Effect of Different Types and Dosages of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) Levels: A Network Meta-analysis.

ABSTRACT: Lipoprotein(a) [Lp(a)] has become an important component of the residual risk of cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors display promising effects in controlling Lp(a) levels. However, the effects of different types and dosages of PCSK9 inhibitors on Lp(a) have not been studied in detail. These include 2 monoclonal antibodies, alirocumab and evolocumab, and inclisiran, a small interfering RNA. We searched PubMed, Web of Science, Embase, and Cochrane Library for randomized controlled trials to investigate the efficacy of PCSK9 inhibitors at the Lp(a) level. Although changes in Lp(a) levels were not the primary endpoint in any of these studies, they all described these valuable data. Forty-one randomized controlled trials with 17,601 participants were included, involving 23 unduplicated interventions. Most PCSK9 inhibitors significantly reduced Lp(a) levels compared with placebo. The pairwise comparison demonstrated no significant difference among most PCSK9 inhibitors. However, in the comparison among different dosages of alirocumab, the dosage of 150 mg Q2W showed a significant reduction in Lp(a) levels compared with the dosages of 150, 200, and 300 mg Q4W. In addition, the comparison results demonstrated the significant efficacy of evolocumab 140 mg Q2W compared with alirocumab at a dosage of 150 mg Q4W. The cumulative rank probabilities demonstrated that evolocumab 140 mg Q2W showed the highest efficacy. This study showed that PCSK9 inhibitors reduced Lp(a) levels by up to 25.1%. A biweekly dose of either 140 mg evolocumab or 150 mg alirocumab was the best treatment option. However, the reduction in Lp(a) levels with a single kind of PCSK9 inhibitor alone did not demonstrate sufficient clinical benefit. Therefore, for patients with very high Lp(a) levels who remain at high residual risk in the context of statin administration, it may be acceptable to use a kind of PCSK9 inhibitor, but the clinical benefit needs further investigation.

Different clinical phenotypes of a pair of siblings with familial hypercholesterolemia: a case report and literature review.

BACKGROUND: Familial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background. CASE PRESENTATION: We treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister. CONCLUSIONS: Patients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.

The crosstalk between NLRP3 inflammasome and gut microbiome in atherosclerosis.

Atherosclerosis (AS) is chronic pathological process based on the inflammatory reaction associated with factors including vascular endothelial dysfunction, inflammation, and autoimmunity. Inflammasomes are known to be at the core of the inflammatory response. As a pattern recognition receptor of innate immunity, the NLRP3 inflammasome mediates the secretion of inflammatory factors by activating the Caspase-1, which is important for maintaining the immune system and regulating the gut microbiome, and participates in the occurrence and development of AS. The intestinal microecology is composed of a large number of complex structures of gut microbiota and its metabolites, which play an important role in AS. The gut microbiota and its metabolites regulate the activation of the NLRP3 inflammasome. Targeting the NLRP3 inflammasome and regulating intestinal microecology represent a new direction for the treatment of AS. This paper systematically reviews the interaction between the NLRP3 inflammasome and gut microbiome in AS, strategies for targeting the NLRP3 inflammasome and gut microbiome for the treatment of AS, and provides new ideas for the research and development of drugs for the treatment of AS.

Comparison of Beneficial Effects of Acupuncture at PC6, LU7 & Non- acupuncture Points on Cardiac Cell Function in Myocardial Ischemia (MI) Rats by Testing Protein Expression of L-type Calcium Channel Protein and its Related Protein.

The mechanism of why electro-acupuncture (EA) at PC6 improves the heart function was investigated by studying how the L-type cardiac voltage-dependent calcium channel in myocardial ischemia (MI) is regulated. Cava,., Cavo and Cava2-61 are main component proteins of L-type calcium channel; CaM and Calmodulin kinase II (CaMKII) are Ca2+ channel associated proteins. In this experiment, MI was induced by injection of isoproterenol (ISO) in rats and electrocardiograms (ECGs) were recorded before and after every injection, and protein expressions of Cava,c, Cavp, Cava2_61, CaM and CaMKII were higher [The protein expression increased 43.39%, 54.85%, 47.08%, 48.29% and 50.36% respectively] than the control rats significantly (p<0.05). After MI induction, the MI rats were divided into three groups, including PC6 (Neiguan-point), LU7 (Lieque-point) and Non-acupuncture-point group, which were acupunctured once a day for 7 days respectively. After EA at PC6, the protein expressions showed obvious decrease [EA at PC6: the protein expressions of Cava1c, CavP, Cava2-81, CaM and CaMKII decreased 26.36%, 27.58%, 25.21%, 27.21% and 26.61% respectively.] and they are all lower than MI rats significantly (p<0.05). After EA at LU7 and Non-acupuncture-point, the protein expressions showed no significant changes. The effect of EA at PC6 was significantly better than LU7 and Non- acupuncture-point (p<0.05). PC6 is an acupoint of the pericardium meridian, and the pericardium meridian, which corresponds to opioid system according to Li P's research, can affect the cardio-vascular function directly. LU7 is located on the lung meridian; it cannot affect the heart function directly although the lung is related to the heart in blood circulation function so PC6 showed the target treating effect of meridian specificity on regulating the L-type calcium channel in MI.

