Sonodynamic therapy for the treatment of atherosclerosis

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

Shedding new light on atherosclerosis therapeutics:Nanomedicines targeting atherosclerotic immune microenvironment

Atherosclerosis(AS)leads to atherosclerotic cardiovascular disease(ASCVD),the predominant cause of death worldwide.As traditional lipid-lowering therapies have encountered a bottleneck in dealing with diverse types of atherosclerotic plaques and ASCVD,alternative therapies that can target other mechanisms are urgently needed.Recent studies have revealed that AS is rooted in disrupted immune responses,such as chronic local inflammation and autoimmune responses,and immunotherapies have emerged as a nascent avenue to control plaque development owing to their satisfactory effects and high cost efficiency.The atherosclerotic immune microenvironment(AIME)is the microenvironment in which diverse immune responses occur dynamically.AIME is characterized by persistent inflammatory responses,shifted immunometabolism,and the formation of adventitial neuroimmune cardiovascular interfaces,all of which are regarded as prospective targets for AS immunotherapy.Recently,the advent of nanotechnology has advanced AS immunotherapy targeting the AIME.Manifold nanoplatforms have greatly enriched AS therapeutics owing to their multimodal imaging and multichannel intervention capabilities.Here,we offer an overview of AIME and discuss how nanomedicines can assist in AS diagnosis and intervention.We introduce nanoplatforms integrated with imaging techniques,such as magnetic resonance imaging,photoacoustic imaging,fluorescence imaging,positron emission tomography,and ultrasound imaging,which can target AIME to realize plaque diagnosis.Moreover,we elaborated on nanomaterials that regulate innate immune responses,adaptive immune responses,and aberrant immunometabolism to achieve AIME modulation.Furthermore,we highlight the possible future directions of AS therapeutics,with a focus on AIME-targeted nanomedicines.

Intracranial Atherosclerosis: The Natural History and Management Strategies

Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.

Clinical Observation on Treatment of Moderate and Severe Periodical Mastalgia with TCM Hot-wet Compress Therapy

[Objectives] To observe the clinical therapeutic efficacy of local hot-wet compress therapy of digestion ointment prescription on the patients with moderate and severe mastalgia. [Methods] Firstly,60 patients with mastalgia were selected,and divided into the experimental group and control group( 30 cases for each group). The control group was treated with acupuncture at distal point,and the experimental group was treated with TCM local hot-wet compress therapy combined with acupuncture at distal point. Then,the clinical therapeutic efficacy of two groups was compared. [Results]The experimental group was superior to the control group in relieving the breast pain,improving emotional integral,reducing breast lumps,improving lump texture,and improving TCM syndrome integral( P < 0. 05). [Conclusions]The digestion ointment prescription local hot-wet compress therapy has a significant therapeutic effect on treatment of mastalgia and can significantly improve the breast pain symptom of patients.

Extracranial Carotid Atherosclerosis and Acute Ischemic Stroke in a Tertiary Hospital in Burkina Faso

Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospective study of patients admitted at neurology department of Yalgado Ouedraogo University Teaching Hospital with ischemic stroke and cerebral large vessel atherosclerosis in the period from January 1, 2012 to December 31, 2016. Results: The prevalence of extracranial carotid atherosclerosis was 23.9%. The mean age of patients was 63.5 years (Range 31 - 90 years). The study population included 65% of men and 35% of women. Hypertension was the most common vascular risk factor (75.6%). Stroke was mostly located in the anterior circulation in 23.9%. Low HDL-C was present in 52% of patients. The majority of plaque was homogeneous (85.2%). Plaque were located in carotid bulbar artery (38.5%) followed by common carotid artery (28.2%) and extracranial internal carotid artery (18.6%). According to cerebral lesion, plaque was bilateral in 45.5%, ipsilateral in 42.3% and contralateral in 12.1% of cases. Tight stenosis was found in 30.1% of patients. There was a significant link between male gender and tight stenosis (p = 0.004). Aspirin was the most antiplatelet therapy used (95.5%). Statin therapy was used in 91% of patients. The mean duration of hospitalization was 12.5 days with a mortality rate of 7.1%. Conclusions: Our study showed that extra carotid atherosclerosis was the most common cause of ischemic stroke in Burkina Faso. Man gender was most represented than women.

