Objective:To investigate the effect of IL-35 on inflammatory response and T cell response in allergic rhinitis.Methods: 37 patients(observation group) with allergic rhinitis and 35 healthy volunteers(control group) after allergen detection of allergic rhinitisin in our hospital from Jan 2012 to Jan 2016 were selected as study subjects.The peripheral blood of observation group and control group were collected,and the serum levels of IL-35 were detected by ELISA.The animal model of allergic rhinitis in mice was established,the peripheral blood of mice was collected,and the serum level of IL-35 and IgE were detected by ELISA.The eosinophils that infiltrated in nasal mucosa were detected after tissue biopsy in mice.The mouse spleen cells were isolated and the ovalbumin antigen was added in the culture medium,IL-35 was or was not added into the culture medium,the ovalbumin specific T cell responses was detected.The cytokines IL-2,IL-4,IL-5,IL-10,IL-13,IL-17,IL-23,IL-27 and TNF-α in culture supernatant of ovalbumin specific T cells were detected by ELISA.The expression of IL-2,IL-4,IL-5,IL-10,IL-13,IL-17,IL-23,IL-27 and TNF-α in ovalbumin specific T cells were detected by Real-time PCR.The activation of JNK,Erk1/2 and p38 signal pathway in ovalbumin specific T cells were detected by Western blot.Results: The serum level of IL-35 in observation group was significantly lower than control group(P<0.05).The results showed that the number of eosinophils which infiltrated in AR mice nasal mucosa was significantly higher than normal mice(P<0.05),while the serum level of IL-35 in AR mice was significantly lower than normal mice(P<0.05).Ovalbumin specific T cell reactivity assay showed that IL-35 could significantly inhibit the T cell response.ELISA and Real-time PCR results showed that IL-35 could significantly down regulate the expression of IL-4,IL-5,IL-13,IL-17,IL-23 and TNF-α,and up regulate the expression of IL-2,IL-10 and IL-27.The Western blot results showed that IL-35 can inhibit the activation of JNK,Erk1/2 and p38 signal pathway of ovalbumin specific T in cells.Conclusion: IL-35 can regulate the expression of inflammatory cytokines in inflammatory response and inhibit T cell response,thus reducing allergic rhinitis,the mechanism may be through regulation of JNK,Erk1/2 and p38 signal pathway activation.

short peptide AS1 screened from the phage random peptide library of 12 amino acids has antigenicity and can react with sera of AS patients. These findings indicate that AS1 could be one of candidate molecules of AS-specific serum markers.

OBJECTIVE: To explore the effects of specific immunotherapy by the nasal spray and/or sublingual contain on the regulation the balance of serum Th1/Th2 cell ratio, and the expression of total IgE (tIgE) level in perennial allergic rhinitis patients. METHOD: Thirty-six cases of allergic rhinitis of perennial (PAR) patients with nasal specific immunotherapy (nasal spray group) were chosen as the object of study, 36 PAR patients with sublingual specific immunotherapy (sublingual group) were chosen for the efficacy comparison group, and 32 cases of healthy adults as control (normal control group). The levels of serum IL-2, IL-4, IL-8 and tIgE in PAR nasal spray group and sublingual group were examined by IRMA and double-antibody sandwich assay before and after the treatment of specific immunotherapy (SIT); The content of IFN-gamma was determined by enzyme-linked immunosorbent assay; The infiltration and changes of eosinophilic granulocyte were observed by the smear of nasal secretions. RESULT: In nasal spray group and sublingual group, the contents of serum Th1 cytokines IL-2 and IFN-gamma were reduced levels significantly, while the contents of Th2 cytokines IL-4, IL-8 and tIgE were significantly increased before the treatment of SIT. After the SIT to the maintenance dose, the levels of IL-2 and IFN-gamma in serum were significantly higher than that before treatment, while IL-4, IL-8 and tIgE content were significantly lower in AR patients (P < 0.01 or P < 0.05). The clinical efficacy of nasal spray group and sublingual group were 97.22% and 94.44%, while the two groups was no statistical difference in efficacy (P > 0.05). CONCLUSION With the presence of Th1/Th2 cell ratio and cytokine imbalance, the AR patients manifested as Th2 cell function in accentuation. Nasal mucosa and/or sublingual in the local SIT can have changed no-balance Th1/Th2 cell of by regulating the balance of serum Th1/Th2 cell ratio, the expression level of cytokine expression and the level of tIgE.
Adolescent ; Adult ; Cytokines ; blood ; Female ; Humans ; Immunoglobulin E ; blood ; Immunotherapy ; Lymphocyte Count ; Male ; Middle Aged ; Rhinitis, Allergic, Perennial ; blood ; immunology ; therapy ; Th1 Cells ; cytology ; Th2 Cells ; cytology ; Young Adult

