Prognostic mutations identified by whole-exome sequencing and validation of the Molecular International Prognostic Scoring System in myelodysplastic syndromes after allogeneic haematopoietic stem cell transplantation.

In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis.

Dexmedetomidine mitigates neuroinflammation and improves early postoperative neurocognitive dysfunction in rats by enhancing autophagy.

Postoperative neurocognitive dysfunction (PND) is a common postoperative complication. Autophagy is correlated with the pathogenesis of PND. This study investigated the potential role of autophagy in the neuroprotection of dexmedetomidine (Dex) pretreatment in PND. The PND rat model was established by abdominal surgery. The cognitive function of rats was evaluated by Y-maze 3 days after surgery. Nissl staining assessed postoperative hippocampal damage. Immunofluorescence detected the expression of microglial activation (Iba-1) and autophagy-related protein (LC3B) in hippocampal tissues. Western blot detected the autophagy-related protein expression (Beclin 1, LC3B, and p62), proinflammatory cytokines, and the protein activation of the autophagy-related LKB1/AMPK/ULK-1 signaling pathway. RT-PCR quantified the expression of IL-1ß, TNF-α, and IL6. In this study, we found that Dex pretreatment improved spatial memory function impairment and reduced abdominal surgery-induced hippocampal tissue damage. Dex pretreatment significantly increased the expression of Beclin 1 and LC3 II/I and decreased the expression of p62 in the hippocampus after surgery. Furthermore, Dex effectively inhibited microglial activation and proinflammatory cytokines by enhancing autophagy in the hippocampus. Pretreatment with 3-MA, an autophagy inhibitor, significantly weakened the inhibitory effect of Dex on postoperative neuroinflammation. We further demonstrated that Dex suppressed surgery-induced neuroinflammation by activating the LKB1/AMPK/ULK-1 signaling pathway. In conclusion, our study indicated that Dex inhibited hippocampal neuroinflammation and ameliorated PND by enhancing autophagy after surgery in rats, which was related to the LKB1/AMPK/ULK-1 signaling pathway. These findings provide a potential therapeutic prospect for PND.NEW & NOTEWORTHY Dex inhibits hippocampal neuroinflammation and attenuates early cognitive impairment by enhancing autophagy following surgery in rats. Dex may protect postoperative cognitive function by activating the LKB1/AMPK/ULK-1 signaling pathway.

Superposed three-dimensional 64QAM constellation design for MIMO-OFDM visible light communication systems.

Multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) has been widely used to improve data rate in visible-light communication (VLC) systems. However, the high correlation of channels restricts the application of MIMO. A superposed constellation, combined with MIMO, can achieve considerable diversity gain even in highly correlated MIMO channels. In this study, what we believe to be novel superposed three-dimensional 64-quadrature amplitude modulation (3D-64QAM) constellation schemes are proposed for MIMO-OFDM VLC systems. First, a superposed 3D-64QAM constellation scheme using two transmitted light emitting diodes (LEDs) is proposed, where two independent signals with 3D-4QAM and 3D-16QAM modulation formats are superposed to form a 3D-64QAM signal at the receiver. Then, for what we believe is the first time, we expand the superposed constellation solution to three-LED application scenarios, wherein the 3D-64QAM constellation is superposed by three different 3D-4QAM constellations. Both schemes benefit from a higher minimum Euclidean distance of 3D-64QAM constellation, 1.67 times that of traditional two-dimensional (2D) 64QAM constellation. Meanwhile, the equal-power superposition design of transmitted signals reduces the nonlinearity of LEDs and power competition of photodiodes. Moreover, the three-LED scheme further improves the transmitted power without increasing the risk of nonlinear distortion. To improve spectral efficiency and reduce complexity, we also propose a 3D OFDM modulation scheme. The superposed 3D-64QAM schemes are first studied through theoretical analysis and computer simulation. Then, an experimental demonstration is established to investigate the system performance comprehensively. Experimental results prove that the superposed 3D-64QAM constellation schemes achieve a superior bit error rate (BER) performance than the traditional superposed 2D-64QAM constellation scheme. Compared with two-LED scheme, the three-LED scheme not only obtains a lower BER, but also improves the dynamic range of driving peak-to-peak voltage significantly.

