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. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain. Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001). Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain. Clinical trial registration: ClinicalTrials.gov, identifier NCT04958746.

Median Effective Dose of Ciprofol Combined With Sufentanil for Inhibiting the Upper Gastrointestinal Endoscopic Placement Reaction in Elderly Patients.

Objective: Ciprofol is a new sedative anesthetic drug that can be used for gastrointestinal endoscopy and induction of general anesthesia, but the appropriate dosage for use in elderly patients has not been determined. Sufentanil is a commonly used opioid in clinical practice, and this study was designed to induce anesthesia in elderly patients using sufentanil in combination with ciprofol. However, the optimal dosage of ciprofol when it is co-administered with sufentanil has not yet been established. This study was designed to find the median effective dose (ED50) and 95% confidence interval (95% CI) of ciprofol for intravenous anesthesia when combined with sufentanil. Methods: We studied 57 patients who were scheduled to undergo a diagnostic upper gastrointestinal endoscopy. According to age, it was divided into two groups: 65∼74 years old (group A) and over 75 years old (group B). Using the modified Dixon sequence test method, intravenous bolus of 0.1 µg/kg sufentanil was given 3 min before ciprofol is administered, the initial dose of ciprofol was 0.4 mg/kg, the upper gastrointestinal endoscopy was placed after reaching the depth of sedation, and vital signs and adverse events were recorded at each perioperative time point (T0-T7). Results: In the group A, when combined with 0.1 µg/kg sufentanil, the ED50 of ciprofol to inhibiting responses to insertion of upper gastrointestinal endoscopy was 0.23 mg/kg, and the 95% CI was 0.09∼0.30 mg/kg; in the group B, the ED50 was 0.18 mg/kg, and the 95% CI was 0.13∼0.22 mg/kg. Conclusion: The ED50 of ciprofol in combination with sufentanil (0.1 µg/kg) for upper gastrointestinal endoscopy in elderly patients: 0.23 mg/kg in group A and 0.18 mg/kg in group B.

Upstream stimulating factor 2 aggravates neuropathic pain induced in spinal nerve ligation-induced mice via regulating SNHG5/miR-181b-5p.

BACKGROUND: Upstream stimulating factor 2 (USF2) belongs to basic-Helix-Loop-Helix-Leucine Zipper transcription factor family, regulating expression of genes involved in immune response or energy metabolism network. Role of USF2 in neuropathic pain was evaluated. METHODS: Mice were intraspinally injected with adenovirus for knockdown of USF2 (Ad-shUSF2), and then subjected to spinal nerve ligation (SNL) to induce neuropathic pain. Distribution and expression of USF2 was detected by western blot and immunofluorescence. Mechanical and thermal pain sensitivity were examined by paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL). Chromatin immunoprecipitation (ChIP) and luciferase activity assays were performed to detect binding ability between USF2 and SNHG5. RESULTS: The expression of USF2 was elevated and colocalized with astrocytes and microglia in L5 dorsal root ganglion (DRG) of SNL-induced mice. Injection of Ad-shUSF2 attenuated SNL-induced decrease of PWT and PWL in mice. Knockdown of USF2 increased level of IL-10, but decreased TNF-α, IL-1ß, and IL-6 in SNL-induced mice. Silence of USF2 enhanced protein expression of CD206, while reduced expression of CD16 and CD32 in SNL-induced mice. USF2 bind to promoter of SNHG5, and weakened SNL-induced up-regulation of SNHG5. SNHG5 bind to miR-181b-5p, and miR-181b-5p to interact with CXCL5. CONCLUSION: Silence of USF2 ameliorated neuropathic pain, suppressed activation of M1 microglia and inhibited inflammation in SNL-induced mice through regulation of SNHG5/miR-181b-5p/CXCL5 axis. Therefore, USF2/SNHG5/miR-181b-5p/CXCL5 might be a promising target for neuropathic pain. However, the effect of USF2/SNHG5/miR-181b-5p/CXCL5 on neuropathic pain should also be investigated in further research.

Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

Remimazolam vs Etomidate: Haemodynamic Effects in Hypertensive Elderly Patients Undergoing Non-Cardiac Surgery.

