A New and Practical Model of Human-like Ascending Aorta Aneurysm in Rats.

INTRODUCTION: Ascending aortic aneurysm is a serious health risk. In order to study ascending aortic aneurysms, elastase and calcium ion treatment for aneurysm formation are mainly used, but their aneurysm formation time is long, the aneurysm formation rate is low. Thus, this study aimed to construct a rat model of ascending aorta aneurysm with a short modeling time and high aneurysm formation rate, which may mimic the pathological processes of human ascending aorta aneurysm. METHODS: Cushion needles with different pipe diameters (1.0, 1.2, 1.4 and 1.6 mm) were used to establish a human-like rat model of ascending aortic aneurysm by narrowing the ascending aorta of rats and increasing the force of blood flow on the vessel wall. The vascular diameters were evaluated using color Doppler ultrasonography after two weeks. The characteristics of ascending aortic aneurysm in rats were detected by Masson's trichrome staining, Verhoeff's Van Gieson staining and hematoxylin and eosin staining while RT-PCR were utilized to assess the total RNA of cytokine interleukin-1ß, interleukin 6, transforming growth factor-beta1 and metalloproteinase 2. RESULTS: Two weeks after surgery, the ultrasound images and the statistical analysis demonstrated that the diameter of the ascending aorta in rats increased more than 1.5 times, similar to that in humans, indicating the success of animal modeling of ascending aortic aneurysm. Moreover, the optimal constriction diameter of the ascending aortic aneurysm model is 1.4 mm by the statistical analysis of the rate of ascending aortic aneurysm and mortality rate in rats with different constriction diameters. CONCLUSIONS: The human-like ascending aortic aneurysm model developed in this study can be used for the studies of the pathological processes and mechanisms in ascending aortic aneurysm in a more clinically relevant fashion.

Landscape of molecular crosstalk between SARS-CoV-2 infection and cardiovascular diseases: emphasis on mitochondrial dysfunction and immune-inflammation.

BACKGROUND: SARS-CoV-2, the pathogen of COVID-19, is a worldwide threat to human health and causes a long-term burden on the cardiovascular system. Individuals with pre-existing cardiovascular diseases are at higher risk for SARS-CoV-2 infection and tend to have a worse prognosis. However, the relevance and pathogenic mechanisms between COVID-19 and cardiovascular diseases are not yet completely comprehended. METHODS: Common differentially expressed genes (DEGs) were obtained in datasets of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2 and myocardial tissues from heart failure patients. Further GO and KEGG pathway analysis, protein-protein interaction (PPI) network construction, hub genes identification, immune microenvironment analysis, and drug candidate predication were performed. Then, an isoproterenol-stimulated myocardial hypertrophy cell model and a transverse aortic constriction-induced mouse heart failure model were employed to validate the expression of hub genes. RESULTS: A total of 315 up-regulated and 78 down-regulated common DEGs were identified. Functional enrichment analysis revealed mitochondrial metabolic disorders and extensive immune inflammation as the most prominent shared features of COVID-19 and cardiovascular diseases. Then, hub DEGs, as well as hub immune-related and mitochondria-related DEGs, were screened. Additionally, nine potential therapeutic agents for COVID-19-related cardiovascular diseases were proposed. Furthermore, the expression patterns of most of the hub genes related to cardiovascular diseases in the validation dataset along with cellular and mouse myocardial damage models, were consistent with the findings of bioinformatics analysis. CONCLUSIONS: The study unveiled the molecular networks and signaling pathways connecting COVID-19 and cardiovascular diseases, which may provide novel targets for intervention of COVID-19-related cardiovascular diseases.

GC gene polymorphisms found with type 2 diabetes and low vitamin D status among rural Chinese in Henan province.

