M2 Microglia-Derived Exosomes Protect Against Glutamate-Induced HT22 Cell Injury via Exosomal miR-124-3p.

As one of the most serious complications of sepsis, sepsis-associated encephalopathy has not been effectively treated or prevented. Exosomes, as a new therapeutic method, play a protective role in neurodegenerative diseases, stroke and traumatic brain injury in recent years. The purpose of this study was to investigate the role of exosomes in glutamate (Glu)-induced neuronal injury, and to explore its mechanism, providing new ideas for the treatment of sepsis-associated encephalopathy. The neuron damage model induced by Glu was established, and its metabolomics was analyzed and identified. BV2 cells were induced to differentiate into M1 and M2 subtypes. After the exosomes from both M1-BV2 cells and M2-BV2 cells were collected, exosome morphological identification was performed by transmission electron microscopy and exosome-specific markers were also detected. These exosomes were then cocultured with HT22 cells. CCK-8 method and LDH kit were used to detect cell viability and toxicity. Cell apoptosis, mitochondrial membrane potential and ROS content were respectively detected by flow cytometry, JC-1 assay and DCFH-DA assay. MiR-124-3p expression level was detected by qRT-PCR and Western blot. Bioinformatics analysis and luciferase reporter assay predicted and verified the relationship between miR-124-3p and ROCK1 or ROCK2. Through metabolomics, 81 different metabolites were found, including fructose, GABA, 2, 4-diaminobutyric acid, etc. The enrichment analysis of differential metabolites showed that they were mainly enriched in glutathione metabolism, glycine and serine metabolism, and urea cycle. M2 microglia-derived exosomes could reduce the apoptosis, decrease the accumulation of ROS, restore the mitochondrial membrane potential and the anti-oxidative stress ability in HT22 cells induced by Glu. It was also found that the protective effect of miR-124-3p mimic on neurons was comparable to that of M2-EXOs. Additionally, M2-EXOs might carry miR-124-3p to target ROCK1 and ROCK2 in neurons, affecting ROCK/PTEN/AKT/mTOR signaling pathway, and then reducing Glu-induced neuronal apoptosis. M2 microglia-derived exosomes may protect HT22 cells against Glu-induced injury by transferring miR-124-3p into HT22 cells, with ROCK being a target gene for miR-124-3p.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Cost-Effectiveness Analysis of Camrelizumab Plus Rivoceranib Versus Sorafenib as a First-Line Therapy for Unresectable Hepatocellular Carcinoma in the Chinese Health Care System.

BACKGROUND AND OBJECTIVES: Camrelizumab plus rivoceranib showed significant clinical benefits in progression-free survival and overall survival compared to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to assess its cost effectiveness from the perspective of Chinese health care system. METHODS: A Markov state-transition model was developed based on the Phase 3 randomized CARES-310 clinical trial data. Health state utility values were obtained from the CARES-310 clinical trial, and direct medical costs were derived from the relevant literature and local charges. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses were performed to assess the uncertainty of the model. RESULTS: In the base-case analysis, the incremental effectiveness and cost of camrelizumab plus rivoceranib versus sorafenib were 0.41 QALYs and $13,684.84, respectively, resulting in an ICER of $33,619.98/QALY, lower than the willingness-to-pay threshold of China ($35,864.61/QALY). Subgroup analyses revealed that the ICERs of camrelizumab plus rivoceranib versus sorafenib were $35,920.01 and $29,717.98 in patients with ALBI grade 1 and grade 2, respectively. One-way sensitivity analyses indicated that the cost of camrelizumab, the proportion of patients receiving subsequent treatment in the camrelizumab plus rivoceranib group, and the cost of rivoceranib were the most significant factors in the base-case analysis. Probabilistic sensitivity analysis suggested that the probabilities of cost effectiveness of camrelizumab plus rivoceranib were 61.27%, 51.46%, and 82.78% for any grade, and ALBI grade 1 and grade 2, respectively. CONCLUSIONS: Camrelizumab plus rivoceranib was more cost effective than sorafenib as first-line therapy for unresectable HCC in the Chinese setting.

