Scoping Review with Topic Modeling on the Diagnostic Criteria for Degenerative Cervical Myelopathy.

STUDY DESIGN: This study is a scoping review. OBJECTIVE: There is a broad variability in the definition of degenerative cervical myelopathy (DCM) and no standardized set of diagnostic criteria to date. METHODS: We interrogated the Myelopathy.org database, a hand-indexed database of primary clinical studies conducted exclusively on DCM in humans between 2005-2021. The DCM inclusion criteria used in these studies were inputted into 3 topic modeling algorithms: Hierarchical Dirichlet Process (HDP), Latent Dirichlet Allocation (LDA), and BERtopic. The emerging topics were subjected to manual labeling and interpretation. RESULTS: Of 1676 reports, 120 papers (7.16%) had well-defined inclusion criteria and were subjected to topic modeling. Four topics emerged from the HDP model: disturbance from extremity weakness and motor signs; fine-motor and sensory disturbance of upper extremity; a combination of imaging and clinical findings is required for the diagnosis; and "reinforcing" (or modifying) factors that can aid in the diagnosis in borderline cases. The LDA model showed the following topics: disturbance to the patient is required for the diagnosis; reinforcing factors can aid in the diagnosis in borderline cases; clinical findings from the extremities; and a combination of imaging and clinical findings is required for the diagnosis. BERTopic identified the following topics: imaging abnormality, typical clinical features, range of objective criteria, and presence of clinical findings. CONCLUSIONS: This review provides quantifiable data that only a minority of past studies in DCM provided meaningful inclusion criteria. The items and patterns found here are very useful for the development of diagnostic criteria for DCM.

Antigen Self-Presented Personalized Nanovaccines Boost the Immunotherapy of Highly Invasive and Metastatic Tumors.

Dendritic cell (DC)-based vaccines have shown promise in adoptive cell therapy for enhancing the antigen-specific response of antitumor immunity. However, their clinical efficacy is limited by the less-presented tumor-associated antigens (TAAs) through MHC I and low lymph node homing efficiency. Herein, to address these issues, we rationally design and fabricate DC-based nanovaccines by coating Cu2-xSe nanoparticles (CS NPs) with the membrane of matured DCs (named as DCNV(CSD) nanovaccines). We reveal the important roles of CS NPs in the DCNV(CSD) nanovaccines from three aspects: (1) inducing the immunogenic cell death of tumor cells to expose abundant TAAs; (2) promoting the escape of TAAs from the lysosomes of DCs during the antigen presenting process through MHC I; (3) sustainably releasing traces of copper ions to promote the proliferation of T cells. Our DCNV(CSD) nanovaccines are characterized with high expressions of MHC I, CD80, CD86, CCR7, and ICAM-1 proteins, which not only endow them with abundantly processed specific TAAs, but also a strong capability of homing to the lymph nodes. The homing capability of our small DCNV(CSD) nanovaccines is better than that of matured DCs. More importantly, they can elicit the strong response of potent antispecific CD8+ T cells for antitumor immunotherapy, as tested in the treatment of highly invasive glioblastoma and highly metastatic melanoma. Additionally, DCNV(CSD) nanovaccines can generate memory T cells (TEM) in the spleen of mice to effectively prevent the recurrence of treated tumors. This work demonstrates a universal approach to fabricate high-performance DC-based nanovaccines for tumor immunotherapy by using versatile CS NPs.

Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL-33/ST2 to Alleviate Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (IRI) is a common disease with high morbidity and mortality. Renal IRI can cause the disorder of immune microenvironment and reprograming the immune microenvironment to alleviate excessive inflammatory response is crucial for its treatment. Cytokine IL-33 can improve the immune inflammatory microenvironment by modulating both innate and adaptive immune cells, and serve as an important target for modulating immune microenvironment of renal IRI. Herein, we report that bilobetin-functionalized ultrasmall Cu2- x Se nanoparticles (i.e., CSPB NPs) can activate the PKA/p-CREB/IL-33/ST2 signaling pathway to regulate innate and adaptive immune cells for reprograming the immune microenvironment of IRI-induced acute kidney injury. The biocompatible CSPB NPs can promote the polarization of M1-like macrophages into M2-like macrophages, and the expansion of ILC2 and Treg cells by activating IL-33/ST2 to modulate the excessive immune inflammatory response of renal IRI. More importantly, they can rapidly accumulate at the injured kidney to significantly alleviate IRI. This work demonstrates that modulating the expression of cytokines to reprogram immune microenvironment has great potential in the treatment of renal IRI and other ischemic diseases.

