Daytime Variation of Chloral Hydrate-Associated Sedation Outcomes: A Propensity-Matched Cohort Study.

BACKGROUND: Physiological processes influencing a drugs' efficacy change substantially over the course of the day. However, it is unclear whether there is an association between the sedative success rate of chloral hydrate and the time of day. We conducted a retrospective study of 41,831 cases, to determine if there was a difference in sedation success rate with chloral hydrate in children seen in the morning and afternoon. METHODS: Patients who accepted the sedation service were included. Eligible patients were divided into two cohorts of morning and afternoon cases, according to the time of day when the initial dose of chloral hydrate was administered. To ensure that the two groups were comparable, a propensity score matching method was utilized. RESULTS: The success rate with the initial dose of chloral hydrate was higher in patients who received sedation services in the afternoon. In the subgroup analysis, the afternoon cases had a higher sedation success rate compared to the morning cases in male patients; whereas, in female patients, no difference was detected between the morning versus afternoon cases. CONCLUSIONS: These results show that the afternoon cases had a higher sedation success rate than the morning cases, despite the afternoon cases receiving relatively lower initial dose than the morning cases. However, the clinical significance remains to be discussed, and further prospective studies are needed to validate the findings.

Analysis of Risk Factors for Chloral Hydrate Sedative Failure with Initial Dose in Pediatric Patients: a Retrospective Analysis.

BACKGROUND: Although chloral hydrate has been used as a sedative for more than 100 years, dozens of studies have reported that it has inconsistent sedative effects and high sedation failure rates with initial dose. The high failure rates may lead to repeated administration of sedatives, guardians' dissatisfaction, parental anxiety, increasing medical workload as well as leading to an increase of adverse events. Our aim is to identify the risk factors associated with chloral hydrate sedative failure with initial dose in children undergoing noninvasive diagnostic procedures. METHODS: Pediatric patients who underwent chloral hydrate sedation for noninvasive diagnostic procedures at our institution between 1 December 2019 and 1 January 2021 were retrospectively analyzed. Data collected included patients' age, gender, weight, sedation history, sedation failure history, type of procedures, initial dose of choral hydrate, sleep deprivation, sedation failure with initial dose, and sedative duration. The initial dose was classified into three levels: reduced dose (< 40 mg/kg), standard dose (40-60 mg/kg), and high dose (> 60 mg/kg). The patients were divided into three cohorts according to the different initial doses. RESULTS: A total of 15,922 patients were included in the analysis; 1928 (12.1%) were not well-sedated after administering the initial dose of chloral hydrate. The highest sedative failure was observed in the reduced dose group. By multivariate regression, we identified that heavier weight, patients with a history of sedation or a history of sedation failure, and patients who received magnetic resonance imaging (MRI) or more than one procedure simultaneously were associated with an increased odds of sedation failure at the initial dose. However, outpatients, patients undergoing hearing screening, and patients with sleep deprivation were favored regarding chloral hydrate sedative success. CONCLUSION: An alternative drug or drug combination is necessary in patients with heavier weight, those with a sedation history or sedation failure history, and those undergoing an MRI or more than one procedure simultaneously, whereas chloral hydrate is an appropriate sedation option for outpatients, patients undergoing hearing screening, and those with sleep deprivation.

Sleep deprivation did not enhance the success rate of chloral hydrate sedation for non-invasive procedural sedation in pediatric patients.

STUDY OBJECTIVE: In Asian countries, oral chloral hydrate is the most commonly used sedative for non-invasive procedures. Theoretically, mild sleep deprivation could be considered as one of assisted techniques. However, there is no consensus on sleep deprivation facilitating the sedation during non-painful procedures in children. The aim of our study is to analyze the clinical data of children undergoing non-invasive procedural sedation retrospectively and to evaluate the association between mild sleep deprivation and sedative effects in non-invasive procedures. MEASUREMENTS: Consecutive patients undergoing chloral hydrate sedation for non-invasive procedures between December 1, 2019 to June 30, 2020 were included in this study. The propensity score analysis with 1: 1 ratio was used to match the baseline variables between patients with sleep deprivation and non-sleep deprivation. The primary outcome was the failure rate of sedation with the initial dose. The secondary outcomes included the failure rate of sedation after supplementation of chloral hydrate, the incidence of major and minor adverse events, initial and supplemental dose of chloral hydrate, and the length of sedation time. MAIN RESULTS: Of the 7789 patients undergoing chloral hydrate sedation, 6352 were treated with sleep deprivation and 1437 with non-sleep deprivation. After propensity score matching, 1437 pairs were produced. The failure rate of sedation with initial chlorate hydrate was not significantly different in two groups (8.6% [123/1437] vs. 10.6% [152/1437], p = 0.08), nor were the failure rates with supplemental chlorate hydrate (0.8% [12/1437] vs. 0.9% [13/1437], p = 1) and the length of sedation time (58 [45, 75] vs. 58 [45, 75] min; p = 0.93). CONCLUSIONS: The current results do not support sleep deprivation have a beneficial effect in reducing the pediatric chloral hydrate sedation failure rate. The routine use of sleep deprivation for pediatric sedation is unnecessary.

