METTL14 plays an oncogenic role in NSCLC by modulating ferroptosis and the m6A modification of GPX4.

CONTEXT: N6-methyladenosine (m6A) of RNA is involved in the progression of non-small cell lung cancer (NSCLC). OBJECTIVE: This study investigated the role of METTL14 in NSCLC and the mechanism. MATERIALS AND METHODS: Expression levels were assessed by quantitative real-time PCR and ELISA assays. Cells viability was assessed by cell counting kit-8. M6A methylation was analysed by methylated RNA immunoprecipitation (MeRIP), RIP, luciferase assay, and mRNA stability assay. RESULTS: The results showed that METTL14 was highly expressed in NSCLC tissues and cell lines. Knockdown of METTL14 inhibited the cell viability while induced ferroptosis of NSCLC cells. Mechanistically, METTL14 interacts with GPX4, mediates m6A modification of GPX4, enhances its mRNA stability, and upregulates its expression. In addition, IGF2BP1 recognises the m6A-methylated GPX4 and mediates the elevated mRNA stability. Moreover, GPX4 reversed the effects of METTL14 depletion. DISCUSSION AND CONCLUSION: The METTL14/GPX4 axis promotes NSCLC progression by inhibiting cell ferroptosis through the recognition of m6A modification mediated by IGF2BP1.

Knockdown of miR-1293 attenuates lung adenocarcinoma angiogenesis via Spry4 upregulation-mediated ERK1/2 signaling inhibition.

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Angiogenesis plays a pivotal role in LUAD progression via supplying oxygen and nutrients for cancer cells. Non-coding miR-1293, a significantly up-regulated miRNA in LUAD tissues, can be potentially used as a novel biomarker for predicting the prognosis of LUAD patients. However, little information is available about the function of miR-1293 in LUAD progression especially cancer-induced angiogenesis. Herein, we found that miR-1293 knockdown could obviously attenuate LUAD-induced angiogenesis in vitro and down-regulate two most important pro-angiogenic cytokines VEGF-A and bFGF expression and secretion. Indeed, miR-1293 abrogation inactivated the angiogenesis-promoting ERK1/2 signaling characterized by decreased ERK1/2 phosphorylation and translocation from nucleus to cytoplasm. Next we found that miR-1293 knockdown reactivated the endogenous ERK1/2 pathway inhibitor Spry4 expression and Spry4 perturbance with specific siRNA transfection abolished the inhibition of ERK1/2 pathway and LUAD-induced angiogenesis by miR-1293 knockdown. Finally, with in vivo assay, we found obvious Spry4 up-regulation and VEGF-A, bFGF, ERK1/2 phosphorylation, micro-vessel density marker CD31 expression down-regulation in vivo, respectively. Collectively, these results indicated that miR-1293 knockdown could significantly attenuate LUAD angiogenesis via Spry4-mediated ERK1/2 signaling inhibition, which might be helpful for uncovering more functions of miR-1293 in LUAD and providing experimental basis for possible LUAD therapeutic strategy targeting miR-1293.

Anthocyanins from Lycium ruthenicum Murray Mitigate Cadmium-Induced Oxidative Stress and Testicular Toxicity by Activating the Keap1/Nrf2 Signaling Pathway.

Cadmium (Cd) is a hazardous heavy metal environmental pollutant that has carcinogenic, teratogenic, and mutagenic properties. Excessive exposure to Cd can induce oxidative stress, which greatly harms the male reproductive system. Anthocyanins have remarkable antioxidative, anti-inflammatory, and anti-stress properties. In this study, we investigated the effects of anthocyanins and the underlying mechanisms through which anthocyanins mitigate Cd-induced reproductive damage. We isolated and purified Lycium ruthenicum Murray anthocyanin extract (LAE) and performed UHPLC-MS/MS to identify 30 different anthocyanins. We established an ICR mouse Cd injury model by administering 5 mg/kg/day CdCl2 for 28 consecutive days. LAE at 500 mg/kg/day effectively ameliorated testicular damage and preserved spermatogenesis. The mice in the LAE-treated group had elevated testosterone and inhibin B levels. Additionally, the treatment restored the activity of antioxidant enzymes, including T-SOD, CAT, and GR, and substantially increased the levels of the non-enzymatic antioxidant GSH. Research findings indicate that LAE can activate the SIRT1/Nrf2/Keap1 antioxidant pathway. This activation is achieved through the upregulation of both the SIRT1 gene and protein levels, leading to the deacetylation of Nrf2. Moreover, LAE reduces the expression of Keap1, alleviating its inhibitory effect on Nrf2. This, in turn, facilitates the uncoupling process, promoting the translocation of Nrf2 to the nucleus, where it governs downstream expression, including that of HO-1 and GPX1. LAE effectively mitigated toxicity to the reproductive system associated with exposure to the heavy metal Cd by alleviating oxidative stress in the testes.

