LncRNA SNHG6 accelerates hyperoxia-induced lung cell injury via regulating miR-335 to activate KLF5/NF-κB pathway.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, and its pathogenesis has not been clarified. Long non-coding RNAs (lncRNA) have important functions in cell bioactivity. However, their role in developmental lung disease remains unclear. OBJECTIVE: The aim of this study was to demonstrate the role of lncRNA SNHG6 (SNHG6) in BPD and its underlying mechanisms. METHODS: The blood of patients with BPD were collected, and BPD model of BEAS-2B cells was established by hyperoxia method. SNHG6, miR-335 and KLF5 mRNA expression were detected by RT-qPCR. Western blot was conducted to measure the levels of apoptosis-related proteins' expression and NF-κB pathway related proteins. BEAS-2B cell viability and apoptosis were assessed by CCK-8 and flow cytometry, respectively. Assay Kit was applied to detect ROS, MDA and SOD levels, respectively. ELISA was performed to assess the levels of inflammatory factors. The binding site of miR-335 with SNHG6 or KLF5 were predicted by using DIANA or TargetScan, and which was verified by double luciferase reporter assay. RESULTS: Firstly, SNHG6 was highly expressed and miR-335 was lowly expressed in BPD model, SNHG6 knockdown and miR-335 mimics both alleviated hyperoxia-induced lung cell injury, and SNHG6 targeted miR-335. Subsequently, KLF5 was targeted by miR-335, and KLF5 promoted lung cell injury via activating NF-κB pathway. Furthermore, SNHG6 mediated lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. CONCLUSION: Our research confirmed that SNHG6 mediated hyperoxia-induced lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. These findings suggest that SNHG6 serves as promising targets for the treatment of newborns with BPD.

Retrograde Type A Dissection after Ascending Aorta Involved Endovascular Repair and Its Surgical Repair with Stented Elephant Trunk.

BACKGROUND: Retrograde type A dissection (RTAD) is a serious complication after ascending aorta involved endovascular repair (AAIER). We here report our surgical approach to this serious complication. METHODS: From July 2011 to July 2014, 8 RTADs after AAIER patients received surgical repair in our institution. Data of these RTAD patients were retrospectively collected for further analysis. All patients received urgent surgical repair based on the stented elephant trunk technique. We took 2 different ways to handle the previous stent during operation. In patients who had a prior hybrid aortic repair, we removed the proximal part of the stent while the distal part was left in place. In patients who had prior ascending aorta stent implantation (AASI), the stent was totally removed. RESULTS: The mean age of the patients was 57.6 ± 11.9 years. Regarding the index intervention, 2 patients received hybrid aortic repair and 6 patients received AASI. In patients who received AASI, 1 patient underwent simultaneous thoracic endovascular aortic repair (TEVAR) and another patient received simultaneous chimney technique in innominate artery and left common carotid artery combined with bypass from left subclavian artery to left common carotid artery to cure the type I endoleak induced by the previous implanted TEVAR stent. All patients received a new elephant trunk implantation during surgical repair. The mean cardiopulmonary bypass, selective cerebral perfusion, and aortic cross-clamp time were 172.1 ± 13.3, 40.8 ± 4.2, and 121.8 ± 11.4 min, respectively. The mean intensive care unit time was 7.8 ± 3.4 days. Two patients (25.0%) experienced transient neurologic dysfunction and recovered completely before discharge. In-hospital death rate was 12.5% (1 of 8). The mean follow-up time was 17.1 ± 9.5 months. No late deaths or complications occurred during follow-up. CONCLUSIONS: AAIER especially AASI used in aortic dissection treatment should be seriously considered since RTAD might occur. Our study indicated that surgical repair with stented elephant trunk was feasible and according to the cause of RTAD, different surgical strategies should be taken to manage the stent.

Preparation of Porous Activated Carbons for High Performance Supercapacitors from Taixi Anthracite by Multi-Stage Activation.