Background: Remimazolam tosilate (RT) is a novel ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with several advantages including rapid induction and recovery, stable haemodynamics, and mild respiratory inhibition. However, studies have not been conducted to explore the haemodynamic effects of RT in elderly hypertensive subjects undergoing non-cardiac surgery. Therefore, we sought to compare the effects of anaesthesia induction using different doses of RT and etomidate on the haemodynamics of this group of patients. Methods: Patients were recruited into this single-center, prospective, randomized, double-blind trial from October 2022 to June 2023. A total of 150 hypertensive elderly undergoing non-cardiac surgery were randomly assigned into 0.2 mg/kg RT group (Group RL), 0.3 mg/kg RT group (Group RH) and 0.3 mg/kg etomidate group (Group E). The primary outcome of the study was haemodynamic changes (mean arterial pressure fluctuation value -∆MAP and heart rate fluctuation value -∆HR) observed during anaesthesia induction. Secondary outcomes included incidence of adverse cardiovascular events and adverse drug reactions (injection pain and myoclonus), cumulative doses of vasoactive drugs and vital signs at different time points. Results: Patients in Group E and Group RL had significantly lower haemodynamic fluctuations (∆MAP), lower incidence of hypotension and cumulative dose of ephedrine than subjects in Group RH. Patients in groups RL and RH had significantly lower incidence of injection pain and myoclonus compared with patients in group E. The results showed no statistically significant differences in ∆HR, hypertension, bradycardia, tachycardia, and time to loss of eye-opening reflex and start of intubation, and vital signs at different time points among the three groups. Conclusion: Use of low-dose RT (0.2 mg/kg) for induction of non-cardiac surgical anaesthesia in elderly hypertensive patients is more effective in maintaining haemodynamic stability and has fewer adverse effects compared with etomidate.

The value of serum Lp-PLA2 combined with MPO in the diagnosis of cerebral infarction caused by large artery atherosclerosis.

OBJECTIVE: To explore the value of serum lipoprotein-associated phospholipase A2（Lp-PLA2）combined with myeloperoxidase（MPO）for the diagnosis of large artery atherosclerosis(LAA) cerebral infarction. METHODS: Baseline data were collected from patients with first-ever acute cerebral infarction, serum Lp-PLA2 and MPO levels were measured. The etiology of cerebral infarction was classified according to the Chinese Ischemic Stroke Subtype Classification Standard. The risk factors associated with LAA cerebral infarction were identified by univariate and multivariate regression analysis. The diagnostic value of serum Lp-PLA2 and MPO for LAA cerebral infarction was assessed by the area under the receiver-operating characteristic (ROC) curve. RESULTS: Overall 368 patients were involved, 148 patients (40.22 %) were LAA. The serum La-PLA2 and MPO levels were higher in the LAA group than those in non-LAA group (23.06 ± 3.39 ng/mL versus 17.48 ± 3.26 ng/mL; 93.60 ± 9.58 ng/mL versus 75.98 ± 15.53 ng/mL; P < 0.001 for both). Multivariate analysis showed that elevated levels of serum Lp-PLA2 (OR 1.742, 95 %CI 1.499-2.025; P < 0.001) and MPO (OR 1.060, 95 % CI 1.026-1.096; P = 0.001) were the independent risk factors of LAA cerebral infarction. The area under curve of the serum Lp-PLA2 combined with MPO for the diagnosis of LAA cerebral infarction was 0.896 [0.866 ∼ 0.927] (P < 0.001). CONCLUSION: Serum Lp-PLA2 combined with MPO could be valued as a predictor of acute cerebral infarction caused by large artery atherosclerosis.

Identification of ferroptosis-related genes in male mice with sepsis-induced acute lung injury based on transcriptome sequencing.

BACKGROUND: Sepsis can result in acute lung injury (ALI). Studies have shown that pharmacological inhibition of ferroptosis can treat ALI. However, the regulatory mechanisms of ferroptosis in sepsis-induced ALI remain unclear. METHODS: Transcriptome sequencing was performed on lung tissue samples from 10 sepsis-induced mouse models of ALI and 10 control mice. After quality control measures, clean data were used to screen for differentially expressed genes (DEGs) between the groups. The DEGs were then overlapped with ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FR-DEGs). Subsequently, least absolute shrinkage and selection operator (Lasso) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were used to obtain key genes. In addition, Ingenuity Pathway Analysis (IPA) was employed to explore the disease, function, and canonical pathways related to the key genes. Gene set enrichment analysis (GSEA) was used to investigate the functions of the key genes, and regulatory miRNAs of key genes were predicted using the NetworkAnalyst and StarBase databases. Finally, the expression of key genes was validated with the GSE165226 and GSE168796 datasets sourced from the Gene Expression Omnibus (GEO) database and using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Thirty-three FR-DEGs were identified between 1843 DEGs and 259 FRGs. Three key genes, Ncf2, Steap3, and Gclc, were identified based on diagnostic models established by the two machine learning methods. They are mainly involved in infection, immunity, and apoptosis, including lymphatic system cell migration and lymphocyte and T cell responses. Additionally, the GSEA suggested that Ncf2 and Steap3 were similarly enriched in mRNA processing, response to peptides, and leukocyte differentiation. Furthermore, a key gene-miRNA network including 2 key genes (Steap3 and Gclc) and 122 miRNAs, and a gene-miRNA network with 1 key gene (Steap3) and 3 miRNAs were constructed using NetworkAnalyst and StarBase, respectively. Both databases predicted that mmu-miR-15a-5p was the target miRNA of Steap3. Finally, Ncf2 expression was validated using both datasets and qRT-PCR, and Steap3 was validated using GSE165226 and qRT-PCR. CONCLUSIONS: This study identified two FR-DEGs (Ncf2 and Steap3) associated with sepsis-induced ALI via transcriptome analyses, as well as their functional and metabolic pathways.

