Oxamate alleviates silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cells / 环境与职业医学

Background The senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear. Objective To explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethods This study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO2 suspension (100 mg·mL−1). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L−1 and 1125 mmol·L−1). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO2. The in vitro experimental groups were ① SiO2 induction groups: control group, 50 μg·mL−1 SiO2 group, 100 μg·mL−1 SiO2 group, and 200 μg·mL−1 SiO2 group, and ② oxamate treatment groups: control group, SiO2 group (100 μg·mL−1), low-dose oxamate (25 mmol·L−1) treatment group, and high-dose oxamate (50 mmol·L−1) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting. Results Compared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO2-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO2-induced group (P＜0.05). Compared with the SiO2 group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). Conclusion Lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Progress of gene-mediated precision immunotherapy in the treatment of acute myeloid leukemia / 中国药科大学学报

@#Acute myeloid leukemia (AML) is a disease caused by abnormal cloning of hematopoietic stem cells in the bone marrow, which leads to accumulation of a large number of abnormally differentiated myeloid cells. It is difficult to cure by traditional treatment. The successful application of chimeric antigen receptor T cell (CAR-T) immunotherapy indicates that the treatment of hematological tumors has entered a new stage of precision immunotherapy. However, CAR-T immunotherapy has been found to have many problems in clinical applications, including long treatment cycle, expensive prices, off-target effects, cytokine release syndrome, etc. Therefore, it is necessary to expand the application of CAR or adopt improved measures to enhance the therapeutic effect. This article reviews the new strategies for genetic engineering modification of CAR immune cells and the research progress and application of in situ programming to generate CAR-T, and besides, briefly introduces the new methods about the delivery of gene drugs in vivo, aiming to provide new ideas and theoretical basis for expanding and improving the application of precision immunotherapy in AML.

Level of serum lipoprotein a in patients with diffuse large B-cell lymphoma and its impact on prognosis / 白血病·淋巴瘤

Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.

A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis / 中华医学杂志(英文版)

BACKGROUND@#Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.@*METHODS@#We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.@*RESULTS@#The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.@*CONCLUSION@#The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 .@*TRIAL REGISTRATION@#No. NCT00454519 ( https://clinicaltrials.gov/ ).

Role of PPARγ in Ulcerative Colitis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a chronic inflammatory bowel disease primarily affecting the colon and rectum， with the typical symptoms such as abdominal pain， bloody diarrhea， and tenesmus. The pathogenesis of UC remains to be fully elucidated. The disease is prone to recurrence， seriously affecting the patients' quality of life. Conventional therapies for UC have limitations， including unsatisfactory clinical efficacy， lengthy courses， and adverse reactions. Therefore， there is an urgent need to explore new therapeutic agents. Peroxisome proliferator-activated receptor gamma （PPARγ）， a ligand-dependent nuclear receptor protein that plays a crucial role in maintaining intestinal homeostasis， is closely associated with the onset and development of UC. Traditional Chinese medicine （TCM） has advantages such as multi-targeting and mild side effects in the treatment of UC. Recent studies have shown that TCM can exert the therapeutic effects on UC by modulating PPARγ. The TCM methods for regulating PPARγ include clearing heat， drying dampness， moving Qi， activating blood， resolving stasis， invigorating the spleen， warming the kidney， and treating with both tonification and elimination. On one hand， TCM directly activates PPARγ or mediates signaling pathways such as nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， Toll-like receptor 4 （TLR4）， and regulates helper T cell 17 （Th17）/regulatory T cell （Treg） balance to promote macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype， thereby inhibiting intestinal inflammation. On the other hand， TCM regulates the intestinal metabolism to activate PPARγ， lower the nitrate level， and maintain local hypoxia. In this way， it can restore the balance between specialized anaerobes and facultative anaerobes， thereby improving the gut microbiota and treating UC. This article summarizes the role of PPARγ in UC and reviews the research progress of TCM in treating UC by intervening in PPARγ in the last five years， aiming to give insights into the treatment and new drug development for UC.

