The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor-CaMKII pathway.

Remifentanil-induced hyperalgesia (RIH) is a common clinical phenomenon that limits the use of opioids in pain management. Esketamine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to prevent and treat RIH. However, the underlying effect mechanism of esketamine on RIH remains unclear. This study aimed to investigate the role and mechanism of esketamine in preventing and treating RIH based on the NMDA receptor-CaMKIIα pathway. In this study, an experimental animal model was used to determine the therapeutic effect of esketamine on pain elimination. Moreover, the mRNA transcription and protein expression levels of CaMKII and GluN2B were investigated to offer evidence of the protective capability of esketamine in ameliorating RIH. The results demonstrated that esketamine attenuated RIH by inhibiting CaMKII phosphorylation and downstream signaling pathways mediated by the NMDA receptor. Furthermore, ketamine reversed the upregulation of spinal CaMKII induced by remifentanil. These findings suggest that the NMDA receptor-CaMKII pathway plays a critical role in the development of RIH, and ketamine's effect on this pathway may provide a new therapeutic approach for the prevention and treatment of RIH.

Sevoflurane attenuates myocardial ischemia/reperfusion injury by up-regulating microRNA-99a and down-regulating BRD4.

PURPOSE: It has been explored that sevoflurane (Sevo) is cardioprotective in myocardial ischemia/reperfusion injury (MI/RI) and mediates microRNA (miRNA) expression that control various physiological systems. Enlightened by that, the work was programmed to decode the mechanism of Sevo and miR-99a with the participation of bromodomain-containing protein 4 (BRD4). METHODS: MI/RImodel was established on mice. MI/RI modeled mice were exposed to Sevo or injected with miR-99a or BRD4-related vectors to identify their functions in cardiac function, pathological injury, cardiomyocyte apoptosis, inflammation, and oxidative stress in MI/RI mice. MiR-99a and BRD4 expression in myocardial tissues were tested, and their relation was further validated. RESULTS: MiR-99a was down-regulated, and BRD4 was up-regulated in MI/RI mice. Sevo up-regulated miR-99a to inhibit BRD4 expression in myocardial tissues of MI/RI mice. Sevo improved cardiac function, relieved myocardial injury, repressed cardiomyocyte apoptosis, and alleviated inflammation and oxidative stress in mice with MI/RI. MiR-99a restoration further enhanced the positive effects of Sevo on mice with MI/RI. Overexpression of BRD4 reversed up-regulation of miR-99a-induced attenuation of MI/RI in mice. CONCLUSIONS: The work delineated that Sevo up-regulates miR-99a to attenuate MI/RI by inhibiting BRD4.

Marital status independently predicts the overall survival in young adult patients with lymphoma: A population-based, propensity-matched study.

We predicted that marital status may have predictive effects on young adult patients with cancer. A total of 37,028 young adult patients (20-39 years old) newly diagnosed with lymphoma by positive histology between 1988 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. Patients were separated into married and unmarried groups. Multivariate regression was utilized to explore the association between marital status and overall survival, and propensity score matching and an inverse probability of treatment weighting were applied to corroborate our results. Among 37,028 eligible lymphoma patients, 12,827 married patients, and 12,827 unmarried patients, had equal propensity scores and were eventually recruited in this research. Moreover, married patients reported enhanced 10-year overall survival in the original group and the matched cohort. The multivariable Cox regression analysis revealed a vital advantageous influence of married status on overall mortality, with an adjusted hazard ratio (HR) of 0.54 (95% CI, 0.51-0.57, P < .001) and the association remained robust after propensity score matching (HR, 0.53, 95% CI 0.51-0.55, P < .001) and inverse probability of treatment weighting (HR, 0.53, 95% CI 0.51-0.56, P < .001) after adjusting for confounding factors. Marital status had predictive significance for overall survival in young adult patients with lymphoma.