Automated pancreatic segmentation and fat fraction evaluation based on a self-supervised transfer learning network.

Accurate segmentation of the pancreas from abdominal computed tomography (CT) images is challenging but essential for the diagnosis and treatment of pancreatic disorders such as tumours and diabetes. In this study, a dataset with 229 sets of high-resolution CT images was generated and annotated. We proposed a novel 3D segmentation model named nnTransfer (nonisomorphic transfer learning) net, which employs generative model structure for self-supervision to facilitate the network's learning of image attributes from unlabelled data. The effectiveness for pancreas segmentation of nnTransfer was assessed using the Hausdorff distance (HD) and Dice similarity coefficient (DSC) on the dataset. Additionally, a histogram analysis with local thresholding was used to achieve automated whole-volume measurement of pancreatic fat (fat volume fraction, FVF). The proposed technique performed admirably on the dataset, with DSC: 0.937 ± 0.019 and HD: 2.655 ± 1.479. The mean pancreas volume and FVF of the pancreas were 91.95 ± 23.90 cm3 and 12.67 % ± 9.84 %, respectively. The nnTransfer functioned flawlessly and autonomously, facilitating the use of the FVF to evaluate pancreatic disease, particularly in patients with diabetes.

Bibliometric analysis of research trends and active research areas in chimeric antigen receptor T cell therapy for hematologic malignancies.

BACKGROUND: In the past decade, chimeric antigen receptor (CAR) T-cells have successfully treated cancers, especially hematologic malignancies. Although many articles have been published on CAR T-cell therapy for hematologic malignancies, bibliometric analysis remains unexplored. AIM: This study aimed to investigate and analyze existing trends and active research areas on CAR T-cell therapy for hematologic malignancies, providing novel perspectives for clinical decision-making and scientific research. METHOD: From 2000 to 2023, the Web of Science Core Collection was searched for articles published on CAR T-cells for the treatment of hematologic malignancies. Comprehensive visual analyses of annual publication, country, institutions, authors, co-cited references, and keywords were performed using CiteSpace software and VOSviewer. RESULTS: A total of 2,451 articles on CAR T-cells were published to treat hematologic malignancies from 01 January 2000 to 31 August 2023. The United States, China, and Germany were the top three nations in publications. In the keyword analysis, "immunotherapy" and "chimeric antigen receptor" were used most frequently. Moreover, the yellow node, which included terms such as "chimeric antigen receptor T cells," "efficacy," "CAR T-cell therapy," "toxicity," "CAR-NK," and "tumor microenvironment" were most active research areas. CONCLUSION: This study provided a comprehensive analysis of publications on CAR T-cell therapy for hematologic malignancies from 2000 to 2023. The findings provide current trends and potential hotspots in CAR T-cell therapy for hematologic malignancies and contribute valuable direction for future studies in this field.

Bibliometric analysis of research trends and topic areas in traditional Chinese medicine therapy for lymphoma.

CONTEXT: Traditional Chinese Medicine (TCM) is effective as a cancer treatment modality. However, this is the first bibliometric analysis of TCM in lymphoma treatment. OBJECTIVE: This study explores the current trends and research topics of TCM in treating lymphoma from 2000 to 2023. MATERIALS AND METHODS: We searched within the Web of Science Core Collection (WoSCC) for publications on TCM in lymphoma treatment, spanning 2000 to 2023. Subsequently, we employed a comprehensive approach utilizing CiteSpace software and VOSviewer to visually analyze research trends, authors, institutions, co-cited references, and keywords. RESULTS: From January 1, 2000, to August 31, 2023, annual scientific publications on TCM for lymphoma treatment have steadily increased. Among the leading institutions in this field, the Beijing University of Chinese Medicine and the Fujian Medical University occupied the top positions. Regarding the authors, Jun Peng, Jiumao Lin, and Hongwei Chen emerged as the top three contributors. In the co-citation analysis of references, the top three co-cited references were authored by Hanahan D, Elmore S, and Livak KJ with citations numbered 13, 14, and 17, respectively. In particular, keywords reflecting current emerging trends included 'pathway', 'traditional Chinese medicine', 'oxidative stress', and 'macrophage polarization'. DISCUSSION AND CONCLUSIONS: This bibliometric analysis provides a comprehensive overview of TCM for lymphoma treatment. This analysis identified the predominant trends and research topics in the field. The findings are expected to be of significant value for researchers who focus on TCM in lymphoma treatment, helping them better understand the development of this field.

Study on a Noncontact Microdroplet Separation Method under the Action of Corona Discharge.

Precision manipulation of various liquids is essential in many fields such as various thermal, optical, and medical applications. This paper proposes an effective noncontact microdroplet separation method that is based on the action of corona discharge. A blade-plate electrode is constructed to generate an ionic wind, thereby enabling the droplet to be separated according to the shape of the blade electrode. Line, curve, S-shape, and parallel separation of the droplet can be realized in the experiment setup. Furthermore, experiment parameters, including the driving voltage, cutting speed, the distance of the upper and lower electrodes, cutting depth, etc., are discussed. Experimental results show that the proposed method is feasible and effective and can be used in application scenarios that require precise manipulation of droplets.

Peroxiredoxin 1 alleviates oxygen-glucose deprivation/ reoxygenation injury in N2a cells via suppressing the JNK/caspase-3 pathway.

Objectives: Cerebral ischemia/reperfusion (I/R) injury inevitably aggravates the initial cerebral tissue damage following a stroke. Peroxiredoxin 1 (Prdx1) is a representative protein of the endogenous antioxidant enzyme family that regulates several reactive oxygen species (ROS)-dependent signaling pathways, whereas the JNK/caspase-3 proapoptotic pathway has a prominent role during cerebral I/R injury. This study aimed to examine the potential mechanism of Prdx1 in Neuro 2A (N2a) cells following oxygen-glucose deprivation and reoxygenation (OGD/R) injury. Materials and Methods: N2a cells were exposed to OGD/R to simulate cerebral I/R injury. Prdx1 siRNA transfection and the JNK inhibitor (SP600125) were used to interfere with their relative expressions. CCK-8 assay, flow cytometry, and lactate dehydrogenase (LDH) assay were employed to determine the viability and apoptosis of N2a cells. The intracellular ROS content was assessed using ROS Assay Kit. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses were conducted to detect the expression levels of Prdx1, JNK, phosphorylated JNK (p-JNK), and cleaved caspase-3. Results: Firstly, Prdx1, p-JNK, and cleaved caspase-3 expression were significantly induced in OGD/R-exposed N2a cells. Secondly, the knockdown of Prdx1 inhibited cell viability and increased apoptosis rate, expression of p-JNK, and cleaved caspase-3 expression. Thirdly, SP600125 inhibited the JNK/caspase-3 signaling pathway and mitigated cell injury following OGD/R. Finally, SP600125 partially reversed Prdx1 down-regulation-mediated cleaved caspase-3 activation and OGD/R damage in N2a cells. Conclusion: Prdx1 alleviates the injury to N2a cells induced by OGD/R via suppressing JNK/caspase-3 pathway, showing promise as a potential therapeutic for cerebral I/R injury.

Study on the Formation and Controllable Movement of Polymer Liquid Columns Based on Dynamic Control of Spatial Electric Field Distribution.

Liquid deformation and motion are very common natural phenomena and of great value in various practical applications. In this study, a dielectric fluid column formation and directional flow phenomenon are presented. Dielectric fluid can grow upward to form a liquid column through a spatial electric field and realize directional and controllable operation of the liquid column by regulating spatial electric field distribution. First, the adjustable electric field space is constructed by connecting the two parallel electrodes to the high-voltage DC power supply. Then, the regional electric field distribution was adjusted by the upper plate graphic and power supply regulation to drive the polymer liquid on the lower plate electrode to form a liquid column at different positions. The results show that the polymer liquid column can be driven by the spatial electric field distributed dynamic control method and that the height and the narrowest width of the liquid column are directly controlled by the voltage. With the experiment conditions that the distance between two parallel electrodes is 5-15 mm, the formation of liquid columns with a height of 5-15 mm can be controlled. In addition, the liquid column can be driven by adjusting the on-states of different conductive regions. When the voltage is 10 kV, the liquid column directional movement speed can reach 1 mm/s. The higher the voltage, the faster the directional movement. The research results can be used as producing polydimethylsiloxane stamp, localized heating and temperature control, fabricating a pulsating heat pipe, and so on.

