1.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
2.Clinical Study of Ibrutinib Combined with Venetoclax Regimen in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Man YANG ; Yan HUANG ; Lu-Yao ZHU ; Ling-Xiu ZHANG ; You-Mei ZI ; Xiu-Feng WANG ; Yuan ZHANG
Journal of Experimental Hematology 2024;32(5):1414-1419
Objective:To investigate the clinical efficacy of ibrutinib combined with venetoclax in the treatment of relapsed/refractory diffuse large B-cell lymphoma(R/R DLBCL),and to analyze the factors affecting efficacy and prognosis.Methods:Clinical data of 62 R/R DLBCL patients admitted to our hospital from August 2017 to July 2022 were retrospectively analyzed.All patients were treated with ibrutinib combined with venetoclax.The clinical efficacy and drug safety were evaluated.The effects of clinical features on short-term efficacy and overall survival(OS)were analyzed.Results:The objective response rate(ORR)of 62 patients was 48.39%.The extranodal lesions,intermediate-high/high risk of NCCN-IPI,intermediate-high/high risk of IPI,progression or recurrence time<12 months were the risk factors affecting the short-term efficacy of chemotherapy in R/R DLBCL patients(all P<0.05).The most common adverse effect was neutropenia(75.19%),and the incidence of grade Ⅱ-Ⅳ neutropenia was 52.71%.The l-year and 2-year OS rates of 62 patients were 48.51%and 31.56%,respectively,and the median OS time was 12 months.Multivariate analysis showed that objective remission after chemotherapy[HR=0.080(95%CI:0.028-0.235)]was a protective factor for OS in R/R DLBCL patients,and intermediate-high/high risk of NCCN-IPI[HR=4.828(95%CI:1.546-15.080)]was an independent risk factor affecting the prognosis of R/R DLBCL patients.Conclusion:Ibrutinib combined with venetoclax can be used as an effective treatment regimen for R/R DLBCL,and NCCN-IPI can be used as a prognostic indicator.Objective remission after chemotherapy is beneficial for R/R DLBCL patients to achieve better OS.
3.Research progress in bioanalysis and pharmacokinetics of liposome nanomedicine
Yi LIU ; Yu-jie ZHANG ; Zi-yu WANG ; Jian-song YOU ; Lei YIN ; Mei-yun SHI
Acta Pharmaceutica Sinica 2023;58(4):834-843
Liposome nanomedicine is a new drug preparation with nano scale, which is encapsulated by lipid bilayer vesicle structure. As a drug delivery carrier, liposome has many advantages such as good biocompatibility, biodegradation
4.Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases.
Ju Mei LIU ; Li LIANG ; Ji Xin ZHANG ; Long RONG ; Zi Yi ZHANG ; You WU ; Xu Dong ZHAO ; Ting LI
Journal of Peking University(Health Sciences) 2023;55(2):299-307
OBJECTIVE:
To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis.
METHODS:
A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively.
RESULTS:
23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001).
CONCLUSION
Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.
Humans
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Stomach Neoplasms/pathology*
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Endoscopic Mucosal Resection
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Retrospective Studies
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Endoscopy
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Precancerous Conditions
5.Chemical reaction mechanism of decoction of traditional Chinese medicines: a review.
Chang-Jiang-Sheng LAI ; Ze-Yan CHEN ; Zi-Dong QIU ; You-Run CHEN ; Chong-Yang WANG ; Nan-Ju MEI ; Jin-Rui LIU
China Journal of Chinese Materia Medica 2023;48(4):890-899
Complicated chemical reactions occur in the decoction of traditional Chinese medicines(TCMs) which features complex components, influencing the safety, efficacy, and quality controllability of TCMs. Therefore, it is particularly important to clarify the chemical reaction mechanism of TCMs in the decoction. This study summarized eight typical chemical reactions in the decoction of TCMs, such as substitution reaction, redox reaction, isomerization/stereoselective reaction, complexation, and supramolecular reaction. With the "toxicity attenuation and efficiency enhancement" of aconitines and other examples, this study reviewed the reactions in decoction of TCMs, which was expected to clarify the variation mechanisms of key chemical components in this process and to help guide medicine preparation and safe and rational use of medicine in clinical settings. The current main research methods for chemical reaction mechanisms of decoction of TCMs were also summed up and compared. The novel real-time analysis device of decoction system for TCMs was found to be efficient and simple without the pre-treatment of samples. This device provides a promising solution, which has great potential in quantity evaluation and control of TCMs. Moreover, it is expected to become a foundational and exemplary research tool, which can advance the research in this field.
Medicine
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Medicine, Chinese Traditional
;
Research Design
6.Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction.
Jia-Ming GAO ; Hao GUO ; Ye-Hao ZHANG ; Ling-Mei LI ; Gao-Jie XIN ; Zi-Xin LIU ; Yue YOU ; Yuan-Yuan CHEN ; Jian-Xun LIU ; Jian-Hua FU
China Journal of Chinese Materia Medica 2023;48(15):4156-4163
This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.
Rats
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Animals
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Rats, Sprague-Dawley
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Drugs, Chinese Herbal/therapeutic use*
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Myocardial Infarction/genetics*
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Myocardium/metabolism*
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Aspirin/therapeutic use*
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TOR Serine-Threonine Kinases/metabolism*
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Membrane Proteins/metabolism*
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Mitochondrial Proteins
7.Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.