Objective To investigate the prognostic value of Ki67 and derived neutrophil to lymphocyte ratio (dNLR) in clinical outcomes of patients with nasopharyngeal carcinoma.Methods A total of 180 patients with undifferentiated nasopharyngeal carcinoma confirmed by pathology from January 2011 to June 2015 in our hospital were enrolled.The neutrophil count and white blood cell count before radiotherapy and chemotherapy were collected,and dNLR was calculated.The positive rate of Ki67 in tumor tissues was detected by immunohistochemistry.The predictive values of Ki67 positive rate and dNLR on the overall survival (OS) rate and progression free survival (PFS) rate were evaluated.Results The 3-year OS rate prediction thresholds for patients with nasopharyngeal carcinoma by Ki67 and dNLR were 73.5％ and 2.21,respectively,which assessed by receiver operating characteristic (ROC) curve.The proportion of TNM Ⅲ-Ⅳ stage in patients with Ki67 ≥73.5％ was higher than that in Ki67 ＜ 73.5％ (100％ vs.89.7％,x2 =5.529,P =0.019);the proportion of T3-4 stage in dNLR ≥2.21 was higher than that in dNLR ＜ 2.21 (91.1％ vs.75.0％,x2 =6.228,P=0.013),and the proportion of TNM Ⅲ-Ⅳ stage in the dNLR≥2.21 group was higher than that in the dNLR ＜ 2.21 group (100％ vs.90.3％,x2 =4.355,P =0.037).Multivariate Cox regression analysis indicated that Ki67≥73.5％ (HR=3.011,95％CI:1.874-4.982,P＜0.001) and dNLR≥2.21 (HR =2.234,95％CI:1.274-3.382,P =0.001) were independent risk factors for OS in patients with nasopharyngeal carcinoma,while Ki67 ≥ 73.5％ (HR =2.842,95 ％ CI:2.055-4.337,P ＜ 0.001) and dNLR ≥ 2.21 (HR =2.086,95％ CI:1.452-2.983,P ＜0.001) were also independent risk factors for PFS in patients with nasopharyngeal carcinoma.Patients were divided into high-risk group,medium-risk group and low-risk group combined with Ki67 and dNLR,the 3-year OS rates were 20.0％,85.7％ and 95.3％ respectively,and the 3-year PFS rates were 12.0％,78.6％ and 89.4％ respectively,with statistical differences (x2 =15.521,P ＜ 0.001;x2 =15.849,P ＜ 0.001).Conclusion Ki67 and dNLR can effectively predict OS and PFS in patients with nasopharyngeal carcinoma,combined with Ki67 and dNLR can prognose stratification of patients with nasopharyngeal carcinoma.