Sevoflurane attenuates myocardial ischemia/reperfusion injury by up-regulating microRNA-99a and down-regulating BRD4

Purpose: It has been explored that sevoflurane (Sevo) is cardioprotective in myocardial ischemia/reperfusion injury (MI/RI) and mediates microRNA (miRNA) expression that control various physiological systems. Enlightened by that, the work was programmed to decode the mechanism of Sevo and miR-99a with the participation of bromodomain-containing protein 4 (BRD4). Methods: MI/RImodel was established on mice. MI/RI modeled mice were exposed to Sevo or injected with miR-99a or BRD4-related vectors to identify their functions in cardiac function, pathological injury, cardiomyocyte apoptosis, inflammation, and oxidative stress in MI/RI mice. MiR-99a and BRD4 expression in myocardial tissues were tested, and their relation was further validated. Results: MiR-99a was down-regulated, and BRD4 was up-regulated in MI/RI mice. Sevo up-regulated miR-99a to inhibit BRD4 expression in myocardial tissues of MI/RI mice. Sevo improved cardiac function, relieved myocardial injury, repressed cardiomyocyte apoptosis, and alleviated inflammation and oxidative stress in mice with MI/RI. MiR-99a restoration further enhanced the positive effects of Sevo on mice with MI/RI. Overexpression of BRD4 reversed up-regulation of miR-99a-induced attenuation of MI/RI in mice. Conclusions: The work delineated that Sevo up-regulates miR-99a to attenuate MI/RI by inhibiting BRD4.

Mobile health-based remote interaction management intervention for patients with low anterior resection syndrome: study protocol for a randomised controlled trial.

INTRODUCTION: Low anterior resection syndrome (LARS) involves bowel dysfunction after sphincter-preserving surgery for rectal resection that significantly impacts patients' quality of life (QoL). The improvement of LARS largely depends on patient self-management behaviour; however, insufficient information about supportive care and weak awareness of self-management lead to poor self-management behaviour. Motivational interviewing (MIs) explore and change patients' ambivalence during the conversation, thereby changing and maintaining healthy behaviours to enhance effective participation. In recent years, mobile health has been widely used in clinical practice, providing continuous information support and remote interaction. However, current online information on LARS is suboptimal, websites are highly variable, important content is often lacking and the material is too complex for patients. Therefore, this study will evaluate the impacts of a remote LARS interaction management intervention based on a WeChat applet ('e-bowel safety') and MIs on patients with LARS. METHODS AND ANALYSIS: This study will be a single-blind, two-arm randomised controlled trial involving patients with LARS in three tertiary grade A general hospitals who will be randomised into two groups. The intervention group will use the 'e-bowel safety' applet and the intervention team will conduct a monthly MI about syndrome management. The control group will receive an information booklet that contains the same information as that provided in the 'e-bowel safety' informational module. The intervention will last for 3 months, followed by 3 months of follow-up. The primary outcome will be global QoL; the secondary outcomes will include bowel function, social support, self-management measured at the baseline, 3 months and 6 months for three times and patients' thinkings at the end of the intervention (at 3 months). ETHICS AND DISSEMINATION: Ethics approval was granted by the Clinical Medical Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University (PJ2022-07-53). TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200061317).

Forecasting patient arrivals at emergency department using calendar and meteorological information.

Overcrowding in emergency departments (EDs) is a serious problem in many countries. Accurate ED patient arrival forecasts can serve as a management baseline to better allocate ED personnel and medical resources. We combined calendar and meteorological information and used ten modern machine learning methods to forecast patient arrivals. For daily patient arrival forecasting, two feature selection methods are proposed. One uses kernel principal component analysis(KPCA) to reduce the dimensionality of all of the features, and the other is to use the maximal information coefficient(MIC) method to select the features related to the daily data first and then perform KPCA dimensionality reduction. The current study focuses on a public hospital ED in Hefei, China. We used the data November 1, 2019 to August 31, 2020 for model training; and patient arrival data September 1, 2020 to November 31, 2020 for model validation. The results show that for hourly patient arrival forecasting, each machine learning model has better forecasting results than the traditional autoRegressive integrated moving average (ARIMA) model, especially long short-term memory (LSTM) model. For daily patient arrival forecasting, the feature selection method based on MIC-KPCA has a better forecasting effect, and the simpler models are better than the ensemble models. The method we proposed could be used for better planning of ED personnel resources.