The number of FOXP3+regulatory T cells (Tregs) decreased and transformed into RORγt+FOXP3+Tregs in lung tissues of mice with bronchopulmonary dysplasia / 细胞与分子免疫学杂志

Objective To explore the phenotypic conversion of regulatory T cells (Tregs) in the lungs of mice with bronchopulmonary dysplasia (BPD)-affected mice. Methods A total of 20 newborn C57BL/6 mice were divided into air group and hyperoxia group, with 10 mice in each group. The BPD model was established by exposing the newborn mice to hyperoxia. Lung tissues from five mice in each group were collected on postnatal days 7 and 14, respectively. Histopathological changes of the lung tissues was detected by HE staining. The expression level of surfactant protein C (SP-C) in the lung tissues was examined by Western blot analysis. Flow cytometry was performed to assess the proportion of FOXP3+ Tregs and RORγt+FOXP3+ Tregs in CD4+ lymphocytes. The concentrations of interleukin-17A (IL-17A) and IL-6 in lung homogenate were measured by using ELISA. Spearman correlation analysis was used to analyze the correlation between FOXP3+Treg and the expression of SP-C and the correlation between RORγt+FOXP3+ Tregs and the content of IL-17A and IL-6. Results The hyperoxia group exhibited significantly decreased levels of SP-C and radical alveolar counts in comparison to the control group. The proportion of FOXP3+Tregs was reduced and that of RORγt+FOXP3+Tregs was increased. IL-17A and IL-6 concentrations were significantly increased. SP-C was positively correlated with the expression level of RORγt+FOXP3+ Tregs. RORγt+FOXP3+ Tregs and IL-17A and IL-6 concentrations were also positively correlated. Conclusion The number of FOXP3+ Tregs in lung tissue of BPD mice is decreased and converted to RORγt+ FOXP3+ Tregs, which may be involved in hyperoxy-induced lung injury.

Mechanism of Taohong Siwutang Alleviating Myocardial Ischemia Reperfusion Injury in Ovariectomized Mice by Up-regulating Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Taohong Siwutang （TSD） on myocardial ischemia reperfusion injury （MIRI） in ovariectomized （OVX） female mice. MethodAfter the OVX model of female mice was established， the estradiol （E2） level was detected by enzyme-linked immunosorbent assay （ELISA） to verify the model. Sixty OVX mice were randomly divided into six groups： Sham operation group， model group， low， medium， and high dose groups （9， 18， 36 g·kg-1） of TSD， and nuclear factor E2-related factor 2 （Nrf2） inhibitor group， with 10 mice in each group. The MIRI model was verified by a laser speckle flowmeter. The pathological changes in myocardial tissue were detected by 2，3， 5-triphenyltetrazolium chloride （TTC） and hematoxylin-eosin （HE） staining. Serum creatine kinase isoenzyme （CK-MB）， cardiac troponin Ⅰ （CTnⅠ）， malondialdehyde （MDA）， superoxide dismutase （SOD）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） levels were detected by ELISA. The expression of Nrf2 and heme oxygenase-1 （HO-1） were observed by immunofluorescence staining. The expressions of Nrf2， HO-1， apoptotic B-cell lymphomato-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， inflammatory cytokines interleukin-18 （IL-18）， and interleukin-1β （IL-1β） were detected by Western blot. ResultCompared with the sham operation group， the serum levels of CK-MB， CTnⅠ， MDA， and IL-6 in the model group were increased （P<0.01）， and the levels of SOD and IL-10 were decreased （P<0.01）. The damage scores of TTC and HE staining in myocardial tissue were increased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were decreased （P<0.01）， and the protein expressions of Nrf2， HO-1， and Bcl-2 in myocardial tissue were decreased. The protein expressions of Bax， IL-18， and IL-1β were increased （P<0.01）. Compared with the model group， serum levels of CK-MB， CTnⅠ， MDA， and IL-6 of TSD groups were significantly decreased （P<0.05， P<0.01）， and SOD and IL-10 were significantly increased （P<0.05， P<0.01）. TTC staining and HE staining damage scores of myocardial tissue were significantly decreased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were increased （P<0.01）. The protein expressions of Nrf2， HO-1， and Bcl-2 were significantly increased （P<0.05， P<0.01）， and those of Bax， IL-18， and IL-1β were significantly decreased （P<0.05， P<0.01）. The effect of the high dose group of TSD was the most significant. The serum levels of CK-MB， CTnⅠ， MDA， and IL-6 in the Nrf2 inhibitor group were significantly increased （P<0.05， P<0.01）， and the levels of SOD and IL-10 were significantly decreased （P<0.05， P<0.01）. The damage scores of TTC and HE staining in myocardial tissue were significantly increased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were significantly decreased （P<0.01）. The protein expressions of Nrf2， HO-1， and Bcl-2 in myocardial tissue were significantly decreased， and those of Bax， IL-18， and IL-1β were significantly increased （P<0.01）. ConclusionTSD can alleviate MIRI in OVX mice， reduce oxidative stress response and the release of inflammatory factors， and inhibit apoptosis， playing a protective role in OVX mice with MIRI， which may be related to the activation of Nrf2/HO-1 signaling pathway.

