 1.0 vs 11.7 ± 3.8 d, P0.001) in patients undergoing fast-track rehabilitation.Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.

To examine the effect of periconceptional multi-micronutrient supplementation on gestation and birth outcomes.A population-based community intervention program was conducted in 18 counties in China. Participants were divided into an intervention group, who received multi-micronutrient supplementation from at least 3 months before pregnancy throughout the first trimester, and a control group. Pregnant women were followed up to record information about birth outcomes. Maternal socio-economic characteristics and main birth outcomes were evaluated. Gestational age was further analyzed using survival analysis, to determine the time distribution of delivery.Periconceptional multi-micronutrient supplementation was associated with higher birth weight, birth length and occipitofrontal head circumference, and with lower incidence rates for stillbirth, low birth weight, and preterm birth. Moreover, periconceptional multi-micronutrient supplementation changed the time distribution of delivery, making the deliveries more clustered in the period between day 275 and day 295 of gestation.Our study shows that periconceptional multi-micronutrient supplementation is beneficial for fetal development and optimizes all measured aspects of health in neonates in socioeconomically disadvantaged areas in China. The change in time distribution of deliveries caused by multi-micronutrient supplementation needs further clarification.

To explore the prevalence rates of disabilities among the ethnic minority people in China.Utilizing stratified, multiphase, and cluster probability sampling design, 2 526 145 persons were investigated and screened by trained interviewers, including 297 761 persons with ethnic minority backgrounds. Respondents scoring positive for potential problems were referred to physician for further diagnosis on disability and on scale measurement.The overall prevalence rate of disability for both ethnic minority and Han population were 6.24% (95%CI: 6.16% - 6.51%) and 6.41% (95%CI: 6.38% - 6.51%) respectively. The total aggregate age-adjusted prevalence rate of disability was 7.31% for persons with ethnic minority. The prevalence rate of disabilities in male was significantly higher than that in females (7.31% vs. 6.75%). The ranking of prevalence rates on different type of disabilities were: physical disability 1.90% (95%CI: 1.89% - 1.91%), hearing disability 1.34% (95%CI: 1.33% - 1.35%), multiple disability 1.14% (95%CI: 1.13% - 1.15%), vision disability 0.99% (95%CI: 0.97% - 1.01%), psychiatric disability 0.38% (95%CI: 0.37% - 0.40%), intellectual disability 0.38% (0.37% - 0.39%) and speech disability 0.12% (0.11% - 0.13%). Cerebral Palsy, genetic diseases, tympanitis, cerebral disease and mental retardation (not including unknown items) were the major causes for disabled children with ethnicity background. Degenerated diseases, including osteoarthropathy, cerebrovascular disease, elderly-related deafness or cataract were most important causes for ethnic minority persons aged 60 or over. Injury, including traffic accident was important disabled-related factor for persons with minority ethnicity aged 15 - 59. The main causes and ranking of causes for ethnical minority were similar with that for Han population.The prevalence rate of disability for ethnic minority persons was significantly higher than that for Han population in China. Prevention for different types of disability should be provided accordingly to persons with ethnic minority, in different age groups.

