Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment.

Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxia-inducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis. In this manuscript, effective gene delivery vector PEI-ß-CD (PC) was reported for the first application in the hindlimb ischemia treatment to deliver HIF-1α plasmid in vitro and in vivo. Our in vitro finding demonstrated that PC/HIF-1α-pDNA could be successfully entered into the cells and mediated efficient gene transfection with good biocompatibility. More importantly, under hypoxic conditions, PC/HIF-1α-pDNA could up-regulate the HUEVC cell viability. In addition, the mRNA levels of VEGF, Ang-1, and PDGF were upregulated, and transcriptome results also demonstrated that the cell-related function of response to hypoxia was enhanced. The therapeutic effect of PC/HIF-1α-pDNA was further estimated in a murine acute hindlimb ischemia model, which demonstrated that intramuscular injection of PC/HIF-1α-pDNA resulted in significantly increased blood perfusion and alleviation in tissue damage, such as tissue fibrosis and inflammation. The results provide a rationale that HIF-1α-mediated gene therapy might be a practical strategy for the treatment of limb ischemia.

Polydopamine-Modified Zeolite Imidazole Framework Drug Delivery System for Photothermal Chemotherapy of Hepatocellular Carcinoma.

Metal-organic frameworks (MOFs) are promising drug-delivering platforms for their intrinsic capability of loading and releasing different cargoes. To further extend their biomedical practices, the development of collaborative MOF systems with good biocompatibility and synergistic efficacy is essential. Herein, the near-infrared and pH dual-response collaborative zeolitic imidazolate framework-8 (ZIF-8) platform SOR@ZIF-8@PDA (SZP) was constructed, in which the chemotherapeutic drug sorafenib (SOR) was encapsulated in ZIF-8 and via polydopamine (PDA) coating on ZIF-8 by hierarchical self-assembly. PDA coating serves as a photothermal agent for PPT while reducing the toxicity of ZIF-8. SZP achieves intelligent release of therapeutic drugs by responding to the lower pH of the tumor microenvironment and thermal stimulation generated by near-infrared light irradiation. In addition, under light irradiation, SZP could effectively realize treatment of cancer cells through synergistic chemo-photothermal therapy, as evidenced by the enhanced cell apoptosis, inhibited tumor cell proliferation and migration. This collaborative MOFs system showed excellent biocompatibility and antitumor ability in vivo on a mouse HepG2 tumor model. Our results demonstrated that PDA-modified MOFs exhibited a fantastic good development prospect in biomedical applications.

Clinical Evaluation of on-Table Extubation in Patients Aged Over 60 Years Undergoing Minimally Invasive Mitral or Aortic Valve Replacement Surgery.

Aims: To evaluate the clinical efficiency of on-table extubation (OTE) versus delayed extubation in patients aged over 60 years that underwent minimally invasive mitral or aortic valve replacement surgery and evaluate the factors associated with successful OTE implementation. Materials: Patients over 60 years with mitral or aortic valve disease who received minimally invasive mitral or aortic valve replacement surgery from October 2020 to October 2021 were selected retrospectively. We divided patients into the on-table extubated (OTE) group (n = 71) and the delayed extubation (DE) group (n = 22). Preoperative, intraoperative, and postoperative clinical variables were compared between the two groups. Results: Patients in the DE group underwent longer surgery time, longer aortic occlusion clamping time and longer cardiopulmonary bypass time than those in the OTE group(217.48 ± 27.83 vs 275.91 ± 77.22, p = 0.002; 76.49 ± 16.00 vs 126.55 ± 54.85, p = 0.001; 112.87 ± 18.91 vs 160.77 ± 52.17, p = 0.001). Patients in the OTE group had shorter postoperative mechanical ventilation time (min), shorter ICU time, shorter postoperative hospital length of stay and lower total cost and medication cost (p < 0.05). The AUC for aortic occlusion clamping time was 0.81 (p < 0.01), making it the most significant predictor of on-table extubation success. Conclusions: On-table extubation following mitral or aortic valve cardiac surgery was associated with a superior clinical outcome and high cost-effectiveness.