Review and Prospect of Development Status of Traditional Chinese Medicine Processing Technology from 1.0 to 4.0 / 中国实验方剂学杂志

The development and application of processing technology is closely related to the quality of Chinese medicine. Currently， Chinese medicine processing is still in the mechanization stage with limited processing equipment， low levels of automation and intelligence. As a result， the imprecise control of parameters during processing leads to unstable quality of Chinese herbal pieces. However， with the arrival of the big data era and the continuous development of "Internet+"， Chinese medicine processing technology and equipment have been continuously improved and updated， and gradually shifted to the development direction of automation and intelligence. The linkage production technology of Chinese herbal pieces optimizes the separate processing equipment coupling into the production line for continuous manufacture of Chinese herbal pieces， intending to improve production efficiency. The large-scale industrialized production of Chinese herbal pieces tends towards digital technology of processing experience and online inspection technology based on machine vision， electronic nose， and electronic tongue. These technologies are crucial prerequisites for standardizing the parameters of Chinese medicine processing. And further by docking the processing process and equipment with the internet， realizing the intelligent control of the production process is an important process for the transformation and upgrading of Chinese herbal piece industry in the future. In this paper， we summarized the development characteristics of different stages of Chinese medicine processing technology， combed application and development of processing theory， the evolution of processing equipment， and problems in the current industrial development stage of Chinese medicine processing， in order to provide ideas and methods for achieving digital and intelligent innovation of processing technology as well as high-efficient and high-quality production of Chinese herbal pieces.

Expression and Correlation Analysis of Serum miR-497-5p and FGF-2 in Patients with Alzheimer's Disease / 医学研究杂志

Objective To investigate the expression level,diagnostic value and correlation of miR-497-5p and human fibroblast growth factor-2(FGF-2)in patients with Alzheimer's disease(AD).Methods The clinical data of 50 patients with first diagnosed AD and 37 normal subjects(control group)were collected,among which AD patients were divided into mild AD group(n=18),moder-ate AD group(n=18)and severe AD group(n=14).The expression level of miR-497-5p was detected by real-time quantitative polymerase chain reaction(RT-qPCR)and FGF-2 was detected by enzyme-linked immunosorbent assay(ELISA).Mini-mental state examination(MMSE)was used to evaluate the cognitive function of AD patients,and the correlation between miR-497-5p and MMSE and FGF-2 levels was analyzed.The diagnostic efficacy of miR-497-5p and FGF-2 levels for AD was evaluated using receiv-er operator characteristic(ROC)curve.Results Compared with the control group and mild AD group,the expression levels of miR-497-5p in moderate and severe AD groups were significantly increased(P＜0.01),and the level of FGF-2 was significantly decreased(P＜0.01).MiR-497-5p in AD group was negatively correlated with MMSE score and FGF-2 level(r were-0.724 and-0.748,P＜0.01).ROC curve analysis results showed that miR-497-5p,FGF-2 and their combined indexes had higher area under the curve,sensitivity and specificity in the diagnosis of moderate and severe AD and in the differentiation of mild and moderate AD,as well as mild and severe AD,and the combined indexes of miR-497-5p and FGF-2had the best diagnostic and differential efficacy.Conclusion Serum miR-497-5p is up-regulated and FGF-2 level is down-regulated in patients with moderate and severe AD.The combined detection of miR-497-5P and FGF-2has certain diagnostic value for moderate and severe AD and provides certain reference.

