Objective:To evaluate whether the mechanism by which high glucose attenuated the cardioprotective effect of sevoflurane postconditioning was associated with the hypoxia-inducible factor-1α (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling pathway in rat cardiomyocytes.Methods:H9C2 cardiomyocytes were cultured at a 1∶4 ratio and then divided into 8 groups ( n=21 each) using a table of random numbers: control group (N+ Con group), hypoxia-reoxygenation (H/R) group (N+ H/R group), sevoflurane postconditioning group (N+ SPostC group), high glucose control group (H+ Con group), high glucose-H/R group (H+ H/R group), high glucose sevoflurane postconditioning group (H+ SPostC group), high glucose sevoflurane postconditioning + HIF-1α agonist group (H+ SPostC+ D group), and high glucose sevoflurane postconditioning + HIF-1α agonist + MCT4 inhibitor group (H+ SPostC+ D+ A group). N+ Con, N+ H/R and N+ SPostC groups were cultured in conventional culture dishes, while high-glucose group was incubated in high-glucose (35 mmol/L) DMEM. Cells were subjected to 3 h of hypoxia in serum-free and glucose-free DMEM using a three-gas incubator, followed by 3 h of reoxygenation in fresh DMEM in a CO 2 incubator. Sevoflurane postconditioning was performed as follows: Cells were incubated at 37 ℃ in a three-gas incubator filled with sevoflurane (2.4%) for 15 min. At 2 h before hypoxia, H+ SPostC+ D group was incubated in medium containing 1 mmol/L DMOG (HIF-1α agonist), and H+ SPostC+ D+ A group was incubated in medium containing 1 mmol/L DMOG and 10 μmol/L AZD0095 (MCT4 inhibitor). The viability of cardiomyocytes (by CCK8 assay), levels of LDH in culture medium (by microplate assay), levels of lactate (by WST-8 assay), levels of ATP (by chemiluminescence assay), apoptosis rate of cells (by flow cytometry), mitochondrial membrane potential (by fluorescence probe assay), and expression of HIF-1α and MCT4 (by Western blot) were measured. Results:Compared with N+ H/R group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in N+ SPostC group ( P<0.05). There were no significant differences in each parameter between H+ H/R group and H+ SPostC group ( P>0.05). Compared with H+ SPostC group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in H+ SPostC+ D group ( P<0.05). Compared with H+ SPostC+ D group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly decreased, the levels of LDH in culture medium and apoptosis rates of cells were increased, and the expression of HIF-1α and MCT4 was down-regulated in H+ SPostC+ D+ A group ( P<0.05). Conclusions:The mechanism by which high glucose attenuates the cardioprotective effect of sevoflurane postconditioning may be related to the inhibition of the HIF-1α/MCT4 signaling pathway in rat cardiomyocytes.

Objective:To evaluate whether the mechanism by which high glucose attenuated the cardioprotective effect of sevoflurane postconditioning was associated with the hypoxia-inducible factor-1α (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling pathway in rat cardiomyocytes.Methods:H9C2 cardiomyocytes were cultured at a 1∶4 ratio and then divided into 8 groups ( n=21 each) using a table of random numbers: control group (N+ Con group), hypoxia-reoxygenation (H/R) group (N+ H/R group), sevoflurane postconditioning group (N+ SPostC group), high glucose control group (H+ Con group), high glucose-H/R group (H+ H/R group), high glucose sevoflurane postconditioning group (H+ SPostC group), high glucose sevoflurane postconditioning + HIF-1α agonist group (H+ SPostC+ D group), and high glucose sevoflurane postconditioning + HIF-1α agonist + MCT4 inhibitor group (H+ SPostC+ D+ A group). N+ Con, N+ H/R and N+ SPostC groups were cultured in conventional culture dishes, while high-glucose group was incubated in high-glucose (35 mmol/L) DMEM. Cells were subjected to 3 h of hypoxia in serum-free and glucose-free DMEM using a three-gas incubator, followed by 3 h of reoxygenation in fresh DMEM in a CO 2 incubator. Sevoflurane postconditioning was performed as follows: Cells were incubated at 37 ℃ in a three-gas incubator filled with sevoflurane (2.4%) for 15 min. At 2 h before hypoxia, H+ SPostC+ D group was incubated in medium containing 1 mmol/L DMOG (HIF-1α agonist), and H+ SPostC+ D+ A group was incubated in medium containing 1 mmol/L DMOG and 10 μmol/L AZD0095 (MCT4 inhibitor). The viability of cardiomyocytes (by CCK8 assay), levels of LDH in culture medium (by microplate assay), levels of lactate (by WST-8 assay), levels of ATP (by chemiluminescence assay), apoptosis rate of cells (by flow cytometry), mitochondrial membrane potential (by fluorescence probe assay), and expression of HIF-1α and MCT4 (by Western blot) were measured. Results:Compared with N+ H/R group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in N+ SPostC group ( P<0.05). There were no significant differences in each parameter between H+ H/R group and H+ SPostC group ( P>0.05). Compared with H+ SPostC group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in H+ SPostC+ D group ( P<0.05). Compared with H+ SPostC+ D group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly decreased, the levels of LDH in culture medium and apoptosis rates of cells were increased, and the expression of HIF-1α and MCT4 was down-regulated in H+ SPostC+ D+ A group ( P<0.05). Conclusions:The mechanism by which high glucose attenuates the cardioprotective effect of sevoflurane postconditioning may be related to the inhibition of the HIF-1α/MCT4 signaling pathway in rat cardiomyocytes.