[Clinical study on treatment of carotid atherosclerosis with extraction of polygoni cuspidati rhizoma et radix and crataegi fructus: a randomized controlled trial].

OBJECTIVE: To observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis. METHOD: Sixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1. RESULT: After 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05). CONCLUSION: Detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.

Copper homeostasis and cuproptosis in atherosclerosis: metabolism, mechanisms and potential therapeutic strategies.

Copper is an essential micronutrient that plays a pivotal role in numerous physiological processes in virtually all cell types. Nevertheless, the dysregulation of copper homeostasis, whether towards excess or deficiency, can lead to pathological alterations, such as atherosclerosis. With the advent of the concept of copper-induced cell death, termed cuproptosis, researchers have increasingly focused on the potential role of copper dyshomeostasis in atherosclerosis. In this review, we provide a broad overview of cellular and systemic copper metabolism. We then summarize the evidence linking copper dyshomeostasis to atherosclerosis and elucidate the potential mechanisms underlying atherosclerosis development in terms of both copper excess and copper deficiency. Furthermore, we discuss the evidence for and mechanisms of cuproptosis, discuss its interactions with other modes of cell death, and highlight the role of cuproptosis-related mitochondrial dysfunction in atherosclerosis. Finally, we explore the therapeutic strategy of targeting this novel form of cell death, aiming to provide some insights for the management of atherosclerosis.

Geniposide for treating atherosclerotic cardiovascular disease: a systematic review on its biological characteristics, pharmacology, pharmacokinetics, and toxicology.

In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body's antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies.

Triglyceride-glucose index's link to cardiovascular outcomes post-percutaneous coronary intervention in China: a meta-analysis.

Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post-treatment. This meta-analysis investigated the relationship between the post-PCI triglyceride-glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random-effects models. Cluster-robust standard errors crafted the dose-response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post-PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65-2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34-2.46; I2 = 92%), 2.57 for non-fatal MI (95% CI 1.49-4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23-3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all-cause mortality, the HR was 1.93 (95% CI 1.35-2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non-fatal MI but low certainty for all-cause mortality, revascularization, and MACE. The TyG index may predict risks of post-PCI MACE, all-cause mortality, non-fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post-PCI was identified. Future research should validate these findings.

Exploring the causal role of immune cells in vascular dementia: A bidirectional mendelian randomization study.

BACKGROUND: The aim of this study was to explore the causal association between immune cells and VaD based on a two-sample bidirectional Mendelian randomization study. METHODS: Bidirectional two-sample MR analyses based on pooled datasets from publicly available genome-wide association studies were performed using inverse variance weighted (IVW), weighted median (WE), and MR-Egger regressions to evaluate the causal relationships between immune cells and vascular dementia. Heterogeneity was assessed using Cochran's Q statistic. The reliability of the MR analysis results was verified by using the MR-PRESSO method for outlier detection, the MR-Egger method for horizontal multivariate analysis, and the leave-one-out method for sensitivity analysis. RESULTS: Specifically, 27 immunophenotypes were associated with VaD pathogenesis, including Sw mem %lymphocyte (P = 0.043), CD38 on CD20- (P = 0.039), CD11c+ monocyte AC (P = 0.024), DC AC (P = 0.002), CCR2 on CD62L+ myeloid DC (P = 0.039), Resting Treg %CD4 (P = 0.042), Activated & resting Treg %CD4+ (P = 0.038), CD28+ CD45RA- CD8br %CD8br (P = 0.047), NK %CD3- lymphocyte (P = 0.042), CD45 on B cell (P = 0.029), FSC-A on NKT (P = 0.033), CD45 on CD33br HLA DR+ CD14- (P = 0.039) were significantly correlated with increased VaD risk. Additionally, four immune phenotypes, namely, CD19 on CD20-, Resting Treg %CD4, Activated & resting Treg %CD4+, and CD11c+ monocyte AC, showed bidirectional effects on VaD. CONCLUSIONS: MR analysis revealed potential causal relationships between certain immune cells and VaD. Our preliminary exploration through immune cell infiltration analysis highlights the significant value of immune cells in VaD. Therefore, this study may provide a new perspective for the prevention and treatment of VaD.

