Effectiveness of general anaesthesia with remimazolam tosilate on intraoperative haemodynamics and postoperative recovery: study protocol for a randomised, positive-controlled, pragmatic clinical trial (GARTH trial).

INTRODUCTION: It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside doctor-reported outcomes and length of hospital stay. At present, studies on the contributions of optimal anaesthetic drugs within the ERAS protocol to patient-reported and doctor-reported outcomes are limited. Therefore, this study aims to pragmatically evaluate the effectiveness and safety of general anaesthesia (GA) with remimazolam tosilate within the ERAS protocol on intraoperative haemodynamics and postoperative recovery in adults undergoing elective surgeries, compared with propofol. METHODS AND ANALYSIS: This study is a single-centre, randomised, blinded, positive-controlled, pragmatic clinical trial. A total of 900 patients, aged ≥18 years old, scheduled for an elective surgical procedure under GA will be included. Patients will be randomised in a 1:1 ratio to the remimazolam group (the GA with remimazolam tosilate within the ERAS protocol group) or propofol group (the GA with propofol within the ERAS protocol group), stratified by general surgery, thoracic surgery and other surgeries (including urological surgery and otolaryngology surgery). The primary outcomes include the 24-hour postoperative quality of recovery-40 score and the rate of intraoperative hypotension. Secondary endpoints include the rate of sedative hypotension requiring treatment, the haemodynamic profiles, the 72-hour postoperative quality of recovery-40 score, the functional anaesthetic capability, adverse events and complications, quality of life within 3 months as well as economic health outcomes. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics committee of Guangdong Provincial People's Hospital (KY-H-2022-005-03-08). Dissemination plans will be presented at scientific meetings and in scientific publications. TRIAL REGISTRATION NUMBER: ChiCTR2200062520.

Effects of double vs triple injection on block dynamics for ultrasound-guided intertruncal approach to the supraclavicular brachial plexus block in patients undergoing upper limb arteriovenous access surgery: study protocol for a double-blinded, randomized controlled trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) has been proposed to be an alternative and promising approach to the supraclavicular block (SCB), in which double injection (DI) of local anesthetics (LA) is sequentially administered between intertruncal planes. We would like to apply a refined injection technique, named triple injection (TI) technique, based on the 3 separate compartments visualized by ultrasound. The aim of this study is to compare the percentage of patients with complete sensory blockade at 20 min of DI vs TI technique, when they are applied in patients undergoing upper limb arteriovenous access surgery. METHODS: This study is a prospective parallel-group randomized controlled trial. A total of 86 end-stage renal disease patients will be randomly allocated to receive IA-SCB using either DI or TI technique with identical LA (0.5% ropivacaine 24 mL). The primary outcome is the percentage of patients with complete sensory blockade of all 4 terminal nerves (median, ulnar, radial, and musculocutaneous nerves) of the brachial plexus measured at 20 min after injection. The secondary outcomes will consist of the sensory or motor blockade of all individual nerves, onset times, performance time, diaphragmatic paralysis, surgical anesthesia, and adverse events. DISCUSSION: It is expected that ultrasound-guided IA-SCB with the TI technique results in better block dynamic in patients undergoing upper limb arteriovenous access surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045075 .

Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure. METHODS: The total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran's study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of - 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events. DISCUSSION: The results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040199 . Registered on 25 November 2020.

[Molecular mechanism underlying the inhibitory effect of propofol on lipopolysaccharide-induced pyroptosis of mouse bone marrow-derived macrophages].

