All-In-One Second Near-Infrared Light-Responsive Drug Delivery System for Synergistic Chemo-Photothermal Therapy.

Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 µg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.

The usefulness of age and sex to predict all-cause mortality in patients with dilated cardiomyopathy: a single-center cohort study.

OBJECTIVE: Recent studies have shown that sex and age are associated with outcomes in patients with cardiomyopathy. The purpose of this study was to determine the all-cause mortality of dilated cardiomyopathy (DCM) by age and sex. METHODS AND RESULTS: The patients were divided into non-elderly (age <60 years, n=811) and elderly (age ≥60 years, n=331) groups. No difference in the all-cause mortality rate was observed between elderly and non-elderly patients (27.2% vs 22.2%, log-rank χ(2)=2.604, P=0.107). Furthermore, no significant difference in mortality was observed between the male and female patients (23.3% vs 24.5%, log-rank χ(2)=0.707, P=0.400). However, subgroup analysis revealed that elderly male patients exhibited a higher mortality rate than non-elderly male patients (29.4% vs 21.3%, log-rank χ(2)=5.898, P=0.015), while no difference was observed between the elderly female patients and non-elderly female patients. In the Cox analysis, neither age nor sex was a significant independent predictor of all-cause mortality in patients with DCM. CONCLUSION: In conclusion, no significant difference in mortality between male and female patients or between the elderly and non-elderly patients was observed. Only among males was a difference in mortality observed; elderly male patients experienced greater mortality than that of non-elderly male patients. No effect of age or sex on all-cause mortality was observed in patients with DCM.

MicroRNA-423-5p targets O-GlcNAc transferase to induce apoptosis in cardiomyocytes.

Congestive heart failure (CHF) remains the single most prevalent cause of mortality and morbidity; therefore, the identification of novel biomarkers is required for the diagnosis of CHF. The aim of the present study was to examine whether microRNA (miR)-423-5p is a novel biomarker for CHF, which was defined by the circulatory biomarker pro-brain natriuretic peptide (BNP). Samples of plasma from patients with CHF and healthy controls were collected and used for quantitative polymerase chain reaction analysis. In addition, the O-GlcNAc transferase (OGT) 3' untranslated region was cloned and used for a luciferase assay. The effects of the expression of miR-423-5p in cardiomyocytes were determined using western blotting and terminal deoxynucleotidyl transferase-deoxyuridine triphosphate nick-end labeling analyses. The results demonstrated that miR-423-5p was associated with CHF and the expression levels of proBNP; in addition, OGT was found to be a direct target of miR-423-5p. The expression of miR-423-5p significantly regulated the expression of OGT and its associated downstream targets and induced apoptosis in the cardiomyocytes. Therefore, the results of the present study indicated that miR-423-5p was involved in CHF via the direct targeting of OGT and the induction of apoptosis in cardiomyocytes.

The prognostic use of serum concentrations of cardiac troponin-I, CK-MB and myoglobin in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To examine the association between survival and serum concentrations of cTnI, CK-MB, and myoglobin in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND: It has been suggested that elevated circulating biomarkers of myocardial damage such as cardiac troponin-I (cTnI), creatine kinase MB (CK-MB) and myoglobin are independent risk factors for mortality in patients with heart failure, and recent studies, although limited, showed that there was a potential association between cTnI and the prognosis of patients with dilated cardiomyopathy (DCM). METHODS: A cohort study was undertaken in 310 patients with IDC. Standard demographic information, transthoracic echocardiography, and routine blood tests were obtained shortly after hospital admission. Outcome was assessed with all-cause mortality. RESULTS: Among the 310 patients studied, 61 (19.7%) died during a mean follow-up of 2.2 years. There was a significant difference in the all-cause mortality rate between patients with serum cTnI >0.05 ng/mL and with cTnI ≤ 0.05 ng/mL (37.5% vs 15%, log-rank χ(2) = 18.423, P < 0.001). After adjustment for other factors associated with prognosis at baseline, serum cTnI >0.05 ng/mL, QRS duration, NYHA functional class and systolic blood pressure predicted all-cause mortality in patients with IDC. There was no association between circulating CK-MB and myoglobin levels and all-cause mortality in the studied IDC patients. CONCLUSION: Serum concentrations of cTnI but not CK-MB or myoglobin are an independent predictor of all-cause mortality in patients with IDC.

The efficacy and safety of ivabradine hydrochloride versus atenolol in Chinese patients with chronic stable angina pectoris.

