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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.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.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 levels1.18 mg/L. Type A AAD, white blood cell count10×10In sum, serum cystatin C concentration is a potential predictor of short-term mortality and the incidence of AKI in AAD patients.

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.

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 β 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.

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.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.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 (TG) were more likely to have T2D compared with AA carriers (OR=2.00, 95% CI: 1.19-3.37). Variants of rs4588 (CA) and rs2282679 (AC) 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).Our study indicates a potential role for GC gene polymorphisms in T2D susceptibility and vitamin D metabolite concentrations in the Chinese rural population.

In this paper, we investigate the impact of directors’ and officers’ insurance (D&O insurance) on firm innovation in China. We find that D&O insurance is significantly positively associated with firm innovation, which indicates that D&O insurance enhances managers’ tolerance for failure. To address endogeneity concerns, we adopt the propensity score matching method and difference-in-differences approach. We find that firms with D&O insurance have a stronger risk bearing capacity. Further analyses show that the impact of D&O insurance on firm innovation is more pronounced in firms with a better legal environment, male executives, and stronger external supervision.

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.

BACKGROUND: Thoracic aortic aneurysm/dissection (TAA/D) are complicated vascular disorders with rapid development and high mortality. Vascular smooth muscle cells (VSMCs) phenotype switching plays an important role in the pathological process of TAA/D. Previous studies have indicated a potential correlation between long non-coding RNA (lncRNA) RP11-465L10.10 and matrix metallopeptidase 9 (MMP9) involved in the development of TAA/D. This study aims to investigate the role of lncRNA RP11-465L10.10 in VSMCs phenotype switching and the molecular mechanism in regulating MMP9 expression. METHODS: The expression of RP11-465L10.10 in vascular tissues and in VMSCs was detected by RT-qPCR. To investigate the role of RP11-465L10.10 on VSMCs phenotype switching, an RP11-465L10.10-overexpressed lentiviral vector was constructed and transfected into VSMCs. Through EdU staining, migration assay, flow cytometry analysis, the roles of RP11-465L10.10 were estimated. Bioinformatics indicated that RP11-465L10.10 upregulating MMP9 expression via NF-κB signaling, and SN50 (a specific inhibitor of NF-κB pathway) was used to inhibit the NF-κB pathway activation, then the expression of MMP9 was detected in RP11-465L10.10 overexpressed VMSCs. RESULTS: In this study, we found RP11-465L10.10 and MMP9 were highly increased in TAD patient tissues, which was consistent in angiotensin II-induced VSMCs phenotype switching. RP11-465L10.10 overexpression facilitated VSMCs phenotype switching and MMP9 expression. Mechanismly, NF-κB signal pathway was involved in RP11-465L10.10 induced VSMCs phenotype switching and MMP9 expression by transcriptome data analysis and experimental confirm. CONCLUSION: This study demonstrated that RP11-465L10.10 induces VSMCs phenotype switching and MMP9 expression via the NF-κB signal pathway, suggesting that RP11-465L10.10 might be a potential therapeutic target for TAA/D treatment.

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.

It has been reported that fucoidan possesses anti-diabetic activities by inhibiting α-glucosidase activity, improving β-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.

Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to investigate whether miR-134-5p affects human VSMC functions and development of TAD. Using miRNA microarray of aorta specimens from 12 TAD and 12 controls, we identified miR-134-5p, which was significantly downregulated in TAD tissues. With qPCR detection, we found that miR-134-5p was also evidently decreased in human AoSMCs. Ectopic expression of miR-134-5p obviously promoted VSMC differentiation and expression of contractile markers, such as α-SMA, SM22α, and MYH11. miR-134-5p potently inhibited PDGF-BB-induced VSMC phenotypic switch and migration. We further identified STAT5B and ITGB1 as downstream targets of miR-134-5p in human VSMCs and proved them to be mediators in VSMC phenotypic switch and progression of TAD. Finally, Ad-miR-134-5p obviously suppressed the aorta dilatation and vascular media degeneration by 39% in TAD mice after vascular injury induced by Ang II. Our findings revealed that miR-134-5p was a novel regulator in vascular remodeling and pathological progress of TAD via targeting STAT5B/ITGB1 expression. Targeting miR-134-5p or its downstream molecules in VSMCs might develop new avenues in clinical treatment of TAD. Keywords: miR-134-5p, media degeneration, VSMC, phenotypic switch, thoracic aortic dissection