OBJECTIVE: To investigate the molecular mechanism underlying the inhibitory effect of propofol on pyroptosis of macrophages. METHODS: Macrophages derived from bone marrow were extracted and divided into three groups: control group, LPS+ATP group and propofol+LPS+ATP group. The control group was not given any treatment; LPS+ATP group was given LPS 1 µg/mL stimulation for 4 h, then ATP 4 mM stimulation for 1 h; Propofol+LPS+ATP group was given propofol+LPS 1 µg/mL stimulation for 4 h, then ATP stimulation for 1 h. After treatment, the supernatant and cells of cell culture were collected. the cell activity was detected by CCK8 and flow cytometry. The inflammatory cytokines IL-1ßand IL-18 were detected by Elisa. Western blot was used to detect the expression of caspase-1 protein and TLR4 on cell membran Immunohistochemical fluorescence was used to detect apoptosis of cells. RESULTS: LPS+ATP significantly decreased the viability of the macrophages and increased the cellular production of IL-1ß and IL-18, activation of caspase-1 protein and the expression of TLR-4 on the cell membrane (P < 0.05). Treatment with propofol obviously reversed the changes induced by LPS+ATP. CONCLUSIONS: LPS+ATP can induce pyroptosis of mouse bone marrow-derived macrophages, and propofol effectively inhibits such cell death, suggesting that propofol anesthesia is beneficial during operation and helps to regulate the immune function of in patients with sepsis.

Abnormal cisatracurium pharmacodynamics and pharmacokinetics among patients with severe aortic regurgitation during anesthetic induction.

BACKGROUND: This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction. METHODS: A total of 32 patients were divided into two groups: the AR group (n = 16) and the control group (n = 16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 min after intravenous injection of 0.15 mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography. RESULTS: The onset time to maximal neuromuscular block was prolonged from 2.07 ± 0.08 min to 4.03 ± 0.14 min, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P < 0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K12 = 0.19 ± 0.02 and K21 = 0.11 ± 0.01 in the AR group vs. K12=0.26 ± 0.01 and K21 = 0.19 ± 0.01 in the control group, P < 0.01) compared to the control group. CONCLUSION: Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of muscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction. REGISTRATION: Name of the registry: Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction. TRIAL REGISTRATION NUMBER: ChiCTR1800019654. Date of registration: November 20th 2018.

The C2H2 zinc-finger protein SlZF3 regulates AsA synthesis and salt tolerance by interacting with CSN5B.

Abiotic stresses are a major cause of crop loss. Ascorbic acid (AsA) promotes stress tolerance by scavenging reactive oxygen species (ROS), which accumulate when plants experience abiotic stress. Although the biosynthesis and metabolism of AsA are well established, the genes that regulate these pathways remain largely unexplored. Here, we report on a novel regulatory gene from tomato (Solanum lycopersicum) named SlZF3 that encodes a Cys2/His2-type zinc-finger protein with an EAR repression domain. The expression of SlZF3 was rapidly induced by NaCl treatments. The overexpression of SlZF3 significantly increased the levels of AsA in tomato and Arabidopsis. Consequently, the AsA-mediated ROS-scavenging capacity of the SlZF3-overexpressing plants was increased, which enhanced the salt tolerance of these plants. Protein-protein interaction assays demonstrated that SlZF3 directly binds CSN5B, a key component of the COP9 signalosome. This interaction inhibited the binding of CSN5B to VTC1, a GDP-mannose pyrophosphorylase that contributes to AsA biosynthesis. We found that the EAR domain promoted the stability of SlZF3 but was not required for the interaction between SlZF3 and CSN5B. Our findings indicate that SlZF3 simultaneously promotes the accumulation of AsA and enhances plant salt-stress tolerance.

A novel type of highly effective nonionic gemini alkyl O-glucoside surfactants: a versatile strategy of design.

A novel type of highly effective gemini alkyl glucosides has been rationally designed and synthesized. The gemini surfactants have been readily prepared by glycosylation of the gemini alkyl chains that are synthesized with regioselective ring-opening of ethylene glycol epoxides by the alkyl alcohols. The new gemini alkyl glucosides exhibit significantly better surface activity than the known results. Then rheological, DLS, and TEM studies have revealed the intriguing self-assembly behavior of the novel gemini surfactants. This study has proved the effectiveness of the design of gemini alkyl glucosides which is modular, extendable, and synthetically simple. The new gemini surfactants have great potential as nano carriers in drug and gene delivery.