1.Adipose derived mesenchymal stem cell exosomes inhibit adverse ventricular remode-ling after myocardial infarction by regulating autophagy and NLRP3 inflammasomes balance of cardiac fibroblasts
Jianjun WANG ; Jing LI ; Xuming MA ; Zhaofei WAN ; Bin ZHU ; Yaping LIU ; Xiangqian GUO ; Jiping PAN ; Yan FAN
Chinese Journal of Arteriosclerosis 2024;32(8):654-662
Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell(ADMSC)exosomes(Exo)on adverse ventricular remodeling after myocardial infarction(MI).Methods The chan-ges of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed.MI rats were in-jected with an equal volume of normal saline,adipose derived mesenchymal stem cell exosomes(MSC-Exo)or fibroblast exosomes(MEF-Exo)via a tail vein.The expression of autophagy related 16 like protein 1(ATG16L1),autophagy re-lated protein 7(ATG7)and NOD-like receptor protein 3(NLRP3),inflammatory response,the degree of myocardial fi-brosis,and the cardiac function were observed in different groups.Results After treatment with H2O2 on cardiac fi-broblasts,the expressions of ATG16L1 and ATG7 were significantly decreased(P<0.001),NLRP3 was significantly in-creased(P<0.001),and the levels of inflammatory cytokines interleukin-1β(IL-1β)and IL-18 were significantly elevated(P<0.001).After MI rats were intervened with MSC-Exo,the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated(P<0.001),NLRP3 was significantly down-regulated(P<0.001),serum IL-1β and IL-18 levels were significantly decreased(P<0.001),fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced(P<0.001),myocardial fibrosis was significantly relieved(P<0.001),and cardiac function was sig-nificantly improved(P<0.001).Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.
2.Comprehensive Clinical Evaluation of Duliang Soft Capsules in Treatment of Migraine with Wind-cold Blood Stasis Syndrome
Xiaoxiao ZHAO ; Xuming ZHANG ; Junyu XI ; Zhenkai LU ; Fumei LIU ; Lianxin WANG ; Yuanyuan LI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):223-232
ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome, and to provide guidance for national medical decision-making, clinical drug promotion, and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version, 2021) using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software, this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions, including safety pre- and post-market launch, effectiveness in treating migraine, economy (cost-effectiveness), and innovation, suitability, accessibility, and traditional Chinese medicine (TCM) characteristics in both its technology and clinical applications. ResultSafety: Duliang soft capsules were found to have good safety based on evidence from known adverse reactions (spontaneous reporting system (SRS) data, literature data, etc.), pre-marketing toxicological research, and post-marketing drug monitoring. Effectiveness: A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy: Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation: Duliang soft capsules, with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components, hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction (CO2 supercritical extraction technology) and formulation (soft capsule) processes. The product's innovation was rated as "Better". Suitability: A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility: Duliang soft capsules are moderately priced, making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics: The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio (Shi Zhai Bai Yi Xuan Fang) from the Song Dynasty, and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue (Jing Yue Quan Shu) as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch, and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness, suitability, and accessibility, and outstanding TCM characteristics. The product's safety, economy, and innovation received good ratings. In summary, Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics, the evidence was sufficient, and the result was confirmed, providing crucial references for clinical decision-making and pharmaceutical management.
3.Advances of Virtual Reality in the Field of Pain Treatment
Chen WU ; Li ZHANG ; Chao MA ; Hongju LIU ; Xuming LIU ; Kepu ZHANG ; Tengti WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(2):272-278
Pain not only affects the physical and mental health of individuals, but also imposes a huge burden on society as a whole. Traditional pain management measures are diverse, but each has its limitations. Therefore, there is an urgent need for new tools. Digital therapies are booming, and virtual reality (VR) has been widely used, especially in the field of pain management. VR uses assistive tools, such as headsets, to build a three-dimensional virtual world with the participation of multiple senses, including vision, hearing, and smell, so that it can make user feel being there. This review aims to summarize the application and mechanism of VR in the field of pain management, with the hope of making VR a new choice for pain management.