Background and aims Several studies have reported that variants in CYP2R1 have been linked with an increased risk of hypertension. However, the interaction between CYP2R1 variants and environmental factors on the susceptibility of hypertension remained unclear. Therefore, this study evaluated the influence of CYP2R1 polymorphisms on hypertension susceptibility, and explored the interaction effect of CYP2R1 variations and obesity on the disease. Methods and results We included 766 incident hypertension cases matched with non-hypertension controls in a 1:1 ratio by sex, age (within 3 years). Two loci in CYP2R1 gene (rs10766197, rs12794714) were genotyped by TaqMan probe assays. The concentration of 25(OH)D was determined by human enzyme-linked immunosorbent assay (ELISA) kits. The associations of CYP2R1 polymorphisms and risks of vitamin D deficiency (VDD) were analyzed by logistic regression. Multifactor dimensionality reduction (MDR) was used to analyze the gene-environment interaction. Multiple logistic regression was used to examine the effect of CYP2R1 gene variations, and the interaction between CYP2R1 variation and obesity on hypertension susceptibility. The results showed that rs10766197 (GG vs. AA) and rs12794714 (GG vs. AA) polymorphisms were both associated with an increased risk of VDD (OR=1.49 95%CI 1.08-2.05 and OR=1.63 95%CI 1.19-2.25, respectively), after adjustment for potential risk factors. Meanwhile, we found that rs12794714 polymorphism was significantly associated with elevated risk of hypertension under the dominant model (OR=1.26, 95% CI 1.01-1.56). In addition, the interactions between rs12794714 with both general obesity (OR=3.93, 95%CI 2.72-5.68) and central obesity (OR=3.22, 95%CI 2.29-4.52) have significant effects on hypertension susceptibility. Conclusions The study provided further evidence that CYP2R1 variation was associated with a higher risk of hypertension in Chinese rural population. The interaction between CYP2R1 rs12794714 and obesity may increase the risk of hypertension.

OBJECTIVE: To determine whether exogenously reduced psychological distress reduces reported low‐back pain (LBP) and is associated with reduced medical visits for LBP. DATA SOURCES: National Health Interview Survey, National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey, 1998‐2004. STUDY DESIGN: We estimate a fuzzy regression discontinuity model in which a discontinuity in the prevalence of psychological distress is identified by exogenous national events. We examine whether this discontinuity induced a corresponding discontinuity in the prevalence of LBP. We additionally estimate a regression discontinuity model to determine associated changes in medical visits with LBP as the primary complaint. PRINCIPAL FINDINGS: The prevalence of LBP was discontinuously reduced by one‐fifth due to the exogenous national discontinuous reduction in psychological distress. This discontinuity in LBP cannot be explained by discontinuities in employment, insurance, injuries/poisoning, general health status, or other factors. We find an associated three‐fifth discontinuous reduction in medical visits with LBP as the primary complaint. CONCLUSIONS: On a monthly basis, 2.1 million (P

