[Fortify clinical advantages and promote innovative development: comparison of the Chinese Colorectal Cancer Surgery Database with foreign databases].

With the continuous development of evidence-based medicine, increasing attention has been paid to the construction of a large medical database to ensure a source of high quality real-world data. The Chinese Medical Association Colorectal Surgery Group created the Chinese Colorectal Cancer Surgery Database (CCCD), whose objective is to promote the development of colorectal surgery and improve patient prognosis with evidence-based medicine theory. Compared to major databases around the world, CCCD contains more comprehensive information on colorectal cancer surgical cases, recording the main epidemiological characteristics and detailed surgical information, but perioperative treatment data still need to be strengthened. It is necessary to continuously expand the coverage, enrich perioperative data and strengthen data, quality control. In the future, CCCD is expected to play a role in promoting homogenization of medical services, promoting smooth and effective graded diagnosis and treatment, giving full role to the characteristics of each center to achieve integrated development, and connecting real-world data and artificial intelligence.

[Evidence-based surgical management for early colon cancer].

In recent years, the incidence of early colon cancer (ECC) in China showed a rising trend. Accurate definition of ECC is of great significance for disease assessment, treatment decision-making and prognosis judgment. Although endoscopic resection has become an option in the treatment of ECC, surgical intervention is still needed for tumor residue and high risk pT1 tumors in order to prevent recurrence and metastasis. There is no consensus on indication, timing, radical resection range and tumor location of ECC surgery. The innovation of laparoscopic surgical techniques strongly promoted the progress of ECC minimally invasive surgery. Postoperative follow-up should be systematic, standardized and individualized, based on the stratification of ECC recurrence risk factors.

[New research advances and clinical treatment of scar].

Scar formation is the abnormal healing process of skin after being damaged. The mechanism of scar formation is not clear, and many studies have shown that it is affected by many factors. Based on the over deposition of collagen in scars, many researchers have carried out studies on the mechanism, pathological manifestation, and treatment method of scars. In the treatment aspect of scar, the combination of traditional and new treatment methods has been well accepted and achieved good results. To understand the new advances of scar research and combine it with clinical treatment transformation could lead to the development of more effective prophylactic and therapeutic strategies for scar treatment in the future.

[Recombinant human tumor necrosis factor receptor type â ¡-IgG Fc fusion protein for treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene].

Objective: To investigate the efficacy and safety of the recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein (rhTNFR: Fc, etanercept) for the treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) . Methods: In September 2011 to February 2016, 12 patients with OMLDT were treated with etanercept 25 mg, subcutaneous injection, twice per week, doubling of first dose. The course of treatment was 6 weeks. The drug eruption area and severity index (DASI) score, the proportion of patients achieving a 50%, 75% and 90% reduction in DASI (DASI50, DASI75, DASI90) and the serum level of TNF-α were used to assess the efficacy at different times. Adverse reactions were also recorded and evaluated. The results were statistically analyzed by nonparametric Friedman test and repetitive measurement ANOVA using the software SPSS19.0. Results: After 4 weeks treatment, the DASI score decreased form 56.33±7.02 to 0.50±0.91 (P<0.01) . The DASI50, DASI75 and DASI90 were all increased to 12 (100%) . The serum level of TNF-α decreased form (43.74±41.62) pg/ml to (3.03±0.47) pg/ml (P<0.01) . Statistically significant difference was observed from the above indexes. There were no adverse reactions in clinical application. Conclusion: Recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein may be a safe and effective drug in the treatment of OMLDT.

Breastfeeding modifies the effects of environment tobacco smoke exposure on respiratory diseases and symptoms in Chinese children: the Seven Northeast Cities Study.

