Objective To observe the therapeutic effect of Jade Maid Decoction(JMD),a Chinese herbal prescription for nourishing yin and clearing stomach-heat,on experimental periodontitis.Methods Twenty-four New Zealand rabbits were randomized into the model group,JMD group(oral use of JMD 23 g?kg-1?d-1),external application group(periodontal injection of minocycline hydrochloride ointment 50mg),and the combination group(oral use of JMD and periodontal injection of minocycline hydrochloride ointment).Experimental periodontitis was induced by ligation method.The treatment lasted 6 weeks.Gingival bleeding on probing(BOP) and probing pocket depth(PPD) were detected each week after medication,and pathological examination of the mandible was used to confirm the therapeutic effect after treatment.Results Gingival BOP was reduced to various degrees at different time in the three medication groups,and the effect was obvious in the combination group;PPD was also decreased to various degrees,and the difference of PPD between the three medication groups and the model group was significant after treatment for 4 weeks(P

ObjectiveTo investigate the relation of obesity parameters,including body mass index (BMI),waist-to-height ratio(WHR),waist circumference,and waist-to-hip ratio(WHR),with hypertension in adolescents.MethodsA cross-section study was conducted among 3953 adolescents aged 12 to 18 years old,who were assigned to the normal blood pressure group (3724) or hypertension group(229).Measurements were height,weight,waist circumference,systolic blood pressure (SBP),and diastolic blood pressure (DBP).ResultsThe data showed that mean BMI,WHR,waist circumference,WHR,SBP,and DBP in the hypertension group Was significantly higher than those in the normal blood pressure group(all P<0.05).In partial correlation analysis,BMI,WHR,waist circumference,and WHR were positively correlated with both SBP and DBP after gender or age were adjusted(r'=0.3228 and 0.2358,both P<0.05).For alias under the receiver operating curve(ROC),the BMI was obserred to strongly predict hypertension in male (0.715;95%CI0.659-0.771)and female (0.702;95%CI0.646-0.757).BMI was also entered into the multiple linear regression modeL ConclusionBMI could be an effective predictive factor of hypertension in adolescents.

Objective The aim of the study was to explore the relationship between hypertriglyceridemic-waist(HTWC) phenotype and clustering of cardiovascular risk factors in adolescents. Methods A cross-sectional study was conducted in 3 136 Han adolescents aged 13-17 years in Qinhuangdao. The HTWC phenotype was defined as serum triglyceride concentrations ≥1. 47 mmol/ L and waist circumference ≥90 th percentile for age and sex. Results The prevalence of HTWC phenotype was 3. 3% . The prevalence of clustering of cardiovascular risk factors was 0. 4%in adolescents with normal waist circumference and serum triglyceride and 14. 7% in adolescents with HTWC phenotype. After adjustment for sex, age, body mass index, and family history of diabetes and hypertension, the prevalence of clustering of cardiovascular risk factors in adolescents with HTWC phenotype was 9. 286 fold(95% CI 3. 161-27. 282, P<0. 01) of that in adolescents with normal waist circumference and triglyceride. Conclusion There was a significant correlation between HTWC phenotype and clustering of cardiovascular risk factors, suggesting that this phenotype may be applied as a simple marker for identifying adolescents with clustering of cardiovascular risk factors.

accumulation and endothelial dysfunction are associated with insulin resistance.

Objective To explore the best cut-point of waist-to-heisht ratio (WHtR) for identifying metabolic syndrome(MS)in adolescents.Methods A cross-sectional study was conducted in 4 507 adolescents aged 13-18 years in Qinhuangdao.Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal WHtR cut-point for detecting MS.Results The prevalences of MS were higher among higher WHtR in both boys and girls.Odds ratios for MS significantly increased from the WHtR≥0.45 in boys(OR =13.85,95%CI 4.08-46.97)and in girls (OR=12.42,95%CI 2.62-58.96,P<0.01).The ROC curve analysis showed that the optimal WHtR cut-point was 0.45 in boys with the sensitivity of 89.4%and specificity of 81.4%.and in girls with sensitivity of 90.3%and specificity of 86.5%.Conclusion There is a significant correlation between WHtR and MS.Optimal WHtR cut-point for predicting MS is 0.45.

