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.

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.

Aim To investigate the effect of Li-Zhong-Tang (LZT) in the treatment of gastric ulcer (GU) with pattern of spleen-stomach vacuity cold in rats based on Raf/MEK/ERK signaling pathway and the underlying molecular mechanism. Methods SD rats were randomly divided into normal group, GU model group, esomeprazole (ESO) group, LZT low dose and high dose groups. The morphological changes of gastric mucosa were observed by naked eyes and HE staining. The activities of gastric acid and pepsin were measured. The contents of prostaglandin E

Sojae Semen Germinatum was firstly recorded in Shennong Bencaojing， and it has a long history of edible and medicinal use. Most ancient medical practitioners described that Sojae Semen Germinatum was processed with black soya bean， while some others recorded that Sojae Semen Germinatum was processed with black soya bean and soybean or with soybean only. In modern times， black soya bean and soybean are both used. Before the Northern and Southern dynasties， the germination process of Sojae Semen Germinatum was mostly soil culture， and then changed into water culture later. The medicinal part of Sojae Semen Germinatum may also change from the initial aboveground part to the whole processed products including the soybean and the bud. The bud length was used to control the processing ending of Sojae Semen Germinatum， but there were different views of the bud length in ancient and modern times. Before the Tang dynasty， Sojae Semen Germinatum was mostly used directly. Since the Tang dynasty， various subsequent processed products of Sojae Semen Germinatum appeared. Most ancient medical practitioners confirmed that Sojae Semen Germinatum was sweet flavor， neutral in nature and non-toxic， and the mainstream believed that it belonged to the spleen， lung and stomach meridians. However， there were different opinions on its efficacy of relieving exterior syndrome by diaphoresis. In this paper， the evolution of Sojae Semen Germinatum was explored after consulting all kinds of ancient books， its historical name， processing history， quality evaluation and others were systematically summarized in order to clarify its historical development and lay a good foundation for the clinical use and further development of Sojae Semen Germinatum.

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(
Case-Control Studies ; China/epidemiology* ; Female ; Growth and Development ; HIV ; HIV Infections/prevention & control* ; Humans ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy* ; Retrospective Studies

Objective:To investigate the association between shift work and the risk of lower extremity osteoarthritis.Methods:The study population came from the Dongfeng-Tongji cohort established in 2008. In September 2008, the Dongfeng Motor Company in Hubei Province was to recruit all retired workers who voluntarily participated in the survey as the research objects. During the follow-up conducted from April to October 2013, a total of 14 438 retired workers, i.e. all of the participants who underwent physical examination were investigated about demographic characteristics, lifestyles, occupation history, and lower extremity joint-related medical history, and additionally completed lower extremity joint examinations. After excluding individuals with missing data regarding lower extremity osteoarthritis, with the history of lower extremity joint trauma, or with history of rheumatoid arthritis (N=532), data from 13 906 participants was analyzed in the study. Multivariate logistic regression models were used to estimate the association between shift work and lower extremity osteoarthritis. After stratified by the duration of shift work, multivariate logistic regression models were used to analyze the relationship between the duration after leaving from shift work and lower extremity osteoarthritis.Results:Finally, a total of 13 906 retired employees included 7 560 (54.4%) females with a mean age of 64.74 (standard deviation 8.23) years old. 5 537 (39.8%) workers had ever engaged in shift work, including 2 004 (14.4%) workers with 1-9 years of shift work and 3 533 (25.4%) workers with ≥ 10 years of shift work. The prevalence of lower extremity osteoarthritis was 7.0%, while the prevalence of knee osteoarthritis and hip osteoarthritis were 6.7% and 0.7%, respectively. Compared with daytime workers, shift workers showed a 22% increase in the risk of lower extremity osteoarthritis ( OR=1.22, 95 %CI:1.06-1.40). Each 5-year increase in the duration of shift work was associated with a 4% increase in the risk of lower extremity osteoarthritis ( OR=1.04, 95 %CI:1.01-1.08). With the extension of the duration after leaving from shift work, the risk of lower extremity osteoarthritis decreased. Similar relationships were found between shift work and the risk of knee osteoarthritis, as well as hip osteoarthritis. Conclusion:Shift work was associated with the increased risk of lower extremity osteoarthritis.

Objective:To investigate the association between shift work and the risk of lower extremity osteoarthritis.Methods:The study population came from the Dongfeng-Tongji cohort established in 2008. In September 2008, the Dongfeng Motor Company in Hubei Province was to recruit all retired workers who voluntarily participated in the survey as the research objects. During the follow-up conducted from April to October 2013, a total of 14 438 retired workers, i.e. all of the participants who underwent physical examination were investigated about demographic characteristics, lifestyles, occupation history, and lower extremity joint-related medical history, and additionally completed lower extremity joint examinations. After excluding individuals with missing data regarding lower extremity osteoarthritis, with the history of lower extremity joint trauma, or with history of rheumatoid arthritis (N=532), data from 13 906 participants was analyzed in the study. Multivariate logistic regression models were used to estimate the association between shift work and lower extremity osteoarthritis. After stratified by the duration of shift work, multivariate logistic regression models were used to analyze the relationship between the duration after leaving from shift work and lower extremity osteoarthritis.Results:Finally, a total of 13 906 retired employees included 7 560 (54.4%) females with a mean age of 64.74 (standard deviation 8.23) years old. 5 537 (39.8%) workers had ever engaged in shift work, including 2 004 (14.4%) workers with 1-9 years of shift work and 3 533 (25.4%) workers with ≥ 10 years of shift work. The prevalence of lower extremity osteoarthritis was 7.0%, while the prevalence of knee osteoarthritis and hip osteoarthritis were 6.7% and 0.7%, respectively. Compared with daytime workers, shift workers showed a 22% increase in the risk of lower extremity osteoarthritis ( OR=1.22, 95 %CI:1.06-1.40). Each 5-year increase in the duration of shift work was associated with a 4% increase in the risk of lower extremity osteoarthritis ( OR=1.04, 95 %CI:1.01-1.08). With the extension of the duration after leaving from shift work, the risk of lower extremity osteoarthritis decreased. Similar relationships were found between shift work and the risk of knee osteoarthritis, as well as hip osteoarthritis. Conclusion:Shift work was associated with the increased risk of lower extremity osteoarthritis.