To evaluate the potential effect of interaction between breastfeeding and environmental tobacco smoke (ETS) exposure on respiratory health, we studied 31 049 children (aged 2-14 years) from 25 districts of seven cities in northeast China. Parents of the children completed standardized questionnaires that characterized the children's histories of respiratory symptoms and illness, feeding methods, ETS exposure, and other associated risk factors. Breastfeeding was defined as having been mainly breastfed for 3 months or more. The results showed that the association of ETS exposure with childhood respiratory conditions/diseases was modified by breastfeeding, and the association for nonbreastfed children was stronger than that for breastfed children. In particular, for nonbreastfed children, the odds ratios (ORs) for the effect of current ETS exposure asthma was 1.71 (95% CI: 1.43-2.05); however, the OR for breastfed children was 1.33 (95% CI: 1.20-1.48), indicating that the interactions between breastfeeding and current ETS exposure on asthma were statistically significant (P = 0.019). When stratified by school (kindergarten vs. elementary school), breastfeeding was more protective for asthma-related symptoms among children from kindergarten. In conclusion, this study shows that breastfeeding is associated with smaller associations between ETS exposure and respiratory conditions in children, suggesting that breastfeeding reduces susceptibility to the respiratory effects of ETS.

Epidemiology of elevated blood pressure and associated risk factors in Chinese children: the SNEC study.

Despite the association of childhood blood pressure (BP) with hypertension later in the life course, there remains dearth of information regarding the prevalence and emergence of hypertension in children, especially in China. To investigate the current status of BP, prevalence of elevated BP and related factors in Chinese children, a cross-sectional survey in a representative sample of 9354 Chinese children 5-17 years old was conducted in seven cities in Northeastern China during 2011 and 2012. BP measurements were taken by mercury sphygmomanometer. Elevated BP in children was defined as an average diastolic BP or systolic BP that is in the 95th percentile or higher for their gender, age and height. Overall, total prevalence of elevated BP was 13.8%, and no significant difference between males and females was identified. Multivariate analyses revealed that children having a higher area of residence had a lower of elevated BP. Increased odds for elevated BP were found for individuals who were lean (odds ratio (OR)=2.12; 95% confidence interval (CI): 1.67-2.69), overweight (OR=2.05; 95% CI: 1.74-2.42), obese (OR=3.15; 95% CI: 2.70-3.68), were born with low birth weight (OR=1.26; 95%CI: 1.01-1.63), premature birth (OR=1.46; 95%CI: 1.13-1.88), and were with home coal use (OR=1.24; 95%CI: 1.02-1.52). In conclusion, elevated BP was found to be prevalent in children in urban areas of Northeast China. These results underscore the importance of implementing a package of measures aimed at reducing malleable risk for this cardiovascular condition in school-aged children in Northeast China.

Isolation and characterization of two VpYABBY genes from wild Chinese Vitis pseudoreticulata.

The establishment of abaxial-adaxial polarity is an important feature of the development of lateral organs in plants. Members of the YABBY gene family may be specific to seed-plant-specific transcriptional regulators that play critical roles in promoting abaxial cell fate in the model eudicot, Arabidopsis thaliana. However, recent study has shown that the roles of YABBY genes are not conserved in the development of angiosperms. The establishment of abaxial-adaxial polarity has not been studied in perennial fruit crops. Grapes are an important fruit crop in many regions of the world. Investigating YABBY genes in grapevines should help us to discover more about the key genetic and molecular pathways in grapevine development. To understand the characterization of YABBY genes in grapevines, two YABBY genes, VpYABBY1 (GenBank accession No. KC139089) and VpYABBY2 (GenBank accession No. KC139090), were isolated from the wild Chinese species Vitis pseudoreticulata. Both of these encode YABBY proteins. Sequence characterization and phylogenetic analyses show that VpYABBY1 is group classified into the FIL subfamily while VpYABBY2 is a member of the YAB2 subfamily of Arabidopsis thaliana. Subcellular localization analysis indicates that VpYABBY1 and VpYABBY2 proteins are localized in the nucleus. Tissue specific expressional analysis reveals that VpYABBY1 is expressed strongly in young leaves of grape but only weakly in the mature leaves. Meanwhile, VpYABBY2 is expressed in grape stems, flowers, tendrils, and leaves. Transgenic Arabidopsis plants ectopically expressing VpYABBY1 caused the partial abaxialization of the adaxial epidermises of leaves, behaving similarly to those over-expressing FIL or YAB3 with abaxialized lateral organs. By contrast, ectopic expression of VpYABBY2 in Arabidopsis did not cause any alteration in the adaxial-abaxial polarity. Sequence characterization and phylogenetic analysis revealed that VpYABBY1 and VpYABBY2 are group-classified into two different subfamilies. They have diverged functionally in the control of lateral organ development. VpYABBY1 may have a function in leaf development, while VpYABBY2 may play a specific role in carpel development and grape berry morphogenesis. It is further possible that during the evolution of different species, YABBY family members have preserved different expression regulatory systems and functions.

