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Abstract Purpose Low back pain (LBP) is a common and recurring public health problem that affects sufferers both physically and mentally and warrants further research. A succession of studies have suggested a plausible role for inflammatory cytokines in the pathogenesis of LBP. To date, there is no conclusive mechanism explaining how inflammatory cytokines affects LBP. Methods A bidirectional two-sample Mendelian randomization (MR) investigation was undertaken in two stages. The initial phase encompassed 41 inflammatory cytokines as the exposure, with LBP as the outcome, and the subsequent phase adopted the inverse approach. A total of 41 blood inflammatory cytokines were extracted from the genome-wide association study meta-analysis database, encompassing 8,293 individuals. Data pertaining to LBP were acquired from the Finnish biobank. Primary findings were computed using inverse-variance weighting (IVW), while sensitivity analyses accounting for pleiotropy and invalid instruments were conducted utilizing the weighted-median estimator, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier. Results Our results suggest that higher levels of Macrophage migration inhibitory factor (MIF) as well as lower levels of C-C motif chemokine ligand 3 (CCL3) are associated with an increased risk of LBP (odds ratio [OR] = 1.134, 95% confidence interval [CI ]= 1.032–1.245, P = 0.009; OR = 0.887, 95% CI = 0.803–0.980, P = 0.018). Moreover, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. In contrast, in studies of the effect of LBP on inflammatory cytokines, genetically determined LBP had no causal effect on 41 inflammatory cytokines (IVW P > 0.05). Conclusions Our study confirms that the levels of circulating MIF and CCL3 may be regarded as valuable circulating inflammatory biomarkers for the management of LBP in clinical practice and as potential molecules for future mechanistic investigation and drug target identification.

Abstract Background Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear. Methods Streptozotocin-induced type 1 diabetic rats were subjected to MI/R injury by occluding the left anterior descending artery (LAD) and followed by reperfusion. IPostC was induced by three cycles of 10s of reperfusion and ischemia at the onset of reperfusion. AAV9-CMV-DJ-1, AAV9-CMV-C106S-DJ-1 or AAV9-DJ-1 siRNA were injected via tail vein to either over-express or knock-down DJ-1 three weeks before inducing MI/R. Results Diabetic rats subjected to MI/R exhibited larger infarct area, more severe oxidative injury concomitant with significantly reduced cardiac DJ-1 expression and increased PTEN expression as compared to non-diabetic rats. AAV9-mediated cardiac DJ-1 overexpression, but not the cardiac overexpression of DJ-1 mutant C106S, restored IPostC-induced cardioprotection and this effect was accompanied by increased cytoplasmic DJ-1 translocation toward nuclear and mitochondrial, reduced PTEN expression, and increased Nrf-2/HO-1 transcription. Our further study showed that AAV9-mediated targeted DJ-1 gene knockdown aggravated MI/R injury in diabetic hearts, and this exacerbation of MI/R injury was partially reversed by IPostC in the presence of PTEN inhibition or Nrf-2 activation. Conclusions These findings suggest that DJ-1 preserves the cardioprotective effect of IPostC against MI/R injury in diabetic rats through nuclear and mitochondrial DJ-1 translocation and that inhibition of cardiac PTEN and activation of Nrf-2/HO-1 may represent the major downstream mechanisms whereby DJ-1 preserves the cardioprotective effect of IPostC in diabetes. Graphical abstract

Cellular senescence, a permanent halt in cell division due to stress, spurs functional and structural changes, contributing to vascular aging characterized by endothelial dysfunction and vascular remodeling. This process raises the risk of ischemic stroke (IS) in older individuals, with its mechanisms still not completely understood despite ongoing research efforts. In this review, we have analyzed the impact of vascular aging on increasing susceptibility and exacerbating the pathology of IS. We have emphasized the detrimental effects of endothelial dysfunction and vascular remodeling influenced by oxidative stress and inflammatory response on vascular aging and IS. Our goal is to aid the understanding of vascular aging and IS pathogenesis, particularly benefiting older adults with high risk of IS.

Abstract Inulin, as a prebiotic, could modulate the gut microbiota. Burn injury leads to gut microbiota disorders and skeletal muscle catabolism. Therefore, whether inulin can improve burn-induced muscle atrophy by regulating microbiota disorders remains unknown. This study aimed to clarify that inulin intake alleviates gut microbiota disorders and skeletal muscle atrophy in burned rats. Rats were divided into the sham group, burn group, prebiotic inulin intervention group, and pseudo-aseptic validation group. A 30% total body surface area (TBSA) third-degree burn wound on dorsal skin was evaluated in all groups except the sham group. Animals in the intervention group received 7 g/L inulin. Animals in the validation group received antibiotic cocktail and inulin treatment. In our study inulin intervention could significantly alleviate the burn-induced skeletal muscle mass decrease and skeletal myoblast cell apoptosis. Inulin intake increased the abundances of Firmicutes and Actinobacteria but decreased the abundance of Proteobacteria. The biosynthesis of amino acids was the most meaningful metabolic pathway distinguishing the inulin intervention group from the burn group, and further mechanistic studies have shown that inulin can promote the phosphorylation of the myogenesis-related proteins PI3K, AKT and P70S6K and activate PI3K/AKT signaling for protein synthesis. In conclusion, inulin alleviated burn induced muscle atrophy through PI3K/AKT signaling and regulated gut microbiota dysbiosis.

ObjectiveCiprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures.MethodsThis phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18–65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at −8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain.ResultsA total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, −4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p

BackgroundThere is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery.MethodsThis multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0–72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0–72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0–72 h postoperatively, NRS scores at rest and on activity at different time points during the 0–72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis.DiscussionWe hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Background: Given that the circadian rhythm is intricately linked to cardiovascular physiological functions, the objective of this investigation was to employ bibliometric visualization analysis in order to scrutinize the trends, hotspots, and prospects of the circadian rhythm and cardiovascular disease (CVD) over the past two decades. Methods: A thorough exploration of the literature related to the circadian rhythm and CVD was conducted via the Web of Science Core Collection database spanning the years 2002–2022. Advanced software tools, including citespace and VOSviewer, were employed to carry out a comprehensive analysis of the co-occurrence and collaborative relationships among countries, institutions, journals, references, and keywords found in this literature. Furthermore, correlation mapping was executed to provide a visual representation of the data. Results: The present study encompassed a total of 3399 published works, comprising of 2691 articles and 708 reviews. The publications under scrutiny were primarily derived from countries such as the United States, Japan, and China. The most prominent research institutions were found to be the University of Vigo, University of Minnesota, and Harvard University. Notably, the journal Chronobiology International, alongside its co-cited publications, had the most substantial contribution to the research in this field. Following an exhaustive analysis, the most frequently observed keywords were identified as circadian rhythm, blood pressure, hypertension, heart rate, heart rate variability, and melatonin. Furthermore, a nascent analysis indicated that future research might gravitate towards topics such as inflammation, metabolism, oxidative stress, and autophagy, thereby indicating new directions for investigation. Conclusion: This analysis represents the first instance of bibliometric scrutiny pertaining to circadian rhythm and its correlation with cardiovascular disease (CVD) through the use of visualization software. Notably, this study has succeeded in highlighting the recent research frontiers and prominent trajectories in this field, thereby providing a valuable contribution to the literature.

Abstract Background The cause of aggravation of diabetic myocardial damage is yet to be elucidated; damage to mitochondrial function has been a longstanding focus of research. During diabetic myocardial ischaemia–reperfusion (MI/R), it remains unclear whether reduced mitochondrial fusion exacerbates myocardial injury by generating free damaged mitochondrial DNA (mitoDNA) and activating the cGAS-STING pathway. Methods In this study, a mouse model of diabetes was established (by feeding mice a high-fat diet (HFD) plus a low dose of streptozotocin (STZ)), a MI/R model was established by cardiac ischaemia for 2 h and reperfusion for 30 min, and a cellular model of glycolipid toxicity induced by high glucose (HG) and palmitic acid (PA) was established in H9C2 cells. Results We observed that altered mitochondrial dynamics during diabetic MI/R led to increased mitoDNA in the cytosol, activation of the cGAS-STING pathway, and phosphorylation of the downstream targets TBK1 and IRF3. In the cellular model we found that cytosolic mitoDNA was the result of reduced mitochondrial fusion induced by HG and PA, which also resulted in cGAS-STING signalling and activation of downstream targets. Moreover, inhibition of STING by H-151 significantly ameliorated myocardial injury induced by MFN2 knockdown in both the cell and mouse models. The use of a fat-soluble antioxidant CoQ10 improved cardiac function in the mouse models. Conclusions Our study elucidated the critical role of cGAS-STING activation, triggered by increased cytosolic mitoDNA due to decreased mitochondrial fusion, in the pathogenesis of diabetic MI/R injury. This provides preclinical insights for the treatment of diabetic MI/R injury. Video Abstract Graphical Abstract

Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs.

Abstract Background Sedative gastrointestinal endoscopy is extensively used worldwide. An appropriate degree of sedation leads to more acceptability and satisfaction. Artificial intelligence has rapidly developed in the field of digestive endoscopy in recent years and we have constructed a mature computer-aided diagnosis (CAD) system. This system can identify the remaining parts to be examined in real-time endoscopic procedures, which may help anesthetists use anesthetics properly to keep patients in an appropriate degree of sedation. Aims This study aimed to evaluate the effects of the CAD system on anesthesia quality control during gastrointestinal endoscopy. Methods We recruited 154 consecutive patients at Renmin Hospital of Wuhan University, including 76 patients in the CAD group and 78 in the control group. Anesthetists in the CAD group were able to see the CAD system’s indications, while anesthetists in the control group could not. The primary outcomes included emergence time (from examination completion to spontaneous eye opening when doctors called the patients’ names), recovery time (from examination completion to achievement of the primary recovery endpoints) and patient satisfaction scores. The secondary outcomes included anesthesia induction time (from sedative administration to successful sedation), procedure time (from scope insertion to scope withdrawal), total dose of propofol, vital signs, etc. This trial was registered in the Primary Registries of the WHO Registry Network, with registration number ChiCTR2100042621. Results Emergence time in the CAD group was significantly shorter than that in the control group (p

Myocardial ischemia-reperfusion injury is a common condition in cardiovascular diseases, and the mechanism of its occurrence involves multiple complex metabolic pathways and signaling pathways. Among these pathways, glucose metabolism and lipid metabolism play important roles in regulating myocardial energy metabolism. Therefore, this article focuses on the roles of glucose metabolism and lipid metabolism in myocardial ischemia-reperfusion injury, including glycolysis, glucose uptake and transport, glycogen metabolism and the pentose phosphate pathway; and triglyceride metabolism, fatty acid uptake and transport, phospholipid metabolism, lipoprotein metabolism, and cholesterol metabolism. Finally, due to the different alterations and development of glucose metabolism and lipid metabolism in myocardial ischemia-reperfusion, there are also complex interregulatory relationships between them. In the future, modulating the equilibrium between glucose metabolism and lipid metabolism in cardiomyocytes and ameliorating aberrations in myocardial energy metabolism represent highly promising novel strategies for addressing myocardial ischemia-reperfusion injury. Therefore, a comprehensive exploration of glycolipid metabolism can offer novel theoretical and clinical insights into the prevention and treatment of myocardial ischemia-reperfusion injury.