To investigate clinicopathological characteristics and the pattern of lymph node metastasis of patients with gastric remnant cancer.The data of the clinicopathological characteristics and the pattern of lymph node metastasis in 56 patients with gastric remnant cancer treated from March 1994 to December 2008 was investigated and compared with those in 1171 patients with primary gastric cancer treated over the same period.Fifty-six patients (4.6%) with gastric remnant cancer were enrolled in this study during the period. Compared with patients with primary gastric cancer, the age of cancer onset was older [(64.3+/-9.0) vs. (58.3+/-12.6) yrs], lymph node metastasis rate was higher (31.8% vs. 25.5%), Borrmann's classification was later and neighbor organ resection rate was higher (57.1% vs. 26.4%) in patients with gastric remnant cancer; the differences were all significant (chi2=18.800, 11.679, 9.177, 25.190; P0.05). Patients with gastric remnant cancer who underwent lymph node dissection tended to have a higher incidence of No.10 (splenic hilar lymph node) and No.11 (splenic artery lymph node) group lymph node metastasis than those in primary gastric cancer (chi2=5.558, 6.099; P0.05). In contrast, patients with primary gastric cancer had a higher incidence of No. 2 (left cardiac lymph node), No.3 (lesser curvature lymph node) and No.8 (common hepatic artery lymph node) group lymph node metastasis than those in gastric remnant cancer (chi2=15.508, 6.003, 4.084; P0.05). The jejunal mesentery lymph node metastasis was 24.0% (6/25) in patients with gastric remnant cancer and the peripheral connective tissue infiltration rate was 14.3% (8/56).It suggested that patients with gastric remnant cancer has different clinicopathologic characteristics and the pattern of lymph node metastasis from those with primary gastric cancer. D2 lymph node dissection of proximate gastric cancer and jejunal mesentery lymph node dissection should be the standard operation for these patients; but combined neighboring organ resection should be taken into consideration.

Background Highly active anti-retroviral therapy (HAART) is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication. Methods Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc) was used to identify potential anti-HIV mechanisms of these extracts. Results Two extracts, one from Euphorbiaceae, Trigonostema xyphophylloides (TXE) and one from Dipterocarpaceae, Vatica astrotricha (VAD) inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus. Conclusion These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking HIV-1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV-1 entry inhibitors.

The occurrence of generic Escherichia coli, E. coli O157, Salmonella, and Campylobacter in cattle manure, beef carcasses, catch basin water, and soils receiving manure application was determined in 21 Alberta feedlots. In cattle manure, generic E. coli (98%, 2069/2100) and Campylobacter (76%, 1590/2100) were frequently detected; E. coli O157 (7%, 143/2100) and Salmonella (1%, 20/2100) were less frequently detected. Samples from beef carcasses in the cooler following Hazard Analysis Critical Control Point interventions yielded only 1 isolate each of generic E. coli and Campylobacter (1/1653) and no Salmonella (0/1653). Catch basin water specimens were positive for generic E. coli in both the spring (62%, 13/21) and the fall (52%, 11/21). Other bacteria were detected only in the spring water specimens, including E. coli O157 (29%, 6/21), Salmonella (5%, 1/21), and Campylobacter (52%, 11/21). Generic E. coli was frequently isolated from soil specimens (30%, 27/88), but E. coli O157 was not found in soil samples obtained in the spring and was only occasionally detected in the fall samples (9%, 3/32). Salmonella were occasionally found in the soil specimens collected in the spring (3%, 2/56), but not in the fall season (0/32). Campylobacter jejuni was frequent in cattle manure (66%, 1070/1623), but rare in carcass and environmental samples. E. coli O157 and Salmonella were rarely detected in cattle or the environment. Generic E. coli and Salmonella were rarely detected on carcasses.

To introduce the application of Family-Based Association Test (FBAT) in detecting the association or linkage between marker alleles and phenotype or traits in genetic epidemiology. A brief overview on basic steps involved in design, implementation, principles of application, available software as well as the use and feature of FBAT method, were explained based on data from nuclear family. Advantages of FBAT were compared to conventional genetic statistics approaches. Data showed that this approach might make the most use of parental genotype, genotype of affected offspring and their phenotype to test the association between biallelic or multi-allelic markers, phenotype or traits to their conditional distributions given the minimal sufficient statistics under the null hypothesis for the genetic model. Covariates, such as traits or environmental exposures, might be included into this procedure so as to effectively control the bias of population admixture through adjustment of variables. FBAT could be used for genetic analysis with data from nuclear family since it is more advantageous than the conventional statistical methods.

