Table of Content

Volume 27 Issue 4
26 April 2022

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New development of lipid-lowering therapy of coronary heart disease: Evinacumab

WANG Qi, ZOU Yunzeng

2022, 27(4):  362-364.  doi:10.12092/j.issn.1009-2501.2022.04.001

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Homozygous familial hypercholesterolemia is a rare genetic disorder of lipid metabolism, traditional lipid-lowering therapies such as statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have little efficacy in these patients. Evinacumab can reduce the levels of LDL-C effectively. In this review, we summarize the latest advances in Evinacumab, and review the phase 2 and phase 3 clinical trials results, adverse events, and the clinical trials results in progress of Evinacumab. Finally, we discuss the current status of Evinacumab in the clinical works.

New development of lipid-lowering therapy of coronary heart disease: Inclisiran

WANG Qi, ZOU Yunzeng

2022, 27(4):  365-368.  doi:10.12092/j.issn.1009-2501.2022.04.002

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Because of high rate of nonadherence to statins, the subcutaneously injection of Inclisiran therapy intervals are from 3 months to 6 months, which will increase the patients' adherence to the Inclisiran therapy. In this review, we summarize the latest advances of Inclisiran, and review the phase 2 and phase 3 clinical trials results, adverse events, and the clinical trials results in progress of Inclisiran. Finally, we discuss the current status of Inclisiran in the clinical works. 

New development of lipid-lowering therapy of coronary heart disease: Bempedoic acid

WANG Qi, ZOU Yunzeng

2022, 27(4):  369-372.  doi:10.12092/j.issn.1009-2501.2022.04.003

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Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Lack of the activating enzyme in skeletal muscle may prevent the muscular adverse effects associated with statins. In this review, we summarize the latest advances in bempedoic acid, and review the phase 2 and phase 3 clinical trials results, adverse events, and the clinical trials results in progress of Bempedoic acid. Finally, we discuss the current status of bempedoic acid in the clinical works. 

Progress of pharmacotherapy for heart failure

PENG Juan, FAN Linlin, LI Ranyi, LI Xiaoyu, LV Qianzhou, ZOU Yunzeng

2022, 27(4):  373-381.  doi:10.12092/j.issn.1009-2501.2022.04.004

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Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure.

Progress of pharmacotherapy for myocardial hypertrophy and cardiac remodeling

PENG Juan, LI Ranyi, FAN Linlin, LI Xiaoyu, LV Qianzhou, ZOU Yunzeng

2022, 27(4):  382-389.  doi:10.12092/j.issn.1009-2501.2022.04.005

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Cardiomyopathy is a disease with abnormal myocardial structure and function. For a long time, due to the limited understanding of cardiomyopathies, cardiomyopathies are treated empirically based on symptoms (such as heart failure, arrhythmia, etc.). Over years, with the improvement of diagnosis technology and the discover of disease mechanism, a variety of drugs have been approved, such as tafamidis, patisiran and Inotersen. Many more drugs have completed preliminary safety and efficacy verification and entered Phase III trials. In addition, some cutting-edge technologies are also being developed, such as siRNA drug patisiran, CRISPR/Cas9 gene editing technology drug NTLA-2001, stem cell therapy, etc. This article discusses two cardiac problems that may be caused by cardiomyopathy: myocardial hypertrophy and cardiac remodeling, and introduces the pharmacology and related research of the latest drugs for these diseases.

Research progress of β2 microglobulin

ZHANG Xiaoyi, KUAI Zheng, ZOU Yunzeng

2022, 27(4):  390-396.  doi:10.12092/j.issn.1009-2501.2022.04.006

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β2 microglobulin (β2-MG) is a key component I molecule of the major histocompatibility complex class that assists in the cytotoxic T lymphocyte (CTL) immune response. Serum β2-MG content is dynamically correlated with many diseases. Most studies on β2-MG mainly focus on the pathogenesis of kidney disease, tumor and amyloid fibrils. In recent years, some studies have found that β2-MG is also involved in the adverse prognosis of cardiovascular system, cognitive impairment of aging and antibacterial effects. This paper summarized the domestic and foreign studies on β2-MG in recent years, and proposed the possible role of β2-MG in multi-system human body and its potential application prospect of drug molecular targeting.