Abstract The purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2’-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated.

Background and Purpose: Ciprofol (HSK3486), a novel 2,6-disubstituted phenol derivative, is a new intravenous anesthetic compound with a similar chemical structure to propofol. Animal studies have also shown that propofol plays a protective role in a variety of cardiovascular diseases, including myocardial infarction, myocardial ischemia-reperfusion injury and takotsubo syndrome. However, whether ciprofol exerts cardioprotective effects on myocardial infarction remains unclear. Thus, the aim of this work was to explore the potential cardioprotective mechanism of ciprofol on isoproterenol (ISO)-induced myocardial infarction.Experimental Approach: In the present study, male C57BL/6 mice were subjected to subcutaneous injection of ISO (100 mg/kg) for 2 consecutive days to induce experimental myocardial infarction. Herein, we found that ciprofol could inhibit the abnormal increase in myocardial injury enzymes, the area of myocardial infarction and cardiac dysfunction in ISO-treated mice. Ciprofol administration increased the activity of superoxide dismutase and reduced the levels of NADPH oxidase and malondialdehyde in ISO-treated hearts. Additionally, ciprofol administration markedly reduced the expression of pro-inflammatory cytokines and cardiomyocyte apoptosis. In an in vitro model, the results also confirmed that ciprofol could inhibit ISO-induced oxidative damage, the inflammatory response and cardiomyocyte apoptosis. Moreover, ciprofol can activate the sirtuin1 (Sirt1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and Sirt1 and Nrf2 inhibition almost abolished ciprofol-mediated cardioprotective effects.Interpretation: Ciprofol protects the heart against ISO-induced myocardial infarction by reducing cardiac oxidative stress, the inflammatory response and cardiomyocyte apoptosis.

Postoperative cognitive dysfunction (POCD) is a common postoperative neurological complication in elderly patients. Circular RNAs (circRNAs) are abundant in the mammalian brain and can probably regulate cognitive function. However, the competitive endogenous RNA (ceRNA) regulatory network in POCD remains illiterate. Transcriptomic signatures in the hippocampus of POCD mice derived from the Gene Expression Omnibus (GEO) dataset GSE190880, GSE95070, and GSE115440 were used to identify the circRNA, miRNA, and mRNA expression profiles of POCD mice compared with controls, respectively. A set of differentially expressed RNAs, including 119 circRNAs, 33 miRNAs, and 49 mRNAs were identified. Transcript validation showed the enhanced expression of circ_0001634, circ_0001345, and circ_0001493. A ceRNA regulatory network composed of three circRNAs, three miRNAs, and six mRNAs was established. The hub mRNAs in the ceRNA network were further found to be involved in the hormone catabolic process and regulation of canonical Wnt signaling pathway, revealing their crucial role in POCD. Finally, three miRNAs and four mRNAs were verified by qRT-PCR. These results based on bioinformatics and PCR array suggest that circ_0001634/miR-490-5p/Rbm47, circ_0001634/miR-490-5p/Sostdc1, circ_0001634/miR-7001-5p/Sostdc1, circ_0001345/miR-7001-5p/Sostdc1, and circ_0001493/miR-7001-5p/Sostdc1 may be novel diagnostic biomarkers and therapeutic targets for POCD.

Introduction To investigate the role of CD36 (fatty acid translocation enzyme) in the myocardial ischemia reperfusion (IR) injury in diabetes with ischemic postconditioning (IPostC).Research design and methods Adult male Sprague-Dawley rats received streptozotocin treatment to establish type 1 diabetic model. After 8 weeks, diabetic rats were subjected to myocardial IR and IPostC with or without sulfo-N-succinimidyl oleate (SSO, an inhibitor of CD36) intervention.Results Diabetic rats showed the upregulation of myocardial CD36 expression and the increase in free fatty acid (FA) and triglycerides (TG) level and FA β oxidation (FAO). The cardioprotection of IPostC was compromised in diabetic rats with myocardial IR as evidenced by increased myocardial infarct size and plasma levels of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin Ⅰ (cTn-I), but not in non-diabetic rats with myocardial IR. SSO significantly decreased the levels of plasma LDH, CK-MB, cTn-I, free FA, and the levels of myocardial malondialdehyde, 8-isoprostane, FA, TG, and CD36 expression, and significantly increased the levels of myocardial glutathione peroxidase, total glutathione/oxidized glutathione, FAO, peroxisome proliferator activated receptor alpha, pyruvate dehydrogenase kinase 4, and the early (E) and late (A) diastolic filling ratio of heart in diabetic rats with IR and IPostC. However, no significant differences were observed in myocardial infarct size, heart rate, ejection fraction, fractional shorting, and dp/dtmax.Conclusions CD36 downregulation partially attenuated myocardial IR injury in diabetic rats with IPostC via ameliorating FA metabolism and oxidative stress.