Background: Diabetic peripheral neuropathy (DPN) is a common complication in patients (pts) with diabetes. However, multinational data do not support any convincing efficacy of the current therapies for treating DPN. This necessitated the evaluation of safety and efficacy of alternative medicine to tackle DPN. Methods: A double-blinded RCT was conducted in 8 Chinese medicine hospitals in China, evaluating the safety and efficacy of 190 g Tangbi Waixi decoction (TW, intervention (Int)) compared with 19 g TW (control (Cont)). Change in Toronto Clinical Scoring System - Total Score (TCSS-TS) at 12 and 24 weeks follow-up was the primary outcome, with treatment ceasing at 12 weeks. Secondary outcomes included change in bilateral motor velocity (BMV) and sensory nerve conduction velocity (SNCV) of the common peroneal nerve (CPN). All pts received standard care for glycaemic management. The pts in the Int (n=317) and Cont (n=315) groups were analysed on ITT principle. All adverse events (AEs) were recorded. Results: The pts were mean 60 years old with median 10 yrs and 2 yrs of diabetes and DPN duration respectively at randomisation. With median TCSS-TS of 10 at randomisation in both groups, the median (95% CI) reduction in Int and Cont: at 12 weeks 2 (1.7, 2.3) and 3 (2.7, 3.3) respectively (median between group difference (MBGD): 1.0, p=0.011); at 24 weeks 3 (2.6, 3.4) in both groups. At 12 weeks, median (95% CI) CPN velocity increased in both Int and Cont - BMV Int vs. Cont: 2.7 (1.9, 4.9) m/s vs. 4.9 (2.7, 5.5) m/s, MBGD - 2.5 m/s (p=0.044); SNCV Int vs. Cont: 1.4 (0, 2) m/s vs. 2.7 (1.9, 4.9) m/s, MBGD - 0.7 m/s (p=0.26). Similar increase in CPN velocity was observed at 24 weeks in both groups. Overall 12% pts experienced at least one AE, with no difference between groups. Conclusion: Treatment of DPN with TW decoction significantly benefitted the pts and is safe, while lower dose of TW appears to be more effective than the higher does. Disclosure F. Guanjie: None. Y. Lin: None. S.K. Paul: Advisory Panel; Self; Sanofi. Research Support; Self; AstraZeneca, Genentech, Inc. H. Huang: None. T. Xianyu: None. Z. Yuehong: None. F. Zhaohui: None. Q. Xiaotang: None. D. Fang: None. S. Wang: None. M. Wang: None. H. Wei: None. Z. Ling: None. L. Zhenjie: None. Y. Fu: None. M. Wu: None. L. Anxiang: None. H. Jinzhu: None. Q. Li: None. Funding National Science and Technology Support Program (2015BAI04B09)

Thoracic aortic aneurysm and dissection (TAAD) is the most fatal macro vascular disease. The mortality of 48h after diagnosis of dissection is up to approximately 50-68%. However, the genetic factors and potential mechanism underlying sporadic TAAD remain largely unknown. Our previous study suggested rs12455792 variant of SMAD4 gene significantly contributed to the increased risk and might participated the pathological progression of TAAD. This investigation aims to test (1) the associations between rs12455792 and MØ recruitment, inflammatory response in aggressiveness of TAAD, and (2) the molecular mechanism accounting for their effects. In TGF-β signaling molecular detection, rs12455792 C>T variant activated the canonical and non-canonical TGF-β mediators. It also increased the secretion of chemotactic factors of HASMCs. To confirm the impact of this change, we detected MØ recruitment and infiltration in HASMCs and aortic tissues of TAAD patients. We found that MØ recruitment in cells and tissues with rs12455792 variant genotypes was increased than that in wild type groups. Moreover, rs12455792 variant increased M1 type inflammatory response, which might contribute much to TAAD progression. To mimic the SMAD4 suppression effect of rs12455792 in vivo, we constructed the SMAD4 KD mouse. After induction with Ang II for 4w, the thoracic aorta dilatation and vascular remodeling were more serious than that of wild type group. In conclusion, rs12455792 increased MØ recruitment, M1 type inflammatory response via activated TGF-β signaling, and further promoted vascular remodeling and pathological progress of TAAD.

