Kawasaki disease(KD) is an acute febrile childhood inflammatory disease,characterized by systemic small artery inflammation as the main pathological changes that can lead to expansion of coronary artery,myocardial infarction and sudden cardiac death.Cytokines secreted by immune cells are small molecules,which can regulate the function of inflammatory cells,play important roles in the process of immune response,stimulate the proliferation and differentiation of cells,and regulate interactions between them.In the acute phase,super antigens activate immune responses.A large number of cytokines and inflammatory mediators are released into the blood,which participate in the occurrence and development of KD and the vascular disease.Many inflammatory cytokines are associated with coronary artery damages in KD patients.In this paper,the roles of various cytokines in the coronary artery lesions of KD are reviewed.

Objective: To screen and identify the mutations in Kawasaki disease by targeted enrichment of genomic region sequencing technique and investigate susceptibility genes associated with coronary artery lesion. Method: This was a case-control study.A total of 114 patients diagnosed as Kawasaki disease treated in Shanghai Children′s Hospital between December 2015 and November 2016 were studied and another 45 healthy children who were physically examined in outpatient department were enrolled as control group. Patients were divided into two groups based on the results of echocardiogram. Peripheral venous blood was obtained from patients and controls. Genomic DNA was extracted. SeqCap EZ Choice libraries were prepared by targeted enrichment of genomic region technology. Then the libraries were sequenced to identify susceptibility genes associated with coronary artery lesion in patients diagnosed as Kawasaki disease.Susceptible genes were identified by Burden test, Pearson chi-square test or Fisher′s exact probability test. Result: There was statistically significant difference in TNFRSF11B(rs2073618)G>C(p.N3K)mutation and GG/GC/CC genotype between Kawasaki disease group and control group(χ²=15.52, P=0.00). There was statistically significant difference in TNFRSF13B(rs34562254)C>T(p.P251L)mutation(χ²=10.40, P=0.01)and LEFTY1(rs360057)T>G(p.D322A)mutation(χ²=8.505, P=0.01)between patients with coronary artery lesions and those without. Conclusion Targeted enrichment of genomic region sequencing technology can be used to do primary screening for the susceptible genes associated with coronary artery lesions in Chinese Kawasaki patients and may provide theoretical basis for larger sample investigation of risk prediction score standard in Kawasaki disease.

Objective To analyze the possible risk factors of IVIG non-response of Kawasaki disease (KD),Shanghai Children's Hospital and Shanghai Junze Software develop an research platform,which is based on E-Science model.Through the mathematical model by integrating the risk factors to explore the method of effective prediction for IVIG non-response,and to provide the clinical basis for timely and effective treatment and prognosis of the disease.Methods The data of KD children who were hospitalized in Shanghai Children's Hospital from January 2013 to November 2016 were included.The indexes included gender,age,time of IVIG treatment,and laboratory examinations.The multivariate logistic regression was used to analyze the influencing factors of IVIG non-response.The indexes in the model were deduced according to the independent variables of the logistic regression equation.The ROC curve and the area under the curve were calculated for the new prediction model.The sensitivity and specificity of the new prediction model were calculated according to the cutoff value.Finally,the new model was compared with the Kobayashi and Egami scoring model.Results The levels of CRP,NLR,LDH,ALB and FDP in children with KD were influencing factors for IVIG nonresponse (P ＜ 0.05).According to the logistic regression equation,the sensitivity and specificity of the model used to predict IVIG non-response were 69.7％ and 80.4％,respectively,and the area under the ROC curve was 0.825 (95％ CI:0.769-0.882).Kobayashi and Egami scoring models were tested,the sensitivity and specificity of the new scoring system were better than previous ones.Condusion The scoring model established in this study has a good effect in predicting IVIG non-response in KD patients and could be used in clinical practice,and it is worthy to be validated and adjusted by large-scale data.

