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.

The IL-31/TRPV1 pathway mediates allergic asthma exacerbated by DINP dermal exposure in OVA-sensitized Balb/c mice.

BACKGROUND: The potential role of dermal exposure diisononyl phthalate (DINP) as an adjuvant in allergic inflammation and asthma has been suggested. However, the current findings do not provide enough evidence to support this claim. OBJECTIVES: The purpose of this investigation was to examine the impact and mechanisms of allergic asthma exacerbation through the dermal exposure to DINP. METHODS: The study was undertaken using OVA-sensitized mice. Lung histopathology and airway hyperreactivity (AHR) were assessed. Expression levels of immunoglobulins (t-IgE, OVA-IgE and OVA-IgG1), cytokines (IL-31, IL-4, IL-5, IL-6, IL-13 and INF-γ), and TRPV1 were measured. To investigate the mechanism by which allergic asthma worsens due to dermal exposure to DINP, the blockade analysis using the IL-31 antagonist SB-431542 and the TRPV1 antagonist capsazepine (CZP) were performed. RESULTS: The findings of the study revealed that the simultaneous exposure to DINP and OVA resulted in an increase in inspiratory resistance (Ri) and expiratory resistance (Re), a decrease in the minimum value of lung dynamic compliance (Cldyn), and worsened airway remodeling. Additionally, it was found that this exposure led to an increase in the levels of IL-31 and TRPV1, which are biomarkers of Th2 cytokines (IL-4, IL-5, IL-6, and IL-13), as well as immunoglobulins (Total IgE, OVA-lgE, and OVA-IgG1), while decreasing the biomarker of Th1 cytokines (IFN-γ). However, these impairments showed improvement after the administration of SB-431542 or CZP. CONCLUSION: The findings of this research indicate that the IL-31/TRPV1 pathway plays a moderating function in OVA-induced allergic asthma worsened by dermal exposure to DINP.

Efficacy of continuous intravenous remimazolam versus midazolam in the extraction of impacted wisdom teeth: protocol of a randomised controlled trial.

INTRODUCTION: Benzodiazepines such as midazolam are widely used to moderately sedate patients during impacted wisdom tooth extraction to reduce anxiety in outpatient surgery. This present protocol was designed to determine whether continuous intravenous remimazolam, a new ultrashort-acting benzodiazepine, produces superior postoperative recovery quality to that of midazolam in patients undergoing extraction of impacted wisdom teeth. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial conducted at Peking Union Medical College Hospital, Beijing Anzhen Hospital and Beijing Shijitan Hospital in China. Approximately 150 participants undergoing extraction of impacted mandibular wisdom teeth will be randomly allocated to two groups (remimazolam and midazolam). The participants will be administered standard interventions to ensure they achieve a sedation level of III on the Ramsay sedation scale during the treatment. Preoperative and anaesthesia management and surgical techniques will be standardised for all participants. The primary outcome is recovery time for complete alertness and the secondary outcomes are anterograde amnesia during and after surgery, and interruption during operation for poor compliance or safety concerns. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Review Committee of Peking Union Medical College Hospital (approval number: ZS-3142), Beijing Anzhen Hospital (approval number: KS2022082) and Beijing Shijitan Hospital (approval number: 2023-4). TRIAL REGISTRATION NUMBER: NCT05350085.

Composite dietary antioxidant index negatively correlates with osteoporosis among middle-aged and older US populations.

OBJECTIVE: To assess whether the composite dietary antioxidant index (CDAI) is associated with osteoporosis (OP) in middle-aged and older US populations. METHODS: We conducted a cross-sectional survey and identified individuals aged 40-85 years (n=11,664) from secondary datasets from the 2007-2010, 2013-2014, and 2017-2018 National Health and Nutrition Examination Survey (NHANES). Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD), and OP was defined as a BMD T-score ≤-2.5 at the femoral neck or lumbar spine. The CDAI score was calculated based on dietary data from the first NHANES 24-hour dietary recall. Multivariate logistic regression models were used to evaluate the association between CDAI and OP. RESULTS: Among the 11,664 participants, the average age was 60.3 (11.8), 5,898 (50.6%) were female, and 925 (7.9%) had OP. The median CDAI was -2.0 (interquartile range, -6.9 to 4.2). After adjusting for age, sex, race, family income, body mass index, physical activity, calorie intake, estimated glomerular filtration rate, smoking and drinking status, hypertension, and diabetes, the CDAI was associated with OP (odds ratio (OR), 0.98; 95% CI: 0.96-0.99). Participants in the highest CDAI quantile were at low risk of osteoporosis (OR, 0.61; 95% CI: 0.44-0.85) versus those in the lowest quantile. Moreover, this association was stable in the subgroup and sensitivity analyses. CONCLUSION: Dietary antioxidant ability assessed by using the CDAI was inversely associated with OP among US adults aged 40-85 years.