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) have been proved to be capable of differentiating into endothelial cells (ECs), however, the differentiation efficiency is rather low. Sonic hedgehog (Shh), an important factor in vascular development and postnatal angiogenesis, exerted promotional effect on new vessel formation in the ischemic animal models. Therefore, the current study aims to investigate whether Shh could induce the endothelial differentiation of BMSCs both in vitro and in vivo , as well as the mechanism of differentiation induction. Methods: The current study over-expressed Shh in BMSCs by lentivirus transduction. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the angiogenic factors in both control BMSCs and Shh over-expressed BMSCs. Immunocytochemistry was also conducted to examine the EC markers. Angiogenesis was determined by in vitro tube-forming assay on Matrigel and in vivo Matrigel plug in severe combined immunodeficient (SCID) mice. Last, mRNA sequencing analysis was used to elaborate the underlying mechanisms. Loss of function study was performed by vascular endothelial growth factor D (VEGF-D) siRNA. Results: Shh expression was increased by about 3,000-fold and 5,000-fold at 3 days-transfection and 7 days-transfection, respectively. Patched 1 (Ptch1), the receptor for Shh, had a two-fold increase after transduction. The angiogenic factors such as hepatocyte growth factor (HGF), angiopoietin-1 (Ang-1), insulin-like growth factor 1 (IGF1) and vascular endothelial growth factor A (VEGF-A) had at least a 1.5-fold increase after transduction. Expression of EC-lineage markers, CD31 and VE-cadherin, on Shh-overexpressed BMSCs were increasingly detected by immunocytostaining. Angiogenesis of BMSCs could be efficiently induced by Shh overexpression in the in vitro tube-formation assay and in vivo Matrigel plug. Additionally, mRNA sequencing analysis revealed that Shh activation upregulated the expression of several pro-angiogenic factors, like Angptl4, Egfl6, VEGF-D. Loss of function study by VEGF-D siRNA confirmed that Shh enhanced the angiogenic ability of BMSCs via VEGF-D. Conclusions: This study demonstrated that Shh could promote endothelial differentiation of BMSCs via VEGF-D.

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.

Over the past years, vascular diseases have continued to threaten human health and increase financial burdens worldwide. Transplantation of allogeneic and autologous blood vessels is the most convenient treatment. However, it could not be applied generally due to the scarcity of donors and the patient’s condition. Developments in tissue engineering are contributing greatly with regard to this urgent need for blood vessels. Tissue engineering-derived blood vessels are promising alternatives for patients with aortic dissection/aneurysm. The aim of this review is to show the importance of advances in biomaterials development for the treatment of vascular disease. We also provide a comprehensive overview of the current status of tissue reconstruction from stem cells and transplantable cellular scaffold constructs, focusing on the combination of stem cells and tissue engineering for blood vessel regeneration and vascular disease treatment.

Wound healing is a multistep phenomenon that relies on complex interactions between various cell types. Calpains are a well-known family of calcium-dependent cysteine proteases that regulate several processes, including cellular adhesion, proliferation, and migration, as well as inflammation and angiogenesis. CAPNS1, the common regulatory subunit of Calpain-1 and 2, is indispensable for catalytic subunit stabilization and activity. Calpain inhibition has been shown to reduce organ damage in various disease models. Here, we report that endothelial calpain-1/2 is crucially involved in skin wound healing. Using a mouse genetic model where Capns1 is deleted only in endothelial cells, we showed that calpain-1/2 disruption is associated with reduced injury-activated inflammation, reduced CD31+ blood vessel density, and delayed wound healing. Moreover, in cultured HUVECs, inhibition of calpain reduced TNF-α-induced proliferation, migration, and tube formation. Deletion of Capns1 was associated with elevated levels of IκB and downregulation of β-catenin expression in endothelial cells. These observations delineate a novel mechanistic role for calpain in the crosstalk between inflammation and angiogenesis during skin repair.

Vascular disorders are complex diseases with high morbidity and mortality. Among them, the dilated macrovascular diseases (MVD), such as aortic aneurysm and aortic dissection, have presented a huge threat to human health. The pathogenesis of vascular diseases is mostly associated with property alteration of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). Studies have confirmed that induced pluripotent stem cells (iPSCs) can be proliferated and differentiated into other somatic cells, such as VECs and VSMCs. And patient-specific cells could provide detailed human-associated information in regard to pathogenesis or drug responses. In addition, differentiated ECs from iPSC have been widely used in disease modeling as a cell therapy. In this review, we mainly discussed the application of hiPSCs in investigating the pathological mechanism of different inherited vascular diseases and provide a comprehensive understanding of hiPSCs in the field of clinical diagnosis and gene therapy.

