Astragalus polysaccharide: implication for intestinal barrier, anti-inflammation, and animal production.

Intestine is responsible for nutrients absorption and plays a key role in defending against various dietary allergens, antigens, toxins, and pathogens. Accumulating evidence reported a critical role of intestine in maintaining animal and human health. Since the use of antibiotics as growth promoters in animal feed has been restricted in many countries, alternatives to antibiotics have been globally investigated, and polysaccharides are considered as environmentally friendly and promising alternatives to improve intestinal health, which has become a research hotspot due to its antibiotic substitution effect. Astragalus polysaccharide (APS), a biological macromolecule, is extracted from astragalus and has been reported to exhibit complex biological activities involved in intestinal barrier integrity maintenance, intestinal microbiota regulation, short-chain fatty acids (SCFAs) production, and immune response regulation, which are critical for intestine health. The biological activity of APS is related to its chemical structure. In this review, we outlined the source and structure of APS, highlighted recent findings on the regulation of APS on physical barrier, biochemical barrier, immunological barrier, and immune response as well as the latest progress of APS as an antibiotic substitute in animal production. We hope this review could provide scientific basis and new insights for the application of APS in nutrition, clinical medicine and health by understanding particular effects of APS on intestine health, anti-inflammation, and animal production.

Unveiling Atherosclerotic Plaque Heterogeneity and SPP1+/VCAN+ Macrophage Subtype Prognostic Significance Through Integrative Single-Cell and Bulk-Seq Analysis.

Background: Dysregulated macrophages are important causes of Atherosclerosis (AS) formation and increased plaque instability, but the heterogeneity of these plaques and the role of macrophage subtypes in plaque instability have yet to be clarified. Methods: This study integrates single-cell and bulk-seq data to analyze atherosclerotic plaques. Unsupervised clustering was used to reveal distinct plaque subtypes, while survival analysis and gene set variation analysis (GSVA) methods helped in understanding their clinical outcomes. Enrichment of differential expression of macrophage genes (DEMGs) score and pseudo-trajectory analysis were utilized to explore the biological functions and differentiation stages of macrophage subtypes in AS progression. Additionally, CellChat and the BayesPrism deconvolution method were used to elucidate macrophage subtype interaction and their prognostic significance at single-cell resolution. Finally, the expression of biomarkers was validated in mouse experiments. Results: Three distinct AS plaque subtypes were identified, with cluster 3 plaque subtype being particularly associated with higher immune infiltration and poorer prognosis. The DEMGs score exhibited a significant elevation in three macrophage subtypes (SPP1+/VCAN+ macrophages, IL1B+ macrophages, and FLT3LG+ macrophages), associated with cluster 3 plaque subtype and highlighted the prognostic significance of these subtypes. Activation trajectory of the macrophage subtypes is divided into three states (Pre-branch, Cell fate 1, and Cell fate 2), and Cell fate 2 (SPP1+/VCAN+ macrophages, IL1B+ macrophages, and FLT3LG+ macrophages dominant) exhibiting the highest DEMGs score, distinct interactions with other cell components, and relating to poorer prognosis of ischemic events. This study also uncovered a unique SPP1+/VCAN+ macrophage subtype, rare in quantity but significant in influencing AS progression. Machine learning algorithms identified 10 biomarkers crucial for AS diagnosis. The validation of these biomarkers was performed using Mendelian Randomization analysis and in vitro methods, supporting their relevance in AS pathology. Conclusion: Our study provides a comprehensive view of AS plaque heterogeneity and the prognostic significance of macrophage subtypes in plaque instability.

Differential miRNA Profiling Reveals miR-4433a-5p as a Key Regulator of Chronic Obstructive Pulmonary Disease Progression via PIK3R2- mediated Phenotypic Modulation.

