1.Research status of the pathological mechanisms of immune regulation in tumors and the intervention of traditional Chinese medicine
Xue-Peng WANG ; Hao-Ming GUO ; Liang-Liang SHI ; Shuai-Zhe WANG ; Ya-Ping CHEN ; Ben-Jun WEI
The Chinese Journal of Clinical Pharmacology 2024;40(20):3051-3055
The occurrence and development of tumors are closely related to the body's immune function.It has been confirmed that immunotherapy plays a role in the treatment of various cancers.Some traditional Chinese medicines can control the growth and metastasis of tumors by enhancing anti-tumor immunity.Even in the immunosuppressive tumor microenvironment,traditional Chinese medicine can exert anti-tumor effects by upregulating immune responses.Further research on the regulation of the immune mechanisms by traditional Chinese medicine will provide new insights into how traditional Chinese medicine controls tumor growth and metastasis and help improve its effectiveness in the clinical treatment of various cancers.This article aims to provide a theoretical reference for the role of immunoregulation in tumors,summarize its mechanisms in tumors,and traditional Chinese medicine intervention research in tumors for the prevention and treatment of tumors with traditional Chinese medicine.
2.Correlation of serum Ang-1 and YKL-40 levels with coagulation function and inflam-matory response in patients with Kawasaki's disease complicated with coronary artery lesion
Zhen WANG ; Shuai ZHANG ; Zhe XU
Chinese Journal of Arteriosclerosis 2024;32(5):424-428
Aim To explore the correlation of serum angiopoietin-1(Ang-1)and human cartilage glycoprotein-39(YKL-40)levels with coagulation function and inflammatory response in patients with Kawasaki's disease(KD)compli-cated with coronary artery lesion(CAL).Methods From January 2018 to December 2022,90 children with KD were selected as the study subjects,and 90 healthy children who were examined in this hospital during the same period were selected as the control group.According to whether CAL was combined,they were divided into non-CAL group(69 cases)and CAL group(21 cases),the levels of serum Ang-1,YKL-40,coagulation function,and inflammatory factors were compared between the two groups.Pearson analysis was used to investigate the relationship between serum Ang-1,YKL-40 levels and coagulation function,inflammatory reaction indicators in children with KD combined with CAL.Multi-variate Logistic regression analysis was used to identify the factors affecting CAL in children with KD.Results There were significant differences in serum Ang-1 and YKL-40 levels among the control group,the non-CAL group and the CAL group(all P<0.05).With the increase of the severity of the disease,the serum Ang-1 level in the control group,the non-CAL group and the CAL group decreased gradually,and the YKL-40 level increased gradually(all P<0.05).Serum Ang-1 was negatively correlated with fibrinogen(FIB),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),in-terleukin-6(IL-6)and white blood cell count(WBC)(all P<0.05),YKL-40 was positively correlated with FIB,CRP,TNF-α,IL-6 and WBC(all P<0.05).Multivariate Logistic regression analysis showed that YKL-40 was a risk factor for CAL in children with KD,and Ang-1 was a protective factor(P<0.05).Conclusion The level of serum Ang-1 de-creased and the level of YKL-40 increased in children with KD complicated with CAL,which was correlated with coagula-tion function and inflammatory response.
3.Preparation of colloidal gold test strips for the detection of antibodies to peste des petits ruminants based on monoclonal antibodies to N protein.
Shuai DONG ; Weiqin MENG ; Ling MO ; Jinlong CHEN ; Jingnan SHI ; Zhe YANG ; Tong LI ; Qianqian XU ; Zhiqiang SHEN ; Jianchai LIU ; Jinliang WANG
Chinese Journal of Biotechnology 2023;39(12):4915-4926
A simple, fast, and visual method for detecting antibodies against peste des petits ruminants virus (PPRV) using colloidal gold strips was developed. In this study, the pET-32a-N was transformed into Escherichia coli Rosetta (DE3) for expression. Hybridoma cell lines were generated by fusing SP2/0 myeloma cells with splenocytes from immunized mice with the expressed and purified N protein of PPRV. The PPRV N protein was labeled with colloidal gold particles as the gold-labeled antigen. The N protein served as the gold standard antigen and as the test (T) line-coated antigen, while the monoclonal antibody served as the quality control (C) line-coated antibody to assemble the colloidal gold immunochromatographic test strips for detecting antibodies against the N protein of PPRV. Hybridoma cell line designated as 1F1 was able to stably secrete the monoclonal antibody against the N protein of PPRV. The titer of 1F1 monoclonal antibody in ascites was 1:128 000 determined by indirect enzyme-linked immunosorbent assays (ELISA), and the immunoglobulin subtype of the monoclonal antibody was IgG1, with kappa chain. The obtained monoclonal antibody was able to specifically recognize the N protein of PPRV, as shown by Western blotting and indirect immunofluorescent assay (IFA). The developed colloidal gold test strip method was able to detect PPRV antibodies specifically, and there was no difference between different batches of the test strips. Testing of a total of 122 clinical sera showed that the compliance rate of the test strip with ELISA test was 97.6%.The test strip assay developed in this study has good specificity, reproducibility, and sensitivity, and it can be used for the rapid detection of PPRV antibodies.
