Downregulation of HMGB1 carried by macrophage-derived extracellular vesicles delays atherosclerotic plaque formation through Caspase-11-dependent macrophage pyroptosis.

BACKGROUND: Macrophage-derived extracellular vesicle (macrophage-EV) is highly studied for its regulatory role in atherosclerosis (AS). Our current study tried to elucidate the possible role of macrophage-EV loaded with small interfering RNA against high-mobility group box 1 (siHMGB1) affecting atherosclerotic plaque formation. METHODS: In silico analysis was performed to find critical factors in mouse atherosclerotic plaque formation. EVs secreted by RAW 264.7 cells were collected by ultracentrifugation and characterized, followed by the preparation of macrophage-EV-loaded siHMGB1 (macrophage-EV/siHMGB1). ApoE-/- mice were used to construct an AS mouse model by a high-fat diet, followed by injection of macrophage-EV/siHMGB1 to assess the in vivo effect of macrophage-EV/siHMGB1 on AS mice. RAW264.7 cells were subjected to ox-LDL, LPS or macrophage-EV/siHMGB1 for analyzing the in vitro effect of macrophage-EV/siHMGB1 on macrophage pyrophosis and inflammation. RESULTS: In silico analysis found that HMGB1 was closely related to the development of AS. Macrophage-EV/siHMGB could inhibit the release of HMGB1 from macrophages to outside cells, and the reduced HMGB1 release could inhibit foam cell formation. Besides, macrophage-EV/siHMGB also inhibited the LPS-induced Caspase-11 activation, thus inhibiting macrophage pyroptosis and preventing atherosclerotic plaque formation. CONCLUSION: Our results proved that macrophage-EV/siHMGB could inhibit foam cell formation and suppress macrophage pyroptosis, finally preventing atherosclerotic plaque formation in AS mice.

Oral probiotics increased the proportion of Treg, Tfr, and Breg cells to inhibit the inflammatory response and impede gestational diabetes mellitus.

BACKGROUND: Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM. METHODS: GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels. RESULTS: GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-ß and IL-10, preventing inflammation and preserving mouse pregnancy. CONCLUSION: Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.

c-JUN-induced upregulation of LINC00174 contributes to colorectal cancer proliferation and invasion through accelerating USP21 expression.

Colorectal cancer (CRC) is one of the most common human malignancies due to its invasiveness and metastasis. Recent studies revealed the pivotal roles of long noncoding RNAs (lncRNAs) in tumorigenesis and progressions of various tumors. However, the biological roles and molecular mechanisms of long intergenic noncoding RNA 00174 (LINC00174) in human CRC remain unclear. Here, we report that LINC00174 expression was higher in human CRC tissues and cell lines than in adjacent normal tissues and a colon epithelial cell line (FHC). High expression of LINC00174 was positively correlated with poor overall and disease-free survival in patients with CRC. Loss- and gain-of-function of LINC00174 demonstrated its critical roles in promoting cell proliferation, apoptosis resistance, migration, and invasion of CRC cells in vitro. Moreover, overexpression of LINC00174 enhanced tumor growth in vivo. Mechanistic experiments revealed that LINC00174 could bind to microRNA (miR)-2467-3p and augment the expression and function of ubiquitin-specific peptidase 21 (USP21). Rescue assays found that miR-2467-3p inhibition can offset the actions of LINC00174 or USP21 knockdown in CRC cells. Additionally, transcriptional factor c-JUN transcriptionally activated LINC00174 expression and mediated LINC00174-induced malignant phenotypes of CRC cell lines. Totally, our findings shed light on a new therapeutic strategy in modulating LINC00174/miR-2467-3p, which may interfere with the expression of USP21, and revealed that LINC00174 could be a new therapeutic target or prognostic marker in CRC.

MiR-199a-5p-containing macrophage-derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis.