Analgesic Efficacy of Quadratus Lumborum Block in Patients Undergoing Nephrectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the analgesic efficacy of quadratus lumborum block (QLB) in adults undergoing nephrectomy. DESIGN: Systematic review and meta-analysis. PATIENTS: Adult patients (≥18 years of age) received nephrectomy under general anesthesia. METHODS: We searched PubMed, Embase, the Cochrane Library, and Web of Science on January 10, 2022, including randomized controlled trials that evaluated the analgesic efficacy of QLB for patients undergoing nephrectomy. RESULTS: A total of 12 randomized controlled trials (N = 821 patients) were included in the study. Compared with the non-block, single-shot QLB reduced postoperative opioid consumption (mean difference [MD], -8.37 mg intravenous morphine equivalent; 95% confidence interval [CI], -12.19 to -4.54 mg) and pain scores at 2 hours, 6 hours, 12 hours, and 24 hours at rest and during movement after nephrectomy. Single-shot QLB also prolonged the time to first analgesic request (MD, 6.44 hours; 95% CI, 2.23 to 10.65 hours), shortened the length of hospital stay (MD, -0.32 day; 95% CI, -0.55 to -0.09 day), and decreased the incidence of postoperative nausea and vomiting (risk ratio, 0.48; 95% CI, 0.36 to 0.65). Compared with continuous epidural anesthesia, repeated QLB could provide comparable postoperative analgesic benefits. CONCLUSIONS: Single-shot QLB provided a statistically significant but clinically small improvement in postoperative analgesia and recovery for patients undergoing nephrectomy. The QLB would be beneficial as part of multimodal analgesia. Future research might need to determine which approach of QLB is superior for postoperative analgesia after nephrectomy.

Exploration of risk factors of platelet transfusion refractoriness and its impact on the prognosis of hematopoietic stem cell transplantation: a retrospective study of patients with hematological diseases.

Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p < .001) and JAK mutation (OR = 17.32, p = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.

What is the context?Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs.Patients with hematological diseases tend to develop PTR.PTR results from immune and nonimmune factors and the latter account for 80­90%.At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear.What is new?In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020.We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases.PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation.PTR might affect megakaryocyte reconstitution after transplantation.What is the impact?This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation.Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring.AbbreviationsPLT: platelets; PTR: platelet transfusion refractoriness; HSCT: hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML: chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD: graft-versus-host disease; BM: bone marrow; PB: peripheral blood.

Upregulation of HIF-1α contributes to complement activation in transplantation-associated thrombotic microangiopathy.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a severe complication of haematopoietic stem cell transplantation (HSCT). Complement activation is involved in the development of TA-TMA. However, the underlying mechanism is unclear. Therefore, 21 samples of TA-TMA and 1:1 matched controls were measured for hypoxia-inducible factor-1α (HIF-1α) and complement protein. The mechanism was investigated both in vitro and in vivo. In this study, we found that levels of HIF-1α were significantly higher in TA-TMA patients than that in non-TA-TMA controls. Upregulation of HIF-1α induced an increase in membrane-bound complement C3 and dysfunction of human umbilical vein endothelial cells (HUVECs) in vitro. Increasing HIF-1α in vivo led to C3 and C5b-9 deposition in the glomerular endothelial capillary complex, thrombocytopenia, anaemia, and increased serum lactate dehydrogenase (LDH) levels in wild-type (WT) but not in C3-/- mice subjected to HSCT. High platelet aggregation in peripheral blood and CD41-positive microthrombi in the kidney were also found in dimethyloxallyl glycine (DMOG)-treated mice, recapitulating the TA-TMA phenotype seen in patients. Comprehensive analysis, including DNA array, luciferase reporter assay, chromatin immunoprecipitation (ChIP)-seq, and quantitative polymerase chain reaction (PCR), revealed that HIF-1α interacted with the promoter of complement factor H (CFH) to inhibit its transcription. Decreased CFH led to complement activation in endothelial cells.

TNF-α increases the risk of bleeding in patients after CAR T-cell therapy: A bleeding model based on a real-world study of Chinese CAR T Working Party.