Glycyrrhetinic Acid Receptor-Mediated Zeolitic Imidazolate Framework-8 Loaded Doxorubicin as a Nanotherapeutic System for Liver Cancer Treatment.

In this study, we designed and developed a DOX nanodrug delivery system (PEG-GA@ZIF-8@DOX) using ZIF-8 as the carrier and glycyrrhetinic acid (GA) as the targeting ligand. We confirmed that DOX was loaded and PEG-GA was successfully modified on the surface of the nanoparticles. The in vitro release profile of the system was investigated at pH 5.0 and 7.4. The cellular uptake, in vitro cytotoxicity, and lysosomal escape characteristics were examined using HepG2 cells. We established an H22 tumor-bearing mouse model and evaluated the in vivo antitumor activity. The results showed that the system had a uniform nanomorphology. The drug loading capacity was 11.22 ± 0.87%. In acidic conditions (pH 5.0), the final release rate of DOX was 57.73%, while at pH 7.4, it was 25.12%. GA-mediated targeting facilitated the uptake of DOX by the HepG2 cells. PEG-GA@ZIF-8@DOX could escape from the lysosomes and release the drug in the cytoplasm, thus exerting its antitumor effect. When the in vivo efficacy was analyzed, we found that the tumor inhibition rate of PEG-GA@ZIF-8@DOX was 67.64%; it also alleviated the loss of the body weight of the treated mice. This drug delivery system significantly enhanced the antitumor effect of doxorubicin in vitro and in vivo, while mitigating its toxic side effects.

Prognostic Role of Mitochondrial Transcription Termination Factor 3 in Thyroid Carcinoma.

Background: Studies have shown that the Mitochondrial Transcription Termination Factor 3 (MTERF3) negatively regulates mitochondrial gene expression and energy metabolism, and plays a significant role in many cancer types. Nevertheless, the expression and prognostic role of MTERF3 in patients with thyroid carcinoma (THCA) is still unclear. Thus, we investigated the expression, clinicopathological significance, and prognostic value of MTERF3 in THCA. Methods: The protein and mRNA expression levels of MTERF3 were, respectively, analyzed using immunohistochemistry (IHC) from THCA tissues and RNA-Seq data downloaded from The Cancer Genome Atlas. In addition, the relationships among the expression of MTERF3, the stemness feature, the extent of immune infiltration, drug sensitivity, the expression of ferroptosis, and N6-methyladenosine (m6A) methylation regulators, were evaluated as prognostic indicators for patients with THCA using the Kaplan-Meier plotter database. Results: The IHC and RNAseq results showed that the protein and mRNA expression levels of MTERF3 in adjacent nontumor tissues were significantly higher than in THCA tissues. The survival analysis indicated that decreased expression of MTERF3 was associated with a poorer prognosis. Furthermore, the expression of MTERF3 not only negatively correlated with the enhancement of the stemness of THCA and the reduction of drug sensitivity but also was implicated in ferroptosis and m6A methylation. Conclusion: The data from this study support the hypothesis that decreased expression of MTERF3 in THCA is associated with a poor prognosis.

Hollow SnO2/CdS QDs/CdCO3 heterostructured nanocubes coupled with hollow PtPd/MnCo-CeO2 nanozyme-mediated synergistic amplification for ultrasensitive PEC immunoanalysis of lung cancer biomarker.