Detecting anti-FcepsilonRI autoantibodies in patients with asthma by flow cytometry.

Autoimmune diseases have been implicated in the development of intrinsic asthma, however little data are available on the role of autoimmunity in the pathogenesis of asthma. The purpose of this study was to investigate circulating autoantibodies against the high-affinity receptor for immunoglobulin E, FcepsilonRI, in patients with asthma. Seventy-eight patients with asthma and 32 healthy control subjects were included. All individuals were tested using a triple-staining flow cytometry-based basophil activation test (BAT) for the potential presence of autoantibodies against FcepsilonRI. Of the 78 asthma patients, 29 (37.2%) had a positive BAT result, indicating that their serum was able to activate basophils, compared with only four (12.5%) of the control group, a statistically significant between-group difference. These data suggest that some asthma patients have aberrant anti-FcepsilonRI autoantibodies, which implies that autoimmunity may be one factor involved in the pathogenesis of intrinsic asthma.

Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors.

A pharmacophore model of the P1' site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1' group provided modest selectivity for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold was incorporated as a tyrosine mimic (P2') to conformationally constrain 2. Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase.

Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives at P1', a series of selective TNF-alpha converting enzyme inhibitors with potent cellular activity in the inhibition of TNF-alpha release.

SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrate for the first time that TACE has a larger S1' pocket in comparison to MMPs and that potent and selective TACE inhibitors can be achieved by incorporation of sterically bulky P1' residues.

Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha.

The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.

Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo.

To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the P1 and P2' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2' linkers. With an N-methylamide at P3', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3'-P4' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC(50) values of

Design, synthesis, and evaluation of a pyrrolinone-based matrix metalloprotease inhibitor.

[reaction: see text] A pyrrolinone-based hydroxamate matrix metalloprotease inhibitor, (-)-1, has been designed and synthesized. Enzymatic assay revealed that (-)-1 inhibited three of the ten matrix metalloprotease enzymes examined and as such represents a new, potentially important lead structure.

The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage.

Aggrecanase-1 (ADAMTS-4) is a member of the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) protein family that was recently identified. Aggrecanase-1 is one of two ADAMTS cartilage-degrading enzymes purified from interleukin-1-stimulated bovine nasal cartilage (Tortorella, M. D., Burn, T. C., Pratta, M. A. , Abbaszade, I., Hollis, J. M., Liu, R., Rosenfeld, S. A., Copeland, R. A., Decicco, C. P., Wynn, R., Rockwell, A., Yang, F., Duke, J. L., Solomon, K., George, H., Bruckner, R., Nagase, H., Itoh, Y., Ellis, D. M., Ross, H., Wiswall, B. H., Murphy, K., Hillman, M. C., Jr., Hollis, G. F., and Arner, E.C. (1999) Science 284, 1664-1666; 2 Abbaszade, I., Liu, R. Q., Yang, F., Rosenfeld, S. A., Ross, O. H., Link, J. R., Ellis, D. M., Tortorella, M. D., Pratta, M. A., Hollis, J. M., Wynn, R., Duke, J. L., George, H. J., Hillman, M. C., Jr., Murphy, K., Wiswall, B. H., Copeland, R. A., Decicco, C. P., Bruckner, R., Nagase, H., Itoh, Y., Newton, R. C., Magolda, R. L., Trzaskos, J. M., and Burn, T. C. (1999) J. Biol. Chem. 274, 23443-23450). The aggrecan products generated by this enzyme are found in cartilage cultures stimulated with cytokines and in synovial fluid from patients with arthritis, suggesting that aggrecanase-1 may be important in diseases involving cartilage destruction. Here we demonstrate that the thrombospondin type-1 (TSP-1) motif located within the C terminus of aggrecanase-1 binds to the glycosaminoglycans of aggrecan. Data from several studies indicate that this binding of aggrecanase-1 to aggrecan through the TSP-1 motif is necessary for enzymatic cleavage of aggrecan. 1) A truncated form of aggrecanase-1 lacking the TSP-1 motif was not effective in cleaving aggrecan. 2) Several peptides representing different regions of the TSP-1 motif effectively blocked aggrecanase-1 cleavage of aggrecan by preventing the enzyme from binding to the substrate. 3) Aggrecanase-1 was not effective in cleaving glycosaminoglycan-free aggrecan. Taken together, these data suggest that the TSP-1 motif of aggrecanase-1 is critical for substrate recognition and cleavage.

