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Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, and antioxidant defense. Copper level has been proved to be closely related to the morbidity and mortality of cardiovascular diseases such as atherosclerosis, heart failure, and diabetic cardiomyopathy (DCM). Copper deficiency can induce cardiac hypertrophy and aggravate cardiomyopathy, while copper excess can mediate various types of cell death, such as autophagy, apoptosis, cuproptosis, pyroptosis, and cardiac hypertrophy and fibrosis. Both copper excess and copper deficiency lead to redox imbalance, activate inflammatory response, and aggravate diabetic cardiomyopathy. This defective copper metabolism suggests a specific metabolic pattern of copper in diabetes and a specific role in the pathogenesis and progression of DCM. This review is aimed at providing a timely summary of the effects of defective copper homeostasis on DCM and discussing potential underlying molecular mechanisms.

Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches.

Cardiometabolic diseases are reaching epidemic proportions worldwide. Dietary fiber intake can improve the risk factors associated with CMD. Psyllium, especially its husk, is one of the most widely used dietary fiber supplements, which is often used to enrich cereals and other food products. Numerous pharmacological studies have investigated the active ingredients and therapeutic effects of psyllium and its extracts, including antioxidant, anti-tumor, antidiabetic, hypotensive, anti-inflammation, neuroprotection, antidiarrheal, and antiviral activities. In this review, we will summarize the available studies on the therapeutic potential and possible mechanisms of psyllium in treating CMDs, such as hyperlipidemia, diabetes mellitus, and its complications, hypertension, hyperuricemia and obesity, and its applications in food systems.

Cardiovascular diseases (CVDs) and diabetes are the leading causes of death worldwide, which underlines the urgent necessity to develop new pharmacotherapies. Cinnamon has been an eminent component of spice and traditional Chinese medicine for thousands of years. Numerous lines of findings have elucidated that cinnamon has beneficial effects against CVDs in various ways, including endothelium protection, regulation of immune response, lowering blood lipids, antioxidative properties, anti-inflammatory properties, suppression of vascular smooth muscle cell (VSMC) growth and mobilization, repression of platelet activity and thrombosis and inhibition of angiogenesis. Furthermore, emerging evidence has established that cinnamon improves diabetes, a crucial risk factor for CVDs, by enhancing insulin sensitivity and insulin secretion; regulating the enzyme activity involved in glucose; regulating glucose metabolism in the liver, adipose tissue and muscle; ameliorating oxidative stress and inflammation to protect islet cells; and improving diabetes complications. In this review, we summarized the mechanisms by which cinnamon regulates CVDs and diabetes in order to provide a theoretical basis for the further clinical application of cinnamon.

Glutamate-mediated excitotoxicity is an important mechanism leading to post ischemic stroke damage. After acute stroke, the sudden reduction in cerebral blood flow is most initially followed by ion transport protein dysfunction and disruption of ion homeostasis, which in turn leads to impaired glutamate release, reuptake, and excessive N-methyl-D-aspartate receptor (NMDAR) activation, promoting neuronal death. Despite extensive evidence from preclinical studies suggesting that excessive NMDAR stimulation during ischemic stroke is a central step in post-stroke damage, NMDAR blockers have failed to translate into clinical stroke treatment. Current treatment options for stroke are very limited, and there is therefore a great need to develop new targets for neuroprotective therapeutic agents in ischemic stroke to extend the therapeutic time window. In this review, we highlight recent findings on glutamate release, reuptake mechanisms, NMDAR and its downstream cellular signaling pathways in post-ischemic stroke damage, and review the pathological changes in each link to help develop viable new therapeutic targets. We then also summarize potential neuroprotective drugs and therapeutic approaches for these new targets in the treatment of ischemic stroke.

Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.