Comparison of Remimazolam Tosilate and Etomidate on Hemodynamics in Cardiac Surgery: A Randomised Controlled Trial.

Background: Remimazolam tosilate (RT) is a new ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with the characteristics of rapid onset and offset, minimal cardiorespiratory depression. Currently, few studies have compared the effect of RT and etomidate on hemodynamics during anesthesia induction. Here, we aimed to compare the hemodynamic effects of different doses of RT and etomidate for anesthesia induction in patients undergoing cardiac surgeries. Methods: Patients were recruited from January to September 2022 in this single-center, prospective, randomized, double-blind trial. A total of 117 patients undergoing selective valve replacement surgery were randomly divided into low-dose RT (0.2 mg/kg) group (group LR), high-dose RT (0.3 mg/kg) group (group HR), or etomidate (1.5 mg/kg) group (group E), respectively. The primary outcome was hemodynamic fluctuations (mean arterial pressure fluctuation value [∆MAP]; heart rate fluctuation value [∆HR]) during anesthesia induction. Secondary outcomes included the incidence of adverse drug reactions (injection pain and myoclonus) and adverse cardiovascular events, vital signs at different time points and the cumulative doses of vasoactive drugs. Results: The hemodynamic fluctuations (∆MAP) in group LR and group E were significantly lower than that in group HR. In addition, the incidence of hypotension and the cumulative norepinephrine doses in group E and group LR were also significantly lower than that in group HR. Furthermore, the incidence of injection pain and myoclonus in group LR and group HR were less frequently recorded compared with group E. There were no significant differences in terms of ∆HR, tachycardia, hypertension, severe bradycardia, vital signs at different time points, lactic acid and blood glucose between both groups. Conclusion: Compared with etomidate, low-dose RT (0.2mg/kg) can not only provide stable hemodynamic parameters but also cause fewer adverse reactions when used for anesthesia induction in patients with cardiac disease.

Efficacy and safety of ciprofol vs. propofol for the induction and maintenance of general anaesthesia: A multicentre, single-blind, randomised, parallel-group, phase 3 clinical trial.

BACKGROUND: HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABA A ) receptor. OBJECTIVE: To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN: A single-blinded, randomised, parallel-group, phase 3 trial. SETTING: Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS: A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonneurosurgical elective surgery. INTERVENTION: Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg -1 ) or propofol (2.0 mg kg -1 ) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg -1 h -1 , and were adjusted to maintain a bispectral index (BIS) of 40-60 until the end of surgery. MAIN OUTCOME MEASURES: Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >-8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS: Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI -4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P  > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P  = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P  = 0.451) in the HSK3486 and propofol groups. CONCLUSION: HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04511728.

Effect of remimazolam tosilate versus etomidate on hemodynamics in patients undergoing valve replacement surgery: study protocol for a randomized controlled trial.