Sites of aggrecan cleavage by recombinant human aggrecanase-1 (ADAMTS-4).

Aggrecan, the major proteoglycan of cartilage that provides its mechanical properties of compressibility and elasticity, is one of the first matrix components to undergo measurable loss in arthritic diseases. Two major sites of proteolytic cleavage have been identified within the interglobular domain (IGD) of the aggrecan core protein, one between amino acids Asn(341)-Phe(342) which is cleaved by matrix metalloproteinases and the other between Glu(373)-Ala(374) that is attributed to aggrecanase. Although several potential aggrecanase-sensitive sites had been identified within the COOH terminus of aggrecan, demonstration that aggrecanase cleaved at these sites awaited isolation and purification of this protease. We have recently cloned human aggrecanase-1 (ADAMTS-4) (Tortorella, M. D., Burn, T. C., Pratta, M. A., Abbaszade, I., Hollis, J. M., Liu, R., Rosenfeld, S. A., Copeland, R. A., Decicco, C. P., Wynn, R., Rockwell, A., Yang, F., Duke, J. L., Solomon, K., George, H., Bruckner, R., Nagase, H., Itoh, Y., Ellis, D. M., Ross, H., Wiswall, B. H., Murphy, K., Hillman, M. C., Jr., Hollis, G. F., Newton, R. C., Magolda, R. L., Trzaskos, J. M., and Arner, E. C. (1999) Science 284, 1664-1666) and herein demonstrate that in addition to cleavage at the Glu(373)-Ala(374) bond, this protease cleaves at four sites within the chondroitin-sulfate rich region of the aggrecan core protein, between G2 and G3 globular domains. Importantly, we show that this cleavage occurs more efficiently than cleavage within the IGD at the Glu(373)-Ala(374) bond. Cleavage occurred preferentially at the KEEE(1667-1668)GLGS bond to produce both a 140-kDa COOH-terminal fragment and a 375-kDa fragment that retains an intact G1. Cleavage also occurred at the GELE(1480-1481)GRGT bond to produce a 55-kDa COOH-terminal fragment and a G1-containing fragment of 320 kDa. Cleavage of this 320-kDa fragment within the IGD at the Glu(373)-Ala(374) bond then occurred to release the 250-kDa BC-3-reactive fragment from the G1 domain. The 140-kDa GLGS-reactive fragment resulting from the preferential cleavage was further processed at two additional cleavage sites, at TAQE(1771)-(1772)AGEG and at VSQE(1871-1872)LGQR resulting in the formation of a 98-kDa fragment with an intact G3 domain and two small fragments of approximately 20 kDa. These data elucidate the sites and efficiency of cleavage during aggrecan degradation by aggrecanase and suggest potential tools for monitoring aggrecan cleavage in arthritis.

[Analysis on voice acoustic parameters and electroglottographic parameters in normal children of Han, Naxi, Bai nationality].