Sojae Semen Germinatum （SSG） was firstly recorded in Shennong Bencaojing. It is a dry processed product which is germinated using mature seeds of Glycine max. It is neutral in nature and sweet flavor， and its functions are to relieve heat， clear away heat and remove dampness. SSG has a long history of being used both as food and medicine， but it was not enrolled in the Chinese Pharmacopoeia until 2010. Doctors of different dynasties had different views of its processing procedures， and thus the quality of its decoction pieces is inconsistent. This article systematically straightened out the records of SSG in ancient books and modern literature， and summarized and analyzed the processing procedures， chemical constituents， quality analysis and pharmacological effects of SSG. It found that SSG contains proteins， isoflavones， saponins and other components， analytical methods for detecting these components include ultraviolet spectrophotometry （UV）， thin-layer chromatography （TLC）， high performance liquid chromatography （HPLC）， etc. It has effect such as antioxidant， anti-inflammatory， anti-osteoporosis， improvement of menopausal syndrome， treatment of cardiovascular diseases， and processing will change the type and content of its chemical components. Therefore， it is necessary to dig out active constituents of SSG， explore those changes in chemical constituents and pharmacological effect during the period of its primary and subsequent processing， and explore its action mechanism. This paper can provide the theoretical basis for standardized processing procedure， modern quality control and clinical application of SSG.

Objective To investigate current situation of Chinese clinical microbiological laboratories participating in management of healthcare-associated infection and antimicrobial use.Methods Fourteen provinces (municipalities), autonomous regions and army hospitals in seven regions of China were selected, the participation of clinical microbiological laboratories in the consultation of HAI diseases, specimen quality control, antimicrobial use, and management of multidrug-resistant organisms (MDROs) before 2000 and every five years from 2000 to 2015 were investigated, the surveyed results were analyzed statistically.Results A total of 187 hospitals were investigated, in 2015, 96 and 172 hospitals (51.34％, 91.98％) participated in the consultation of infectious diseases and multi-department collaborative management on MDROs respectively.However, 44 hospitals (23.53％) still manually performed statistical analysis on drug susceptibility, only 26 hospitals (13.90％) had the ability of identifying homology of pathogens.Rate of MDRO surveillance data feedbacked to clinical departments increased from 66.84％ (n=125) in 2010 to 95.72％ (n=179) in 2015, the frequency of feedback was mainly monthly and quarterly;rate of antimicrobial susceptibility results feedbacked to clinic departments increased from 62.03％ (n=116) to 94.12％ (n=176), 82.35％ (n=154) of clinical microbiological laboratories conducted quarterly feedback;the quality control rate of microscopic sputum smear before sputum culture increased from63.10％ (n=118) to 87.17％ (n=163);rate of bilateral double blood culture increased from 35.83％ (n=67) to 72.73％ (n=136);rates of other aseptic body fluid culture (except blood and urine) increased from 4.86％ to 5.74％;differences were all significantly different between 2010 and 2015 (all P＜0.05).Conclusion Clinical microbiological laboratories have played an important role in promoting the development of HAI management in China, especially during the period of 2011-2015.However, the homology analysis on HAI pathogens, informatization of result feedback, and sterile body fluid specimens detection need to be further strengthened.

Objective: To investigate the value of ultrasound in the localization of peripherally inserted central catheter (PICC) in neonates. Methods: A retrospective analysis of the PICC catheterization was conducted at Department of Neonatology, Beijing Chaoyang District Maternal and Child Healthcare Hospital from June 2017 to December 2018.The ultrasound monitoring was performed immediately after PICC catheterization.The probe was placed into the midline position of the lower xiphoid or the subclavian parasternal line for scanning, and it would be the PICC if a high-echo " equal sign" was observed by ultrasound.It was believed that the PICC was successfully placed when ultrasound detected that the PICC tip was located in the junction of inferior vena cava or superior vena cava in the right atrium. Results: (1)Among 112 infants with PICC catheterization, 103 cases (92.0%) were accurately placed, 9 cases (8.0%) were not placed in the ideal site, among them, 2 cases were too deep, 4 cases were too shallow and 3 cases were catheter heterotopia.The tip position was accurate after the readjustment under ultrasound monitoring in those patients whose the first ultrasound showed the tip position was not ideal.(2)The PICC indwelling time was as short as 2 days (removed due to severe arrhythmia) and as long as 56 days with an average of (15.1±10.7) days.(3)The catheter-related complications occurred in 3 cases with an incidence of 2.7%. Conclusions Using ultrasound to determine the PICC tips position is accurate and reliable, which is worthy of extensive application in the neonatal wards.