PURPOSE: The aim of this study was to assess the efficacy and safety of ivabradine (Iva) noninferiority to atenolol (Aten) in Chinese patients with chronic stable angina pectoris. METHODS: In this double-blind, double-dummy trial, patients with symptomatic angina pectoris and positive exercise tolerance test were randomized into the Iva [5 or 7.5 mg bis in die (BID)] or Aten group (12.5 or 25 mg BID) according to computer-generated random numbers for 12 weeks. RESULTS: One hundred and sixty-eight patients were randomized to the Iva group and 166 to the Aten group. In a full analysis set, increases in the total exercise duration (TED) were 54.3 ± 120.1 seconds with Iva 5 mg and 58.8 ± 114.7 seconds with Aten 12.5 mg at the fourth week, and at the 12th week, TED improved by 84.1 ± 130.5 seconds with Iva and 77.8 ± 126.6 seconds with Aten (95%CI: -21.4-34.1 seconds, p = 0.0011 for noninferiority). The analysis of per protocol set yielded similar results (95%CI: -31.4-33.0 seconds, p = 0.0131 for noninferiority). Heart rate was reduced in both groups at rest and during peak exercise. There were small, nonsignificant differences in the number of adverse events between the two groups (66 in Iva and 73 in Aten, p > 0.05). Nine patients (5.42%) were reported to develop phosphenes/luminous phenomena and blurred vision in the Iva group (p = 0.0035). CONCLUSIONS: Iva is effective in reducing heart rates and improving exercise capacity and noninferior to Aten in Chinese patients with chronic stable angina pectoris. Iva is well tolerated and safe.

[Design and accuracy analysis of upper slicing system of MSCT].

The upper slicing system is the main components of the optical system in MSCT. This paper focuses on the design of upper slicing system and its accuracy analysis to improve the accuracy of imaging. The error of slice thickness and ray center by bearings, screw and control system were analyzed and tested. In fact, the accumulated error measured is less than 1 microm, absolute error measured is less than 10 microm. Improving the accuracy of the upper slicing system contributes to the appropriate treatment methods and success rate of treatment.

Using sheathless standard guiding catheters for transradial percutaneous coronary intervention to treat bifurcation lesions.

OBJECTIVE: To investigate the feasibility and safety of using sheathless standard guiding catheters for transradial percutaneous coronary intervention (PCI) to treat bifurcation lesions. METHODS: Coronary bifurcation lesions were identified using angiography in 43 patients with coronary artery disease. These patients underwent transradial PCI using sheathless standard guiding catheters, and the procedural success and complication rates were recorded. RESULTS: All 43 patients underwent successful PCI. The Culotte stenting technique was used in 22 (51.2%) subjects, the Crush stenting technique was used in eight (18.8%) subjects and the crossover stenting implantation technique was used in 13 (30.0%) subjects. Of the 43 coronary artery bifurcation lesions, the final kissing balloon technique was performed in 39 (90.1%) lesions. Adjunctive devices used in the cohort included intravascular ultrasound for 32 (74.4%) patients, thrombus aspiration catheters for two patients and cutting balloon for five patients. During the perioperative period, no major complications associated with vessel puncture or adverse cardiac or cerebrovascular events occurred in any of the 43 patients enrolled in the present study. At day 30, radial artery occlusion was detected in only three (2.5%) patients and radial artery stenosis in four (9.3%) patients. At six-month follow-up, 24 (55.8%) patients exhibited coronary artery patency with no significant intimal hyperplasia. CONCLUSIONS: Transradial PCI using the sheathless technique may be a feasible and safe technique to treat coronary bifurcation lesions.

Polymorphism of ZBTB17 gene is associated with idiopathic dilated cardiomyopathy: a case control study in a Han Chinese population.

BACKGROUND: Dilated cardiomyopathy (DCM) has been extensively investigated for many years, but its pathogenesis remains uncertain. The ACTC1 gene was the first sarcomeric gene whose mutation was shown to cause DCM; recent studies have indicated that the HSPB7 and ZBTB17 genes are also associated with DCM. To assess the potential role of these three genes in DCM, we examined 11 single nucleotide polymorphisms (SNPs) in the ZBTB17, HSPB7 and ACTC1 genes: namely, rs10927875 in ZBTB17; rs1739843, rs7523558, and rs6660685 in HSPB7; rs533021, rs589759, rs1370154, rs2070664, rs3759834, rs525720 and rs670957 in ACTC1. METHODS: A total of 97 DCM patients and 189 controls were included in the study. All SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: The genotype of SNP rs10927875 in ZBTB17 (OR=5.19, 95% CI =1.00 to 27.03, P=0.05) was associated with DCM in a Han Chinese population. There was no difference in genotype or allele frequencies in ACTC1 or HSPB7 between DCM patients and control subjects. CONCLUSION: The ZBTB17 polymorphism rs10927875 appears to play a role in the susceptibility of the Han Chinese population to DCM.