GC Fingerprint and Multi-component Content Determination of Xiangsha Yangwei / 医药导报

Objective To establish the method of fingerprint and content determination of multi-component for Xiangsha Yangwei pill by gas chromatography(GC).Methods The GC fingerprint of Xiangsha Yangwei pill was found,and the peak attribution was carried out.The contents of limonene,eucalyptol,camphor,borneol,bornyl acetate,patchouli alcohol,pogostone,and α-cyperone were determined.Results The fingerprint similarity of 56 batches of Xiangsha Yangwei pill were 0.33-0.99,28 common peaks were confirmed,and 14 known components were identified.Limonene,eucalyptol,camphor,borneol,bornyl acetate,patchouli alcohol,pogostone and α-cyperone showed good linearity within the determined ranges(14.30-286.08,24.52-490.44,16.14-322.88,9.40-187.95,15.39-307.83,25.78-515.60,19.95-398.90,and 24.87-497.30 μg·mL-1).The average recoveries were 101.20％,97.90％,93.97％,94.23％,102.94％,100.54％,99.16％,and 98.31％;with the RSDs were 2.41％,1.48％,1.65％,2.00％,1.93％,2.30％,2.07％,and 2.38％,respectively.The concentrations of eight components were 0.2-959.1,0.3-420.4,1.0-542.6,0.0-64.5,0.0-364.2,0.0-339.6,0.0-130.7,0.0-82.0 μg·g-1,respectively.Conclusion The fingerprint and multi-component determination method can be used for the quality control and evaluation of Xiangsha Yangwei pill.

Low intensity pulsed ultrasound suppressed the proliferation of fibroblast-like synoviocytes in rheumatoid arthritis through p38/JNK-interleukin-6 trans-signaling pathway / 中国康复医学杂志

Objective:To explore the effect of low intensity pulsed ultrasound(LIPUS)on inhibiting the abnormal cell phenotype of fibroblast-like synoviocytes in rheumatoid arthritis(RA-FLS)and possible mechanism. Method:Synoviocytes were isolated by using enzyme digestion,and the morphology of cells was observed un-der microscope.At the same time,the expression of Vimentin protein was detected by immunofluorescence method to identify RA-FLS.Cells cultured in vitro were divided into four groups:control group,LIPUS group,tumor necrosis factor(TNF-α)group and TNF-α+LIPUS group or three groups:control group,interleu-kin-6(IL-6)group and IL-6+LIPUS group.The effects of LIPUS on RA-FLS cell viability and proliferation were detected by CCK8 and EDU assay respectively,and the effects of LIPUS on RA-FLS migration were ob-served by scratch test and Transwell migration assay.RT-qPCR was used to detect the gene expression of im-portant cytokines,chemokines and matrix metalloproteinases(MMPs)in RA-FLS.ELISA was used to further detect the effect of LIPUS on the expression of IL-6,a key effector of RA-FLS,and the effects of LIPUS on mitogen-activated protein kinase(MAPK)signaling pathway in RA-FLS were detected by Western Blot. Result:Purified RA-FLS were obtained.Firstly,LIPUS could suppress the cell activity(P＜0.00l)and prolifer-ation(P=0.007)induced by TNF-α in RA-FLS cultured in vitro.However,the migration and the transcription levels of MMPs related to migration(MMP2 and MMP9)were not significantly different between groups(P＞0.05).LIPUS could inhibit the high expression of IL-6 and interleukin-8(IL-8)at the mRNA level in the in-flammatory environment induced by TNF-α(P＜0.001),but there was no significant difference in the suppres-sion of interleukin-1β(IL-1β),MMP1 and MMP13(P＞0.05).In addition,compared with untreated group,LI-PUS could inhibit the secretion of IL-6 in RA-FLS induced by TNF-α(P＜0.001),and also inhibited the pro-liferation of RA-FLS induced by IL-6(P-0.003).Finally,LIPUS could inhibit the phosphorylation of p38 MAPK and c-Jun N-terminal kinase(JNK)in MAPK signaling pathway(P=0.033),but the effect on the phosphorylation of extracellular signal-regulated kinas 1/2(ERK1/2)was not significantly(P＞0.05). Conclusion:LIPUS could reduce the abnormal proliferation of RA-FLS in inflammatory state without affecting its migration,which might be related to the inhibition of p38/JNK-IL-6 signaling pathway.