Coal-based porous materials for supercapacitors were successfully prepared using Taixi anthracite (TXA) by multi-stage activation. The characterization and electrochemical tests of activated carbons (ACs) prepared in different stages demonstrated that the AC from the third-stage activation (ACIII) shows good porous structures and excellent electrochemical performances. ACIII exhibited a fine specific capacitance of 199 F g-1 at a current density of 1 A g-1 in the three-electrode system, with 6 mol L-1 KOH as the electrolyte. The specific capacitance of ACIII remained 190 F g-1 even despite increasing the current density to 5 A g-1, indicating a good rate of electrochemical performance. Moreover, its specific capacitance remained at 98.1% of the initial value after 5000 galvanostatic charge-discharge (GCD) cycle tests at a current density of 1 A g-1, suggesting that the ACIII has excellent cycle performance as electrode materials for supercapacitors. This study provides a promising approach for fabricating high performance electrode materials from high-rank coals, which could facilitate efficient and clean utilization of high-rank coals.

Retrograde Type A Dissection after Thoracic Endovascular Aortic Repair: Surgical Strategy and Literature Review.

BACKGROUND: In this study, we investigated the surgical strategy for managing retrograde type A dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) by reporting our experience and literature review. METHODS: From June 2011 to January 2014, nine patients with RTAD received surgical repair in our institution. The mean age of these patients was 49.3±10.7 years. Data on these RTAD patients was retrospectively collected for further analysis. Literature related to RTAD after TEVAR from 2006 to 2014 was reviewed using the following terms: thoracic endovascular aortic repair, retrograde type A dissection, stent induced new entry, and surgical repair. RESULTS: We adopted a total arch replacement combined with a stented elephant trunk implantation and partly preserved the previous TEVAR stent during operation. In-hospital death rate was 11.1% (one of nine). One patient (11.1%) developed paraparesis after operation. No late deaths or complications occurred during follow-up. Literature review identified four articles on the surgical management of RTAD after TEVAR. Our literature review also showed total arch replacement with the stented elephant trunk implantation might be associated with a better prognosis. CONCLUSIONS: Retrograde type A dissection is a serious complication after TEVAR. The induced factors of RTAD were various and complicated. Our experience and literature review indicates a combination of total arch replacement, stented elephant trunk implantation and partly preserving the previous TEVAR stent is feasible for the surgical repair of RTAD after TEVAR.

Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.

Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up-regulation. ATG4B knockdown blocked IL-6-induced autophagy and α-SMA and SM22α degradation, while ATG4B overexpression partly replaced the function of IL-6 in human VSMCs. In conclusion, our study demonstrated that IL-6 downregulated expression of VSMCs contractile proteins α-SMA and SM22α via enhancing ATG4B-mediated autophagy in TAD.

Self-Powered, One-Stop, and Multifunctional Implantable Triboelectric Active Sensor for Real-Time Biomedical Monitoring.

Operation time of implantable electronic devices is largely constrained by the lifetime of batteries, which have to be replaced periodically by surgical procedures once exhausted, causing physical and mental suffering to patients and increasing healthcare costs. Besides the efficient scavenging of the mechanical energy of internal organs, this study proposes a self-powered, flexible, and one-stop implantable triboelectric active sensor (iTEAS) that can provide continuous monitoring of multiple physiological and pathological signs. As demonstrated in human-scale animals, the device can monitor heart rates, reaching an accuracy of ∼99%. Cardiac arrhythmias such as atrial fibrillation and ventricular premature contraction can be detected in real-time. Furthermore, a novel method of monitoring respiratory rates and phases is established by analyzing variations of the output peaks of the iTEAS. Blood pressure can be independently estimated and the velocity of blood flow calculated with the aid of a separate arterial pressure catheter. With the core-shell packaging strategy, monitoring functionality remains excellent during 72 h after closure of the chest. The in vivo biocompatibility of the device is examined after 2 weeks of implantation, proving suitability for practical use. As a multifunctional biomedical monitor that is exempt from needing an external power supply, the proposed iTEAS holds great potential in the future of the healthcare industry.

Comparation of the outcomes between ProGlide based post-closure technique and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation decannulation.