The role of the Hsp90/Akt pathway in myocardial calpain-induced caspase-3 activation and apoptosis during sepsis.

BACKGROUND: Recent studies have demonstrated that myocardial calpain triggers caspase-3 activation and myocardial apoptosis in models of sepsis, whereas the inhibition of calpain activity down-regulates myocardial caspase-3 activation and apoptosis. However, the mechanism underlying this pathological process is unclear. Therefore, in this study, our aim was to explore whether the Hsp90/Akt signaling pathway plays a role in the induction of myocardial calpain activity, caspase-3 activation and apoptosis in the septic mice. METHODS: Adult male C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Next, myocardial caspase-3 activity and the levels of Hsp90/p-Akt (phospho-Akt) proteins were detected, and apoptotic cells were assessed by performing the TUNEL assay. RESULTS: In the septic mice, there was an increase in myocardial calpain and caspase-3 activity in addition to an increase in the number of apoptotic cells; however, there was a time-dependent decrease in myocardial Hsp90/p-Akt protein levels. The administration of calpain inhibitors (calpain inhibitor-Ш or PD150606) prevented the LPS-induced degradation of myocardial Hsp90/p-Akt protein and its expression in cardiomyocytes in addition to inhibiting myocardial caspase-3 activation and apoptosis. The inhibition of Hsp90 by pretreatment with 17-AAG induced p-Akt degradation, and the inhibition of Akt activity by pretreatment with wortmannin resulted in caspase-3 activation in wildtype C57 murine heart tissues. CONCLUSIONS: Myocardial calpain induces myocardial caspase-3 activation and apoptosis in septic mice via the activation of the Hsp90/Akt pathway.

[Role of C-type natriuretic peptide receptor and large-conductance calcium-activated potassium channels in brain natriuretic peptide-induced porcine coronary artery dilation].

OBJECTIVE: To investigate the role of C-type natriuretic peptide receptor (NPR-C) and large-conductance calcium-activated potassium channels (BK(Ca)) in brain natriuretic peptide (BNP) induced porcine coronary artery dilation. METHODS: Porcine coronary artery rings were obtained and treated with BNP (10(-6) mol/L), BNP + NPR-C antagonist cANF4-28 (10(-6) mol/L) and BNP + BK(Ca) blocker tetraethylammonium (TEA, 1 mmol/L). The vascular tone experiments were observed on 10 vessel segments. BK(Ca) current density was measured by the whole-cell patch clamp technique. RESULTS: The maximum diastolic rate was similar between BNP group (68.51% ± 11.50%) and cANF4-28 + BNP group (65.67% ± 11.90%, P > 0.05) while significantly reduced in TEA + BNP group (28.87% ± 4.55%, all P < 0.05). When the holding potential was set at +60 mV, the BK(Ca) current density of BNP group was (78.48 ± 5.86) pA/pF, which was significantly higher than control group [(53.84 ± 4.55) pA/pF, P < 0.05], which was equally reduced in the TEA group and TEA + BNP group [(28.80 ± 2.76) pA/pF and (30.60 ± 3.88) pA/pF respectively, all P < 0.05 vs. control group]. CONCLUSION: BNP could relax the porcine coronary arterial smooth muscles by increasing BK(Ca) current, and this effect is not mediated by NPR-C.

Human leukocyte antigen-DQ beta 1 chain (DQB1) gene polymorphisms are associated with dilated cardiomyopathy: a systematic review and meta-analysis.

BACKGROUND: Previous studies reported an association between the human leukocyte antigen (HLA)-DQ antigen beta 1 chain (DQB1) alleles and dilated cardiomyopathy (DCM). However, the results of those studies have been inconsistent. To clarify the association between HLA-DQB1 and DCM, we performed a systematic review and meta-analysis of case-control studies. METHODS: Searches were performed using the PubMed database, the Excerpta Medica Database (EMBASE), the Cochrane Central Register of Controlled Trials database, the Science Citation Index database, the China Biology Medicine disc, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search terms included "dilated cardiomyopathy" and "DQB1." Ten case-controlled studies were included in the systematic review to assess the association between DCM and the HLA-DQB1*0201, *0302, *0504, *0301, and *0602 alleles. RESULTS: In total, 8 studies were included in the meta-analysis of the HLA-DQB1 *0201 allele. The pooled odds risk (OR) for this allele was .47, with a 95% confidence interval (CI) of .28 to .77 (P < .01). With respect to the HLA-DQB1 *0504 allele, only 3 studies were included in our meta-analysis. The pooled OR was .36 (95% CI, .15 to .84; P < .05). Nine, 8, and 7 studies of the HLA-DQB1 *0301, *0302, and *0602 alleles, respectively, were included in our meta-analysis. No statistically significant difference was evident in the frequency of these 3 alleles between the DCM and normal control groups. CONCLUSION: The HLA-DQB1 *0201 and *0504 alleles may be protective against DCM.