BACKGROUND: Endothelial cell disturbance underpins a role in pathogenesis of atherosclerosis. Notably, accumulating studies indicate the substantial role of microRNAs (miRs) in atherosclerosis, and miR-199a-5p dysregulation has been associated with atherosclerosis and other cardiovascular disorders. However, the effect of miR-199a-5p on the phenotypes of endothelial cells and atherosclerosis remains largely unknown. METHODS: ApoE-/- male mice were fed with high-fat diet for detection of inflammation and aorta plaque area. Extracellular vesicles (EVs) were separated from THP-1-derived macrophage (THP-1-DM) that was treated by oxidized low-density lipoprotein, followed by co-culture with human aortic endothelial cells (HAECs). Ectopic expression and downregulation of miR-199a-5p were done in THP-1-DM-derived EVs to assess pyroptosis and lactate dehydrogenase (LDH) of HAECs. Binding relationship between miR-199a-5p and SMARCA4 was evaluated by luciferase activity assay. RESULTS: EVs derived from ox-LDL-induced THP-1-DM expedited inflammation and aorta plaque area in atherosclerotic mice. Besides, miR-199a-5p expression was reduced in EVs from ox-LDL-induced THP-1-DM, and miR-199a-5p inhibition facilitated HAEC pyroptosis and LDH activity. Moreover, miR-199a-5p targeted and restricted SMARCA4, and then SMARCA4 activated the NF-κB pathway by increasing PODXL expression in HAECs. CONCLUSION: EV-packaged inhibited miR-199a-5p from macrophages expedites endothelial cell pyroptosis and further accelerates atherosclerosis through the SMARCA4/PODXL/NF-κB axis, providing promising targets and strategies for the prevention and treatment of atherosclerosis.

Peak Blood Lactate at 24 h after ECMO Can Predict 30-day Mortality in Infants after Complex Cardiac Surgery.

OBJECTIVE: Peak blood lactate at 24 h after extracorporeal membrane oxygenation (ECMO) can predict 30-day mortality in infants after complex cardiac surgery. METHODS: Twenty-eight infants with ECMO after complex congenital heart disease surgery were selected from March 2019 to March 2022 in our hospital. The infants were divided into survival group (n = 11) and non-survival group (n = 17) according to 30-day survival after discharge from hospital. The risk factors at 30-day mortality after discharge were analyzed by Cox regression analysis. RESULTS: When compared to the non-survival group, there were significant differences in peak blood lactate at 24 h after ECMO, liver dysfunction and multiple organ dysfunction syndrome (MODS) in the survival group (p < 0.05). Cox regression analysis showed that peak blood lactate at 24 h after ECMO (HR = 1.074, 95% CI: 1.005-1.149, p = 0.036) and MODS (HR = 4.120, 95% CI: 1.373-12.362, p = 0.012) were related risk factors affecting the prognosis of infants. The best cutoff value for the peak blood lactate at 24 h after ECMO was 10.2 mmol/L. The area under the curve (AUC) for predicting the 30-day survival rate of the ECMO assisted infants after discharge from hospital was 0.770 (95% CI: 0.592-0.948, p = 0.018), with a sensitivity of 94.1% and specificity of 54.5%. CONCLUSION: The peak blood lactate at 24 h after ECMO can predict the 30-day mortality after discharge of infants treated with ECMO after complex cardiac surgery. The best cut-off value for peak blood lactate at 24 h after ECMO was 10.2 mmol/L.

TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. METHODS: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. RESULTS: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. CONCLUSIONS: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.

ONOO- -mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells.

Atherosclerosis (AS) is a principal contributor to stroke and coronary heart disease in humans characterized by chronic low-grade inflammation. The extracellular matrix (ECM) plays critical roles in regulating the function of arteries. However, the effect of changes in ECM on AS development is rarely studied. In this context, we intend to study the effect of oxidizing agent peroxynitrite (ONOO- )-mediated oxidization of ECM proteins on the biological behaviors of vascular smooth muscle cells (SMCs) and the development of AS. AS mouse models were established, and mouse coronary artery smooth muscle cells (MCASMCs) were cultured in vitro to derive ECM (SMC-ECM), which was obtained by deoxycholate (DOC)-based decellularization. Further, MCASMCs were subjected to the determination of ECM oxidative damage and ECM protein structure. Finally, roles of ONOO- -mediated oxidization of ECM in SMC adhesion and migration and in AS development were explored through Transwell assay, transcriptome sequencing, and gene enrichment analysis. High concentration of ONOO- was found in the serum of AS mice, and ONOO- could stimulate the development of AS. SMC-ECM with intact structure can be obtained in vitro by DOC treatment. Functionally, ONOO- -mediated oxidization destroyed the three-dimensional structure of SMC-ECM proteins, affected SMC adhesion and migration and promoted the absorption efficiency of lipids while reducing the efflux of cholesterol. In addition, the expression of inflammation- and oxidative stress-related genes was significantly increased in ECM subjected to ONOO- -mediated oxidization, thereby contributing to AS progression. ONOO- -mediated oxidative modification of ECM aggravates AS by affecting the biological behavior of SMCs.