PURPOSE: To compare outcomes between post-closure technique based on ProGlide and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation in this study. MATERIALS AND METHODS: Patients who received VA-ECMO treatment and successfully removed from its support in Changhai Hospital from January 2018 to December 2021 were included in this study. Patients was divided into post-closure group and surgical repair group according to the artery access closure method used. Clinical data of these patients were retrospectively collected and analyzed. RESULTS: A total of 58 patients were eventually enrolled in this study, including 26 (44.83%) patients in post-closure group and 32 (55.17%) patients in surgical repair group. Post-closure group had shorter procedure time, less minor bleeding events, estimated blood loss and packed cells transfused compared with the surgical repair group. The intensive care unit (ICU) length of stay after decannulation and the hospital length of stay after ICU in post-closure group were both shorter than surgical repair group. Nine patients (15.52%) died of multiple system organ failure after decannulation in this cohort and there were no significant differences between two groups. CONCLUSIONS: Our study showed the post-closure technique based on ProGlide for VA-ECMO decannulation is feasible, safe and effective.

Risk factors for in-hospital mortality after total arch procedure in patients with acute type A aortic dissection.

Object: Knowledge about the risk factors of in-hospital mortality for acute type A aortic dissection (ATAAD) patients who received total arch procedure is limited. This study aims to investigate preoperative and intraoperative risk factors of in-hospital mortality of these patients. Methods: From May 2014 to June 2018, 372 ATAAD patients received the total arch procedure in our institution. These patients were divided into survival and death groups, and patients` in-hospital data were retrospectively collected. Receiver operating characteristic curve analysis was adopted to determine the optimal cut-off value of continuous variables. Univariate and multivariable logistic regression analyses were used to detect independent risk factors for in-hospital mortality. Results: A total of 321 patients were included in the survival group and 51 in the death group. Preoperative details showed that patients in the death group were older (55.4 ± 11.7 vs. 49.3 ± 12.6, P = 0.001), had more renal dysfunction (29.4% vs. 10.9%, P = 0.001) and coronary ostia dissection (29.4% vs. 12.2%, P = 0.001), and decreased left ventricular ejection fraction (LVEF) (57.5 ± 7.9% vs. 59.8 ± 7.3%, P = 0.032). Intraoperative results showed that more patients in the death group experienced concomitant coronary artery bypass grafting (35.3% vs. 15.3%, P = 0.001) with increased cardiopulmonary bypass (CPB) time (165.7 ± 39.0 vs. 149.4 ± 35.8 min, P = 0.003), cross-clamp time (98.4 ± 24.5 vs. 90.2 ± 26.9 min, P = 0.044), and red blood cell transfusion (913.7 ± 629.0 vs. 709.7 ± 686.6 ml, P = 0.047). Logistic regression analysis showed that age >55 years, renal dysfunction, CPB time >144 min, and RBC transfusion >1,300 ml were independent risk factors for in-hospital mortality in patients with ATAAD. Conclusion: In the present study, we identified that older age, preoperative renal dysfunction, long CPB time, and intraoperative massive transfusion were risk factors for in-hospital mortality in ATAAD patients with the total arch procedure.

Uncertainty-guided cross learning via CNN and transformer for semi-supervised honeycomb lung lesion segmentation.

Objective. Deep learning networks such as convolutional neural networks (CNN) and Transformer have shown excellent performance on the task of medical image segmentation, however, the usual problem with medical images is the lack of large-scale, high-quality pixel-level annotations, which is a very time-consuming and laborious task, and its further leads to compromised the performance of medical image segmentation under limited annotation conditions.Approach. In this paper, we propose a new semi-supervised learning method, uncertainty-guided cross learning, which uses a limited number of annotated samples along with a large number of unlabeled images to train the network. Specifically, we use two networks with different learning paradigms, CNN and Transformer, for cross learning, and use the prediction of one of them as a pseudo label to supervise the other, so that they can learn from each other, fully extract the local and global features of the images, and combine explicit and implicit consistency regularization constraints with pseudo label methods. On the other hand, we use epistemic uncertainty as a guiding message to encourage the model to learn high-certainty pixel information in high-confidence regions, and minimize the impact of erroneous pseudo labels on the overall learning process to improve the performance of semi-supervised segmentation methods.Main results. We conducted honeycomb lung lesion segmentation experiments using a honeycomb lung CT image dataset, and designed several sets of comparison experiments and ablation experiments to validate the effectiveness of our method. The final experimental results show that the Dice coefficient of our proposed method reaches 88.49% on the test set, and our method achieves state-of-the-art performance in honeycomb lung lesion segmentation compared to other semi-supervised learning methods.Significance. Our proposed method can effectively improve the accuracy of segmentation of honeycomb lung lesions, which provides an important reference for physicians in the diagnosis and treatment of this disease.