Application of etomidate and propofol mixture in hematoma removal in patients with intracranial epidural hematoma.

OBJECTIVE: To innvestigate the application of etomidate and propofol mixture in the evacuation of hematoma in patients with epidural hematoma. METHODS: 98 patients with epidural hematoma were randomly divided into two groups: the joint group (n=49, anesthesia induction with etomidate and propofol) and the etomidate group (n=49, anesthesia induction with etomidate) using a random number table. Hemodynamics, stress response and cerebral oxygen metabolism were compared between the two groups at T0 (pre-anesthesia induction), T1 (after endotracheal intubation), T2 (10 min after the beginning of the operation) and T3 (the end of the operation). Adverse reactions were also analyzed. RESULTS: Compared with T0, the mean arterial pressure (MAP) at T1, T2 and T3 in the joint group decreased first and then increased, and the MAP at T1 was significantly lower than that in the etomidate group (P<0.05). Compared with T0, blood oxygen saturation of internal jugular vein bulb (SjvO2) increased in T1-T3 groups, and SjvO2 in the joint group was higher than that in the etomidate group (all P<0.05). Compared with T0, cerebral oxygen uptake rate (CERO2) in the T1-T3 groups decreased significantly, and CERO2 at T3 in the joint group was higher than that in the etomidate group (all P<0.05). Compared with T0, the levels of cortisol and superoxide dismutase (SOD) at T3 in the two groups were significantly lower, but those in the etomidate group were higher than those in the combination group (all P<0.05). There was no significant difference in the incidence of postoperative anesthesia-related adverse reactions between the two groups (P>0.05). CONCLUSION: Etomidate has less effect on hemodynamics and stress reaction during intravenous anesthesia, but its combination with propofol can improve cerebral oxygen metabolism to a certain extent with fewer adverse reactions.

Block-based association tests for rare variants using Kullback-Leibler divergence.

Although genome-wide association studies have successfully detected numerous associations between common variants and complex diseases, these variants typically can only explain a small part of the heritable component of a disease. With the advent of next-generation sequencing, attention has turned to rare variants. Recently, a variety of approaches for detecting associations of rare variants have been proposed, including the Kullback-Leibler divergence-based tests (KLTs) for detecting genotypic differences between cases and controls. However, few of these approaches consider linkage disequilibrium (LD) structure among rare variants and common variants. In this study, we propose two block-based association tests for testing the effects of rare variants on a disease. The main idea for this approach comes from the hypothesis that a region of interest may consist of two or more LD blocks such that single-nucleotide variants (SNVs) within each block are correlated, whereas SNVs in different blocks are independent or weakly correlated. Under this hypothesis, we propose two tests that are generalizations of the KLTs by taking the block structure into account. A simulation study under various scenarios shows that the proposed methods have well-controlled type I error rates and outperform some leading methods in the literature. Moreover, application to the Dallas Heart Study data demonstrates the feasibility and performance of the two proposed methods in a realistic setting.

Effects of Wharton's jelly cells of the human umbilical cord on acute spinal cord injury in rats, and expression of interleukin-1ß and nerve growth factor in spinal cord tissues.

To study the effects of Wharton's jelly cells (WJCs) on acute spinal cord injury (SCI), 81 rats were divided into a sham surgery group, a model group, and a WJC transplantation group (n = 27). Motor functions of the model and WJC transplantation groups were partially recovered, and the recovery was better in the latter group. The WJC transplantation group had integral spinal cord tissues. Compared with the model group, the WJC transplantation group expressed significantly less interleukin-1ß (IL-1ß) and more nerve growth factor (NGF) (P < 0.05). WJC transplantation changed the microenvironment of the SCI site, inhibited IL-1ß expression, increased NGF expression, promoted the recovery of neurological function, and relieved secondary SCI.

Melatonin lowers edema after spinal cord injury.

Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial fibrillary acidic protein.