Objective:To explore the application value of silent MR angiography (MRA) in imaging of brain arteriovenous malformation (BAVM) in children.Methods:A total of 20 children with BAVM confirmed by digital subtraction angiography (DSA) were retrospectively collected. All children were imaged by silent MRA and time-of-flight MRA (TOF MRA) in the same examination. The image quality of feeding artery, nidus and drainage vein of BAVM was evaluated using the four-point method. Wilcoxon rank-sum test was utilized to compare the image quality scores between silent MRA and TOF MRA. Weighted Kappa statistics used to evaluate the inter-modality agreement of silent MRA and TOF MRA with DSA in displaying of angioarchitecture characteristics and determination of Spetzler-Martin grading.Results:Among the 20 BAVMs, significant differences in image quality scores of the nidus (2.75±0.55 versus 2.20±0.70) and drainage vein (2.60±0.68 versus 2.20±0.77) were observed between silent MRA and TOF MRA ( Z=-3.05, P=0.002; Z=-2.13, P=0.033, respectively). The agreement between silent MRA and DSA was excellent in nidus size grading, deep venous drainage, associated aneurysm and SM grading (Kappa 0.91, 1.00, 0.83 and 0.93, respectively); The agreement between TOF MRA and DSA was fair to moderate (Kappa 0.46, 0.59, 0.35 and 0.47, respectively). Conclusions:Silent MRA showes better image quality compared to TOF MRA and improves the evaluation of angioarchitecture characteristics and Spetzler-Martin grading of BAVMs in children.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective To investigate the effect of continuous renal replacement therapy ( CRRT) on the reg-ulation of Treg/Th17 in patients with severe sepsis,and related inflammatory factors IL-6,IL-17,IL-10,and TNF-α.Methods 60 patients with severe sepsis were randomly divided into two groups,30 cases in each group.The control group received conventional treatment,and the observation group was treated with CRRT on the basis of the control group.Flow cytometry was used to detect the levels of Tregs and Th17 cells,and IL-6,IL-10,IL-17 and TNF-αwere detected by ELISA method.At the same time,the APACHEII score,ICU length of hospital stay were observed and recorded.Results After treatment,APACHE Ⅱscore,ICU length of hospital of the observation group were lower than the control group,there were statistically significant differences(t=4.258,t=4.518,all P<0.05). The expression levels of Th17,Treg and Tregs/Th17 in the observation group were significantly lower than the control group,the differences were statistically significant (t=5.872,4.267,4.285,all P<0.05).The expression levels of IL-6,IL-17,TNF-αin the observation group decreased more significantly than the control group,the differences were statistically significant (t=5.829,5.257,5.983,all P<0.05).But the expression level of IL-10 in the two groups had no obvious change[(35.26 ±18.63) pg/mL vs (35.52 ±20.09) pg/mL,t=2.164,P>0.05].Conclusion CRRT can not only remove the inflammatory mediators of abnormal expression,improve the function of T cells,but also can maintain the balance between Th17 and Treg,improve the immune disorders,and improve the prognosis of sepsis.

Abstract] Objective To study the roles of IL-12 and IL-23 in the development of protective im-munity and pathological changes during chlamydial urogenital infection.Methods C57BL/6J wild type (wt) mice and mice deficient in IL-12p35 (IL-12p35 KO) or IL-12p40 (IL-12p40 KO)were inoculated in-travaginally with 1×104 IFU of live Chlamydia muridarum ( C.muridarum) organisms.Half mice of each group were reinfected on day 114 after primary infection.Vaginal swabs were taken every 3 or 4 days to mo-nitor live organism shedding.The mice were sacrificed after 114 or 143 days of primary infection and the va-ginal tract and kidney samples were collected for pathological analysis.The numbers of chlamydial inclusion bodies and bacteria in kidney homogenates were titrated after 100 days of primary infection.Results The infection time courses of mice deficient in either IL-12p35 or IL-12p40 were similar after primary infection, but were prolonged as compared with the wild type mice.All mice regardless of genotypes developed severe pathological damages in upper genital tracts with no significant difference among different groups.Almost all IL-12p40 KO mice and some IL-12p35 KO mice showed pathological changes in kidney samples.No obvious abnormality was observed in any of the kidneys from wild type mice.Neither the age-matched IL-12p35 KO nor IL-12p40 KO mice developed any gross pathological changes in kidney in the absence of chlamydial in-fection.C.muridarum inclusions were detected in kidney samples with gross pathological damages from IL-12p35 KO mice and IL-12p40 KO mice.No inclusions were ever detected in kidneys from the wild type mice.The numbers of chlamydial inclusions in the IL-12p40 KO mice were much higher than those of the IL-12p35 KO mice.Live bacteria were detected in mice deficient in either IL-12p35 or IL-12p40, but not in the wild type mice.No significant difference with the number of live bacteria was found between IL-12p35 KO mice and IL-12p40 KO mice.Conclusion IL-12 and IL-23 could inhibit the spread of C.muridarum in-fection from genital tract to kidney.The deficiency of IL-12 or IL-23 might relate to the renal lesions induced by Chlamydia infection.