Epidemiological and Clinical Characteristics of Measles in Jinan, Shandong Province, China, from 1991 to 2022.

Objective: This study aimed to analyze the epidemiological and clinical characteristics of measles in Jinan, Shandong, China, over a 32-year stage to facilitate measles prevention in the future. Methods: Data on measles cases from 1991 to 2022 were obtained from the public health department and medical records of patients at Shandong Public Health Clinical Center. Retrospective analysis was conducted on the distribution of measles cases in different years, months, and age groups, and observation of the differences in clinical manifestations and complications among different age groups. Results: From January 1991 to December 2022, 7531 measles cases were recorded at Shandong Public Health Clinical Center. During the 32-year period, there were two outbreaks of measles in 2008 and 2016, respectively. During the COVID-19 pandemic period from 2020 to 2022, the number of cases reached the lowest point in the past 30 years. The number and percentage of cases in the 0-1y groups was significantly higher than in other age groups, and 97.75% patients in this group did not receive measles vaccine. Complications such as pneumonia and myocarditis appeared more frequent in patients under 12 years of age, but liver function damage is more common in adult patients. Conclusion: Although the measles epidemic has been greatly controlled since the use of measles vaccine, intermittent outbreaks still exist, so there is still a long way to go to eliminate measles. The proportion of infants under the age of 1 without measles vaccine and adults over 24 years old accounts for nearly 80% of the total. This group of people should be of concern, and feasible measures should be designated to protect these susceptible populations.

Control of grasshoppers by combined application of Paranosema locustae and an insect growth regulator (IGR) (cascade) in rangelands in China.

The relatively low direct mortality caused by Paranosema locustae (Canning) has limited its application for controlling grasshopper when densities are high, and this study sought to determine if the simultaneous use of this pathogen and the IGR, Flufenoxuron (Cascade) could provide effective control. Nine treatments were tested: 45% Malathion EC at 1500 ml/ha, 5% Cascade at 150 ml/ha, 5% Cascade at 75 ml/ha, 5% Cascade at 37.5 ml/ha, P. locustae at 7.5 x 10(9) spores/ha, combinations of 5% Cascade at 75 ml/ha and P. locustae at 7.5 x 10(9) spores/ha, applied in different rations (1:1, 1:2, 1:3) in the same plot, the untreated control. P. locustae was applied on nonoverlapping plots with the IGR. The different in-plot combinations of P. locustae and Cascade in different ratios provided significantly better overall control of grasshoppers (all species) than the treatment of 5% Cascade of 150 ml/ha after 5d, but combinations were not significantly different from the other concentrations of Cascade after 12 and 31 d. When results were examined separately for specific species of grasshoppers, reduction of Dasyhippus harbipes (Fischer-Waldheim), was higher than that of Myrmeleotettix palpalis (Zubovsky). While combinations showed significant differences in the infection of different grasshopper species at 5 and 12 d posttreatment, no significant differences in rate of infection among the primary species (M. palpalis, D. harbipes, and Oedaleus asiaticus Bei-Bienko) were detected 31 d posttreatment. Our study found that P. locustae by itself could control grasshopper populations at medium densities but the combined application of P. locustae and Cascade at a ratio of 1:2 was more effective against high-density grasshopper populations.

