Dexmedetomidine treatment prevents cerebral ischemic reperfusion injury through HIF-1α/Beclin1-mediated autophagy.

OBJECTIVE: Cerebral ischemic reperfusion injury (CIRI) is a common cerebrovascular disorder with high disability and morbidity that threatens human health. Former investigations found that dexmedetomidine (DEX) has a protective effect against CIRI, but regulatory mechanism is unclear. METHODS: The current study utilized C57BL/6 mice to establish a focal cerebral ischemic reperfusion model. Cerebral infarct volume was defined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. BV2 cells and primary neurons were utilized for molecular mechanism studies after treatment with DEX or autophagy inhibitor 3-Methyladenine (3-Ma). RESULTS: Data revealed that DEX pretreatment protected nerves against CIRI. In vitro studies also found that DEX pretreatment enhanced microglial M2 polarization and protected against neuronal apoptosis by autophagy activation. Downregulation of hypoxia inducible factor (HIF)-1α or Beclin-1 inhibited the promotional effects of DEX on microglial M2 polarization and inhibited the protective effects of DEX against neuronal apoptosis. CONCLUSION: The present study found that DEX treatment protects against CIRI by modulating microglial polarization via HIF-1α/Beclin1-mediated autophagy.

Local infiltration vs epidural analgesia for postoperative pain control after total knee or hip arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: Inconsistent results have been obtained regarding postoperative pain control using local infiltration and epidural analgesia for patients after total knee or hip arthroplasty (TKA and THA). We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of local infiltration vs epidural analgesia for TKA and THA. METHODS: Electronic searches were conducted on PubMed, EmBase, and the Cochrane library to identify eligible RCTs conducted up to February 2020. Weighted mean difference (WMD) and relative risk with 95% confidence interval (95%CI) were applied to calculate pooled effect estimates between local infiltration and epidural analgesia using the random-effects model. RESULTS: Seven RCTs including a total of 412 TKA patients, and three RCTs including a total of 200 THA patients were selected for this meta-analysis. We noted that local infiltration was associated with lower visual analog scale (VAS) scores at rest after 48 hours (WMD: -1.31; 95%CI: -2.44 to -0.18; P = .024) and 72 hours (WMD: -0.95; 95%CI: -1.39 to -0.52; P < .001) for patients with TKA, while local infiltration significantly reduced VAS scores at rest after 12 hours for patients with THA (WMD: -1.00; 95%CI: -1.49 to -0.51; P < .001). Moreover, local infiltration was associated with lower VAS scores during movement after 48 hours in TKA patients (WMD: -1.08; 95%CI: -1.86 to -0.29; P = .007), while there were higher VAS scores during movement after 24 hours for patients with THA (WMD: 1.06; 95%CI: 0.67 to 1.45; P < .001). Furthermore, we noted that local infiltration was associated with higher flexion angles compared with epidural analgesia after 24 hours (WMD: 7.11; 95%CI: 2.30-11.93; P = .004), 48 hours (WMD: 6.69; 95%CI: 3.78 to 9.59; P < .001), and 72 hours (WMD: 5.19; 95%CI: 0.95-9.44; P = .016). There were no significant differences between local infiltration and epidural analgesia for the length of hospital stay, nausea, or wound infection. CONCLUSIONS: Local infiltration is superior to epidural analgesia for postoperative pain control after TKA, whereas for THA patients inconsistent results were obtained at various times.

Early Acute Kidney Injury Associated with Liver Transplantation: A Retrospective Case-Control Study.

BACKGROUND A retrospective case-control study was carried out to assess the occurrence of acute kidney injury (AKI) in liver transplantation (LT) recipients and its related risk factors. MATERIAL AND METHODS The study enrolled 131 patients undergoing LT from December 2017 to June 2019 at Beijing Tsinghua Chang Gung Hospital, China. AKI and its classification were defined according to KDIGO guidelines. We collected patients' demographic characteristics and perioperative parameters, and identified independent risk factors of AKI by multivariate logistic regression analysis. RESULTS We included 122 patients in analysis. AKI occurred in 52 (42.6%) patients (22.1% stage I, 8.2% stage II, and 12.3% stage III). AKI was notably associated with 12 factors: sex, body mass index (BMI), hepatic etiology, MELD score, ascites, prothrombin time (PT), international normalized ratio of prothrombin time (INR), preoperative total bilirubin (TBIL), operative time, total fluid intake, fresh frozen plasma (FFP), and estimated blood loss (EBL) (P<0.05). The factors independently associated with AKI were BMI (adjusted odds ratio: 0.605, 95% confidence interval: 0.425-0.859; P=0.005) and intraoperative FFP infusion (adjusted odds ratio: 0.998, 95% confidence interval: 0.995-1.000; P=0.047). Compared with the non-AKI group, the AKI group showed higher likelihood of renal replacement therapy (RRT), and longer ICU and hospital stays, higher in-hospital mortality, and higher hospitalization costs (P<0.05). CONCLUSIONS There is a high risk of AKI in patients undergoing LT. BMI and intraoperative FFP infusion are factors independently correlated with AKI. AKI can result in extended hospital stays and higher hospitalization expenses.

