Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response.

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK-3ß activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR-treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4-mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK-3ß through four covalent bonds and reduced GSK-3ß activity. In conclusion, our findings suggest that CUR treatment inhibits GSK-3ß activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA-induced neuropathic pain.

Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial.

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

Silent spontaneous posterior uterine rupture of a prior caesarean delivery at 36 weeks of gestation.

BACKGROUND: In caesarean section patients, the spontaneous rupture of the posterior wall of the uterus is extremely rare, with nonspecific signs and symptoms being present. Perinatal and maternal morbidity and mortality are high. CASE PRESENTATION: A 28-year-old woman at 36 + 6 weeks of gestation presented with mild uterine contractions and developed a sudden abdominal distension. An emergency laparotomy was performed, and the posterior wall of the uterus had ruptured. A baby boy was born. CONCLUSION: Silent uterine rupture is very rare and easy to ignore due to nonspecific clinical symptoms, unexplained haemoglobin reduction and haemoperitoneum, but these features caution us to more closely consider uterine rupture in patients.

Pain control for patients with hepatocellular carcinoma undergoing CT-guided percutaneous microwave ablation.

BACKGROUND: Hepatic percutaneous microwave ablation (MWA) is usually performed in patients under conscious sedation. Nonetheless, many patients reported pain during the procedure. The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure. METHODS: A total of 100 patients with hepatocellular carcinomas (HCCs) were included in this study. These patients underwent CT-guided percutaneous MWA between February and October 2017. Patients were randomized into two groups: Experimental group (n = 50) and Control group (n = 50). Patients in the Control group were given 5 mg of morphine intravenously, followed by 10 mg of morphine injected subcutaneously 30 min before surgery. Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4. Other clinical and treatment parameters were also analysed. RESULTS: A significantly less amount of morphine (p < 0.001) was used in the experimental group (7.18 ± 1.65 mg) than in the control group (17.40 ± 2.52 mg). No significant differences were found in the number of patients who needed to discontinue the surgery (p = 0.242). Other clinical parameters including heart rate, systolic and diastolic blood pressures at various time points were comparable. Importantly, a lower VAS was reported in the experimental group, indicating a lower pain intensity experienced by patients during the procedure. CONCLUSION: The administration of personalized dosage of morphine to HCC patients undergoing percutaneous MWA is an effective and safe procedure for pain control.

Effectiveness and safety of CT-guided percutaneous radiofrequency ablation of adrenal metastases.

OBJECTIVE: The imaging-guided percutaneous radiofrequency (RF) ablation of adrenal metastases is a relatively new treatment procedure, compared to the more widespread application of the technique for the treatment of liver and renal cancers. The present study aims to evaluate the safety and efficacy of the CT-guided percutaneous RF ablation of adrenal metastases in a cohort of patients. METHODS: 33 patients with 38 adrenal metastases who received percutaneous CT-guided RF ablation between 2012 to 2015 were retrospectively reviewed. The average diameter of the treated adrenal metastases was 3.0 ± 1.6 cm. The treatment outcomes, including presence of residual tumours, technical success rate, recurrence rate, and complications, were evaluated. Patients were followed up for every 3 months to monitor the progression of the disease. RESULTS: Postoperative CT images showed the lack of tumour enhancement in 30 tumours (30/38 tumours, technical success rate = 78.9%), and residual disease was found in 7 tumours (7/37 tumours, 18.9%). The rate of residual disease was significantly lower in the group with tumour size <3 cm than the group with tumour size ≥3 cm (p = 0.025). The severe complication rate was 4.3%, and the mild complication rate was 48%, with intraoperative hypertensive crisis as the most frequently observed complication (27.3%). The follow-up data showed that 76.3% of patients had recurrence-free survival in 27.4 months. CONCLUSION: The current study demonstrated that radiofrequency ablation is a relatively safe and effective treatment for controlling adrenal metastases, especially for patients with tumour size <3 cm. Advances in knowledge: Surgical resection of the adrenal metastases was advocated as one of the treatment options for patients. The present study showed that radiofrequency ablation is a relatively safe and effective treatment for controlling adrenal metastases.

Robot-assisted versus conventional laparoscopic surgery for endometrial cancer staging: A meta-analysis.

