[Coronary artery bypass grafting surgery in left ventricular dysfunction patients complicated with mitral regurgitation].

Objective: To evaluate the efficacy of coronary artery bypass grafting (CABG) surgery in left ventricular dysfunction patients complicated with different degrees of ischemic mitral regurgitation (IMR). Methods: The clinical data of 525 patients (428 males and 97 females) undergoing CABG in Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen, and Tianjin Medical University General Hospital between January 2015 and December 2018 were collected. The average age was (61±7) years old. Among them, the patients with moderate to serve IMR and left ventricular ejection fraction(LVEF)≤40% were further selected, and the outcomes of CABG were analyzed. Results: In total, 67 patients (48 males and 19 females) with moderate to severe IMR and LVEF≤40% were enrolled, among which 52 patients had moderate IMR, with a LVEF of 38%(35%, 40%). Transesophageal echocardiography (TEE) of 52 cases displayed no damage of papillary muscles, and ventricular wall motion was improved after CABG. Therefore, no treatment on the mitral valve was performed in this group. Six patients were with moderate-severe mitral insufficiency, with a LVEF of 38%(35%, 39%). After surgery, TEE found that the ventricular wall motion and regurgitation were improved, and the mitral valve structures were well. Thus, mitral valves were not treated in these patients. Nine patients were with severe mitral regurgitation, with a LVEF of 38%(35%, 39%). Two of them received valve repair because the papillary muscle function and the ring were well. Another 7 patients received valve replacements because the valve ring was dilatated and the leaflet was prolapsed. All patients recovered well. The LVEF increased significantly at 6 months after surgery [47%(45%, 48%) vs 38%(35%, 39%), P=0.024], and the left ventricular end diastolic diameter also became smaller [57(56, 59) mm vs 61(59, 64) mm, P=0.002]. Conclusions: For patients suffered from left ventricular dysfunction complicated with IMR, TEE is crucial to evaluate the valve function. To those with moderate-severe regurgitation, if papillary muscle function and the ring were seriously affected by ischemia, the valve replacement could facilitate the improvement of postoperative cardiac function.

Enhanced MC3T3-E1 preosteoblast response and bone formation on the addition of nano-needle and nano-porous features to microtopographical titanium surfaces.

Micro/nanotopographical modifications on titanium surfaces constitute a new process to increase osteoblast response to enhance bone formation. In this study, we utilized alkali heat treatment at high (SB-AH1) and low temperatures (SB-AH2) to nano-modify sandblasted titanium with microtopographical surfaces. Then, we evaluated the surface properties, biocompatibility and osteogenic capability of SB-AH1 and SB-AH2 in vitro and in vivo, and compared these with conventional sandblast-acid etching (SLA) and Ti control surfaces. SB-AH1 and SB-AH2 surfaces exhibited micro/nanotopographical modifications of nano-needle structures and nano-porous network layers, respectively, compared with the sole microtopographical surface of macro and micro pits on the SLA surface and the relatively smooth surface on the Ti control. SB-AH1 and SB-AH2 showed different roughness and elemental components, but similar wettability. MC3T3-E1 preosteoblasts anchored closely on the nanostructures of SB-AH1 and SB-AH2 surfaces, and these two surfaces more significantly enhanced cell proliferation and alkaline phosphatase (ALP) activity than others, while the SB-AH2 surface exhibited better cell proliferation and higher ALP activity than SB-AH1. All four groups of titanium domes with self-tapping screws were implanted in rabbit calvarial bone models, and these indicated that SB-AH1 and SB-AH2 surfaces achieved better peri-implant bone formation and implant stability, while the SB-AH2 surface achieved the best percentage of bone-implant contact (BIC%). Our study demonstrated that the micro/nanotopographical surface generated by sandblasting and alkali heat treatment significantly enhanced preosteoblast proliferation, ALP activity and bone formation in vitro and in vivo, and nano-porous network topography may further induce better preosteoblast proliferation, ALP activity and BIC%.

Investigation of the pharmacokinetic interaction between ritonavir and CMDCK, a new non-nucleoside reverse transcriptase inhibitor.

The aim of this study was to investigate the pharmacokinetic interaction between ritonavir (RTV) and an anti-HIV agent 3-cyanomethyl-4-methyl-DCK (CMDCK). CMDCK was administered orally (8 mg/kg) and intravenously (2 mg/kg) to rats in the absence or presence of RTV (1 or 2.5 mg/kg). By comparing the pharmacokinetic parameters between the control and the RTV treated groups, it was found that co-administration with RTV could significantly increase the plasma exposure of CMDCK, through improving the hepatic and intestinal availabilities. The AUCinf of CMDCK was increased by 2.4 or 8.7 times for intravenous or oral route, respectively. The oral bioavailability of CMDCK was increased from 15% of the control group to 45% of the RTV concomitant group (2.5 mg/kg). In the in vitro studies with liver and intestinal microsomes, the K i values of RTV on the CMDCK metabolism were determined and found to be 0.22 and 0.48 µM for human, 0.33 and 1.60 µM for rat, respectively. Caco-2 cells study showed that CMDCK is not a P-glycoprotein (P-gp) substrate and its transepithelial transport is mainly through passive diffusion. The in vitro and in vivo results indicate that RTV could improve the bioavailability of CMDCK by inhibiting CYP3A mediated metabolism in both liver and intestine.