1.Mechanism of 1,25(OH)2D3 improving liver inflammation in a rat model of nonalcoholic steatohepatitis induced by choline-deficient L-amino acid-defined diet
Haiyang ZHU ; Jingshu CUI ; Liu YANG ; Mengting ZHOU ; Jian TONG ; Hongmei HAN
Journal of Clinical Hepatology 2025;41(2):254-262
ObjectiveTo investigate the effect of 1,25(OH)2D3 on the level of peroxisome proliferator-activated receptor-γ (PPAR-γ) in the liver, the phenotype of hepatic macrophages, and liver inflammation in a rat model of nonalcoholic steatohepatitis (NASH), as well as the mechanism of 1,25(OH)2D3 improving liver inflammation. MethodsAfter 1 week of adaptive feeding, 24 specific pathogen-free Wistar rats were randomly divided into normal group [choline-supplemented L-amino acid-defined (CSAA) diet], normal+1,25(OH)2D3 group [CSAA diet+1,25(OH)2D3], model group [choline-deficient L-amino acid-defined diet (CDAA) diet], and model+1,25(OH)2D3 group [CDAA diet+1,25(OH)2D3], with 6 rats in each group. The dose of 1,25(OH)2D3 was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured, liver histopathology was observed, and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages, and ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in liver tissue, and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups, and the least significant difference t-test was used for further comparison; the Pearson method was used for correlation analysis. ResultsCompared with the normal group, the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT (P=0.019 and P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P<0.001), as well as a significant increase in the level of TNF-α (P<0.001) and a significant reduction in the level of IL-4 in liver tissue (P=0.025). The 1,25(OH)2D3 group had significant reductions in the serum levels of ALT (P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P=0.001), the level of IL-1β (P<0.001) and a significant increase in the level of M2 hepatic macrophages (P=0.017), the level of IL-10 (P=0.039), the level of IL-4 (P<0.001), the level of PPAR-γ (P=0.016). There were significant interactions between CDAA diet-induced NASH model and 1,25(OH)2D3 in serum the levels of AST and ALT (P=0.007 and P=0.008), the SAF scores of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), the level of M2 hepatic macrophages (P=0.008), the ratio of M1 and M2 of hepatic macrophages (P=0.005), the level of TNF-α (P<0.001), the level of IL-10 (P=0.038), the level of IL-4 (P<0.001) and the level of PPAR-γ (P=0.009). The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages (r=-0.415, P=0.044) and was positively correlated with M2 hepatic macrophages (r=0.435, P=0.033), IL-10 (r=0.433, P=0.035), and IL-4 (r=0.532, P=0.007). ConclusionThis study shows that 1,25(OH)2D3 improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.
2.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
3.Optimization of temperature parameters for screening unexpected antibodies in Rh system by manual polybrene test
Xin ZOU ; Minjie CHEN ; Sifei MA ; Hongmei YANG
Chinese Journal of Blood Transfusion 2025;38(1):97-100
[Objective] To explore the temperature parameters affecting the polybrene test and determine the optimal temperature conditions for detecting unexpected antibodies of the Rh system. [Methods] The reaction of IgG human anti-D antibody with different dilutions (undiluted, 1∶2, 1∶4, 1∶8, 1∶16, 1∶32,1∶64) with D antigen-positive red blood cells was detected by manual polybrene test (MPT). Different temperatures (25℃ and 37℃) were set, and the reaction time with low ionic medium was 4 minutes. The agglutination integral value of anti-D and red cell depolymerization time were compared to observe the effect of enhanced agglutination reaction, thereby establishing the test temperature reaction conditions for enhancing the MPT. The same reaction condition was applied to 36 blood samples containing unexpected antibodies of the Rh system, and the effect of enhanced MPT was observed in comparison with the polybrene method and the antiglobulin test (column agglutination). [Results] With all other conditions held constant, when low ionic medium was added, the incubation temperature of 25℃ and 37℃ resulted in different total agglutination integral values for anti-D (20.9±2.025 vs 25.5±2.635), and the comparison showed a significant difference (P<0.05). When the antibody dilution was 1∶16, the incubation temperature of 25℃ and 37℃ resulted in different agglutination integral values (3.9±0.738 vs 5.8±0.632), and the comparison showed a significant difference (P<0.05). Erythrocyte depolymerization time (62.8±8.149 vs 90.1±10.713) was significantly different (P<0.05). At a dilution of 1∶32, the incubation temperatures of 25℃ and 37℃ resulted in different agglutination integral values (2.5±0.527 vs 4.3±0.675), as well as different red blood cell dissociation times (35.4±7.792 vs 57.4±10.885)(P<0.05), and the comparison showed a significant difference (P<0.05), with no differences observed in the other groups. In the detection of 36 Rh system unexpected antibody samples, when the antibody titer was ≤2, the enhanced polybrene method had a higher positive rate, and when the antibody titer was ≥4, the detection rates of the three methods were consistent. [Conclusion] The reference temperature condition for the modified MPT is incubation at 37℃ for 4 min after the addition of low ionic medium. The application of this temperature condition to unexpected antibody samples of Rh system could achieve a significant enhancement effect, thereby increasing transfusion safety for the treatment of emergency patients, and is worth popularizing.