OBJECTIVE: In this study, a high-throughput sequencing technology was used to screen the differentially expressed miRNA in the patients with "fast" and "slow" progression of chronic obstructive pulmonary disease (COPD). Moreover, the possible mechanism affecting the progression of COPD was preliminarily analyzed based on the target genes of candidate miRNAs. METHODS: The "fast" progressive COPD group included 6 cases, "slow" and Normal progressive COPD groups included 5 cases each, and COPD group included 3 cases. The peripheral blood samples were taken from the participants, followed by total RNA extraction and high throughput miRNA sequencing. The differentially expressed miRNAs among the progressive COPD groups were identified using bioinformatics analysis. Then, the candidate miRNAs were externally verified. In addition, the target gene of this miRNA was identified, and its effects on cell activity, cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed. RESULTS: Compared to the Normal group, a total of 35, 16, and 7 differentially expressed miRNAs were identified in the "fast" progressive COPD, "slow" progressive COPD group, and COPD group, respectively. The results were further confirmed using dual-luciferase reporter assay and transfection tests with phosphoinositide- 3-kinase, regulatory subunit 2 (PIK3R2) as a target gene of miR-4433a-5p; the result showed a negative regulatory correlation between the miRNA and its target gene. The phenotype detection showed that the activation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway might participate in the progression of COPD by promoting the proliferation of inflammatory A549 cells and inhibiting cellular apoptosis. CONCLUSIONS: MiR-4433a-5p can be used as a marker and potential therapeutic target for the progression of COPD. As a target gene of miR-4433a-5p, PIK3R2 can affect the progression of COPD by regulating phenotypes, such as cellular proliferation and apoptosis.

Autophagy core protein BECN1 is vital for spermatogenesis and male fertility in mice†.

Mammalian spermatogenesis is a highly complex multi-step biological process, and autophagy has been demonstrated to be involved in the process of spermatogenesis. Beclin-1/BECN1, a core autophagy factor, plays a critical role in many biological processes and diseases. However, its function in spermatogenesis remains largely unclear. In the present study, germ cell-specific Beclin 1 (Becn1) knockout mice were generated and were conducted to determine the role of Becn1 in spermatogenesis and fertility of mice. Results indicate that Becn1 deficiency leads to reduced sperm motility and quantity, partial failure of spermiation, actin network disruption, excessive residual cytoplasm, acrosome malformation, and aberrant mitochondrial accumulation of sperm, ultimately resulting in reduced fertility in male mice. Furthermore, inhibition of autophagy was observed in the testes of germ cell-specific Becn1 knockout mice, which may contribute to impaired spermiogenesis and reduced fertility. Collectively, our results reveal that Becn1 is essential for fertility and spermiogenesis in mice.

Icariin improves cardiac function and remodeling via the TGF-ß1/Smad signaling pathway in rats following myocardial infarction.

BACKGROUND: Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI). METHODS: Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF-ß1, p-Smad2, and p-Smad3 levels. RESULTS: The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-ß, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group. CONCLUSIONS: In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-ß1/Smad signaling pathway.

Astragalus (Astragalus mongholicus) Improves Ventricular Remodeling via ESR1 Downregulation RhoA/ROCK Pathway.

Astragalus (Astragalus mongholicus) alleviates myocardial remodeling caused by hypertension. However, the detailed molecular mechanism is unclear. This study aims to investigate the effect of Astragalus on ventricular remodeling in ovariectomized spontaneous hypertensive rats (OVX-SHR).Female SHR/NCrl rats were subjected to bilateral ovariectomy to establish the OVX-SHR model and treated with Astragalus extract by gavage. The hemodynamics and cardiac function parameters were measured. HE and Masson staining were used to detect the pathological structure of myocardial remodeling and observe the hyperplasia of myocardial collagen fibers. The immunohistochemistry tested the level of α-SMA. The expression levels of inflammatory cytokines, IκB, p65, Cleaved-Caspase3, RhoA, and ROCK1/2 were detected using Western blot. The method of qRT-PCR measured the expression of matrix metalloproteinase (MMP-2 and MMP-9).Hemodynamic and cardiac function parameters were significantly improved after a high dose of Astragalus extract and Valsartan treatment. The myocardial integrity of the model group was significantly reduced, arranged loosely, and disordered, while the expression of α-SMA was increased. However, Astragalus extract and Valsartan treatments significantly reduced the pathological damage and α-SMA. The levels of TNF-α, IL-1ß, IL-6, TGF-ß, MMP-2, and MMP-9 in the model group were increased but decreased after Astragalus extract treatment. Adding an ESR1 inhibitor attenuated the improvement effect of Astragalus extract on myocardial remodeling and restored the expression of RhoA and ROCK1/2.Astragalus extract attenuates the cardiac damage in OVX-SHR by downregulating the RhoA/ROCK pathway through ESR1.

