CircBCL2L13 attenuates cardiomyocyte oxidative stress and apoptosis in cardiac ischemia‒reperfusion injury via miR-1246/PEG3 signaling.

Ischemia‒reperfusion (I/R) is a common complication in the clinical treatment of acute myocardial infarction (MI), in which cardiomyocytes play a pivotal role in the recovery of cardiac function after reperfusion injury. The expression of numerous circular ribonucleic acids (circRNAs) is disrupted in I/R-induced cardiac damage, but the potential role of circRNAs in I/R damage has not been fully elucidated. The purpose of the present study was to clarify the biological action and molecular mechanism of circRNA 002166 (also termed circCL2L13) in postmyocardial I/R. Oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vivo model was performed to simulate I/R damage. real-time polymerase chain reaction analysis was also conducted to evaluate the relationships of the SOD1, SOD2, NRF2, HO1 and GPX4 indicators with oxidative stress injury. TUNEL immunofluorescence was used to evaluate the degree of cardiomyocyte apoptosis in the different treatment groups. The circBCL2L13 level was markedly upregulated in myocardial tissues from a mouse I/R model. Overexpression of circBCL2L13 markedly attenuated the expression of oxidative stress-related genes and apoptosis in OGD/R-induced cardiomyocytes. A mechanistic study revealed that circBCL2L13 functions as a ceRNA for miR-1246 and modulates paternally expressed gene 3 (PEG3). Eventually, circBCL2L13 was proven to regulate PEG3 by targeting miR-1246, thereby protecting against OGD/R-induced cardiomyocyte oxidative damage and apoptosis. In conclusion, our study confirmed that the circBCL2L13/miR-1246/PEG3 axis suppressed the progression of OGD/R injury in cardiomyocytes, which might lead to new therapeutic strategies for cardiac I/R injury.

Secrecy Energy Efficiency Enhancement in UAV-Assisted MEC System.

A secrecy energy efficiency optimization scheme for a multifunctional unmanned aerial vehicle (UAV) assisted mobile edge computing system is proposed to solve the computing power and security issues in the Internet-of-Things scenario. The UAV can switch roles between a computing UAV and jamming UAV based on the channel conditions. To ensure the security of the content and the system energy efficiency in the process of offloading computing tasks, the UAV trajectory, uplink transmit power, user scheduling, and offload task are jointly optimized, and an updated-rate assisted block coordinate descent (BCD) algorithm is used. Simulation results show that this scheme efficiently improves the secrecy performance and energy efficiency of the system. Compared with the benchmark scheme, the secrecy energy efficiency of the scheme is improved by 38.5%.

The psc-CVM assessment system: A three-stage type system for CVM assessment based on deep learning.

BACKGROUND: Many scholars have proven cervical vertebral maturation (CVM) method can predict the growth and development and assist in choosing the best time for treatment. However, assessing CVM is a complex process. The experience and seniority of the clinicians have an enormous impact on judgment. This study aims to establish a fully automated, high-accuracy CVM assessment system called the psc-CVM assessment system, based on deep learning, to provide valuable reference information for the growth period determination. METHODS: This study used 10,200 lateral cephalograms as the data set (7111 in train set, 1544 in validation set and 1545 in test set) to train the system. The psc-CVM assessment system is designed as three parts with different roles, each operating in a specific order. 1) Position Network for locating the position of cervical vertebrae; 2) Shape Recognition Network for recognizing and extracting the shapes of cervical vertebrae; and 3) CVM Assessment Network for assessing CVM according to the shapes of cervical vertebrae. Statistical analysis was conducted to detect the performance of the system and the agreement of CVM assessment between the system and the expert panel. Heat maps were analyzed to understand better what the system had learned. The area of the third (C3), fourth (C4) cervical vertebrae and the lower edge of second (C2) cervical vertebrae were activated when the system was assessing the images. RESULTS: The system has achieved good performance for CVM assessment with an average AUC (the area under the curve) of 0.94 and total accuracy of 70.42%, as evaluated on the test set. The Cohen's Kappa between the system and the expert panel is 0.645. The weighted Kappa between the system and the expert panel is 0.844. The overall ICC between the psc-CVM assessment system and the expert panel was 0.946. The F1 score rank for the psc-CVM assessment system was: CVS (cervical vertebral maturation stage) 6 > CVS1 > CVS4 > CVS5 > CVS3 > CVS2. CONCLUSIONS: The results showed that the psc-CVM assessment system achieved high accuracy in CVM assessment. The system in this study was significantly consistent with expert panels in CVM assessment, indicating that the system can be used as an efficient, accurate, and stable diagnostic aid to provide a clinical aid for determining growth and developmental stages by CVM.