Objective To investigate the acute phase expression of serum cytokines in children with Kawasaki disease (KD) and its association with coronary artery lesions (CALs). Methods Expression of 13 cytokines in serum of 104 KD patients including 11 cases with CALs and 74 febrile control cases admitted to the hospital from October 2016 to March 2017 were retrospectively analyzed. Results Interleukin (IL)-8, IL-1, IL-2, IL-6, IL-10, IL-17A, IL-18, tumor necrotic factor-α and SCD25 (IL-2R) were declined significantly after intravenous immunoglobulin administration (IVIG) in KD patients (all P<0.05). Compared with the fever control group, Pre-IVIG, an IL-17A level ≥ 0.155 pg/mL had a sensitivity of 50% and 93.2% specificity for predicting KD; IL-18 level ≤ 15.43 pg/mL had a sensitivity of 71.2%, and the specificity was 54.1%; SCD25 (IL-2R) ≥ 29475.29 pg/mL had a 65.4% sensitivity and 81.1% specificity for predicting KD. Before IVIG treatment, the level of IL-10 was significantly lower in KD patients with CALs than in those without CALs. Conclusions Determination of various cytokines profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

OBJECTIVETo evaluate the ovarian response and pregnancy outcomes in patients with excessive ovarian response receiving long-protocol pituitary down-regulation during repeated in vitro fertilization and embryo transfer (IVF-ET).

METHODSSixty IVF-ET cycles from January 2008 to December 2011 were analyzed retrospectively. The clinical characteristics were compared between the various treatment cycles.

RESULTSCompared with those with the first treatment cycle, the patients receiving repeated cycles had a significantly older age (P<0.001), reduced initial doses of Gn (P=0.049), and moderately lowered estrogen level on the day of hCG administration (E₂) (P=0.027) and the number of oocytes retrieved (P=0.030). The high-quality embryo formation rate (P<0.001) and clinical pregnancy rate (P=0.009) were both significantly higher in patients with repeated cycles. The dose for down-regulation, total Gn dose, duration of Gn stimulation, number of two pronuclei (PN), number of fertilized oocyte, and the cancellation rate for a high risk of ovarian hyperstimulation syndrome (OHSS) were all comparable between the two groups (P>0.05). The recurrence rate of ovarian excessive respond was 40% (12/30).

CONCLUSIONSFor patients receiving repeated IVF treatment cycle with a high ovarian response, a smaller initial dose of Gn should be used to minimize the risk of hyper-response and improve the outcome of assisted reproductive treatment.

Down-Regulation ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropins ; therapeutic use ; Humans ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies ; Risk Factors

Objective:To explore the correlation between periodontitis (PD) and chronic kidney disease (CKD) in adults, as well as the potential mechanisms involved.Methods:Data on PD and CKD from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2014 were downloaded. Weighted univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with PD and CKD, considering demographic and clinical indicators. Using publicly available genome-wide association study (GWAS) summary datasets for CKD and PD as outcome variables, as well as 731 immune cell phenotypes and 91 inflammatory proteins as exposure factors from the OPEN GWAS database, a two-sample Mendelian randomization (TSMR) analysis was performed using the inverse-variance weighted (IVW) method.Results:Seven demographic indicators including gender, age, race, education level, marital status, income, and health are related to the incidence of CKD and PD. Among them, the elderly (≥60 years old), poverty (poverty-income ratio <1.3), divorce or widowhood, and male ratio in the comorbidity group of CKD and PD [67.12% (833/1 241), 36.83% (457/1 241), 34.41% (427/1 241), and 57.78% (717/1 241) respectively] were significantly higher than those in the control group [23.71% (4 179/17 623), 29.17% (5 141/17 623), 18.16% (3 200/17 623), and 48.73% (8 587/17 623) respectively] (all P<0.001). Those with high educational level (university and above) and self-rated excellent health accounted for a relatively small proportion in the comorbidity group [14.10% (175/1 241) and 8.22% (102/1 241) respectively]. The prevalence of PD increased among individuals with abnormal renal function indices, including glomerular filtration rate, urine protein/creatinine ratio, serum creatinine, serum uric acid, and blood urea nitrogen. Univariate logistic regression analysis showed a positive correlation between the incidence of PD and CKD ( OR=2.14, 95 %CI: 1.90-2.42, P<0.001). Multivariate logistic regression analysis also indicated that PD and CKD were potential risk factors for each other (PD for CKD: OR=1.22, 95 %CI: 1.07-1.40, P=0.004; CKD for PD: OR=1.19, 95 %CI: 1.04-1.37, P=0.012). Furthermore, after adjusting the model based on demographic indicators, there was still a significant correlation between PD and CKD ( P=0.010). Mechanistically, the results of the TSMR analysis support the existence of a common risk factor mediated by immune cells between CKD and PD, namely the expression of CD64 on multiple innate immune cells mediates the occurrence of CKD and PD. The absolute count of CD64 + monocytes is associated with an increased risk for both CKD ( HR=1.11) and PD ( HR=1.07), while same tendency showed in the absolute count of CD64 + neutrophils for CKD ( HR=1.22) and PD ( HR=1.23). Conclusions:There is a positive correlation between CKD and PD, particularly moderate to severe PD, and the shared pathogenesis involves CD64 + monocytes in the circulatory system. Targeted interventions focusing on CD64 molecules or monocyte subsets may be beneficial.