Chimeric antigen receptor (CAR) T-cell therapy has shown excellent clinical efficacy in patients with hematologic malignancies. However, severe bleeding after this treatment is a life-threatening complication for most patients. This study evaluated the risk factors associated with bleeding in CAR T treatment and developed a predictive model for this complication. Analysis performed in the First Affiliated Hospital of Suzhou University and external validation launched in Suzhou Hongci Hematology Hospital (Jiangsu, China). We conducted a real-world study incorporating data from 400 patients with hematologic malignancies treated with CAR T between 1 November 2015 and 1 September 2019. Also, 39 patients from another hospital were selected for external validation. Patients with severe bleeding (hazard ratio [HR] 13.04, 95% confidence interval 5.82-29.18; p < 0.001) had a higher risk of death after CAR T. Stage III and IV cytokine release syndrome (CRS) (odds ratio [OR] 6.07, 95% CI 2.35-16.76; p < 0.001) and higher tumor necrosis factor-α (TNF-α) levels (OR 4.00, 95% CI 1.53-11.35; p < 0.001) were independent factors of bleeding in patients after CAR-T treatment. The predictive model developed by Lasso regression, which selected factors such as CRS period, transfusion volume, platelet percentage, platelet count, thrombinogen time, interleukin 6, and TNF-α levels, and showed Nomogram, yielded excellent agreement (C-statistics = 0.905) with the calibration curve, which improved clinical benefit with respect to established bleeding scores such as outpatient bleeding risk index (MOBRI). External validation was performed using 39 patients from another hospital with an AUC of 0.700. Patients with severe bleeding after Car-T therapy had increased the risk of death. A cross-validated bleeding risk score based on CRS stages and TNF-α level show significant prognostic value in patients undergoing CAR-T treatment.

Association between preoperative hypokalemia and postoperative complications in elderly patients: a retrospective study.

BACKGROUND: Hypokalemia is a common form of electrolyte disorder, which has a higher incidence in hospitalized patients and is closely related to perioperative complications and prognosis. Due to decreased skeletal muscle mass which causes total body potassium reduction, and increased comorbidities, the elderly are more susceptible to hypokalemia. OBJECTIVE: To investigate preoperative hypokalemia in elderly patients and its effect on postoperative complications. METHODS: Data were retrospectively collected from the elderly patients who underwent elective surgery from April 2018 to March 2019 and had preoperative blood gas data available. Patients, with age 60 to 100 years, were divided into hypokalemia group (potassium level < 3.5 mmol/L) and normokalemia group (potassium level between 3.5 and 5.5 mmol/L) according to preoperative blood gas analysis. Hypokalemia can be divided into mild (potassium level 3.0 to 3.5 mmol/L), moderate (potassium level 2.5 to 3.0 mmol/L) and severe (potassium level < 2.5 mmol/L), respectively. The risk factors of preoperative hypokalemia and its impact on postoperative complications and prognosis were primary outcomes. Secondary outcomes included postanesthesia care unit (PACU) stay time and hospital length of stay (LOS). RESULTS: Of 987 participants, 436 (44.17%) developed preoperative hypokalemia, among them 357 (81.88%) mild, 87 (16.74%) moderate and 6 (1.38%) severe. Multivariate logistic regression showed that female gender (OR, 1.851; 95% CI, 1.415-2.421), pre-existing hypokalemia at admission (OR, 4.498; 95% CI, 2.506-8.071), and oral laxative twice or more (OR, 1.823; 95% CI, 1.266-2.624) are risk factors of preoperative hypokalemia. Gynecological and biliopancreatic surgery were more common in hypokalemia group than normokalemia group (P <  0.001, P <  0.05). There was no significant difference in postoperative complications, PACU stay time, LOS, and 30-day mortality between the two groups (all P >  0.05). CONCLUSIONS: Female gender, pre-existing hypokalemia at admission, and oral laxative twice or more are independent risk factors for preoperative hypokalemia in elderly patients. However, postoperative complications and 30-day mortality were not increased, which may be related to monitoring blood gas analysis and prompt correction of potassium levels during surgery.

Sedative effect of remimazolam combined with alfentanil in colonoscopic polypectomy: a prospective, randomized, controlled clinical trial.