Clinical Effects of the Qi-acupuncture Therapy of TCM on Portal Hypertension

Objective:To explore the effective prevention and treatment of portal hypertension(PH).Methods:A total of 220 patients who came to our hospital from March 2015 to October 2018 were treated.They were randomly divided into the treatment group and the control group,each with 110 cases.Before treatment,there was no significant differences in age,sex,clinical symptoms,signs,laboratory tests and color Doppler ultrasound related examinations between the 2 groups(P>0.05).Among them,the treatment group on the basis of traditional Chinese and Western medicine treatment in our hospital,the Qi-acupuncture therapy of TCM was added.The extra meridian acupoints along with acupoints were selected.The control group received conventional treatment with traditional Chinese and Western medicine in our hospital.Results:There were significant differences in clinical symptoms,signs and chemistry between groups after treatment(P<0.01).There were significant differences in test,color ultrasound related examination and so on(P<0.01).Those in the treatment group was significantly better than the control group(P<0.01).Conclusion:On the basis of the Qi-acupuncture therapy of TCM,selecting extra meridian acupoint and acupoints can effectively treat PH.

Non-pharmacological therapy of TCM for the treatment of essential hypertension

Non-pharmacotogicat treatment is an important means to control hypertension, with many advantages such as tow cost, tess medication, stable btood pressure, tess compHcations, and improved prognosis. This article reviews the research progress of non-drug treatment of hypertension in Chinese medicine in the past five years, and evaluates traditional Chinese medicine such as TCM Qigong, Wuhuo opera, Ba Duanjin and Taijiquan, and Chinese medicine acupuncture, moxibustion, massage, apptication, acupoint embedding and other traditional Chinese medicine. The effect of external treatment in hypertension control provides guidance for non-drug therapy to control hypertension.

Systematic review and meta analysis of the TCM therapy of Fuzheng and Kangai combined with chemotherapy in treating advanced NSCLC

Objective:To systematically evaluate TCM of Fuzheng and Kangai combined with chemotherapy in the treatment of Advanced NSCLC,including the efficacy and effect on the quality of life of patients.Methods:Two researchers independently searched the literature of clinical trails from Jan.2010 until Jun.2020 in the Cochrane Library,Pubmed,Embase,CBM,CNKI,WanFang Data and VIP database.Also,they had been evaluated and extracted strictly by REVMAN 5.3.Results:A total of 1303 patients were included in 15 articles.The meta analysis shows that the TCM of Fuzheng and Kangai combined with chemotherapy can improve the objective response rate[OR=2.14,95%CI(1.67,2.74),P<0.00001],disease control rate[OR=2.54,95%CI(1.88,3.42),P<0.00001]and KPS score[OR=3.28,95%CI(1.92,5.60),P<0.0001],decrease the incidence rate of liver injury[OR=0.34,95%CI(0.21,0.54),P=0.003],hemoglobin reduction[OR=0.53,95%CI(0.28,1.01),P=0.05],leukopenia[OR=0.22,95%CI(0.13,0.39),P<0.00001],thrombocytopenia[OR=0.32,95%CI(0.21,0.50),P<0.00001],toxic effects on the digestive systems[OR=0.30,95%CI(0.19,0.46),P<0.00001].Conclusions:the experimental group was better than control one in short-term efficacy and KPS score.Furthermore,the experimental group can reduce the incidence rate of myelosuppression,toxicity of digestive system and liver.

EXTREMELY HIGH FREQUENCY (EHF) PUNCTURE THERAPY AND SYNDROMES OF TRADITIONAL CHINESE MEDICINE

ExtremeIy high frequency (EHF) puncture is a new method of treatment based uponbiological effects of low power electromagnetic waves of millimetric band and acupuncture theory oftraditional Chinese medicine (TCM). It is non-invasive, painless and effective. Extensiveness and variety of the specific sensations (Deqi phenomenon) during EHF-puncture re-flect intensive reactions of the patient’s organism and provide individualization of therapy. EHF-puncture is a step of integration of traditional Chinese with modern Western medicines.

