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 and value of peripheral blood lymphocyte subset characteristics in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for distinguishing cytomegalovirus (CMV) infection.Methods:This retrospective study gathered data from allo-HSCT patients treated at Beijing Ludaopei Hospital between May 2021 and January 2023. This study included 50 patients in the CMV infection group and 47 patients in the non-CMV infection group. Flow cytometry was used to detect peripheral blood lymphocyte subsets 1 month after the allo-HSCT. The absolute lymphocyte count and their subsets were analyzed to assess their predictive significance in the occurrence of CMV infection. Mamn-whiney U test and χ 2 test were used. Indicators with statistical significance in univariate analysis were further subjected to binary logistic regression analysis and receiver operating characteristic (ROC) curves construction. The generation of survival curves for different outcomes was conducted using the Kaplan-Meier method, and the Log-rank test was applied. A two-sided P-value of<0.05 was considered statistically significant. Results:1. Among patients in the CMV infection group, 22% (11/50) were diagnosed with CMV viremia combined with CMV disease. The maximum CMV viral load in peripheral whole blood in these patients was 1 600 (1 400, 5 800) copies/ml, which was significantly higher than that in patients without confirmed CMV disease 970 (670, 2 300) copies/ml, with a statistically significant difference ( Z=-2.281, P=0.029). 2. The overall survival (OS) at the follow-up endpoint was 80% (40/50) in the CMV infection group and 87.2% (41/47) in the non-CMV infection group. There was no statistically significant difference in OS between the two groups at the follow-up endpoint ( χ2=0.231, P=0.630). 3. In the binary logistic regression model, the number of CD34 cells transfused into the patient, the percentage of CD3+CD38+T cells in CD3+T cells, and the percentage of CD4+CD38+T cells in CD4+lymphocytes were identified as important independent risk factors for infection. The ROC curve analysis demonstrated that the area under the curve (AUC) for these independent risk factors of CMV infection was 0.914 (>0.7, P<0.001), with a decision value of 0.702, a sensitivity of 0.857, and a specificity of 0.844. Conclusion:Followingallo-HSCT, the immune subsets in the CMV infection group exhibited a diminished proportion of T cells and CD4+T cells in comparison to the non-CMV infection group. In terms of T cell differentiation, there was an increase in TEM cells and a decrease in Naive T cells. Additionally, the expression level of the activation marker CD38 on T cells exhibited a high degree of predictive value for the occurrence of CMV infection. Understanding the immune characteristics of post-transplant CMV-infected patients is beneficial for the analysis of their immune reconstitution status, providing valuable insights for clinicians in the diagnosis and treatment of CMV infection after transplantation.

Objective:To investigate the significance and value of peripheral blood lymphocyte subset characteristics in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for distinguishing cytomegalovirus (CMV) infection.Methods:This retrospective study gathered data from allo-HSCT patients treated at Beijing Ludaopei Hospital between May 2021 and January 2023. This study included 50 patients in the CMV infection group and 47 patients in the non-CMV infection group. Flow cytometry was used to detect peripheral blood lymphocyte subsets 1 month after the allo-HSCT. The absolute lymphocyte count and their subsets were analyzed to assess their predictive significance in the occurrence of CMV infection. Mamn-whiney U test and χ 2 test were used. Indicators with statistical significance in univariate analysis were further subjected to binary logistic regression analysis and receiver operating characteristic (ROC) curves construction. The generation of survival curves for different outcomes was conducted using the Kaplan-Meier method, and the Log-rank test was applied. A two-sided P-value of<0.05 was considered statistically significant. Results:1. Among patients in the CMV infection group, 22% (11/50) were diagnosed with CMV viremia combined with CMV disease. The maximum CMV viral load in peripheral whole blood in these patients was 1 600 (1 400, 5 800) copies/ml, which was significantly higher than that in patients without confirmed CMV disease 970 (670, 2 300) copies/ml, with a statistically significant difference ( Z=-2.281, P=0.029). 2. The overall survival (OS) at the follow-up endpoint was 80% (40/50) in the CMV infection group and 87.2% (41/47) in the non-CMV infection group. There was no statistically significant difference in OS between the two groups at the follow-up endpoint ( χ2=0.231, P=0.630). 3. In the binary logistic regression model, the number of CD34 cells transfused into the patient, the percentage of CD3+CD38+T cells in CD3+T cells, and the percentage of CD4+CD38+T cells in CD4+lymphocytes were identified as important independent risk factors for infection. The ROC curve analysis demonstrated that the area under the curve (AUC) for these independent risk factors of CMV infection was 0.914 (>0.7, P<0.001), with a decision value of 0.702, a sensitivity of 0.857, and a specificity of 0.844. Conclusion:Followingallo-HSCT, the immune subsets in the CMV infection group exhibited a diminished proportion of T cells and CD4+T cells in comparison to the non-CMV infection group. In terms of T cell differentiation, there was an increase in TEM cells and a decrease in Naive T cells. Additionally, the expression level of the activation marker CD38 on T cells exhibited a high degree of predictive value for the occurrence of CMV infection. Understanding the immune characteristics of post-transplant CMV-infected patients is beneficial for the analysis of their immune reconstitution status, providing valuable insights for clinicians in the diagnosis and treatment of CMV infection after transplantation.

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.

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.

OBJECTIVETo study responses of physiological ecology and quality evaluation of Rehmannia glutinosa in continuous cropping.

METHODThe potted plant R. glutinosa which consists of first cropping, 1 year continuous cropping and 2 year continuous cropping were used as experimental materials. The photosynthetic activity, descending axis vitality, the protective enzymes system and MDA content were measured, the quality was evaluated by FTIR and HPLC.

RESULTContinuous cropping reduced the content of chlorophyll in the non-first cropping R. glutinos, the photosynthetic activity and descending axis vitality were weakened. Because of the increase of the free radical in the R. glutinos due to the continuous cropping, the activity of protective enzymes including POD, SOD and CAT were enhanced and MDA content were increased, more importantly the medical potency declined . And along with the increasing years of the continuous cropping, this effect becomes even stronger.

CONCLUSIONContinuous cropping affects the descending axis ability of absorbing water and nutrition and photosynthesis are inhibited R. glutinosa, at the same time, it also causes the disorders of antioxidation systems in R. glutinos, resulting in continuous cropping obstacle and decline of the medicinal materials quality.

Antioxidants ; metabolism ; Ecology ; Photosynthesis ; physiology ; Rehmannia ; enzymology ; growth & development ; metabolism ; physiology ; Superoxide Dismutase ; metabolism

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