GhPYL9-5D and GhPYR1-3 A positively regulate Arabidopsis and cotton responses to ABA, drought, high salinity and osmotic stress.

BACKGROUND: Abscisic acid (ABA) receptor pyrabactin resistance 1/PYR1-like/regulatory components of ABA receptor proteins (PYR/PYL/RCARs) have been demonstrated to play pivotal roles in ABA signaling and in response to diverse environmental stimuli including drought, salinity and osmotic stress in Arabidopsis. However, whether and how GhPYL9-5D and GhPYR1-3A, the homologues of Arabidopsis PYL9 and PYR1 in cotton, function in responding to ABA and abiotic stresses are still unclear. RESULTS: GhPYL9-5D and GhPYR1-3A were targeted to the cytoplasm and nucleus. Overexpression of GhPYL9-5D and GhPYR1-3A in Arabidopsis wild type and sextuple mutant pyr1pyl1pyl2pyl4pyl5pyl8 plants resulted in ABA hypersensitivity in terms of seed germination, root growth and stomatal closure, as well as seedling tolerance to water deficit, salt and osmotic stress. Moreover, the VIGS (Virus-induced gene silencing) cotton plants, in which GhPYL9-5D or GhPYR1-3A were knocked down, showed clearly reduced tolerance to polyethylene glycol 6000 (PEG)-induced drought, salinity and osmotic stresses compared with the controls. Additionally, transcriptomic data revealed that GhPYL9-5D was highly expressed in the root, and GhPYR1-3A was strongly expressed in the fiber and stem. GhPYL9-5D, GhPYR1-3A and their homologs in cotton were highly expressed after treatment with PEG or NaCl, and the two genes were co-expressed with redox signaling components, transcription factors and auxin signal components. These results suggest that GhPYL9-5D and GhPYR1-3A may serve important roles through interplaying with hormone and other signaling components in cotton adaptation to salt or osmotic stress. CONCLUSIONS: GhPYL9-5D and GhPYR1-3A positively regulate ABA-mediated seed germination, primary root growth and stomatal closure, as well as tolerance to drought, salt and osmotic stresses likely through affecting the expression of multiple downstream stress-associated genes in Arabidopsis and cotton.

Bilateral carpal tunnel syndrome and motor dysfunction caused by gout and type 2 diabetes: A case report.

BACKGROUND: Carpal tunnel syndrome (CTS) has been associated with gout and type 2 diabetes mellitus (T2DM). However, due to insufficient clinical understanding of gout-related CTS and reliance on the diagnostic importance of elevated serum uric acid levels, such cases are prone to missed diagnosis, misdiagnosis, and delayed treatment. In addition, the effect of T2DM on gout - induced carpal tunnel syndrome has not been reported. CASE SUMMARY: Herein, we present an unusual case of CTS and motor dysfunction caused by miliary tophaceous gout and T2DM. The patient presented to the hand and foot clinic with paresthesia of the fingers of both hands, especially at night. The patient was diagnosed with type 2 diabetes a month ago. Ultrasonography revealed bilateral transverse carpal ligament thickening with median nerve compression during hospitalization. The patient was successfully treated with carpal tunnel decompression and tendon release. The postoperative pathological examination revealed typical gout nodules. This case suggests that the presence of T2DM could accelerate tophi formation and worsen CTS symptoms, although no definitive proof in this regard has been described previously. CONCLUSION: Tophi formation may most likely cause the co-occurrence of CTS and flexor dysfunction in gout and incipient diabetes patients.

Is there any association between early trimester Triglyceride-glucose index and incidence of hypertensive disorder of pregnancy and adverse pregnancy outcomes?