Nowadays, lung cancer is one of the most dangerous cancers threatening human life all over the world. As a crucial biomarker, cytokeratin 19 fragment 21-1 (CYFRA 21-1) is extraordinary important for diagnosis of non-small cell lung cancer (NSCLC). In this work, we synthesized hollow SnO2/CdS QDs/CdCO3 heterostructured nanocubes with high and stable photocurrents, which applied to construction of a sandwich-typed photoelectrochemical (PEC) immunosensor for detection of CYFRA 21-1, integrated by in-situ catalytic precipitation strategy with home-built PtPd alloy anchored MnCo-CeO2 (PtPd/MnCo-CeO2) nanozyme for synergistic amplification. The interfacial electron transfer mechanism upon visible-light irradiation was investigated in details. Further, the PEC responses were seriously quenched by the specific immunoreaction and precipitation catalyzed by the PtPd/MnCo-CeO2 nanozyme. The established biosensor showed a wider linear range of 0.001-200 ng mL-1 and a lower limit of detection (LOD = 0.2 pg mL-1, S/N = 3), coupled by exploring such analysis even in diluted human serum sample. This work opens a constructive avenue to develop ultrasensitive PEC sensing platforms for detecting diverse cancer biomarkers in clinic.

Carbonic Anhydrase 4 Serves as A Novel Prognostic Biomarker and Therapeutic Target for Non-Small Cell Lung Cancer: A Study Based on TCGA Samples.

BACKGROUND: Carbonic anhydrase 4 (CA4) is a member of a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide and was found to have low expression in non-small cell lung cancer (NSCLC). However, the specific role of CA4 in NSCLC and the underlying mechanisms remain unknown. METHODS: The bioinformatic analysis on lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets downloaded from The Cancer Genome Atlas (TCGA) database was performed. We found that CA4 expression was lower in tumors than that in normal tissues, which were verified by Real-time PCR. Lower CA4 levels were significantly associated with higher T stages in LUAD and LUSC cohorts. Multivariate analysis showed that CA4 is an independent prognostic factor for NSCLC. Furthermore, the expression of CA4 also correlated with immune infiltration and drug sensitivity. RESULTS: Ectopic expression of CA4 decreased NSCLC cell proliferation in vitro by CCK-8 assay. CA4 caused G0/G1 cell cycle arrest by cell experiments. Mechanistic studies found that CA affects the cell cycle and inhibits cell proliferation by downregulating the expression of CDK2. CONCLUSION: The present findings highlight the role of CA4 in NSCLC and identify CA4 as a potential novel diagnostic and prognostic biomarker for the treatment of NSCLC.

Adequate Number of Lymph Nodes Sampled May Determine Appropriate Surgical Modality for Early-Stage NSCLC: A Population-Based Real-World Study.

BACKGROUND: The standard surgical procedure for ≤ 2 cm non-small cell lung cancer (NSCLC), including the number of lymph nodes sampled (nLN) and surgical modality, remains controversial. This study was designed to determine the optimal cohort in which sublobectomy could be an alternative to lobectomy. MATERIALS (OR PATIENTS) AND METHODS: Patients from 1998 to 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff value of nLN was identified using a restrictive cubic spline graph (RCS). Kaplan-Meier analysis was used to determine cancer-specific survival (CSS). The COX proportional hazard regression model was used to identify the influence of clinical and demographic variables on survival, and propensity score matching (PSM) was used to balance differences in baseline characteristics. Finally, we used an external cohort from a single-center medical institution to verify the conclusions drawn from the SEER database. RESULTS: A total of 6150 patients were included. The sublobectomy subgroup included segmentectomy (308, 5.0%) and wedge resection (1611, 26.2%). The cutoff value for nLN was 7. In the nLN ≥7 subgroup of the PSM cohort, the CSS of segmentectomy and wedge resection was close to that of the lobectomy subgroup (P = .12), whereas in the nLN <7 subgroup, the CSS of the lobectomy subgroup was significantly higher than that of the sublobectomy with P < .001). Surgical methods, nLN, age, sex, and differentiated grade were independent predictors of CSS. External cohort validation: A total of 1106 patients from the Affiliated Jinhua Hospital of Zhejiang University School of Medicine between 2013 and 2020 were included. The grouping criteria were consistent with the SEER database. In the nLN≥7 subgroup, sublobectomy had a survival outcome similar to that of lobectomy (P = .81). CONCLUSION: Sublobectomy and nLN < 7 were strongly associated with poorer CSS for early-stage NSCLC. On the premise of nLN ≥ 7, sublobectomy could provide similar survival outcomes to lobectomy for these patients.