Objective To evaluate the relationship between obesity and serum soluble intercellular adhesion molectde-1 (sICAM-1) in adolescents. Methods Totally, 158 adolescents aged 13-15 years were divided into three groups based on their body mass index (BMI) , 80 in control group, 44 in overweight group and 34 in obesity group. Height, weight, waist circumference (WC) and blood pressure were measured for all of them and sICAM-1 was assayed from fasting venous blood collected. Results BMI, WC and systolic blood pressure were significantly higher in overweight group than those in control group (P < 0. 01). BMI, WC, systolic blood pressure and diastolic blood pressure were significantly higher in obesity group than those in overweight group (P<0. 05). Level of sICAM-1 was significantly higher in obesity group than that in control group (P <0.05). Their sICAM-1 showed positive correlation with BMI (r = 0.168, P=0.035) and WC (r=0. 179, P =0.025). Multiple linear regression analysis using sICAM-1 as a dependent variable showed that WC (β= 0.009, 95% CI 0. 001-0.018, P=0.025) was an independent predictors for sICAM-1 adjusted for age, sex, BMI and blood pressure. Conclusions Results mentioned above suggest that endothelial dysfunction associates with obesity, particularly with abdominal obesity. sICAM-1 can be used as an early marker of atherosclerosis in adolescents.

Objective To simultaneously determine of shikimic acid,catechin,quercetin,kaempferol,isorhamnetin,3'-hydroxypuerarin,puerarin,3'-methoxypuerarin,daidzin and genistein in Songling Xuemaikang Capsules by quantitative analysis of multi-components by single-marker(QAMS),and to establish fusion model of weighted technique for order preference by similarity to an ideal solution(TOPSIS)and grey relational analysis(GRA)for evaluating the quality of 15 batches of samples.Methods HPLC method was used to calculate the relative correction factor and content of each component,using kaempferol as internal reference.The feasibility of QAMS method was verified by comparing with the measured value of external standard method.The content results were analyzed by chemometrics to explore the quality difference markers of Songling Xuemaikang Capsules.Taking the VIP value of each component as the weight,we performed differential analysis on sample quality through fusion model of weighted TOPSIS and GRA.Results There was no significant difference between the results of QAMS and external standard method.The 15 batches of samples were clustered into three categories.Puerarin,3'-hydroxypuerarin,quercetin,3'-methoxypuerarin and shikimic acid were the quality difference markers of Songling Xuemaikang Capsules.The results of fusion model of weighted TOPSIS and GRA showed that there were some quality differences in Songling Xuemaikang Capsules produced at different times.Conclusion The hybrid model combining QAMS,weighted TOPSIS and GRA can be used for the comprehensive evaluation of the quality of Songling Xuemaikang Capsules.

Objective:To investigate the significance of multicolor flow cytometry (MFC) monitoring of minimal residual disease (MRD) in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CD19-chimeric antigen receptor(CAR)-T cell immunotherapy for patients with refractory, relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL).Methods:37 patients with r/r B-ALL admitted to Hebei Yanda Lu Daopei Hospital from January to July 2019, aged 15 (6, 19) years old, including 24 males and 13 females, were treated with CD19-CAR-T cell immunotherapy bridging allo-HSCT. MFC with cytoplasmic CD79a antibody to set up B-cell gates was used to monitor patients′ bone marrow (BM), cerebrospinal fluid (CSF), and tissue samples on day 0 (prior to the CAR-T cell immunotherapy), day 15, day 28 post CAR-T cell immunotherapy, and post transplantation.The MRD values of these samples were analyzed to evaluate the residual tumor cells and metastasis. The killing effect of the CAR-T cells was evaluated by the recovery of CD19+B cells before transplantation and the period between the timepoint when CD19+B cells was recovered and the timepoint when CAR-T cells were infused. Peripheral blood CAR-T cells were counted at different time points. Statistic analysis was performed by Kaplan-Meie assay and Log-rank test to analyze the difference of univariate cumulative survival.Results:(1)Among the 37 patients, 8 died and 29 survived. 5 patients relapsed after transplantation, of which 4 relapsed patients died and 1 survived. (2)MFC MRD negative remission rate of the death group was lower than that of the survival group at the following time points: post-CAR-T therapy and prior to transplantation (5/8 vs. 28/29, χ 2=7.540, P=0.006); day 15 of the CAR-T cell reinfusion (3/8 vs. 24/29, χ 2=6.512, P=0.011); day 28 of the reinfusion (3/8 vs. 276/29, χ 2=10.065, P=0.002). The probability of extramedullary MFC MRD positive tumor infiltration in the death group was higher than that in the survival group(7/8 vs. 14/29, χ 2=3.931, P=0.047). After CAR-T cell immunotherapy, the recovery period of CD19-positive cells in the death group, or the time for CAR-T cells to kill CD19-positive cells, was shorter than that in the survival group [42.00 days(30.00,49.00) vs. 55.00 days(41.50,73.50), Z=0.022, P=0.020]. Conclusion:The positive results of MRD by MFC at the following timepoints may predict unfavorable outcomes, such as post-CAR-T therapy and prior to transplantation, day 15 and 28 of the CAR-T cell immunotherapy, which may provide some guidance for clinical management.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.