Background: Insulin resistance (IR) is a normal feature of pregnancy and plays a crucial role in the pathophysiology of hypertensive disorder of pregnancy (HDP). The triglyceride-glucose index (TyG index) has been shown as a simple and reliable alternative IR marker. This work aimed to investigate the association between the TyG index and the incidence of HDP and adverse pregnancy outcomes. Methods: From January 2016 to December 2018, 289 women with HDP and 861 women without HDP were recruited at Shanghai Fifth People's Hospital, Fudan University to determine the relationship between the TyG index and the incidence of HDP and adverse pregnancy outcomes. Results: In the case-control study, the incidence of HDP was found to be significantly associated with the TyG index. Moreover, logistic regression indicated that the TyG index is an independent risk factor for HDP development and incidence of low birth weight (LBW) and fetal distress. In the cohort study, the results showed that the TyG index increased, there was a stepwise increase in HDP incidence, SBP, and DBP levels one week before delivery as well as in LBW and fetal distress incidence. The early trimester TyG index was positively associated with pre-pregnancy BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) one week before delivery. Spline regression showed that there was a significant linear association between HDP incidence and early trimester TyG index when it was >8.5. Conclusions: This work suggested that the early trimester TyG index was closely associated with the development of HDP and adverse pregnancy outcomes.

Effects of preoperative oral enzyme-hydrolyzed rice flour solution on gastric emptying and insulin resistance in patients undergoing laparoscopic cholecystectomy: a prospective randomized controlled trial.

BACKGROUND: The effect of preoperative oral carbohydrates (POC) on insulin resistance (IR) of laparoscopic cholecystectomy (LC) remains debatable. Enzyme-hydrolyzed rice flour (EHR) is a kind of water-soluble micromolecular carbohydrates. This study aimed to investigate the impact of preoperative oral EHR solution on gastric emptying and IR in patients undergoing LC. METHODS: Patients (n = 100) undergoing LC were divided into oral-water group (group C) or oral-EHR solution (group E) randomly (n = 50 each), and the patients drank 300 ml water or EHR solution 2-3 h before surgery respectively. Gastric emptying which was quantized by gastric volume (GV) from antrum ultrasonography, IR indicators, subjective comfort indicators, handgrip strength, postoperative recovery indexes, and complications were recorded. RESULTS: There were no differences in GV between the two groups before oral administration (V0), immediately after oral administration (V1) and before anesthesia induction(V2). The GV at V2 (GV2) reduced to the level of V0 (GV0) in the two groups. Fasting glucose (FG), fasting insulin (FINS) and Homa-IR in the two groups increased at postoperative day 1 (Pos 1d) compared with those at preoperative day 1(Pre 1d). Homa-IS and Homa-ß in the two groups decreased at Pos 1d compared with those at Pre 1d. FG, FINS and Homa-IR in group E were lower than those in group C at Pos 1d, and Homa-IS and Homa-ß were higher in group E than those in group C at Pos 1d. Subjective comfort indictors (hunger, fatigue and anxiety) in group E were lower than those in group C at preoperative 15 min (Pre 15 min) and postoperative 1 h (Pos 1 h). Handgrip strength in group E was raised compared with that in group C at Pre 15 min, Pos 1 h and Pos 1d. There was a lower incidence of nausea and earlier exhaust time in group E. CONCLUSION: Oral 300 ml EHR solution 2-3 h before LC surgery did not increase the occurrence of reflux and aspiration during anesthesia induction with a normal gastric emptying, ameliorated postoperative IR, improved subjective comfort, and promoted postoperative gastrointestinal function recovery. TRIAL REGISTRATION: Prospectively registered at the China Clinical Trial Registry, registration number: ChiCTR2000039939, date of registration:14/11/2020.

Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells.

Breast cancer is the most prevalent cancer in female patients worldwide. Tissue factor pathway inhibitor 2 (TFPI-2) is identified as an important tumor suppressor in various cancers. Recent studies have shown that TFPI-2 translocates into the nucleus, where it modulates the transcription of the matrix metalloproteinase-2 (MMP-2) gene. However, its biological role and molecular mechanisms in the progression of breast cancer remain unclear. In this study, we identified 5125 differentially expressed genes (DEGs) from RNA sequencing (RNA-seq) in TFPI-2-overexpressing MDA231 cells compared with control cells. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) analysis shown that cell cycle, cell differentiation, proteoglycans in cancer, and pathways associated with cancer were highly enriched in downregulated DEGs. Integration of the RNA-seq and ChIP-sequencing (ChIP-seq) data identified 73 genes directly controlled by TFPI-2 in MDA231 cells. Among them, melanocyte inducing transcription factor (MITF) gene expression was repressed by TFPI-2, which was further verified by a luciferase reporter assay and ChIP-quantitative PCR. Our study provides evidence of a novel role of TFPI-2 in human breast cancer involving targeting of the MITF.

Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK-3ß/ß-catenin activation.

BACKGROUND: Neural stem cells (NSCs) are considered as candidates for cell replacement therapy in many neurological disorders. However, the propensity for their differentiation to proceed more glial rather than neuronal phenotypes in pathological conditions limits positive outcomes of reparative transplantation. Exogenous physical stimulation to favor the neuronal differentiation of NSCs without extra chemical side effect could alleviate the problem, providing a safe and highly efficient cell therapy to accelerate neurological recovery following neuronal injuries. RESULTS: With 7-day physiological electric field (EF) stimulation at 100 mV/mm, we recorded the boosted neuronal differentiation of NSCs, comparing to the non-EF treated cells with 2.3-fold higher MAP2 positive cell ratio, 1.6-fold longer neuronal process and 2.4-fold higher cells ratio with neuronal spontaneous action potential. While with the classical medium induction, the neuronal spontaneous potential may only achieve after 21-day induction. Deficiency of either PI3Kγ or ß-catenin abolished the above improvement, demonstrating the requirement of the PI3K/Akt/GSK-3ß/ß-catenin cascade activation in the physiological EF stimulation boosted neuronal differentiation of NSCs. When transplanted into the spinal cord injury (SCI) modelled mice, these EF pre-stimulated NSCs were recorded to develop twofold higher proportion of neurons, comparing to the non-EF treated NSCs. Along with the boosted neuronal differentiation following transplantation, we also recorded the improved neurogenesis in the impacted spinal cord and the significantly benefitted hind limp motor function repair of the SCI mice. CONCLUSIONS: In conclusion, we demonstrated physiological EF stimulation as an efficient method to boost the neuronal differentiation of NSCs via the PI3K/Akt/GSK-3ß/ß-catenin activation. Pre-treatment with the EF stimulation induction before NSCs transplantation would notably improve the therapeutic outcome for neurogenesis and neurofunction recovery of SCI.

Coronary CT angiography and serum biomarkers are potential biomarkers for predicting MACE at three-months and one-year follow-up.

AIMS: To assess the prognostic value of coronary computed tomography angiography (CTA) and serum biomarkers for the prediction of major adverse cardiac events (MACE) at three-month and one-year follow-ups. METHODS AND RESULTS: A total of 720 patients with acute chest pain and normal electrocardiography (ECG) were included in the prospective cohort study. These patients received both coronary CTA screening and serum biomarkers testing, followed by three-month and one-year follow-ups for the occurrence of major adverse cardiac events (MACE). The primary outcome was the occurrence of MACE, which is defined as acute coronary syndrome (ACS), nonfatal MI, and all-cause mortality. The MACE rate was 17.8% (128 cases) and 25.2% (182 cases) at three-months and one-year follow-up. ApoB/apoA1(OR = 7.45, P < 0.001) and the number of atherosclerotic vessels (OR = 2.86, P < 0.001) were independent predictors for MACE at the three-month follow-up, so were apoB/apoA1 (OR = 5.23, P = 0.003), Serum amyloid protein A (SAA, OR = 1.04, P < 0.001) and the number of atherosclerotic vessels (OR = 2.54, P < 0.001) at the one-year follow-up. While apoB/apoA1 suggested its sensitivities of 84% for predicting MACE at three-month follow-ups, the number of atherosclerotic vessels had 81% specificity at one-year follow-up. CONCLUSIONS: Among patients with acute chest pain and normal ECG, apoB/apoA1, SAA and the number of atherosclerotic vessels are the most powerful predictors of MACE at three-month and one-year follow-ups.