[Sodium channel changes in human atrial cells isolated from various ages].

OBJECTIVE: To investigate if the increased incidence of atrial fibrillation with age was associated with changes of Na(+) channel in atrial myocytes. METHODS: Twenty-three patients underwent valve replacement operations were divided into adult [< 60 years, n = 15, 9 males, mean age (42.1 +/- 7.1) years] and aged group [> or = 60 years, n = 8, 5 males, mean age (63.3 +/- 3.1) years]. All patients were in normal sinus rhythm. Whole cell patch clamp techniques were used to record the Na(+) currents (I(Na)) of right auricle myocytes. RESULTS: Both current density and time-dependent recovery of I(Na) were similar in the cells from the 2 groups. Voltage-dependent inactivation of I(Na) of myocytes in the aged atria was shifted to more positive voltages. CONCLUSION: Current density of I(Na) was similar between the 2 age groups, and Na(+) channel might not be an important determinant for the increased incidence of atrial fibrillation in aged patients.

[Vasodilatory effects of CNP on aortic arteries of rabbits].

OBJECTIVE: To investigate the mechanism of vasodilatory effects of C-type natriuretic peptide (CNP). METHODS: Tension changes in aortic rings of rabbits were recorded with the presence of CNP or C-type natriuretic peptide receptor (NPR-C) agonist (cANF4-23) after pretreatment with epinephrine (NE) or 60 mmol/L KCl. The vasodilatory effects of four types of potassium channel blocker and NPR-C antagonist (cANF4-28) were also tested. RESULTS: A maximal vasorelaxant effects of (33.5 +/- 5.9) % and (38.4 +/- 10.6)% were recorded in the presence of 1 micromol/L CNP and cANF4-23, respectively, cANF4-28 attenuated the action of CNP [(19.8 +/- 8.3)%]. The vasorelaxant effects of CNP and cANF4-23 decreased significantly after pretreatment with 60 mmol/L KCl (P < 0.01). Glibenclamide and BaCl2 also attenuated the relaxant activities of CNP (P < 0.05). But only BaClZ decreased the vasodilatory action of cANF4-23 (P < 0.05). CONCLUSION: The relaxant activity of CNP is mediated through three paths: NPR-B/KATP, NPR-C/KIR and NPR-C/calcium channels.

[Efficacy of selective continuous transarterial infusion chemotherapy on advanced pancreatic cancer].

BACKGROUND & OBJECTIVE: Advanced pancreatic cancer is mainly treated by chemotherapy with poor prognosis. This study was designed to evaluate clinical efficacy and application of selective continuous transarterial infusion chemotherapy in treating patients with advanced pancreatic cancer. METHODS: Twenty patients with advanced pancreatic cancer were treated by selective continuous transarterial infusion chemotherapy. The interventional treatment was performed with Seldinger technique,12 patients received percutaneous femoral artery cannulization and catheter retention, 8 received percutaneous left subclavian artery port-catheter system implantation. Chemotheraputic drugs were continuously infused when the catheter was selectively placed in turner feeding artery. Nine patients were treated with pirarubicin (THP)/adriamycin (ADM) plus hydroxycamptothecin (HCPT),and 5-fluorouracil (5-FU)/calcium folinate (CF) regimen,and 11 were treated with gemcitabine (GEM) plus carboplatin (CBP),and 5-FU/CF regimen. Treatment regimens were repeated every 4-6 weeks with each cycle of 4 days. Tumor response rate,clinical benefit response (CBR),and survival time were observed. RESULTS: Objective response rate was 10% with 1 case of complete remission (CR), and 1 case of partial remission (PR), CBR was 70% (14/20), 6-,and 9-month survival rates were 58.8%,and 39.2%. Median survival time for all patients was 8.8 months. No complication related to cannulization was found. CONCLUSION: Selective continuous transarterial infusion chemotherapy is safe,and has good efficacy in treating patients with advanced pancreatic cancer, it may prolong survival time of patients.