Sepsis is a series of clinical syndromes caused by immunological response to severe infection. As the most important and common complication of sepsis, acute respiratory distress syndrome (ARDS) is associated with poor outcomes and high medical expenses. However, well-described studies of analysis-based researches, especially related bioinformatics analysis on revealing specific targets and underlying molecular mechanisms of sepsis and sepsis-induced ARDS (sepsis/se-ARDS), still remain limited and delayed despite the era of data-driven medicine. In this report, weight gene co-expression network based on data from a public database was constructed to identify the key modules and screen the hub genes. Functional annotation by enrichment analysis of the modular genes also demonstrated the key biological processes and signaling pathway; among which, extensive immune-involved enrichment was remarkably associated with sepsis/se-ARDS. Based on the differential expression analysis, least absolute shrink and selection operator, and multivariable logistic regression analysis of the screened hub genes, SIGLEC9, TSPO, CKS1B and PTTG3P were identified as the candidate biomarkers for the further analysis. Accordingly, a four-gene-based model for diagnostic prediction assessment was established and then developed by sepsis/se-ARDS risk nomogram, whose efficiency was verified by calibration curves and decision curve analyses. In addition, various machine learning algorithms were also applied to develop extra models based on the four genes. Receiver operating characteristic curve analysis proved the great diagnostic and predictive performance of these models, and the multivariable logistic regression of the model was still found to be the best as further verified again by the internal test, training, and external validation cohorts. During the development of sepsis/se-ARDS, the expressions of the identified biomarkers including SIGLEC9, TSPO, CKS1B and PTTG3P were all regulated remarkably and generally exhibited notable correlations with the stages of sepsis/se-ARDS. Moreover, the expression levels of these four genes were substantially correlated during sepsis/se-ARDS. Analysis of immune infiltration showed that multiple immune cells, neutrophils and monocytes in particular, might be closely involved in the process of sepsis/se-ARDS. Besides, SIGLEC9, TSPO, CKS1B and PTTG3P were considerably correlated with the infiltration of various immune cells including neutrophils and monocytes during sepsis/se-ARDS. The discovery of relevant gene co-expression network and immune signatures might provide novel insights into the pathophysiology of sepsis/se-ARDS.

Abstract Background Ultrasound-guided parasternal intercostal nerve block is rarely used for postoperative analgesia, and its value remains unclear. This study aimed to evaluate the effectiveness of ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in patients undergoing median sternotomy for mediastinal mass resection. Methods This randomized, double-blind, placebo-controlled trial performed in Renmin Hospital, Wuhan University, enrolled 41 participants aged 18–65 years. The patients scheduled for mediastinal mass resection by median sternotomy were randomly assigned were randomized into 2 groups, and preoperatively administered 2 injections of ropivacaine (PSI) and saline (control) groups, respectively, in the 3rd and 5th parasternal intercostal spaces with ultrasound-guided (USG) bilateral parasternal intercostal nerve block. Sufentanil via patient-controlled intravenous analgesia (PCIA) was administered to all participants postoperatively. Pain score, total sufentanil consumption, and postoperative adverse events were recorded within the first 24 h. Results There were 20 and 21 patients in the PSI and control group, respectively. The PSI group required 20% less PCIA-sufentanil compared with the control group (54.05 ± 11.14 μg vs. 67.67 ± 8.92 μg, P

(1) SAH induces cellular stress and endoplasmic reticulum stress, activating the unfolded protein response (UPR) in nerve cells. IRE1 (inositol-requiring enzyme 1) is a protein that plays a critical role in cellular stress response. Its final product, Xbp1s, is essential for adapting to changes in the external environment. This process helps maintain proper cellular function in response to various stressors. O-GlcNAcylation, a means of protein modification, has been found to be involved in SAH pathophysiology. SAH can increase the acute O-GlcNAcylation level of nerve cells, which enhances the stress capacity of nerve cells. The GFAT1 enzyme regulates the level of O-GlcNAc modification in cells, which could be a potential target for neuroprotection in SAH. Investigating the IRE1/XBP1s/GFAT1 axis could offer a promising avenue for future research. (2) Methods: SAH was induced using a suture to perforate an artery in mice. HT22 cells with Xbp1 loss- and gain-of-function in neurons were generated. Thiamet-G was used to increase O-GlcNAcylation; (3) Results: Severe neuroinflammation caused by subarachnoid hemorrhage leads to extensive endoplasmic reticulum stress of nerve cells. Xbp1s, the final product of unfolded proteins induced by endoplasmic reticulum stress, can induce the expression of the hexosamine pathway rate limiting enzyme GFAT1, increase the level of O-GlcNAc modification of cells, and have a protective effect on neural cells; (4) Conclusions: The correlation between Xbp1s displayed by immunohistochemistry and O-GlcNAc modification suggests that the IRE1/XBP1 branch of unfolded protein reaction plays a key role in subarachnoid hemorrhage. IRE1/XBP1 branch is a new idea to regulate protein glycosylation modification, and provides a promising strategy for clinical perioperative prevention and treatment of subarachnoid hemorrhage.