4.Construction and gene identification of myeloid-specific Spi1 knockout mice
Xuming WU ; Huihui WANG ; Xiangling ZHU ; Yuanyuan ZHOU ; Anqi WANG ; Huiru ZHANG ; Chong LIU ; Jiajie TU
Acta Universitatis Medicinalis Anhui 2024;59(3):413-417
Objective To construct myeloid-specific Spi1 gene knockout mice and analyze their genotypes,so as to provide animal model basis for the study of pathological mechanism of diseases and drug targets.Methods Ac-cording to the principle of CRISPR/Cas9 technology and Cre/LoxP system,sgRNA and Donor vectors were de-signed and constructed.The transcript of Exon 2(Exon 2)was used as the knockout region,and Loxp elements were placed on both sides of Exon 2.Cas9 protein,sgRNA and Donor vector were mixed and microinjected into the fertilized eggs of C57BL/6J mice,the fertilized eggs were transplanted into the uterus of C57BL/6J pregnant female mice,and F0 generation was obtained after 19~20 days.Positive F0 mice were mated with C57BL/6J mice to ob-tain stable F1 Spi1flox/+mice.Spi1flox/+mice of F1 generation were selfed to obtain Spi1flox/flox mice.Spi1flox/flox mated with Lyz2-Cre+mice to obtain Spi1flox/+/Lyz2-Cre+mice,and then mated with Spi1flox/flox,the Spi1flox/flox/Lyz2-Cre+mice were myeloid-specific Spi1 gene knockout(KO)mice.Spi1flox/flox/Lyz2-cre-mice were used as wild-type(WT)mice.DNA of WT and KO mice was extracted,and the genotypes were identified by agarose gel electro-phoresis after PCR amplification.Western blot was used to detect the expression of spleen focus forming virus provi-ral integration oncogene,Spi-1/purine rich box-1(PU.1)in immune cells of WT and KO mice.Results The results of PCR identification showed that the genotype of mice with only 220 bp amplified by flox primer was Spi1flox/flox homozygote,and the genotype of mice with 700 bp amplified by Lyz2-Cre primer was Lyz2-Cre+.Western blot showed that compared with WT group,the protein PU.1 was not expressed in bone marrow-derived macropha-ges(BMDMs)and peritoneal macrophages(PM)in KO group(P<0.01).There was no significant difference of statistics in the expression level of PU.1 in T cells between KO mice and WT mice.The results of PCR and West-ern blot showed that myeloid-specific Spi1 KO mice were successfully constructed.Conclusion The myeloid-spe-cific Spi1 gene KO mice are successfully constructed and identified,which provides animal model basis for further revealing the potential mechanism of PU.1 inimmune regulation.
5.Breeding and genotyping of T lymphocyte-conditional Spi1 knockout mice
Huihui WANG ; Xiangling ZHU ; Xuming WU ; Huiru ZHANG ; Yuanyuan ZHOU ; Anqi WANG ; Chong LIU ; Jiajie TU
Acta Universitatis Medicinalis Anhui 2024;59(4):595-599
Objective To breed and identify the T lymphocyte-conditional Spi1 knockout mice for the further in-vestgation of the specific role of Spi1-encoded protein PU.1.Methods The Lck-Cre mice were mated with Spi1flox/flox mice to obtain Lck-Cre×Spi1flox/flox mice(T lymphocyte-specific Spi1 knockout mice),and the genotype was determined by polymerase chain reaction(PCR)and agarose gel electrophoresis.Magnetic beads were used to sort out the splenic T lymphocytes,and the knockdown efficiency of PU.1 in T cells was detected by Western blot,quantitative real-time PCR(qPCR)and flow cytometry.Results The Lck-Cre×Spi1flox/flox mouse genotype was stably inherited.Compared with Spi1flox/flox mice,the expression level of PU.1 was significantly reduced in splenic T cells of Lck-Cre×Spi1flox/flox mice.Conclusion In this study,the T lymphocyte-specific Spi1 knockout mice was successfully constructed by applying Cre/LoxP system and CRISPR/Cas9 technology,which provided a reliable an-imal model for the subsequent experiments of the specific role of PU.1 in T cell-related diseases.