Expression Analysis of Ligand-Receptor Pairs Identifies Cell-to-Cell Crosstalk between Macrophages and Tumor Cells in Lung Adenocarcinoma.

Background: Lung adenocarcinoma is one of the most commonly diagnosed malignancies worldwide. Macrophage plays crucial roles in the tumor microenvironment, but its autocrine network and communications with tumor cell are still unclear. Methods: We acquired single-cell RNA sequencing (scRNA-seq) (n = 30) and bulk RNA sequencing (n = 1480) samples of lung adenocarcinoma patients from previous literatures and publicly available databases. Various cell subtypes were identified, including macrophages. Differentially expressed ligand-receptor gene pairs were obtained to explore cell-to-cell communications between macrophages and tumor cells. Furthermore, a machine-learning predictive model based on ligand-receptor interactions was built and validated. Results: A total of 159,219 single cells (18,248 tumor cells and 29,520 macrophages) were selected in this study. We identified significantly correlated autocrine ligand-receptor gene pairs in tumor cells and macrophages, respectively. Furthermore, we explored the cell-to-cell communications between macrophages and tumor cells and detected significantly correlated ligand-receptor signaling pairs. We determined that some of the hub gene pairs were associated with patient prognosis and constructed a machine-learning model based on the intercellular interaction network. Conclusion: We revealed significant cell-to-cell communications (both autocrine and paracrine network) within macrophages and tumor cells in lung adenocarcinoma. Hub genes with prognostic significance in the network were also identified.

Preoperative 6-minute walk test predicts prolonged hospitalization after transcatheter tricuspid valve replacement.

The purpose of this study is to determine whether preoperative 6-minute walk test (6MWT) is associated with prolonged postoperative hospitalization in high risk patients with severe tricuspid regurgitation (TR) after transcatheter tricuspid valve replacement (TTVR). Forty-one patients with severe TR who underwent TTVR and discharged between September 2018 and April 2021 were enrolled in this study. Patients were divided into 2 groups according to whether the postoperative hospital stay was >10 days and patients' data were retrospectively collected. 6MWT was performed before operation. Twenty-one patients were in the control group (≤10 days) and 20 patients were in the prolonged postoperative stay (PPS) group (>10 days). 6MWT distance was significantly decreased in PPS group (192.70 ±â€…62.34 vs 274.57 ±â€…52.09 m, P < .05). PPS group had more patients with severe liver disease (50.00% vs 19.05%, P < .05), higher systolic pulmonary artery pressure (45.05 ±â€…9.28 vs 35.57 ±â€…8.91 mm Hg, P < .05) and longer procedure time (159.85 ±â€…56.61 vs 124.43 ±â€…31.67 min, P < .05). Multivariable logistic regression analysis found 6MWT <267 m was an independent risk factor with the odds ratio of 10.95 (1.66-72.39, P < .05) for prolonged postoperative hospitalization in patients who received TTVR. In the present study, we identified that preoperative decreased 6MWT distance was an independent risk factor for prolonged hospitalization in high risk TR patients after TTVR.

Extensive Arch Repair with a Novel Two-Branched Stent Graft in Acute Type A Aortic Dissection.

PURPOSE: In this study, we compared the early results between the extensive arch repair with a novel two-branched stent graft (TSG) and the traditional technique. METHODS: Between 2013 July and 2015 March, 63 acute type A aortic dissection (ATAAD) patients from four cardiac centers with indications for extensive arch repair were included in this study. Finally, 28 patients were involved in the traditional procedure (TP) group (23 males with the age of 49.75 ± 9.26 years) and 35 patients were involved in the TSG group (29 males with the age of 53.82 ± 8.17 years). RESULTS: The operation was successful in all patients. The selective cerebral perfusion time, total operation time, and chest drainage within 24 hours after the operation in the TSG group were significantly less than those in the TP group (P ≤0.05). The mean follow-up time was 11.17 ± 1.74 months in the TP group and 11.94 ± 4.29 months in the TSG group. No statistical differences were found in aortic diameter, false lumen diameter, and true lumen diameter at the diaphragmatic level during the follow-up. CONCLUSION: Our technique with a novel TSG simplified the extensive arch repair procedure and was an effective way for the treatment of ATAAD.