Higher Mean Arterial Pressure during Cardiopulmonary Bypass May Not Prevent Acute Kidney Injury in Elderly Patients Undergoing Cardiac Surgery.

We aimed to evaluate the role of higher mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) in preventing development of acute kidney injury (AKI). Methods. We evaluated a population of elderly individuals >60 years of age undergoing CPB to find correlation of MAP during CPB with development of AKI after the surgery. Patients who experienced sustained low MAP during the CPB defined as that of <65 mmHg were compared with those that had sustained high MAP of >65 mmHg for their outcome with regard to AKI. The KDIGO criteria were used to define presence of acute kidney injury. Results. Of the total 92 patients, 50 were in the low-pressure group and 42 were in the high-pressure group. The MAP was 61.14 ± 5.54 mmHg in the low-pressure group and 68.97 ± 3.65 mmHg in the high-pressure group (p < 0.001). 13 (26%) in the low-pressure group and 17 (40.48%) in the high-pressure group developed AKI (p = 0.140). Male sex was associated with an increased incidence of cardiac surgery-associated AKI (p = 0.034). Conclusions. A higher MAP in the range of 65-75 mmHg during the cardiopulmonary bypass does not significantly prevent acute kidney injury in elderly patients undergoing cardiac valve surgery.

Effects of intraoperative PEEP on postoperative pulmonary complications in high-risk patients undergoing laparoscopic abdominal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative pulmonary complications (PPCs), strongly associated with higher mortality risk, can develop in up to 58% of patients undergoing abdominal surgery. More and more evidence shows that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery, however, the role of positive end-expiratory pressure (PEEP) during the intraoperative period in preventing PPCs for laparoscopic surgery is not clearly defined. METHODS AND ANALYSIS: A total of 208 patients with a high risk of PPC, undergoing laparoscopic abdominal surgery, will be enrolled and randomised into a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive a fraction of inspired oxygen of 0.50 and a tidal volume of 8 mL/kg ideal body weight (IBW). Standard perioperative fluid management and analgesic treatments are applied in both groups. The primary end point is PPC within 7 days after surgery. Secondary end points are the modified Clinical Pulmonary Infection Score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, 30-day mortality. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medicine College) (registration number KY2018026) on 22 October 2018. The first participant was recruited on 15 April 2019 and the estimated completion date of the study is October 2021. The results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR1800019865. Registered on 2 December 2018; preresults.

Levobupivacaine inhibits lipopolysaccharide-induced high mobility group box 1 release in vitro and in vivo.

BACKGROUND: The aim of the study was to investigate whether levobupivacaine (LB) suppressed lipopolysaccharide (LPS)-induced high mobility group box 1 (HMGB1) release in vitro and in vivo, and to determin its molecular mechanisms of action. MATERIALS AND METHODS: RAW264.7 cells were treated with LPS and LB for 24 h. Levels of HMGB1, nuclear factor-kappa B (NF-κB) and phosphorylated p38 mitogen-activated protein kinase (MAPK) were measured by Enzyme-linked immunosorbent assay and Western blotting; the levels of HMGB1 messenger RNA were measured by real-time polymerase chain reaction. In addition, cecal ligation and puncture-induced septic C57BL/6 received LB infusion, and the levels of HMGB1 and functional parameters of multiple organs determined using several detection kits. RESULTS: LB inhibited HMGB1 release in vitro and in vivo. Furthermore, LB inhibited the translocation of NF-κB and phosphorylation of p38 MAPK in vitro. Mice treated with LB infusion improved survival in mice and significantly reduced cecal ligation and puncture-induced dysfunction of organs. CONCLUSIONS: LB suppresses LPS-induced HMGB1 release in vitro and in vivo by partially inhibiting NF-κB/p38 MAPK pathways. LB can rescue mice from sepsis and protect against organ dysfunction in septic mice.