Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice.

BACKGROUND: After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. METHODS: MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. RESULTS: Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-ß, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. CONCLUSION: Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.

MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway.

MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2 ) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p-eNOS and p-Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L-NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia-induced ECs injury partially through Akt/eNOS pathway.

Correction: A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

Correction for 'A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma' by Ping Tan et al., Chem. Commun., 2021, DOI: 10.1039/d0cc07336a.

A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

A one-step synthesized LD specific fluorescent probe TTIE with high specificity, good photostability and great capacity in generating cytotoxic reactive oxygen species (ROS) under low powered white light irradiation is designed and synthesized for LD specific image-guided photodynamic therapy (PDT) in human clear cell renal cell carcinoma (ccRCC) primary cells and tissues.

Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

OBJECTIVES: We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis. BACKGROUND: TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies. METHODS: Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon. RESULTS: A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days. CONCLUSIONS: Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

Transcatheter and Surgical Aortic Valve Replacement in Patients With Previous Cardiac Surgery: A Meta-Analysis.

Background: Many patients who have aortic stenosis and are transcatheter aortic valve replacement (TAVR) candidates have underwent prior cardiac surgery (PCS). The aim of this study was to provide a robust summary comparison between patients with PCS who underwent TAVR vs. surgical aortic valve replacement (SAVR). Methods: We conducted a systematic review and meta-analysis of all published articles on PubMed/Medline, Ovid, EMBASE, and Scopus from 2002 to 2019. Results: A total of 13 studies were finally included, yielding a total of 23,148 participants. There was no statistical difference with 30-day [OR: 1.02 (0.86-1.21)] or 1-year mortality [OR: 1.18 (0.86-1.61)] between the two groups. Subgroup analysis revealed that high-risk patients who underwent TAVR with the transapical approach were associated with increased risk of mortality [OR: 1.45 (1.00-2.11)]. However, those who underwent TAVR with endovascular approach had a comparable outcome with SAVR. Conclusions: Primary outcomes after endovascular TAVR were similar to those with SAVR and superior to transapical TAVR treatment group in patients with PCS.

The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

Diabetes mellitus is an independent prognostic factor for mid-term and long-term survival following transcatheter aortic valve implantation: a systematic review and meta-analysis.

Prior studies have proposed the unfavourable roles of diabetes mellitus (DM) in surgical populations. For patients who underwent transcatheter aortic valve implantation, the prognostic value of DM remains controversial. This review summarizes the effects of DM on short-term, mid-term and long-term prognosis in patients who undergo transcatheter aortic valve implantation. We searched the PubMed database to identify eligible articles. The odds ratio and hazard ratio with the corresponding 95% confidence interval were adopted for synthesizing short-term and medium- to long-term survival outcomes, respectively. The heterogeneity level and publication bias between studies were also estimated. Finally, 20 observational studies enrolling 19 260 patients met the eligibility criteria and, thus, were included in this review. An overall analysis identified that DM was significantly associated with the poor medium- to long-term overall survival (hazard ratio 1.21, 95% confidence interval 1.03-1.41; P = 0.019). However, no significant impact of DM on 30-day mortality was observed (odds ratio 1.10, 95% confidence interval 0.86-1.41; P = 0.46) in patients undergoing transcatheter aortic valve implantation. Further subgroup analyses indicated that the prognostic value of DM for medium- to long-term overall survival remained significant in the subgroups of multivariable origins of incorporated data, duration of follow-ups (1-year/≥2-year follow-up), Western populations and insulin-dependent diabetes mellitus. This meta-analysis demonstrates that DM is a strongly independent predictor for poor medium- to long-term overall survival but shows no significant effect of DM on 30-day mortality. Our findings need to be further verified and modified by more worldwide studies.

Acute Myocardial Infarction as the Initial Manifestation of Delayed Bioprosthesis Thrombosis After Transcatheter Aortic Valve Replacement.