Abstract The circadian clock is closely related to the development of diabetes mellitus and cardiovascular disease, and disruption of the circadian clock exacerbates myocardial ischaemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop that controls the expression pattern of the circadian nuclear receptor Rev-erbα to maintain the stability of circadian genes such as BMAL1. However, the mechanism by which the HDAC3-orchestrated Rev-erbα/BMAL1 pathway increases MI/RI in diabetes and its relationship with mitophagy have yet to be elucidated. Here, we observed that the clock genes Rev-erbα, BMAL1, and C/EBPβ oscillations were altered in the hearts of rats with streptozotocin (STZ)-induced diabetes, with upregulated HDAC3 expression. Oscillations of Rev-erbα and BMAL1 were rapidly attenuated in diabetic MI/R hearts versus non-diabetic I/RI hearts, in accordance with impaired and rhythm-disordered circadian-dependent mitophagy that increased injury. Genetic knockdown of HDAC3 significantly attenuated diabetic MI/RI by mediating the Rev-erbα/BMAL1 circadian pathway to recover mitophagy. Primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA were exposed to hypoxia/reoxygenation (H/R) in vitro. The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high-glucose conditions compared with low-glucose conditions, with decreased BMAL1 expression and mitophagy levels. After H/R stimulation, high glucose aggravated H/R injury, with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 and mitophagy levels. HDAC3 and Rev-erbα siRNA can alleviate high glucose-induced and H/R-induced injury by upregulating BMAL1 to increase mitophagy. Collectively, these findings suggest that disruption of HDAC3-mediated circadian gene expression oscillations induces mitophagy dysfunction, aggravating diabetic MI/RI. Cardiac-specific HDAC3 knockdown could alleviate diabetic MI/RI by regulating the Rev-erbα/BMAL1 pathway to restore the activation of mitophagy.

Background: To determine whether abnormal coagulation parameters are associated with disease severity and poor prognosis in patients with 2019 Corona Virus Disease (COVID-19). Methods: A systematic literature search was conducted using the databases PubMed, Embase, and Web of sciences until April 25, 2020. We included a total of 15 studies with 2277 patients. Platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), and fibrinogen (FIB) were collected and analyzed. The statistical results were expressed as the effect measured by mean difference (MD) with the related 95% confidence interval (CI). Results: The PLT level of severe cases was lower than that of mild cases, while the levels of PT, D-D, and FIB were higher than those of mild cases (P < 0.05). The level of APTT had no statistical difference between two groups (P > 0.05). PT of ICU patients was significantly longer (P < 0.05) than that of non-ICU patients. In non-survivors, PT and D-D were higher, yet PLT was lower than that of survivors (P < 0.05). There was no significant difference in APTT between survivors and non-survivors (P > 0.05). The funnel plot and Egger's regression test demonstrated that there was no publication bias. Conclusions: Our data support the notion that coagulopathy could be considered as a risk factor for disease severity and mortality of COVID-19, which may help clinicians to identify the incidence of poor outcomes in COVID-19 patients.

In the past 16 years, research on mitophagy has increasingly expanded to a wider range of subjects. Therefore, comprehensively analyzing the relevant progress and development trends on mitophagy research requires specific methods. To assess the hotspots, directions, and quality of results in this field worldwide, we used multiple tools to examine research progress and growing trends in research on the matter during the last 16 years (from 2005 to 2020). We also compared the quantity and quality of the literature records on mitophagy published by research institutions in China and other developed countries, reviewed China’s contribution, and examined the gap between China and these developed countries. According to the results of our bibliometric analysis, the United States and its research institutes published the most papers. We identified cell biology as the most commonly researched subject on mitophagy and AUTOPHAGY as the most popular journal for research on mitophagy. We also listed the most cited documents from around the world and China. With gradually increased funding, China is progressively becoming prominent in the field of mitophagy; nevertheless, the gap between her and major countries in the world must be closed.

(1) Background: As the most common malignant tumor type worldwide, it is necessary to identify novel potential prognostic biomarkers to improve the poor prognosis of lung cancer. The Timeless gene, a circadian rhythm-related gene, is associated with several types of cancer. However, studies analyzing the clinical significance of the Timeless gene in patients with lung cancer are currently limited. (2) Methods: In the present study, the expression levels and prognostic potential of the Timeless gene and its co-expressed genes in different subtypes of lung cancer were explored using multiple bioinformatics approaches. The correlations between the Timeless gene and its co-expressed genes were validated using A549 and NCI-H226 cells by transfecting them with expression vectors and analyses using Western blot and reverse transcription-quantitative PCR. (3) Results: The Oncomine and GEPIA database analyses indicated that the expression of the Timeless gene was significantly higher in lung cancer as compared to that in the normal tissue. Using the UALCAN database, significant differences in Timeless gene expression were determined among different stages of lung cancer and between genders. A Kaplan–Meier plotter analysis indicated that high expression of the Timeless gene was associated with poor overall survival (OS) and progression-free survival (PFS) of patients with lung cancer. In the cBioPortal and GEPIA database analyses, extra spindle pole bodies like 1 (ESPL1) was the top correlated gene of Timeless in patients with lung cancer. Similar to the Timeless gene, high expression of the ESPL1 gene was also associated with poor OS and PFS. Of note, overexpression of the Timeless gene increased the expression level of ESPL1 at both the mRNA and protein levels. (4) Conclusion: The present study explored the clinical significance of the Timeless gene and its correlated gene ESPL1 in patients with lung cancer, thereby providing a potential therapeutic target for lung cancer.