To explore the prevalence of visual, hearing, speech, physical, intellectual and mental disabilities in China, 2006.The reference time of the Second National Sample Survey on Disability was zero hour, April 1, 2006, and 2,526,145 individuals were investigated from 31 provinces autonomous regions or municipalities under the "Disability Classification and Standards for the Second National Sampling Survey on Disability". The classified prevalence rates of 6 types of disability was analyzed.(1)The overall prevalence of disabilities was 6.39%, which was 1.49 percent higher than the prevalence rate in 1987. The prevalence of physical disability was the highest (2.34%), while the speech disability was the lowest (0.53%). (2)29.49% of all the disabled persons were classified as severe who suffered grade-1 and grade-2 while 70.51% of them were moderately and mildly disabled suffering from grade-3 and grade-4. Over 65% of the speech disability and over 45% of the mental disability were identified, which were much higher than the other 4 types of disability. (3) The correlation between age, gender, residential place and each of 6 types of disability were statistically significant (P0.001). (4) Among all the disabling factors of speech disability and mental retardation disability, congenital factors made great contribution (22.67% and 22.41% respectively).According to the analysis results,the characteristics of disabled persons in China were as follows: ageing population had high prevalence rate of disability; all the population mainly suffered moderate and mild disability, but the proportion of severe disability was not low; the prevalence rate was higher and the main reasons caused disability were diversification in rural area.

This research was to compare the occurrence levels of birth defect, to describe the distribution of primary birth defects in different range of monitored ages and to provide data to China birth-defect monitoring system.A retrospective study on birth defect was conducted in two counties, Shanxi province, China, which covered birth defects among fetuses after 20 weeks' gestational age from 2002 through 2004. Data collected on birth defect cases mainly included extrinsic and visceral anomaly.The occurrence rates of the monitored structural birth defects significantly increased with the increase of age. The occurrence rates were 17.6, 34.0, 43.6, and 53.7 per 1000 births, for different statistical range, from 20-week to 27-week gestational age, 7 days, 1 year and 3 years after birth, respectively. The range from 28-week gestational age to 7 days after birth was usually regarded as the routinely monitored range. If the occurrence rate was calculated from the 20-week gestational age, it appeared a 2.1-time increase. However, if the range was changed to 1 or 3 years after birth, the occurrence rate increased to 2.7 or 3.3 times high, respectively. The distribution of time when birth-defect was identified was significantly different by categories with majority of neural tube defect cases diagnosed at antepartum or 7 days after birth. Visceral defects were mainly found at 7 days after birth but increased with age, even some were diagnosed at 1 year after birth.The routine Chinese monitoring program might detect approximately 1/3 of those structural birth defects with the base of current technique and monitoring range from 28-week gestational age to 7 days after birth. The result of our findings should be of help to other related studies.

This paper was to analyze the difference of exposure levels of the environmental risk factors on birth defects during peri-conceptional period between intended and unintended pregnancies, and to estimate the role of intended pregnancies in reducing exposure of environmental risk factors.Data used in this paper were from a retrospective survey of maternal women from 2002 through 2004 conducted in Wuxi city. The total number of women under study was 1628. Logistic regression model was employed to control women's childbearing age and education level for analysis of the role of intended pregnancies in reducing risk of unsafe use of medicine during pregnancy, exposure to toxic substance in working or living environments and unhealthy lifestyles.The proportion of intended pregnancies was 73.2%. The proportion of intended pregnancies in urban women was slightly lower than that in rural women,and the proportion of intended pregnant women whose childbearing age was over 30 years old,was significantly higher than that whose childbearing age was under 30 years old. There were significant differences in exposure risks of unsafe use of medicine and some unhealthy lifestyles between the intended and the unintended. In the intended group, the proportions of taking the suspicious teratogenic drugs and staying up were 2.5% and 2.9% respectively, significantly lower than those in unintended group whose proportion were 6.0% and 5.5%. When compared with the unintended pregnant women, the exposure risk of taking the suspicious teratogenic drugs and staying up in intended pregnant women decreased by 60% and 50% respectively.Intended pregnancies could significantly reduce the risk of taking the suspicious teratogenic drugs and unhealthy lifestyles. Reducing the incidence of unwanted pregnancy and increasing the proportion of intended pregnancies were both cost-effective methods for preventing birth defects.

