1.Mechanism of Qishen Yiqi Dropping Pills in regulating gut microbiota and ROS/TXNIP/NLRP3 signaling pathway to improve chronic heart failure in rats
Lifei LYU ; Tingting ZHU ; Fan DING ; Yingdong LU ; Xiangning CUI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):354-369
Objective:
This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods:
Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing.
Results:
Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05).
Conclusion
QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.
2.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
3.Mechanism of dexmetomidine alleviating inflammatory injury in rats with lipopolysaccharide-induced myocarditis
Di-Sheng CAI ; Jian-Guang REN ; Xiao-Mei LU ; Zhi-Ying ZHOU
Journal of Regional Anatomy and Operative Surgery 2024;33(6):479-485
Objective To investigate the effect of dexmedetomidine(Dex)on inflammatory injury in rats with lipopolysaccharide(LPS)-induced myocarditis(Myo)by regulating AMP-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods Rats were randomly divide into the NC group,the Myo group,and the L-Dex group(10 μg/kg Dex),the M-Dex group(30 μg/kg Dex),the H-Dex group(50 μg/kg Dex),the AICAR group(100 mg/kg AMPK/SIRT1/NF-κB signal pathway activator),the H-Dex+GSK690693 group(50 μg/kg Dex+0.2 μmol/kg AMPK/SIRT1/NF-κB signal pathway inhibitor GSK690693),with 10 rats in each group.M-mode echocardiography system was used to evaluate the cardiac function of rats;ELISA kit was used to detect the levels of serum interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),and malondialdehyde(MDA)in rats;TUNEL staining was used to observe cell apoptosis;HE staining was used to observe the pathological changes of myocardial tissue;RT-qPCR was used to detect the mRNA expression of C-X-C motif chemokine ligand 1(CXCL1),C-X-C motif chemokine ligand 2(CXCL2),and vascular cell adhesion molecule-1(VCAM-1)in rat myocardial tissue;Western blot was used to detect the expression of AMPK/SIRT1/NF-κB pathway-related proteins in rat myocardial tissue.Results There was no abnormal change in cardiomyocytes in the NC group,and cardiomyocytes in the Myo group showed deformation,necrosis,inflammatory cell infiltra-tion,and mesenchymal congestion;necrosis,inflammatory cell infiltration,and mesenchymal congestion in the L-Dex group,the M-Dex group,the H-Dex group,and the AICAR group were improved compared with that in the Myo group;changes in cardiomyocytes in the H-Dex group and the AICAR group were similar to those in the NC group,and changes in cardiomyocytes in the H-Dex+GSK690693 group were similar to those in the Myo group.Compared with the NC group,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the Myo group were obviously decreased(P<0.05),left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),expression levels of IL-1β,IL-6,TNF-α,MDA,CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB,NF-κB p65 and cardiomyocyte apoptosis rate were obviously increased(P<0.05).Compared with the Myo group,the LVEF,LVFS,expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the L-Dex group,the M-Dex group,the H-Dex group and the AICAR group were obviously increased(P<0.05),LVESV,LVEDV,LVESD,LVEDD,expression levels of IL-1β,IL-6,TNF-α,MDA,CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB,NF-κB p65 and cardiomyocyte apoptosis rate were obviously decreased(P<0.05),and the effects were more obvious with the increase of the dosage of Dex.There was no significant difference in the above results between the AICAR group and the H-Dex group(P>0.05).Compared with the H-Dex group,the LVEF,LVFS,expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the H-Dex+GSK690693 group were obviously decreased(P<0.05),LVESV,LVEDV,LVESD,LVEDD,levels of IL-1β,IL-6,TNF-α,MDA,cardiomyocyte apoptosis rate,the expression of CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB and NF-κB p65 protein were obviously increased(P<0.05).Conclusion Dex may alleviate LPS-induced inflammatory injury in Myo rats by up-regulating AMPK/SIRT1/NF-κB signaling pathway.