Tongxinluo Capsule(TXLC) is a well-known traditional Chinese medicine prescription with effects of tonifying Qi and activating blood based on the Chinese herbal medicine theory that has been recommended as routine adjuvant treatment in patients with coronary heart disease (CHD) in China.This meta-analysis aimed to evaluate the efficacy and safety of TXLC as supplementation in the prevention of adverse cardiovascular events in patients with CHD.We performed a literature search in Pubmed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan Fang Database, and Chinese Biomedical Database (CBM) from their inceptions to March 2020. Only randomized controlled trials (RCTs) that assessed supplementation with TXLC or placebo and with adverse cardiovascular outcomes, were included in this meta-analysis. Primary end points were myocardial infarction (MI), target vessel revascularization (TVR) or in-stent restenosis (ISR), and cardiovascular death. Secondary end points included cerebrovascular accidents, heart failure (HF), and unscheduled readmission for cardiovascular diseases (CVDs). Adverse drug events were also evaluated. Trial sequential analysis (TSA) was conducted to reduce random errors introduced by possible insufficient sample size.Eleven RCTs involving 1505 patients were analyzed. The mean(SD) age of included patients were 59.03(9.7) years. Treatment duration varied from 2 months to 12 months. Compared with placebo, TXLC supplementation showed significant effects on reducing the risk of MI (RR = 0.44, [95% CI, 0.24-0.80]), TVR or ISR (RR = 0.43, [95% CI, 0.31-0.58]), cerebrovascular accidents(RR = 0.17, [95% CI, 0.06-0.46]), HF (RR = 0.41, [95% CI, 0.21-0.79]), and unscheduled readmission for CVDs (RR = 0.72, [95% CI], P = 0.04), but did not have associations with incidence of cardiovascular death (RR = 0.53, [95% CI, 0.15-1.91]). Subgroups of trials with 2-month (MI: RR = 0.44, [95% CI, 0.13-1.53]; cardiovascular death: RR = 0.30, [95% CI, 0.01-7.67]; cerebrovascular accidents: RR = 0.04, [95% CI, 0.01-0.26]; unscheduled readmission for CVDs: RR = 0.43, [95% CI, 0.20-0.94]) and 12-month (MI: RR = 0.42, [95% CI, 0.20-0.89]; TVR or ISR: RR = 0.42, [95% CI, 0.31-0.58]; HF: RR = 0.34, [95% CI, 0.14-0.78]; unscheduled readmission for CVDs: RR = 0.85, [95% CI, 0.59-1.22]) intervention period were analyzed. The adverse drug reactions were mild with no significant difference between TXLC and placebo.This meta-analysis indicated that TXLC supplementation had beneficial effects on the prevention of cardiovascular adverse events, especially in TVR or ISR after coronary revascularization and may possibly lower the incidence of first or recurrent MI and HF within 12 months in patients with CHD, while insufficient sample size implied that these results lacked certain stability. And the effects of TXLC on cardiovascular mortality, cerebrovascular events, and unscheduled readmission for CVDs could not be confirmed due to insufficient cases. Clinical trials with large-sample sizes and extended follow-up time are of interest in the future researches.

IntroductionPulmonary alveolar proteinosis (PAP) is an ultrarare disorder characterised by the accumulation of alveolar surfactant and the dysfunction of alveolar macrophages that results in hypoxemic respiratory failure. Whole-lung lavage (WLL) is currently the primary therapy for PAP. However, systematic evaluation of the clinical efficacy of WLL is lacking. We aim to perform a systematic review and meta-analysis of existing evidence to support WLL for the clinical treatment of PAP.Methods and analysisWe will search the PubMed (MEDLINE), Cochrane Library, Embase, Web of Science and Google Scholar databases from inception to December 2021 for observational studies using WLL for the treatment of PAP. Two authors will independently screen the eligible studies, assess the quality of the included papers and extract the required information. Review Manager V.5.4 will be used to perform the meta-analysis. We will evaluate the overall quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. All steps of this protocol will be performed using the Cochrane Handbook for Preferred Reporting Items for Systematic Review and Meta-analysis statement.Ethics and disseminationThis systematic review and meta-analysis will be based on published data. Therefore, ethical approval is not required. We will publish our results in a peer-reviewed journal.PROSPERO registration numberCRD42022306221 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306221).

Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata （Willd.）Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.

Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. Ferroptosis shows unique characteristics in biology, chemistry, and gene levels, compared to other cell death forms. The metabolic disorder of intracellular LOOH catalyzed by iron causes the inactivity of GPX4, disrupts the redox balance, and triggers cell death. Metabolism of amino acid, iron, and lipid, including associated pathways, is considered as a specific hallmark of ferroptosis. Epidemiological studies and animal experiments have shown that ferroptosis plays an important character in the pathophysiology of cardiovascular disease such as atherosclerosis, myocardial infarction (MI), ischemia/reperfusion (I/R), heart failure (HF), cardiac hypertrophy, cardiomyopathy, and abdominal aortic aneurysm (AAA). This review systematically summarized the latest research progress on the mechanisms of ferroptosis. Then we report the contribution of ferroptosis in cardiovascular diseases. Finally, we discuss and analyze the therapeutic approaches targeting for ferroptosis associated with cardiovascular diseases.