BACKGROUNDLung cancers are classified as squamous cell carcinoma (SQ), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). SQ is the major subtype of lung cancer. Currently, there are no targeted therapies for SQ due to lack of understanding its driving oncogenes. In this study, we validated an SQ specific biomarker hsa-miR-205 in Chinese patients with lung cancer and screened its candidate target genes for further functional studies to enrich knowledge in SQ target therapies.

METHODSQuantitative reverse-transcription PCR (quantitative RT-PCR) was performed on 197 macro-dissected (cancerous cells >75%) surgical lung tissues (45 SQ, 44 AC, 54 SCLC and 54 adjacent normal tissues) to validate the expression profiles of miR-205. Furthermore, the targets of this microRNA were predicted through the gateway miRecords and mapped to lung cancer-associated pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Then quantitative RT-PCR was performed on an independent cohort of 44 snap-frozen surgical lung tissues to concurrently assess the expression profiles of miR-205 and its 52 putative targeted genes.

RESULTSMicroRNA-205 yielded high diagnostic accuracy in discriminating SQ from AC with an area under the curve (AUC) of 0.985, and discriminating SQ from SCLC with an AUC of 0.978 in formalin-fixed paraffin-embedded (FFPE) surgical lung tissues. Predicted targets of miR-205 were associated with 52 key members of lung cancer signaling pathways. Ten target genes (ACSL1, AXIN2, CACNA2D2, FOXO3, PPP1R3A, PRKAG3, RUNX1, SMAD4, STK3 and TBL1XR1) were significantly down-regulated in SQ and had a strong negative correlation with miR-205, while one target gene (CDH3) was up-regulated in SQ and exhibited a strong positive correlation with miR-205.

CONCLUSIONSWe confirmed the high diagnostic accuracy of miR-205 in discriminating SQ from AC and SCLC in Chinese patients. Moreover, we identified 11 significant target genes of miR-205 which could be used for further functional studies as the basis for the development of SQ targeted therapies.

Adenocarcinoma ; genetics ; Aged ; Carcinoma, Squamous Cell ; genetics ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; MicroRNAs ; genetics ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; genetics

Objective To investigate the immune injury in genital tract of BALB/c mice induced by plasmid protein pORF5 of Chlamydia trachomatis and its possible mechanism.Methods GST(glutathione-S-transferases)-pORF5 fusion protein was expressed and digested with PreScission Protease to obtain the target protein without GST tag.After further purification and endotoxin removal,pORF5 protein was injected into the posterior fornix of BALB/c mice on day 1,3 and 6,while the control groups were injected with PBS or GST protein respectively,and then all the mice were sacrificed on day 7 to evaluate genital tract gross pathology and histopathological characterization.The levels of TNF-α,IL-1β and IL-6 in serum,splenocytes culture supernatant and vaginal douche were detected by ELISA.Results Mice in pORF5 group developed different degrees of swelling in isthmic portion and ampulla of uterine tube,connective tissue adhesion and hydrosalpinx in the genital tract tissues,while the PBS group and the GST group did not show any obvious change.The inflammatory score showed that the genital tract pathology in pORF5 group was much more severe than PBS and GST control groups (P＜0.O1).The levels of TNF-α,IL-1β and IL-6 in vaginal douche and splenocytes culture supernatants in pORF5 group were obviously higher than those of PBS and GST groups (P＜0.05).The levels of TNF-α and IL-1β in serum were also higher than those of GST and PBS groups (P＜0.01).Conclusion pORF5 plasmid protein could induce pathological immune response in the genital tract of BALB/c mice,which may be associated with the increase of the production of the inflammatory cytokines TNF-α,IL-1β and IL-6 in BALB/c mice.