BACKGROUND AND OBJECTIVES: Accumulating evidence suggests that vitamin D may be involved in the pathogenesis of type 2 diabetes (T2D). Group-specific component (GC) gene is the most important transporter of vitamin D and plays a regulatory role in vitamin D metabolism. We aimed to evaluate the association of GC gene polymorphisms with T2D susceptibility and vitamin D status in the Chinese rural population. METHODS AND STUDY DESIGN: A total of 1372 subjects were eligible in this cross-sectional study. Three SNPs of the GC gene (rs7041, rs4588, and rs2282679) were genotyped by TaqMan probe assays. Logistic regression and Kruskal-Wallis one-way analysis were performed to determine the possible risk genotype for T2D and vitamin D metabolite concentrations, respectively. RESULTS: The serum 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D binding protein (DBP) concentrations were significantly lower in the T2D group than the non-T2D group. GG genotype carriers of rs7041 (T>G) were more likely to have T2D compared with AA carriers (OR=2.00, 95% CI: 1.19-3.37). Variants of rs4588 (C>A) and rs2282679 (A>C) were associated with a lower risk of T2D under the dominant inheritance model (OR=0.65, 95% CI: 0.48-0.88; OR=0.66, 95% CI: 0.49-0.90, respectively). We further found that non-T2D subjects with the AA genotype of rs4588 had significantly higher 25(OH)D3 concentrations than the CC genotype (p=0.022). In contrast, the T2D cases with the CC genotype of rs2282679 had lower DBP concentrations compared to the AA genotype (p=0.020). CONCLUSIONS: Our study indicates a potential role for GC gene polymorphisms in T2D susceptibility and vitamin D metabolite concentrations in the Chinese rural population.

Urine proteomics identifies biomarkers for diabetic kidney disease at different stages.

BACKGROUND: Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the 'gold standard' for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. METHODS: In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. RESULTS: We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. CONCLUSIONS: Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.

A novel functional polymorphism of GSTM3 reduces clear cell renal cell carcinoma risk through enhancing its expression by interfering miR-556 binding.

Dysregulation of glutathione-S-transferase M3 (GSTM3) has been related to clear cell renal cell carcinoma (ccRCC) in our former study. GSTM3 plays a pivotal role of detoxification and clearance of reactive oxygen species (ROS) in tumour tissues. This study aimed to examine: (1) the associations between GSTM3 single nucleotide polymorphisms (SNPs) and risk of ccRCC, and (2) the potential molecular mechanism accounting for its effects. 5 SNPs in 3'UTR of GSTM3 were initially genotyped in 329 cases and 420 healthy controls. A SNP-rs1055259 was found to be significantly associated with the susceptibility of ccRCC (OR = 0.59, 95% CI = 0.41-0.92; P = .019). The minor allele of rs1055259 (G allele) was associated with RCC risk. This SNP was predicted to affect microRNA (miR)-556 binding to 3'UTR of GSTM3 mRNA. To determine the functional impact, plasmid constructs carrying different alleles of rs1055259 were created. Compared to rs1055259 A-allele constructs, cells transfected with rs1055259 G-allele construct had higher transcriptional activity and were less responsive to miR-556 changes and gene expression. Elevated GSTM3 expression in G-allele cells was associated with ROS activity and ccRCC development. Taken together, this study indicated that a functional polymorphism of GSTM3 -rs1055259 reduced susceptibility of RCC in the Chinese population. It influenced GSTM3 protein synthesis by interfering miR-556 binding, subsequently suppressed ROS activity and ccRCC progression.

Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect and therefore may have a therapeutic potential in T-cell-dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). METHODS: Bone marrow-derived DCs and BMSCs were co-cultured, with CD45RB expression on the surface of DCs measured by flow cytometry. qRT-PCR and Western blotting were used to detect mRNA and protein levels. Cytometric bead array was performed to determine the serum level of IL-10. Survival time of transplanted heart and expression of CD4+ , CD8+ , IL-2, IL-4, IL-10, IFN-γ were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. RESULTS: DCs co-cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RB+ DCs co-cultured with T-cells CD4+ displayed increased T-cell CD4+ Foxp3 ratio and IL-10 than DCs. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD4+ , expression levels of IL-2 and IFN-γ, and increased the CD4+ Foxp3 ratio and levels of IL-4 and IL-10. CD45RB+ DCs achieved better protective effects than DCs. CONCLUSION: BMSCs increased the expression of CD45RB in the bone marrow-derived DCs, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.

Aortic Valve Myxoma in a Young Man: A Case Report and Review of Literature.