The two-component system TCS08 of Streptococcus pneumoniae contributes to the virulence in vivo and regulates phosphotransferase system (PTS) genes in an avirulent strain. However, its role in pathogenic strains and virulence mechanism are largely unknown. In this study, we constructed TCS08 knockout mutants in a serotype 4 encapsulated pathogenic strain TIGR4, and investigated target genes regulated by TCS08 through transcriptional profile analysis. Compared to TIGR4, expression of the rlrA islet genes (SP0461–SP0468) encoding pneumococcal pili was found to be up-regulated in the rr08 mutant (Δ rr08 ). Further quantitative real-time PCR (qRT-PCR) analysis revealed that such induction was more significant when the strains were grown to late-logarithmic phase. In phenotype analyses, disruption of both hk08 and rr08 genes (Δ TCS08 ) resulted in increased adherence to human lung epithelial cells (A549) at 3 h at late-logarithmic and stationary phases. However, the invasion level of Δ TCS08 was reduced at different growth phases. Similar phenotype changes, though less significant, were also observed when the assays were performed on human nasopharyngeal epithelial cells (Detroit 562). These data suggest that TCS08 is involved in adhesion and invasion of host epithelial cells, which is likely mediated via regulation of the pilus locus genes in a growth phase-dependent manner.

Full-length form of spleen tyrosine kinase [Syk(L)] is a tumor suppressor gene in breast cancer, which may translocate into cell nucleus and act as a transcriptional repressor. This study was to explore the mechanism of Syk(L) regulated gene transcription in breast cancer cells.Flag-tagged Syk(L) was transfected into human embryonic kidney (HEK) 293 cells, and the interaction of Syk(L) and histone deacetylases (HDACs) was detected by immunoprecipitation. The binding of endogenous HDAC1 and Syk(L) in breast cancer cell line MB468 was also detected by immunoprecipitation. Flag-tagged Syk(L) domains SH2, KD, and IDB(L) were transfected into HEK293 cells, respectively, and their interaction with HDAC1 was detected. The activity of HDACs in the immunoprecipited complexes of Syk(L) was tested by HDAC activity detecting system.Exogenous Syk(L) was bound with HDAC1, 3, 6, and 7 in HEK293 cells, and endogenous Syk(L) was bound with HDAC1 in MB468 cells. SH2 and KD, but not IDB(L), were coimmunoprecipitated with HDAC1. The activity of HDACs was detected in the immunoprecipited complexes of Syk(L).Syk(L) regulates gene transcription in breast cancer by binding with HDACs to form transcription repressive complexes.

To study the levels of prevalence and to describe the epidemiological features of birth defects in high-prevalence areas in China.A population-based retrospective study was conducted in two counties of Shanxi province that including birth defects among fetuses and live births born after 20 weeks' gestational age in the study areas from 2002 through 2004.During 2002 - 2004, the prevalence of birth defects was 844.2 per 10 000 births in study areas and the first five main birth defects were inguinal hernia (182.2 per 10,000 births), anencephaly (104.4 per 10 000 births), congenital mental retardation (79.4 per 10,000 births), congenital heart diseases (73.2 per 10,000 births) and spina bifida (63.9 per 10,000 births). These five main birth defects accounted for about 60% of total birth defect cases. Inguinal hernia, undescended testicle, congenital mental retardation were usually not included for statistical analysis on birth defect. Excluding these birth defects, the prevalence of birth defects in study areas was 537.2 per 10,000 births and the first five main birth defects were anencephaly, congenital heart diseases, spina bifida, hydrocephaly (40.5 per 10 000 births) and encephalocele (31.2 per 10 000 births). The male prevalence of birth defects was 966.2 per 10 000 births, which was significantly higher than prevalence in females. The prevalence rates of birth defects for maternal age groups under 20 years old and over 30 years old were remarkably higher than those for 20-24 year and 25-29 year old mothers. The teenage mothers were at higher risk of having a child with neural tube defects(NTDs) or congenital heart diseases. Prevalence rates under 20 year maternal age group were 408.8 and 188.7 per 10 000 births for NTDs and congenital heart diseases respectively, whereas corresponding rates were 204.8 and 91.0 per 10 000 births for groups over 30 years of age. The prevalence rates increased with increasing gravidity or parity.This study showed that the patterns of birth defects in study areas were very different from those of other areas, with an unusually high prevalence of NTDs. The study also suggested that both young and advanced mothers were at increased risk of having a child with a birth defect.