ObjectiveTo construct a mouse model for studying pathophysiology and mechanism of human Chlamydia trachomatis genital infection.MethodsInnate immunity-deficient C3H/HeJ female mice were infected intravaginally with human C.trachomatis serovar D urogenital isolates for screening the highest violent clinical strain.The clinical strain UT0603 as well as standard strain D/UW-3/CX were then used to reinfect na(i)ve mice,the lower genital tract shedding were monitored by swabbing every 3-7 day over the entire infection period by culture.Some mice were sacrificed at early infection stage to detection of in site Chlamydia growth by immunofluorescence assay,then all the mice were sacrificed at later infection stage to evaluate upper genital tract gross pathology and histopathological characterization.ResuIts In the lower genital tract,Chlamydia shedding time course were significantly prolonged in clinical strain infected mice.Chlamydia not only growth in the lower genital tract,the live organism also ascending and growth in the upper genital tissue.The gross appearance under naked eyes and dilation and inflammation scores under microscope all showed that the genital tract pathology from the clinical strain infected mice were much more severe than standard strain infected control mice.Conclusion Together,all these results demonstrated that a mouse model for Chlamydia genital infection was constructed.

Objective To investigate the specific humoral immune response and cellular immune response induced by DNA vaccine with Neisseria gonorrhoeae porin B (PorB) fused with B subunit of Escherichia coli heat-labile enterotoxin B (LTB) in mice. Methods Target genes of porB, ltB and ltB-porB were amplified by polymerase chain reaction (PCR) and cloned into eukaryotic vector pcDNA3.1(-). The recombinants were identified by PCR, enzyme digestion and DNA sequencing.The vectors were transfected into Hela cells, and expressed proteins were checked by cytoimmunofluorescence. Female BALB/c mice were intranasally immunized with recombination vectors. The humoral immune response and cellular immune response were detected by enzyme linked immunosorbent assay (ELISA) and methyl thiazolyl tetrazolium (MTT) colorimetric assay. The expressions of recombination vectors in intranasal mucosal tissues of the immunized mice were detected by immunohistochemistry. The means between groups were compared by analysis of variance. Results All the three recombinants were expressed in Hela cells and intranasal mucosal tissues. The PorB specific IgG in serum and sIgA in vaginal secretions in DNA vaccine immunized mice were significantly higher than those in controls (P＜0.01 ; P＜0.05). Moreover, the sIgA level in pcDNA3.1 (-)/ltB-porB group was higher than that in peDNA3, 1(-)/porB group (P＝0. 002). The levels of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in the supernatants and stimulation index (SI) of spleen lymphocyte culture in pcDNA3, 1(-)/porB group were (170.04±23.89) pg/mL, (114.68±14.27) pg/mL and 1. 68±0.19, respectively; and those in pcDNA3, 1(-)/ltB-porB group were (161.42±27.50) pg/mL, (124.16±19.04) pg/mL and 1.73±0.28, respectively; which were both higher than those in pcDNA3.1(-)/ phosphate buffered saliae (PBS) group (P＜0. 01; P＜0.05) and pcDNA3.1 (-)/ltB group (all P＜0.05), while there was no significant difference between pcDNA3.1 (-)/ltB-porB group and pcDNA3. 1 (-)/porB group (0. 998, 0. 696, 0. 994; all P＞0.05). Conclusions The constructed DNA vaccines are all successfully expressed in Hela cells and murine intranasal mucosal tissues. The mucosal immunization of the vaccines [pcDNA3. 1 (- )/porB and pcDNA3.1 ( -)/ltBporB] could induce humoral immune response and cellular immune response, especially mucosal immune response. It is confirmed that mucosal adjuvant LTB could promote PorB to induce higher level of mucosal immune response in mice.