Myxoma is the most commonly found cardiac primary tumor. The left atrium is the most common localization of myxoma, followed by the right atrium. However, it is rare in the left and right ventricles. Myxoma originating from cardiac valves is extremely rare. This article presents a case of a 17-year-old male who was admitted due to heart murmur for one year. Transthoracic echocardiography indicated a 1.9 cm round solid mass in the left ventricular outflow tract. Excision surgery and aortic valve replacement were performed in this patient. Histopathology revealed the mass as a myxoma. The aortic valve remains a very rare myxoma localization position. Echocardiography can provide a precise method for myxoma diagnosis. Early excision associated with valve replacement can provide good curative effects.

Preoperative ejection fraction determines early recovery of left ventricular end-diastolic dimension after aortic valve replacement for chronic severe aortic regurgitation.

BACKGROUND: In patients with chronic severe aortic regurgitation (AR), aortic valve replacement (AVR) has been proved to promote left ventricular (LV) remodeling, especially LV end-diastolic dimension (LVEDD) reduction. However, there is little research whether postoperative LVEDD could return to normal parameter after AVR. The objective of this study was to determine predictors for the recovery of dilated LVEDD early after AVR. METHODS: The echocardiographic data of 105 patients, who underwent AVR for chronic pure AR between January 2005 and December 2011, were analyzed at the preoperative (3-7 d), early (6-8 mo), and late (2-y) postoperative stages, retrospectively. According to the baseline level, LVEDD >70 mm or LV end-systolic dimension (LVESD) >50 mm or LVESD index >25 mm/m(2) were defined as severe LV dilation. Patients were then categorized into two groups (group 1: severe LV dilation; group 2: nonsevere LV dilation). RESULTS: In all patients, four-fifth of the reduction in LV dimension occurred at early (6-8 mo) postoperative stage. The patients in both groups had significant decreases in the LVEDD and LVESD early after AVR, with an additional but insignificant reduction at late postoperative stage. The ejection fraction (EF) in both groups significantly increased at either early or late stage. However, the LVEDD and LVESD in group 1 were larger than those in group 2, and the EF in group 1 was lower than that in group 2 at early postoperative stage. By multivariate analysis, we found that the preoperative EF was a good predictor for the recovery of dilated LVEDD early after AVR (P = 0.009). Receiver-operating characteristics analysis showed that EF >52% was the best cut-off value for the recovery of LVEDD. CONCLUSIONS: In patients with chronic pure AR, preoperative EF may be a good predictor for successful recovery of dilated LVEDD early after AVR.

Injection of Sca-1+/CD45+/CD31+ mouse bone mesenchymal stromal-like cells improves cardiac function in a mouse myocardial infarct model.

The objective of this study was to screen mouse bone marrow mesenchymal stromal cells (BMSCs) according to expression of cardiac stem cell (CSC) surface antigens and to assess the effects of resulting BMSC-like subsets on cardiac function after injection in a mouse myocardial infarct model. BMSCs were sorted by magnetic beads according to the expression of differentiation antigens on the surface of mouse CSCs, and four subsets were identified on the basis of CD45 and CD31 expression: stem cell antigen-1+ (Sca-1+)/CD45-/CD31-, Sca-1+/CD45-/CD31+, Sca-1+/CD45+/CD31-, and Sca-1+/CD45+/CD31+. When co-cultured with myocardial stem cells and 5-aza-2'-deoxycytidine for 14 days, each subset showed expression of cardiac markers α-actin, connexin 43, desmin, and cardiac troponin I; however, expression was greatest in Sca-1+/CD45+/CD31+ cells. To assess the ability of these cells to improve cardiac function, each subset was injected separately into mice with myocardial infarct induced by ligation of the left anterior descending coronary artery, and in vivo cardiac dual inversion recovery (DIR) imaging and Doppler echocardiography were performed 48 h, 96 h, and 7 days after injection. Results indicated that Sca-1+/CD45+/CD31+ cells were superior in improving cardiac function compared with the other subsets and with unsorted BMSCs. These results suggest that mouse BMSC cells are polyclonal and that the BMSC-like Sca-1+/CD45+/CD31+ subset was effective in directing cardiac differentiation and improving cardiac function in mice with myocardial infarcts.