Pro-Apoptotic Effect of Zeolitic Imidazolate Framework-8 (ZIF-8)-Loaded Dihydromyricetin on HepG2 Cells.

Dihydromyricetin (DHM) has garnered attention due to its promising antitumor activity, but its low bioavailability restricts its clinical application. Thus, developing nano-drug delivery systems could enhance its antitumor activity. We prepared DHM@ZIF-8 nanoparticles using the zeolite imidazole framework-8 (ZIF-8) as a carrier loaded with dihydromyricetin. A series of characterizations were performed, including morphology, particle size, zeta potential, X-single crystal diffraction, ultraviolet spectroscopy, infrared spectroscopy, and Brunauer-Emmett-Teller (BET). The in vitro release characteristics of DHM@ZIF-8 under pH = 5.0 and pH = 7.4 were studied using membrane dialysis. The antitumor activity and pro-apoptotic mechanism of DHM@ZIF-8 were investigated through CCK-8 assay, reactive oxygen species (ROS), Annexin V/PI double-staining, transmission electron microscopy, and Western blot. The results depicted that DHM@ZIF-8 possessed a regular morphology with a particle size of 211.07 ± 9.65 nm (PDI: 0.19 ± 0.06) and a Zeta potential of -28.77 ± 0.67 mV. The 24 h drug releasing rate in PBS solution at pH = 7.4 was 32.08% and at pH = 5.0 was 85.52% in a simulated tumor micro acid environment. DHM@ZIF-8 could significantly enhance the killing effect on HepG2 cells compared to the prodrug. It can effectively remove ROS from the tumor cells, promote apoptosis, and significantly affect the expression of apoptosis-related proteins within tumor cells.

Ultrasound Imaging Using the Coherence of Estimated Channel Data.

This article introduces a novel method to estimate the coherence of ultrasound channel data from beamformed radio frequency (RF) data. Estimates of ultrasound channel data are obtained by spatially filtering acquired RF data in the frequency domain. The frequency response of the spatial filters yields outputs similar to frequency domain representations of individual channel signals. This technique performs multiple normalized cross-correlations from the outputs of multiple spatial filters. The coefficients are summed together for each pixel in the coherence-based image. Simulation results using a 64 element 2.5-MHz phased array showed an improvement in contrast-to-noise ratio (CNR) of 67%-93% and a 125%-183% improvement in speckle signal-to-noise ratio (SNR) compared with standard beamformed data. Experimental CNR using a tissue-mimicking phantom showed improvement of 43%-58%, and experimentalSNR improvement was 23%-154%. Comparisons to a previously coherence method, short-lag spatial coherence, are also presented. Preliminary in vivo images of the heart and gall bladder are also shown. This method improves CNR enabling improved visualization of anechoic regions such as cyst and blood vessels.

IL-36γ and IL-36Ra Reciprocally Regulate Colon Inflammation and Tumorigenesis by Modulating the Cell-Matrix Adhesion Network and Wnt Signaling.

Inflammatory bowel disease and colorectal cancer are associated with dysregulation of cytokine networks. However, it is challenging to target cytokines for effective intervention because of the overlapping functions and unpredictable interactions of cytokines in such diverse networks. Here, it is shown that IL-36γ and IL-36Ra, an agonist and an antagonist for IL-36R signaling respectively, reciprocally regulate the experimental colitis and the colon cancer development in mice. Knockout or neutralization of IL-36γ alleviates dextran sulfate sodium (DSS)-induced colitis and inhibits colon cancer development, whereas knockout of IL-36Ra exacerbates DSS-induced colitis and promotes colonic tumorigenesis in multiple colon cancer models in mice. Mechanistically, IL-36γ upregulates extracellular matrix and cell-matrix adhesion molecules and facilitates Wnt signaling, which is mitigated by IL-36Ra or IL-36γ neutralizing antibody. Consistently, IL-36γ levels are positively correlated with extracellular matrix levels and ß-catenin levels in human colorectal tumor biopsies. These findings suggest the critical role of IL-36γ and IL-36Ra in gut inflammation and tumorigenesis and indicate that targeting the IL-36γ/IL-36Ra signal balance provides potential therapeutic strategy for inflammatory bowel disease and gastrointestinal cancers.