MicroRNA-4429 restrains colorectal cancer cell invasion and migration via regulating SMAD3-induced epithelial-mesenchymal transition.

Colorectal cancer (CRC) is one of the commonest human cancers and the fourth primary cause of cancer-related death. Previous studies have reported that miR-4429 develops anticancer function in follicular thyroid carcinoma and non-small cell lung cancer. However, whether miR-4429 is implicated in the CRC progression remains to be clarified. The aim of our current study was to explore the potential role of miR-4429 in CRC. According to the result of quantitative real-time polymerase chain reaction analysis, miR-4429 was expressed at a low level in CRC cells. Gain-of-function assays showed that the upregulation of miR-4429 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in CRC, whereas miR-4429 inhibition led to the opposite results. It was uncovered from mechanism experiments that miR-4429 targeted forkhead box M1 (FOXM1) and therefore regulating SMAD family member 3 (SMAD3) expression. Rescue experiments elucidated that miR-4429 influenced cell proliferation, migration, invasion, and EMT process in CRC by targeting FOXM1 to inactivate SMAD3. In conclusion, our study revealed that miR-4429 targeted FOXM1 to decrease SMAD3 expression and thus impeding cell proliferation, migration, invasion, and EMT process of CRC cells.

LINC01116 facilitates colorectal cancer cell proliferation and angiogenesis through targeting EZH2-regulated TPM1.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor globally. Meanwhile, LINC01116 has been proposed as risk factor for various tumors, including CRC. But the regulation of LINC01116 in CRC required more validated data. This study aimed to elucidate the potential function of LINC01116 in regulating cell proliferation and angiogenesis of CRC. METHODS: LINC01116 expression in 80 pairs of CRC tumor and adjacent non-tumor tissues was determined by qRT-PCR. After transfection of pcDNA3.1-LINC01116, sh-LINC01116, sh-TPM1, pcDNA3.1-EZH2 or sh-EZH2 in SW480 and HCT116 cells, the levels of LINC01116, TPM1 and EZH2 were measured by qRT-PCR or Western blot. The cell biological function of CRC cell lines was determined by CCK-8, colony formation assays, tube formation and scratch assays. RNA pull-down and RIP assays were applied to detect the binding of LINC01116 with EZH2 and H3K27me3. Binding of EZH2 to the TPM1 promoter was assessed by ChIP assay. Finally, xenograft models in nude mice were established to validate the results of in vitro experiments. RESULTS: LINC01116 was overexpressed in CRC tissues and high expression of LINC01116 was negatively correlated with postoperative survival. In vitro study showed LINC01116 expression could significantly enhance CRC progression, including increasing cell proliferation, migration and angiogenesis. Besides, investigations into the mechanism disclosed that LINC01116 could regulate EZH2 to inactivate TPM1 promoter, thus promoting CRC cell proliferation and angiogenesis. Moreover, consistent results of in vivo experiments were conformed in vitro experiments. CONCLUSION: LINC01116 promotes the proliferation and angiogenesis of CRC cells by recruiting EZH2 to potentiate methylation in the TPM1 promoter region to inhibit the transcription of TPM1.

Carbon nanotube-mediated antibody-free suspension array for determination of typical endocrine-disrupting chemicals.

A carbon nanotube (CNT)-mediated antibody-free suspension array (CASA) by integration of functionalized CNTs and aptamer (Apt) into xMAP® technology for simultaneous determination of typical endocrine-disrupting chemicals (EDCs) was developed . The interaction between CNTs and Apt acts as an effective and straightforward signal recognition, transformation, and amplification strategy. The amino-functionalized CNTs are covalently modified on the carboxyl-functionalized magnetic bead (MB) and further physically bridging with biotinylated Apt. CNTs on the surface of MBs not only increase the amount of Apt for target binding and signal amplification but also maintain the biological activity of Apt. After magnetic separation, the encoded MB address was distinguished and the concentration of the target in the liquid was negatively correlated with median fluorescence intensity. A series of environmental water samples were analysed by CASA, traditional immuno-SA, and competitive inhibition enzyme-linked immunosorbent assay for validation. The results obtained using CASA well matched for the multiplexed detection of various targets with dynamic concentration range from 6.40 × 10-5 to 4.00 µg L-1 within 1 h. The method also confirmed good selectively, accuracy, and consistency with high-performance liquid chromatography. Graphical abstractSchematic representation of amino-functionalized carbon nanotube (CNT)-bridged antibody-free suspension array for detecting of three typical endocrine-disrupting chemicals. The amino-functionalized CNTs are covalently modified and further physically interacted with biotinylated aptamer featuring in the recognition and binding with the target of interest.