Sonographic assessment of carotid artery in postmenopausal women receiving long-term low-dose hormone replacement therapy

Objective: The aim of this study was to determine the influence of long-term low-dose hor mone replacement therapy (HRT) on the intima-media wall of the carotid artery in postmenopa usal women by ultrasound.Methods: 146 postmenopausal women were divided into the HRT group(n= 68, HRT over 5years after menopause) and the control group(n= 78, no HRT). The intima-media thickness (IMT) of the carotid arteries was measured bilaterally, the characteristics of the atherosclerotic plaques were described, the peak systolic velocity (PSV) and resistance index (RI) were measured by ultrasound examination.Results: The IMT of HRT group was significantly smaller than that of the control group,(0. 089±0. 22) cm vs (0. 093±0.29) cm, (P＜0. 01). The occurrence of plaques was reduced in HRT group than the control group (7.7% vs 12.7%, P＜0. 05). The plaques were most frequently found at the bifurcation of the arteries. The soft and mixed plaques in HRT group were found significantly less than that of the control group (soft 1.7% vs 4. 5%, mixed 3.1% vs 6. 7%, both P＜0.05), while the hard plaques in HRT group were more than those of the control group(2.6% vs 1.3%, P＜0. 05). The maximum plaque thickness of HRT group was less than that of control group (0. 191±0. 057) cm vs (0. 226±0. 073) cm, (P＜0.05). The internal carotid artery PSV and RI in the two groups were similar [PSV (65.61±26.55) cm/s vs (64.82±27. 22) cm/s, RI (0.67±0. 082) vs (0. 68±0. 075), both P＞0.05].Conclusion: Our study indicated that HRT may has an effect to reduce the carotid IMT thickness, inhibit the plaque formation, and make the plaques harder and more stable. The long-term low-dose HRT may protect the postmenopausal women against the artherosclerosis of the carotid artery.

Treatment of 140 cerebral palsied children with a combined method based on traditional Chinese medicine(TCM)and western medicine

Objective:To observe and evaluate a method that is effective and practical for treatment of cerebral palsied(CP)children in China.Method:The patient's age and disease type and individual specific conditions were considered in choosingtherapy methods accordingly:Chinese herbs,acupuncture,auricnlar seed pressure,point finger pressing,massage,orthopedichand manipulation,physiotherapy,occupational therapy,language therapy,etc.Meanwhile we created a new CP treatment modelthat combines hospitalized treatment with family therapy.Results:The majority of CP patients improved greatly in motor andsocial adaptation capacities after treatment.Wilcoxon paired rank sum test analysis showed that there were significant differencesbetween the data before and after treatment(P<0.01).Conclusion:This combined therapy method,based on traditional Chinesemedicine and western medicine plus family supplemental therapy,is an effective and practical treatment strategy for CP children inChina.

Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.

Therapy of acute severe pancreatitis awaits further improvement

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Research Progress of Non-drug Therapy of Traditional Chinese Medicine in the Treatment of Obese Polycystic Ovary Syndrome

Polycystic ovarian syndrome(PCOS)as a relatively common clinical reproductive endocrine disease,the incidence is increasing year by year and the treatment is difficult,among which obese PCOS accounts for nearly 50%of the total.In recent years,non-drug therapy of traditional Chinese medicine(TCM)has been effective in the treatment of PCOS.This article summarizes the relevant literature in the past ten years from acupuncture,acupoint embedding,moxibustion,and auricular points,and observes the effects of TCM non-drug therapy on endocrine and glucose and lipid metabolism in obese PCOS patients.The impact of various indicators such as body mass index,body mass index,etc.,and discuss the problems in such treatments,as well as put forward suggestions to achieve the purpose of better guiding the clinical treatment of obese PCOS.

Direct anti-atherosclerotic therapy preventing intracellular cholesterol retention

The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is an absolute requirement for lesion development. This allows us to consider intracellular cholesterol retention as a novel target for anti-atherosclerotic therapy. In this case, the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review summarizes the results of our basic studies shedding light on the mechanisms of intracellular cholesterol retention. We describe our cellular models to search for anti-atherosclerotic agents and demonstrate the use of these models for the development of anti-atherosclerotic drugs. We use natural products as the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy should be long-term or even lifelong. Using cellular models and natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured subendothelial aortic cells. We have developed drugs that reduce intracellular cholesterol retention, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinics. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.