Bioprosthesis thrombosis after transcatheter aortic valve replacement (TAVR) raised concerns about further clinical events. We report the case of a patient who suffered acute myocardial infarction (AMI) after TAVR for 3 years. Thrombosis was confirmed in the right coronary sinus of Valsalva by transthoracic echocardiography. Coronary angiography demonstrated the ostium of the right coronary artery was occluded. As an attempt to perform percutaneous coronary intervention (PCI) was unsuccessful, long-term therapeutic anticoagulation with warfarin was undertaken. Within 2 weeks, symptoms were relieved, and the right coronary ostium thrombus disappeared on computed tomography (CT) angiography. This case highlights the AMI as initial manifestation of delayed bioprosthesis thrombosis and the importance of anticoagulation against the bioprosthesis thrombosis. Meanwhile, the difficulty of PCI after TAVR is not only the stent frame of bioprosthesis, but also the location of the thrombosis.

The 'obesity paradox' does exist in patients undergoing transcatheter aortic valve implantation for aortic stenosis: a systematic review and meta-analysis.

Most recent studies have proposed the paradoxical benefits of obesity in surgical populations. For patients who underwent transcatheter aortic valve implantation (TAVI) for aortic stenosis, the prognostic roles of obesity and high body mass index remain controversial. Therefore, the objective of this meta-analysis was to evaluate whether the 'obesity paradox' exists in patients undergoing TAVI. We searched in PubMed and EMBASE to identify the eligible articles. Odds ratios and hazard ratios with the corresponding 95% confidence intervals (CI) were adopted for synthesizing short-term and long-term survival outcomes, respectively. The level of heterogeneity and the publication bias between studies were also estimated. Finally, there were 16 studies with 12 330 patients who met the eligibility criteria and who were thus included in this review. When body mass index was analysed as a continuous variable, each increase of 1 kg/m2 was significantly associated with the lower 30-day mortality rate (odds ratio = 0.95; 95% CI = 0.93-0.97; P < 0.001) and better long-term overall survival (hazard ratio = 0.96; 95% CI = 0.94-0.97; P < 0.001) for patients undergoing TAVI. The obese patients had a significantly lower risk of 30-day mortality after TAVI than did normal patients (odds ratio = 0.69; 95% CI = 0.50-0.95; P = 0.024). Further analyses indicated that the obesity could be predictive of more favourable long-term overall survival of TAVI (hazard ratio = 0.84; 95% CI = 0.72-0.97; P = 0.021). However, we found no difference in procedural complications between the obese and normal patients. In conclusion, higher body mass index and obesity seem to have protective benefits on both short-term and long-term survival of TAVI patients. Current evidence suggests that the 'obesity paradox' may really exist in TAVI.

The influence of body composition on renal function in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.

OBJECTIVE: We try to analyse the effect of renal functions on death in CAD patients with different body compositions. METHODS: A retrospective analysis was conducted in 2989 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into two categories: basically preserved renal function (PRF) (eGFR ≥60 ml/min) and obviously reduced renal function (RRF) (eGFR <60 ml/min). The influence of renal insufficiency on mortality of CAD was detected in every tertile of body composition, including body mass index (BMI), body fat (BF) and lean mass index (LMI). The end points were all-cause mortality. RESULTS: The mean follow-up time was 29.1 ± 12.5 months and death events occurred in 271 cases. The percentage of patients with RRF was positively correlated with BF and inversely correlated with the LMI, but no relationship to BMI. The survival curves showed that the risk of death was significantly higher in the RRF patients in all subgroups stratified using BMI, BF, or LMI (log rank test, all p < 0.001). The COX multivariate regression analysis showed that the risk of death was significantly higher in the RRF patients with high BF (HR 1.95, CI 1.25-3.05) and low LMI (HR 1.82, CI 1.19-2.79). Meanwhile, risk of death was significantly higher in RRF patients with a high BMI (HR 2.08, CI 1.22-3.55) or low BMI (HR 1.98, CI 1.28-3.08) but this risk was not significant in patients with a medium BMI (HR 1.12, 0.65-1.94). The subgroup analysis of patients with acute coronary syndrome (ACS) showed similar results. CONCLUSIONS: For patients with CAD, renal insufficiency was positively correlated with BF, inversely correlated with LMI, and unrelated to BMI. The effect of renal insufficiency on the risk of death of CAD was related to body composition.

