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.

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.

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.

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.

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.

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/ ).

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.

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.

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.

Effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging mice / 中国针灸

OBJECTIVE@#To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke.@*METHODS@#Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m3 for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA.@*RESULTS@#The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group.@*CONCLUSION@#The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.

Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi / 中国医学科学院学报

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1 / 中华儿科杂志

Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.

Evaluation of thermal environment and human thermal comfort in 8 types of public places from 2019 to 2021 / 中华劳动卫生职业病杂志

Objective: To evaluate the thermal environment of different types of public places and the thermal comfort of employees, so as to provide scientific basis for the establishment of microclimate standards and health supervision requirements. Methods: From June 2019 to December 2021, 50 public places (178 times) of 8 categories in Wuxi were selected, including hotels, swimming pools (gymnasiums), bathing places, shopping malls (supermarkets), barber shops, beauty shops, waiting rooms (bus station) and gyms. In summer and winter, microclimate indicators such as temperature and wind speed were measured in all kinds of places, combined with the work attire and physical activity of employees in the places. Fanger thermal comfort equation and center for the built environment (CBE) thermal comfort calculation tool were used to evaluate the predicted mean vote (PMV), predicted percent dissatisfied (PPD) and standard effective temperature (SET) according to the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) 55-2020. The modification effects of seasonal and temperature control conditions on thermal comfort were analyzed. The consistency of GB 37488-2019 "Hygienic Indicators and Limits in Public Places" and ASHRAE 55-2020 evaluation results on thermal environment was compared. Results: The thermal sensation of hotel, barber shop staff and the gym front-desk staff were moderate, while the thermal sensation of swimming place lifeguard, bathing place cleaning staff and gym trainer were slightly warm in summer and winter. Waiting room (bus station) cleaning and working staff, shopping mall staff felt slightly warm in summer and moderate in winter. Service staff in bathing places felt slightly warm in winter, while staff in beauty salons felt slightly cool in winter. The thermal comfort compliance of hotel cleaning staff and shopping mall staff in summer was lower than that in winter (χ(2)=7.01, 7.22, P=0.008, 0.007). The thermal comfort compliance of shopping mall staff in the condition of air conditioning off was higher than that in the condition of air conditioning on (χ(2)=7.01, P=0.008). The SET values of front-desk staff in hotels with different health supervision levels were significantly different (F=3.30, P=0.024). The PPD value and SET value of the front-desk staff, and the PPD value of cleaning staff of hotels above three stars were lower than those of hotels below three stars (P<0.05). The thermal comfort compliance of front-desk staff and cleaning staff in hotels above three stars was higher than that in hotels below three stars (χ(2)=8.33, 8.09, P=0.016, 0.018). The consistency of the two criteria was highest among waiting room (bus station) staff (100.0%, 1/1) and lowest among gym front-desk staff (0%, 0/2) and waiting room (bus station) cleaning staff (0%, 0/1) . Conclusion: There are different degrees of thermal discomfort in different seasons, under the condition of air conditioning and health supervision, and the microclimate indicators can not fully reflect the thermal comfort of human body. The health supervision of microclimate should be strengthened, the applicability of health standard limit value should be evaluated in many aspects, and the thermal comfort of occupational group should be improved.

Influence of the interaction between tumor microenvironment and liver cancer stem cells on the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

In recent years, liver cancer stem cells (LCSC) have been considered one of the main causes of treatment failure and recurrence of hepatocellular carcinoma (HCC). Many studies have shown that LCSC are a small fraction of cells with the abilities of self-renewal, differentiation, and tumorigenesis in HCC tumor, which can initiate the onset of HCC and affect its proliferation, invasion, metastasis, recurrence, and drug resistance. Therapies based on tumor microenvironment (TME) have been developed recently, and a number of studies have found that targeting the relevant elements of TME has a higher therapeutic value than targeting tumor cells themselves. TME is the microenvironment for the growth of LCSC and HCC cells, and it interacts with LCSC and has a synergistic effect, thereby playing a positive role in the development and progression of HCC. This article introduces how various cellular components and non-cellular components in TME interact with LCSC to regulate the development and progression of the HCC. In addition, this article also describes the molecular targets, therapies, and drugs associated with the main components of TME and LCSCs, in order to seek safer and more effective targeted therapies for HCC.