Swin-Transformer -YOLOv5 for lightweight hot-rolled steel strips surface defect detection algorithm.

An essential industrial application is the examination of surface flaws in hot-rolled steel strips. While automatic visual inspection tools must meet strict real-time performance criteria for inspecting hot-rolled steel strips, their capabilities are constrained by the accuracy and processing speed of the algorithm used to identify defects. To solve the problems of poor detection accuracy, low detection efficiency, and unsuitability of low computing power platforms of the hot-rolled strip surface defect detection algorithm The Swin-Transformer-YOLOv5 model based on the improved one-stage detector is proposed. By employing GhostNet, the model's lightweight design, and guaranteed detection accuracy are both achieved. The C3 module introduces Swin-Transformer to address the issues of cluttered backdrops of defect photos and easily confused defect categories. With the addition of the CoordAttention module, the model's capacity to extract defective features is improved, and its performance keeps getting better. The issue of huge differences in different scales and poor detection of small flaws is resolved by employing BiFPN for feature fusion, and the detector's capacity to adapt to targets of different scales is improved. The experimental results demonstrate that the improved Swin-Transformer-Yolov5 model significantly outperforms the industry-standard target detection algorithms, and the model's mAP value still improves by 8.39% over the original model while reducing the number of parameters, GFLOPs, and weight by 36.6%, 40.0%, and 34.7%, respectively. The model is better suited for use on low-arithmetic platforms as a result.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Combined intrathymic and intravenous injection of mesenchymal stem cells can prolong the survival of rat cardiac allograft associated with decrease in miR-155 expression.

BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to improve graft outcomes and promote allograft tolerance. In this study, we examined the effects and mechanism of combined intrathymic (i.t.) and intravenous (i.v.) injection of MSCs on the survival of transplanted hearts in a rat allograft model. METHODS: Recipient Sprague-Dawley rats were transplanted with hearts from Wistar rats. Wistar rat MSCs were infused via i.t. or i.v. or combined i.t. and i.v. (i.t./i.v.) injection at designated intervals. In vitro mixed lymphocyte reaction assays were performed to assess the immunosuppressive capacity of MSCs. Mesenchymal stem cell surface markers and CD4+, CD25+, and Foxp3+ T-cells in the peripheral blood were detected using flow cytometry analysis. The expression of microRNAs and cytokines in graft infiltrating lymphocytes was analyzed by real-time polymerase chain reaction. RESULTS: The MSCs cultured in vitro had multipotential differentiation capacity. Mixed lymphocyte reaction assays showed that donor-derived MSCs could not stimulate a proliferative response of recipient lymphocytes and could markedly suppress T-cell responses. Survival of the allografts was significantly prolonged by administration of i.t./i.v. injection of MSCs compared with controls, with a mean survival of 32.2 versus 6.5 d, respectively. Compared with the syngeneic groups posttransplant, miR-155 expression was significantly increased in the allogeneic group, and could be restored by injection of MSCs, especially i.t./i.v. injection of MSCs. Moreover, i.t./i.v. injection of MSCs decreased the level of interleukin (IL)-2 and interferon-gamma, but increased the levels of IL-4 and IL-10 in the allogeneic group. More important, i.t./i.v. injection of MSCs was the best way to increase the percentage of CD4+, CD25+, and Foxp3+ T-cell peripheral blood. CONCLUSIONS: Our results indicated that i.t./i.v. injection of MSCs can prolong the survival of rat cardiac allograft, which may be associated with down-regulating miR-155 expression, a shift in the Th1/Th2 balance, and up-regulation of Treg cells expression.

[Efficacy of subgroup mouse bone mesenchymal stem cells on mobilizing autologous cardiac stem cells and repairing ischemic myocardial tissue].