To screen the target genes regulated by the transcriptional repressor Syk (L) so as to explore the mechanism of Syk (L) in suppressing breast cancer.Adeno-X expression system from Clontech Company was used to construct the adenovirus-Syk. Syk negative breast cancer cells of the line MB231 were cultured and infected with adeno-Syk (L), adeno-Syk (S), and the control adeno-Lac Z respectively. cDNA microarray was used to screen the genes regulated by Syk (L) and Syk (S). Northern blotting was used to examine the cDNA microarray results.The transcriptional repressor Syk (L) was able to down-regulate the expression of the oncogenes ID1, cyclin D1, Fra1, and B-myb in the breast cancer cells. Northern blotting confirmed this regulation.Syk (L) suppresses the progression of breast cancer by down regulating the expression of the oncogenes ID1, cyclin D1, Fra1, and B-myb.

Prader-Willi Syndrome (PWS) is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13 region. Clinical symptoms are difficult to diagnose in infants and only become clearer at later ages as the patients develop hyperphagia and morbid obesity. Molecular genetic tests are able to definitively diagnose PWS and allow early diagnosis of the syndrome. High resolution cytogenetic testing, methylation-specific PCR (MS-PCR), and linkage analysis are routinely used to diagnose PWS. To establish a linkage analysis method for Chinese patients, this study identified a useful set of STR markers in the typical PWS deletion and adjacent area, for linkage analysis in two Chinese families with PWS offspring. Using this method, the authors confirmed that one patient had a paternal deletion in chromosome 15q11-q13 and the other patient had maternal uniparental heterodisomy of chromosome 15. MS-PCR and high resolution chromosome G-banding also confirmed this diagnosis. This linkage analysis method can detect both deletion and uniparental disomy, thus providing valuable information for genetic counseling and the opportunity to analyze the relationship between the genotype and phenotype of PWS.

To investigate the clinicopathological characteristics and prognosis of patients with recurrent colorectal cancer.Clinicopathological characteristics and postoperative survival of 235 patients with recurrent colorectal cancer after radical resection were retrospectively analyzed, and was compared with that of 993 patients with radical resection.The overall 5- and 10-year survival rates after radical resection were 67.7% and 55.8%, respectively. The 5- and 10-year survival rates in patients with recurrent colorectal cancer was 43.9% and 28.1% (P=0.000), respectively. Among patients with recurrent colorectal cancer, the 5- and 10-year survival rates of the patients underwent second radical resection were 50.2% and 32.7%, while the 5- and 10-year survival rates of the patients without second surgery were 25.8% and 0, respectively (P=0.000). On univariate analysis, postoperative recurrence was associated with age at diagnosis, cancerous ileus, ascites, lymphs nodes involvement, gross types, infiltration of tumor and Duke's stage. Multivariate analysis revealed that cancerous ileus, ascites, gross types and Duke's stage were independent predictive factors for postoperative recurrence.Cancerous ileus, ascites, gross types and Duke's stage were independent predictive factors for recurrence and metastasis of colorectal cancer after radical resection. The 5- and 10-year survival rates and quality of life could be improved by second radical resection.