Background: SARS-CoV-2 infection was referred to sympathetic hyperactivity, which might increase the susceptibility of neuraxial anesthesia-related hypotension resulted from sympathetic inhibition. We conducted a multicenter, retrospective, propensity score matched (PSM) cohort study to determine whether COVID-19 parturients have an increased risk of hypotension after neuraxial anesthesia for cesarean delivery.Methods: Clinical data of COVID-19 parturients were collected from the electronic medical records from 1th January to 31th May, 2020 in three hospitals of Hubei Province, China. Information of Control parturients (without COVID-19) were obtained at the same institutions over a similar period in 2019. All American Society of Anaesthesiologists (ASA) Physical Status II full termed pregnant women who received cesarean delivery under neuraxial anesthesia were included. The primary objective was to obtain and compare the incidence of neuraxial anesthesia-related hypotension. Secondary objectives were the analysis of anesthetic implementation and administration, intraoperative maternal vital signs and adverse reactions, and neonatal Apgar scores at 1 and 5 min after delivery. The clinical characteristics of COVID-19 parturients were also analyzed. PSM was derived to balance the predictors for neuraxial anesthesia-related hypotension based on previous studies.Results: In present study, 101 COVID-19 parturients and 186 Control parturients were derived from 1,403 cases referenced to propensity score matching. The incidence of neuraxial anesthesia-related hypotension was 57.4% in COVID-19 parturients and 41.9% in Control parturients with an incidence risk ratio (IRR) of 1.37 (95% CI 1.08–1.74; P = 0.012; post-hoc Cramér's V = 0.15) in the PSM cohort. The incidences of nausea, vomiting, dizziness, and shaking were significantly higher in the COVID-19 group than Control group (48.5 vs. 17.2%, P < 0.001; 10.9 vs. 4.3%, P = 0.03; 18.8 vs. 3.2%, P < 0.001; 51.5 vs. 18.3%, P < 0.001; respectively). The Apgar scores at 1 min was significantly lower in newborns from COVID-19 parturients than that in Control babies (P = 0.04).Conclusions: An increased risk of neuraxial anesthesia-related hypotension in COVID-19 parturients undergoing cesarean delivery should be stressed.

Objective: This study was to explore the research status and research hotspots of ferritinophagy in the past eight years. Methods: Relevant papers on ferritinophagy from 2014 to 2021 was retrieved from the science citation extended database of the Web of Science. Through the application of bibliometrics research methods and bibliometrics analysis software VOSviewer to extract, analyze and visualize journals, authors, research institutions and keywords, to clarify the hot spots and development history of peritoneal dialysis research. Results: A total of 134 studies were screened and included in this study. Overall, the output of ferritinophagy research had fluctuated in the past 8 years. China’s research on ferritinophagy had the largest number of published articles. The United States still maintained a leading position in research in this field, and its citation frequency, H-index and funding output are all at the forefront. Among them, international cooperation with relevant institutions was also more frequent. Ferritinophagy was currently mainly focused on cell biology. Tumor research might be the next major clinical research direction in this field. The related research on oxidative stress pathways, cell death methods, and nuclear receptor co-activator 4 (NCOA4) in the field of ferritinophagy were current research hotspots. Conclusions: It could be understanding the research status and hotspots of ferritinophagy in the world more clearly and intuitively by using the bibliometric method.

Thirty-six anesthesia departments in 36 hospitals in four provinces of China where an outbreak of COVID-19 occurred were surveyed. We found that there were ten anesthesiologists (5 male and 5 female) who contracted the infection after performing intubation, as well as 4 nurses (1 male and 3 female) who contracted the infection after assisting with the intubation. This is a retrospective investigation and no intervention was applied.The numbers are presented as mean ± Standard Deviation (SD). We used Graphpad Prism (version 8.2.1 Windows version, GraphPad Software, San Diego). Fisher's exact test at a two-sided significance level of 0.05 was used to identify potential risk factor (s) for intubation providers. A P value less than 0.05 is considered statistically significant. A total of 211 anesthesiologists from four provinces were involved in the intubation of 664 patients with confirmed or potential COVID-19. Of these 644 patients, 640 cases were eventually confirmed with a diagnosis of COVID-19. Among the 211 anesthesiologists who performed intubation, 10 of them had a confirmed diagnosis of COVID-19 afterwards. Coughing is a risk factor for provider infection (P = 0.0001). The number of intubation attempts (within three attempts) did not increase the risk of the infection. All of the affected anesthesiologists had symptoms 2–12 days after the intubation encounter (average 6 ± 3 days). All had radiological image evidence of bilateral pneumonia and all reported relatively mild symptoms. The affected doctors were out of clinical service for 20–60 days (average 46 ± 12 days). Seven of the doctors have been discharged from the hospital, but three of them remain hospitalized. Four nurses who assisted with intubations contracted COVID-19. One of these nurses was in critical condition but was eventually discharged with a loss of 50 days of clinical service. The remaining three nurses have had mild symptoms so far, but one is still hospitalized.