OBJECTIVE: To search for the bone mesenchymal stem cell (MSC) subgroup which might be more effective on repairing myocardial damage. METHODS: In this experiment, four MSC subgroups were defined based on the surface differentiation antigen detection of mouse bone mesenchymal stem cells (mBMSCs): SCA-1(+)/CD45(+)/CD31(+), SCA-1(+)/CD45(+)/CD31(-), SCA-1(+)/CD45(-)/CD31(-) and SCA-1(+)/CD45(-)/CD31(+). These subgroup cells and unselected mBMSCs were injected into infarcted mouse via tail vein. Echocardiographic heart function measurement and in vivo DiR-labeled stem cells imaging were performed at 48 h after injection. In situ C-kit (a flag antigen of cardiac stem cells) and cardiac-specific differentiation antigen immunohistochemistry detection was made in the infarcted myocardium. RESULTS: The capacity of the SCA-1(+)/CD45(+)/CD31(+) cells on improving heart function was significantly higher than other cell groups (all P < 0.05). In vivo imaging showed that the mean fluorescence intensity of the SCA-1(+)/CD45(+)/CD31(+) cells was also higher than other cell groups (all P < 0.05). Number of cardiac stem cells in the infracted myocardium was significantly increased after the injection of all subgroup cells and unsorted mBMSCs cells for 48 h compared untreated infracted myocardium. The capacity of mobilizing cardiac stem cells is as follows: SCA-1(+)/CD45(+)/CD31(+) >SCA-1(+)/CD45(-)/CD31(+) >SCA-1(+)/CD45(-)/CD31(-) >SCA-1(+)/CD45(+)/CD31(-). CONCLUSION: The SCA-1(+)/CD45(+)/CD31(+) subgroups of mBMSCs exhibites the highest capacity to improve cardiac function after myocardial infarction and to mobilize autologous cardiac stem cells compared with other mBMSCs subgroups and unsorted mBMSCs cells.

Effect of Vitamin D and/or Calcium Supplementation on Pancreatic ß-Cell Function in Subjects with Prediabetes: A Randomized, Controlled Trial.

So far, the potential role of vitamin D in ß-cell function remains a matter of debate. Therefore, a randomized, placebo-controlled trial (RCT) was conducted to evaluate the effect of a vitamin D supplement with or without calcium on ß-cell function in a Chinese population with prediabetes. Two hundred and forty-three subjects were randomly assigned in a 2-by-2 factorial-design RCT to receive either 1600 IU/day vitamin D3 with/or 500 mg/day calcium for 24 weeks. The results showed that oral administration of vitamin D and calcium could increase the secretion of insulin. Vitamin D-insufficient individuals displayed an increment in the disposition index (adjusted change = 0.31, 95%CI: 0.07, 0.56) after treatment by vitamin D + calcium. It illustrated that supplementation with vitamin D and calcium might improve the function of pancreatic ß-cell in prediabetes with low serum 25(OH)D levels. However, further studies are needed to confirm the findings. Given the low vitamin D content in natural foods, it is necessary to fortify processed foods with vitamin D.

Fucoidan protects the pancreas and improves glucose metabolism through inhibiting inflammation and endoplasmic reticulum stress in T2DM rats.

It is important to maintain the normal function of the pancreas in the prevention and intervention of type 2 diabetes mellitus (T2DM). This study was undertaken to explore the protective effects of fucoidan on the pancreas in T2DM rats induced by using a high fat diet (HFD) and low dose of streptozotocin (STZ) injection. The results showed fucoidan remarkably decreased the levels of fasting blood glucose, serum insulin and glycated serum protein, and increased the level of glucagon-like peptide-1 in T2DM rats. Also, fucoidan improved insulin sensitivity and reduced the postprandial blood glucose level. Meanwhile, fucoidan alleviated pancreas damage and improved the islet ß cell function in T2DM rats. Additionally, fucoidan activated the PI3K/AKT signaling pathway and regulated glucose homeostasis, which seemed to be related to the protection of the pancreas from damage by inhibiting inflammation and endoplasmic reticulum stress in T2DM rats. Collectively, these results indicated that fucoidan had a potential protective effect on the pancreas, which enriched ideas for the use of fucoidan as a nutritional agent in the cure of T2DM.

Evaluation of Circulating Endothelial Progenitor Cells in Abdominal Aortic Aneurysms after Endovascular Aneurysm Repair.