Abnormal blood transfusion compatibility test results caused by delayed hemolytic reaction: a case report and transfusion strategy / 中国输血杂志

【Objective】 To investigate the blood transfusion compatibility test results of a child with thalassemia after delayed hemolysis reaction, and to formulate transfusion strategies based on other clinical data to ensure the safety of clinical blood use. 【Methods】 A comprehensive analysis was conducted on the transfusion compatibility test results of a child with thalassemia, combined with Rh blood type system detection, blood transfusion history, serum bilirubin changes, clinical symptoms and other data to determine the occurrence of delayed hemolytic reaction, and formulate the subsequent appropriate blood matching strategies. 【Results】 On admission, the blood type of the patient was B DccEE, with hemoglobin (Hb) 38 g/L, reticulocyte ratio (Ret%) 2.92%, total bilirubin (TBil) 65.8 μmol/L, direct bilirubin (DBil) 12.0 μmol/L, indirect Bilirubin (IBil) 53.8 μmol/L, negative for unexpected antibody screening, no agglutination or hemolysis on both primary and secondary sides of the cross-matching over with type B DCcEe donors, negative for direct anti human globulin test(DAT), negative for indirect anti human globulin test (IAT), lactate dehydrogenase(LDH) 1 050 U/L, aspartate aminotransferase(AST) 113 U/L, urine occult blood 2+, urine bilinogen 4+, and a history of red blood cell transfusion 5 days before admission. The above results indicated that the child had a delayed hemolytic reaction, then type B DccEE leukocyte-depleted suspension red blood cell was transfused, and various indicators improved after transfusion. 【Conclusion】 Appropriate blood matching strategies should be formulated based on the results of blood transfusion compatibility testing and other clinical data before transfusion for children with thalassemia in order to effectively ensure transfusion safety.

Influencing Factors of Inter-arm Systolic Blood Pressure Differences in Hypertensive Population Aged 40 Years and Younger / 中国循环杂志

Objectives:To explore the influencing factors of inter-arm systolic blood pressure difference(sIAD)in young hypertensive population. Methods:A total of 12 895 young Kailuan employees aged≤40 years,who participated in the physical examination from 2010 to 2020,were enrolled in this study.All of them underwent blood pressure measurements of four limbs in supine position.Young hypertensive group(n=3 584)and young non-hypertensive group(n=3 584)were 1∶1 matched by sex and age(±1 year),and participants were further divided into sIAD＜10 mmHg(1 mmHg=0.133 kPa)and sIAD≥10 mmHg subgroups.A stepwise multivariate logistic regression model was established to analyze the determinants of sIAD≥10 mmHg. Results:The detection rate of sIAD≥10 mmHg was significantly higher in the young hypertensive group than in the young non-hypertensive group(31.72%vs.27.76%,P＜0.001).Stepwise multivariate logistic regression analysis showed that in young hypertensive population,ankle-brachial index(ABI)＜0.9,male,obesity,overweight,elevated low density lipoprotein cholesterol(LDL-C)level,and systolic blood pressure were positively associated with sIAD≥10 mmHg,while college education or above,physical exercise were negatively correlated with sIAD≥10 mmHg(all P＜0.05).In the young non-hypertensive population,ABI＜0.9,systolic blood pressure were positively correlated with sIAD≥10 mmHg,while age was negatively associated with sIAD≥10 mmHg(all P＜0.05). Conclusions:The detection rate of sIAD≥10 mmHg is higher in young hypertensive population than in young non-hypertensive population.Decreased ABI,male sex,obesity,overweight,increased LDL-C level,systolic blood pressure,college education and above,and physical exercise are the influencing factors of sIAD≥10 mmHg in young hypertensive population.

Study on Ecological Suitability of Scutellaria baicalensis Georgi in China Based on MaxEnt Model / 中国中医药信息杂志

Objective To understand the distribution of ecological suitability of Scutellaria baicalensis Georgi;To screen the main ecological factors affecting its distribution;To predict its suitable planting area in China.Methods A total of 231 batches of Scutellaria baicalensis Georgi were collected through the fourth national survey of TCM resources.The environment information of sampling points were recorded,and 55 ecological factors were analyzed by MaxEnt model and GIS.Results Rainfall,vegetation type and soil types had a greater influence on the distribution of Scutellaria baicalensis Georgi.The ecological suitable areas of Scutellaria baicalensis Georgi mainly concentrated in the eastern part of Shaanxi Province,the western part of Hebei Province and most areas of Chengde,the most part of Shanxi Province,the western part of Beijing,the western part of Liaoning Province,the central and eastern part of Shandong Province,the junction of Jiangsu and Anhui Province,the northern part of Yunnan Province,and the eastern and southern part of Sichuan Province.Conclusion The ecological suitability areas of Scutellaria baicalensis Georgi were classified in this study,and the results could provide reference for the selection of cultivation areas of Scutellaria baicalensis Georgi.