Effects of the advanced mandibular spring on mandibular retrognathia treatment: a three-dimensional finite element study.

BACKGROUND: The Advanced Mandibular Spring (AMS) was newly developed as a dentofacial orthopedic appliance in conjunctive use of clear aligners to treat Class II malocclusion with mandibular retrognathia in adolescents. This study aimed to launch a biomechanical assessment and evaluate whether the stress patterns generated by AMS promote mandibular growth. METHODS: A three-dimensional finite element model was constructed using images of CBCT and spiral CT. The model consisted of craniomaxillofacial bones, articular discs, retrodiscal elastic stratum, masticatory muscle, teeth, periodontal ligament, aligner and AMS. Mechanical effects were analyzed in three types of models: mandibular postural position, mandibular advancement with AMS, and mandibular advancement with only muscular force. RESULTS: The stress generated by AMS was distributed to all teeth and periodontal ligament, pushing mandibular teeth forward and maxillary teeth backward. In the temporomandibular joint area, the pressure in the superior and posterior aspects of the condyle was reduced, which conformed to the stress pattern promoting condylar and mandibular growth. Stress distribution became even in the anterior aspect of the condyle and the articular disc. Significant tensile stress was generated in the posterior aspect of the glenoid fossa, which conformed to the stress pattern stimulating the remodeling of the fossa. CONCLUSIONS: AMS created a favorable biomechanical environment for treating mandibular retrognathia in adolescents.

Hypersensitivity Caused by Cosmetic Injection: Systematic Review and Case Report.

OBJECTIVE: Botulinum toxin injection, micro-needling injection, and filler injection are the most widely used non-surgical facial cosmetic treatments. Hypersensitivity reactions associated with injections have not received sufficient attention due to their low incidence rates. The authors tried to summarize the characteristics of the hypersensitivity caused by cosmetic injections and helped to improve the diagnosis and treatment. METHODS: A comprehensive search of the PubMed database to September 2019 was performed. Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, injection information (injected material, trade name, location of injection, symptoms of allergy, time of onset), diagnostic examination, treatment, and prognosis. RESULTS: A total of 14 articles (57 patients) were included. There were 3 patients receiving botulinum toxin injection, 3 patients receiving micro-needling injection, and 46 patients receiving hyaluronic acid injection. Five patients were injected with collagen, polyacrylamide, paraffin, alkyl-imide or hyaluronidase, separately. The symptoms were redness, swelling, itching or induration at the injection site. The diagnosis and treatment methods vary greatly depending on the injection fillers. Removing the injected filler is the primary treatment. CONCLUSION: Although hypersensitivity reaction is a relatively uncommon adverse event, more practice guidelines and research on diagnosis and treatment are demanded to help improve the outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .

Higher risk of revision in total knee arthroplasty after high tibial osteotomy: a systematic review and updated meta-analysis.