Apolipoprotein M (apoM) is a recently identified human apolipoprotein that is associated with the formation of high-density lipoprotein (HDL). Studies have demonstrated that statins may affect the expression of apoM; however, the regulatory effects of statins on apoM are controversial. Furthermore, the underlying mechanisms by which statins regulate apoM remain unclear. In the present study, in vivo and in vitro models were used to investigate whether the anti-atherosclerotic effects of statins are associated with its apoM-regulating effects and the underlying mechanism. Hyperlipidemia was induced by in apolipoprotein E-deficient mice by providing a high-fat diet. Atorvastatin was administered to hyperlipidemic mice and HepG2 cells to investigate its effect on apoM expression. The liver X receptor α (LXRα) agonist T0901317 was also administered together with atorvastatin to hyperlipidemic mice and HepG2 cells. The results revealed that atorvastatin increased apoM expression, which was accompanied with decreased expression of LXRα in the liver of hyperlipidemic apolipoprotein E-deficient mice and HepG2 cells. Additionally, apoM upregulation was inhibited following treatment with T0901317. In summary, atorvastatin exhibited anti-atherosclerotic effects by upregulating apoM expression in hyperlipidemic mice, which may be mediated by the inhibition of LXRα.

Background As a common complication of diabetes, the incidence of diabetic peripheral neuropathy (DPN) is 60–70% worldwide. DPN is a major risk factor for diabetic foot, which may lead to foot ulceration and even amputation. The treatment of DPN remains challenging. Our preliminary study demonstrated that the external application of Tangbi Waixi (TW) decoction to the lower extremities relieved clinical symptoms and improved nerve conduction velocity in DPN patients. The aim of this study was to verify the efficacy of TW among DPN patients and evaluate the herb mixture’s safety using rigorous methodological designs. Methods/design This study is a multicenter, double-blind, randomized controlled trial. A total of 640 DPN patients will be recruited and randomized to receive a foot bath with either the TW decoction or control drug. Participants will be assessed at baseline and 12 and 24 weeks after treatment. The primary outcome was the change of the Toronto Clinical Scoring System (TCSS). Secondary outcomes were nerve conduction velocity, blood glucose, blood lipids, serum inflammatory cytokines, and the European Quality of Life Five-Dimension Scale (EQ-5D) and TCM symptom scores. Discussion This multicenter, prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of foot bath treatment with TW decoction. Positive results would provide a novel treatment regimen for DPN patients. Trial registration Chinese Clinical Trial Registry, ChiCTR-IOR-16009331. Registered on 8 October 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2856-4) contains supplementary material, which is available to authorized users.

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 CD45RBBone 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 CD4DCs co-cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RBBMSCs 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.

Objective. The study aim to investigate the role of microRNA-155 (miR-155) on the immunoregulatory function of bone marrow mesenchymal stem cells (MSCs). Methods. MSCs were isolated from 2-week-old Sprague-Dawley rats and identified by flow cytometry using anti-CD29, anti-CD44, anti-CD34, and anti-CD45 antibodies. MSCs were transfected with miR155-mimics, miR155-inhibitor, and control oligos, respectively, and then cocultured with spleen mononuclear cells (SMCs). The mRNA levels of Th1, Th2, Th17, and Treg cell-specific transcription factors (Tbx21, Gata3, Rorc, and Foxp3, resp.) and the miR-155 target gene SOCS1 were detected by quantitative real-time PCR (qPCR) in SMCs. The proportion of CD4+ FOXP3+ Treg cells was detected by flow cytometry. In addition, the effects of MSCs transfected with miR-155 on the migration of rat SMCs were investigated by transwell chamber. Results. CD29 and CD44 were expressed in MSCs, while CD34 and CD45 were negative. The percentage of CD4+ FOXP3+ Treg cells in the SMC population was significantly higher compared with that noted in SMCs control group (p<0.001) following 72 hours of coculture with miR155-mimics-transfected SMCs. In contrast, the percentage of CD4+ FOXP3+ Treg cells in the SMCs cocultured with miR155-inhibitor-transfected MSCs was significantly lower compared with that noted in SMCs control group (p<0.001). MiR155-mimics-transfected MSCs inhibited the expression of Tbx21, Rorc, and SOCS1, while the expression of Gata3 and Foxp3 was increased. In contrast to the downregulation of the aforementioned genes, miR155-inhibitor-transfected MSCs resulted in upregulation of Tbx21, Rorc, and SOCS1 expression levels and inhibition of Gata3 and Foxp3. In the transwell assay, miR155-mimics-transfected MSCs exhibited lower levels of SMCs migration, while the miR155-inhibitor-transfected MSCs demonstrated significantly higher levels of migration, compared with the blank control group (p<0.01, resp.). Conclusion. miR-155 favors the differentiation of T cells into Th2 and Treg cells in MSCs, while it inhibits the differentiation to Th1 and Th17 cells.