The relationship between mild cognitive impairment and postoperative delirium undergoing total knee arthroplasty: The PNDABLE study.

Background: Patients undergoing surgery are at a higher risk of developing postoperative delirium (POD) as a result of anesthesia and surgical procedures. This study examined the association between POD and mild cognitive impairment (MCI) and whether MCI influences POD through the core pathology of POD. Methods: We enrolled Chinese Han patients undergoing unilateral total knee arthroplasty (aged 50-90, weighing 50-80 kg, and using ASAI-II), combined with epidural anesthesia between October 2020 and June 2021. All the participants were assessed using Winblad's criteria for diagnosing MCI on pre-operation and using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS) postoperative 1-7 days (or before discharge) for diagnosing POD by an anesthesiologist. Cerebrospinal fluid (CSF) biomarkers of POD were measured by enzyme-linked immunosorbent assay (ELISA). To examine the mechanism by which POD pathologies affect cognition, causal mediation analyses were performed. Results: POD incidence was 20.2%, including 32.5% in the MCI group and 12.4% in the non-mild cognitive impairment (NMCI) group. The MCI and CSF levels of T-tau and P-tau were risk factors, and the CSF levels of Aß42, Aß42/ T-tau, and Aß42/ P-tau were protective factors in POD (p < 0.05). Part of the effects of MCI on cognition can be attributed to amyloid pathology and tau. Conclusion: MCI may be a reasonably good prognostic factor in POD development. Overall, amyloid pathology and tau protein might partially mediate the influence of MCI on POD. Clinical trial registration: www.clinicaltrials.gov, identifier: ChiCTR2000033439.

Sciatic nerve schwannoma complicated by nerve bundle membrane effusion: Two case reports and a literature review.

Schwannoma is a benign tumor that originates from Schwann cells in the peripheral nerve tunica or bundle of nerves and grows along the longitudinal axis of the nerve. Schwannoma can occur in multiple anatomic locations but rarely in the sciatic nerve. To our knowledge, there are no previous reports in the literature related to schwannoma combined with effusion of the nerve bundle membranes. Here, we report two cases of sciatic nerve schwannoma combined with nerve bundle membrane effusion, and the relationship between them is uncertain. We have boldly speculated about this uncertain relationship by combining the two patients' imaging manifestations to help determine the mechanism of schwannoma or effusion generation as well as a clinical treatment.

[Effect of M1 microglia-derived exosomal microRNA-20a-5p on neuronal injury after oxygen-glucose deprivation and restoration injury].