Research progress and application prospects of circRNA in cardiovascular diseases

CAI Zichun, JIANG Yuanzhen, ZHANG Chunsheng, LI Jiming

2022, 27(4):  397-404.  doi:10.12092/j.issn.1009-2501.2022.04.007

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CircRNA is a single-stranded, covalently closed non-coding RNA, whose mechanism mainly involves sponge adsorption of micro RNA (miRNA), regulation of protein transcription and post-transcriptional levels, interaction with RNA-binding proteins and few coding proteins of circRNA. Meanwhile, because of its abundant expression, highly conserved and dynamic changes, circRNAs have promising applications such as becoming biomarkers of diseases, developing circRNA vaccines and gene editing therapies for circRNAs. Cardiovascular diseases are the leading cause of death from diseases worldwide, and existing therapeutic approaches can delay the development of heart diseases, but are still limited by the unknown pathogenesis and therapeutic targets. Many studies have reported the mechanistic link between circRNAs and cardiac diseases, therefore, this review is to explain the progress of circRNA research in cardiovascular diseases and to illustrate the three clinical applications in which circRNAs are currently involved.

Progress of medical treatment of coronary heart disease

CHANG Shufu

2022, 27(4):  405-408.  doi:10.12092/j.issn.1009-2501.2022.04.008

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Coronary heart disease (CHD) treatment methods are changing rapidly, and new drugs are constantly entering the clinic. Antiplatelet drugs are the basis for the treatment of CHD, but there are currently no new drugs that can challenge the status of aspirin and P2Y12 receptor inhibitors. Inflammation is the mechanism of the occurrence and development of CHD, and anti-inflammatory treatment is just beginning, and further exploration is still needed. This paper aims to summarize the progress of drug treatment for CHD and provide a new perspective for clinical practice.

Effects of PCSK9 inhibitors on blood lipids and inflammatory factors in patients with coronary heart disease

WANG Ruijie, WANG Liang, XU Dan, ZHOU Miaomiao, LI Jiming

2022, 27(4):  409-417.  doi:10.12092/j.issn.1009-2501.2022.04.009

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AIM: To observe the effect of PCSK9 inhibitors on blood lipid levels and common inflammatory factors in patients with coronary heart disease. METHODS: The clinical data of 201 patients with coronary heart disease who were admitted to the Department of Cardiology of Shanghai East Hospital from April 2020 to June 2021 were retrospectively analyzed. The patients were divided into PCSK9 inhibitor treatment group (101 cases: statin + PCSK9 inhibitor) and control group (100 cases: statin treatment only) according to their medication status. Blood lipids, blood routine, CRP and FIB were re-examined after 1 month of treatment. The changes of blood lipids and inflammatory factors before and after treatment were compared. RESULTS: Before treatment, there was no significant difference in blood lipids, blood routine, CRP and FIB between the two groups (P>0.05). The levels of sdLDL and Lp(a) were significantly decreased (P<0.05); the levels of WBC, CRP, N and FIB were significantly decreased (P<0.05). Compared with the control group, the levels of TC, HDL, LDL-C, CRP and FIB in the PCSK9 inhibitor group were significantly changed (P<0.05), and the results were statistically significant. CONCLUSION: PCSK9 inhibitors can not only reduce LDL-C levels, but also reduce Lp(a) levels. PCSK9 inhibitors can reduce CRP and FIB levels, suggesting that it can partially improve inflammation in peripheral blood in patients with coronary heart disease.

Application of chronopharmacology in the hypertension treatment

ZHANG Ningzhi, ZHAO Yuhong, TANG Minna, ZHANG Yongqiao, NING Sisi, CUI Zhaoqiang

2022, 27(4):  418-422.  doi:10.12092/j.issn.1009-2501.2022.04.010

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The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications. 

Application of β-blockers for hypertension

CUI Sumei, CUI Zhaoqiang

2022, 27(4):  423-427.  doi:10.12092/j.issn.1009-2501.2022.04.011

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β-blockers are widely administered to patients with various cardiovascular diseases including hypertension. However, in recent years, studies have questioned or even denied the antihypertensive effect of β-blockers, which has caused confusion to cardiovascular clinicians. Based on the systematic analysis of a number of studies, the author believes that β-blockers still remain the status as the first-line antihypertensives.

Treatment of hypertension complicated with hyperuricemia

LI Yuanfang, CUI Zhaoqiang

2022, 27(4):  428-432.  doi:10.12092/j.issn.1009-2501.2022.04.012

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Hypertension and hyperuricemia often coexist, and have a high incidence and often incur great harm. The current guidelines recommend active control of uric acid and blood pressure levels. But patients with high uric acid and high blood pressure still need detailed guidelines to standardize the treatment to avoid incurring more drug-related side effects. This article reviews the epidemiology and clinical harm, the therapeutic target value, the consensus and controversy on therapeutic treatment of high blood pressure combined with high uric acid.