BACKGROUND: Remimazolam is a newer benzodiazepine with properties of rapid onset, short duration of action, and fast recovery. Our study was to evaluate the effects of different doses of remimazolam combined with alfentanil in colonoscopic polypectomy. METHODS: One hundred twenty patients were randomly divided into four groups: alfentanil and propofol (AP) group, alfentanil and remimazolam 0.1 mg/kg (AR1 group), 0.15 mg/kg (AR2 group), or 0.2 mg/kg (AR3 group). Patients in the four groups received alfentanil 10 µg/kg, followed by propofol 2 mg/kg and three dosages of remimazolam. Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale, heart rate (HR), oxygen saturation (SpO2), respiratory rate (RR), bispectral index (BIS) values and mean arterial pressure (MAP) were collected at intervals of 5 min and analyzed at different time points: before anesthesia (T0), 5 min (T1), 10 min (T2), 15 min after anesthesia (T3) and at the end of surgery (T4). The average MAP was calculated utilizing the average of all MAP values. The primary outcome was the success rate of sedation. Secondary outcomes included time to full alert and adverse events. RESULTS: The success rate of sedation was 100% among the four groups. The incidence of hypotension was significantly decreased (all P < 0.05) and the average MAP was higher in AR1-AR3 groups than AP group (all P < 0.001). None of the patients developed bradycardia or hypertension during surgery in all study groups. BIS values were higher (all P < 0.001) and the time to full alert was statistically shorter in AR1-AR3 groups (all P < 0.05) compared with the AP group. The MOAA/S score in AR1 was higher than AR2 (P < 0.05) and the AR3 group (P < 0.05) at T1 and BIS values in the AR1 group were significantly higher than AR3 group (P < 0.05) at T4. CONCLUSIONS: Remimazolam combined with alfentanil have a non-inferior sedative effect than propofol during the colonoscopic polypectomy. Moreover, this combination of two short-acting drugs might be a safer alternative. TRIAL REGISTRATION: The clinical trial was registered on (16/05/2021, ChiCTR2100046492).

Investigation of fibrinogen in early bleeding of patients with newly diagnosed acute promyelocytic leukemia.

Early hemorrhagic death remains a major cause of treatment failure in acute promyelocytic leukemia (APL). This study investigated the role of fibrinogen concentrations in early hemorrhage and overall survival (OS) of APL patients. Laboratory and clinical data, including fibrinogen concentrations and other coagulation indexes, bleeding events, and survival data, of 198 patients newly diagnosed with APL from February 2012 to December 2017 were extracted from patient records and retrospectively investigated. Patients with moderate/severe bleeding had significantly lower median fibrinogen concentrations (p = .023), higher Chinese disseminated intravascular coagulation scoring system (CDSS) (p < .001), and were more often female (p = .034) than patients with no such bleeding. Additionally, patients with fibrinogen <1.0 g/L and 1.0-1.6 g/L had significantly higher moderate/severe bleeding rates than those with fibrinogen >1.6 g/L (p = .015; p = .023). However, moderate/severe (p = .088) and severe bleeding rates (p = .063) were comparable for patients with fibrinogen <1.0 g/L and 1.0-1.6 g/L. Multivariate analysis showed that fibrinogen ≤1.6 g/L (p = .036), platelet counts ≤10 × 109/L (p = .037), and CDSS scores ≥5 (p = .023) were independent risk factors for moderate/severe bleeding. Survival analysis indicated that moderate/severe bleeding (p = .018), fibrinogen ≤1.6 g/L combined with prothrombin time >12.8 s (p = .005), age ≥60 years (p = .001), and CDSS ≥5 (p = .044) were independent predictors of 1-year OS. Fibrinogen ≤1.6 g/L may be an independent risk factor for early bleeding in newly treated patients with APL and is associated with a worse 1-year OS. Increasing fibrinogen to >1.6 g/L may help to prevent bleeding.

FLT3-ITD and CEBPA Mutations Predict Prognosis in Acute Myelogenous Leukemia Irrespective of Hematopoietic Stem Cell Transplantation.