BACKGROUND: Patients with a history of cardiac disease are prone to develop cardiovascular adverse events such as hypotension, hypertension, and tachycardia during anesthesia induction. Therefore, hemodynamic stability is one of the most important concerns for induction of anesthesia in patients undergoing cardiac surgery. Remimazolam tosilate is a new, ultra-short-acting benzodiazepine agent, with the advantages of rapid onset, rapid offset, and minimal cardiorespiratory depression. We aim to compare the effect of remimazolam tosilate and etomidate on hemodynamics during anesthesia induction in patients undergoing valve replacement surgery. METHODS/DESIGN: The trial is a prospective, randomized, double-blinded, controlled, single-center trial to compare the effect of remimazolam tosilate and etomidate on hemodynamics in patients undergoing valve replacement surgery. One hundred seventeen patients undergoing selective valve replacement surgery between January 1, 2022, and December 31, 2023, will be enrolled and randomly allocated into one of three groups: low-dose remimazolam group (Group LR), high-dose remimazolam group (Group HR), or etomidate group (Group E). The primary outcome is hemodynamic fluctuations during anesthesia induction (the difference between mean arterial pressure [MAP] to baseline, ▴MAP; and the difference between maximum or minimum heart rate [HR] and baseline, ▴HR). Secondary outcomes include the incidence of adverse cardiovascular events (hypotension, severe bradycardia, hypertension, tachycardia, and arrhythmia), the cumulative doses of vasoactive drugs used per patient, incidence and degree of injection pain and myoclonus, blood glucose values, and vital signs at different time points. DISCUSSION: This research will determine the effectiveness and safety of remimazolam tosilate induction on hemodynamics in patients undergoing valve replacement surgery. TRIAL REGISTRATION: www.chictr.org .cn identifier ChiCTR2100052535 . Registered on 17th Dec 2021, http://www.chictr.org.cn/ ).

Effect of Remimazolam Tosilate on Respiratory Depression in Elderly Patients Undergoing Gastroscopy: A Multicentered, Prospective, and Randomized Study.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABAA) receptor agonist, having the possibility to be an ideal sedative drug for procedural sedation. At present, there are few studies on the effect of RT on respiratory depression in elderly patients. We aimed to evaluate the effect of RT on respiratory depression in elderly patients undergoing gastroscopy. Methods: This prospective, randomized, single-blinded trial recruited patients from eight centers in China between May 2022 and July 2022. A total of 346 elderly patients undergoing gastroscopy were randomly divided into RT group (0.2 mg/kg) or propofol group (1.5 mg/kg), respectively. The primary outcome was the incidence of respiratory depression. Secondary outcomes include the incidence of sedative-related adverse events, the success rate of sedation, time to fully alert, time to loss of consciousness (LOC), time to ready for discharge, as well as the the patients, endoscopists and anethetists' satisfaction. Results: The incidence of respiratory depression was significantly reduced in the RT group compared with the propofol group (9.8% vs 17.9%, P=0.042). The time of LOC and fully alert in the RT group were longer than that in the propofol group (P < 0.05). The incidences of hypotention (50.9% vs 32.4%, P=0.001) and hypotension requiring treatment (5.8% vs 1.7%, P=0.031) were significantly higher in the propofol group than that in the RT group. The incidence and severity of injection pain were more frequently recorded in the propofol group than that in the RT group (40.5% vs 12.1%, P<0.05). There were no statistically significant differences between the two groups in terms of sedation success rates, time to ready for discharge, endoscopists and anethetists' satisfaction and other sedative-related adverse events. Conclusion: RT may be a suitable alternative sedative agent for elderly patients undergoing gastroscopy due to its safety profile.

Rapid Detection of Strawberry Mild Yellow Edge Virus with a Lateral Flow Strip Reverse Transcription Recombinase Polymerase Amplification Assay.

Strawberry mild yellow edge virus (SMYEV) is a latent virus that severely affects the yield and quality of strawberry fruit. The technology suitable for rapid and accurate detection of SMYEV on site is important to effectively control its spread. In this study, a reverse transcription recombinase polymerase amplification combined with lateral flow strip (SMYEV-RT-RPA-LF), targeting the conserved genome of Beijing SMYEV isolate, was established to diagnose SMYEV in strawberries. The SMYEV-RT-RPA-LF assay showed no cross-reaction with other strawberry viruses. The sensitivity of SMYEV-RT-RPA-L assay was 100 times higher than that of RT-PCR (10 pg/µL). In addition, through the detection of suspected samples in the field, it was found that the accuracy of SMYEV-RT-RPA-L assay was consistent with the RT-PCR results. However, compared with RT-PCR, SMYEV-RT-RPA-LF assay has the advantages of simple operation, time savings, and high specificity and sensitivity, indicating the potential application of SMYEV-RT-RPA-LF in the rapid field diagnosis of SMYEV.

Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.