Evaluation of Burosumab in the treatment of X-linked hypophosphatemic rickets in children / 中华内分泌代谢杂志

Objective:To evaluate the efficacy and safety of Burosumab in patients with X-linked hypophosphatemic rickets.Methods:Clinical data of 9 children diagnosed with X-linked hypophosphatemic rickets and treated with Burosumab in the Department of Pediatric Nephrology, Anhui Children′s Hospital from November 2021 to September 2023 were retrospectively analyzed, including the general information, clinical manifestations, auxiliary examination, Burosumab treatment and follow-up.Results:Among the 9 cases, there were 5 males and 4 females, with a median age at diagonosis of 2 years. After traditional treatment, the fluctuation of serum phosphorus ranged from 0.7 to 0.9 mmol/L. The median age at the initiation of Burosumab treatment was 2.8 years, and the initial dosage was 0.8 mg/kg, administrated subcutaneously every 2 weeks. The laboratory and imaging indexes were improved after 6 months of Burosumab treatment, and the mean serum phosphorus level increased from(0.81±0.14) mmol/L to(1.02±0.10) mmol/L at 1 month( t=3.85, P=0.001) and(1.14±0.25) mmol/L at 6 months( t=3.58, P=0.002). The average alkaline phosphatase(ALP) level decreased from(509.89±110.10) U/L before treatment to(447.89±106.76) U/L after 1 month( t=1.21, P=0.243). After 6 months, the ALP level significantly decreased to(385.89±60.33) U/L ( t=2.96, P=0.009). The average height percentile increased from 18.42±10.09 before treatment to 26.56±16.59 after 6 months( t=1.26, P=0.227). Rachitis severity scores of both lower limbs ranged from 4.61±1.36 before treatment to 3.06±1.51 after 6 months( t=2.29, P=0.036). No serious adverse events occurred during treatment. Conclusion:Burosumab is safe and effective in treating X-linked hypophosphatemic rickets, exhibiting minimal side effects and significant clinical applicability value.

Study on formulation and revision of detection methods of "Standards for indoor air quality (GB/T 18883-2022)" in China / 中华预防医学杂志

The formulation and revision of the detection methods of indoor air quality standards is an important, rigorous and delicate endeavor. This paper introduced the formulation and revision of the detection methods of the standards for indoor air quality (GB/T 18883-2022), focusing on the revision process, revision principles, main adjustments and technical points of some key indicators to facilitate users to better understand and apply the detection methods in standards for indoor air quality (GB/T 18883-2022).

Impact of neferine on airway inflammation in asthmatic young rats by regulating cGAS-STING signal pathway / 免疫学杂志

This study was performed to analyze the impact of neferine on airway inflammation in young rats with asthma,and its effect on cGAS-STING signal pathway.Total of 50 SD rats were randomly grouped into control group,model group,low-dose neferine group(20 mg/kg),high-dose neferine group(40 mg/kg),high-dose neferine+ 2'3'-cGAMP group(40 mg/kg neferine+500 μg/kg 2'3'-cGAMP).In addition to the control group,asthma models were established in all other groups.ELISA was used to measure the levels of CysLTs and CysLTR1 in the bronchoalveolar lavage fluid of rats;HE staining and PAS staining were performed on the lung tissue of rats to evaluate the formation of goblet cells and the inflammatory infiltration around the bronchus and blood vessels;the levels of IL-4 and IFN-γ in lung tissue were measured with ELISA kits;the levels of cGAS-STING pathway related proteins in lung tissue were detected by Western blotting.Compared with the control group,a large number of inflammatory cells infiltrated into the inner wall of bronchi and blood vessels,and goblet cells proliferated obviously in the model group;the airway inflammation of rats in the two neferine groups were reduced;compared with the high-dose neferine group,the airway inflammation of rats in the high-dose neferine+2'3'-cGAMP group was aggravated.Compared with the control group,the levels of CysLTs and CysLTR1 in the alveolar lavage fluid,lung inflammation score,mucus score,IL-4 level,and the expression of cGAS and STING proteins in lung tissue of the model group were increased,while the level of IFN-γ in lung tissue was decreased(P<0.05).Neferine(both low-dose and high-dose)could reverse these changes mentioned above in model rats(P<0.05),in a dose-dependent manner.While 2'3'-cGAMP could suppress these effects of neferine(P<0.05).Taken together,neferine may alleviate airway inflammation in neonatal asthmatic rats by inhibiting the activation of cGAS-STING pathway.

