RAG mutations cause a spectrum of severe immunodeficiencies ranging from classical severe combined immunodeficiency( SCID) and Omenn syndrome to an increasing number of peculiar phenotypes. Based on the distinct levels of RAG expression in various patients, their immunophenotypes, histopathological findings and clinical manifestations are diverse. The subtypes of RAG-defect diseases have been described as classical SCID,SCID with maternal T cells,classical Omenn syndrome,atypical Omenn syndrome,granuloma-tous inflammation,predominance/expansion of γδ-T cells and maternal T-cell engraftment. The complete failure or partial blockage of lymphocyte development and differentiation can cause repeated infections with autoimmune reactions frequently,and may be lethal. Thorough assessment and interpretation of various phenotypes will guide accurate diagnosis,definitive treatment and the mechanism research.

Objective To discuss the prevalence of non-EV71,non-CA16 virus strains of hand,foot and mouth disease(HFMD) in Guangdong province between 2008 and 2009,and analyze the genetic evolution of these non-EV71,non-CA16 virus strains.Methods Isolated viruses from stool samples collected from outpatient and in-patient cases of HFMD between 2008 and 2009 by human rhabdomyosarcoma(RD) cell and HEp-2 cell,cultures that exhibited a characteristic enterovirus cytopathic effect were evaluated by RT-PCR.Those strains which identified non-EV71,non-CA16 were analyzed by VP1 sequencing and then were identified by BLAST program.A phylogenetic tree was constructed using the Neighor-Joinning method in the MEGA 4.0 software.Results Twenty-two virus strains of non-EV71,non-CA16 were obtained,and nine of the twenty-two virus strains in 2008 were classified into CA2,CA4,and CB3 by BLAST; thirteen of the twenty-two virus strains in 2009 were classified into EV80,Echo13,Echo30,CBS,Echo24,CA10,CA6,and poliovirus 1 by BLAST.The honology of all strains was low,and all the strains belonged to CA,CB,Echoviruses,Enterovirus and poliovirus subgroup.Conclusion Except for EV71 and CA16 was a major causative agent in prevail of HFMD in Guangdong province between 2008 and 2009,there also existed other subgroup Enterovirus.The other twenty-two strains respectively belonged to CA,CB,Echoviruses,Enterovirus and poliovirus subgroup,and none of those strains was predominant.Muti-species Enterovirus occurred concomitantly.

Objective To investigate and evaluate the clinical effect of the application of medical adhesive in limited septoplasty by endoscope.Methods 57 patients were selected to undergo operation of limited septoplasty by endoscope.The patients were divided into packing group and bonding group.The packing group had 29 patients,whose nasal cavity was packed with vaseline gauze.While the bonding group had 28 patients,their nasal septum mucosa was adhesive fixed by medical adhesive,and the nasal cavity without packing.The indexes included the cardinal symptoms(nasal pain and headach,sleep status),signs (seepage amount of bleeding,mucosal edema),degree of discomfort in nasal cavity processing after operation(pain and bleeding) and length of stay were compared between the two groups.Results The above indexes in the bonding group were apparently lightened than the packing group and the length of stay was shortened.The differences were statistically significant (all P ＜ 0.05).Conclusion In operation of limited septoplasty by endoscope,the using of medical adhesive replacing nasalpacking could reduce the trauma on patients by operation and lighten the pain.The curative effect is satisfactory and it has excellent clinical application value.

Objective To expore the clinical therapeutic effect of allergic rhinitis using endoscopic more nasal structures orthopedic surgery combined with steroid nasal spray. Methods Sixty allergic rhinitis patients accompanied by deviation of nasal septum, middle turbinate lesions, or/and inferior turbinate lesions, were divided into two groups: observation group with 30 cases, applying endoscopic more nasal structures orthopedic surgery combined with steroid nasal spray (mometasone furoate nasal spray) during perioperative period; control group with 30 patients, only applying steroid nasal spray (mometasone furoate nasal spray). Long-term effect was compared between two groups. Results Sixty cases were followed up for 1 year. The total effective rate was 90.0%(27/30) in observation group,22 cases of significant effect, 36.7% (11/30) in control group,3 cases of significant effect. The total effective rate had significant difference between two groups (P＜0.01). Conclusion Using endoscopic more nasal structures orthopedic surgery combined with steroid nasal spray (mometasone furoate nasal spray) to treat allergic rhinitis has good long-term effect.