6.Construction and efficiency detection of Csf1r-CreERT2 R26REYFP reporter gene mouse based on Cre/Loxp system
Xiangling ZHU ; Xuming WU ; Huihui WANG ; Yuanyuan ZHOU ; Anqi WANG ; Huiru ZHANG ; Chong LIU ; Jiajie TU
Acta Universitatis Medicinalis Anhui 2024;59(7):1175-1180
Objective To construct Csf1r-CreERT2 R26REYFP reporter gene mice and assess the efficacy of Csf1r-CreERT2-mediated enhancement of CSF1R in CD45+cells labeled with yellow fluorescein protein EYFP.Methods Csf1r-CreERT2 mice were crossbred with R26REYFP homozygous mice,and Csf1r-CreERT2R26REYFP mice were identified through PCR and Western Blot analyses.Flow cytometry was employed to evaluate CSF1R tag-efficiency in CD45+cells across different mouse tissues following tamoxifen induction.Results Csf1r-CreERT2 R26REYFP reporter gene mice were acquired.In addition,it was found that Csf1r-CreERT2-mediated EYFP could effectively mark CSF1R in various tissues of mice and CD45+cells in different locations.Compared to the R26REYF P group,the highest labeling efficiency was observed in the brain tissue(P<0.001),the lowest in the thymus tissue(P<0.05),and no sig-nificant difference was observed in the spleen tissue.Conclusion Adult Csf1r-CreERT2 mice and R26REYFP mice are effective ways to obtain Csf1r-CreERT2 R26REYFP induced conditional fluorescence mice.Csf1r-CreERT2 can mediate EYFP to effectively trace CSF1R in CD45+cells in different parts of mice.
7.Research progress on origin of abnormal aorta in coronary artery
Mingtang YE ; Yang WANG ; Di YU ; Jirong QI ; Xuming MO
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(2):117-123
Anomalous aortic origin of the coronary artery(AAOCA) refers to the abnormal initiation, route, or distribution of coronary arteries, which is generally believed to be caused by abnormal or incomplete development of embryonic coronary arteries, and is a rare congenital cardiovascular malformation. It can exist independently without other congenital heart disease. With the development of medical science and people's understanding of AAOCA, more and more AAOCA has been detected, and its clinical significance has attracted more and more attention. Based on abnormal coronary artery opening, malignant or potential contorts can cause long-term blood flow dynamic change, appear abnormal blood vessel hardening of the arteries, at the same time due to walk in the pulmonary artery and the ascending aorta between two vessels, vulnerable to the extrusion of large blood vessels, which caused a temporary blood flow in coronary artery interruption, can cause acute angina pectoris, myocardial infarction, arrhythmia, exercise-induced cardiac syncope. This review focuses on the anatomy, diagnosis and treatment of coronary artery abnormalities arising from aorta.
8.Paclitaxel drug-coated balloons combined with bare metal stents vs. bare metal stents for the treatment of superficial femoral atherosclerosis obliterans
Qijian ZHAO ; Jianbin ZHANG ; Hao ZHAO ; Bin HE ; Xuming WANG ; Bo MA ; Jie CHEN ; Chong CHEN ; Zhidong YE
Chinese Journal of General Surgery 2023;38(7):500-505
Objective:To compare the efficacy and safety of drug-coated balloons (DCB) combined with bare metal stents (BMS) and BMS only for superficial femoral atherosclerosis obliterans.Methods:The clinical and follow-up data of 80 patients (82 limbs) who received combined treatment or BMS implantation at Cardiovascular Surgery Department of China Japan Friendship Hospital from Jan 2017 to Aug 2022 were retrospectively analyzed.Results:43 patients (43 limbs) were included in combined treatment group. 37 patients (39 limbs) were in BMS only. The average lesion length of combined group was longer than BMS group (19.54±7.04 cm vs. 16.25±6.43 cm, P=0.031). The primary patency rate of combined group at 36 months was not statistically different with BMS only group (56.9% vs. 38.5%, P=0.171). The subgroup analysis of superficial femoral artery TASC C/D (Trans-Atlantic Inter-Society Consensus) and CTO (chronic total occlusion) lesions indicated that efficacy of the combined group was superior to BMS only group. The patency rates of the combined group compared with the BMS group at 36 months were 57.6% vs. 23.8%, P=0.046, 60.2% vs. 31.4%, P=0.028, respectively. There was no significant difference in the FCD-TLR (free from clinical driven target lesion revascularization) between the two groups at 36 months (72.6% vs. 66.5%, P=0.706). There was no significant difference in major adverse events between the two groups ( P>0.05). Conclusion:Paclitaxel drug-coated balloon combined with bare metal stent is a safe and effective treatment for superficial femoral atherosclerosis obliterans, which is superior to bare metal stent, especially in TASC C/D and chronic total occlusive lesions.
9.Construction of a chimeric antigen receptor CAR THP -1 cell line targeting HER2
Yizhao Chen ; Lihua Liu ; Xiangling Zhu ; Huihui Wang ; Xuming Wu ; Xuewen Tan ; Yilong Fang ; Haifeng Jiang ; Zhen Xu ; Wei Wei ; Jiajie Tu
Acta Universitatis Medicinalis Anhui 2023;58(3):352-357
Objective:
To obtain chimeric antigen receptor macrophages ( CAR-M) targeting HER2 stably transfected.