As one of the common complications of diabetes mellitus (DM), Diabetic Peripheral Neuropathy (DPN) threatens human lives seriously. Emerging evidences have confirmed the protective effects of lidocaine on DPN. However, the possible role and underlying mechanisms of lidocaine in DPN have not been clarified. In this study, the potential role of lidocaine in DPN is explored, and the possible mechanisms are investigated. The rat DPN model is constructed through administration of streptozotocin (STZ, 60 mg/kg). All rats are randomly divided into four groups, including the control group, DPN group, lidocaine (3.78 mg/time) group, and lidocaine combined with the SP600125 (15 mg/kg) group. Mechanical threshold, thermal latency, and blood glucose of rats before and after treatment are detected, and Nerve Conduction Velocity (NCV) is assessed. Moreover, qRT-PCR and western blot assays are carried out to determine the expressions of the c-Jun signaling pathway. The experimental results demonstrate that lidocaine remarkably downregulates the mRNA and protein expressions of the c-Jun signaling pathway in serum and DRGs induced with DPN. Besides, lidocaine combined with SP600125 can obtain better effects than lidocaine alone. It is clearly evident that lidocaine has a certain therapeutic effect on DPN.

Effect of different doses of esketamine compared with fentanyl combined with propofol on hypotension in patients undergoing painless abortion surgery: a prospective, randomized, double-blind controlled clinical trial.

BACKGROUND: Opioids analgesics commonly used in abortion procedures are associated with respiratory and circulatory depression. Esketamine is a N-methyl-D-aspartate receptor (NMDA) antagonist and a common analgesic. The drug has several advantages including rapid onset and offset and it causes minimal cardiorespiratory depression. However, studies have not explored the effects of esketamine in patients undergoing painless abortion surgery. Therefore, the present study sought to evaluate the effect of different doses of esketamine compared with the effect of fentanyl on incidence of perioperative hypotension in patients undergoing painless abortion surgery and to explore the optimal esketamine dose for this population. METHODS: A total of 178 female patients undergoing painless abortion surgery were enrolled to the current study. The patients were aged 18-45 years, had a body mass index (BMI) of 18-28 kg m- 2 and a class I or II physical status as determined using the American Society of Anesthesiologists (ASA) system. Patients were randomly assigned to four groups as follows: group F (n = 45) in which patients underwent intravenous (IV) administration of 1 µg kg- 1 fentanyl followed by IV administration of 2 mg kg- 1 propofol, and group EL, group EM and group EH (n = 45, 44, 44) with patients receiving IV administration of 0.2 mg kg- 1, 0.25 mg kg- 1, 0.3 mg kg- 1 esketamine, respectively, followed by IV administration of 2 mg kg- 1 propofol. The primary outcome of the study was the incidence of hypotension whereas secondary outcomes included incidence of adverse events, perioperative changes of vital signs, anesthesia induction time, recovery time and dischargeable time, propofol addition, as well as patient, surgeon and anesthesiologist satisfaction levels. RESULTS: The findings showed that the incidence of hypotension was significantly lower in subjects in group EL, group EM and group EH (0, 0, 0%) relative to the incidence in patients in group F (20%) (χ2 = 19.648; P = 0.000). In this study, the incidence of hypoxia of subjects in group EL, group EM and group EH (0, 2.3, 2.3%) was significantly lower compared with that of patients in group F (11.1%) (χ2 = 8.622; P = 0.035). The findings indicated that the incidence of somatic motor reactions was significantly lower in participants in group EM and group EH (9.1, 4.5%) relative to that of patients in group F and group EL (26.7, 15.6%) (χ2 = 10.254; P = 0.016). The results showed that the incidence of nausea and vomiting and potential psychiatric symptoms were significantly higher in patients in group EH (15.9, 11.4%) compared with that of participants in group F (2.2, 0%), group EL (4.4, 0%) and group EM (2.3, 2.3%) (χ2 = 7.493; P = 0.038 and χ2 = 8.248; P = 0.003). In this study, the mean arterial pressure (MAP) and heart rate (HR) of subjects in group EL, group EM and group EH were more stable compared with that of patients in group F. Frequency of the additional propofol dose was markedly less in group EM and EH (26.7%, 17,8%) compared with that in group F and EL (9.1, 4.5%) (χ2 = 10.254; P = 0.016). The findings indicated that the dischargeable time was significantly shorter for patients in group EM compared with that of subjects in group F, group EL and group EH. CONCLUSIONS: The findings of the present study showed that single-dose esketamine (0.25 mg kg- 1) effectively decreased incidence of hypotension and total adverse events and reduced the frequency of additional propofol dose required for patients undergoing painless abortion with preservation of physician-patient satisfaction.