Objective To clone the human Islet neogenesis associated protein(rhINGAP)gene,express the gene extraeellulary in Pichia yeast for.further study on biological function and animal test on INGAP.Methods INGAP gene Was amplified with PCR and inserted into the recombinant plasmidα/pUC18.Then,the fusion gene of α and INGAP was digested and inserted into the expression plasmid pPIC9K.The positive recombinant plasmid which integrated INGAP Was confirmed by restriction enzyme digestion and sequencing,and it Was linearized with Sal Ⅰ digestion and transfered into the yeast host strain GS115 through electroporation.The yeast transformants that harbor the desired gene INGAP with high copy were selected by the auxotroph mediam G418,and verified by PCR.The condition of hake-flask culture was optimized,and the recombinant human INGAP Was induced expression with methanol as the only Carbone source.The antigen activity of the desired protein Was detected by Western blotting and ELISA method.Results Recombinant plasmid αINGAP/pPIC9K were successfully constructed and three positive Pichia yeast transformants were obtained.The expressed protein had satisfactory antigen activity,which Was confirmed by the Western blotting and ELISA method.Conclusions Pichia yeast expressing human Islet neogenesis associated protein (rhINGAP)gene was successfully constructed.

OBJECTIVETo study the effect of genistein (Gen) on MAPK signal pathway in the CIA rat fibroblast-like synoviocytes (FLS).

METHODSThe rat model of collagen-induced arthritis (CIA) was established. The cultured FLS of CIA rats were divided using randomized method. The effects of Gen (at the concentration of 50, 100, and 200 micromol/L, respectively) on the proliferation of FLS in CIA rats using methyl thiazolyl tetrazolium (MTT) assay. Effects of Gen (at the concentration of 50, 100, and 200 pmol/L, respectively) on the expressions of extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) in the FLS of CIA rats were detected.

RESULTSGen could inhibit the proliferation of FLS in CIA rats. The FLS proliferation in the high dose Gen group at 72 h was only 1.10+/-0.04, significantly lower than that in the model group (2.12+/-0.03, P<0.01). Besides, after Gen's action on FLS, the expression of p-ERK was down-regulated. It was only 0.34+/-0.02 in the high dose Gen group, significantly lower than that in the model group (2.68+/-0.14, P<0.01). There was no change in the expression of ERK (P>0.05).

CONCLUSIONSGen could inhibit the proliferation of FLS in CIA rats. Its mechanism of action was mainly correlated to down-regulating the tyrosine kinase of MAPK signal transduction pathway and inhibiting phosphorylation of ERK.

Animals ; Arthritis, Experimental ; metabolism ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Female ; Genistein ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; cytology ; drug effects ; metabolism

Objective To investigate the pharmacological effect and mechanism of mouse intermedin (IMD)for antagonizing cardiac hypertrophy by using isoproterenol (ISO)induced mouse cardiomegaly model.Methods The mouse cardiomegaly model was constructed by small dose of ISO subcutaneous injection.The mouse blood dynamic indexes and heart weight/body weight rati-o were investigated.Then the cardiomyocyte cross-sectional area,apoptosis and cardiac tissue fibrosis were evaluated by using the cardiac tissue section.ANP,BNP,mRNA expression levels of endogenous IMD and its receptors system in cardiac tissues were de-tected by using real time fluorescence PCR method.Results Compared with the ISO induced mouse cardomegaly model group,the intraperitoneal injection of IMD significantly decreased the heart weight/body weight ratio and cardiomyocyte cross-sectional area increased by ISO treatment,cardiomegaly marker ANP and BNP mRNA level,cardiomyocyte apoptosis and cardiomyocyte fibrosis, improved the cardiac function,left ventricular pressure,maximal and minimal rate of LV pressure increase and decrease during the isovolumetric contraction phase,stroke volume,cardiac output and ejection fraction,but significantly decreased the left ventricle end-diastolic pressure.In addition,the ISO treatment significantly induced the expressions of endogenous IMD and its receptors in heart tissues.Conclusion ISO induces the expressions of endogenous IMD and its receptors in cardiac tissues,and exogenous IMD sup-plementation therapy realizes the pharmacological protective effect for antagonizing cardiomegaly by ISO activated IMD receptor system.