The Frequency of Symptoms in Patients With a Diagnosis of Degenerative Cervical Myelopathy: Results of a Scoping Review.

STUDY DESIGN: Delayed diagnosis of degenerative cervical myelopathy (DCM) is associated with reduced quality of life and greater disability. Developing diagnostic criteria for DCM has been identified as a top research priority. OBJECTIVES: This scoping review aims to address the following questions: What is the diagnostic accuracy and frequency of clinical symptoms in patients with DCM? METHODS: A scoping review was conducted using a database of all primary DCM studies published between 2005 and 2020. Studies were included if they (i) assessed the diagnostic accuracy of a symptom using an appropriate control group or (ii) reported the frequency of a symptom in a cohort of DCM patients. RESULTS: This review identified three studies that discussed the diagnostic accuracy of various symptoms and included a control group. An additional 58 reported on the frequency of symptoms in a cohort of patients with DCM. The most frequent and sensitive symptoms in DCM include unspecified paresthesias (86%), hand numbness (82%) and hand paresthesias (79%). Neck and/or shoulder pain was present in 51% of patients with DCM, whereas a minority had back (19%) or lower extremity pain (10%). Bladder dysfunction was uncommon (38%) although more frequent than bowel (23%) and sexual impairment (4%). Gait impairment is also commonly seen in patients with DCM (72%). CONCLUSION: Patients with DCM present with many different symptoms, most commonly sensorimotor impairment of the upper extremities, pain, bladder dysfunction and gait disturbance. If patients present with a combination of these symptoms, further neuroimaging is indicated to confirm the diagnosis of DCM.

The value of Clinical signs in the diagnosis of Degenerative Cervical Myelopathy - A Systematic review and Meta-analysis.

STUDY DESIGN: Delayed diagnosis of degenerative cervical myelopathy (DCM) is likely due to a combination of its subtle symptoms, incomplete neurological assessments by clinicians and a lack of public and professional awareness. Diagnostic criteria for DCM will likely facilitate earlier referral for definitive management. OBJECTIVES: This systematic review aims to determine (i) the diagnostic accuracy of various clinical signs and (ii) the association between clinical signs and disease severity in DCM? METHODS: A search was performed to identify studies on adult patients that evaluated the diagnostic accuracy of a clinical sign used for diagnosing DCM. Studies were also included if they assessed the association between the presence of a clinical sign and disease severity. The QUADAS-2 tool was used to evaluate the risk of bias of individual studies. RESULTS: This review identified eleven studies that used a control group to evaluate the diagnostic accuracy of various signs. An additional 61 articles reported on the frequency of clinical signs in a cohort of DCM patients. The most sensitive clinical tests for diagnosing DCM were the Tromner and hyperreflexia, whereas the most specific tests were the Babinski, Tromner, clonus and inverted supinator sign. Five studies evaluated the association between the presence of various clinical signs and disease severity. There was no definite association between Hoffmann sign, Babinski sign or hyperreflexia and disease severity. CONCLUSION: The presence of clinical signs suggesting spinal cord compression should encourage health care professionals to pursue further investigation, such as neuroimaging to either confirm or refute a diagnosis of DCM.

CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a poor prognosis and growing incidence. In this study, we explored the potential roles of CDK1, CDK2, CDK4, and CDK6 in the progression of early-stage PDAC. Clinicopathologic and mRNA expression data and treatment information of 140 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy were obtained from the Cancer Genome Atlas data set. Our bioinformatic analysis showed that higher CDK1, CDK2, CDK4, or CDK6 expression was associated with a shorter median survival of the early-stage PDAC patients. Of note, in the low-proliferating pancreatic cancer group, CDKs expressions were significantly associated with proteins functioning in apoptosis, metastasis, immunity, or stemness. Among the low-proliferating PDAC, higher expression of CDK1 was associated with the shorter survival of patients, suggesting that CDK1 may regulate PDAC progression through cell cycle-independent mechanisms. Our experimental data showed that CDK1 knockdown/inhibition significantly suppressed the expression levels of AHR and POU5F1, two critical proteins functioning in cancer cell metastasis and stemness, in low-proliferating, but not in high-proliferating pancreatic cancer cells. In all, our study suggests that CDKs regulate PDAC progression not only through cell proliferation but also through apoptosis, metastasis, immunity, and stemness.

Deletion of Emc1 in photoreceptor cells causes retinal degeneration in mice.