4.Evaluation of life cycle management system on patients'prognosis after transcatheter aortic valve replacement
Ruo-Yun LIU ; Ran LIU ; Mei-Fang DAI ; Yue-Miao JIAO ; Yang LI ; San-Shuai CHANG ; Ye XU ; Zhi-Nan LU ; Li ZHAO ; Cheng-Qian YIN ; Guang-Yuan SONG
Chinese Journal of Interventional Cardiology 2024;32(6):311-316
Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9%vs.17.7%,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P<0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95%CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.
5.Clinical Analysis of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Children
Tian-Dan LI ; Shao-Yan HU ; Zong ZHAI ; Guang-Hua CHEN ; Jun LU ; Hai-Long HE ; Pei-Fang XIAO ; Jie LI ; Yi WANG
Journal of Experimental Hematology 2024;32(1):78-84
Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)%,(95.0±4.9)%and(90.7±6.3)%respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.
6.Extracorporeal fenestration vs. laser in situ fenestration for reconstruction of the left subclavian artery in patients with aortic arch diseases
Jinbao QIN ; Sen YANG ; Xing ZHANG ; Qiming WANG ; Guang LIU ; Xiaobing LIU ; Weimin LI ; Xinwu LU
Chinese Journal of General Surgery 2024;39(9):681-685
Objective:To compare the effectiveness and safety of in vitro fenestration and in situ fenestration for reconstruction of the left subclavian artery in patients with aortic arch diseases.Methods:A retrospective analysis was conducted on 80 patients with thoracic aortic dissection, aortic aneurysm, and aortic intramural hematoma involving the left subclavian artery at our center from Jan 2020 to Oct 2023.Results:Thirty-eight patients underwent in vitro fenestration to reconstruct the left subclavian artery, while 42 patients underwent in situ laser fenestration to reconstruct the left subclavian artery. The technical success rates were 97.4% and 97.6% respectively, without statistically significance ( P>0.05). Postoperative CTA examination showed that the primary rupture of the dissection was completely closed, 3 cases had type Ⅱ endoleak in vitro fenestration, and 2 cases had type Ⅱ endoleak in laser in situ fenestration. The blood flow inside the fenestration stent was fluent. During the perioperative period, one patient in the in vitro fenestration group experienced mild cerebral infarction (2.6%), one patient had mild paraplegia, and no related complications occurred in the other patients. Conclusion:For patients with aortic arch diseases, both in situ laser fenestration and in vitro fenestration are safe and effective.
7.Research progress of oral wearable devices
Wu-Di LU ; Yu-Guang WANG ; Yu ZHANG
Chinese Medical Equipment Journal 2024;45(8):91-101
The research progress of oral wearable devices was reviewed,including protective trays,dental sensors,wearable electromyography devices,pacifier-shaped wearable devices,tongue devices and etc.The advantages and disadvantages of oral wearable devices were analyzed,and the challenges faced by oral wearable devices were described.It's pointed out the futural oral wearable devices would involve in unified and effective standard diagnosis data system,enhanced comfort and concealment of the devices,development of the materials and processes and intelligent integration of collection,diagnosis and treatment.[Chinese Medical Equipment Journal,2024,45(8):91-101]
8.The application of modified Hanley surgery in abscess of anal tube space and its influences on anal function, interleukin-8 and interleukin-6
Desheng ZOU ; Lifeng LU ; Jiayang ZHOU ; Guang LIU
Chinese Journal of Postgraduates of Medicine 2024;47(5):422-427