Irigenin treatment alleviates doxorubicin (DOX)-induced cardiotoxicity by suppressing apoptosis, inflammation and oxidative stress via the increase of miR-425.

Doxorubicin (DOX) is an eff ;ective chemotherapeutic drug to suppress the progression of various types of tumors. However, its clinical application has been largely limited due to its potential cardiotoxicity. MicroRNAs (miRNAs) are emerged as critical regulators of cardiac injury. This study was aimed to explore the effects of irigenin (IR), as an isoflavonoid isolated from the rhizome of Belamcanda chinensis, on DOX-induced cardiotoxicity using the in vivo and in vitrostudies. The results indicated that DOX-induced fibrosis, cardiac dysfunction and injury were markedly attenuated by IR through reducing apoptosis, oxidative stress and inflammation in heart tissue samples. Importantly, DOX resulted in a remarkable decrease of miR-425 in heart tissues and cells, which was significantly rescued by IR. Receptor-interacting protein kinase 1 (RIPK1) was discovered to be a direct target of miR-425. DOX induced over-expression of RIPK1 both in vivo and in vitro, which were greatly decreased by IR. Transfection with miR-425 mimic could inhibit RIPK1 expression, whereas reducing miR-425 increased RIPK1 expression levels. In parallel to miR-425 over-expression, RIPK1 knockdown could attenuate apoptosis, reactive oxygen species (ROS) production and inflammation in HL-1 cells. However, over-expression of RIPK1 markedly abolished miR-425 mimic-induced apoptosis, ROS accumulation and inflammatory response in DOX-exposed cells. Herein, miR-425 could ameliorate cardiomyocyte injury through directly targeting RIPK1. Furthermore, activation of miR-425 by IR markedly improved DOX-induced cardiotoxicity, and therefore IR could be considered as a promising therapeutic agent for the treatment of cardiac injury.

Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR­Î³ and UCP2.

The present study aimed to investigate whether pretreatment with rosuvastatin (RS) can provide cardioprotection in a myocardial ischemia/reperfusion (MI/R) model. The protective effect of RS on myocardial oxygen­glucose deprivation/reperfusion (OGD/R) injury was also evaluated by upregulating peroxisome proliferator­activated receptor­Î³ (PPAR­Î³). In the present study, MI/R model was established and activities of superoxide dismutase (SOD), lactate dehydrogenase (LDH), creatine kinase­muscle/brain (CK­MB), malondialdehyde (MDA), and troponin I/T were measured. The infarct size was measured using Evans blue staining and cell viability was measured by MTT assay. Reactive oxygen species (ROS) levels were assessed by flow cytometry. Caspase­9, cytochrome c (cyt c), mitochondrial uncoupling protein 2 (UCP2) and PPAR­Î³ expression levels were detected by reverse transcription­quantitative polymerase chain reaction and western blotting. The results indicated that RS increased SOD activity, and decreased LDH, CK­MB, MDA and troponin I/T activities. The effect of RS was reversed by atractyloside (ATR). RS inhibited myocardial infarct size, downregulated expression of caspase­9 and cyt c and upregulated expression of UCP2 and PPAR­Î³ by inhibiting ATR. Furthermore, the results indicated that RS promoted cardiomyocyte viability, inhibited LDH release, reduced ROS production, decreased expression of caspase­9 and cyt c, and increased expression of UCP2 and PPAR­Î³ following OGD/R damage. Therefore, the present study demonstrated that RS protects primary myocardial cells against OGD/R injury by regulating PPAR­Î³ and UCP2. RS may be a promising therapeutic agent for treatment of MI/R injury.

Efficacy of Acupuncture Is Noninferior to Nicotine Replacement Therapy for Tobacco Cessation: Results of a Prospective, Randomized, Active-Controlled Open-Label Trial.