Downregulation of NCL attenuates tumor formation and growth in HeLa cells by targeting the PI3K/AKT pathway.

BACKGROUND: Nucleolin (NCL, C23) is a multifunctional phosphoprotein that plays a vital role in modulating the survival, proliferationand apoptosis of cancer cells. However, the effects of NCL on cervical cancer and the underlying mechanisms behind this are poorly understood. METHODS: Lentiviral transfection technology was used to construct NCL knockdown cell lines. MTT, colony formation assays, and tumorigenic assays in vivo were performed to observe cell proliferation. HOECHST 33342 staining, flow cytometry, and caspase activity assay were used to test cell apoptosis. RNA-Seq, Western blotting, and RT-PCR were conducted to investigate the specific molecular mechanism. RESULTS: NCL knockdown inhibited cell proliferation and promoted apoptosis both in vivo and in vitro. Mechanistic studies revealed that NCL knockdown inhibited the PI3K/AKT pathway by upregulating FGF, ITGA, TNXB, VEGF, Caspase 3, and Bax, as well as by downregulating AKT, GNB4, CDK6, IL6R, LAMA, PDGFD, PPP2RSA and BCL-2. In addition, the expression levels of apoptosis-related genes after using a PI3K inhibitor LY294002 were consistent with shRNA studies, while treatment with a 740Y-P agonist showed the opposite effect. CONCLUSIONS: Our findings indicate that downregulation of NCL may be a novel treatment strategy forcervical cancer.

Nanoplasmonic Sandwich Immunoassay for Tumor-Derived Exosome Detection and Exosomal PD-L1 Profiling.

Tumor-derived exosomes play a vital role in the process of cancer development. Quantitative analysis of exosomes and exosome-shuttled proteins would be of immense value in understanding cancer progression and generating reliable predictive biomarkers for cancer diagnosis and treatment. Recent studies have indicated the critical role of exosomal programmed death ligand 1 (PD-L1) in immune checkpoint therapy and its application as a patient stratification biomarker in cancer immunotherapy. Here, we present a nanoplasmonic exosome immunoassay utilizing gold-silver (Au@Ag) core-shell nanobipyramids and gold nanorods, which form sandwich immune complexes with target exosomes. The immunoassay generates a distinct plasmonic signal pattern unique to exosomes with specific exosomal PD-L1 expression, allowing rapid, highly sensitive exosome detection and accurate identification of PD-L1 exosome subtypes in a single assay. The developed nanoplasmonic sandwich immunoassay provides a novel and viable approach for tumor cell-derived exosome detection and analysis with quantitative molecular details of key exosomal proteins, manifesting its great potential as a transformative diagnostic tool for early cancer detection, prognosis, and post-treatment monitoring.

Second-generation cryoballoon versus contact force radiofrequency ablation for atrial fibrillation: an updated meta-analysis of evidence from randomized controlled trials.

Catheter ablation has been recommended for patients with symptomatic atrial fibrillation (AF), with pulmonary vein isolation being the cornerstone of the ablation procedure. Newly developed technologies, such as cryoballoon ablation with a second-generation cryoballoon (CB2) and the contact force radiofrequency (CF-RF) ablation, have been introduced in recent years to overcome the shortcomings of the widely used RF ablation approach. However, high-quality results comparing CB2 and CF-RF remain controversial. Thus, we conducted this meta-analysis to assess the efficacy and safety between CB2 and CF-RF using evidence from randomized controlled trials (RCTs). Databases including Embase, PubMed, the Cochrane Library, and ClinicalTrials.gov were systematically searched from their date of inception to January 2021. Only RCTs that met the inclusion criteria were included for analysis. The primary outcome of interest was freedom from atrial tachyarrhythmia (AT) during follow-up. Secondary outcomes included procedure-related complications, procedure time and fluoroscopy time. Six RCTs with a total of 987 patients were finally enrolled. No significant differences were found between CB2 and CF-RF in terms of freedom from AT (relative risk [RR] = 1.03, 95% confidence interval [CI] 0.92-1.14, p = 0.616) or total procedural-related complications (RR = 1.25, 95% CI 0.69-2.27, p = 0.457). CB2 treatment was associated with a significantly higher risk of phrenic nerve palsy (PNP) than CF-RF (RR = 4.93, 95% CI 1.12-21.73, p = 0.035). The occurrences of pericardial effusion/tamponade and vascular complications were comparable between the CB2 and CF-RF treatments (RR = 0.41, p = 0.398; RR = 0.82, p = 0.632). In addition, CB2 treatment had a significantly shorter procedure time than CF-RF (weighted mean difference [WMD] = - 20.75 min, 95% CI - 25.44 ~ - 16.05 min, P < 0.001), whereas no difference was found in terms of fluoroscopy time (WMD = 4.63 min, p = 0.179). CB2 and CF-RF treatment are comparable for AF patients regarding freedom from AT and procedure-related complications. Compared to CF-RF, CB2 treatment was associated with a shorter procedure time but a higher incidence of PNP. Further large-scale studies are warranted to compare these two techniques and provide an up-to-date recommendation.