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Background. To cure ischemic diseases, angiogenesis needs to be improved by various strategies in ischemic area. Considering that microRNA-132 (miR-132) regulates endothelial cell behavior during angiogenesis and the safe and efficacious delivery of microRNAs in vivo is rarely achieved, an ideal vehicle for miR-132 delivery could bring the promise for ischemic diseases. As a natural carrier of biological molecules, exosomes are more and more developed as an ideal vehicle for miRNA transfer. Meanwhile, mesenchymal stem cells could release large amounts of exosomes. Thus, this study aimed to investigate whether MSC-derived exosomes can be used for miR-132 delivery in the treatment of myocardial ischemia. Methods. MSC-derived exosomes were electroporated with miR-132 mimics and inhibitors. After electroporation, miR-132 exosomes were labelled with DiI and added to HUVECs. Internalization of DiI-labelled exosomes was examined by fluorescent microscopy. Expression levels of miR-132 in exosomes and HUVECs were quantified by real-time PCR. The mRNA levels of miR-132 target gene RASA1 in HUVECs were quantified by real-time PCR. Luciferase reporter assay was performed to examine the targeting relationship between miR-132 and RASA1. The effects of miR-132 exosomes on the angiogenic ability of endothelial cells were evaluated by tube formation assay. Matrigel plug assay and myocardial infarction model were used to determine whether miR-132 exosomes can promote angiogenesis in vivo. Results. miR-132 mimics were effectively electroporated and highly detected in MSC-derived exosomes. The expression level of miR-132 was high in HUVECs preincubated with miR-132 mimic-electroporated exosomes and low in HUVECs preincubated with miR-132 inhibitor-electroporated exosomes. The expression level of RASA1, miR-132 target gene, was reversely correlated with miR-132 expression in HUVECs pretreated with exosomes. Luciferase reporter assay further confirmed that RASA1 was a direct target of miR-132. Exosomes loaded with miR-132, as a vehicle for miRNA transfer, significantly increased tube formation of endothelial cells. Moreover, subcutaneous injection of HUVECs pretreated with miR-132 exosomes in nude mice significantly increased their angiogenesis capacity in vivo. In addition, transplantation of miR-132 exosomes in the ischemic hearts of mice markedly enhanced the neovascularization in the peri-infarct zone and preserved heart functions. Conclusions. The findings suggest that the export of miR-132 via MSC-derived exosomes represents a novel strategy to enhance angiogenesis in ischemic diseases.

To determine the risk factors associated with adverse aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with Stanford type B aortic dissection, we performed a retrospective analysis of 54 patients between January 2009 and June 2012 at the First Affiliated Hospital of Soochow University. All patients underwent TEVAR of the descending thoracic aorta. Multiple-logistic regression analyses were performed to identify risk factors associated with aortic remodeling. True-lumen and false-lumen volumes were increased (P < 0.001) and decreased (P < 0.001) after surgery, respectively. Therefore, the remodeling index increased after surgery (1.04 ± 0.6 to 2.06 ± 1.12, P < 0.001). Remodeling index and true-lumen volume were higher in the favorable aortic remodeling group compared to the adverse aortic remodeling group (P < 0.001), while the false-lumen volume was lower in the favorable aortic remodeling group (P < 0.001). Multivariate analyses revealed a branch originating from the false lumen (OR = 39.9, P < 0.01) and multiple tears (OR = 27.4, P < 0.01) to be independent risk factors for adverse aortic remodeling. Therefore, a branch originating from the false lumen and multiple tears were determined to be independent risk factors for adverse aortic remodeling after TEVAR in patients with Stanford type B aortic dissection.