BACKGROUND: High tibial osteotomy is commonly performed in young patients with high activity demand. Several studies have reported outcome of HTO. The reported 10-year survival ranged from 79 to 97.6%. The reported 15-year survival ranged from 56 to 65.5%, resulting in the need for conversion to TKA. Primary TKA now provides satisfactory long-term outcome in terms of function and survival. Researches have been conducted to compare clinical outcome between primary TKA and TKA after HTO to see if TKA should be the prior treatment rather than HTO in some cases. But the results were inconsistent. This study aims to compare the risk of revision and other parameters between total knee arthroplasty after high tibial osteotomy and primary total knee arthroplasty. METHODS: Searches and screens of the relevant literature were conducted, after which data were extracted and pooled analysis was performed to compare the clinical outcomes between the two groups. RESULTS: A total of 14 studies with 144,692 cases were included. Pooled analysis showed significantly more revisions and complications, and more tibial component loosening and impingement in postoperative X-ray in the HTO-TKA group. Surgical complexity during conversion to total knee arthroplasty was summarised and listed in table. CONCLUSION: High tibial osteotomy offers satisfactory pain relief and functional outcome in selected patients with high activity demand. However, the need for subsequent TKA should be noted, which might be a technically challenging procedure with significantly higher risk of revision comparing to primary TKA.

Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis.

BACKGROUND: In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. METHODS: Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. RESULT: Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P < 0.02) and inferior 5 year recurrence free survival(P = 0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P = 0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P = 0.24). CONCLUSION: Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

Loss of long non-coding RNA CRRL promotes cardiomyocyte regeneration and improves cardiac repair by functioning as a competing endogenous RNA.

Long noncoding RNAs (lncRNAs) play critical roles in the development of myocardial hypertrophy and may stimulate endogenous myocardial regeneration to prevent heart failure after myocardial infarction (MI). However, whether lncRNAs are involved in regulating myocardial regeneration after MI remains unclear. The present study aimed to identify human-derived lncRNAs that are involved in endogenous cardiomyocyte (CM) regeneration. By analyzing publicly available RNA-seq data of human fetal and normal adult cardiac tissues, we identified a novel human-derived adult upregulated lncRNA designated cardiomyocyte regeneration-related lncRNA (CRRL). Bioinformatics analysis indicated that CRRL is involved in the negative regulation of CM proliferation. First, we observed that the loss of CRRL attenuates post-MI remodeling and preserves cardiac function in adult rats. Through loss-of-function approaches, we found that CRRL knockdown promotes neonatal rat CM proliferation both in vivo and in vitro. Furthermore, we demonstrated that CRRL acts as a competing endogenous RNA (ceRNA) by directly binding to miR-199a-3p and thereby increasing the expression of Hopx, a target gene of miR-199a-3p and a critical negative regulatory factor of CM proliferation. Thus, CRRL suppresses cardiomyocyte regeneration by directly binding to miR-199a-3p, indicating that loss of CRRL facilitates myocardial regeneration and may be a new potential therapeutic strategy for heart failure.

LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing.

BACKGROUND/AIMS: In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. METHODS: Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. RESULTS: A total of 269 lncRNAs (159 up-regulated and 110 down-regulated) and 2, 255 mRNAs (1 294 up-regulated and 961 down-regulated) were aberrantly expressed in human TAD (fold-change> 1.5, P< 0.05). QRT-PCR results of five dysregulated genes were consistent with HTS data. A lncRNA-mRNA coexpression analysis showed positive correlations between the up-regulated lncRNA (ENSG00000269936) and its adjacent up-regulated mRNA (MAP2K6, R=0.940, P< 0.01), and between the down-regulated lncRNA_1421 and its down-regulated mRNAs (FBLN5, R=0.950, P< 0.01; ACTA2, R=0.96, P< 0.01; TIMP3, R=0.96, P< 0.05). The lncRNA-miRNA-mRNA network indicated that the up-regulated lncRNA XIST and p21 had similar sequences targeted by has-miR-17-5p. The results of luciferase assay and fluorescence immuno-cytochemistry were consistent with that. And qRT-PCR results showed that lncRNA XIST and p21 were expressed at a higher level and has-miR-17-5p was expressed at a lower level in TAD than in NA. The predicted binding motifs of three up-regulated lncRNAs (ENSG00000248508, ENSG00000226530, and EG00000259719) were correlated with up-regulated RUNX1 (R=0.982, P< 0.001; R=0.967, P< 0.01; R=0.960, P< 0.01, respectively). CONCLUSIONS: Our study revealed a set of dysregulated lncRNAs and predicted their multiple potential functions in human TAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD.