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

Objective: To compare the effect of intranasal dexmedetomidine and oral chloral hydrate in deep sedation of children. Methods: The Pubmed, EMBase, CENTRAL (Issue 4, 2018), Web of science, CBM, Wanfang Data, CNKI and VIP databases from the inception to January 2019 were searched. Randomized controlled trials (RCTs) with dexmedetomidine and chloral hydrate as interventions were included and the data were analyzed by RevMam 5.3 and Stata 12.0 software. The success rate of deep sedation, the indicator of sedation onset time, the recovery time, the incidence of vomiting and bradycardia were compared. Results: A total of 7 RCTs involving 1 007 patients were included for analysis. The results showed that the success rate of deep sedation (OR=2.55, 95%CI:1.46-4.44, P<0.01) and the incidence of bradycardia (OR=4.42, 95%CI:1.82-10.74, P<0.01) in the dexmedetomidine nasal group were significantly higher than those in the chloral hydrate oral group. The recovery time was significantly shorter (MD=-16.41, 95%CI:-21.54-11.28, P<0.01) and the incidence rate of vomiting (OR=0.04, 95%CI:0.01-0.17, P<0.01) in dexmedetomidine nasal group was significantly lower than those in the chloral hydrate oral group. There was no significant difference in the indicator of sedation onset time (MD=-0.47, 95%CI:-2.71-1.22, P=0.46). Conclusion Compared with the traditional oral chloral hydrate, intranasal dexmedetomidine has a higher sedation success rate and shorter recovery time after sedation with a lower incidence of nausea and vomiting.

Objective To systematically review the cardioprotection induced by sevoflurane postconditioning in the patients undergoing cardiac surgery with cardiopulmonary bypass.Methods Databases including Pubmed,EMBase,Web of Science,Cochrane Library,CBM,WangFang Data,CNKI and VIP were searched by a computer from the date of database establishment up to February 2019 and there was no limitation for language.The randomized control trials involving the cardioprotection induced by sevoflurane postconditioning in the patients undergoing cardiac surgery with cardiopulmonary bypass were collected.Evaluation indexes included:incidence of perioperative cardiac events,duration of intensive care unit stay,plasma concentrations of cardiac troponin I and creatine kinase-MB at 6 and 24 h after aortic opening,plasma concentrations of interleukin-6 at 2,12 and 24 h after aortic opening and percentage of spontaneous recovery of heart beat.Meta-analysis was conducted using the RevMan 5.3 and Stata 12.0 softwares.Results Seventeen randomized controlled trials involving 763 patients were included in our meta-analysis.Compared with control group,the incidence of reperfusion arrhythmia was decreased,the plasma concentrations of cardiac troponin I and creatine kinase-MB at 6 and 24 h after aortic opening and interleukin-6 at 2,12,and 24 h after aortic opening were decreased,the percentage of spontaneous recovery of heart beat was increased (P＜0.05 or 0.01),and no significant change was found in duration of intensive care unit stay in sevoflurane postconditioning group (P ＞ 0.05).Conclusion Sevoflurane postconditioning can produce cardioprotection in the patients undergoing cardiac surgery with cardiopulmonary bypass.

Objective To explore the treatment method with combined dorsal flap based on the second toe and tibial flap for repairing the finger distal degloving injury.Methods From March 2008 to September 2011,our department chose treatment with combined use of free dorsal flap based on the second toe and contralateral second toe tibial flap for repairing finger distal degloving injury.The 11 fingers in 11 cases were treated and followed up after surgery.Results The flaps in 11 cases all survived; The donor site with skin grafting successfully healed; The follow-up was 4-15 months,averaged of 6 months.There was not obvious atrophy for the toe dorsal flaps in the finger back side and toe tibial flaps in the palm side.The finger pulp was full,the nails grew well and the appearance of the fingers was good.There was satisfactory sensory function restoration for finger pulp,two cases for S4,five cases for S3,three cases for S2 and 1 case for S1.The protective sensation was restored in the finger back for all the cases; the finger function was restored to normal; the foot donor site was healing well without scarring.Walking was completely normal.Conclusion It is an ideal treatment with combined use of free dorsal flap based on the second toe and contralateral second toe tibial flap for repairing finger distal.