OBJECTIVE: To investigate the relationship between the prevalent species and the seasonal drift law of airborne fungi and respiratory allergic disease in the city of Wuhan. METHOD: Airborne fungi was investigated by exposed sides from 2007 to 2008, and 1674 patients with respiratory allergic disease that were used to do allergens skin test simultaneously, in order to analyze the simultaneous. RESULT: Airborne fungi could be detected in air all over the year. In 2007, the exposed films collected 26 734 fungi spores, and 686 other fungi (hypha and not well known fungi), to the sum of 27420. Otherwise, in 2008, the exposed films collected 26 531 fungi spores, and 730 other fungi, to the sum of 27 261. In the survey, 17 types of species of the collected fungi spores were identified, and the predominant species were alternaria sp, ustilaginales, deightoniella sp, uredinales, and the quantity of Fungi alternaria was most of all . And the peak period mainly concentrated from April to June, and from September to October. Otherwise, the positive rate of fungi skin test in patients with respiratory allergic disease was 10.48% in 2007, but 10.07% in 2008. The main period of onset of respiratory allergic disease was from April to June, and from September to October, similar as the seasonal drift law of airborne fungi. CONCLUSION The period of onset of respiratory allergic disease was consistent with the seasonal drift law of airborne fungi.
Adolescent ; Adult ; Aged ; Air Microbiology ; Allergens ; immunology ; Child ; China ; epidemiology ; Cities ; Colony Count, Microbial ; Female ; Fungi ; immunology ; Humans ; Male ; Middle Aged ; Mycoses ; epidemiology ; Respiratory Hypersensitivity ; epidemiology ; immunology ; microbiology ; Young Adult

Objective: To investigate the CRISPR genotypes (clusters) and regional distribution of Yersinia pestis in Qinghai-plateau. Methods: One hundred and two isolates of Y. pestis isolated from human plague patients, host animal and insect vectors from Qinghai-plateau were selected. The DNAs were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. Three CRISPR loci YPa, YPb and YPc of 102 isolates of Y. pesits were amplified and sequenced, and then the CRISPR sequence analysis was carried out by comparing the latest published CRISPR spacer dictionary and the NCBI database to identify the spacer and spacer array. CRISPR genotyping of isolates of Y. pesits were finally conducted according to the polymorphism of the spacer arrays and the regional distribution pattern of isolates of Y. pesits in Qinghai-plateau was described. Results: Forty spacers including 22 of YPa, 13 of YPb and 5 of YPc were observed among 102 isolates of Y. pestis in Qinghai-plateau, of which 5 spacers (a1', a103, a104, b4'' and b4''') were firstly identified. Meanwhile, 16, 10, and 5 different spacer arrays were obtained in YPa, YPb and YPc respectively, including 11 new spacer arrays detected in this study. One hundred and two isolates were divided into 24 CRISPR genotypes and classified into 9 CRISPR clusters (Cb4, Cb4', Cb2, Ca37, Ca7, Ca7', CaΔ5', Ca35' and Cc3'). Each dominant cluster presented significant aggregation geographically: Ca7 were found in Yushu, Nangqian, Chenduo, Zaduo, Zhiduo and Qumalai countries. Ca7' were found in Xunhua, Tongren, Zeku, Tongde, Maqin and Guinan countries. CaΔ5' were restricted to Qilian, Gangcha, Menyuan and Datong countries. CaΔ35' were found in Huangyuan, Haiyan, Gangcha, Tianjun, Delingha, Wulan, Doulan, Gonghe, Xinghai, Guide and Tongde countries. Conclusion CRISPR-based genotyping analyses showed complicated population of Y. pestis in Qinghai-plateau. Four clusters, Ca7, Ca7', CaΔ5' and Ca35' were the most epidemic dominant four clusters and presented obvious regional distribution patterns, which instructed us to strengthen the surveillance and prevention and control by CRISPR-genotyping technique.

OBJECTIVE: To explore the genetic basis of cerebral palsy (CP). METHODS: A pair of twins with cerebral palsy and different phenotypes were subjected to whole genome sequencing, and other 8 children with CP were subjected to whole exome sequencing. Genetic variations were screened by a self-designed filtration process in order to explore the CP-related biological pathways and genes. RESULTS: Three biological pathways related to CP were identified, which included axon guiding, transmission across chemical synapses and protein-protein interactions at synapses, and 25 susceptibility genes for CP were identified. CONCLUSION The molecular mechanism of CP has been explored, which may provide clues for development of new treatment for CP.
Cerebral Palsy ; genetics ; Child ; Genetic Testing ; Humans ; Phenotype ; Whole Exome Sequencing ; Whole Genome Sequencing

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.