Inhibitory effects of 1% atropine on form deprivation-induced myopia development in guinea pigs and its mechanism / 中华实验眼科杂志

Objective:To observe the prevention and control effect of 1% atropine on the progression of form deprivation myopia (FDM) in guinea pigs and the potential biological mechanism.Methods:Sixty-nine 3-week-old tricolor guinea pigs with normal refraction were randomly divided into a normal control group ( n=19), a FDM group ( n=19), a FDM+ atropine group ( n=19), and an atropine group ( n=12). No intervention was given to guinea pigs in normal control group.The FDM model was established by covering the right eye of guinea pigs with a semitransparent latex facemask for 4 weeks in FDM and FDM+ atropine groups.For the FDM+ atropine group, 1% atropine gel was topically administered to the form-deprived right eyes once a day for 4 weeks.For the atropine group, the right eye was treated with 1% atropine gel once a day for 4 weeks.Refraction and axial length of guinea pigs were measured by retinoscopy and ophthalmic A-scan ultrasonography respectively at baseline, experiment week 2 and week 4.In experiment week 4, eyeballs were enucleated to make sections via the paraffin wax processing procedure, and the microstructural and ultrastructural changes of the sclera were observed under the light microscope and transmission electron microscope, respectively.The isobaric tags for relative and absolute quantitation labeling combined with liquid chromatography-tandem mass spectrometry were used to identify the differentially expressed proteins.Use and care of the animals complied with the Regulation for the Administration of Affairs Concerning Experiment Animals by State Science and Technology Commission.The study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.TJYY2020111028). Results:There were statistically significant differences in the diopter of guinea pigs at different time points among the four groups ( Fgroup=138.892, P<0.001; Ftime=167.270, P<0.001). Compared with normal control group, the diopter of guinea pigs in FDM group at experiment weeks 2 and 4, and FDM+ atropine group at experiment week 4 developed toward myopia, showing statistically significant differences (all at P<0.001). Compared with FDM group, the diopter of guinea pigs in FDM+ atropine group at experiment weeks 2 and 4 developed toward hyperopia, showing statistically significant differences (both at P<0.001). There were statistically significant differences in the axial length of guinea pigs at different time points among the four groups ( Fgroup=32.346, P<0.001; Ftime=353.797, P<0.001). The axial lengths of FDM group at experiment weeks 2 and 4 and FDM+ atropine group at experiment week 4 were longer than those of normal control group, and the axial lengths in FDM+ atropine group at experiment weeks 2 and 4 were shorter than those in FDM group, and the differences were statistically significant (all at P<0.001). The collagenous fibers of posterior sclera of guinea pigs were loose and disordered in FDM group, and were regular in FDM+ atropine group.The posterior scleral thickness of normal control group, FDM group, FDM+ atropine group and atropine group was (141.74±16.98), (101.46±9.15), (112.74±6.24) and (134.30±18.19) μm, respectively, with a statistically significant difference ( F=6.709, P=0.005). The posterior sclera was significantly thinner in FDM group than in normal control group and FDM+ atropine group (both at P<0.05). The diameter of posterior scleral collagen fiber gradually increased from inside to outside in normal control group, FDM+ atropine group and atropine group, and the diameters of the inner, middle and outer posterior scleral collagen fibers were smaller in FDM group than in normal control group.Proteomic analysis revealed 85 differentially expressed proteins (fold change>1.30) between FDM group and normal control group, FDM+ atropine group and FDM group, of which 38 were up-regulated and 47 were down-regulated after atropine treatment.Gene Ontology enrichment analysis showed that biological processes mainly involved were biological regulation, cell process, localization and metabolic process.Molecular function mainly involved were binding, catalytic activity, molecular function regulator, structural molecule activity and transporter activity.Cell components mainly involved were in cellular anatomical entity, intracellular and protein-containing complex. Conclusions:Atropine can increase the diameter of scleral collagen fibers in guinea pigs of FDM model, improve the arrangement of scleral collagen fiber, inhibit scleral thinning.The mechanism of atropine to control myopia progression is closely related to the tight junction between scleral cells, cytoskeleton and extracellular matrix remodeling.