Prenatal diagnosis of a right coronary artery to right atrial fistula with a giant coronary artery aneurysm: A case report.

Coronary artery fistula (CAF) is a rare cardiac anomaly. Here, we diagnosed a right coronary artery-right atrium fistula with giant coronary artery aneurysm (CAA) via fetal echocardiography at 35 weeks' gestation. An urgent caesarean delivery was performed at 36 weeks' gestation because CAA caused mitral obstruction, and fetal atrial flutter was present. Following delivery, we performed aneurysm ligation because the new-born developed atrial tachycardia. The intraoperative findings confirmed the sonographic findings. To the best of our knowledge, prenatal ultrasound diagnosis of CAF and giant CAA has not been reported in the literature. We focus on the ultrasonic characteristics and differential diagnosis in this literature.

Midterm Results of Transaxillary Occluder Device Closure of Perimembranous Ventricular Septal Defect Guided Solely by Transesophageal Echocardiography.

BACKGROUND: Perimembranous ventricular septal defect (pmVSD) is a common congenital heart disease. Transaxillary occluder device closure of the pmVSD has been proved effective and an alternative to surgical closure. The study aimed to evaluate the immediate operation outcomes and the early and midterm follow-up outcomes of transaxillary occluder device closure. METHODS: From January 2014 to December 2017, we retrospectively analyzed the patients who underwent transaxillary device closure of the pmVSD. All patients underwent transthoracic echocardiography (TTE), chest x-ray, and electrocardiogram (ECG) before and after the procedure (before discharging). Follow-up evaluation was completed at the time of 3, 6, 12 months and yearly thereafter in outpatient setting with TTE and ECG. RESULTS: A total of 428 patients (216 male, 212 female) underwent transaxillary occluder device closure of the pmVSD under the guidance of transesophageal echocardiography (TEE). The mean age at the operation time was 2.2 ± 1.5 year (range 0.5-16.2 year). The mean weight was 8.5 ± 4.1 kg (range 6-61 kg). The mean size of the occluder implanted in the operation was 5.3 ± 1.4 (range 4-8 mm), matching the mean defect size of 4.2 ± 1.1 (range 3-6 mm). The device closure operation was successfully achieved in 422 pmVSD patients (98.6%), and 6 patients failed in occluding and were converted to open surgery because of a great residual shunt and obvious device-related aortic regurgitation . Immediate complete closure was detected by postoperative TEE in all, but 3 patients had trivial residual shunting. Total early adverse events emerged in 47 patients (11.1%). New mild tricuspid and aortic regurgitation occurred in 17 and 3 patients and disappeared in follow-up. Abnormal atrioventricular conduction events emerged in 23 patients, including left anterior block, complete right bundle branch block (CRBBB), incomplete right bundle branch block (IRBBB), administrated with close follow-up. Pericardial effusion occurred in 2 other patients, managed with puncture drainage. During a median follow-up period of 26.8 months (range 6-48 months), no serious adverse event and later-on complete atrioventricular block were encountered. CONCLUSION: In our experience, transaxillary device closure was performed via right infra-axillary mini-incision (invisible) guided by TEE, with low incidence of postoperative adverse events, confirming that transaxillary device closure of the pmVSD under the guidance of TEE is an effective alternative to surgical closure in well-selected pmVSD patients.

Increased Expression of TREK-1 K+ Channel in the Dorsal Root Ganglion of Rats with Detrusor Overactivity After Partial Bladder Outlet Obstruction.