Objective:To investigate the application of modified Hanley surgery in abscess of anal tube space (AATS), and its influences on anal function, interleukin (IL)-8 and IL-6.Methods:The clinical data of 96 patients with AATS from February 2020 to February 2022 in Shaoxing Central Hospital were retrospectively analyzed. Among them, 48 patients were treated with incision-thread drawing procedure (ITDP group), and 48 patients were treated with modified Hanley group (modified Hanley group). The curative effect, anal function, inflammatory factor level, neovascularization factor level and wound healing status were compared between the two groups.Results:There was no significant difference in the recovery rate between modified Hanley group and ITDP group: 100.00% (48/48) vs. 95.83% (46/48), χ2 = 0.51, P>0.05. The poor rate of anal function 2 months after surgery in modified Hanley group was significantly lower than that in ITDP group: 0 vs. 12.50% (6/48), and there was statistical difference ( P<0.05). The tumor necrosis factor-α(TNF-α), IL-8 and IL-6 24 h after surgery in modified Hanley group were significantly lower than those in ITDP group: (127.11 ± 13.96) ng/L vs. (160.59 ± 11.57) ng/L, (92.20 ± 11.62) ng/L vs. (124.33 ± 12.05) ng/L and (79.38 ± 12.47) ng/L vs. (100.07 ± 12.50) ng/L, and there were statistical differences ( P<0.01). The monocyte chemotactic protein-1 1 week after surgery in modified Hanley group was significantly lower than that in ITDP group: (92.85 ± 14.63) ng/L vs. (122.90 ± 15.59) ng/L, the vascular endothelial growth factor-A and transforming growth factor-β 1 were significantly higher than those in ITDP group: (188.06 ± 22.53) ng/L vs. (137.80 ± 19.52) ng/L and (1 897.6 ± 97.3) ng/L vs. (1 608.6 ± 98.1) ng/L, and there were statistical differences ( P<0.01). The pain score, edema score and neonatal granulation score 7, 14 and 21 d after surgery in modified Hanley were significantly lower than those in ITDP group, and there were statistical differences ( P<0.01). Conclusions:In the treatment of AATS, the modified Hanley surgery not only contributes to the thorough removal of the lesions, but also plays a positive role in protecting the anal function, reducing the level of inflammation, and promoting the recovery of endothelial function.
9.Clinical study on the treatment of high perianal abscess with floating line drainage through small incision
Desheng ZOU ; Lifeng LU ; Yingfeng ZHU ; Jiayang ZHOU ; Yuan BIAN ; Guang LIU
Chinese Journal of Postgraduates of Medicine 2024;47(12):1148-1152
Objective:To explore the clinical efficacy of small incision floating line drainage for the treatment of high perianal abscess.Methods:A retrospective analysis was conducted on the clinical data of 95 patients with high perianal abscess treated at the Medical Community General Hospital of Shaoxing Central Hospital from April 2019 to April 2021. Among them, 47 cases were treated with small incision floating line drainage (experimental group), and 48 cases were treated with conventional multi incision drainage (control group). The surgical time, intraoperative bleeding, postoperative pain, urination status, anal function evaluation, wound healing status and the clinical efficacy of the patient after 2 months of treatment were compared between the two groups.Results:The surgical time, intraoperative bleeding volume in the experimental group were lower than those in the control group: (18.70 ± 0.48) min vs. (38.10 ± 2.52) min, (32.35 ± 3.56) ml vs. (51.56 ± 6.24) ml, there were statistical differences ( P<0.05). The postoperative pain, urination status, anal function evaluation in the experimental group were better than those in the control group. In the experimental group, multiple incision drainage had a greater impact on patients and the wound healing cycle was longer. After treatment for 2 months, the total effective rate in the experimental group was better than that in the control group: 100.00%(47/47) vs. 91.67%(44/48), there was statistical difference ( χ2 = 4.09, P<0.05). Conclusions:Patients with high perianal abscess and treated with small incision floating line drainage has a shorter wound healing cycle, less pain, lower anal damage, and better clinical efficacy.
10.Development and Analysis of Standards for Drugs Under Special Management
Kuikui GENG ; Ling JIANG ; Jiancun ZHEN ; Tianlu SHI ; Wei ZHANG ; Jin LU ; Jianqing WANG ; Xiaoyang LU ; Qianzhou LYU ; Zhiqing ZHANG ; Ying CHEN ; Hong XIA ; Qin GUANG ; Hongpeng BI
Herald of Medicine 2024;43(8):1217-1221
Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.


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