The endoplasmic reticulum membrane protein complex (EMC) plays a critical role in the synthesis of multipass membrane proteins. Genetic studies indicated that mutations in EMC1 gene were associated with retinal degeneration diseases; however, the role of EMC1 in photoreceptor has not been confirmed. Here, we show that Emc1 ablation in the photoreceptor cells of mice recapitulated the retinitis pigmentosa phenotypes, including an attenuated scotopic electroretinogram response and the progressive degeneration of rod cells and cone cells. Histopathological examination of tissues from rod-specific Emc1 knockout mice revealed mislocalized rhodopsin and irregularly arranged cone cells at the age of 2 months. Further immunoblotting analysis revealed decreased levels of membrane proteins and endoplasmic reticulum chaperones in 1-month-old rod-specific Emc1 knockout mice retinae, and this led us to speculate that the loss of membrane proteins is the main cause of the degeneration of photoreceptors. EMC1 most likely regulated the membrane protein levels at an earlier step in the biosynthetic process before the proteins translocated into the endoplasmic reticulum. The present study demonstrates the essential roles of Emc1 in photoreceptor cells, and reveals the mechanism through which EMC1 mutations are linked to retinitis pigmentosa.

Machine learning in TCM with natural products and molecules: current status and future perspectives.

Traditional Chinese medicine (TCM) has been practiced for thousands of years with clinical efficacy. Natural products and their effective agents such as artemisinin and paclitaxel have saved millions of lives worldwide. Artificial intelligence is being increasingly deployed in TCM. By summarizing the principles and processes of deep learning and traditional machine learning algorithms, analyzing the application of machine learning in TCM, reviewing the results of previous studies, this study proposed a promising future perspective based on the combination of machine learning, TCM theory, chemical compositions of natural products, and computational simulations based on molecules and chemical compositions. In the first place, machine learning will be utilized in the effective chemical components of natural products to target the pathological molecules of the disease which could achieve the purpose of screening the natural products on the basis of the pathological mechanisms they target. In this approach, computational simulations will be used for processing the data for effective chemical components, generating datasets for analyzing features. In the next step, machine learning will be used to analyze the datasets on the basis of TCM theories such as the superposition of syndrome elements. Finally, interdisciplinary natural product-syndrome research will be established by unifying the results of the two steps outlined above, potentially realizing an intelligent artificial intelligence diagnosis and treatment model based on the effective chemical components of natural products under the guidance of TCM theory. This perspective outlines an innovative application of machine learning in the clinical practice of TCM based on the investigation of chemical molecules under the guidance of TCM theory.

Circ-CPSF1 Worsens Radiation-Induced Oxidative Stress Injury in Caenorhabditis elegans.

Radioactive substances have been used in various aspects in daily life. However, high-energy radiation could cause environmental problems, which would damage the human body. Circular RNA (CircRNA) has great potential in the minimization of ionizing radiation damage. To find a potential diagnostic and therapeutic target for reducing the damage of ionizing radiation, we selected circRNA cleavage and polyadenylation specificity factor subunit 1 (circ-CPSF1) based on its up-regulated expression after X-ray radiation and explored its effect on response to ionizing radiation using Caenorhabditis elegans (C. elegans). Circ-CPSF1 was screened out and its up-regulated expression was verified. The measurement of lifespan and germ cell apoptosis showed that circ-CPSF1 RNAi treatment extended lifespan and reduced apoptotic germ cells. ROS levels were significantly reduced after the interference of circ-CPSF1 in C. elegans with radiation. Mitochondrial membrane potential assay showed that the suppression of circ-CPSF1 could alleviate mitochondrial damage after radiation. Relative genes expression showed the involvement of circ-CPSF1 in radiation mediated DNA damage response pathways and apoptosis pathways. In conclusion, circ-CPSF1 exerts deleterious effects on lifespan, eggs production and germ cell apoptosis of C. elegans through oxidative stress, the DNA damage response (DDR) pathway, and the core apoptotic pathway after ionizing radiation, indicating the potential of circ-CPSF1 to be an important therapeutic target of radiation damage.

Carotid artery dissection presenting as exercise-induced monocular visual loss.

A man in his 60s presented to the urgent treatment centre with isolated transient monocular visual loss in the right eye soon after completing a 5 km run. He had no preceding events, no history of neck pain and no other associated symptoms. His only medical history was presumed giant cell arteritis 3 months prior. The ophthalmology team reviewed the patient urgently and retinal artery occlusion was excluded. Carotid Doppler imaging showed a total occlusion of the right internal carotid artery. CT angiogram of the head and neck vessels revealed a dissection flap immediately proximal to the occlusion. The carotid dissection was treated with aspirin 300 mg for 2 weeks followed by clopidogrel 75 mg for a minimum of 3 months. The patient was discussed with the vascular team who confirmed that no surgical intervention would be required to treat the occlusion. With the relatively simple treatment of antiplatelet therapy, the patient is making good progress with no recurrence of symptoms.