To understand the status and capacity of monitoring system on birth defects in China.Data regarding 27 groups of birth defects from 57 monitoring programs in World Atlas of Birth Defects (2nd Edition) published by WHO/ICBDMS/EUROCAT/HGP and descriptive analysis by their ranking and contribution were carried out.Both hospital-based (Chinese Birth Defects Monitoring Network, CBDMN) and population-based (Birth Defect Surveillance System in Thirty Counties of Four Provinces, Beijing) monitoring systems showed the same characteristics as below: (1) Not enough groups were monitored, with trisomy 13/18 and congenital heart disease not reported. (2) Prevalence on those 'easily observed' group was high and cleft lip with or without cleft palate in CBDMN ranked 5 among 57 programs, with similar situation in polydactyly. (3) While prevalence rates of internal system and choromosal anomaly were low, CBDMN ranked 56 with Beijing the only non-reported city among all the 57 programs. (4) Unreasonable relationship was seen with prevalence of cleft lip was 5.76,4.02 times higher than that of cleft palate in CBDMN and in Beijing program. Which was 1.58 times of the world's means. Prevalence rates of anencephaly and total anotia/microtia rose 10.39% while spina bifida, hydrocephaly, and gastroschisis had a 4%-5% increase. The prevalence of hypospadias decreased by 4.13% and Down syndrome by 3.02%.The capacity of birth defects monitoring, both hospital-based and population-based, was poor in the 1990s, in China.

To investigate the surgical treatment of Crohn disease(CD) complicated with perforation or fistula.The clinical data of 24 CD cases complicated with perforation or fistula treated in our department from Jan. 1980 to Apr. 2005 were analyzed retrospectively.There were 24 cases of CD complicated with perforation or fistula among 181 CD patients,and the incidence of perforation or fistula was 13.3%. Steroid treatment before perforation was given in 8 patients, while not in 9 patients and unclear in 7 patients. Eighteen patients had single perforation, 4 patients two free perforations and 2 patients more than three extra-abdominal fistula. Emergency operation was performed in 8 cases and selective operation in 16 cases. Five cases had postoperative complications including incision infection in 2, intra-abdominal abscess in 2 and stomal fistula in one case, and were all cured by surgical drainage and anti-infection treatment. The morbidity rate was 20.8%. The postoperative mortality rate was 12.5% (3/24). Eighteen patients were followed up from 6 months to 18 years, and the 5-year recurrent rate was 16.7%. The 10-year reoperation rate was 33.3%.Steroid use is not the main cause of perforation or fistula in CD. Perforation or fistula is the definite indication for surgical treatment.

To evaluate the impact on sexual function, local recurrence and survival after total mesorectal excision (TME) with autonomic nerve preservation (PANP) of rectal cancer.One hundred and five patients after TME with PANP were followed by means of questionnaire on postoperative genital function [TME + PANP(+) group], and the results of 110 patients after TME without PANP [TME + PANP(-) group] were compared with, also their local recurrence and 5-year survival were retrospectively analyzed.TME + PANP(+) group was compared to TME + PANP(-) group: the erection dysfunction, 33.3% vs 63.2%; the ejaculation dysfunction, 43.8% vs 70.0% (P0.01), there were significant differences between two groups, but no difference in local recurrent rate and 5-year survival rate (7.6% vs 5.5%; 63.4% vs 59.7%, P0.05).The TME with PANP of rectal surgery ensure the radical cure of rectal cancer, at the same time reasonably save the postoperative sexual function and obtain satisfactory postoperative survival.

To summarize the short-term outcomes of radical resection of gastric or colorectal carcinoma combined with liver transplantation for gastric or colorectal carcinoma with multiple hepatic metastases.Radical resection of gastric or colorectal carcinoma combined with liver transplantation were performed on one gastric carcinoma case and two rectal carcinoma cases with severe liver metastasis, and partial resection of left lung was performed in one of the two rectal cancer cases for pulmonary tuberculosis.There was no perioperative death. The gastric cancer patient died of recurrence 5 months after operation. The rectal cancer patient with pulmonary tuberculosis died of hepatic function failure 7 months after operation without recurrence. Another rectal cancer patient recovered well with normal liver functions, blood cells, without recurrence signs, and was back to work.Radical operation combined with liver transplantation may provide survival opportunity for some patients with gastric or colorectal carcinoma synchronous with severe liver metastasis, but the long-term outcome needs to be observed.