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.

Continuous block at the proximal end of the adductor canal provides better analgesia compared to that at the middle of the canal after total knee arthroplasty: a randomized, double-blind, controlled trial.

BACKGROUND: The optimal position for continuous adductor canal block (ACB) for analgesia after total knee anthroplasty (TKA) remians controversial, mainly due to high variability in the localization of the the adductor canal (AC). Latest neuroanatomy studies show that the nerve to vastus medialis plays an important role in innervating the anteromedial aspect of the knee and dives outside of the exact AC at the proximal end of the AC. Therefore, we hypothesized that continuous ACB at the proximal end of the exact AC could provide a better analgesic effect after TKA compared with that at the middle of the AC (which appeared to only block the saphenous nerve). METHODS: Sixty-two adult patients who were scheduled for a unilateral TKA were randomized to receive continuous ACB at the proximal end or middle of the AC. All patients received patient-controlled intravenous analgesia with sufentanil postoperatively. The primary outcome measure was cumulative sufentanil consumption within 24 h after the surgery, which was analyzed using Mann-Whitney U tests. P-values < 0.05 (two-sided) were considered statistically significant. The secondary outcomes included postoperative sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters. RESULTS: Sixty patients eventually completed the study (30/group). The 24-h sufentanil consumption was 0.22 µg/kg (interquartile range [IQR]: 0.15-0.40 µg/kg) and 0.39 µg/kg (IQR: 0.23-0.52 µg/kg) in the proximal end and middle groups (P = 0.026), respectively. There were no significant inter-group differences in sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters. CONCLUSIONS: Continuous ACB at the proximal end of the AC has a better opioid-sparing effect without a significant influence on quadriceps motor strength compared to that at the middle of the AC after TKA. These findings indicates that a true ACB may not produce the effective analgesia, instead, the proximal end AC might be a more suitable block to alleviate pain after TKA. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT03942133 ; registration date: May 06, 2019; enrollment date: May 11, 2019).

The efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy: a multicentered, randomized, positive-controlled, phase III clinical trial.

This study aimed to evaluate the efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy. In this multicentered, blinded, randomized, active-controlled, non-inferior phase III trial, 384 eligible patients who were about to undergo colonoscopy were randomized as a ratio of 1:1 into remimazolam and propofol group. Procedure success was assessed and defined as the completion of colonoscopy without administration of rescue sedative agent or more than 5 top-ups of trial drug in any 15 minute-period after initial administration of trial drug. Sedation quality was evaluated by Modified Observer's Assessment of Alertness/Sedation score. Treatment-emergent adverse events were recorded. Procedure success rate was 96.91% (188/194) in remimazolam group and 100% (190/190) in propofol group, and the difference in rate was -3.09% with 95% confidence interval (CI) of -5.53%~-0.66%. Since the lower limit of 95% CI was greater than the non-inferiority margin of -8.00%, the efficacy of remimazolam tosylate was non-inferior to propofol. Besides, induction time of sedation was increased (P<0.001), while hypotension and respiratory depression was decreased in remimazolam group compared to propofol group; however, time to fully alert (P>0.05) or time to discharge (P>0.05) were unchanged. For safety assessment, total treatment-emergent adverse events were decreased in remimazolam group compared to propofol group (P<0.001); specifically, administration site pain (P<0.001), increased bilirubin (P=0.019), decreased respiratory rate (P<0.001) and decreased SpO2 (P<0.001) were less frequent in remimazolam group compared with propofol group. In conclusion, remimazolam tosylate is non-inferior in sedation efficacy while safer than propofol in patients undergoing colonoscopy.

Ginsenoside Rg3 attenuates endometriosis by inhibiting the viability of human ectopic endometrial stromal cells through the nuclear factor-kappaB signaling pathway.