Development of a colloidal gold immunochromatographic strip with enhanced signal for the detection of bovine parvovirus.

Bovine parvovirus (BPV) is a pathogen responsible for respiratory and digestive tract symptoms in calves and abortion and stillbirth in pregnant cows. In this study, we developed a colloidal gold immunochromatographic (GICG) strip with an enhanced signal for detecting BPV according to the double-antibody sandwich principle and an enzyme-based signal amplification system to amplify the signal. This system utilizes horseradish peroxidase reacting with a substrate solution containing 3,3',5,5'-tetramethylbenzidine and dextran sulfate to obtain insoluble blue products on the test and control lines. We optimized different reaction conditions, including the amount of monoclonal antibodies (mAbs), pH of the colloidal gold solution, coating solution, blocking solution, sample pad treatment solution, antibody concentration in the control line, and antibody concentration in the detection line. The sensitivity of the signal-enhanced GICG strip showed that the minimum amount for detecting BPV was 102 TCID50, 10 times higher than that of the traditional GICG strip. The results of the specificity test showed that the signal-enhanced GICG strip had no cross-reactivity with BRV, BVDV, or BRSV. The results of the repeatability test showed that the coefficient of variation between and within batches was less than 5%, showing good repeatability. Moreover, for validation, PCR and the signal-enhanced GICG strip were used to detect 280 clinical bovine fecal samples. The concordance rate compared with PCR was 99.29%. Hence, the developed strip exhibited high sensitivity and specificity for the detection of BPV. Therefore, this strip could be a rapid, convenient, and effective method for the diagnosis of BPV infection in the field.

Identification of Genes Related to Endoplasmic Reticulum Stress (ERS) in Chronic Obstructive Pulmonary Disease (COPD) and Clinical Validation.

Objective: Endoplasmic reticulum stress (ERS) is key in chronic obstructive pulmonary disease (COPD) incidence and progression. This study aims to identify potential ERS-related genes in COPD through bioinformatics analysis and clinical experiments. Methods: We first obtained a COPD-related mRNA expression dataset (GSE38974) from the Gene Expression Omnibus (GEO) database. The R software was then used to identify potential differentially expressed genes (DEGs) of COPD-related ERS (COPDERS). Subsequently, the identified DEGs were subjected to protein-protein interaction (PPI), correlation, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Following that, qRT-PCR was used to examine the RNA expression of six ERS-related DEGs in blood samples obtained from the COPD and control groups. The genes were also subjected to microRNA analysis. Finally, a correlation analysis was performed between the DEGs and key clinical indicators. Results: Six ERS-related DEGs (five upregulated and one downregulated) were identified based on samples drawn from 23 COPD patients and nine healthy individuals enrolled in the study. Enrichment analysis revealed multiple ERS-related pathways. The qRT-PCR and mRNA microarray bioinformatics analysis results showed consistent STC2, APAF1, BAX, and PTPN1 expressions in the COPD and control groups. Additionally, hsa-miR-485-5p was identified through microRNA prediction and DEG analysis. A correlation analysis between key genes and clinical indicators in COPD patients demonstrated that STC2 was positively and negatively correlated with eosinophil count (EOS) and lymphocyte count (LYM), respectively. On the other hand, PTPN1 showed a strong correlation with pulmonary function indicators. Conclusion: Four COPDERS-related key genes (STC2, APAF1, BAX, and PTPN1) were identified through bioinformatics analysis and clinical validation, and the expressions of some genes exhibited a significant correlation with the selected clinical indicators. Furthermore, hsa-miR-485-5p was identified as a potential key target in COPDERS, but its precise mechanism remains unclear.

Torsade de pointes caused by citalopram during the pacemaker battery-depletion phase: A case report.