Objective To improve the understanding of the characteristics of obstructive sleep apnea-hypopnea syndrome (OSAHS) in the elderly patients, and to improve the diagnosis and treatment level. Methods Monitoring results of polysomnography (PSG) from 110 elderly OSAHS patients were analyzed retrospectively. The general conditions, sleep architecture, apnea and hypopnea events, oxygen reduction as well as possible correlations between various indicators were analyzed using SPSS18.0 statistical software. Results The median rapid eye movement (REM) and non-REM (NREM) sleep time of elderly patients with OSAHS accounted for 2. 17% and 76.73%,respectively. The median arousal index was 45.6 times/h. The longest time of sleep apnea was (51.94±22.06) s, the median of average sleep apnea time was 22.50 s, the longest time of hypopnea was (47.06±12.52) s and the average hypopnca time was (21.50±4.63) s. The median respiratory disturbance index (RDI) of all patients was 21.50, the patients with RDI between 5 and 20 accounted for 46.40%, with RDI between 20 and 40 accounted for 31.80% and with RDI over 40 accounted for 21.8%. The average oxygen saturation accounted for (93.45% ± 2.81%), the lowest oxygen saturation accounted for (76.3%± 10. 5%) and the median oxygen desaturation index was 31.6;times/h. BMI was negatively correlated with lowest oxygen saturation (r=-0. 378, P＜0.01) and average oxygen saturation ( r = - 0. 355, P ＜ 0. 01 ), while was positively correlated with oxygen desaturation index (r=0. 338, P＜0. 01 ). The lowest oxygen saturation was negatively correlated with the longest time of obstructive apnea (r= -0. 47, P＜0. 01 ), the average time of obstructive apnea (r=-0.316, P＜0.01), the longest time of hypopnea (r=-0.293, P＜0.01) and the average time of hypopnea (r=-0. 277, P＜0.01). The median time intervals of oxygen desaturation during supine, left side and right side position were 2.36 min, 11.54 min and 12.45 min,respectively. The median time intervals of oxygen desaturation during left side and right side position were both longer than that of supine position (Z= -6.12 and -7. 10 respectively, both P＜0.01).Conclusions Elderly patients with OSAHS manifest obvious disorder of sleep structural and sleep fragmentation. According to RDI, the majority of the patients are classified as mild to moderate in severity. However, elderly patients with OSAHS are severe regarding to hypoxia relatively. The severity of hypoxia is related with BMI and the lasting time of sleep-disordered breathing events, and hypoxia are less severe when sleeping on left side or on right side.

Objective To investigate the possible correlation of the clinical parameters, such as age, obesity, Epworth sleepiness score (ESS), with the severity of snoring and obstructive sleep apnea hypopnea syndrome (OSAHS). Methods One hundred and forty-eight patients with snoring during sleep admitted from May to Jul. 2008 were asked to answer the questions from a questionnaire concerning snoring, daytime sleepiness, and habits such as smoking and drinking, etc. All patients underwent at least a polysomnography (PSG) and the physical examination included height, weight, and body mass index (BMI). Age, BMI, the lowest SaO_2(%), ESS score, the biggest reduction of oxygen (%), a total suspension of time, the average correlation between respiratory disorder index (RDI) applied computing Pearson correlation test. Simple snoring and OSAHS group of mild, moderate and severe inter-group comparison analysis using generalized linear models. Results The prevalence of OSAHS was increased with age, higher in males than in females. A statistically significant correlation between ESS, BMI, the lowest SaO_2 with the RDI was detected. The difference of ESS, the lowest SaO_2 and the BMI was significant between the different serious patients (P<0.05). Conclusions OSAHS has a high morbidity rate in outpatients with snoring. Age and obesity are liability factors of OSAHS. BMI, the lowest SaO_2, ESS and RDI have well correlationship, which can be used to assess the pathogenetic condition, even make a primary diagnosis.