4.Stem cell therapy for amyotrophic lateral sclerosis:cell source,number,modification,and administration route
Wen ZHAO ; Yulin BI ; Xuyang FU ; Hongmei DUAN ; Zhaoyang YANG ; Xiaoguang LI
Chinese Journal of Tissue Engineering Research 2025;29(19):4083-4090
BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.
5.Evaluation of the efficacy and safety of cryopreserved deglycerolized red blood cells infusion based on propensity score matching method
Wei YANG ; Fanfan FU ; Lei NIU ; Tingchen XU ; Xin ZHANG ; Hongmei SHI ; Lihui FU ; Chunya MA ; Yang YU
Chinese Journal of Blood Transfusion 2025;38(4):531-536
[Objective] To compare the efficacy and safety of deglycerolized red blood cells (DRBC) and suspended red blood cells (SRBC) based on the propensity score matching (PSM) method, so as to provide evidence for the rational use of DRBC resources in clinical practice. [Methods] A total of 89 patients who received DRBC transfusion and 2 916 patients who received SRBC transfusion in our hospital from January 2023 to September 2024 were included. A 1∶1 nearest neighbor PSM was used to balance covariates such as gender, age, and body mass index (BMI). The changes of hemoglobin (Hb), red blood cell (RBC) count, hematocrit (HCT), and inflammatory markers such as white blood cell (WBC) count, neutrophil (NE) count, C-reactive protein (CRP), and Interleukin-6(IL-6) in the last 72 hours after transfusion were analyzed by SPSS 26.0 and R software to evaluate clinical efficacy and transfusion safety. [Results] The baseline of the two groups was balanced after PSM (P>0.05). There was no significant difference in the total effective rate between the DRBC group (80.9%) and the SRBC group (86.5%) (P>0.05). In the SRBC group, WBC (×10
/L) increased from 9.634±6.742 to 10.147±6.835, CRP (mg/dL) increased from 5.468±4.647 to 6.174±6.114, and IL-6(pg/mL) decreased from 213.733±587.191 to 157.255±552.626. In the DRBC group, WBC (×10
/L) decreased from 11.123±7.880 to 11.011±8.549, CRP (mg/dL) decreased from 5.729±4.761 to 5.326±4.466, and IL-6(pg/mL) decreased from 238.806±639.060 to 152.255±266.558. Compared with the before treatment, the differences between the SRBC group and DRBC group were not statistically significant (P>0.05). Among all patients included in the statistics, the overall incidence of transfusion adverse reactions was 0.205% (6/2 916) in the SRBC group, and no adverse reactions occurred in the DRBC group. The incidence in the SRBC group was higher than that in the DRBC group. [Conclusion] Based on PSM analysis, there was no significant difference in the efficacy and safety of DRBC transfusion compared with SRBC transfusion, which can provide evidence-based support for routine application.
6.Systematic review on medication risk prediction models for hospitalized adult patients
Yang YANG ; Xuefeng SHAN ; Haidong LI ; Yaozheng LI ; Qiwen ZHOU ; Hongmei WANG
China Pharmacy 2025;36(10):1254-1259
OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed, Embase, Web of Science, CNKI, Wanfang data, VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature, extracting data, and evaluating the quality of the literature, descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included, involving 12 models. Nine studies used Logistic regression algorithm for modeling, and the number of included predictive factors ranged from 3 to 11; the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias; 10 studies had high applicability risk. A total of 31 predictive factors were extracted, including 15 items of basic patient information, 3 test indicators, and 5 items of medication information, and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm, with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved, and the overall risk of bias is relatively high.
7.Research progress on PD-1/PD-L1 inhibitors in neoadjuvant therapy for esophageal cancer
Liji CHEN ; Hongmei MA ; Shifa ZHANG ; Kaize ZHONG ; Dongbao YANG ; Jiuhe SUN ; Hongfeng LIU ; Ru SONG ; Jishan ZHANG ; Haibo CAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):714-721
Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.