OBJECTIVE: To explore the normal vocal acoustic parameters and electroglottographic (EGG) parameters and their differences in normal children of the Han, the Naxi, the Bai nationality. METHOD: By using computer and Dr. speech software, We studied six parameters of voice acoustic and the E.G.G. in 951 children (Han 342, Naxi 224, Bai 385), aged 4-8 years old. We also examined 30 cases who suffered from vocal nodule and local proliferation. RESULT: The major parameters 1. Jitter, 2. Shimmer, 3. Mean F0, 4. SD F0, 5. NNE) of the voice acoustic and E.G.G. of the three nationality. CONCLUSION: 1. All parameters in Han nationality school-age children and preschool children were not different in years old. But Naxi and Bai nationality school-age children's Mean F0 and SD F0 were different from preschool children. The parameters(Mean F0, SD F0) of school-age children in Han, Naxi and Bai nationality were significant different. 2. The tested parameters were significant different between normal children of the Han nationality and the vocal nodule patients.

Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family.

Aggrecan is responsible for the mechanical properties of cartilage. One of the earliest changes observed in arthritis is the depletion of cartilage aggrecan due to increased proteolytic cleavage within the interglobular domain. Two major sites of cleavage have been identified in this region at Asn(341)-Phe(342) and Glu(373)-Ala(374). While several matrix metalloproteinases have been shown to cleave at Asn(341)-Phe(342), an as yet unidentified protein termed "aggrecanase" is responsible for cleavage at Glu(373)-Ala(374) and is hypothesized to play a pivotal role in cartilage damage. We have identified and cloned a novel disintegrin metalloproteinase with thrombospondin motifs that possesses aggrecanase activity, ADAMTS11 (aggrecanase-2), which has extensive homology to ADAMTS4 (aggrecanase-1) and the inflammation-associated gene ADAMTS1. ADAMTS11 possesses a number of conserved domains that have been shown to play a role in integrin binding, cell-cell interactions, and extracellular matrix binding. We have expressed recombinant human ADAMTS11 in insect cells and shown that it cleaves aggrecan at the Glu(373)-Ala(374) site, with the cleavage pattern and inhibitor profile being indistinguishable from that observed with native aggrecanase. A comparison of the structure and expression patterns of ADAMTS11, ADAMTS4, and ADAMTS1 is also described. Our findings will facilitate the study of the mechanisms of cartilage degradation and provide targets to search for effective inhibitors of cartilage depletion in arthritic disease.

[Chromosome homologies between human and Francois' monkey (Semnopithecus francoisi) established by chromosome painting].

Chromosomal homologies were established between human and Francois' monkey (Semnopithecus francoisi, 2n = 44) by chromosome painting with chromosome-specific DNA probes of all human chromosomes except the Y. Except for human chromosome 1, 2, 6, 16 and 19 probes which gave signals on two nonhomologous S. francoisi chromosomes respectively, all other probes each hybridized to a single chromosome. Only two S. francoisi chromosomes (No. 12 and No. 21) were each labelled by two separate probes (14 and 15, 21 and 22, respectively). In total, 23 human chromosome-specific probed detected 30 homologous chromosomes and chromosomal segments in the haploid S. francoisi genome. The results indicated a high degree of conservation of chromosomal synteny between human and this langur. Only some chromosomal rearrangements occurred in this langur. Comparison of the hybridization patterns of human painting probes on this langur with the data on other primates suggested that Asian langurs were karyotypically more closely related to each other than to African langurs.

[Genetic relationships of Nyctereutes procyonopides: as inferred from random amplified polymorphic DNA analysis].

Random amplified polymorphic DNAs (RAPDs) were used to investigate genetic relationships of eight raccoon dogs (Nyctereutes procyonopides). Using 28 arbitrary primers (10 bp), about 130 RAPD markers were observed in each individual. The average, maximum, and minimum genetic distance among 8 raccoon dogs are 11.20%, 14.93%, and 2.94% respectively. Our molecular phylogenetic trees constructed by UPGMA and NJ methods suggest that those 8 Chinese raccoon dogs may be divided into 4 clusters: (1) Guangxi raccoon dog, (2) Anhui raccoon dog, (3) Shaanxi raccoon dog, (4) Yunnan and Vietnam raccoon dog. Guangxi raccoon dog is more closely related to Anhui raccoon dog than to Yunnan-Vietnam raccoon dog. If the Yunnan-Vietnam cluster is a valid subspecies, it is reasonable to give the Guangxi, Anhui and Shaanxi clusters the same classification status as that of the Yunnan-Vietnam Cluster.