Nan YANG ; Wei ZHAO ; Wen-An QI ; Chen YAO ; Chong-Ya DONG ; Zhen-Guo ZHAI ; Tong CHEN ; En-Mei LIU ; Guo-Bao LI ; You-Lin LONG ; Xin-Yi WANG ; Zi-Jun WANG ; Ruo-Bing LEI ; Qi ZHOU ; Yao-Long CHEN ; Liang DU
Chinese Journal of Traumatology 2022;25(6):312-316
Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
Humans
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Practice Guidelines as Topic
8.Effect of Traditional Chinese Medicines in Treatment of Post-traumatic Stress Disorder
Qiu-yu LI ; Jian-you GUO ; Zi-wei YAO ; Xiao-mei WANG ; Jin-li SHI
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(7):211-217
Post-traumatic stress disorder (PTSD) is a mental disorder characterized by restitution of trauma and emotional irritability and avoidance caused by sudden, threatening or catastrophic life events. PTSD occurs not only abnormal behavioral indicators but also abnormal neurobiological indicators. Studies on the pathogenesis of PTSD have focused on neuroendocrine system, central nervous system and immune system, mainly finding abnormal levels of stress hormones, pro-inflammatory cytokines, neurotransmitters and neuroprotective factors. Traditional Chinese medicines(TCM) have many advantages in the treatment of PTSD due to their multi-target, multi-component and multi-pathway characteristics. Current studies have showed that a variety of TCM can improve the abnormal behaviors of animals in the models of post-traumatic stress disorder and reverse the neurobiological indicators. As many of these TCM compounds have been used in clinic and have good efficacy, TCM treatment of PTSD has a broad application prospect. However, there is no specific medicine for PTSD, and its mechanisms have not been fully understood. Therefore, this paper reviews the current studies on the treatment of PTSD with TCM, and focuses on the occurrence and treatment progress of PTSD in terms of TCM, mechanisms of action and animal models, so as to provide references for the treatment of PTSD.
9.Role of allograft inflammatory factor-1 in regulating the proliferation, migration and apoptosis of colorectal cancer cells.
Xiao-Lan AI ; Fang YAO ; Xiao-Jing WANG ; Dong-Bei DUAN ; Ke LI ; Zi-You HU ; Guo YIN ; Mei WANG ; Bing-Yi WU
Journal of Southern Medical University 2018;38(5):511-519
OBJECTIVETo investigate the role of allograft inflammatory factor-1 (AIF-1) in colorectal cancer (CRC) progression and explore the possible mechanism.
METHODSThe expression levels of AIF-1 in 70 CRC tissues and paired adjacent tissues were detected using immunohistochemistry and Western blotting, and the correlation of AIF-1 expression with the clinicopathological features of the patients was analyzed. In the CRC cell line SW480, the functional role of AIF-1 in regulating tumor progression was investigated by transfecting the cells with an AIF-1-overexpressing plasmid (AIF-1) and a negative control plasmid (NC). EdU proliferation assay and flow cytometry were used to assess the cell proliferation and cell cycle changes; Transwell migration assay and Annexin V-APC/7-AAD apoptosis assay kit were used to analyze the cell migration and apoptosis. The changes in the biological behaviors of the cells were observed after application of SB203580 to block the p38 MAPK pathway. The expression levels of CDK4, cyclin D1, P21, P27, MMP2, MMP9, Bax, Bcl2, Bcl-xl, p38 and p-p38 were detected using Western blotting.
RESULTSAIF-1 was down-regulated in CRC tissues compared with the adjacent normal tissues, and its expression level was positively correlated with lymph node metastasis (P=0.008), TNM stage (P=0.003) and tumor size (P=0.023). Overexpression of AIF-1 in SW480 cells significantly reduced EdU-positive cells and caused obvious cell cycle arrest in G1 phase (P<0.05). AIF-1 overexpression resulted in significantly lowered protein expressions of CDK4 and cyclin D1, enhanced expressions of P21 and P27, attenuated cell migration ability (P<0.001), and decreased protein levels of MMP2 and MMP9. AIF-1 overexpression also induced obvious apoptosis of SW480 cells (P<0.01), significantly increased the protein levels of Bax and p-p38, and decreased the protein levels of Bcl-2 and Bcl-xl; SB203580 significantly attenuated the apoptosis-inducing effect of AIF-1 overexpression.
CONCLUSIONAIF-1 plays the role of a tumor suppressor in CRC by inhibiting cell proliferation, suppressing cell migration and inducing cell apoptosis. AIF-1 overexpression promotes the apoptosis of CRC cells by activating the p38 MAPK pathway.
10.Effects of miR-143 on invasion and migration of B cell lymphoma cells through regulating expression of PAN3 protein
Man YANG ; Sun WU ; Xiu Ling ZHANG ; Yan HUANG ; Mei You ZI ; Yuan ZHANG
Chinese Journal of Immunology 2017;33(12):1774-1778
Objective:To investigate the effect of miR-143 on the invasion and migration of B cell lymphoma cells .Methods:The expression of miR-143 in normal bone marrow and lymphoma was detected by qPCR .The expression levels of miR-143 in different cell lines were examined by qPCR .qPCR was used to detect the ability of miR-143 on PAN3.The relationship between miR-143 and PAN3 was detected by double luciferase assay .The effect of miR-143 expression on the migration ability of B cell lymphoma E 6-1 cells was examined by scratch test .The effect of miR-143 expression on the invasion ability of B cell lymphoma E 6-1 cells was exa mined by transwell test.Results:Compared with normal bone marrow ,miR-143 was down-regulated in B-cell lymphoma.Double luciferase assay showed that miR-143 could regulate the expression of PAN 3.Overexpression of miR-143 ,E6-1 cells significantly reduced the ability to attack and migrate.Conclusion:miR-143 can regulate the migration and invasion of B cell lymphoma cells by regulating the expression of PAN3.

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