[Effects of huannao yicong recipe extract on the learning and memory and related factors of Abeta generation in the brain of APP transgenic mice].

OBJECTIVE: To study the effects of Huannao Yicong Recipe (HNYCR)extract on the learning and memory ability, and the expressions of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), presenilin-1 (PS-1), and beta amyloid protein (Abeta)in hippocampus CA1 area of APP transgenic mice, and to explore its mechanisms for treating Alzheimer's disease (AD). METHODS: Totally 3-month-old APP695V7171 transgenic mice were used to establish the AD model in this research. They were randomly divided into the model group, the Donepezil group, the large dose HNYCR extract group, the small dose HNYCR extract group, and the normal control group (C57BL/6J mice), 15 in each group. These animals were gavaged for 4 continuous months. Relevant indicators were detected: Morris water maze test was used to measure the spatial learning and memory ability. The immunohistochemical assay was used to detect the expressions of APP, BACE1, PS-1, and Abeta. RESULTS: The times of crossing the original platform and the swimming time and distance in the fourth quadrant of the 7-month-old APP transgenic mice were significantly reduced in Morris water maze test, when compared with the normal control group (P < 0.01). The times of crossing original platform and the swimming time and distance in the fourth quadrant of all treatment groups significantly increased in Morris water maze test, when compared with the model group (P < 0.05). The expressions of APP, BACE1, PS-1, and Abeta in hippocampus CA1 area of 7-month-old model mice increased significantly (P < 0.01), when compared with the normal control group. The expressions of APP, BACE1, PS-1, and Abeta in each 7-month-old intervention groups were significantly reduced, when compared with the model group (P < 0.01). CONCLUSION: Early application of HNYCR extract can obviously improve the learning and memory ability of APP transgenic mice that has declined, reduce the expressions of APP, BACE1, PS-1, and Abeta in the hippocampal CA1 area, reduce the production of Abeta, and slow down the pathological process of brains in APP transgenic mice.

Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview.

Background and ethnopharmacological relevance: The morbidity and mortality of cardiovascular diseases (CVDs) are among the highest of all diseases, necessitating the search for effective drugs and the improvement of prognosis for CVD patients. Paeoniflorin (5beta-[(Benzoyloxy)methyl] tetrahydro-5-hydroxy-2-methyl-2,5-methano-1H-3,4-dioxacyclobuta [cd] pentalen-1alpha (2H)-yl-beta-D-glucopyranoside, C23H28O11) is mostly derived from the plants of the family Paeoniaceae (a single genus family) and is known to possess multiple pharmacological properties in the treatment of CVDs, making it a promising agent for the protection of the cardiovascular system. Aim of the study: This review evaluates the pharmacological effects and potential mechanisms of paeoniflorin in the treatment of CVDs, with the aim of advancing its further development and application. Methods: Various relevant literatures were searched in PubMed, ScienceDirect, Google Scholar and Web of Science. All eligible studies were analyzed and summarized in this review. Results: Paeoniflorin is a natural drug with great potential for development, which can protect the cardiovascular system by regulating glucose and lipid metabolism, exerting anti-inflammatory, anti-oxidative stress, and anti-arteriosclerotic activities, improving cardiac function, and inhibiting cardiac remodeling. However, paeoniflorin was found to have low bioavailability, and its toxicology and safety must be further studied and analyzed, and clinical studies related to it must be carried out. Conclusion: Before paeoniflorin can be used as an effective therapeutic drug for CVDs, further in-depth experimental research, clinical trials, and structural modifications or development of new preparations are required.

Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Polydatin is a bioactive ingredient extracted from the roots of the Reynoutria japonica Houtt, and it is a natural precursor of resveratrol. Polydatin is a useful inhibitor of inflammation and acts as a regulator of lipid metabolism. However, the specific mechanisms of action of polydatin in atherosclerosis (AS) remains poorly explained. AIM OF THE STUDY: The aim of this study was to assess the efficacy of polydatin on inflammation induced by the inflammatory cell death and autophagy in AS. MATERIALS AND METHODS: Apolipoprotein E knockout (ApoE-/-) mice were fed with a high-fat diet (HFD) for 12 weeks to induce the formation of atherosclerotic lesions. The ApoE-/- mice were then randomly divided into the following six groups: (1) model group, (2) simvastatin group, (3) MCC950 group, (4) low dose polydatin group (Polydatin-L), (5) medium dose polydatin group (Polydatin-M), (6) and high dose polydatin group (Polydatin-H). The C57BL/6J mice were treated as controls and administered a standard chow diet. All mice were gavaged once daily for 8 weeks. The distribution of aortic plaques was observed by En Oil-red-O staining and hematoxylin and eosin staining (H&E). Oil-red-O staining was used to observe lipid content in the aortic sinus plaque; Masson trichrome staining was used to gauge collagen content in the plaque; and immunohistochemistry was used to evaluate smooth muscle actin (α-SMA) and CD68 macrophages marker expression levels in the plaque, which were used to assess the vulnerability index of the plaque. The lipid levels were measured using an enzymatic assay with an automatic biochemical analyzer. The level of inflammation was detected by enzyme-linked-immunosorbent assay (ELISA). Autophagosomes were detected by transmission electron microscopy (TEM). Pyroptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)/caspase-1 and other proteins related to the expression levels of autophagy and pyroptosis were detected by Western blot analysis. RESULTS: Nucleotide oligomerization (NOD)-like receptor (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome activation leads to pyroptosis, including the cleavage of caspase-1, interleukin (IL)-1ß and IL-18 production, and the co-expression of TUNEL/caspase-1-all of these are inhibited by polydatin, whose inhibitory effect is similar to that of MCC950, a specific inhibitor of NLRP3. Further, polydatin decreased the protein expression of NLRP3 and the phosphorylated mammalian target of rapamycin (p-mTOR), and increased the number of autophagosomes as well as the increased the cytoplasmic microtubule-associated protein light chain 3 (LC3)/autophagosome membrane-type LC3 ratio. Moreover, the protein expression levels of p62 decreased, suggesting that polydatin can increase autophagy. CONCLUSIONS: Polydatin can inhibit the activation of the NLRP3 inflammasome and cleavage of caspase-1, thereby inhibiting pyroptosis and secretion of inflammatory cytokines, and promoting autophagy through NLRP3/mTOR pathway in AS.

[Effects of huannao yicong formula extract on behavior and ultrastructure of hippocampus mitochondria of APP transgenic mice of different months].

OBJECTIVE: To study the effects of Huannao Yicong formula (HNYCF) extract on behavior and ultrastructure of mitochondria in hippocampus CA1 area of APP transgenic mice of different months, and explore its partial mechanism in treating Alzheimer's disease (AD) through the perspective of energy metabolism. METHOD: One hundred and twenty APP695V717I transgenic mice of 3-month old were divided randomly into model group, Donepezil group (0.65 x 10(-3) g x kg(-1) x d(-1)), HNYCF extract large dose group (2.8 g x kg(-1) x d(-1)) and HNYCF extract small dose group (1.4 g x kg(-1) x d(-1)), and 30 mice in each group. Another 30 C57BL/6J mice with the same age and background were used as normal control group. All animals were administered once daily by gavage with the corresponding drug or distilled water. The course of intervention was 4 and 6 months. Behavioral changes were observed by Morris water maze test and step down test. Ultrastructure of mitochondria in hippocampus CA1 area was observed by transmission electron microscope. RESULT: At the age of 7 and 9 month, the number of times of passing through platform, swimming time and path length of model group increased significantly (P < 0.05, P < 0.01) in Morris water maze test, and the latent period decreased (P < 0.01) in step down test compared with normal group, and it would get worse with the development of disease course. HNYCF extract could increase the number of times of passing through platform, swimming time and path length (P < 0.05, P < 0.01) in Morris water maze test, prolong latent period in step down test of different age. At the age of 7 and 9 month, mitochondrial of hippocampus CA1 area was disrupted and dissolved. Most ridge structure arranged in a mess, and some ridge showed expanding, matrix loosing and swollen appearance, and it would get worse with the development of disease course. HNYCF extract could improve ultrastructure of mitochondria in hippocampus CA1 area, and increase its quality. CONCLUSION: Learning and memory ability decreased in APP transgenic mice model, and the quantity of neural mitochondria in hippocampus CA1 area with structure disrupting, and it would get worse with the development of disease course. HNYCF extract could improve the learning and memory ability of APP transgenic mice model, its mechanism might relate with improving ultrastructure of mitochondria in hippocampus, and increasing its quantity.