Research progress in pharmacological and non-pharmacological treatments of hypertension

XU Jianfei, LIN Li

2022, 27(4):  433-441.  doi:10.12092/j.issn.1009-2501.2022.04.013

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Hypertension is the most common chronic non-communicable disease in the world and the most important risk factor for cardiovascular and cerebrovascular diseases. At present, the control rate of hypertension treatment standard is less than 50%, and it is still not effectively managed to a large extent. Despite numerous clinical studies and trials over the past four decades, the progress of new antihypertensive drugs has not been satisfactory. This review discusses recent advances in pharmacological and non-pharmacological treatments for patients with hypertension, and may provide new options for clinical hypertension treatment in the future.

Angiotensin receptor neprilysin inhibitor in elderly with hypertension

KUAI Zheng, ZHANG Xiaoyi, ZOU Yunzeng

2022, 27(4):  442-445.  doi:10.12092/j.issn.1009-2501.2022.04.014

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Angiotensin receptor/neprilysin inhibitor (ARNI) is a novel combination drug that is a dual inhibitor of angiotensin receptor and neprilysin. In June 2021, the National Medical Products Administration approved ARNI for hypertension indications. This review provides an update of current literature on ARNI in elderly hypertension.

Progress of hypertension pharmacological treatment

LIU Guijian, CHENG Kuan, ZHU Wenqing, GE Junbo

2022, 27(4):  446-449.  doi:10.12092/j.issn.1009-2501.2022.04.015

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Hypertension is a common cardiovascular disease. Chinese guidelines for the management of hypertension, the global practice guidelines for hypertension of the International Hypertension Society (ISH) and the guidelines for the treatment of adult hypertension drugs of the World Health Organization have been issued successively, which play an important role in guiding the clinical medication of hypertension. Calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitor (ARNI), thiazide diuretics and β-receptor blockers are commonly used in clinical antihypertensive drugs. The goal of hypertension drug control, the application timing of hypertension drugs, the selection of combined medication scheme, the drug selection of hypertension complicated with other diseases, and the medication of gestational hypertension are all problems that clinicians need to master.

New progress in research and application of fenneridone

CHENG Kuan

2022, 27(4):  450-456.  doi:10.12092/j.issn.1009-2501.2022.04.016

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Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex, which acts on receptors in the distal and collecting tubules of the nephron, causing reabsorption of sodium and secretion of potassium. Aldosterone can promote inflammatory response and lead to myocardial remodeling and fibrosis. Aldosterone acts through mineralocorticoid receptor (MR), which is mainly expressed in heart, kidney and blood vessels. Excessive activation of MR can cause endothelial dysfunction, fibrinolysis disorder, oxidative stress, cardiovascular and renal fibrosis, and eventually lead to organ injury, dysfunction and even organ failure. Mineralocorticoid receptor antagonist (MRA) can achieve cardiorenal protection by inhibiting inflammation and fibrosis caused by MR activation. The novel nonsteroidal MRA fenneridone can effectively block MR with its high selectivity and bring definite cardiac and renal protective effects.

Effect of Qiteng Xiaozhuo granule mediating miR-339-5p on inflammatory indexes in rats with chronic glomerulonephritis 

GAO Jiarong, SHI Miaomiao, CHEN Hao, JIANG Hui, QIN Xiujuan

2022, 27(4):  457-465.  doi:10.12092/j.issn.1009-2501.2022.04.017

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AIM: To investigate the effect of Qiteng Xiaozhuo granule on inflammation indexes in rats with chronic glomerulonephritis (CGN) through miR-339-5p. METHODS: CGN model was established by adriamycin (ADR) injection into tail vein of rats. Qiteng Xiaozhu granules (21.6, 10.8, 5.4 g/kg) of different doses were intragastric-fed for 30 days. Pathological changes in kidney tissues of CGN rats were observed by HE staining and electron microscopy. The contents of IL-1β, IL-6, IL-10 and TNF-α in serum and kidney tissue of CGN rats were detected by qRT-PCR, ELISA and Western blot. Relative expressions of miR-339-5p, Syk and p-Syk proteins were detected by Western blot, the relative expressions of miR-339-5p mRNA and Syk mRNA were detected by qRT-PCR. RESULTS: There were thickening of basement membrane and glomerular atrophy in the model group. Compared with the normal group, the expression of miR-339-5p and IL-10 in the model group was significantly down-regulated, while the expression of IL-1β, IL-6, TNF-α and Syk was significantly up-regulated. Qiteng Xiaozhuo granule group could significantly reduce the protein and mRNA expression levels of IL-1β, IL-6, TNF-α, Syk in kidney tissue.CONCLUSION: Qiteng Xiaozhuo granule may down-regulate the expression of inflammatory factors through miR-339-5p in the treatment of inflammatory symptoms in CGN rats.