Antiplatelet Therapy Considerations in Women

Coronary artery disease(CAD)is the leading cause of death worldwide,but because of several factors,one of which is antiplatelet therapy,the mortality rates have steadily declined.However,women continue to experience higher CAD mortality rates than men.This may be explained by differences in comorbidities,increased time to presentation,higher bleeding rates,and differences in management.There are numerous landmark trials in the field of antiplatelet therapy;however,women are consistently underrepresented in these trials.The results of these trials reveal that women experience the same benefit as men from antiplatelet therapy but experience higher bleeding rates;therefore bleeding-reduction strategies are imperative in this patient population.This review provides an overview of the available evidence on CAD in women and its implications for antiplatelet medications.

Intracellular Cholesterol Retention—New Target for Direct Anti-Atherosclerotic Therapy

Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular cholesterol retention is the principal event in the genesis of atherosclerotic lesions. This allows us to consider cellular retention of cholesterol as a novel target for anti-atherosclerotic therapy. In this case the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review describes our approach based on the use of cultured human arterial cells for the development of direct anti-atherosclerotic therapy. We use natural products as the basis of promising drugs for anti-atherosclerotic therapy. Using natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured cells. Our knowledge of the mechanisms of atherosclerosis is the foundation on which we have developed drugs that have a direct anti-atherosclerotic effect, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with allicor or inflaminat has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Karinat prevents the development of carotid atherosclerosis in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinical practice. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.

Interventional therapy for chronic simple atherosclerotic occlusive disease of lower extremity

Objective： To explore the efficacy of interventional therapy for chronic atherosclerotic occlusive disease of the lower extremity. Methods： Fifty-six cases of simple atherosclerotic occlusive disease of lower extremity were divided into 3 types according to the location of occhision, including 17 cases of abdominal aorta-iliac artery, 18 cases of iliac-femoral artery, and 21 cases of inferior popliteal artery. Catheter and guide wire combined with blunt dissection and subtle banding were used to dredge the occluded vessels, and stents were implanted when interlayer appeared. Results： After the treatment, 46 cases of occlusion were dredged （82.1%）, 6 cases remained occluded with the same symptoms （10.7%）, and 4 cases had severer symptoms （7.1%）. Among the 46 successful cases, there were 16 cases of abdominal aorta-iliac artery （94.1%）, 16 cases of iliac-femoral artery （88.9%） and 14 cases of inferior popliteal artery, artery （66.6%）. There was no statistical difference between the abdominal aorta-iliac artery cases and iliac-femoral artery cases （P〉0.05）, but there was statistical difference between these two types and the inferior popliteal artery cases （P〈0.05）. In the successful cases, 9 cases of abdominal aorta-iliac artery （52.9%）, 10 cases of iliac-femoral artery （55.5%） and 10 cases of inferior popliteal artery （33.3%） had 5-10 cm of occlusion, with no statistical difference between the first two types （P〉0.05）, but with statistical difference between the first two types and the third type （P〈0.05）. Compared with the 14 dredged cases （71.4%）, the 7 cases （33.3%） of inferior popliteal artery cases had richer compensatory circulation （P〈0.05）. Conclusion： It＇s safe and effective to treat simple atherosclerotic occlusive disease of the lower extremity with interventional therapy. The location and length of occlusion and the abundance of compensatory circulation had effect on the therapy.

Optimization of the pharmacological therapy in patients with polyvascular disease: A multidisciplinary approach

The recent shift of the concept of cardiovascular disease as a chronic progressive condition,potentially involving multiple districts,has driven attention to the optimal management of patients with concomitant coronary and peripheral artery disease,representing a subset of patients with an increased risk of events and impaired survival.Recent pharmacological achievements in terms of antithrombotic therapy and lipid-lowering drugs allow multiple therapeutical combinations,thus requiring optimizing the treatment in a tailored fashion according to patients’risk profiles.Nevertheless,data dedicated to this specific subset of patients are still modest.We summarize currently available strategies and indications for the management of antithrombotic and lipid-lowering drugs in patients with the poly-vascular disease.