Methods :
CAR lentivirus vector targeting HER2 was constructed and infected with human monocytic leukemia cell line (THP-1) .CAR THP-1 cells with green fluorescent labeling were selected by sorting flow cytometry and continued to be cultured in vitro.The CAR THP-1 cells targeting HER2 were co-cultured with the endometrial cancer cell line Ishikawa with negative and positive HER2 expression,and their targeted phagocytosis of CAR-M to HER2 positive tumor cells was detected by imaging flow cytometry ,and the targeted phagocytosis efficiency of CAR-M to HER2 positive tumor cells was detected by flow cytometry.
Results :
CAR lentivirus infection with THP- 1 cells was less efficient ; After co-culture with cancer cells,flow cytometry and imaging flow cytometry showed that CAR THP-1 cells had enhanced phagocytosis of HER2 positive Ishikawa cells compared with the empty body group (P<0. 01) .
Conclusion
In this experiment,CAR THP-1 cell line targeting HER2 was established by constructing CAR lentivirus vector and transfecting THP-1 cells ,and it was proved that CAR THP-1 could phagocytize HER2 positive Ishikawa cells through specific targeting.
10.Relationship of in-hospital mortality and using intra-aortic balloon pump with extracorporeal cardiopulmonary resuscitation in patients with cardiac arrest: a secondary analysis based on literature data
Xiaohua CHEN ; Junyu CHEN ; Rundong WANG ; Jiezhao ZHENG ; Qilin YANG ; Jieru CHEN ; Deliang WEN ; Xuming XIONG
Chinese Critical Care Medicine 2022;34(3):269-273
Objective:To assess the effect of intra-aortic balloon pump (IABP) on in-hospital mortality in patients with cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:A retrospective study was performed on 696 patients with intra-hospital cardiac arrest undergoing ECPR from Samsung Medical Center in Korea between January 2004 and December 2013. According to whether IABP was used, the patients were divided into ECPR group and ECPR+IABP group. Cox regression and propensity score matching (PSM) were used to examine the correlation between IABP usage and in-hospital mortality, and standardized mean difference ( SMD) was used to check the degree of PSM. Survival analysis of in-hospital mortality was performed by the Kaplan-Meier method, and further analyzed by the Log-Rank test. Using the propensity score as weights, multiple regression model and inverse probability weighting (IPW) model were used for sensitivity analysis. In-hospital mortality, extracorporeal membrane oxygenation (ECMO) withdrawal success rate and neurological function prognosis were compared between the two groups. Results:A total of 199 patients with cardiac arrest undergoing ECPR were included, including 120 males and 79 females, and the average age was (60.0±16.8) years. Thirty-one patients (15.6%) were treated with ECPR and IABP, and 168 patients (84.4%) only received ECPR. The total hospitalized mortality was 68.8% (137/199). The 1 : 1 nearest neighbor matching algorithm was performed with the 0.2 caliper value. The following variables were selected to generate propensity scores, including age, gender, race, marital status, insurance, admission type, service unit, heart rate, mean arterial pressure, respiratory rate, pulse oxygen saturation, white blood cell count. After the propensity score matching, 24 pairs of patients were successfully matched, with the average age of (63.0±12.8) years, including 31 males and 17 females. The in-hospital mortality was 72.6% (122/168) and 48.4% (15/31) in the ECPR group and the ECPR+IABP group [hazard ratio ( HR) = 0.48, 95% confidence interval (95% CI) was 0.28-0.82, P = 0.007]. Multiple regression model, adjusted propensity score, PSM and IPW model showed that the in-hospital mortality in the ECPR+IABP group was significantly lower compared with the ECPR group ( HR = 0.44, 0.50, 0.16 and 0.49, respectively, 95% CI were 0.24-0.79, 0.28-0.91, 0.06-0.39 and 0.31-0.77, all P < 0.05). The combined application of IABP could improve the ECMO withdrawal success rate [odds ratio ( OR) = 8.95, 95% CI was 2.72-29.38, P < 0.001] and neurological prognosis ( OR = 4.06, 95% CI was 1.33-12.40, P = 0.014) in adult cardiac arrest patients. Conclusion:In patients with cardiac arrest using ECPR, the combination of IABP was independently associated with lower in-hospital mortality, higher ECMO withdrawal success rate and better neurological prognosis.


Result Analysis
Print
Save
E-mail