Objective To evaluate the ovarian response and pregnancy outcomes in patients with excessive ovarian response receiving long-protocol pituitary down-regulation during repeated in vitro fertilization and embryo transfer (IVF-ET). Methods Sixty IVF-ET cycles from January 2008 to December 2011 were analyzed retrospectively. The clinical characteristics were compared between the various treatment cycles. Results Compared with those with the first treatment cycle, the patients receiving repeated cycles had a significantly older age (P<0.001), reduced initial doses of Gn (P=0.049), and moderately lowered estrogen level on the day of hCG administration (E2) (P=0.027) and the number of oocytes retrieved (P=0.030). The high-quality embryo formation rate (P<0.001) and clinical pregnancy rate (P=0.009) were both significantly higher in patients with repeated cycles. The dose for down-regulation, total Gn dose, duration of Gn stimulation, number of two pronuclei (PN), number of fertilized oocyte, and the cancellation rate for a high risk of ovarian hyperstimulation syndrome (OHSS) were all comparable between the two groups (P>0.05). The recurrence rate of ovarian excessive respond was 40%(12/30). Conclusion For patients receiving repeated IVF treatment cycle with a high ovarian response, a smaller initial dose of Gn should be used to minimize the risk of hyper-response and improve the outcome of assisted reproductive treatment.

Objective To evaluate the ovarian response and pregnancy outcomes in patients with excessive ovarian response receiving long-protocol pituitary down-regulation during repeated in vitro fertilization and embryo transfer (IVF-ET). Methods Sixty IVF-ET cycles from January 2008 to December 2011 were analyzed retrospectively. The clinical characteristics were compared between the various treatment cycles. Results Compared with those with the first treatment cycle, the patients receiving repeated cycles had a significantly older age (P<0.001), reduced initial doses of Gn (P=0.049), and moderately lowered estrogen level on the day of hCG administration (E2) (P=0.027) and the number of oocytes retrieved (P=0.030). The high-quality embryo formation rate (P<0.001) and clinical pregnancy rate (P=0.009) were both significantly higher in patients with repeated cycles. The dose for down-regulation, total Gn dose, duration of Gn stimulation, number of two pronuclei (PN), number of fertilized oocyte, and the cancellation rate for a high risk of ovarian hyperstimulation syndrome (OHSS) were all comparable between the two groups (P>0.05). The recurrence rate of ovarian excessive respond was 40%(12/30). Conclusion For patients receiving repeated IVF treatment cycle with a high ovarian response, a smaller initial dose of Gn should be used to minimize the risk of hyper-response and improve the outcome of assisted reproductive treatment.

Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.