This meta-analysis broadly compared the safety and efficacy of robot-assisted laparoscopy (RAL) with that of conventional laparoscopy (CL) for endometrial cancer staging. The advantages of RAL were evaluated through the outcomes in terms of conversion rates, complications, length of operation, blood loss, number of lymph nodes harvested, and length of hospitalization. Three electronic databases (PubMed, MEDLINE, and EmBASE) were searched to identify eligible studies. We selected all retrospective studies documenting a comparison between RAL and CL for endometrial cancer staging between 2005 and 2015, and tallied with meta-analyses criteria. Only studies published in English were included in this analysis. The outcomes of the extracted data were pooled and estimated by the Review Manager version 5.1 software. Seventeen studies met the eligibility criteria. Among the 2105 patients reported, 912 underwent RAL and the other 1193 underwent CL for endometrial cancer staging. Compared with CL, RAL had lower conversion rates [risk ratio, 0.4; 95% confidence interval (CI), 0.25-0.64; p = 0.0002]. Its complications were also less than that of CL (risk ratio, 0.72; 95% CI, 0.56-0.94; p = 0.02). RAL was associated with significantly less intraoperative blood loss (weighted mean difference, -79.2 mL; 95% CI, from -103.43 to -54.97; p < 0.00001) and a shorter length of hospitalization (weighted mean difference, -0.37 days; 95% CI, from -0.57 to -0.17; p = 0.0003). We found no significant differences in the length of operation and number of lymph nodes harvested between the two groups. From our meta-analysis results, RAL is a safe and effective alternative to CL for endometrial cancer staging. Further studies are required to determine potential advantages or disadvantages of RAL.

Robot-assisted versus conventional laparoscopic surgery in the treatment of advanced stage endometriosis: a meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of robot-assisted laparoscopy (RAL) versus conventional laparoscopy (CL) in the treatment of advanced stage endometriosis. MATERIALS AND METHODS: Utilizing electronic databases (PubMed, Embase, and Elsevier), a systematic literature review was performed between 2008 and 2015 to compare the RAL surgery with CL surgery (CLS) in the treatment of advanced stage endometriosis. According to meta-analysis criteria, two comparative clinical trials were selected. Outcome measures including length of operation, blood loss, operative complications, and the length of hospitalization, were estimated by the RevMan 5.1 software. RESULTS: In the meta-analysis, there were no significant differences in blood loss, complication, and hospital stay between RAL and CL surgeries in the treatment of advanced stage endometriosis. However, RAL surgery required a higher mean operating time than CL surgery (WMD: 73.85, 95% CI: 56.77-90.94; p < 0 .00001). Comparative studies demonstrated that RAL displayed no outstanding advantages. CONCLUSIONS: As a new minimally invasive method, RAL technology is safe and efficient alternative to CL in the treatment of advanced stage endometriosis. The latent benefits of RAL technology for the treatment of advanced stage endometriosis remain uncertain.

Predictive value of GRACE risk scores for contrast-induced acute kidney injury in patients with ST-segment elevation myocardial infarction before undergoing primary percutaneous coronary intervention.

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is a well-known serious complication of percutaneous coronary intervention (PCI) and may cause increased morbidity and mortality. We aim to identify the predictive value of Global Registry for Acute Coronary Events (GRACE) risk scores for CI-AKI in patients with ST-segment elevation myocardial infarction (STEMI) before primary PCI, allowing pre-procedural decisions regarding prevention therapy for CI-AKI. METHODS: We enrolled 251 consecutive patients with STEMI undergoing primary PCI. Receiver operating characteristic curves were used to identify the optimal sensitivity for the observed range of GRACE risk scores. CI-AKI was defined as any of the following: absolute increase in serum creatinine (SCr) of ≥ 0.3 or ≥ 0.5 mg/dL within 48-72 h after contrast exposure, or a percentage increase in SCr level of ≥ 50 %. RESULTS: Forty-three patients (17.1 %) developed CI-AKI0.3, 22 (8.8 %) CI-AKI0.5, and 19 (7.6 %) CI-AKI50. The GRACE quartiles were as follows: Q1 (<136), Q2 (136-159), Q3 (159-180), and Q4 (>180). Patients with high GRACE risk scores had higher risk for CI-AKI0.3, 0.5, and 50 (6.6, 6.6, 23.4, 31.7 %, respectively, p < 0.001; 1.6, 1.6, 9.4, 22.2 %, respectively, p < 0.001; and 3.3, 3.2, 9.4, 14.3 %, respectively, p = 0.009). ROC showed that a GRACE risk score >160 was a fair discriminator for CI-AKI0.3, 0.5, and 50 (C statistic = 0.723, 0.788, 0.668, respectively). After adjusting for potential confounding predictors, GRACE risk score >160 remained significantly associated with CI-AKI0.3 or 0.5 (OR 3.84; 95 % CI 1.61-9.17; p = 0.002, or OR 5.54; 95 % CI 1.42-21.66; p = 0.014), and high-sensitivity C-reactive protein (Hs-CRP) >15.5 mg/L was a highly significant predictor of CI-AKI0.3, 0.5, and CI-AKI50. CONCLUSIONS: GRACE risk score (>160) and post-procedural Hs-CRP >15.5 mg/L are independent and significant predictors of CI-AKI in patients with STEMI before primary PCI.

Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the development of murine systemic lupus erythematosus-like diseases in MRL/lpr autoimmune mice and BDF1 hybrid mice.

INTRODUCTION: Naturally occurring CD4+CD25+ regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune diseases. We have examined the effects of Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL/lpr autoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27 involves modulation of CD4+CD25+ Treg cells has also been investigated. METHODS: Female MRL/lpr mice that spontaneously develop lupus were treated orally by gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of parental female DBA/2 splenic lymphocytes, characterized by immunocomplex-mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD mice for 12 weeks. Nephritic symptoms were monitored and the percentage of CD4+CD25+FoxP3+ Treg peripheral blood leukocyte was detected with mouse regulatory T cell staining kit by flowcytometry. Purified CD4+CD25+ Tregs were assessed for immune suppressive activity using the mixed lymphocyte reaction. RESULTS: The life-span of MRL/lpr mice treated with Y27 for 10 weeks was significantly prolonged, proteinuria and renal lesion severity were ameliorated, and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA antibodies were decreased. Similar results were found in chronic GVHD mice. Administration of Y27 had little impact on percentage of the peripheral blood lymphocyte CD4+CD25+Foxp3+ Treg cells in both groups of mice. In contrast, the suppressive capacity of CD4+CD25+ Treg cells in splenocytes was markedly augmented in Y27-treated mice ex vivo. CONCLUSIONS: Experimental evidence of the protect effects of Y27 against autoimmune nephritis has been shown. The mechanism may involve enhancement of the suppressive capacity of CD4+CD25+ Treg cells.

H1521, a novel derivative of 4-hydroxyquinoline-3-carboxamide, suppresses the development of lupus in mice by inducing Th1 cytokine profile in T cells.

Transferring parental splenocytes into unirradiated F1 mice induces a chronic graft-versus-host disease (GVHD), characterized by the production of Th2 cytokines and immunocomplex-mediated glomerulonephritis resembling systemic lupus erythematosus (SLE). The effects of H1521, a new derivative of 4-hydroxyquinoline-3-carboxamide, were investigated in chronic GVHD lupus model. H1521 was administered to chronic GVHD mice for 10 weeks. Nephritic symptoms were monitored and cytokine expression in the spleen was detected. To clarify the direct effect of H1521 on CD4(+) T cell, CD4(+) T cells were isolated and co-cultured with H1521 under neutral and Th1 or Th2 driving conditions in vitro. H1521 (32 mg/kg) reduced the incidence of proteinuria by 50% in chronic GVHD mice. Ameliorated lupus symptoms and improved renal histopathology damage were also observed. Administration of H1521 had little impact on Th1 cytokine IL-2 and IFN-gamma or Th2 cytokine IL-4 and IL-10 mRNA expression. In contrast, severely deficient IFN-gamma production by concanavalin A-stimulated spleen cells in chronic GVHD mice was completely restored by H1521. In accordance with this, decreased T-bet mRNA expression became normalized with H1521 (32 mg/kg) treatment. In addition, in vitro studies demonstrated that H1521 preferentially favored Th1 differentiation in CD4(+) T cell and promoted IFN-gamma secretion in Th1 differential CD4(+) T cell. However, IL-4 secretion in naive or Th2 differential CD4(+) T cell was unaffected by H1521. In conclusion, H1521 can induce Th1 cytokine profile in CD4(+) T cells and has possible therapeutic value in Th2-predominant immune diseases.