The Combined Cultivation of Feruloyl Esterase-Producing Strains with CMCase and Xylanase-Producing Strains Increases the Release of Ferulic Acid.

Feruloyl esterase (FAE)-producing micro-organisms to obtain ferulic acid (FA) from natural substrates have good industrial prospects, and the synergistic effect of multiple bacteria can better improve the yield of FA. In this study, on the premise of the synergistic effect of FAE, hemicellulose, and cellulase, the key strain Klebsiella oxytoca Z28 with FAE was combined with CMCase and Xylanase-producing strains to produce FA. The combination of strains with higher FA production are Klebsiella oxytoca Z28, Klebsiella pneumoniae JZE, Bacillus velezensis G1, and their FA production can reach 109.67 µg/g, which is 15% higher than that of single bacteria. To explore the effects of temperature, Ph, inoculum amount, distillers grains concentration and fermentation time on the FAE activity of the combination of strains in the fermentation process, and determined that temperature, Ph, and fermentation time were the main influencing factors and optimized through orthogonal design. The optimized fermentation conditions are 34 °C, Ph 8.0, and fermentation days for 6 days, the FAE activity can reach 270.78 U/L, and the FA yield of the combined strain is 324.50 µg/g, which is 200% higher than that of single-strain fermentation.

Saponins and their derivatives: Potential candidates to alleviate anthracycline-induced cardiotoxicity and multidrug resistance.

Anthracyclines (ANTs) continue to play an irreplaceable role in oncology treatment. However, the clinical application of ANTs has been limited. In the first place, ANTs can cause dose-dependent cardiotoxicity such as arrhythmia, cardiomyopathy, and congestive heart failure. In the second place, the development of multidrug resistance (MDR) leads to their chemotherapeutic failure. Oncology cardiologists are urgently searching for agents that can both protect the heart and reverse MDR without compromising the antitumor effects of ANTs. Based on in vivo and in vitro data, we found that natural compounds, including saponins, may be active agents for other both natural and chemical compounds in the inhibition of anthracycline-induced cardiotoxicity (AIC) and the reversal of MDR. In this review, we summarize the work of previous researchers, describe the mechanisms of AIC and MDR, and focus on revealing the pharmacological effects and potential molecular targets of saponins and their derivatives in the inhibition of AIC and the reversal of MDR, aiming to encourage future research and clinical trials.

CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt/cadherin axis.

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder that can cause vision loss. CTNND1 encodes a cellular adhesion protein p120-catenin (p120), which is essential for vascularization with unclear function in postnatal physiological angiogenesis. Here, we applied whole-exome sequencing to 140 probands of FEVR families and identified 3 candidate variants in the human CTNND1 gene. We performed inducible deletion of Ctnnd1 in the postnatal mouse endothelial cells (ECs) and observed typical phenotypes of FEVR with reactive gliosis. Using unbiased proteomics analysis combined with experimental approaches, we conclude that p120 is critical for the integrity of adherens junctions (AJs) and that p120 activates Wnt signaling activity by protecting ß-catenin from glycogen synthase kinase 3 beta-ubiqutin-guided (Gsk3ß-ubiquitin-guided) degradation. Treatment of CTNND1-depleted human retinal microvascular ECs with Gsk3ß inhibitors LiCl or CHIR-99021 enhanced cell proliferation. Moreover, LiCl treatment increased vessel density in Ctnnd1-deficient mouse retinas. Variants in CTNND1 caused FEVR by compromising the expression of AJs and Wnt signaling activity. Genetic interactions between p120 and ß-catenin or α-catenin revealed by double-heterozygous deletion in mice showed that p120 regulates vascular development through the Wnt/cadherin axis. In conclusion, variants in CTNND1 can cause FEVR through the Wnt/cadherin axis.

Targeted Immunoimaging of Tumor-Associated Macrophages in Orthotopic Glioblastoma by the NIR-IIb Nanoprobes.