Cytogenetic and genetic changes have prognostic significance in acute myelogenous leukemia (AML). In our study, we compared the cytogenetic changes and gene mutations (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) with clinical outcomes in 1132 patients with AML enrolled at our center over a 10-year period. A total of 977 patients provided gene mutation data. There were subsets of patients who exhibited mutations in NPM1 (17.9%), CEBPA (16.4%), FLT3-ITD (18.5%), FLT3-TKD (3.9%), DNMT3A (8.6%), and C-KIT (8.8%). A total of 557 patients (49.2%) underwent hematopoietic stem cell transplantation (HSCT) as consolidation therapy. Multivariate analysis identified an adverse karyotype (hazard ratio [HR], 1.48; P = .001), the presence of FLT3-ITD (HR, 1.90; P < .001), and receipt of nonstandard first-line induction chemotherapy (HR, 1.45; P = .003) as significant risk factors for poor overall survival (OS), and the presence of CEBPAmut (HR, .42; P < .001) and receipt of HSCT (HR, .35; P < .001) as prognostic factors for favorable OS. In addition, the presence of FLT3-ITDmut (HR, 2.11; P < .001) was identified as an independent risk factor for poor disease-free survival (DFS), and receipt of HSCT was correlated with improved DFS (HR, .74; P = .046). Compared with chemotherapy as consolidation therapy, HSCT improved the prognosis and overcame the prognostic effect of karyotype from the initial diagnosis; however, the presence of FLT3-ITD or CEBPA mutation can predict prognosis in AML irrespective of HSCT.

Incidence, risk factors, and clinical significance of Epstein-Barr virus reactivation in myelodysplastic syndrome after allogeneic haematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) reactivation is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). In this study, we investigated the characteristics of EBV reactivation in 186 consecutive myelodysplastic (MDS) patients who underwent allo-HSCT in our centre. In 35 patients (18.8%) who experienced EBV reactivation after allo-HSCT, the median onset was 53 days (range 4-381 days). The cumulative incidence of EBV reactivation at the first, sixth, and twelfth month after allo-HSCT was 10.7%, 15.1%, and 17.9%, respectively. Twenty-five patients (71.4%) received pre-emptive rituximab therapy, and no patients developed post-transplant lymphoproliferative disorders. Stem cell source was proven to be a risk factor correlated with EBV reactivation. The cumulative incidence of relapse in the EBV-positive group was 11.4%, 25.2%, and 31.0% at the first, second, and third year after transplantation, respectively, being significantly higher than the corresponding 6.8%, 10.2%, and 10.2%, in the EBV-negative group (P = 0.014). Prognostic analysis showed that EBV reactivation was an independent risk factor for relapse-free survival (RFS). Patients in the EBV-positive group showed obviously shorter RFS than those in the EBV-negative group, with 3-year RFS of 62% and 85%, respectively (P = 0.017).

Protective Role of Electroacupuncture Against Cognitive Impairment in Neurological Diseases.

Many neurological diseases can lead to cognitive impairment in patients, which includes dementia and mild cognitive impairment and thus create a heavy burden both to their families and public health. Due to the limited effectiveness of medications in treating cognitive impairment, it is imperative to develop alternative treatments. Electroacupuncture (EA), a required method for Traditional Chinese Medicine, has the potential treatment of cognitive impairment. However, the molecular mechanisms involved have not been fully elucidated. Considering the current research status, preclinical literature published within the ten years until October 2022 was systematically searched through PubMed, Web of Science, MEDLINE, Ovid, and Embase. By reading the titles and abstracts, a total of 56 studies were initially included. It is concluded that EA can effectively ameliorate cognitive impairment in preclinical research of neurological diseases and induce potentially beneficial changes in molecular pathways, including Alzheimer's disease, vascular cognitive impairment, chronic pain, and Parkinson's disease. Moreover, EA exerts beneficial effects through the same or diverse mechanisms for different disease types, including but not limited to neuroinflammation, neuronal apoptosis, neurogenesis, synaptic plasticity, and autophagy. However, these findings raise further questions that need to be elucidated. Overall, EA therapy for cognitive impairment is an area with great promise, even though more research regarding its detailed mechanisms is warranted.

Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial.

Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE). Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation. Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged (p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower (p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group (p = 0.002) but not in the R group (p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group. Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863.

Perfusion index for early identification of regional anesthesia effectiveness: a narrative review.