Background and Objectives: Circulating endothelial progenitor cells (EPCs) participate in vascular repair and predict cardiovascular outcomes. The aim of this study was to investigate the correlation between EPCs and abdominal aortic aneurysms (AAAs). Methods and Results: Patients (age 67±9.41 years) suffering from AAAs (aortic diameters 58.09±11.24 mm) were prospectively enrolled in this study. All patients received endovascular aneurysm repair (EVAR). Blood samples were taken preoperatively and 14 days after surgery from patients with aortic aneurysms. Samples were also obtained from age-matched control subjects. Circulating EPCs were defined as those cells that were double positive for CD34 and CD309. Rat models of AAA formation were generated by the peri-adventitial elastase application of either saline solution (control; n=10), or porcine pancreatic elastase (PPE; n=14). The aortas were analyzed using an ultrasonic video system and immunohistochemistry. The levels of CD34＋/CD309＋ cells in the peripheral blood mononuclear cell populations were measured by flow cytometry. The baseline numbers of circulating EPCs (CD34＋/CD309＋) in the peripheral blood were significantly smaller in AAA patients compared with control subjects. The number of EPCs doubled by the 14th day after EVAR. A total of 78.57% of rats in the PPE group (11/14) formed AAAs (dilation ratio ＞150%). The numbers of EPCs from defined AAA rats were significantly decreased compared with the control group. Conclusions: EPC levels may be useful for monitoring abdominal aorta aneurysms and rise after EVAR in patients with aortic aneurysms, and might contribute to the rapid endothelialization of vessels.

Fucoidan ameliorates glucose metabolism by the improvement of intestinal barrier and inflammatory damage in type 2 diabetic rats.

It has been reported that fucoidan possesses anti-diabetic activities by inhibiting α-glucosidase activity, improving ß-cell dysfunction, and enhancing insulin sensitivity. However, as a macromolecular carbohydrate, fucoidan is rarely absorbed and indigestible in gastrointestinal tract. The study aimed to explore whether the fucoidan can regulate glucose metabolism by improving intestinal barrier and inflammation in type 2 diabetes mellitus (T2DM) rats. A high-fat diet combined with streptozotocin was used to induce T2DM rats. Different doses of fucoidan (50, 100 and 200 mg/kg) were administered respectively by lavage to T2DM rats for 8 weeks and saline was given to controls. The results showed that in addition to hyperglycemia and hyperlipidemia, T2DM rats were also characterized by increased intestinal permeability and proinflammatory cytokines. Notably, fucoidan reduced fasting blood glucose and insulin resistance index along with alleviated the accumulation of proinflammatory cytokines in T2DM rats. Furthermore, fucoidan repaired the intestinal barrier function, which was accompanied by the up-regulation of tight junction proteins and the improvement of intestinal inflammation via inhibiting TLR4/NF-κB signaling. Meanwhile, fucoidan also mitigated the liver damage, and alleviated insulin resistance by activating PI3K/AKT signaling. Collectively, these findings supported the potential of fucoidan to be used as a functional ingredient to prevent T2DM.

The Association Between GC Gene Polymorphisms and Metabolic Syndrome in Chinese Rural Population: A Case-Control Study.

BACKGROUND: GC (group-specific component globulin) encoding VDBP (Vitamin D binding protein) polymorphisms have been associated with susceptibility to some diseases such as diabetes, obesity, osteoporosis, and polycystic ovary syndrome, but the evidence for metabolic syndrome (MetS) in the Chinese rural population is inconclusive. Therefore, we investigated the relationship between GC variants (rs7041, rs4588, rs2282679, and rs705117) and MetS risk as well as VDBP levels in the Chinese rural population. PATIENTS AND METHODS: The participants (range of age: 20-90 years) of this case-control study were recruited from the northern Chinese Han rural population. We matched 445 MetS cases with non-MetS controls in a 1:1 ratio by sex, age (within 5 years). Real-time PCR technology was carried out by TaqMan assays to examine the four variants of rs7041, rs4588, rs2282679, and rs705117 within the GC gene. To identify the association of GC gene polymorphisms with MetS, we calculated ORs using a conditional logistic regression model adjusted for potential confounding factors. RESULTS: We observed inverse associations of CA and AA genotypes of rs4588 with risk of MetS (OR = 0.678, 95% CI 0.505-0.910, P = 0.010; 0.603, 95% CI 0.373-0.973, P = 0.039, respectively) compared with carriers of CC genotype. A similar relationship was also found between rs2282679 and MetS, showing that carrying AC genotype of rs2282679 can decrease the risk of MetS (OR = 0.683, 95% CI 0.509-0.917, P = 0.011) compared with carriers of AA genotype. The results of correlation analysis between MetS components and GC polymorphisms showed that the ORs of AA genotype of rs4588 with high level of TG (triglycerides) and low level of HDL-C (high-density lipoprotein cholesterol) were 0.473 (95% CI 0.245-0.911, P = 0.025) and 0.268 (95% CI 0.117-0.615, P = 0.002), respectively; the ORs of CC genotype of rs2282679 with high level of TG and low level of HDL-C were 0.428 (95% CI 0.217-0.842, P = 0.014) and 0.263 (95% CI 0.110-0.628, P = 0.003), respectively. However, there was no significant association between the concentration of VDBP and MetS risk. CONCLUSION: Among the Chinese rural population, GC polymorphism was associated with lower metabolic syndrome susceptibility, which might be through affecting blood lipid levels (TG and HDL-C).