BACKGROUND Changes in expression and activity of ion channels are important pathophysiological mechanisms underlying detrusor overactivity (DO) in partial bladder outlet obstruction (PBOO). The objective of this study was to examine the expression of TREK-1 channel in the bladder and central nervous system of DO rats. MATERIAL AND METHODS Thirty Sprague-Dawley rats were subjected to PBOO operations and those displaying non-voiding contractions (NVCs) in cystometry were classified as DO. Sham-operated rats without NVCs in cystometry served as controls. The expression and distribution of TREK-1 in the bladder, spinal cord, and dorsal root ganglion (DRG) were detected by real time-PCR, western blot, and immunohistochemistry. RESULTS TREK-1 channel expression in the DRG was significantly increased at the mRNA level (11.20±3.762 vs. 3.209±1.505, P<0.01) and protein level (2.195±0.058 vs. 1.713±0.066, P<0.01) in DO rats as compared to control rats. However, the expression of TREK-1 mRNA in the bladder (1.380±0.810 vs. 4.206±3.827, P>0.05) and spinal cord (0.764±0.357 vs. 0.696±0.188, P>0.05) was comparable between the 2 groups. Immunohistochemistry showed enhanced immunoreactive signals of TREK-1 channel in the DRG, but not in the spinal cord and bladder. CONCLUSIONS TREK-1 channel was upregulated in the DRG of DO rats after chronic PBOO, which might suppress neuronal excitability and play a protective role in bladder overactivity in PBOO.

Three-dimensional printing enhances preparation for repair of double outlet right ventricular surgery.

OBJECTIVE: To assess the clinical value of three-dimensional (3D) printing technology for treatment strategies for complex double outlet right ventricle (DORV). METHODS: Twenty-five patients with complex double outlet right ventricle were enrolled in this study. The patients were divided into two groups: 3D printing group (eight patients) and a non-3-D printing control group (17 patients). The cardiac images of patients in the 3D printing group were transformed to Digital Imaging and Communications and were segmented and reconstructed to create a heart model. No cardiac models were created in the control group. A Pearson coefficient analysis was used to assess the correlation between measurements of 3D printed models and computed tomography angiography (CTA) data. Pre-operative assessment and planning were performed with 3D printed models, and then operative time and recovery time were compared between the two groups. RESULTS: There was good correlation (r = 0.977) between 3D printed models and CTA data. Patients in the 3D printing group had shorter aortic cross-clamp time (102.88 vs 127.76 min, P = 0.094) and cardiopulmonary bypass time (151.63 vs 184.24 min; P = 0.152) than patients in the control group. Patients with 3D printed models had significantly lower mechanical ventilation time (56.43 vs 96.76 h, P = 0.040) and significantly shorter intensive care unit time (99.04 vs 166.94 h, P = 0.008) than patients in the control group. CONCLUSIONS: 3D printed models can accurately demonstrate anatomic structures and are useful for pre-operative treatment strategies in DORV.

The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway.

BACKGROUND/AIMS: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. METHODS: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. RESULTS: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. CONCLUSION: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.

Perventricular device closure of doubly committed sub-arterial ventricular septal defects via a left infra-axillary approach.

BACKGROUND: This study sought to evaluate the feasibility, safety, and efficacy of perventricular device closure of a doubly committed sub-arterial ventricular septal defect (dcVSD) through a left infra-axillary approach. METHOD: Forty-five patients, with a dcVSD of less than 8 mm in diameter, were enrolled in this study. The pericardium was exposed and opened through a left infra-axillary mini-incision. Two parallel purse-string sutures were placed on the right ventricle outflow tract and under transesophageal echocardiography guidance, a delivery sheath loaded with the device was inserted into the right ventricle and advanced through the defect into the left ventricle. The device, connected to a delivery cable, was then deployed. RESULTS: Forty-one patients achieved successful device closure. In four patients, the device failed to occlude the VSD due to device dislodgement, device-related aortic regurgitation, and residual shunts, and open surgical repair was required. The mean dcVSD diameter was 4.5 ± 1.0 mm (range, 3.0-8.0 mm). The implanted device size was 6.0 ± 1.5 mm (range, 4-10 mm). All patients were implanted with an eccentric device. The mean intracardiac manipulation time was 20.9 ± 7.1 min (range, 9-45 min). The procedure time was 62.5 ± 19.5 min (range 34-105 min). There were no severe adverse events. CONCLUSIONS: Perventricular device closure of a dcVSD through a left infra-axillary approach is feasible, safe, and efficacious in selected patients with dcVSD.

Transjugular closure of secundum atrial septal defects.