Drug-induced QT prolongation, primarily antiarrhythmic drugs, is a common cause of torsade de pointes (TdP). Although there have been previous reports of drug-induced TdP in patients, it has not been well documented when caused by citalopram during the pacemaker battery-depletion phase. To improve delirium recognition, we report a case of citalopram-induced TdP during the pacemaker battery-depletion phase. An 84-year-old Chinese female was brought to the hospital presenting recurrent syncope. She lost consciousness and was admitted after her syncope TdP was documented. Her pacemaker was inspected and found to be operating in an extremely ineffective manner. Although she had prolonged QT interval after the pacemaker was replaced, she did not suffer another syncope attack, and ECG monitoring revealed no cardiac arrhythmia or TdP. During her admission, she was treated with citalopram for depression. Citalopram was discontinued when the QT interval shortened progressively. In this study, we described a case of citalopram-induced TdP during the depletion phase of a pacemaker battery. This case should serve as a cautionary lesson to clinicians to avoid using citalopram during the pacemaker battery-depletion phase.

Functional changes of airway epithelial cells and mitochondria in rat models of asthenic lung and phlegm blocking combined with cough variant asthma.

The aim of this study was to investigated the functional changes of airway epithelial cells and mitochondria in rat models of asthenic lung and phlegm blocking combined with cough variant asthma (CVA). Sixteen Sprague-Dawley rats were randomly divided into two groups: Control and model group, with 8 rats in each group. On the basis of the CVA rat model induced and sensitized by ovalbumin and aluminum hydroxide, the rat models with asthenic lung and phlegm blocking combined with CVA were established via smoking stimulation. The rats in the control group were injected with equivalent normal saline. All rats were sacrificed after the model was successfully prepared. The lung histopathological sections of the two groups of rats were observed, and respiratory control ratio (RCR) of mitochondria and membrane potential changes were compared. The results showed that the rats in the model group had tracheal structure abnormities, epithelial cell damages, cilia structure defects, capillary injection, alveolar exudates, and inflammatory cells compared to those in the control group. RCR of mitochondria and membrane potential of rats in the model group were significantly lower than those of rats in the control group (P<0.05). Damaged lung tissue and decreased mitochondrial activity and membrane potential are detected in the rat models of asthenic lung and phlegm blocking combined with CVA.

The comparison of methods to identify the presence of fibrocytes in formalin-fixed, paraffin-embedded archival cardiac tissue with coronary heart disease.

The purpose of this study was to find the optimal technical approach to identify the presence of fibrocytes in formalin-fixed, paraffin-embedded archival cardiac tissue with CHD (coronary heart disease). Using the coexpression markers CD45 and αSMA, the presence of fibrocytes was examined by three different methods, including double immunohistochemistry staining, combination labeling of immunohistochemistry and immunofluorescence and double immunofluorescence labeling. Double immunohistochemistry staining was very difficult to identify the CD45(+)/αSMA(+) fibrocytes. Although combination staining of immunohistochemistry and immunofluorescence has made it possible to evaluate the co-localization of CD45 and αSMA in the fibrocytes, this method was prone to produce many false positive cells. In contrast, CD45(+)/αSMA(+) fibrocytes could be clearly recognized by double immunofluorescence labeling. In conclusion, double immunofluorescence labeling is the optimal technical approach to identify the presence of fibrocytes in routinely processed cardiac tissue with CHD.

Extracorporeal cardiac shock wave therapy ameliorates myocardial fibrosis by decreasing the amount of fibrocytes after acute myocardial infarction in pigs.

