Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

Objective:To evaluate the effect of the remimazolam-flumazenil regimen on the emergence of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Methods:Eighty-four American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, regardless of gender, aged 18-78 yr, with body mass index of 18-30 kg/m 2, undergoing elective ERCP under general anesthesia, were allocated into 2 groups ( n=42 each) using a random number table method: remimazolam-flumazenil group (RF group) and propofol group (P group). Anesthesia was induced as follows: Remimazolam 0.2 mg/kg and remifentanil 2 μg/kg were intravenously injected in RF group, and propofol 1.5 mg/kg and remifentanil 2 μg/kg were intravenously injected in P group. Anesthesia was maintained as follows: Remimazolam was intravenously infused at a rate of 0.5-2.0 mg·kg -1·h -1 and remifentanil at a rate of 0.1-0.2 μg·kg -1·min -1 in RF group, and propofol was intravenously infused at a rate of 2-8 mg·kg -1·h -1 and remifentanil at a rate of 0.1-0.2 μg·kg -1·min -1 in P group, maintaining a bispectral index value of 40-60. At the end of procedure, RF group received an intravenous injection of flumazenil at 0.2 mg, while P group received an equal volume of normal saline. The emergence time, laryngeal mask removal time, duration of post-anesthesia care unit stay, development of adverse events during the emergence period, patients′ satisfaction scores, endoscopists′ satisfaction scores, and 15-item Quality of Recovery scale scores at 24 h after operation were recorded. Results:Compared to P group, the emergence time, laryngeal mask removal time and duration of post-anesthesia care unit stay were significantly shortened, and the incidence of euphoria was decreased in RF group ( P<0.05). There were no statistically significant differences between the two groups in the incidence of agitation, dizziness, nausea/vomiting, and re-sedation, patients′ satisfaction scores, endoscopists′ satisfaction scores, and 15-item Quality of Recovery scale scores at 24 h after operation ( P>0.05). Conclusions:Compared to propofol, the remimazolam-flumazenil regimen can shorten the emergence time and improve the quality of recovery when used for ERCP procedures.

OBJECTIVES: Spinal cord ischemia-reperfusion injury (SCIRI) remains a major challenge in the field of organ protection due to the lack of effective prevention and therapeutic strategies. Hyperglycemia, a common perioperative condition, contributes to neurological injury via multiple mechanisms. However, its role and underlying mechanism in SCIRI are still unclear. This study aims to investigate the involvement of the precursor of brain-derived neurotrophic factor (proBDNF) in hyperglycemia-induced SCIRI in mice. METHODS: Eight-week-old male C57BL/6 mice were randomly assigned to a control group (Vehicle) or a diabetes mellitus (DM) group. The DM group was established using intraperitoneal injection of streptozotocin (STZ) combined with 10% sucrose water. The Vehicle group received an equal volume of 50 mmol/L sodium citrate buffer (pH 4.5). Fasting blood-glucose levels ≥11.1 mmol/L were considered successful DM modeling. Both Vehicle and DM groups underwent SCIRI modeling via descending aortic clamping, while the Sham group underwent a sham procedure without aortic occlusion. Lower limb motor function was assessed using the Basso Mouse Scale (BMS) and its subscale (sub-BMS). Locomotor activity was evaluated using an open field test. Immunohistochemistry was performed to detect changes in neuronal nuclear protein (NeuN) and proBDNF expression in spinal cord tissues. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). To explore the effect of proBDNF inhibition, diabetic mice were divided into groups: A DM+SCIRI+monoclonal anti-proBDNF antibody (McAb-proB) group received an intraperitoneal injection of 100 μg of McAb-proB 30 minutes before SCIRI modeling, and a DM+SCIRI+Vehicle group received an equal amount of isotype immunoglobulin G. BMS and sub-BMS scores were recorded, and the gene expression of inflammatory cytokines mentioned above were evaluated. RESULTS: Compared with the Vehicle+SCIRI group, the DM+SCIRI group showed significantly reduced BMS and sub-BMS scores, decreased NeuN expression, shorter total movement distance, slower locomotion, increased proBDNF expression, and elevated IL-1β, IL-6, and TNF-α mRNA levels (all P<0.05 or P<0.01). Compared with the DM+SCIRI+Vehicle group, the DM+SCIRI+McAb-proB group exhibited significantly improved BMS and sub-BMS scores and decreased mRNA expression of IL-1β, IL-6, and TNF-α (all P<0.05 or P<0.01). CONCLUSIONS Hyperglycemia exacerbates neural injury and inflammatory response in SCIRI through upregulation of proBDNF expression, delaying motor functional recovery. Antagonizing proBDNF expression can alleviate neurological damage and promote functional recovery in diabetic mice after SCIRI.
Animals ; Male ; Hyperglycemia/metabolism* ; Brain-Derived Neurotrophic Factor/genetics* ; Mice, Inbred C57BL ; Reperfusion Injury/metabolism* ; Mice ; Diabetes Mellitus, Experimental/metabolism* ; Inflammation/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Protein Precursors/genetics* ; Spinal Cord Ischemia/metabolism* ; Interleukin-6/metabolism* ; Interleukin-1beta/metabolism*