8.Meta analysis of effects of healthy eating patterns on mortality,ESKD and CVD incidence in patients with CKD
Yang LI ; Hongmei PENG ; Xia HUANG ; Shi PU ; Xiangchun TANG ; Yu SHI
Chongqing Medicine 2024;53(2):264-269
Objective To investigate the impact of healthy eating patterns on the mortality rate and in-cidence rates of end-stage kidney disease(ESKD)and cardiovascular disease(CVD)in the patients with chronic kidney disease(CKD)by meta analysis.Methods The studies on the relationship between the dietary patterns on the mortality,and the incidence rates of ESKD and CVD in the patients with CKD were retrieved from PubMed,Embase,Cochrane Library,CNKI,Wanfang Database and VIP Database.The retrieval time was from the database establishment to January 2023.The two researchers independently screened the literatures,ex-tracted the data and conducted the literature quality evaluation.The RevMan5.3 software was used for the meta-analysis of the included literatures.Results A total of 10 studies were included in this study,involving 27 291 patients.The results showed that the mortality(HR=0.70,95%CI:0.57-0.87,Z=3.18,P=0.001)and the ESKD incidence rate(HR=0.80,95%CI:0.71-0.91,Z=3.44,P<0.001)and CVD inci-dence rate(HR=0.77;95%CI:0.61-0.97,Z=2.21,P=0.003)had statistical differences between the pa-tients with high dietary score and the patients with low dietary score.Conclusion Persisting in the healthy dieta-ry patterns could decrease the mortality rate,and incidence rates of ESKD and CVD in the patients with CKD.
9.Inhibition of prohibitin 2 enhances the sensitivity of non-small cell lung cancer cell line A549 to erlotinib
Jing ZHANG ; Zigeng YANG ; Wenqin CAI ; Weiwei CAO ; Hongmei WEI ; Xixi XUE ; Bin WU
Basic & Clinical Medicine 2024;44(3):325-332
Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P<0.05),while the TUNEL-positive A549 cells increased significantly(P<0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P<0.05)and the levels of cytochrome c increased in mitochondrial fractions(P<0.05)and decreased in cytosolic fractions(P<0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.
10.Distribution of platelet antibodies and their specificity in Zhongshan area
Huiyan LIN ; Yonglun WU ; Ainong SUN ; Yuru FANG ; Qianying CHEN ; Qiao LI ; Yujue WANG ; Hongmei WANG ; Zhizhao YANG ; Xiaoyi JIAN ; Xianguo XU ; Shengbao DUAN
Chinese Journal of Blood Transfusion 2024;37(1):63-67
【Objective】 To investigate the frequency of platelet antibodies in voluntary blood donors and patients in Zhongshan, Guangdong Province, and to study the specificity and cross-matching of platelet antibodies. 【Methods】 Platelet antibodies of blood donors and patients were screened by solid-phase immunoadsorption (SPIA), rechecked by flow cytometry (FCM), and antibody specificity was identified by PakPlus enzyme immunoassay, and platelet cross-matching was simulated by SPIA. 【Results】 A total of 1 049 blood donor samples and 598 patient samples were tested, with 6 (0.57%) and 49 (8.19%) samples positive for SPIA,respectively(P<0.05); In SPIA positive samples, the positive concordance rate of FCM in blood donors and patients was 100% vs 95%, and that of enzyme immunoassay was 100% vs 88%. Among the initial screening positive samples of blood donors, 5 were anti-HLA Ⅰ antibodies, accounting for 83%, and 1 was anti CD36 antibody, accounting for 17%, with an incidence rate of 0.10%. Among the 14 samples of enzyme immunoassay positive patients, 2 were anti-GP Ⅱb/Ⅲa, 1 was anti-GP Ⅱa/Ⅱa, 8 were anti HLA Ⅰ, and 3 were mixed antibodies (HLA Ⅰ, GP Ⅱb/Ⅲa, GP Ⅰa/Ⅱa). According to the types of antibodies, HLA Ⅰ antibodies were the most common, accounting for 65% (11/17), followed by HPA related anti GP, accounting for 35% (6/17). The majority of patients had a platelet antibody positive typing rate below 30%, accounting for 71.4% (10/14). 【Conclusions】 The positive rate of platelet antibody of patients in Zhongshan area is significantly higher than that of voluntary blood donors, and most of them are anti-HLA Ⅰ and anti-GP, and the incidence of anti-CD36 is extremely low. Therefore, it is necessary to establish a known platelet antigen donor bank, and at the same time, carry out platelet antibody testing and matching of patients, which is helpful to solve the issue of platelet transfusion refractoriness.

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