ObjectiveThe outbreak of coronavirus disease 2019 (COVID-19) has considerably burdened the healthcare system in the Hubei Province, the most severely affected region in China. The aim of our study was to assess the psychological effects of COVID-19 epidemic on the healthcare workers in Hubei.MethodsA total of 2737 healthcare workers were sampled using a two-dimensional code shared online between Mar 4 and Mar 9, 2020. The questionnaires consisted of three elements: baseline characteristics, Pittsburgh Sleep Quality Index (PSQI), and Hospital Anxiety and Depression Scale (HADS). The primary outcome variables were PQSI, anxiety and depression scores of non-medical staff, non-frontline medical staff and frontline medical staff. Binary logistical regression analyses were used to compare between respondents with and without sleep disturbance.ResultsAbout 61.6% of the respondents reported sleep problems, 22.6% experienced anxiety, and 35% exhibited depressive symptoms. The prevalence of sleep disorders was higher among the frontline healthcare workers compared to the non-frontline and non-medical staff, while anxiety and depression were prevalent in the entire cohort. Logistic regression analysis identified medical occupation, family burden, bereavement, anxiety, and depression as significantly predictive of poor sleep quality.ConclusionsFrontline medical staff are more vulnerable to sleep disturbances. Psychosocial interventions are needed to help allied healthcare personnel to better respond to COVID-19 and future outbreaks.

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P

Neuropathic pain is an intractable comorbidity of spinal cord injury. Increasing noncoding RNAs have been implicated in neuropathic pain development. lncRNAs have been recognized as significant regulators of neuropathic pain. lncRNA Small Nucleolar RNA Host Gene 4 (SNHG4) is associated with several tumors. However, the molecular mechanisms of SNHG4 in neuropathic pain remain barely documented. Here, we evaluated the function of SNHG4 in spinal nerve ligation (SNL) rat models. We observed that SNHG4 was significantly upregulated in SNL rat. Knockdown of SNHG4 was able to attenuate neuropathic pain progression via regulating behaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, knockdown of SNHG4 could repress the neuroinflammation via inhibiting IL-6, IL-12, and TNF-α while inducing IL-10 levels. Additionally, miR-423-5p was predicted as the target of SNHG4 by employing bioinformatics analysis. miR-423-5p has been reported to exert significantly poorer in several diseases. However, the role of miR-423-5p in the development of neuropathic pain is needed to be clarified. Here, in our investigation, RIP assay confirmed the correlation between miR-423-5p and SNHG4. Meanwhile, we found that miR-423-5p was significantly decreased in SNL rat models. SNHG4 regulated miR-423-5p expression negatively. As exhibited, the loss of miR-423-5p contributed to neuropathic pain progression, which was rescued by the silence of SNHG4. Therefore, our study indicated SNHG4 as a novel therapeutic target for neuropathic pain via sponging miR-423-5p.

Abstract Background There has been tremendous change on neuropathic pain research in the past 20 years in China and around the world. We analyzed the global trend of neuropathic pain research and compared China’s quantity and quality of neuropathic pain-related publications with other developed countries. Methods Using terms “neuropathic pain”, we retrieved related publications from the Web of Science (WOS) database and PubMed database. From different aspects, such as the number of papers, total citations, average citations per item, H-index, research types, orientation, institutions, journals and funding, global neuropathic pain publications were classified and analyzed. Results From 1998 to 2017, 21,733 articles regarding neuropathic pain research were published worldwide. Of these, 9.394% were contributed by authors from Chinese institutions, which followed USA and ranked second. However, the quality indicators of publications, including total citations, average citations per item and H-index, were relatively low in China. High contribution journals and the 10 most-cited articles on neuropathic pain in world and China were also listed, which also can reflect the quality of neuropathic pain. Based on National Natural Science Foundation of China (NSFC), basic research was the main articles type, accounting for 32.91% of China’s neuropathic pain research. Conclusion Global neuropathic pain research increased rapidly during the 1998 to 2017 period. The USA was still the leader of neuropathic research. Although China had made great achievements, there was a significant gap in the high-quality studies between China and other leading countries.

Abstract Purpose: To investigate whether modulating GSK-3β could attenuate myocardial ischemia reperfusion injury (MIRI) induced acute lung injury (ALI) and analyze the underlying mechanism. Methods: Male SD rats were subjected to MIRI with or without myocardial ischemic post-conditioning in the presence or absence of GSK-3β inhibitor. GSK-3β inhibitor was injected peritoneally 10min before MIRI. Lung W/D weight ratio, MPO, PMNs, histopathological changes, TUNEL, Bax, Bcl-2, IL-6, IL-8, IL-10, GSK-3β, and caspase-3 were evaluated in the lung tissues of all rats. Results: After MIRI, lung injury was significantly increased manifested as significant morphological changes and increased leukocytes in the interstitial capillaries, Lung W/D ratio, MPO, and PMN in BALF, which was associated with enhanced inflammation evidenced by increased expressions of IL-6, IL-8 and reduced expression of IL-10. MIRI significantly increased cell apoptosis in the lung as increased levels of apoptotosis, Bax, cleaved caspase-3, and reduced expression of Bcl-2 was observed, which was concomitant with reduced p-GSK-3β. All these changes were reversed/prevented by ischemic post-conditioning, while these beneficial effects of ischemic post-conditioning were abolished by GSK-3β inhibition. Conclusion: Myocardial ischemia reperfusion injury induces acute lung injury by induction of inflammation and cell apoptosis. Ischemic post-conditioning protects the lung from ALI following MIRI by increasing p-GSK-3β.

Abstract Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1β, TNF-α in spinal cord were determined. Results: Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1β, TNF-α were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.

Abstract Purpose: To investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R). Methods: Male Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot. Results: Propofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group, Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin. Conclusion: PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.