Lymphatic metastasis affects the prognosis of colorectal cancer patients. The binding of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3) promotes lymphangiogenesis and lymphatic metastasis. This study was to investigate the interrelation of VEGF-C, VEGFR-3 and lymphangial density (LAD), and to identify their correlations to clinicopathologic factors of colorectal cancer.The tissue microarrays containing 105 cases of colorectal cancer and 105 cases of normal colorectal tissue were produced separately. The expression of VEGF-C and VEGFR-3 was detected by immunohistochemistry; LAD was assessed through Podoplanin immunohistochemical staining.The positive rates of VEGF-C and VEGFR-3, and LAD were significantly higher in colorectal cancer than in normal colorectal tissue (61.0% vs. 22.8%, P0.01; 55.2% vs. 20.0%, P0.01; 8.91+/-3.75 vs. 6.68+/-1.38, P0.01). The expression of VEGF-C had no correlation to that of VEGFR-3. LAD was significantly higher in VEGF-C-positive colorectal cancer than in VEGF-C-negative colorectal cancer (10.89+/-3.36 vs. 5.83+/-1.67, P0.01). VEGF-C was up-regulated in colorectal cancer at Dukes'C stage, or with lymph node metastasis or distant metastasis; VEGFR-3 was up-regulated and LAD was higher in colorectal cancer at Dukes'C stage, or with lymph node metastasis.VEGF-C and VEGFR-3 are related with the lymphangiogenesis, lymphatic metastasis, and progression of colorectal cancer.

To analyse the multi-dimension nature of severe acute respiratory syndrome (SARS) transmission.Based on the data of SARS in 2003 and the geographic information system of Beijing, as well as under the broad range of the theorems and techniques of data-driven and model-driven knowledge mining, hierarchical techniques were used to test the hot spots. Wavelet technique was also used to decompose Moran's I frequency to survey the spatial clustering process of SARS. For factors analysis, BW test was used to distinguish factors which influencing SARS process. In temporal aspects, susceptive-infective-removal model (SIR) without Taylor expansion was solved by a genetic-simulated annealing algorithm, that directly provided a new approach to obtain epidemic parameters from the SIR model.Different order of spatial hot spots were noticed and the clustering were relevant with the means of transportation. Diffusion dynamics were changed along with the temporal process of SARS. Regarding factor analysis, geographic relationship, population density, the amount of doctors and hospitals appeared to be the key elements influencing the transmission of SARS. The predictable number of SARS cases evolving with time were also calculated.Cluster detection of close contacts of SARS infective in Beijing revealed the spatial characters of urban population flow and having important implications in the prevention and control of this communicable diseases. Some human and physical environment factors played statistical significant roles in different periods during SARS epidemics. An efficient algorithm was developed to solve SIR model directly, enabling the estimation of epidemic parameters from SIR and early forecast.

Intrauterine infection is an important cause of some birth defects worldwide. The most common pathogens include rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. General information about these pathogens in epidemiology, consequence of birth defects, and the possible mechanisms in the progress of birth defects, and the interventions to prevent or treat these pathogens' infections are described. The infections caused by rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they are proved to be fatal during the pregnant period, especially during the first trimester. These infections may cause sterility, abortion, stillbirth, low birth weight, and affect multiple organs that may induce loss of hearing and vision, even fetal deformity and the long-term effects. These pathogens' infections may influence the microenvironment of placenta, including levels of enzymes and cytokines, and affect chondriosome that may induce the progress of birth defect. Early diagnosis of infections during pregnancy should be strengthened. There are still many things to be settled, such as the molecular mechanisms of birth defects, the effective vaccines to certain pathogens. Birth defect researches in terms of etiology and the development of applicable and sensitive pathogen detection technology and methods are imperative.