OBJECTIVE: To investigate the effects of ginsenoside Rg3 on human ectopic endometriotic stromal cells in vitro. MATERIALS AND METHODS: Ectopic endometrial tissue specimens were obtained from 6 female patients with ovarian endometriosis who underwent laparoscopic surgical procedures. Endometrial stromal cells derived from isolated ectopic endometriotic lesions were cultured, and the purity and homogeneity of cells were verified by Immunocytochemistry. The effect of Rg3 on cell proliferation was detected by Cell Counting Kit-8 (CCK8). After treatment with Rg3, the protein expression of NF-κB p65 subunit, VEGF, and caspases3 were measured by western blot analysis. Meanwhile, the mRNA expression of NF-κB p65 subunit was determined by Quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Rg3 inhibited the proliferation of ectopic endometriotic cells in a time- and dose-dependent manner. The treatment with Rg3 significantly diminished the level of NF-κB p65 subunit as well as TNF-α induced nuclear translocation of NF-κB p65 subunit in ectopic endometriotic cells. Moreover, Rg3 upregulated the expression of caspases3 but suppressed the expression of VEGF. CONCLUSION: Our results indicate that Ginsenoside Rg3 suppresses endometriosis by reducing the viability of human ectopic endometrial stromal cells involving the nuclear factor-kappaB signaling pathway in vitro.

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.

The adjuvant effect induced by di-(2-ethylhexyl) phthalate (DEHP) is mediated through oxidative stress in a mouse model of asthma.

Di-(2-ethylhexyl) phthalate, as the most commonly used plasticizer, is considered to be related to the asthma prevalence. There are studies affirming that the DEHP has an adjuvant effect in the pathogenesis of allergy asthma. Oxidative stress is one possible pathway for DEHP-adjuvant effect. Thus, this study explored whether DEHP could induce adjuvant effect in mouse asthma model via oxidative stress pathway. Male BALB/c mice were randomly divided into six groups: (1) saline group, (2) DEHP group, (3) ovalbumin (OVA) group, (4) DEHP+OVA group, (5) OVA+vitamin E (Vit E) group, (6) DEHP+OVA+Vit E group. The exposure dose of DEHP was 30 mg/kg body weight (bw)/day. After 18 days of the exposure protocol. Reactive oxygen species (ROS), glutathione (GSH) and malonaldehyde (MDA) levels and biomarkers related to asthma model were measured. Collectively, these data indicated higher ROS and MDA levels and lower GSH contents in DEHP+OVA group than that in OVA group, while Vit E, an antioxidant, could restore ROS, MDA and GSH levels to control levels and attenuate the DEHP and/or OVA effects. Our observations suggested that there was a relationship between oxidative stress and the adjuvant effect induced by DEHP in this mouse asthma model.

[The correlation of anemia and contrast-induced nephropathy in patients with chronic kidney disease undergoing percutaneous coronary intervention].

OBJECTIVE: To investigate the correlation of anemia and contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 292 patients with CKD undergoing PCI admitted to Guangdong General Hospital from October 2010 to December 2012 were consecutively enrolled in this study. Anemia was defined as hemoglobin <130 g/L in male and <120 g/L in female. All patients were divided into the following two groups by their preoperative hemoglobin: anemic group (n = 101) and non-anemic group (n = 191). The incidence of CIN and other major adverse cardiac events in hospital were evaluated. The correlation between CIN and anemia was evaluated by multivariate logistic regression analysis. RESULTS: The incidence rates of CIN were 9.9% (29/292) in all subjects, 17.8% (18/101) in the anemic group and 5.8% (11/191) in the non-anemic group. Compared with the non-anemic group, more patients in the anemic group required renal replacement therapy and intra-aortic balloon pump therapy, mechanical ventilation and manifested as acute heart failure (4.0% vs 0.0%, P = 0.006; 9.9% vs 1.0%, P < 0.001; 3.0% vs 0.0%, P = 0.017; 5.9% vs 1.0%, P = 0.015; respectively). Adjusted for age >75 years, basic renal function and the history of diabetic mellitus in the logistic regression analysis, anemia remained as a significant and independent risk predictor for CIN in patients with CKD (OR = 2.7, 95%CI 1.2-6.3, P = 0.017). CONCLUSIONS: Pre-procedure anemia is a significant and independent predictor of CIN in patients with CKD undergoing PCI. Caution and treatment for the pre-procedure anemia could be very useful for the prevention of CIN in those patients.

Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function.

BACKGROUND: Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide. METHODS: The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations. RESULTS: The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates. CONCLUSIONS: Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.