FXR agonist GW4064 ameliorates tacrolimus-induced abnormalities in glucose metabolism

LI Hao, LI Ling, XIA Zhiping, YE Qifa, PENG Guizhu

2022, 27(4):  466-472.  doi:10.12092/j.issn.1009-2501.2022.04.018

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AIM: To investigate the expression of glucose metabolism genes associated with tacrolimus-induced post-transplant diabetes in the mouse kidney and the mechanisms involved in the regulation of glucose metabolism by farnesylate X (FXR) receptor activator.  METHODS: The gene expression levels of FXR, small heterodimeric partner-1 (SHP-1), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter protein-2 (GLUT2) were measured after 72 h in HK-2 cell lines treated with tacrolimus and tacrolimus+FXR agonist (GW4064) and control groups, respectively. C57BL/6J male mice were gavaged with tacrolimus and tacrolimus+FXR agonist for 12 weeks, respectively, and the control group was given saline to observe the changes in body weight and blood glucose; after the animals were treated, the gene expression levels of FXR, SHP-1, PEPCK, and GLUT2 were detected, respectively. RESULTS: In cellular experiments, the expression of FXR, SHP-1 and GLUT2 genes was decreased in the tacrolimus-treated group (P<0.05) and the expression of the PEPCK gene was significantly upregulated compared with the control group (P<0.05). In animal experiments, compared with the control group, the blood glucose values were significantly increased in the tacrolimus-treated group and significantly decreased in the tacrolimus+FXR agonist combination intervention group (P<0.05), and the expression of FXR, SHP-1 and GLUT2 genes were upregulated (P<0.05) and the expression of PEPCK genes was significantly decreased in the mice kidney (P<0.05).CONCLUSION: FXR agonists can improve tacrolimus-induced abnormal glucose metabolism after transplantation. Therefore, FXR may be a potential new target for the prevention and treatment of post-transplant diabetes.

Optimization and verification of orthotopic non-muscle invasive bladder cancer model in nude mice 

YE Xiaodi, MIAO Yunping, CHEN Aiying, CHENG Min, TIAN Xuejun, ZHENG Gaoli

2022, 27(4):  473-480.  doi:10.12092/j.issn.1009-2501.2022.04.019

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AIM: To optimize an orthopedic non-muscle invasive bladder cancer (NMIBC) model in nude mouse by comparing four different ways of cellular transplantation, and to evaluate the efficacy of drug by bladder instillation, so as to provide a stable and efficient animal model for the treatment of bladder cancer.  METHODS: After disruption of bladder mucosa by dilute acid-alkali or silver nitrate, T24 cells were instilled into the nude mouse bladder. T24 cells were injected directly into the bladder with mechanical injury of bladder mucosa. T24 cells were injected into the bladder wall. On the 14th day after making models, the nude mice were sacrificed. And the bladder mass and histopathological changes of tumor (including bladder) was observe to confirm the formation of orthopedic bladder cancer. The dynamic changes of orthopedic bladder cancer were observed after injecting T24 cells into the bladder wall. Gemcitabine was used to verify the applicability of the model of injecting T24 cells into the bladder wall in vivo. RESULTS: No tumor was found in the bladder after intravesical instillation of T24 cells with dilute acid-alkali or silver nitrate treatment. With mechanical injury of bladder mucosa, all nude mice had tumors after injection T24 cells. But the number of tumors varied and often occurred at multiple sites. The tumor was found in the bladder of all nude mice by injecting T24 cells into bladder wall, and there was only one tumor. The tumor showed slow linear growth within 15 days and rapid linear growth from day 18 to 31. In vivo efficacy evaluation, gemcitabine 150 mg/kg intravesical perfusion could significantly inhibit the growth of NMIBC in nude mice replicated by direct injection of T24 cells into the bladder wall, and the tumor inhibition rate was 97.1%. CONCLUSION: The orthotopic NMIBC model can not be established with the bladder mucosa injuried by dilute acid-alkali or silver nitrate treatment. The number and size of orthotopic bladder cancer are different by mechanical injury of bladder mucosa. Injection of T24 cells into the bladder wall of nude mouse can successfully establish the orthotopic NMIBC model, which can be used for the evaluation of NMIBC therapeutic drugs.