Diagnostic Ultrasound and Microbubbles Treatment Improves Outcomes of Coronary No-Reflow in Canine Models by Sonothrombolysis.

OBJECTIVES: Effective treatment for microvascular thrombosis-induced coronary no-reflow remains an unmet clinical need. This study sought to evaluate whether diagnostic ultrasound and microbubbles treatment could improve outcomes of coronary no-reflow by dissolving platelet- and erythrocyte-rich microthrombi. DESIGN: Randomized controlled laboratory investigation. SETTING: Research laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: Coronary no-reflow models induced by platelet- or erythrocyte-rich microthrombi were established and randomly assigned to control, ultrasound, recombinant tissue-type plasminogen activator, ultrasound + microbubbles, or ultrasound + microbubbles + recombinant tissue-type plasminogen activator group. All treatments lasted for 30 minutes. MEASUREMENTS AND MAIN RESULTS: Percentage of microemboli-obstructed coronary arterioles was lower in ultrasound + microbubbles group than that in control group for platelet- (> 50% obstruction: 10.20% ± 3.56% vs 31.80% ± 3.96%; < 50% obstruction: 14.80% ± 4.15% vs 28.20% ± 3.56%) and erythrocyte-rich microthrombi (> 50% obstruction: 8.20% ± 3.11% vs 30.60% ± 4.83%; < 50% obstruction: 12.80% ± 4.15% vs 25.80% ± 3.70%) (p < 0.001). Percentage change of myocardial blood flow in left anterior descending artery-dominated region, left ventricular ejection fraction, fractional shortening, and ST-segment resolution were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme were lower in ultrasound + microbubbles group than that in control group for both types of microthrombi (p < 0.001). Percentage change of myocardial blood flow, ejection fraction, fractional shortening, and ST-segment resolution were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme were lower in ultrasound + microbubbles and ultrasound + microbubbles + recombinant tissue-type plasminogen activator groups than that in recombinant tissue-type plasminogen activator group for platelet-rich microthrombi (p < 0.05). CONCLUSIONS: Ultrasound + microbubbles treatment could dissolve platelet- and erythrocyte-rich microthrombi, thereby improving outcomes of coronary no-reflow, making it a promising supplement to current reperfusion therapy for acute ST-segment elevation myocardial infarction.

Large Size Microneedle Patch to Deliver Lidocaine through Skin.

PURPOSE: Current topical treatments using lidocaine (LD) for analgesia have limited applications due to their delayed analgesic actions, resulted from slow drug permeation through skin. The aim of this study is to fabricate a large size microneedle (MN) array patch containing LD, with fast onset of action, for the treatment of acute and chronic pain. METHODS: The MN patch was developed through photolithography and tested for its mechanical characteristics. In vitro and in vivo skin permeation, plasma pharmacokinetics, histology and skin irritation testing have also been performed for the MN patches. RESULTS: The MN have a mechanical strength of 10-30 N and more than 90% of the microneedles on the patch penetrated skin. It was shown that LD permeated through skin within 5 min of patch application. Subsequently, the in vivo skin permeation study using a porcine model showed that LD administrated by the MN patch was able to achieve the therapeutic level locally within 10 min and sustained for 8 h. It shows most of the drug diffuses perpendicularly against skin, with little lateral diffusion. After skin permeation LD remains within skin and unquantifiable amount of LD was found in the plasma of the pigs. Minor skin irritations were observed after 6 h of microneedle contact. However, the skin irritations resolved within 1 day following the removal of MN patch. CONCLUSION: The large size MN patches showed fast onset and sustained delivery of LD through skin, potentially useful to increase the application scope of topical LD for pain management.

Short- and Long-term Therapeutic Efficacies of Intravenous Transplantation of Bone Marrow Stem Cells on Cardiac Function in Rats with Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials.