Recent studies indicate important roles for SMAD4 in SMCs proliferation, extracellular matrix maintenance, and blood vessel remodeling. However, the genetic effects of SMAD4 in the pathogenesis of thoracic aortic aneurysm and dissection (TAAD) are still largely unknown. Here we identified a functional variant of SMAD4 which might be involved in the pathological progression of TAAD. Five tagging SNPs of SMAD4 were genotyped in 202 TAAD cases and 400 controls using MALDI-TOF. rs12455792 CT or TT variant genotypes was associated with an significantly elevated TAAD risk (adjusted OR = 1.58, 95%CI = 1.09–2.30) under a dominant genetic model. It was located in the 5’UTR and predicted to influence transcription activity and RNA folding of SMAD4. In luciferase reporter assay, rs12455792 T allele markedly decreased luciferase activities. Accordingly, SMAD4 expression in tissues was lower in patients with CT or TT genotypes, compared with CC. Movat's pentachrome showed that rs12455792 T allele enhanced SMCs loss and fibers accumulation. With angiotensin II induction, rate of Apoptotic SMCs was significantly higher while SMAD4 silenced. Moreover, rs12455792 T allele also increased Versican degradation via ADAMTS-4. In conclusion, this variant might promote SMCs apoptosis and proteoglycans degradation, and further facilitate the progress of TAAD. Our findings identified rs12455792 as a predictor for progression of vascular media pathological changes related thoracic aortic disorders., Highlights • The variant on 5'UTR of SMAD4 gene significantly increased thoracic aortic aneurysm and dissection risk. • The variant rs12455792 reduced SMAD4 expression and influenced its effects on proteoglycans degradation, SMCs apoptosis and fiber accumulation. • rs1rs12455792 might be a potential therapeutic marker in vascular media pathological changes related thoracic aortic disorders. Understanding the genetic features of thoracic aortic aneurysm and dissection can lead to precision surgery strategy. In this study, we demonstrated that SMAD4 rs12455792 is located in the transcription factor binding site and the allele change influences transcription activity and SMAD4 expression. Decrease of SMAD4 expression promotes proteoglycans degradation, vascular SMCs apoptosis and fiber accumulation, which are involved in pathological progression of TAAD. rs12455792 might be a potential therapeutic marker in vascular media pathological changes related thoracic aortic disorders.

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 (IT) and intravenous (IV) 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 IT or IV or combined IT and IV (IT/IV) 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 IT/IV 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 IT/IV injection of MSCs. Moreover, IT/IV 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, IT/IV 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 IT/IV 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.

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.

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.

Background Metastasis-associated gene 1(MTA1) has been identified as an oncogene in many tumors, and aberrant MTA1 expression has been linked to carcinogenesis and metastasis. We aim to investigate the mechanism of MTA1 and metastasis in malignant pleural mesothelioma (MPM). Methods Real-time polymerase chain reaction (PCR) and immunohistochemical staining were employed to detect MTA1 and E-cadherin expression in MPM tissues and corresponding adjacent tissues. Stable clone with knock-down of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Wound-healing assay, transwell assay and PCR array were carried out for detecting invasion and migration of MPM cells. Luciferase reporter assay was performed to validate the effect of MTA1 on E-cadherin. Results MTA1 expression is up-regulated in MPM and shown a negative correlation with E-cadherin expression. MTA1 could enhance the invasion and migration of MPM cells via suppressing the expression of E-cadherin. MTA1 overexpression is associated with pathology, metastasis and survival rate of MPM patients. Conclusions MTA1 plays an important role in Epithelial-to-mesenchymal transition (EMT) to promote metastasis via suppressing E-cadherin expression, resulting in a poor prognosis in MPM. MTA1 is a novel biomarker and indicative of a poor prognosis in MPM patients. Electronic supplementary material The online version of this article (doi:10.1186/s13046-015-0269-8) contains supplementary material, which is available to authorized users.

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.

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.