Clinical application of individualized total arterial coronary artery bypass grafting in coronary artery surgery.

BACKGROUND: Total arterial revascularization is associated with increased patency and long-term efficacy and decreased perioperative morbidity and mortality and incidence of cardiac-related events and sternal wound infection compared with conventional coronary artery bypass surgery (CABG), in which the left internal mammary artery (LIMA) is typically grafted to the left anterior descending artery with additional saphenous vein grafts often used. This study determined whether these favorable clinical results could be realized at the authors' institute. AIM: To summarize the early efficacy and clinical experience of individualized total arterial coronary artery bypass grafting surgery. METHODS: CABG was performed on 35 patients with non-single-vessel coronary artery disease by adopting total arterial grafts at Fourth Affiliated Hospital of Harbin Medical University between April 2016 and December 2019. LIMA was used in 35 patients, radial artery (RA) was used in 35 patients, and right gastroepiploic artery (RGEA) was used in 9 patients. Perioperative complications were observed, short-term graft patency rate was followed-up, and quality of life was assessed. RESULTS: All patients underwent off-pump coronary artery bypass and the surgeries were successful. All of them were discharged without any complications or deaths. During the follow-up, it was found that patients' angina symptoms were relieved and New York Heart Association classification for cardiac function was class I to class II. A total of 90 vessels were grafted with no occlusion for internal mammary artery, three occlusions for RA, and one occlusion for RGEA. CONCLUSION: The individualized total arterial strategy based on the vessels targeting individual anatomic characteristics can achieve complete revascularization with satisfactory short-term grafting patency rate.

Transcriptionomic Study on Apoptosis of SKOV-3 Cells Induced by Phycoerythrin from Gracilaria lemaneiformis.

OBJECTIVE: To investigate the effects of Phycoerythrin (PE) on the human ovarian cancer cell line SKOV-3 and its antitumor mechanisms from a transcriptional point of view. METHODS: SKOV-3 cells were exposed to different concentrations of phycoerythrin. The efficiency of this treatment was evaluated through cell growth inhibition, changes in cell morphology, apoptosis and intracellular ROS levels. High throughput sequencing (RNA-seq) was performed to screen Differentially Expressed Genes (DEGs), which was verified using RT-PCR and Western blotting. RESULTS: PE showed a significant inhibitory effect on the growth of SKOV-3 cells in a time- and dose-dependent manner. H&E staining, electron microscopy and flow cytometry revealed that PE induced apoptosis in SKOV-3 cells. Transcriptome analysis showed that 2963 genes were differentially expressed between untreated or PEtreated cells. GO and KEGG pathway analyses identified 16 classical pathways that were enriched. We verified 8 DEGs including, JNK, GADD45A, EDEM2, RAD23, UBQLN, CAPN1, XBP1, and OS9. These results were consistent with the results from transcriptional sequences. CONCLUSION: The inhibitory effect of PE on SKOV-3 cells was a result of interaction with multiple pathways and signaling molecules. Among these, the ROS/JNK/Bcl-2 signaling pathway, upregulation of JNK, GADD45A and RAD23 as well as downregulation of XBP1 and OS9 played a critical role in the PE -induced apoptosis in human ovarian cancer cells.

Comparative efficacy and safety of catheter ablation interventions for atrial fibrillation: comprehensive network meta-analysis of randomized controlled trials.