Fibrin-based cardiac patch containing neuregulin-1 for heart repair after myocardial infarction.

Cardiac patch, a scaffold layered on the surface of the heart that can provide mechanical and regeneration support for damaged myocardium, has provided a promising solution to treat severe myocardial infarction (MI). In this work, a fibrin based cardiac patch loaded with neuregulin-1 (NRG-1) is developed to attach locally to the infract area of heart. The composite patch exhibited good biocompatibility and promoted cardiomyocyte proliferation in vitro via NRG-1/ErbB signaling. Moreover, implantation of this patch to the infracted border zone reduced cell apoptosis, promoted angiogenesis and inhibited fibrosis, which reduced infraction size and improved cardiac function consequently. Thus, the combination of natural biomaterial fibrin and bioactive factor NRG-1 might have a promising potential for clinical application of MI treatment.

Serum cystatin C is a potential predictor of short-term mortality and acute kidney injury in acute aortic dissection patients: a retrospective cohort study.

Background: Serum cystatin C concentration is associated with cardiovascular disease. However, the relationship between cystatin C and acute aortic dissection (AAD) remains unclear. In the current study, we aim to evaluate the predictive value of cystatin C in the occurrence of acute kidney injury (AKI) and the prognosis of AAD patients. Methods: The patients with AAD admitted to our hospital from November 2019 through January 2022 were consecutively included in the retrospective cohort study. A complete blood cell count, serum biochemistry tests, including cystatin C and creatinine, in-hospital mortality and the incidence of AKI were recorded. All the patients were categorized into four groups according to the quartile of their serum cystatin C levels. Multivariate logistic and Cox regression analyses were conducted to determine the independent risk factors for the incidence of AKI and the prognosis of AAD patients, respectively. Kaplan-Meier analyses and log-rank tests were used to evaluate differences in survival. Receiver operating characteristic (ROC) curves were used to assess the predictive value of cystatin C for short-term mortality and the incidence of AKI in AAD patients. Results: A total of 357 patients were included in this study. The results showed that the higher the concentration of cystatin C, the higher the level of serum creatinine and the higher the incidence of AKI. Mortality was significantly higher in the group with serum cystatin C levels >1.18 mg/L. Type A AAD, white blood cell count >10×109/L, platelet count <100×109/L, and serum cystatin C concentration >1.18 mg/L [adjusted hazards ratio (HR) =2.405, 95% confidence interval (CI), 1.029-4.063, P=0.041] were independent risk factors for in-hospital mortality. Cystatin C levels >1.18 mg/L remained an independent predictor of AKI in AAD after adjusting for the confounding [odds ratio (OR) 76.489, 95% CI, 25.586-228.660]. The areas under the ROC curves of cystatin C in predicting the mortality and incidence of AKI in AAD patients were 0.655 (95% CI, 0.551-0.760) and 0.807 (95% CI, 0.758-0.856), respectively. Conclusions: In sum, serum cystatin C concentration is a potential predictor of short-term mortality and the incidence of AKI in AAD patients.