To explore the effect of masking therapy for the early stage of the patients with noise-induced tinnitus,and imply the treatment for patients with noise-induced tinnitus.Sixty-eight cases with tinnitus were studied. All the patients took the audiological examinations and tinnitus tests firstly, and accepted the masking therapy for 6 months. The therapeutic effiency was evaluated according to tinnitus handicap inventory (THI) and subjective visual-analogue scale (VAS). The minimum masking intensity was also evaluated.The majority of the patients with noise-induced tinnitus (59 cases, 86. 8%) had tinnitus frequency of 4 kHz,and most of them (44 cases, 64. 7%) had positive residual inhibition tests. Tinnitus completely disappeared in 3 cases after masking therapy, and the efficiency of this treatment is 83. 8%. There was significant difference in the scores of THI and VAS before and after therapy(P0. 01), and there was also significant difference in the minimum masking intensity (P0. 01).Masking therapy is the most important treatment for the patients in the early stage of noise-induced tinnitus. The therapeutic effiency is significant and should be promoted.

To analyze and summarize nystagmus of patients with posterior canal benign paroxysmal positional vertigo (BPPV) in positioning test,and to improve the diagnosis and treatment of posterior canal BPPV (PSC-BPPV).The present study was conducted on 175 patients who had unilateral BPPV of the posterior semicircular canal (PSC). Their positional nystagmus recorded by videnonystagmography in Dix-Hallpike test,roll test and roll over test were analyzed to summarize the characteristics of nystagmus on nystagmograph of PSC-BP-PV.Of the 175 patients, lesion was located in the left PSC in 69 (39.4%) patients,the right PSC in 106 (60. 6%)patients. The nystagmus of patients with PSC-canalithiasis showed upward on the vertical phase of nystagmograph and orientated the different side on horizontal phase in the head hangging position. The horizontal phase pointed to the contralateral side in 47(26. 9%) patients, the ipsilateral contralateral side in 100(57. 1%) patients,no significant reverse ingredients in 28(16.0%) patients. When these patients returned to sit,139(79.4%) patients showed down beating positioning nystagmus, whereas 36 (20. 6%) patients with no nystagmus only had a short vertigo or dizziness. The horizontal phase of the 139 patients pointed to the contralateral side in 40(22. 9%) patients,the ipsilateral contralateral side in 68(38. 9%) patients,no significant reverse ingredients in 31(17. 7%) patients. In roll test,12 patients of the right PSC-BPPV presented an up-beating rotatory nystagmus when the head turned to right,and 5 patients of the left PSC-BPPV presented a down-beating rotatory nystagmus when the head turned to left. When the patients changed body from the left lateral position to the right lateral position in the roll over test, 74(42. 3%) patientsshowed vertical positioning nystagmus. In 30 patients who presented an up-beating nystagmus, there were 25(83. 3%) patientscame from the right PSC-BPPV. In 44 patients who presented a down-beating nystagmus, there were 36(81. 8%) patientscame from the left PSC-BPPV. The direction of the vertical nystagmus was highly correlated with the judgment about the side of the PSC-BPPV in roll over test (P0. 01).The patient with PSC-canalithiasis showed an uncertain direction in torsional nystagmus in Dix-Hallpike test,the diagnosis was mainly concern with the vertical nystagmus. When we found a rotatory nystagmus with much more up-beating nystagmus in roll test, it might be PSC-BPPV. We also can use the roll over test to diagnose the location of the otolith in which side of the PSC-BPPV.

China lacks large scale authorized epidemiological study results in allusion to subarachnoid hemorrhage (SAH) within recent 15 years since MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study revealed SAH situation in China in 2000. The main cause of SAH in China is aneurysm which takes up 30-50%, while over 90% aneurysm locates at Willis circle. Early surgery for SAH after aneurysm rupture is the dominant procedure to deal with SAH in China. Moreover, calcium antagonists rank the absolute leading position for cerebral vascular spasm (CVS) among medication-based treatment options. However, traditional Chinese medicine such as Salvia miltiorrhiza, Acanthopanax senticosus, Ginkgo biloba, Pueraria lobata, Liguisticum chuanxiong, cow bezoar, Diospyros kaki and Gynostemma pentaphyllum have been proven beneficial in CVS prevention and treatment, while Salvia miltiorrhiza and TCM soup have unique effects on bleeding absorption. In addition, aescine and some TCM soup might relieve strong headache after SAH. In general, TCM integrated with western medicine have shown unique advantages in the current treatment of SAH in China. However, it is a pity that China still lacks larger scale randomized controlled trials and research on SAH treatment focusing on TCM and the related mechanism of TCM on SAH still need to be investigated further.