A novel method to obtain rat aortic media for primary culture of rat aortic smooth muscle cells.

An efficient and simple method to obtain aortic media for primary culture of rat vascular smooth muscle cells (RVSMCs) is developed. The main steps to obtain aortic media include isolation of rat aortic artery, removal of the fat tissue and branches, separation of longitudinal cutting edge, and peeling off the adventitia. Then, aortic media was used to obtain RVSMCs by our tissue explants method and the enzyme digestion method. The removal efficiency of the intima and adventitia was confirmed by hematoxylin-eosin and immunohistochemical staining. Morphology and immunofluorescent staining were used to identify cells and cell purity. RVSMCs at the 3rd and 8th passages were isolated by our tissue explants method; the enzyme digestion method and the traditional tissue explants method were compared respectively. Western blotting and gel contraction assay were used to investigate the phenotype and contraction ability of RVSMCs obtained by the different methods. Compared with the other methods, RVSMCs isolated by our method showed higher purity and demonstrated "contractile" phenotype with retained contraction ability for more passages. And the aortic media obtained showed no visible damage with few endothelial cells and fibroblasts remained. An efficient and simple method was established to obtain rat aortic media for primary culture of RVSMCs with high purity, "contractile" phenotype characteristics, and more stable during subculturing.

Up-regulation of KLF17 expression increases the sensitivity of gastric cancer to 5-fluorouracil.

It has been reported that the expression of Krüppel-like factor 17 (KLF17) was associated with the occurrence, development, invasion, metastasis and chemotherapy resistance of various tumors. However, the detailed mechanisms by which KLF17 promotes chemotherapy resistance in gastric cancer (GC) have not been fully investigated. In the present study, we collected the GC tissues and non-tumor tissues (matched adjacent normal tissues with corresponding GC tissues) of 60 GC patients, used qRT-PCR, Western blot and immunohistochemistry assay to analyze the relationship between the expression of KLF17 and the clinical pathological data of the patients. The effect of KLF17 on the sensitivity of GC cell lines to 5-fluorouracil (5-FU), and the potential mechanism were detected by MTS assay, Flow cytometry assay, and Western blot. Compared with non-tumor tissues, the expression level of KLF17 in GC tissue was significantly down-regulated, and the expression level of KLF17 in GES-1 cell line and GC cell lines also had a similar trend. Down-regulated expression of KLF17 is related to tumor size, invasion, regional lymph node metastasis, and TNM staging. Furthermore, through upregulating the expression of KLF17, the sensitivity of BGC-823 and SGC-7901 cell lines to 5-FU was obviously increased. Mechanistically, upregulation the expression of KLF17 can inhibit the expressions of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and B-Cell lymphoma-2 (BCL-2), which have been reported to be associated with drug resistance and cell proliferation. Collectively, these data implied that KLF17 has the biological effect of inhibiting chemotherapy resistance of GC, and it could be a potential strategy for the GC chemotherapy resistance.

Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

Background: Pacemaker implantation is currently used in patients with symptomatic bradycardia. Since a pacemaker is a lifetime therapeutic device, its energy consumption contributes to battery exhaustion, along with its voltage stimulation resulting in local fibrosis and greater resistance, which are all detrimental to patients. The possible resolution for those clinical issues is an injection of a conductive hydrogel, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), to reduce the myocardial threshold voltage for pacemaker stimulation. Methods: PAMB-G is synthesized by covalently linking PAMB to gelatin, and its conductivity is measured using two-point resistivity. Rat hearts are injected with gelatin or PAMB-G, and pacing threshold is evaluated using electrocardiogram and cardiac optical mapping. Results: PAMB-G conductivity is 13 times greater than in gelatin. The ex vivo model shows that PAMB-G significantly enhances cardiac tissue stimulation. Injection of PAMB-G into the stimulating electrode location at the myocardium has a 4 times greater reduction of pacing threshold voltage, compared with electrode-only or gelatin-injected tissues. Multi-electrode array mapping reveals that the cardiac conduction velocity of PAMB-G group is significantly faster than the non- or gelatin-injection groups. PAMB-G also reduces pacing threshold voltage in an adenosine-induced atrial-ventricular block rat model. Conclusion: PAMB-G hydrogel reduces cardiac pacing threshold voltage, which is able to enhance pacemaker efficacy.