Statin use and mortality of patients with prostate cancer: a meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to investigate the effect of statin use on the mortality of patients with prostate cancer (PCa). METHODS: An electronic search of PubMed, Embase, and CENTRAL databases from inception to August 2015 was performed to find eligible studies. Articles investigating the association between statin use and mortality of PCa were identified. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. RESULTS: In total, 13 studies that enrolled 100,536 participants were included in this meta-analysis. Results showed that prediagnostic statin use had a significantly lower risk of both all-cause mortality (ACM; HR, 0.56; 95% CI, 0.38-0.83) and PCa-specific mortality (PCSM; HR, 0.53; 95% CI, 0.36-0.77). Similarly, postdiagnostic statin use was correlated with reductions in both ACM (HR, 0.77; 95% CI, 0.69-0.87) and PCSM (HR, 0.64; 95% CI, 0.52-0.79). When stratified by primary treatment, postdiagnostic use of statins had a 0.4-fold lower risk of ACM in patients with PCa who were treated with local therapy; both pre- and postdiagnostic use of statins was correlated with a significantly lower risk of PCSM in patients who were treated with androgen deprivation therapy. CONCLUSION: Both pre- and postdiagnostic use of statins is associated with better overall survival and PCa-specific survival. This suggests a need for randomized controlled trials of statins in patients with PCa.

Meta-Analysis of the Effectiveness and Safety of Transcatheter Aortic Valve Implantation Without Balloon Predilation.

Evidence regarding the safety and feasibility of transcatheter aortic valve implantation without balloon predilation (BP) is scarce. A literature search of PubMed, EMBASE, CENTRAL, and major conference proceedings was performed from January 2002 to July 2015. There were 18 studies incorporating 2,443 patients included in the present study. No differences were observed in the baseline characteristics between patients without BP (no-BP) and with BP. Compared with BP, no-BP had a shorter procedure time (no-BP vs BP, 124.2 vs 138.8 minutes, p = 0.008), used less-contrast medium (no-BP vs BP, 126.3 vs 156.3 ml, p = 0.0005) and had a higher success rate (odds ratio [OR] 2.24, 95% CI 1.40 to -3.58). In addition, no-BP was associated with lower incidences of permanent pacemaker implantation (OR 0.45, 95% CI 0.3 to 0.67), grade 2 or greater paravalvular leakage (OR 0.55, 95% CI 0.37 to 0.83), and stroke (OR 0.57, 95% CI 0.32 to 1.0). Furthermore, no-BP was associated with a 0.6-fold decreased risk for 30-day all-cause mortality (OR 0.60, 95% CI 0.39 to 0.92). However, the difference in the risk for permanent pacemaker implantation, grade 2, or higher aortic regurgitation, stroke was noted to be significant only in the subgroup of the CoreValve-dominating studies. In conclusion, no-BP before transcatheter aortic valve implantation was not only safe and feasible but was also associated with fewer complications and short-term mortality in selected patients especially using self-expandable valve.

Perineural invasion is an independent predictor of biochemical recurrence of prostate cancer after local treatment: a meta-analysis.

Controversy still existed regarding the role of perineural invasion (PNI) in prostate cancer. The present meta-analysis aimed to investigate the association between PNI and biochemical recurrence (BCR) of prostate cancer after local treatment. A systematic search of Medline, Embase and CENTRAL was performed for eligible studies. Pooled estimates of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were acquired by using the generic inverse variance method. Subgroup analyses were performed by the method treating prostate cancer including radical prostatectomy (RP) and radiotherapy (RT) as well as the specimens which were acquired from RP and biopsy. A total of 12 studies incorporating 5188 patients were included in the meta-analysis. Overall, PNI was significantly associated with BCR (HR 1.59, 95% CI 1.37-1.84). Similarly, a significant correlation between PNI and BCR was also found in RP series (HR 1.51, 95% CI 1.25-1.83) and RT series (HR 1.70, 95% CI 1.35-2.13). PNI predicted BCR of prostate cancer in both RP (HR 1.51, 95% CI 1.23-1.85) and biopsy specimens (HR 1.68, 95% CI 1.36-2.09). PNI was demonstrated to be associated with higher risk for BCR of prostate cancer after local treatment. Therefore, PNI should be considered when assessing the risk of BCR in prostate cancer, thereby to achieve the best treatment.