Objective:To evaluate the effect of remimazolam on hemodynamics when used for anesthesia induction in patients undergoing coronary artery bypass grafting (CABG).Methods:Sixty patients of either sex, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ-Ⅲ, with ejection fraction>35%, cardiac index (CI) >2.0 L·min -1·m -2 and body mass index <28 kg/m 2, undergoing CABG under general anesthesia, were divided into 2 groups ( n=30 each)using a random number table method: remazolam group (group R) and midazolam group (group M). Group R received intravenous remimazolam 0.08 mg/kg, and group M received intravenous midazolam 0.05 mg/kg, and both groups used sufentanil, etomidate, and rocuronium bromide for anesthesia induction to maintain the BIS value at 40-65. Before anesthesia induction, at 1-2 min after intravenous injection of remimazolam/midazolam-sufantanil-etomidate, immediately before tracheal incubation, at 30 s-15 min after tracheal intubation, and immediately before skin incision, blood pressure, heart rate, mean arterial pressure, CI, stroke volume index, systemic vascular resistance index, and left heart systolic index were measured, and vasoactive drugs were used to maintain the stability of vital signs and to record the cardiovascular events. Results:Compared with group M, the incidence of hypotension and usage rate of vasoactive drugs were significantly decreased, and the incidence of decrease in CI and stroke volume index by more than 20% and changes in left heart systolic index were decreased in group R( P<0.05). Conclusions:Remimazolam can reduce the disturbance of hemodynamics to a certain extent when used for anesthesia induction as compared with midazolam in patients undergoing CABG.

Objective:Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection.Due to lack of effective treatments,it has always been the difficulty and focus of clinical treatment of sepsis.Studies have shown that pro-brain-derived neurotrophic factor(proBDNF)binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor(p75NTR),which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. Methods:From the healthy donors(control group,n=40)and sepsis patients(sepsis group,n=40)admitted to the hospital for the first time,peripheral blood samples and blood routine clinical detection indicators were obtained.By using flow cytometry,the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined.The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide(LPS).Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets.On this basis,we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. Results:White blood cell count,neutrophil count,and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group;on the contrary,lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group(all P＜0.001).The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group(both P＜0.05).In the peripheral blood of sepsis patients,proBDNF expression was upregulated on CD19+ B cells,whereas p75NTR expression was elevated on B cells,CD4+ T cells,and CD8+ T cells(all P＜0.05).ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group(P＜0.05),and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group.Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages,cytokine expression of IL-4 and IL-10,and reduced IL-1β and IL-6 production(all P＜0.05). Conclusion:The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils.ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients,and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.

Since the outbreak of COVID-19, the prevention and control of nosocomial infections has been highly valued. Airway management, including endotracheal intubation, extubation, and suction, has been considered as the high-risk virus-spreading procedures, which can put the health providers at a high risk of nosocomial infections. As hospitals at all levels will gradually resume their routine medical work, effective managements for the airway of the silent asymptomatic carriers and patients with delayed symptoms, treatment for severe patients, and prevention of cross infection in hospital have become the focus for the current prevention and control of nosocomial infections. Under the guidance of partitioned and graded prevention and differential control strategies at this stage, we comprehensively analyzed four main intubation methods used in the current clinical work including rapid sequence intubation, laryngeal mask insertion, intubation guided by video flexible intubating scope and awake tracheal intubation. Furthermore, we discussed and summarized intubation and protection strategies for 3 categories of patients during the COVID-19 pandemic, providing evidence for protecting medical stuff in operating room and ICU against severe acute respiratory syndrome coronavirus 2 infection.
Airway Management ; Betacoronavirus ; Coronavirus Infections ; prevention & control ; therapy ; Cross Infection ; prevention & control ; Humans ; Intubation ; Laryngeal Masks ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control ; therapy