OBJECTIVE: This study reports the results of a steerable delivery system under the guidance of transesophageal echocardiography (TEE) for the treatment of transjugular closure of secundum atrial septal defects (ASD). METHODS: From July 2015 to May 2016, 33 patients underwent transjugular closure of a secundum ASD under general anesthesia with TEE guidance. The right internal jugular vein was punctured and a FuStar™ steerable sheath was implanted into the right atrium and aligned vertically with the septum, and a closure device was deployed to close the defect. RESULTS: Thirty-two patients with an ASD were successfully occluded; one patient required ASD closure on cardiopulmonary bypass. Procedure time ranged from 5 to 15 (8.2 ± 3.8) min. The length of stay was three to five days after the operation. The follow-up time ranged from 1.1 to 11.0 (5.5 ± 1.5) months. There was no valve regurgitation, no malignant arrhythmias, no device dislocation, or other serious complications. CONCLUSIONS: A steerable delivery system under the guidance of TEE is a safe, effective, and cosmetic method for the transjugular closure of secundum ASDs.

Enhanced expression of TWIK-related arachidonic acid-activated K+ channel in the spinal cord of detrusor overactivity rats after partial bladder outlet obstruction.

BACKGROUND: Detrusor overactivity (DO) secondary to partial bladder outlet obstruction (PBOO) is closely associated with alteration of ion channels. The objective of this study is to investigate the expression of the TWIK-related arachidonic acid-activated K(+) channel (TRAAK) in the L6-S1 spinal cord of DO rats after PBOO. METHODS: Female Sprague-Dawley rats undergoing PBOO surgery were screened for DO by cystometry. Sham-operated rats served as controls. The expression of TRAAK in the L6-S1 spinal cord was detected by real-time polymerase chain reaction, western blotting and immunohistochemistry. RESULTS: DO was successfully induced after chronic PBOO in rats, with an incidence rate of 62.5 %. Compared with sham-operated rats, the expression of TRAAK in the L6-S1 spinal cord of DO rats was significantly increased at the mRNA (1.886 ± 0.710 versus 0.790 ± 0.679, P < 0.05) and protein level (0.510 ± 0.087 versus 0.255 ± 0.107, P < 0.05). Immunohistochemical staining showed increased expression of TRAAK in the dorsal horn and ventral horn of the spinal cord. CONCLUSIONS: Upregulation of TRAAK was observed in the spinal cord of DO rats after chronic PBOO, which may exert a protective effect against DO by suppressing the excitability of neurons.

Genetic Algorithm (GA)-Based Inclinometer Layout Optimization.

This paper presents numerical simulation results of an airflow inclinometer with sensitivity studies and thermal optimization of the printed circuit board (PCB) layout for an airflow inclinometer based on a genetic algorithm (GA). Due to the working principle of the gas sensor, the changes of the ambient temperature may cause dramatic voltage drifts of sensors. Therefore, eliminating the influence of the external environment for the airflow is essential for the performance and reliability of an airflow inclinometer. In this paper, the mechanism of an airflow inclinometer and the influence of different ambient temperatures on the sensitivity of the inclinometer will be examined by the ANSYS-FLOTRAN CFD program. The results show that with changes of the ambient temperature on the sensing element, the sensitivity of the airflow inclinometer is inversely proportional to the ambient temperature and decreases when the ambient temperature increases. GA is used to optimize the PCB thermal layout of the inclinometer. The finite-element simulation method (ANSYS) is introduced to simulate and verify the results of our optimal thermal layout, and the results indicate that the optimal PCB layout greatly improves (by more than 50%) the sensitivity of the inclinometer. The study may be useful in the design of PCB layouts that are related to sensitivity improvement of gas sensors.

Effectiveness and safety of tetracyclines and quinolones in people with Mycoplasma pneumonia: a systematic review and network meta-analysis.

Background: The escalating resistance of Mycoplasma pneumoniae to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of M. pneumoniae infection while considering the age-specific safety issues associated with these interventions. Methods: In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with M. pneumoniae infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing M. pneumoniae infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with M. pneumoniae infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383. Findings: The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; I2 = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; I2 = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; I2 = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events. Interpretation: Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these results should be interpreted with caution, given the limited number of studies and patients included, and the heterogeneity between included studies. Based on a limited number of studies in children, levofloxacin is likely to have one of the highest rates of adverse reactions. The majority of the studies included in the NMA were from the Asian region, and more randomised controlled trials comparing different therapeutic strategies in patients with M. pneumoniae are warranted. This comparative study provides clinical pharmacists and clinicians with important information to enable them to make informed decisions about treatment options, considering drug efficacy and safety. Funding: The Natural Science Foundation of Fujian Province, China.