Target lesion calcification and risk of adverse outcomes in patients with drug-eluting stents. A meta-analysis.

BACKGROUND: Studies focusing on the relationship between calcified lesions and adverse outcomes in the drug-eluting stent (DES) era have presented inconsistent conclusions. The aim of this study was to assess the association between target lesion calcification and adverse outcomes in patients undergoing DES implantation. METHODS: A systematic search was conducted on Medline (Ovid SP, 1946 to 28 February 2014), Embase (Ovid SP, 1974 to 28 February 2014), and the Chinese Biomedical Literature Database (CBM, 1978 to 28 February 2014). Abstracts from the 2012 and 2013 scientific meetings of the American College of Cardiology and American Heart Association were manually searched. Hazard ratios (HRs) were pooled using a fixed or random effects model in the context of heterogeneity. RESULTS: A total of 13 studies comprising 66,361 patients were included. Target lesion calcification was associated with an increased risk of all-cause mortality (HR = 1.41; 95 % CI = 1.27-1.56), cardiac death (HR = 1.97; 95 % CI = 1.68-2.31), myocardial infarction (HR = 1.33; 95 % CI = 1.13-1.57), target lesion revascularization (TLR; HR 1.47, 95 % CI 1.18-1.83), stent thrombosis (HR 1.63, 95 % CI 1.36-1.96), and major cardiovascular events (HR 1.37, 95 % CI 1.19-1.58). The results proved robust in subgroup analyses for TLR and stent thrombosis. CONCLUSION: Calcified target lesions are risk factors for adverse outcomes in the DES era. Further studies focusing on comprehensive therapy in patients with coronary calcification are urgently needed.

Docetaxel, cisplatin and fluorouracil (DCF) regimen compared with non-taxane-containing palliative chemotherapy for gastric carcinoma: a systematic review and meta-analysis.

BACKGROUND: Gastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC. METHODS: PubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities. RESULTS: Twelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p<0.0001) and minor raises of leucopenia (RR = 1.25, p<0.00001), neutropenia (RR = 1.19, p<0.00001), and diarrhea (RR = 1.59, p<0.00001), while in other toxicities there were no significant differences. CONCLUSION: DCF regimen has better response than non-taxane containing regimen and could potentially improve the survival outcomes. The chemotherapy-related toxicity of DCF regimen is acceptable to some extent.

Sensing of corrosion on aluminum surfaces by use of metallic optical fiber.

We present a new method for monitoring aluminum corrosion by determining the kind of light output that is as corrosion occurs. We prepared some metallized multimode optical fibers by physical vacuum deposition of aluminum to monitor metal corrosion. The sensing area was 1-2 cm in length and had an uncladded part. We used scanning-electron microscopy (SEM) to observe the microappearance of the aluminum before and after corrosion by sodium hydroxide or hydrochloric acid. The film's thickness was also measured by SEM. The factors that affect the rate of corrosion were also investigated.

Intensity-based optical fiber sensor for monitoring corrosion of aluminum alloys.

A new method, based on the shift of light power transmitted through fiber, to measure corrosion of aluminum is presented. A multimode fiber was metallized by use of physical vacuum to deposit aluminum onto an unclad part of a fiber of 1 to 2 cm length. Scanning-electron microscopy and x-ray diffraction were used to show, the formation and corrosion of the metallized film. The light signal driven by metal corrosion was affected by the film's thickness and the concentration of the corrosive solution of sodium hydroxide.