Targets of statins intervention in LDL-C metabolism: Gut microbiota.

Increasing researches have considered gut microbiota as a new "metabolic organ," which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.

Exploring the therapeutic mechanism of Baduanjin in the treatment of elderly stable angina pectoris based on the gut microbiota-lipid metabolism spectrum: Study protocol for a randomized controlled trial.

Importance: Stable angina pectoris (SAP) often occurs in the elderly and is relatively stable for 1-3 months; however, if patients do not receive effective treatment, life-threatening acute myocardial infarction could occur. Patients with different clinical types of coronary heart disease have different intestinal flora. Baduanjin, a traditional Chinese Qigong, has been used as adjuvant therapy to improve the symptoms of patients with SAP. Objective: To determine the effect of Baduanjin exercise on the symptoms of patients with SAP and the intestinal flora, explore the action links and targets of Baduanjin intervention in elderly patients with SAP, and explain its mechanism. Design: A single-center, single-blind, randomized controlled trial. Patients and outcome assessors were blinded to group allocation. Setting: The trial will be conducted at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. Participants: One hundred and eighty patients aged 60 to 80 years with stable angina pectoris (I-III) were intervened for 8 weeks and followed up for half a year. Interventions: Among the screened patients, 180 patients will be randomly assigned to either the Baduanjin or the control group at a 1:1 ratio (exercise duration: for 3-5 times a week, for 8 weeks) of moderate-intensity Baduanjin or free activities. Main and secondary results: The main result is the total effective rate for angina pectoris symptoms; secondary results include the duration of angina pectoris, number of angina pectoris episodes per week, nitroglycerin consumption, nitroglycerin reduction rate, Seattle angina score (SAQ), quality of life (SF-36),Traditional Chinese Medicine (TCM) syndrome scores, electrocardiogram (ECG) changes, blood lipid serum hypersensitive C-reactive protein levels, intestinal flora changes, serum changes in the intestinal flora metabolite Trimetlylamine oxide (TMAO), and non-targeted liposome detection. Adverse events will be recorded throughout the experiment, and the data will be analyzed by researchers who did not know about the assignment. Discussion: This study provides compelling evidence for at-home use of Baduanjin exercise to relieve SAP-associated symptoms. Trial registration: This study was approved by the ethics committee of Guang'anmen Hospital of China Academy of Chinese Medical Sciences (2022-121-KY). The trial has been registered in Chinese Clinical Trial Registration Center (ChiCTR2200062450).

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines. METHODS: Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software. RESULTS: Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group. CONCLUSION: Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

[Clinical study on the treatment of abnormal blood lipids complicated with carotid atherosclerosis with lipid-reducing red rice minute powder: a randomized controlled trial].

OBJECTIVE: To observe the clinical effects of lipid-reducing red rice minute powder (LRRMP) on the levels of blood lipids, carotid artery intima-media thickness (IMT), and the plaque integral of hyperlipidemia patients complicated with carotid atherosclerosis. METHODS: This study was conducted from April 2005 to April 2006 according to inclusion criteria. Sixty hyperlipidemia patients complicated with carotid atherosclerosis were randomly assigned to the treatment group (20 cases), the Chinese medicine control group (CM control group, 20 cases), and the Western medicine control group (WM control group, 20 cases). They were recruited from the community of secondary machine tool factory of Jinan. Patients in the treatment group took LRRMP (175 mg/pill), one pill each time, twice daily. Patients in the CM control group took Xuezhikang Capsule (300 mg/pill), 2 pills each time, twice daily. Patients in the WM control group took Lovastatin Tablet (20 mg/tablet), 1 tablet each time, once daily. The course of treatment was 6 successive months for all. They avoided taking any lipid-regulating or anti-atherosclerotic drugs during the therapeutic course. The changes of Chinese medicine symptom scores, serum TC, TG, LDL-C, and HDL-C levels, IMT of the carotid artery, and the plaque integral before and after treatment were observed. RESULTS: After 6 months of treatment the Chinese medicine symptom scores reduced in each group ( P<0.05 or P<0.01), and the treatment group was superior to WM control group (P<0.05). Serum TC, TG and LDL-C levels were significantly lowered (P<0.05 or P<0.01), showing no significant difference in inter-group comparison (P>0.05). There was no statistical significance of the serum HDL-C level in each group (P>0.05). The IMT and the plaque integral significantly reduced (P<0.05, P<0.01), showing no statistical difference among all groups. One patient in the WM control group dropped out because of transaminase elevation. No serious adverse reaction correlated with the drugs occurred during the therapeutic course in the rest two groups. CONCLUSIONS: LRRMP showed definite effects on lipid-regulating and anti atherosclerosis. Its effects were equivalent to Xuezhikang Capsule and Lovastatin Tablet. Besides, it was safe and economic, and deserved further studies.