[Objective]To study the dental status,the development of jaw and the size of sella turcica of children with ectoder-mal dysplasia(ED).[Methods]Panaramic radiography and lateral cephalograms of six ED individuals(age range of 6~7 years,five males and one female)were obtained. The dental status was record. 17 measurements about the jaws and the sella turcica were mea-sured and compare them to Chinese children without ED syndrome.[Results]The mean number of missing teeth was 22.3 in perma-nent dentition and 16.2 in primary dentition;The teeth that most likely to absent were permanent lateral incisor ,maxillary first premo-lar,maxillary primary lateral incisor and mandibular primary central incisor,and all remaining teeth are in conical shape. Lateral cephalometric measurements showed that all ED subjects had lower ANS-Ptm,which suggested a short maxilla. Low Co-Po,ANB, NA-PA,N-Me,N-ANS and ANS-Me values that were found in all subjects,as well as low SNA,Y-axis,MP-FH,S-Co,and high SNB,NP-FH,NP-FH that were noted in some subjects showed counterclockwise rotation and protrusion of mandible with short-er length in ED subjects. Some subjects had low ANS-Me/N-Me × 100%and high N-ANS/N-Me × 100%,representing a short facial height. Five cases represented lower length and diameter of sella turcica;two cases showed lower depth of sella turcica ,indicating the abnormal development of sella turcica.[Conclusion]The results of this study suggest that the dentition ,jaws and sella turcica in ED children differs when compared to individuals without this syndrome.

Abstract: Objective　To understand the density changes and seasonal fluctuation of larvae and adults of Aedes albopictus in Hainan Province from 2017 to 2021, and to provide a scientific basis for the prevention and control of dengue fever and other vector-borne diseases in Hainan Province. Methods　The Breteau index method was used to monitor the larvae of Aedes mosquitoes, and the breeding sites of all small indoor and outdoor water containers and their larvae was checked and recorded. The adult mosquitoes were monitored by double lamination and light trap. Results　A total of 1 962 adult female Aedes albopictus mosquitoes were captured in Hainan Province from 2017 to 2021, accounting for 2.17% of the total captured mosquitoes. There were significant differences in mosquito species composition in different habitats in different years (χ2=312.258, P<0.01). In 2017, the density of mosquitoes in livestock sheds was the highest (9.71 per lamp·night), but the composition ratio of Aedes albopictus was the lowest (1.29%). In 2020, the mosquito density in hospitals was the lowest (2.22 mosquitoes per lamp·night), and in 2019, the proportion of Aedes albopictus in residential areas and hospitals was the highest (3.27% on average).The mosquito density in different habitats was the lowest in 2020. The proportion of Aedes albopictus in residential areas and livestock sheds showed an increasing trend from 2017 to 2021, while the proportion of other habitats showed significant fluctuations. The proportion of Aedes albopictus in hospitals showed an obvious decreasing trend in 2020. From 2017 to 2021, the average mosquito density was 5.97, 4.26, 3.82, 3.39 and 3.68 mosquitoes per lamp·night, respectively, showing a decreasing trend year by year except 2021. Except for 2019, the lure index also showed a decreasing trend, with an average value of 1.5/(hour·net), showing a decreasing trend year by year. From 2017 to 2021, the annual average density of Aedes albopictus in Hainan Province was 0.09 mosquitoes per lamp·night, showing obvious seasonal fluctuation. The Breteau index showed a slow decline from 2017 to 2021, and its annual peak was between June and August, which was 1-2 months later than the peak of adult mosquito density. Conclusions　The population density of Aedes albopictus in Hainan shows obvious seasonal characteristics. Mosquito control activities should be carried out according to the seasonal characteristics of mosquitoes to reduce the risk of dengue fever and other infectious diseases.

The potential antiviral and anti-inflammatory mechanism of Anti-601 Mixture, a traditional Chinese medicine compound preparation, was studied by network pharmacology and molecular docking. The chemical constituents and targets of astragali radix, phellodendri chinensis cortex, rhei radix et rhizome, isatidis radix and lonicerae japonicae flos in Anti-601 Mixture were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the target were searched through the UniProt database, and the drug-compound-target (gene) network was constructed by Cytoscape 3.7.2. Then the functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted through Webgestalt to predict the mechanism. The network of drug-compound-target (gene) contained 5 drugs, 100 compounds and 207 targets. Functional enrichment analysis resulted in 717 GO items (P≤0.05), among which 240 were biological process (BP) items, 240 were cell composition (CC) items, and 237 were molecular function (MF) items. The 209 signaling pathways were obtained by enrichment screening of KEGG pathway (P≤0.05). Molecular docking showed that the active ingredients of Anti-601 Mixture, such as Stigmasterol, quercetin, luteolin, acacetin, β-sitosterol, kaempferol,had strong affinity with PTGS2 target. Active compounds in Anti-601 Mixture may regulate multiple signaling pathways including advanced glycation end products and its receptor (AGE-RAGE), IL-17, tumor necrosis factor (TNF) through target of prostaglandin-endoperoxidase synthase 2(PTGS2), thus playing an antiviral and anti-inflammatory role.