OBJECTIVE: To investigate the effect of M1 microglia-derived exosomes (M1-exo) on neuronal injury after oxygen-glucose deprivation and restoration, and to explore its mechanism. METHODS: The mouse microglia BV2 cells grown in logarithmic growth phase were added with 100 µg/L liposolysaccharide (LPS) and 20 µg/L interferon-γ (IFN-γ) to induce the polarization of microglia into M1 phenotype. M1 microglia were identified by Western blotting, quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence. The supernatant of M1 microglia was collected, and exosomes were extracted by ExoQuick-TCTM kit. The morphology of exosomes were observed by transmission electron microscope and nanoparticle tracking analysis (NTA), and the expression of characteristic proteins CD9 and CD63 of exosomes were detected by Western blotting. The well-growing mouse neuroblastoma N2a cells were divided into six groups: the cells in group C were conventionally-cultured; and the cells in group O were subjected to oxygen-glucose deprivation for 3 hours followed by restoration of oxygen-glucose supply 24 hours to establish the model of oxygen-glucose deprivation and restoration injury; and the N2a cells in group E were co-cultured with M1-exo 24 hours after oxygen-glucose deprivation 3 hours; NC group, M group and I group constructed negative control, overexpression and knockdown of microRNA-20a-5p (miR-20a-5p) M1-exo, respectively. The succession of transfection was detected by qPCR and N2a cells in group NC, group M and group I were co-cultured with such transfected M1-exo for 24 hours after oxygen-glucose deprivation 3 hours. Cell viability were detected by cell counting kit-8 (CCK-8) assay, cell apoptosis were detected by flow cytometry, and the expression of miR-20a-5p were detected by qPCR. RESULTS: Compared with M0 microglia, the fluorescence intensity and mRNA and protein expressions of CD32 and inducible nitric oxide synthase (iNOS), specific markers of M1 microglia, were increased [CD32 (fluorescence intensity): 36.919±1.541 vs. 3.533±0.351, CD32 mRNA (2-ΔΔCt): 4.887±0.031 vs. 1.003±0.012, CD32/ß-actin: 2.663±0.219 vs. 1.000±0.028; iNOS (fluorescence intensity): 29.513±1.197 vs. 7.933±0.378, iNOS mRNA (2-ΔΔCt): 4.829±0.177 vs. 1.000±0.016, iNOS/ß-actin: 1.991±0.035 vs. 1.000±0.045; all P < 0.01], indicating M1 microglia were successfully activated. Under electron microscopy, M1-exo had round or oval vesicular bodies with obvious membranous structures, with diameters ranging from 100 nm. Western blotting showed that the exosomes expressed specific CD63 and CD9 proteins. Compared with group C, the cell viability was decreased, the apoptosis rate and the expression of miR-20a-5p were significantly increased in group O [cell viability (A value): 0.540±0.032 vs. 1.001±0.014, apoptosis rate: (19.857±0.910)% vs. (13.508±0.460)%, miR-20a-5p (2-ΔΔCt): 5.508±0.291 vs. 1.033±0.101, all P < 0.01]. Compared with O group, cell viability was decreased, apoptosis rate and the expression of miR-20a-5p were increased in group E [cell viability (A value): 0.412±0.029 vs. 0.540±0.032, apoptosis rate: (31.802±0.647)% vs. (19.857±0.910)%, miR-20a-5p (2-ΔΔCt): 8.912±0.183 vs. 5.508±0.291, all P < 0.01], indicating that M1 microglia-derived exosomes further aggravated the damage of N2a cells after oxygen-glucose deprivation and restoration. Compared with group E, cell viability was decreased, apoptosis rate and the expression of miR-20a-5p were increased in group M [cell viability (A value): 0.311±0.028 vs. 0.412±0.029, apoptosis rate: (36.343±0.761)% vs. (31.802±0.647)%, miR-20a-5p (2-ΔΔCt): 32.348±0.348 vs. 8.912±0.183, all P < 0.01]; and the cell viability was increased, apoptosis rate and the expression of miR-20a-5p were decreased in group I [cell viability (A value): 0.498±0.017 vs. 0.412±0.029, apoptosis rate: (26.437±0.793)% vs. (31.802±0.647)%, miR-20a-5p (2-ΔΔCt): 6.875±0.219 vs. 8.912±0.183, all P < 0.01]. There was no significant difference in cell viability, apoptosis rate and the expression of miR-20a-5p between group E and group NC. CONCLUSIONS: M1 microglia-derived exosomes aggravate the injury of neurons after oxygen and glucose deprivation and reoxygenation, which may be related to miR-20a-5p carried by M1-exo.

Pontine Myopericytoma: Case Report and Literature Review.

Myopericytoma (MPC) is a benign soft tissue tumor that develops from perivascular myoid cells and is part of the perivascular tumor group. MPC most commonly occurs in the subcutaneous soft tissues of the extremities, while intracranial MPC is remarkably rare. Herein, we report the case of a 45-year-old woman with myopericytoma who had a 2-week history of recurrent dizziness. Magnetic resonance imaging (MRI) revealed an irregular mass in the pons, with nodular enhancement of the mass on contrast-enhanced scans. The mass was considered a vascular lesion and was highly suspected to be a hemangioblastoma, prompting surgical intervention for the patient. The postoperative pathological report corrected the initial diagnosis, hemangioblastoma, to MPC. Intracranial MPC is extremely rare and there are no detailed imaging sources for this condition; furthermore, MPC occurrence in the pons has not been reported previously. This report presents the etiological characteristics intracranial MPC as visualized through MRI data alongside a comparative discussion on other reported diagnoses that resemble MPC. The case findings will provide a more widespread understanding for radiologists regarding the differential diagnosis of intracranial blood-rich supply lesions.