Regional anesthesia (RA) is a common and irreplaceable technique in clinical, which can be used in different surgery sites and control of acute and chronic pain, especially for outpatients, pediatrics and the elderly. RA demands are increasing during COVID-19 pandemic because many surgeries could be performed under RA to reduce the risk of cross-infection between patients and health care workers. Early and accurate identification of the effects of RA can help physicians make timely decisions about whether to supplement analgesics or switch to general anesthesia, which will save time and improve patient satisfaction in a busy operating room. Perfusion index (PI) is a parameter derived from photoplethysmography (PPG) and represents the ratio of pulsatile and non-pulsatile blood flow at monitoring sites. It reflects local perfusion and is mainly affected by stroke volume and vascular tone. With characteristics of non-invasive, rapid, simple, and objective, PI is widely used in clinical practice, such as fluid responsiveness prediction, nociceptive assessment, etc. Recently, many studies have assessed the accuracy of PI in early prediction of RA success, including brachial plexus block, sciatic nerve block, neuraxial anesthesia, paravertebral block, caudal block and stellate ganglion block. Successful RA often parallels increased PI. In this narrative review, we describe the principles and influencing factors of PI, and introduce the effects of PI on early identification of RA effectiveness.

α5GABAA receptor: A potential therapeutic target for perioperative neurocognitive disorders, a review of preclinical studies.

Perioperative neurocognitive disorders (PND) are a common complication in elderly patients following surgery, which not only prolongs the recovery period but also affects their future quality of life and imposes a significant burden on their family and society. Multiple factors, including aging, vulnerability, anesthetic drugs, cerebral oxygen desaturation, and severe pain, have been associated with PND. Unfortunately, no effective drug is currently available to prevent PND. α5 γ-aminobutyric acid subtype A (α5GABAA) receptors have been implicated in cognitive function modulation. Positive or negative allosteric modulators of α5GABAA receptors have been found to improve cognitive impairment under different conditions. Therefore, targeting α5GABAA receptors may represent a promising treatment strategy for PND. This review focuses on preclinical studies of α5GABAA receptors and the risk factors associated with PND, primarily including aging, anesthetics, and neuroinflammation. Specifically, positive allosteric modulators of α5GABAA receptors have improved cognitive function in aged experimental animals. In contrast, negative allosteric modulators of α5GABAA receptors have been found to facilitate cognitive recovery in aged or adult experimental animals undergoing anesthesia and surgery but not in aged experimental animals under anesthesia alone. The reasons for the discordant findings have yet to be elucidated. In preclinical studies, different strategies of drug administration, as well as various behavioral tests, may influence the stability of the results. These issues need to be carefully considered in future studies.

Comparative analysis of the effect of electromyogram to bispectral index and 95% spectral edge frequency under remimazolam and propofol anesthesia: a prospective, randomized, controlled clinical trial.

Background: Bispectral index (BIS), an index used to monitor the depth of anesthesia, can be interfered with by the electromyogram (EMG) signal. The 95% spectral edge frequency (SEF95) also can reflect the sedation depth. Remimazolam in monitored anesthesia care results in higher BIS values than propofol, though in the same sedation level assessed by Modified Observers Assessment of Alertness and Sedation (MOAA/S). Our study aims to illustrate whether EMG is involved in remimazolam causing higher BIS value than propofol preliminarily and to explore the correlations among BIS, EMG, and SEF95 under propofol and remimazolam anesthesia. Patients and methods: Twenty-eight patients were randomly divided into propofol (P) and remimazolam (RM) groups. Patients in the two groups received alfentanil 10 µg/kg, followed by propofol 2 mg/kg and remimazolam 0.15 mg/kg. Blood pressure (BP), heart rate (HR), and oxygen saturation (SpO2) were routinely monitored. The BIS, EMG, and SEF95 were obtained through BIS VISTATM. The primary outcomes were BIS, EMG, and the correlation between BIS and EMG in both groups. Other outcomes were SEF95, the correlation between BIS and SEF95, and the correlation between EMG and SEF95. And all the statistical and comparative analysis between these signals was conducted with SPSS 26.0 and GraphPad Prism 8. Results: BIS values, EMG, and SEF95 were significantly higher in the RM group than in the P group (all p < 0.001). There was a strong positive correlation between BIS and EMG in the RM group (r = 0.416). Nevertheless, the BIS in the P group showed a weak negative correlation with EMG (r = -0.219). Both P (r = 0.787) and RM group (r = 0.559) had a reasonably significant correlation coefficient between BIS and SEF95. SEF95 almost did not correlate with EMG in the RM group (r = 0.101). Conclusion: Bispectral index can be interfered with high EMG intensity under remimazolam anesthesia. However, EMG can hardly affect the accuracy of BIS under propofol anesthesia due to low EMG intensity and a weak negative correlation between EMG and BIS. Moreover, SEF95 may have a great application prospect in predicting the sedation condition of remimazolam.

