Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures.

Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals.

LCN2 and ELANE overexpression induces sepsis.

Sepsis is a syndrome characterized by a systemic inflammatory response due to the invasion of pathogenic microorganisms. The relationship between Lipocalin-2 (LCN2), elastase, neutrophil expressed (ELANE) and sepsis remains unclear. The sepsis datasets GSE137340 and GSE154918 profiles were downloaded from gene expression omnibus generated from GPL10558.

Potential biomarker for diagnosis and therapy of sepsis: Lactylation.

Introduction: As a disease that has plagued human health for decades, sepsis has so far had no specific diagnostic or therapeutic indicators. The discovery of lactylation modifications not only uncovered the deep-rooted causes of changing between lactate level and pathophysiology and immunology of sepsis, but also reaffirmed the inevitable link between metabolic reprogramming and epigenetic reprogramming in sepsis. Lactylation modification became a potential marker for diagnosis and guiding the treatment of sepsis.

The mA reader YTHDC2 promotes SIRT3 expression by reducing the stabilization of KDM5B to improve mitochondrial metabolic reprogramming in diabetic peripheral neuropathy.

Aims: Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Aberrant mitochondrial function causes neurodegeneration under hyperglycemia-induced metabolic stress, which in turn results in DPN progression. mA and mA reader (YTHDC2) are closely related to diabetes and diabetes complications, while the role of YTHDC2 in regulating mitochondrial metabolism in DPN needs to be further probed.

Lysine demethylase KDM5B down-regulates SIRT3-mediated mitochondrial glucose and lipid metabolism in diabetic neuropathy.

Background: Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes mellitus without efficient interventions. Both lysine demethylase 5B (KDM5B) and sirtuin-3 (SIRT3) have been found to regulate islet function and glucose homeostasis. KDM5B was predicted to bind to the SIRT3 promoter by bioinformatics.

MicroRNA-7a-5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c-JUN pathway.

Aims: The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA-7a-5p (miR-7a-5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR-7a-5p in DPN.

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.

Hydrogen alleviated organ injury and dysfunction in sepsis: The role of cross-talk between autophagy and endoplasmic reticulum stress: Experimental research.

Aims: Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Although much progress has been made in understanding the pathophysiology of sepsis, further discussion and study of the detailed therapeutic mechanisms are needed. Autophagy and endoplasmic reticulum stress are two pathways of the complicated regulatory network of sepsis.

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine.

Prevention of Remifentanil Induced Postoperative Hyperalgesia by Dexmedetomidine via Regulating the Trafficking and Function of Spinal NMDA Receptors as well as PKC and CaMKII Level In Vivo and In Vitro.

Remifentanil-induced secondary hyperalgesia has been demonstrated in both animal experiments and clinical trials. Enhancement of N-methyl-D-aspartate (NMDA) receptor trafficking as well as protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) have been reported to be involved in the induction and maintenance of central sensitization. In the current study, it was demonstrated that dexmedetomidine could prevent remifentanil-induced hyperalgesia (RIH) via regulating spinal NMDAR-PKC-Ca2+/ CaMKII pathway in vivo and in vitro.

Spinal peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via enhancement of divalent metal transporter 1 without iron-responsive element-mediated iron accumulation in rats.

Background: Hyperalgesia is one of the negative consequences following intraoperative analgesia with remifentanil. Peroxynitrite is a critical determinant in nociceptive process. Peroxynitrite inactivates iron-sulfur cluster that results in mitochondrial dysfunction and the release of iron, leading to mitochondrial iron accumulation.

Glycogen synthase kinase-3β inhibition prevents remifentanil-induced postoperative hyperalgesia via regulating the expression and function of AMPA receptors.

Background: Many studies have confirmed that brief remifentanil exposure can enhance pain sensitivity. We previously reported that activation of glycogen synthase kinase-3β (GSK-3β) contributes to remifentanil-induced hyperalgesia via regulating N-methyl-D-aspartate receptor plasticity in the spinal dorsal horn. In this study, we demonstrated that GSK-3β inhibition prevented remifentanil-induced postoperative hyperalgesia via regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and function in the spinal dorsal horn.

[Regulative effects of hydrogen-rich medium on monocytic adhesion and vascular endothelial permeability].

Objective: To explore the regulative effects of hydrogen-rich medium on lipopolysaccharide (LPS)-induced monocytes adhesion to human umbilical vein endothelial cells (HUVEC) and vascular endothelial permeability in vitro.

Methods: Endothelial cells were seeded in 6-well plates and randomly divided into 4 groups (n = 42 each):control (A), hydrogen-rich medium (B), LPS (C) and LPS+hydrogen-rich medium (D). Cells were cultured in plain culture medium in groups A and C or in hydrogen-saturated culture medium in groups B and D.

Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages.

Background: Molecular hydrogen (H2) as a new medical gas has an anti-inflammatory effect. In the present study, we investigated whether heme oxygenase-1 (HO-1) contributes to the anti-inflammatory effect of H2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.

[Effects of intrathecal injection of ginsenoside Rg1 on the level of glutamate transporter in the arthritis rats with chronic morphine tolerance].

Objective: To investigate the effects of intrathecal injection of ginsenoside Rg1 at different doses on the changes of the behavior and the expressions of excitatory amino-acid transporter 1 (EAAT1), i. e., glutamate-aspartate transporter (GLAST) in the spinal dorsal horn of the arthritis rats with chronic morphine tolerance, and further to explore its mechanisms for morphine tolerance.

Glycogen synthase kinase-3β contributes to remifentanil-induced postoperative hyperalgesia via regulating N-methyl-D-aspartate receptor trafficking.

Background: Although remifentanil provides perfect analgesia during surgery, postoperative hyperalgesia after remifentanil administration might be a challenge to anesthesiologists. The trafficking and activation of N-methyl-D-aspartate (NMDA) receptors have a pivotal role in the development and maintenance of remifentanil-induced postoperative hyperalgesia. However, the underlying mechanisms of hyperalgesia are poorly elucidated.

[Changes of glycogen synthase kinase-3β and its phosphorylation in spinal cord neurons in rats with incisional pain-remifentanil-induced hyperalgesia].

Objective: To investigate the change in glycogen synthase kinase-3β (GSK-3β) in spinal cord neurons in rats with incisional pain (IP)-remifentanil-induced hyperalgesia.

Methods: 32 SD male rats (240 - 260 g) were randomly divided into 4 groups (n = 8 each): group R, group I, group R + I and group C. IP was established as Brennan's description.

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain.

Background: Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold.

[Participation of glucocorticoid receptors in morphine tolerance development through the signal pathway of extracellular signal-regulated kinase].

Objective: To investigate the mechanism of glucocorticoid receptors (GR) participating in morphine tolerance development via the extracellular signal-regulated kinase (ERK) signal pathway.

Methods: Forty healthy male SD rats were implanted with intrathecal catheters and then randomized into 4 groups: Group C received an intrathecal injection of 10 µl saline, Group M 10 µg morphine, Group MR 10 µg morphine followed by 2 µg GR antagonist RU38486 and Group MD 10 µg morphine followed by 4 µg GR agonist dexamethasone (DEX) respectively. Each intrathecal drug was administered twice daily for 7 days.

The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats.

The aim of this study was to investigate whether propofol could provide postconditioning to ischemic brain injury and the role of phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway in this phenomenon. Rats underwent 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion were randomly divided into nine groups (n=15 each): sham-operated group, MCAO group, propofol 10, 20 and 35 mg x kg(-1) x h(-1) group (propofol 10, 20, 35 mg x kg(-1) x h(-1) infused at the onset of reperfusion for 30 min), wortmannin group (wortmannin 0.6 mg/kg administered 30 min before MCAO), and the other three groups received wortmannin followed by 10, 20 and 35 mg x kg(-1) x h(-1) propofol respectively.

[Propofol provides ischemic postconditioning on myocardial ischemia-reperfusion injury in rats].

Objective: To investigate whether the infusion of propofol during early reperfusion provides ischemic postconditioning (I-postC) on myocardial ischemia-reperfusion injury in rats.

Methods: Sixty adult rats were randomly divided into 5 groups (n = 12 each): sham operation (group S); normal saline (group C); propofol 1 mg/kg (group P1); propofol 2 mg/kg (group P2); propofol 5 mg/kg (group P3). The left anterior descending coronary artery (LAD) was occluded for 60 min and reperfused for 120 min.

[Monocyte response and regulatory effect of emodin and shenmai injection on it in patients with severe sepsis].

Objective: To investigate the impact of monocyte releasing tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) stimulated by lipopolysaccharide (LPS) in severe sepsis (SS) patients, and the regulatory effect of emodin and Shenmai Injection (SMI) on monocyte response.

Methods: ocyte (PBMC) sampled from SS patients due to severe abdominal inflammation and healthy controls, PBMC were incubated with or without LPS, respectively. PBMC media pretreated with emodin and SMI, and then the levels of cytokine factors including TNF-alpha and IL-10 in supernatants were determined after stimulated with or without LPS in the two groups.

Change of TH1/TH2 cytokine equilibrium in rats with severe sepsis and therapeutic effect of recombinant interleukin-12 and Shenmai injection.

Objective: To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinant interleukin-12 (rIL-2) and Shenmai injection (SMI), a Chinese medicinal preparation.

Methods: Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B.