Animals
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Mice
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Peste-des-Petits-Ruminants/prevention & control*
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Antibodies, Monoclonal
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Reproducibility of Results
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Peste-des-petits-ruminants virus
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Antibodies, Viral
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Enzyme-Linked Immunosorbent Assay
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Goats
4.Development and validation of a score predicting mortality for older patients with mitral regurgitation.
De-Jing FENG ; Yun-Qing YE ; Zhe LI ; Bin ZHANG ; Qing-Rong LIU ; Wei-Wei WANG ; Zhen-Yan ZHAO ; Zheng ZHOU ; Qing-Hao ZHAO ; Zi-Kai YU ; Hai-Tong ZHANG ; Zhen-Ya DUAN ; Bin-Cheng WANG ; Jun-Xing LV ; Shuai GUO ; Run-Lin GAO ; Hai-Yan XU ; Yong-Jian WU
Journal of Geriatric Cardiology 2023;20(8):577-585
OBJECTIVE:
To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.
METHODS:
The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.
RESULTS:
Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).
CONCLUSIONS
The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.
5. Effects of liraglutide on inflammation and mitochondrial fusion/division in Parkinson' s disease model of mice induced by paraquat
Zhe-Chuan LIU ; Kun LI ; Shuai-Nan MA ; Jia-Qi MENG ; Yan-Qin WANG
Acta Anatomica Sinica 2023;54(6):676-681
Objective To investigate the protective effect and mechanism of liraglutide on the paraquat (PQ)⁃ induced Parkinson's disease (PD) mouse model. Methods Totally 24 Kunming mice were randomly divided into control group, PQ group and PQ +liraglutide group, 8 mice in each group. PD model was established by intraperitoneal injection of PQ (10 mg/kg) for 5 consecutive days, and liraglutide (50 nmol/kg) was injected intraperitoneally for 7 consecutive days. The free⁃standing and locomotor activity of mice were measured by behavioral method. Immunofluorescence was used to observe the number of tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive cells. Western blotting was used to detect the expression of protein TH, glial fibrillary acidic protein (GFAP), mitofusin⁃2 (Mfn2) and dynamin⁃related protein 1 (Drp1). Results The numbers of free⁃standing and locomotor activity numbers decreased significantly (P<0.01, P < 0.05) in PQ group compared with the control group, and the number of TH immunoreactive cells and TH protein expression in substantia nigra decreased significantly (P<0.01, P<0.01) compared with the control group, while the number of Iba1 immunoreactive cells and GFAP protein expression increased significantly (P<0.01, P<0.01) compared with the control group; the expression of Drp1 protein in PQ group was significantly higher than that in control group (P<0.05), while the Mfn2 protein expression decreased significantly (P<0.05) compared with the control group. After treatment with liraglutide, the number of TH positive cells in PQ + liraglutide group was significantly lower than that in control group (P<0.05); the numbers of free⁃standing and locomotor activity increased significantly (P<0.05, P<0.05) in PQ + liraglutide group compared with the PQ group, and the number of TH positive cells and expression of TH protein in PQ + liraglutide group were significantly higher than that in PQ group (P<0.01, P< 0.01); while the number of Iba1 positive cells and GFAP protein expression decreased significantly (P<0.01, P<0.05) compared with the PQ group; the Drp1 protein expression decreased significantly (P<0.01) compared with the PQ group, while the expression of Mfn2 protein in PQ + liraglutide group was significantly higher than that in PQ group (P<0.01). Conclusion Liraglutide has neuroprotective effect by reducing neuroinflammation in substantia nigra, regulating mitochondrial fusion and fission.
6.Preclinical studies of the triazolo1,5-apyrimidine derivative WS-716 as a highly potent, specific and orally active P-glycoprotein (P-gp) inhibitor.