Appropriate pre-transplant strategy for patients with myelodysplastic syndromes receiving allogeneic haematopoietic stem cell transplantation after myeloablative conditioning.

Purpose: Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis. Methods: We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019. Results: The median age of the patients was 38 years (range, 12-64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5-year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001). Conclusion: The findings of the study indicate that receiving an appropriate pre-transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation.

Dexmedetomidine attenuates perioperative neurocognitive disorders by suppressing hippocampal neuroinflammation and HMGB1/RAGE/NF-κB signaling pathway.

Surgical trauma can induce an inflammatory response in the central nervous system. Neuroinflammation is a crucial pathological mechanism of perioperative neurocognitive disorders (PND). Dexmedetomidine (Dex) is an alpha (α)-2 adrenoceptor agonist that is widely used in the perioperative period. Previous studies have shown that Dex has neuroprotection in various nerve injury models, but its role in PND remains unclear. Our study aimed to observe the neuroprotective effect of Dex pretreatment on postoperative cognitive change and explore the effects of hippocampal neuroinflammation, microglial polarization and HMGB1/RAGE/NF-κB signaling pathway involved in Dex on PND in rats. Rats were pretreated with Dex alone or in combination with yohimbine (α-2 adrenoceptor antagonist) before surgery. Behavioral tests results showed that Dex ameliorated surgery-induced cognitive impairment in rats. Nissl, immunohistochemistry and TUNEL-NeuN staining results indicated that Dex reduced hippocampus damage and neuronal apoptosis caused by surgery. Dex preconditioning reduced the expression of the proinflammatory cytokines IL-1ß, TNF-α and IL-6 in hippocampus. Immunohistochemical and immunofluorescence results showed that Dex preconditioning inhibited the activation of glial cells induced by surgery. Western blot analysis showed that Dex preconditioning downregulated the expression of M1 phenotype markers (CD86 and iNOS), HMGB1, RAGE and nuclear NF-κB and upregulated the expression of M2 phenotype markers (Arginase 1 and CD206) and cytoplasmic NF-κB. Yohimbine could inhibit the neuroprotective effect of Dex. These results indicated that Dex pretreatment could improve postoperative short-term cognitive impairment, and the neuroprotective mechanism may involve the suppression of hippocampal neuroinflammation, regulation of M1/M2 polarization, and inhibition of HMGB1/RAGE/NF-κB signal transduction.

Electroacupuncture Alleviates Neuroinflammation by Inhibiting the HMGB1 Signaling Pathway in Rats with Sepsis-Associated Encephalopathy.

Sepsis-Associated Encephalopathy (SAE) is common in sepsis patients, with high mortality rates. It is believed that neuroinflammation is an important mechanism involved in SAE. High mobility group box 1 protein (HMGB1), as a late pro-inflammatory factor, is significantly increased during sepsis in different brain regions, including the hippocampus. HMGB1 causes neuroinflammation and cognitive impairment through direct binding to advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4). Electroacupuncture (EA) at Baihui (GV20) and Zusanli (ST36) is beneficial for neurological diseases and experimental sepsis. Our study used EA to treat SAE induced by lipopolysaccharide (LPS) in male Sprague-Dawley rats. The Y maze test was performed to assess working memory. Immunofluorescence (IF) and Western blotting (WB) were used to determine neuroinflammation and the HMGB1 signaling pathway. Results showed that EA could improve working memory impairment in rats with SAE. EA alleviated neuroinflammation by downregulating the hippocampus's HMGB1/TLR4 and HMGB1/RAGE signaling, reducing the levels of pro-inflammatory factors, and relieving microglial and astrocyte activation. However, EA did not affect the tight junctions' expression of the blood-brain barrier (BBB) in the hippocampus.