Objective: Complete documentation is provided outlining a process for surgical treatment of the ascending aorta using open triple-branched aortic arch stent grafts to treat acute Stanford type A aortic dissection based on clinical observations. Methods: A total of 34 patients underwent replacement of the ascending aorta or aortic root in combination with open placement of a triple-branched stent graft. Results: Mean cardiopulmonary bypass, mean myocardial ischemic, and selective cerebral perfusion times were 186 ± 38, 101 ± 27, and 39 ± 11 minutes, respectively. Two deaths occurred during hospitalization. Of the remaining patients, postoperative computed tomography angiography confirmed that all implanted stent grafts were fully opened; however, the dissected aorta and false lumen size showed evidence of reduced thickness. Conclusions: This applies mainly to those who need extensive surgical reconstruction of the thoracic aorta with acute Stanford type A aortic dissection, and it can reduce cardiopulmonary bypass complexities of the traditional surgeries and potential complication.

This study was designed to investigate the effect of the overexpression of heme oxygenase-1 (HO-1) on the immunoregulation in the model of abdominal cardiac xenotransplantation from the guinea pig to the rat.To increase the expression of HO-1, both donors and recipients were injected with heme through the abdomen before the operation. The donors (guniea pigs) and the recipients (Sprague-Dawley [SD] rats) were divided randomly into three groups: group A, the heart from a guinea pig transplanted into the abdomen of an SD rat; group B, the recipients were injected with Chinese cobra venom factor (CVF) into the abdomen (40 μg/kg and 60 μg/kg 24 hours later) prior to transplantation; group C, CVF + HO-1 high-expression group: donors and recipients were abdominally injected with heme (75 μmol/kg for 2 days before transplantation). The mean survival time (MST), pathological changes, the positive area of HO-1 in the grafted hearts, as well as the expressions of C-C chemokine receptor 5 (CCR5), intercellular adhesion molecule-1 (ICAM-1), and natural killer (NK) cell activity in recipients.1. The MST was longest in group C treated with heme. 2. The pathologic changes of hyperacute rejection were showed on the donor heart in group A, while delayed xenograft rejection changes took place on donor heart in other groups. 3. Compared with group B, The HO-1 positive area in the donor hearts of group C was significantly higher. (P.05). 4. The lever of ICAM-1 and CCR5 in the peripheral blood of recipients (pg/mL) was attenuated in group C injected with heme. 5. Compared with group B, the activity of NK cell in the peripheral blood of recipients was much lower in group C (P.05).The MST was prolonged by increasing expressions of HO-1, but acute vascular rejection was not completely overcome. Activation of vascular endothelial cells could be decreased by strengthening the expression of HO-1. NK cell activity was weakened by reinforced expression of HO-1.

Background Tricuspid regurgitation (TR) is common in patients with mitral valve disease; however, there are no straightforward, rapidly determinably criteria available for deciding whether TR repair should be performed during mitral valve replacement. The aim of our retrospective study was to identify a simple and fast criterion for determining whether TR repair should be performed in patients undergoing mitral valve replacement. Methods We reviewed the records of patients who underwent mitral valve replacement with or without (control) TR repair (DeVega or Kay procedure) from January 2005 to December 2008. Preoperative and 2-year postoperative echocardiographic measurements included right ventricular and atrial diameter, interventricular septum size, TR severity, ejection fraction, and pulmonary artery pressure. Results A total of 89 patients were included (control, n = 50; DeVega, n = 27; Kay, n = 12). Demographic and clinical characteristics were similar between groups. Cardiac variables were similar between the DeVega and Kay groups. Right atrium and ventricular diameter and ejection fraction were significantly decreased postoperatively both in the control and operation (DeVega + Kay) group (P < 0.05). Pulmonary artery pressure was significantly decreased postoperatively in-operation groups (P < 0.05). Our findings indicate that surgical intervention for TR should be considered during mitral valve replacement if any of the following preoperative criteria are met: right atrial transverse diameter > 57 mm; right ventricular end-diastolic diameter > 55 mm; pulmonary artery pressure > 58 mmHg. Conclusions Our findings suggest echocardiography may be used as a rapid and simple means of determining which patients require TR repair during mitral valve replacement.