Sai-Qi WANG ; Qiu-Xu TENG ; Shuai WANG ; Zi-Ning LEI ; Hui-Hui HU ; Hui-Fang LV ; Bei-Bei CHEN ; Jian-Zheng WANG ; Xiao-Jing SHI ; Wei-Feng XU ; Hong-Min LIU ; Xiao-Bing CHEN ; Zhe-Sheng CHEN ; Bin YU
Acta Pharmaceutica Sinica B 2022;12(8):3263-3280
Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.
7.Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.
Xiaoyan LIU ; Zhe LI ; Shuai LIU ; Jing SUN ; Zhanghua CHEN ; Min JIANG ; Qingling ZHANG ; Yinghua WEI ; Xin WANG ; Yi-You HUANG ; Yinyi SHI ; Yanhui XU ; Huifang XIAN ; Fan BAI ; Changxing OU ; Bei XIONG ; Andrew M LEW ; Jun CUI ; Rongli FANG ; Hui HUANG ; Jincun ZHAO ; Xuechuan HONG ; Yuxia ZHANG ; Fuling ZHOU ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2020;10(7):1205-1215
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.
8.Rapid identification of chemical components in compound Nanxing acesodyne plaster by UPLC-Q-TOF-MS/MS.
Guo-Shuai LI ; Yang MA ; Ting GENG ; Xia GAO ; Wen-Zhe HUANG ; Liang CAO ; Wei XIAO ; Zhen-Zhong WANG
China Journal of Chinese Materia Medica 2019;44(2):298-307
The study aims to qualitatively analyze the chemical composition of compound Nanxing acesodyne plaster by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C_(18)( 4. 6 mm×250 mm,5 μm) column. The mobile phase consisted of methanol and 0. 2% formic acid-water was used as gradient elution. The flow rate was 1 mL·min~(-1) and column temperature was 30 ℃. The Mass spectrometry was acquired in both positive and negative ion modes using ESI. The components were identified by the precise mass-to-charge ratio,secondary fragmentation and other information combined with reference substance and literature data. As a result,58 compounds were identified and predicted,including alkaloids,flavonoids,coumarins,organic acids and lactone compounds,of which 12 compounds were verified by the reference substances. The results provide reference for the quality control of compound Nanxing acesodyne plaster,and lay the foundation for elucidating the active components mechanism.
Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal
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chemistry
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Phytochemicals
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analysis
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Tandem Mass Spectrometry
9.Clinical study of neuroendoscope-assisted microscopes for the resection of Sellar region tumors
Shuai ZHOU ; Shengjun LI ; Wenlong SU ; Zhe WANG ; Shouxian WANG
Chinese Journal of Postgraduates of Medicine 2019;42(2):144-148
Objective To explore the role and value of neuroendoscopy-assisted microscope technique in the operation of sellar region tumor. Methods Sixty-three cases of saddle area treated by neuroendoscopy-assisted microscopy during 2015—2017 of neurosurgery in Weifang people' s hospital (neuroendoscopy-assisted microscope technique group) were collected and analyzed. Seven-six patients with sellar area treated by simple microscopic resection from 2013 to 2015(simple microscope group) were retrospectively analyzed. Tumor resection rate, postoperative complication rate and postoperative recurrence rate, the effect of operation was compared and evaluated. Results In the neuroendoscopy-assisted microscope technique group and simple microscope group, the total resection rate of tumor was 95.24%(60/63) and 80.26%(61/76), the incidence of vasospasm was 3.17%(2/63) and 13.16%(10/76), and the incidence of nerve injury was 0(0/63) and 6.58%(5/76). There were significant differences (P<0.05). The postoperative infection, cerebrospinal fluid leakage and postoperative recurrence rate between two groups had no significant differences (P>0.05). Conclusions Endoscopic microscopically assisted resection of sellar area can not only increase the total resection rate of tumor, but also reduce the incidence of complications.
10.Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis.
Ying-Zhe CUI ; Si-Ying QU ; Lu-Lu CHANG ; Jia-Rui ZHAO ; Lili MU ; Bo SUN ; Hu-Lun LI ; Tong-Shuai ZHANG ; Guang-You WANG ; Qing-Fei KONG
Neuroscience Bulletin 2019;35(3):507-518
Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.
Animals
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B-Lymphocytes
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immunology
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Disease Models, Animal
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Female
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Immunity, Humoral
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Lymph Nodes
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immunology
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Myasthenia Gravis, Autoimmune, Experimental
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immunology
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Protein Subunits
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immunology
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Proto-Oncogene Proteins c-bcl-6
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immunology
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Rats, Inbred Lew
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Receptor Cross-Talk
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Receptors, Cholinergic
;
immunology
;
T-Lymphocytes, Helper-Inducer
;
immunology

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