Advances in reconstructing intestinal functionalities in vitro: From two/three dimensional-cell culture platforms to human intestine-on-a-chip.

Standard two/three dimensional (2D/3D)-cell culture platforms have facilitated the understanding of the communications between various cell types and their microenvironments. However, they are still limited in recapitulating the complex functionalities in vivo, such as tissue formation, tissue-tissue interface, and mechanical/biochemical microenvironments of tissues and organs. Intestine-on-a-chip platforms offer a new way to mimic intestinal behaviors and functionalities by constructing in vitro intestinal models in microfluidic devices. This review summarizes the advances and limitations of the state-of-the-art 2D/3D-cell culture platforms, animal models, intestine chips, and the combined multi-organ chips related with intestines. Their applications to studying intestinal functions, drug testing, and disease modeling are introduced. Different intestinal cell sources are compared in terms of gene expression abilities and the recapitulated intestinal morphologies. Among these cells, cells isolated form human intestinal tissues and derived from pluripotent stem cells appear to be more suitable for in vitro reconstruction of intestinal organs. Key challenges of current intestine-on-a-chip platforms and future directions are also discussed.

Transcatheter tricuspid valve replacement in patients with severe tricuspid regurgitation.

OBJECTIVE: Tricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR. METHODS: This was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients' data at baseline, before discharge, 30 days and 6 months after the procedure were collected. RESULTS: All patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months. CONCLUSIONS: The present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR.

Inhibitory effect of siRNA-Annexin A7 on growth, migration, and invasion in BGC823 cells and gastric cancer xenograftsin nude mice.

OBJECTIVE: To explore the inhibitory effect of siRNA-Annexin A7 on growth, migration, and invasion of transplanted gastric cancer in nude mice. METHODS: The siRNA sequence targeting to human Annexin A7 gene was designed, and based on that a pair of complementary oligonucleotides were synthesized, annealed, and cloned into plasmid pGenesil-1.1 to construct recombinant plasmid siRNA-Annexin A7. Transplanted gastric cancer model was established by injecting s.c. nude mice with human gastric cancer BGC823 cells, and siRNA-Annexin A7 was injected into the tumors formed. The nude mice were observed for clinical manifestation relying on the size and weight of transplanted tumors. The tumor tissue and angiogenesis were examined by pathologic sections. Flow cytometry was used to detect the changes of cell cycle. Western blot and qRT-PCR were used to analyze the expression of PCNA, P27, MMP-2, and TIMP-2. RESULTS: Both the size and weight of transplanted tumors of nude mice injected with siRNA-Annexin A7 were less than those of control groups (P<0.05). The examination of pathologic sections showed that, compared with in the control group, obvious necrosis of tumor cells was observed in siRNA-Annexin A7 group. The cells in stage S were fewer in siRNA-Annexin A7 group than those in the other two groups, while the cells in stage G0/G1 were much more in siRNA-Annexin A7 group. The results of western blot and qRT-PCR confirmed that the expression of PCNA and MMP-2 was down-regulated, whereas the expression of p27 was up-regulated. CONCLUSION: Gastric cancer xenografts were established in nude mice with human gastric cancer BGC823 cells. The volume and weight of tumor were decreased after inhibition of Annexin A7 expression in BGC823 cells. Tumor cells were arranged sparsely after inhibition of Annexin A7 expression in BGC823 cells. The siRNA-Annexin A7 inhibits Annexin A7 expression in transplanted gastric cancer of nude mice, and influences the growth, migration, and invasion of tumors by down-regulating the expression of PCNA and MMP-2, as well as up-regulating the expression of p27.