Rapid detection of strawberry mottle virus using reverse transcription recombinase polymerase amplification with lateral flow strip.

Strawberry mottle virus (SMoV) is one of the main RNA viruses that profoundly affects the growth of strawberries worldwide. The rapid on-site detection of SMoV described here can be applied to produce virus-free strawberry seedlings. Reverse transcriptase recombinase polymerase amplification (RT-RPA) was combined with lateral flow (LF) strip to rapidly detect SMoV. The detection limit was 500 fg of RNA under optimized conditions. The SMoV-RT-RPA-LF assay was optimal with a combination of 2 µL reverse primer (5 µM) and 0.6 µL probe (10 µM) in a 50 µL RT-RPA reaction mixture for isothermal amplification at 40 â„ƒ for 15 min. In addition, 100 suspected samples were collected from different regions in the Shanghai suburbs. The SMoV-RT-RPA-LF assay showed that 3 of these 100 samples were positive for SMoV, which was in good concordance with the reverse transcription polymerase chain reaction (RT-PCR) results. The primers and probe had a unique specificity to SMoV because there was no cross-reaction with other strawberry viruses. This study provides an effective technique for the rapid on-site detection of SMoV to ensure a virus-free strawberry nursery.

Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study.

BACKGROUND: Fiberoptic bronchoscopy is a complex procedure with the need for sufficient patient anesthesia/sedation while maintaining safety. This trial aimed to evaluate the efficacy, safety, and pharmacokinetics of HSK3486 during fiberoptic bronchoscopy. METHODS: This multicenter, double-blind, randomized, non-inferiority, parallel-group phase 3 trial was conducted in patients who underwent fiberoptic bronchoscopy. Patients randomly received HSK3486 0.4 mg/kg (N = 134) or propofol 2.0 mg/kg (N = 133). The primary efficacy endpoint was the successful rate of fiberoptic bronchoscopy, and secondary efficacy endpoints included successful induction of anesthesia/sedation, duration, time to being fully alert, and time to patient discharge. Safety assessments and drug concentrations were also measured. RESULTS: A total of 267 patients completed fiberoptic bronchoscopy, with a success rate of 100% and a 95% confidence interval of - 2.8 to 2.8% for the difference between the groups, which met the predesigned criteria of > - 8%, confirming the non-inferiority of anesthesia/sedation produced by HSK3486 compared to propofol. Among the secondary efficacy endpoints, only time to full alertness (median 8.50 vs. 6.00 min, P = 0.012) and time to discharge (median 13.00 vs. 9.87 min, P = 0.002) were slightly longer in the HSK3486 group. The incidence of adverse events was significant lower in the HSK3486 group (52.6 vs. 76.5%, P < 0.001) mainly because of less pain on injection (4.4 vs. 39.4%, P < 0.001) compared to the propofol group. HSK3486 had a similar terminal elimination half-life as propofol. CONCLUSIONS: HSK3486 exhibited non-inferiority anesthesia/sedation compared to propofol in patients undergoing fiberoptic bronchoscopy, and had a good safety profile with a lower incidence of pain on injection. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04111159, registered on 1 October 2019.

Genome-wide identification of expansin in Fragaria vesca and expression profiling analysis of the FvEXPs in different fruit development.

Strawberry is a highly efficient and economical horticultural crop plant, and strawberry fruits are easy to soften after ripening and decay after harvest, which severely impacts the economic benefits. Expansins are plant cell-wall loosening proteins involved in the process of fruit softening, loosening cell walls and reducing fruit firmness. In this study, 35 FvEXPs genes were identified in the F. vesaca genome. These genes were divided into four subfamilies (27 FvEXPAs, 5 FvEXPBs, 1 FvEXLAs, and 2 FvEXLBs) and were unevenly distributed on 7 chromosomes. Gene structure and motif analysis showed the conserved structure and motif in same subgroup, however, the different motifs and structures may reveal functional divergence of multigene family members of FvEXPs in different developmental stages of fruits. The expression profiling by RNA-seq and qRT-PCR analysis revealed that the FvEXP genes have distinct expression patterns among different stages of strawberry development and ripening. Among them, 3 genes (FvEXPA9, FvEXPA12, and FvEXPA27) were highly expressed in the ripening stage, FvEXPA9 and FvEXPA12 were especially highly expressed in turning stage, whereas FvEXPA27 was especially highly expressed in red stage. Our study provides a better understanding of the FvEXP genes, which may benefit strawberry biotechnological breeding and genetic modification for improving fruit quality and delaying fruit softening.