Objective To investigate the short- and long-term therapeutic efficacies of intravenous trans- plantation of bone marrow stem cells (MSCs) in rats with experimental myocardial infarction by meta- analysis. Methods Randomized controlled trials were systematically searched from PubMed, Science Citation Index (SCI), Chinese journal full-text database (CJFD) up to December 2014. While the experimental groups (MSCs groups) were injected MSCs intravenously, the control groups were injected Delubecco's minimum essential medium (DMEM) or phosphate buffered saline (PBS). Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for outcome parameters including ejection fraction (EF) and fractional shortening (FS), which were measured by echocardiogram after intravenous injection and analyzed by RevMan 5.2 and STATA 12.0. Results Data from 9 studies (190 rats) were included in the meta-analysis. As compared to the control groups, the cardiac function of the experimental groups were not improved at day 7 (EF: WMD=0.08, 95%CI -1.32 to 1.16, P>0.01; FS: WMD=-0.12, 95%CI -0.90 to 0.65, P>0.01) until at day 14 after MSCs' transplantation (EF: WMD=10.79, 95%CI 9.16 to 12.42, P<0.01; FS: WMD=11.34, 95%CI 10.44 to 12.23, P<0.01), and it lasted 4 weeks or more after transplantation of MSCs (EF: WMD=13.94, 95%CI 12.24 to 15.64, P<0.01; FS: WMD=9.64, 95%CI 7.98 to 11.31, P<0.01). Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.

Drug permeation through skin is inversely correlated with carrier gel rigidity.

Controlled release plays an essential role in formulating topical and transdermal drug delivery systems. In this study, we correlated the skin permeation of Sesamin, a lipophilic drug, with the rheological properties of two different organogel carriers, i.e., low molecular weight gelling agent N-lauroyl-l-glutamic acid di-n-butylamide (GP-1) and Carbopol polymeric gels. Although these two gels have distinct network structures, they share the same trend: the more rigid the gel network and the higher the gelator concentration, the lower the steady flux of Sesamin through skin. This negative correlation lies in the fact that organogel network hinders the diffusion of drug to the gel-skin interface; as a result, the depletion zone near the interface is non-negligible and contributes to the resistance of the whole diffusion system, and thus, the permeation flux is reduced. More interestingly, the dependence of the steady flux against gel complex modulus at the linear viscoelastic region followed a "universal" power law regardless of the gel types, i.e., 1/J = 1/J0 + a(G*)(ε)/C0 with a = 11.25, ε = 0.21 ± 0.03 for GP-1 gels, and a = 0.16, ε = 1.05 ± 0.06 for Carbopol gels, J0 is the steady flux without gel (G* = 0), and C0 is the initial concentration of drug in gels. The empirical formulae are crucial in developing transdermal organogel systems with controlled release of drug content through readily obtainable data of their rheological properties. The explanation for the power law dependence of the steady flux on gel complex modulus is discussed.

Microneedle-Mediated Delivery of Copper Peptide Through Skin.

PURPOSE: Copper peptide (GHK-Cu) plays an important role in skin regeneration and wound healing. However, its skin absorption remains challenging due to its hydrophilicity. Here we use polymeric microneedle array to pre-treat skin to enhance GHK-Cu skin penetration. METHODS: Two in vitro skin models were used to assess the capability of microneedles in facilitating skin delivery of GHK-Cu. Histological assay and confocal laser scanning microscopy were performed to characterize and quantify the microconduits created by the microneedles inside skin. Cellular and porcine models were used to evaluate the safety of microneedle-assisted copper peptide delivery. RESULTS: The depth and percentage of microneedle penetration were correlated with application forces, which in turn influenced the extent of enhancement in the skin permeability of GHK-Cu. In 9 h, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated though the microneedle treated human skin, while almost no peptide or copper permeated through intact human skin. No obvious signs of skin irritation were observed with the use of GHK-Cu after microneedle pretreatment. CONCLUSIONS: It is effective and safe to enhance the skin permeation of GHK-Cu by using microneedles. This approach may be useful to deliver similar peptides or minerals through skin.

Construction of Fu brick tea polysaccharide-cold plasma modified alginate microgels for probiotic delivery: Enhancing viability and colonization.