[Therapeutic efficacy assessment of Chinese medicine on mild cognitive impairment].

OBJECTIVE: To systematically analyze the therapeutic efficacy and safety of Chinese medicine on aged patients with mild cognitive impairment (MCI). METHODS: The PubMed, EMbase, Cochrane Library, CNKI, VIP, Wanfang Database, and CBM database were retrieved by computer. On the basis of strictly assessing the quality of literatures, the evidence quality was assessed using GRADE Software. RESULTS: Totally 680 papers were primarily retrieved and analyses were conducted in the finally selected 22 RCT articles. Descriptive analyses were conduced due to different interventions in each study. The therapeutic efficacy was assessed as follows. (1) As to the conversion of MCI to Alzheimer's disease (AD), no case conversed to MCI in Jiawei Wuzi Yanzong Granule Group and Shenyin Oral Liquid Group. But there was no statistical difference when compared with that in the placebo group and the vitamin E group. Significant difference was shown between Tiantai No. 1 and the placebo. (2) As for the improvement of cognitive functions, relative therapeutic efficacies of Chinese herbs were different. (3) The improvement of the activities of daily life, serum SOD and MDA contents, and P amyloid concentration in MCI patients was different due to the application of different therapeutic drugs. CONCLUSION: Chinese herbs showed certain therapeutic efficacy in improving MCI. But clinical application could not be recommended due to poor qualities of literatures and evidence.

[Effects of early intervention with Huannao Yicong formula effective components on behavior and cholinergic system of ß-amyloid precursor protein transgenic mice].

OBJECTIVE: To observe the effects of early intervention with effective components from a Chinese herbal formula (Huannao Yicong formula, HNYCF) on behavior and related indicators of cholinergic system in ß-amyloid precursor protein (APP) transgenic mice. METHODS: Sixty 3-month-old APP695 V717I transgenic mice were randomly divided into model group, high-dose HNYCF group (2.80 g/(kg·d)), low-dose HNYCF group (1.40 g/(kg·d)) and donepezil group (0.65 mg/(kg·d)), with 15 mice in each group. Fifteen non-transgenic mice of the same genetic background were used as normal group. The model group and normal group were fed with equal volume of distilled water by gavage. After 6-month continuous medication, the Morris water maze and the passive avoidance test were used to detect the visual spatial learning and memory ability of each mouse. Then the mice were decapitated and their cerebral cortex and hippocampus were isolated to homogenate by sonication. Contents of acetylcholine (ACh) and acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity in the homogenate were determined by enzyme-linked immunosorbent assay, and protein contents of cerebral cortex and hippocampus were measured by Coomassie brilliant blue method. RESULTS: Compared with the model group, high- and low-dose HNYCF and donepezil hydrochloride all improved spatial learning of APP mice in the Morris water maze. The ratio of swimming distance in the central area in the high-dose HNYCF group was longer than that in the model group (P<0.05). In the passive avoidance test, high- and low-dose HNYCF and donepezil hydrochloride improved memory function of APP mice by improving the escape latency and reducing the number of errors (P<0.05, P<0.01). High- and low-dose HNYCF and donepezil hydrochloride reduced the content of AChE, increased the activity of ChAT (P<0.01, P<0.05) and improved the content of ACh in hippocampus (P<0.05); high- and low-dose HNYCF and donepezil hydrochloride increased the content of ACh in cortex (P<0.05). Donepezil hydrochloride reduced the content of AChE in cortex (P<0.05), however, high- and low-dose HNYCF had no obvious influence (P>0.05). High- and low-dose HNYCF increased the content of ChAT in cortex (P<0.05), whereas donepezil hydrochloride had no obvious influence (P>0.05). CONCLUSION: Early intervention with HNYCF effective components can improve the learning and memory ability of APP transgenic mice. The mechanism may be related to enhancing the function of cholinergic system.