Developing dynamic and highly sensitive methods for imaging M2-type tumor-associated macrophages (TAMs) is vital for monitoring the tumor progression and assessing the therapeutic efficacy. Here, the fabrication and application of rationally designed Er-based rare-earth nanoprobes for the targeted imaging of M2-type TAMs in glioblastoma (GBM) through the second near-infrared (NIR-II) fluorescence beyond 1500 nm is reported. The NIR-IIb fluorescence of Er-based rare-earth nanoparticles can be remarkably enhanced by optimizing their core-shell structures and the shell thickness, which allows for in vivo imaging under excitation by a 980 nm laser with the lowest power density (40 mW cm-2 ). These bright Er-based nanoparticles functionalized with M2pep polypeptide show notable targeting ability to M2-type macrophages, which has been well tested in both in vitro and in vivo experiments by their up-conversion (UC) fluorescence (540 nm) and down-shifting (DS) fluorescence (1525 nm), respectively. The targeting capability of these nanoprobes in vivo is also demonstrated by the overlap of immunofluorescence of M2-type TAMs and Arsenazo III staining of rare-earth ions in tumor tissue. It is envisioned that these nanoprobes can serve as a companion diagnostic tool to dynamically assess the progression and prognosis of GBM.

A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10-15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10-3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10-16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Establishing Diagnostic Criteria for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 3].

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process. METHODS: Literature review summarising current evidence of establishing diagnostic criteria for DCM. RESULTS: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM. CONCLUSION: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities.

Boosting Vascular Imaging-Performance and Systemic Biosafety of Ultra-Small NaGdF4 Nanoparticles via Surface Engineering with Rationally Designed Novel Hydrophilic Block Co-Polymer.

Revealing the anatomical structures, functions, and distribution of vasculature via contrast agent (CA) enhanced magnetic resonance imaging (MRI) is crucial for precise medical diagnosis and therapy. The clinically used MRI CAs strongly rely on Gd-chelates, which exhibit low T1 relaxivities and high risks of nephrogenic systemic fibrosis (NSF) for patients with renal dysfunction. It is extremely important to develop high-performance and safe CAs for MRI. Herein, it is reported that ultra-small NaGdF4 nanoparticles (UGNs) can serve as an excellent safe MRI CA via surface engineering with rationally designed novel hydrophilic block co-polymer (BPn ). By optimizing the polymer molecular weights, the polymer-functionalized UGNs (i.e., UGNs-BP14 ) are obtained to exhibit remarkably higher relaxivity (11.8 mm-1 s-1 at 3.0 T) than Gd-DTPA (3.6 mm-1 s-1 ) due to their ultracompact and abundant hydrophilic surface coating. The high performance of UGNs-BP14 enables us to sensitively visualize microvasculature with a small diameter of ≈0.17 mm for up to 2 h, which is the thinnest blood vessel and the longest time window for low field (1.0 T) MR angiography ever reported, and cannot be achieved by using the clinically used Gd-DTPA under the same conditions. More importantly, renal clearable UGNs-BP14 show lower risks of inducing NSF in comparison with Gd-DTPA due to their negligible release of Gd3+ ions after modification with the novel hydrophilic block copolymer. The study presents a novel avenue for boosting imaging-performance and systemic biosafety of UGNs as a robust MRI CA with great potential in precise diagnosis of vasculature-related diseases.

The immunotoxicity of decabromodiphenyl ether (BDE-209) on broiler chicks by transcriptome profiling analysis.

Decabromodiphenyl ether (BDE-209) has drawn significant attention due to its suppression of immune functions in animals and even humans. In order to explore the mechanism through which BDE-209 affects the immune system, broiler chicks were fed a diet containing various concentrations of BDE-209 (0, 0.004, 0.04, 0.4, and 4 g/kg) for 42 days. Histopathological observations of immune organs found damaged and necrotic lymphocytes in the spleen and bursa, and losses of lymphoid cells in thymic gland. The activities of catalase, glutathione, glutathione peroxidase, and superoxide dismutase in both the spleen and serum were affected by BDE-209. Obvious bioaccumulation effect was found in spleen tissues (high to 1339 ± 181.9 µg/kg). Furthermore, transcriptome sequencing analyses of the spleen identified 424 upregulated and 301 downregulated DEGs, and the cytokine-cytokine receptor interaction signal pathway was most significantly enriched based on the Kyoto Encyclopedia of Genes and Genomes database. Quantitative real-time PCR affirmed the decreased expressions of interleukin IL18, IL18R1, IL18RAP, IL21, as well as interferon gamma IFNG and tumor necrosis factor superfamily members TNFSF8, indicating significant interference to immunomodulation function and possible disease progression in inflammatory effects resulting from BDE-209 exposure. The immunotoxicity of BDE-209 may cause the suppression of immune and physiological functions of spleen cells, leading to inflammation and apoptosis and ultimately spleen atrophy.

Roles and mechanisms of puerarin on cardiovascular disease：A review.

Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named "Ge gen" in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression of atherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance of lipid metabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and other effects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.