Effects of short-term use of atropine with different concentrations and frequencies on eye safety in children / 中华实验眼科杂志

Objective:To evaluate the effect of short-term topical administration of atropine eye drops with various concentrations and frequencies on eye safety in children.Methods:A double-blind randomized controlled trial was conducted.Sevevty-two children with ametropia or pre-myopia (72 eyes) were enrolled in Tianjin Medical University Eye Hospital from December 2020 to January 2022.The subjects were randomly divided into 0.01% atropine group, 0.02% atropine group and 0.04% atropine group according to a random number table, with 24 cases (24 eyes) in each group.Automatic refraction with an automatic computer optometry device, subjective refraction with a phoropter, intraocular pressure with a non-contact tonometer, axial length by optical biometrics, the amplitude of accommodation (AMP) by the push-up method, pupil diameter with pupilometer, near visual acuity at 33 cm with a standard logarithmic visual acuity chart, tear evaluation with Keratograph 5M and Ocular Surface Disease Index (OSDI) questionnaire survey were performed among all subjects.One drop of 0.01%, 0.02%, and 0.04% atropine was administrated to the study eye according to grouping, and the pupil diameter was measured every 10 minutes until the pupil did not enlarge three times, then the data after a single treatment of the three groups were recorded.After one-week application of the corresponding concentration of atropine eye drops once at night, the data after one-week treatment were recorded.For the next week, the application frequency of 0.01% and 0.02% atropine groups changed to once daily in the morning and evening, and 0.04% atropine group maintained once at night, then the data after two-week treatment were recorded.Data of the right eyes were analyzed.The changes in pupil diameter, AMP and other eye parameters before and after atropine eye drops of the three groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-51). All subjects and their guardians were fully informed of the method and purpose of this study before entering the cohort.Written informed consent was obtained from guardians.Results:Pupil diameters of 0.01%, 0.02% and 0.04% atropine groups were (5.59±0.48), (5.35±0.76) and (5.65±0.43)mm before treatment respectively, (7.00±0.68), (7.17±0.58) and (8.40±1.71)mm after a single treatment, (6.67±0.62), (6.56±0.65) and (7.60±0.69)mm after one-week treatment, (6.96±0.49), (7.04±0.53) and (7.60±0.36)mm after two-week treatment.There were significant differences in pupil diameter at different time points after treatment among the three groups ( Fgroup=9.430, P<0.001; Ftime=156.620, P<0.001). The AMP of 0.01%, 0.02% and 0.04% atropine groups were (12.94±3.02), (13.25±2.81) and (13.42±2.60)D before treatment respectively, (11.62±2.61), (11.53±2.06) and (9.64±1.93)D after a single treatment, (11.14±2.61), (11.33±2.33) and (8.30±1.18)D after one-week treatment, (9.99±1.81), (8.72±1.25) and (8.76±2.12)D after two-week treatment.There was no significant difference in the AMP among the three groups ( Fgroup=2.800, P=0.063). In the three groups, the AMP at different time points after treatment were significantly lower than that before treatment ( Ftime=61.400, P<0.001). There was no difference in spherical equivalent refraction, intraocular pressure, near visual acuity, axial length, first none-invasive tear break-up time, average none-invasive tear break-up time, tear meniscus height and OSDI score among the three groups ( Fgroup=0.030, 0.630, 1.420, 0.580, 0.140, 0.120, 0.340, 0.142; all at P>0.05). There were significant differences in spherical equivalent refraction, intraocular pressure, first none-invasive tear break-up time, average none-invasive tear break-up time, tear meniscus height and OSDI score at different time points between before and after medication among the three groups ( Ftime=12.560, 4.730, 4.720, 5.220, 3.720; all at P<0.05). Conclusions:Varying pupil dilation and AMP reduction occur after the use of different concentrations of atropine and are more severe at higher concentrations.Increased administration frequency of atropine is associated with more pupil dilation and AMP reduction, but there is no intolerable adverse effect.

Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids / 药物分析学报

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and patho-logical conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of＞1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in N-desethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal infor-mation for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.