Patients with diabetes are vulnerable to myocardial ischemia reperfusion (IR) injury, which may also induce acute lung injury (ALI) due to overaccumulation of reactive oxygen species (ROS) and inflammation cytokine in circulation. Despite autophagy plays a significant role in diabetes and pulmonary IR injury, the role of autophagy in ALI secondary to myocardial IR in diabetes remains largely elusive. We aimed to investigate pulmonary autophagy status and its roles in oxidative stress and inflammation reaction in lung tissues from diabetic rats subjected to myocardial IR. Control or diabetic rats were either treated with or without autophagy inducer rapamycin (Rap) or autophagy inhibitor 3-methyladenine (3-MA) before myocardial IR, which was achieved by occluding the left anterior descending coronary artery for 30 min and followed by reperfusion for 120 min. Diabetic rats subjected to myocardial IR showed more serious ALI with higher lung injury score and WET/DRY ratio and lower PaO2 as compared with control rats, accompanied with impaired autophagy indicated by reduced LC-3II/LC-3I ratio and Beclin-1 expression, decreased superoxide dismutase (SOD) activity, and increased 15-F2t-Isoprostane formation in lung tissues, as well as increased levels of leukocyte count and proinflammatory cytokines in BAL fluid. Improving autophagy with Rap significantly attenuated all these changes, but the autophagy inhibitor 3-MA exhibited adverse or opposite effects as Rap. In conclusion, diabetic lungs are more vulnerable to myocardial IR, which are involved in impaired autophagy. Improving autophagy could attenuate ALI induced by myocardial IR in diabetic rats, possibly through inhibiting inflammatory reaction and oxidative stress.

Background. Patients with diabetes are more vulnerable to myocardial ischemia reperfusion injury (IRI), which is involved in PKCβ2 activation and mitochondrial dysfunction. Glycine has been documented as a cytoprotective agent to attenuate diabetes-related abnormalities and reduce myocardial IRI, but the underlying mechanisms are still unclear. We determined whether glycine could attenuate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by inhibiting PKCβ2 activation and improving mitochondrial quality in cultured H9C2 cells. Methods. H9C2 cells were either exposed to low glucose (LG) or HG conditions with or without treatment of glycine or CGP53353 (a selective inhibitor of PKCβ2) for 48 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration were detected using corresponding commercial kits. Mitochondrial quality control-related proteins (LC-3II, Mfn-2, and Cyt-C) and PKCβ2 activation were detected by Western blot. Results. HG stimulation significantly decreased cell viability and SOD activity and increased LDH release, MDA production, and PKCβ2 activation as compared to LG group, all of which changes were further increased by H/R insult. Glycine or CGP53353 treatment significantly reduced the increase of LDH release, MDA production, PKCβ2 activation, and Cyt-C expression and the decrease of cell viability, SOD activity, MMP, Mfn-2 expression, and LC-3II/LC-3I ratio induced by HG and H/R stimulation. Conclusions. Supplementary glycine protects H9C2 cells from HG- and H/R-induced cellular injury by suppressing PKCβ2 activation and improving mitochondria quality.

Inadvertent intraoperative hypothermia (core temperature 2 h) (OR = 2.60, 95% CI 2.09-3.24).The incidence of intraoperative hypothermia in China is high, and the rate of active warming of patients during operation is low. Hypothermia is associated with more postoperative shivering, increased ICU admissions, and longer postoperative hospital days.

Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.

Voltage instability, power imbalance, and unreliability are caused mainly by equipment failure in the distribution system, so it is important to accurately and quickly assess the status of distribution network equipment. However, it is challenging to detect equipment failures, the traditional XGBoost algorithm is unsuitable because some evaluation indices are incompetent to quantify. To address these issues, we propose a fast evaluation method for the state of electrical distribution equipment based on fuzzy decision-making. Firstly, key indices are selected from the multi-source equipment information. Secondly, this paper constructs the mapping between key indices and equipment status scores by combining the fuzzy iterative method and the XGBoost algorithm. Finally, the proposed assessment model is confirmed by using the distribution transformers as an example. The result shows that the proposed multi-source information assessment method can quickly and accurately determine the operation status of electrical distribution equipment, and the proposed method has better accuracy than the traditional method. [ABSTRACT FROM AUTHOR]

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease that currently cannot be completely cured with a great health burden. Since the production of autoantibodies plays a key role in the pathogenesis of SLE, discovering the underlying immunoregulation mechanism of B cells will be helpful for developing promising immunotherapy for SLE. In recent studies, dopamine receptors (DRDs), G protein-coupled receptors that include D1-like and D2-like subtypes, are expressed on B cells and participate in various physiological processes, involving immune responses. However, the regulatory effect of DRDs on B cells has not been determined. Methods This study explored the expression of DRDs on B-cell subsets from SLE patients and healthy individuals. The effects of D1-like receptor on B-cell activation and differentiation were further explored using D1-like receptor agonists or antagonists. RNA-seq and bioinformatics analyses were used to identify specific molecular mechanisms involved. Results The D1-like DRDs on B cells of SLE patients were highly expressed compared with those of healthy controls (HCs). D1-like receptor agonist treatment exacerbated lupus-like symptoms in pristane-induced lupus-like mice, while D1-like receptor antagonists alleviated the lupus-like phenotypes. Inhibition of D1-like receptor signals impeded B-cell differentiation, while activation of D1-like receptor signals could promote B cell differentiation. Further RNA-seq confirmed that PTGS2, a gene related to B-cell differentiation, was up-regulated once the D1-like receptor signals were activated, while BMP6 and IL-24 were up-regulated once the D1-like receptor signals were inhibited. Conclusion D1-like receptors probably promote B-cell differentiation through the PTGS2/PRDM1 pathway.