Intermittent epidural bolus versus continuous epidural infusions for labor analgesia: A meta-analysis of randomized controlled trials.

There are inconsistent results regarding the efficacy and safety of intermittent epidural bolus (IPB) versus continuous epidural infusions (CPI) for labor analgesia. This study used a meta-analytic approach to assess the safety and treatment efficacy of IPB versus CPI for labor analgesia based on randomized controlled trials (RCTs). Four electronic databases were used to identify eligible RCTs. Pooled effect estimates at 95% confidence intervals (CIs) were calculated using a random-effects model. Twenty-two RCTs with 2,573 parturients were selected for final analysis. The findings revealed no significant differences between IPB and CPI for the incidences of cesarean and instrumental delivery. IPB was shown to be associated with shorter total duration of labor [weighted mean difference (WMD): -21.46; 95% CI: -25.07 to -17.85; P < 0.001], duration of the first of stage of labor (WMD: -13.41; 95% CI: -21.01 to -5.81; P = 0.001), and duration of the second stage of labor (WMD: -4.98; 95% CI: -9.32 to -0.63; P = 0.025). Furthermore, IPB significantly reduced the incidences of required anesthetic interventions compared with CPI [relative risk (RR): 0.61; 95% CI: 0.39-0.95; P = 0.030], whereas there was no significant difference between IPB and CPI for the time required in the first anesthetic intervention (WMD: 7.73; 95% CI: -33.68-49.15; P = 0.714). The local anesthetic IPB (bupivacaine equivalents) was associated with lower milligrams per hour of local anesthetic (WMD: -0.89; 95% CI: -1.41 to -0.36; P = 0.001) and better maternal satisfaction (WMD: 8.76; 95% CI: 4.18-13.35; P < 0.001). There were no significant differences between IPB and CPI for the risk of adverse events. This study found that parturients with IPB have short total duration of labor and duration of the first and second stage of labor, reduced requirements for additional anesthetic interventions, and improved maternal satisfaction.

Clinical study of ultrasound-guided transversus abdominis plane block for analgesia after cesarean section.

BACKGROUND: Patient-controlled intravenous analgesia (PCIA) and patient-controlled epidural analgesia are 2 common methods of maintaining analgesia after cesarean section. In recent years, transversus abdominis plane block (TAPB) has been gradually applied clinically to reduce opioid analgesics and has achieved good results. Therefore, we performed this study to compare the efficacy and side effects of TAPB and PCIA in analgesia after cesarean section. METHODS: One hundred patients who underwent cesarean section were randomly classified into 2 groups. Following surgery, one group underwent ultrasound-guided TAPB and the other group underwent PCIA. Pain intensity according to the visual analog scale (VAS; 0 for no pain and 10 for severe intolerable pain) was assessed at 2, 4, 6, 8, 12, and 24-hour postsurgery in both groups. The postoperative complication rate and patient satisfaction were also measured. RESULTS: No significant differences were found in the VAS scores between the groups (P > .05). However, the incidence of postoperative complications in the TAPB group was significantly lower than that in the PCIA group (P < .05). Furthermore, patient satisfaction in the TAPB group was significantly higher than that in the PCIA group (P < .05). CONCLUSION: This study demonstrated that ultrasound-guided TAPB can achieve the same analgesic effect as PCIA after cesarean section but with even higher patient satisfaction.

DNA damage and apoptosis induced by a potent orally podophyllotoxin derivative in breast cancer.

BACKGROUND: Targeting TopoisomeraseII (TopoII) and generate enzyme mediated DNA damage is an effective strategy for treatment of breast cancer. TopoII is known as a validated target for drug discovery and cancer chemotherapy. METHODS: XWL-1-48, a new orally podophyllotoxin derivative, was designed and synthesized. The effect of XWL-1-48 on TopoII binding and activity was determined by molecular docking software and kDNA-decatenation assay, respectively. In vitro and in vivo breast cancer models were used to document the antitumor activity of XWL-1-48. Cellular apoptosis, cell cycle and ROS were analyzed by flow cytometry. Alteration of XWL-1-48-mediated downstream pathways was determined by western blot analysis. RESULTS: The cytotoxicity of XWL-1-48 is more potent than that of its congener GL331. Molecular docking demonstrated that XWL-1-48 could bind to TopoII through forming two strong hydrogen bonds and potential pi-pi interactions. Noticeably, XWL-1-48 exerts potent antitumor activity in in vitro and in vivo breast cancer model. Treatment with XWL-1-48 caused ROS generation and triggered DNA damage through induction of γ-H2AX and activation of ATM/p53/p21 pathway. Further studies showed that XWL-1-48 led to S-phase arrest and mitochondrial apoptosis. Meanwhile, XWL-1-48 significantly blocked PI3K/Akt/Mdm2 pathway and enhanced Mdm2 degradation. CONCLUSION: XWL-1-48 may be a promising orally topoII inhibitor, its mechanisms are associated with suppression of TopoII, induction of DNA damage and apoptosis, blockage of PI3K/AKT/Mdm2 pathway.