OBJECTIVES: Extracorporeal shock wave (SW) therapy ameliorates cardiac remodeling after acute myocardial infarction (AMI). However, it remains to be examined whether and how SW therapy ameliorates myocardial fibrosis after AMI. Fibrocytes are associated with myocardial fibrosis. Thus, we examined whether SW therapy ameliorates myocardial fibrosis and whether fibrocytes are associated after AMI in pigs. MATERIALS AND METHODS: AMI was created by coronary embolism. Twenty-five pigs were divided into three groups: AMI+SW group (AMI with SW therapy, n=15), AMI group (without SW therapy, n=5), and sham+SW group (SW therapy without AMI, n=5). The collagen area fraction was examined by Masson's trichrome staining. The presence of fibrocytes was identified by immunofluorescence and confocal microscopy. The location of CXCL12 was examined by immunohistochemistry. RESULTS: Compared with the AMI group, the AMI+SW group showed significantly ameliorated myocardial fibrosis in terms of collagen area fraction (27.21±8.13 vs. 10.13±4.96, P<0.05) and reduced fibrocytes (CD34/α-smooth muscle actin: 35.40±11.72 vs. 12.27±7.71, P<0.05; CXCR4/α-smooth muscle actin: 40.80±8.96 vs. 16.54±6.38, P<0.05). There were positive correlations between the collagen area fraction and the number of fibrocytes (r=0.936; P<0.05) and between the number of CXCR4 fibrocytes and the SDF-1/CXCL12 cells (r=0.802; P<0.05) in the three groups. CONCLUSION: The results show that SW therapy ameliorates myocardial fibrosis after AMI in pigs, which is associated with the decreased amount of fibrocytes.

Fibrocytes are associated with the fibrosis of coronary heart disease.

Fibrocytes contribute significantly to fibrosis in many cardiac diseases. However, it is not clear whether fibrocytes are associated with the fibrosis in coronary heart disease (CHD). The aim of this study was to determine whether fibrocytes are involved in cardiac fibrosis in CHD. We identified the presence of fibrocytes in CHD heart by immunofluorescence and confocal microscopy, examined the collagen volume fraction by Masson's Trichrome staining, and evaluated the correlation between fibrocytes and cardiac fibrosis. In conjunction, we examined the location of CXCL12, a homing factor and specific ligand for CXCR4, by immunohistochemistry. Fibrocytes were identified in 26 out of 27 CHD hearts and in 10 out of 11 normal hearts. Combinations, including CD34/αSMA, CD34/procollagen-I, CD45/αSMA, CXCR4/procollagen-I and CXCR4/αSMA, stained significantly more fibrocytes in CHD hearts as compared with those in normal hearts (p<0.05). There were positive correlations between the collagen volume fraction and the amount of fibrocytes (r=0.558; p=0.003<0.01) and between the number of CXCR4(+) fibrocytes and the CXCL12(+) cells (r=0.741; p=0.000<0.01) in CHD hearts. Based upon these findings, we conclude that fibrocytes, likely recruited through the CXCR4/CXCL12 axis, may contribute to the increase in the fibroblast population in CHD heart.

A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease.

BACKGROUND: Cardiac shock wave therapy (CSWT) improves cardiac function in patients with severe coronary artery disease (CAD). We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. METHODS: The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14) received only medical therapy. In group A ( n = 20), CSWT was performed 3 times within 3 months. In group B ( n = 21), patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT). Other measurements were also evaluated. RESULTS: The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. CONCLUSIONS: A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. CLINICAL TRIAL REGISTRY: We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.

[Extracorporeal cardiac shock wave therapy improved myocardial micro-vascular circulation after acute myocardial infarction at early stage in pigs].

OBJECTIVE: To explore the effect of low-energy extracorporeal shock wave therapy to improve myocardial micro-vascular circulation after acute myocardial infarction at the early stage in pig model. METHODS: A total of 25 domestic pigs were used in this study. Model of acute myocardial infarction (AMI) was created successfully by the implantation of angioplasty balloon in mid-distal segment of left anterior descending coronary artery (n=20). These AMI animals were divided two groups. Extracorporeal shock wave therapy to the ischemic myocardial region was performed for the group of shock wave therapy (n=15) at 3 days after acute myocardial infarction; The remaining AMI animals were treated in the same manner, but without the shock wave therapy (n=5), The other health animals (n=5) were used as blank control group. The number of endothelium cell, capillary density, VEGF mRNA level and collateral vessel Rentrop score in each group were evaluated and compared. RESULTS: Shock wave treatment up-regulated the mRNA expression of VEGF in the model of acute myocardial infarction (P < 0.05). Furthermore, the number of capillaries was significantly higher in the shock wave group than that of positive and blank control group (P < 0.05). The Rentrop score of collateral vessel indicated the reconstruction of collateral circulation in shock wave group. CONCLUSION: Extracorporeal cardiac shock wave therapy could effectively induce angiogenesis, up-regulate the expression of angiogenic factor, resulting in an improvement in micro-vascular circulation reconstruction of ischemic myocardial region.

[Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease].

OBJECTIVE: To evaluate the feasibility and efficiency of extracorporeal cardiac shock wave therapy (CSWT) for treatment of coronary artery disease. METHODS: Twenty-five patients with 1 - 16 years history of chronic angina pectoris underwent the CSWT. Before and after the treatment, low-dose Dobutamine stress echocardiography and (99)Tc(m)-MIBI myocardial perfusion SPECT were applied to locate the ischemic segments, detect the viable myocardium and evaluate the effect of CSWT. Under the guidance of echocardiography, CSWT was applied in R-wave-triggered manner with low energy (0.09 mJ/mm(2)) at 200 shoots/spot for 9 spots (-1-0-+1 combination). Patients were divided group A and group B. Sixteen patients in group A were applied 9 sessions on 29 segments within 3 month and nine patients in group B were applied 9 sessions on 13 segments within 1 month. Ten chronic angina pectoris patients receiving standard medication served as controls. RESULTS: All patients completed the 9 sessions without procedural complications or adverse effects. CSWT significantly improved symptoms as evaluated by NYHA, Canadian Cardiovascular Society (CCS) class sores, Seattle angina questionnaire (SAQ), 6-min walk and the use of nitroglycerin (P < 0.05). CSWT also improved myocardial perfusion and regional myocardium function as evaluated by rest SPECT and stress peak systolic strain rate (PSSR) (P < 0.01). Myocardial perfusion improvement was more significant in group A compared with group B (1.21 ± 0.86 vs. 0.83 ± 0.80, P < 0.01). All parameters remained unchanged in control group during follow up. CONCLUSION: These preliminary results indicate that CSWT is safe and effective on ameliorating anginal symptoms for chronic angina pectoris patients.

Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease.

BACKGROUND: Safe and effective therapeutic management of refractory coronary artery disease (CAD) in heart patients is critical to enhance cardiovascular function and improve quality of life. Current therapies for refractory CAD are inadequate in ameliorating angina and promoting revascularization of ischemic myocardium. HYPOTHESIS: Cardiac shock wave therapy (CSWT) is a safe and effective noninvasive intervention in the management of patients with refractory CAD. METHODS: The study enrolled 9 male patients age 50 to 70 years (5.11 ± 5.46 years) with a diagnosis of CAD and stent implantation (3.00 ± 2.24 stents). CSWT was carried out for 3 months at 3 intervals during the first week of each month (first, third, and fifth day), for a total of 9 therapies per patient. Dobutamine stress echocardiography and radionuclide angiography identified the myocardial ischemic segments. The effects of CSWT on myocardial perfusion and systolic function were examined. Other outcome measures included myocardial injury enzyme markers, angina scale, nitroglycerin dosage, and cardiopulmonary fitness assessments. RESULTS: Improved myocardial blood flow and regional systolic function (stress peak systolic strain rate - 1.10 to - 1.60 s(-1), P = 0.002) were detected in patients following CSWT. Reductions in creatine kinase (87.89 ± 36.69 to 86.22 ± 35.96 IU/L, P = 0.046), creatine kinase MB (10.89 ± 5.73 to 10.11 ± 5.93 IU/L, P = 0.008), aspartate transaminase (interquartile range [IQR], 28.00 to 27.00 IU/L, P = 0.034) were also found. Angina (Canadian Cardiovascular Society scale IQR 3.0 to 2.0, P = 0.035) and nitroglycerin dose reduction (IQR 3.0 to 1.0 times/wk, P = 0.038) were reported. CONCLUSIONS: This study is a preliminary assessment of CSWT in patients with refractory CAD. We report that CSWT is a noninvasive, effective, and safe intervention in the treatment of refractory CAD.