Emerging food processing technologies provide broader avenues for enhancing probiotic delivery systems. In this study, the new Fu brick tea polysaccharide (FBTP) was extracted and combined with cold plasma-modified alginate nano-montmorillonite (AMT) to prepare microgels by ionic gelation to improve the viability of encapsulated Lactobacillus kefiranofaciens JKSP109. Results showed that cold plasma treatment for 3 min changed the surface charge of AMT biopolymer solution, and FBTP addition reduced the particle size to the lowest of 223 ± 5.50 nm. Morphological analysis showed that the AMT treated with cold plasma for 3 min and FBTP (C3AMT + FBTP) formed a dense microgel through electrostatic interaction, and the probiotics were randomly distributed in their internal polysaccharide network, as well as the interlayer and surrounding of nanoparticles. The probiotics immobilized in C3AMT + FBTP microgel exhibited the highest viability (8.48 ± 0.03 log CFU/g) and colonic colonization after exposure to simulated gastrointestinal conditions. In addition, the good antioxidant activity of FBTP reduced the loss of probiotic viability during storage, with only 2.58 log CFU/g decreased after 4 weeks. Therefore, such probiotic products enriched with natural bioactive ingredients can be developed as a potential functional food additive.

IFRD1 promotes tumor cells "low-cost" survival under glutamine starvation via inhibiting histone H1.0 nucleophagy.

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.

Mechanism of and therapeutic strategy for atrial fibrillation associated with diabetes mellitus.

Diabetes mellitus (DM) is one of the most important risk factors for atrial fibrillation (AF) and is a predictor of stroke and thromboembolism. DM may increase the incidence of AF, and when it is combined with other risk factors, the incidence of stroke and thromboembolism may also be higher; furthermore, hospitalization due to heart failure appears to increase. Maintenance of well-controlled blood glucose and low levels of HbA1c in accordance with guidelines may decrease the incidence of AF. The mechanisms of AF associated with DM are autonomic remodeling, electrical remodeling, structural remodeling, and insulin resistance. Inhibition of the renin-angiotensin system is suggested to be an upstream therapy for this type of AF. Studies have indicated that catheter ablation may be effective for AF associated with DM, restoring sinus rhythm and improving prognosis. Catheter ablation combined with hypoglycemic agents may further increase the rate of maintenance of sinus rhythm and reduce the need for reablation.

Effects of low-level autonomic stimulation on prevention of atrial fibrillation induced by acute electrical remodeling.

BACKGROUND: Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP. METHODS AND RESULTS: Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ≤ 30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect.

Comparison of risk of complication between neuraxial anaesthesia and general anaesthesia for hip fracture surgery: a systematic review and meta-analysis.

BACKGROUND: Controversy remains over the choice of anaesthetic technique for patients undergoing surgery for hip fracture. AIM: The aim was to compare the risk of complication of neuraxial anaesthesia with that of general anaesthesia in patients undergoing hip fracture surgery. METHODS: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and was registered at PROSPERO (CRD42022337384). The study included eligible randomised controlled trials published before February 2022. Data synthesis was performed to compare the differences between general and neuraxial anaesthesia. Meta-regression analysis was performed to investigate the influence of the publication year. A subgroup analysis was performed based on patient age and the anaesthetic technique used. A grading of recommendations, assessment, development and evaluations assessment was performed to assess the quality of each outcome. RESULTS: Twenty randomised controlled trials and 4802 patients were included. Data synthesis revealed significant higher risk of acute kidney injury in the general anaesthesia group ( P =0.01). There were no significant differences between the two techniques in postoperative short-term mortality ( P =0.34), delirium ( P =0.40), postoperative nausea and vomiting ( P =0.40), cardiac infarction ( P =0.31), acute heart failure ( P =0.34), pulmonary embolism ( P =0.24) and pneumonia ( P =0.15). Subgroup analysis based on patient age and use of sedative medication did not reveal any significant differences. Meta-regression analysis of the publication year versus each adverse event revealed no statistically significant differences. CONCLUSION: A significantly higher risk of postoperative acute kidney injury was found in patients receiving general anaesthesia. This study revealed no significant differences in terms of postoperative mortality and other complications between general and neuraxial anaesthesia. The results were consistent across the age groups.