Objective: To explore the imaging and clinical features of Behcet's disease with coronary artery involvement in order to improve the diagnosis and treatment in clinical practice. Methods: A total of 6 Behcet's disease patients with coronary involvement diagnosed and treated in our hospital from 1999-08 to 2016-11 were analyzed. Coronary angiography (CAG) and coronary CTA were performed for diagnosis. There were 5 cases received CAG and 5 cases received CTA examinations. Results: All 6 patients had the first clinical visit by sudden pericardial tapenade, myocardial infarction or cardiac shock. For diagnosis: the imaging presentation included coronary stenosis, occlusion and pseudo aneurysm formation. 3 patients had anterior descending artery involvement, 1 had the far-end of left circumflex involvement and 2 had the middle segment of right coronary involvement; all patients were combining large amount of pericardial effusion. For treatment: there were 3 patients with aneurysm received conservative treatment (1 case had open thoracic exploration), 1/3 lost contact and 2 having long-term normal life; 3 patients received coronary stent implantation without optimal effect. Conclusion: The patients of Behcet's disease with coronary involvement may easily form pseudo aneurysm; CAG/CTA has been helpful for diagnosis. Clear pre-operative diagnosis of etiology is important for treatment.

Objective To investigate the expression of interleukin-6 (IL-6) and its role in incisional pain in the rat model.Methods Incisional pain rat model was established by a longitudinal incision in right plantar hind paw of isoflurane-anesthetized rats.Spinal cords were removed at various postoperative times (1,6,24,72 h).The gene expression of IL-6 in the spinal cord was determined by a Real-time PCR.Immunohistochemistry and double-labeling immunofluorescence were performed to determine the expression of IL-6 after incision.Intrathecal injection of IL-6 antibodies was performed to modulate the spinal IL-6 after surgical incision,and the mechanical hypersensitivity was assessed by paw withdrawal thresholds from mechanical stimuli of von Frey filaments.Results After hind-paw incision,the IL-6 mRNA level was upregulated in the ipsilatcral lumbar spinal cord.The immunoreactivity of IL-6 in spinal cord was increased after hind-paw incision at 6 hours after incision.The upregulated spinal IL-6 was mainly localized in the neurons and endothelial cells.Intrathecal injection of IL-6 antibodies dramatically inhibited the surgical incision that evoked pain hypersensitivity.Conclusions The present study showed that the upregulated IL-6 in the spinal cord contributed to the pain hypersensitivity after surgical incision,inhibiting the upregulated IL-6 in the spinal cord may be a possible new therapeutic target for the treatment of postoperative pain.

OBJECTIVETo investigate the retrograde changes in the dorsal motor nuclei (DMV) of the vagus nerve after vagotomy in rats.

METHODSNissl staining and immunohistochemistry were used to observe the morphological and quantitative changes of the DMV and alterations of the expression of iNOS and NADPH after severing of the vagus nerve in adult male Wistar rats.

RESULTSCompared with the control group, the rats with right vagotomy showed obvious morphological changes and a significantly decreased number of neurons in the right DMV (P<0.05). Numerous iNOS- and NADPH-immunopositive cells were detected in the right DMV 5 and 10 days after right vagotomy.

CONCLUSIONVagotomy causes obvious retrograde changes in rat DMV shown by a significantly decreased number and obvious morphological changes of the neurons in the DMV.

Animals ; Male ; NADP ; metabolism ; Neurons ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vagotomy ; Vagus Nerve ; pathology ; physiopathology ; surgery

OBJECTIVE: To develop a molecular genetic assay to detect the GJB2 235 delC and mtDNA A1555G mutations simultaneously based on fluorescent labeled multiplex PCR and automatic DNA fragment analyzing techniques. METHOD: One hundred and twenty samples were pooled in our experiment to test the feasibility of new method. The PCRs were performed and the size fragment of PCR products were analyzed on ABI 3100 Genetic Analyzer. Data analysis were taken using the software package of GeneScan and GeneMarker. RESULT: Seventeen samples of DNA with 235 delC and 17 samples with A1555G were tested using this protocol. A false-positive sample without GJB2 235 delC mutation was tested. CONCLUSION This assay can detect both mutations in pooled DNA tests and will be a useful tool for newborn screening and carrier screening for the hereditary hearing loss in Chinese population.
Connexin 26 ; Connexins ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Genetic Testing ; methods ; Hearing Loss ; diagnosis ; genetics ; Heterozygote ; Humans ; Mutation ; Polymerase Chain Reaction ; methods