BACKGROUND: We designed and conducted this multicenter randomized active-controlled open-label trial to evaluate the efficacy of acupuncture, auricular point pressing, and nicotine replacement therapy (NRT) on tobacco cessation in the Chinese population. METHODS: This randomized controlled trial was conducted in seven hospitals in China between October 2013 and February 2016. Eligible participants were recruited and randomly assigned to receive acupuncture or auricular point pressing or NRT via a central randomization system with a 1:1:1 ratio. All treatment was given for a total of 8 weeks, and follow-up visit was at 16 weeks. The primary outcome measure was carbon monoxide (CO)-confirmed 24-h point abstinence rate (<10 parts per million), 24 weeks after quit day. RESULTS: A total of 300 participants were recruited and 195 participants finished, with a dropout rate of 35.00%. Two cases of adverse events in the acupuncture group and 2 cases in the NRT group were observed. The CO-confirmed 24-h point abstinence rate was 43.00% at 24 weeks in the acupuncture group, which was similar to 44.00% in the NRT group (P > .05), but significantly higher than the 30.00% in the auricular point group (P < .05). At 24 weeks, the Fagerstrom Nicotine Dependence Test and the Minnesota Nicotine Withdrawal Scale scores in the acupuncture group were significantly lower than those in the auricular point group and in the NRT group (P < .05). Kaplan-Meier analysis showed the time to relapse for acupuncture (44.12 days) was insignificantly longer than NRT (41.18 days), but significantly longer than auricular point pressing (29.53 days). CONCLUSIONS: We found acupuncture was safe and a possible treatment for tobacco cessation, but it requires further study to establish its role. TRIAL REGISTRY: Chinese Clinical Trial Registry; No.: ChiCTR-TRC-13003544; URL: http://www.chictr.org.cn/abouten.aspx.

[The therapeutic effect and its mechanism of adiponectin on ApoE-/- mice with atherosclerosis].

Objective To analyze the role of adiponectin (APN) in the treatment of ApoE-/- mice with atherosclerosis (AS) and its possible mechanism. Methods Twenty male ApoE-/- mice were enrolled to establish AS model with high-fat diet, and then randomly divided into control group (saline, intraperitoneal injection, 4 weeks) and APN-treated group (25 µg/d, intraperitoneal injection, 4 weeks). HE staining, immunohistochemistry, ELISA, immunofluorescence, reverse transcription PCR and Western blotting were performed to analyze the effect of APN on ApoE-/- mice and the changes of related signaling pathways. Results Compared with the control group, the APN-treated group had smaller atheroma macular areas and lower levels of inflammatory cytokines (IL-8 and TNF-α) in blood vessels. The APN-treated group had less inflammatory cell infiltration in perivascular adipose tissues than those of the control group. The APN-treated group had lower levels of CD86 and IL-1ß, but higher levels of CD206 and IL-10 in perivascular adipose tissues than those of the control group. Western blot analysis showed that APN treatment significantly increased the expression of p-STAT6 in perivascular adipose tissues as compared with that of the control group. Conclusion APN has a definitely therapeutic effect on ApoE-/- mice, and the possible mechanism may be associated with the induced macrophage polarization through STST6 signal in perivascular adipose tissues.

Perioperative plasma mitochondrial DNA dynamics and correlation with inflammation during infantile cardiopulmonary bypass.

OBJECTIVE: Numerous studies in animals and humans have demonstrated that inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 play a role in cardiopulmonary bypass (CPB), which might affect surgical outcomes. Plasma mitochondrial DNA (mtDNA), a recently discovered pro-inflammatory agent, is released by cells upon insult. This study aimed to detect changes in plasma mtDNA levels at different time points after infantile CPB and explore its potential association with inflammatory mediators. METHODS: In the present study, we analyzed the perioperative plasma mtDNA and inflammatory cytokine levels of 48 infants undergoing ventricular septal defect closure. Blood samples were collected before aortic cross-clamping (T1), at the end of CPB (T2), and 6h (T3), 12h (T4), and 24h (T5) post-CPB. Reverse transcription-polymerase chain reaction and specific enzyme-linked immunosorbent assay were used to quantify the plasma mtDNA and inflammatory cytokines, respectively. Bivariate correlation analysis was used to determine the correlations between plasma mtDNA and inflammatory cytokines. RESULTS: Plasma mtDNA levels increased at T2 and peaked at T3. Significant positive correlations were found between peak plasma mtDNA (at T3) and several inflammatory biomarkers, including IL-6 (at T3) (r=0.62, P<0.001), IL-8 (at T2) (r=0.53, P<0.001), and TNF-α (at T3) (r=0.61, P<0.001). CONCLUSION: Here we report that mtDNA may participate in a systemic inflammatory response to CPB.