PURPOSE: Point-by-point radiofrequency (RF) ablation has been the cornerstone of pulmonary vein isolation (PVI) for patients with atrial fibrillation (AF); however, it remains a complex and time-consuming procedure. Many novel AF catheter ablation (CA) techniques have been introduced, but whether they represent valuable alternatives remains controversial. Thus, we conducted a network meta-analysis to comprehensively evaluate the efficacy and safety of different CA interventions. METHODS: We systematically searched several databases (Embase, PubMed, the Cochrane Library, and ClinicalTrials.gov ) from inception to March, 2020. The primary outcomes of interest were freedom from atrial tachyarrhythmia (AT) and procedure-related complications; secondary outcomes included procedure time and fluoroscopy time. RESULTS: Finally, 33 randomized controlled trials (RCTs) with a total of 4801 patients were enrolled. No significant differences were found among the different interventions in terms of primary efficacy or safety outcomes. PVAC was most likely to have the shortest procedure time (Prbest = 61.5%) and nMARQ the shortest fluoroscopy time (Prbest = 60.6%); compared with conventional irrigated RF (IRF) ablation, cryoballoon ablation (CBA) showed comparable clinical efficacy and safety; CBA with second-generation CB (CB2) had a significantly shorter procedure time than IRF with contact force technology (CF-IRF) (WMD = - 20.75; p = 0.00). CONCLUSION: There is insufficient evidence to suggest that one CA technique is superior to another. However, PVAC may be associated with a shorter procedural duration, and the CB2 catheters also seemed to reduce the procedure time compared with that of CF-IRF. Further large-scale studies are warranted to compare the available CA techniques and provide an up-to-date optimum recommendation.

[Clinical application value of liquid dressing after circumcision].

OBJECTIVE: To explore and analyze the effect of liquid dressing in relieving pain and preventing incision adhesion after circumcision and its clinical application value. METHODS: Ninety male patients underwent circumcision in Hangzhou Third People's Hospital from September to November 2019, with the incision covered with liquid dressing + vaseline gauze (group A, n = 30), liquid dressing alone (group B, n = 30) or vaseline gauze only (group C, n = 30). At 2, 4 and 6 days after surgery, we compared the Visual Analogue Scale (VAS) pain intensity at dressing change, incision bleeding after dressing removal and incidence of postoperative complications among the three groups of patients. RESULTS: At 2, 4 and 6 days after surgery, the VAS pain score and incidence of incision bleeding were significantly lower in groups A and B than in C (P < 0.05). At 2 days, both the VAS pain score and incidence of incision bleeding were markedly decreased in group A as compared with those in group B (P < 0.05). At 4 and 6 days, the VAS pain score remained lower in group A than in B (P < 0.05), but the incidence rate of incision bleeding showed no significant difference between the two groups (P > 0.05). No statistically significant differences were observed in the incidence of postoperative complications among the three groups (P > 0.05). CONCLUSIONS: Liquid dressing can reduce pain intensity at dressing change, prevent incision adhesion and consequent dressing change-induced tearing and bleeding, and therefore promote incision healing after circumcision. Its combination with vaseline gauze can achieve an even better effect.

Mapping current research and identifying hotspots on mesenchymal stem cells in cardiovascular disease.

BACKGROUND: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in the cardiovascular disease. This study provides information on the latest progress, evolutionary path, frontier research hotspots, and future research developmental trends in this field. METHODS: A knowledge map was generated by CiteSpace and VOSviewer analysis software based on data obtained from the literature on MSCs in the cardiovascular field. RESULTS: The USA and China ranked at the top in terms of the percentage of articles, accounting for 34.306% and 28.550%, respectively. The institution with the highest number of research publications in this field was the University of Miami, followed by the Chinese Academy of Medical Sciences and Harvard University. The research institution with the highest ACI value was Harvard University, followed by the Mayo Clinic and the University of Cincinnati. The top three subjects in terms of the number of published articles were cell biology, cardiovascular system cardiology, and research experimental medicine. The journal with the most publications in this field was Circulation Research, followed by Scientific Reports and Biomaterials. The direction of research on MSCs in the cardiovascular system was divided into four parts: (1) tissue engineering, scaffolds, and extracellular matrix research; (2) cell transplantation, differentiation, proliferation, and signal transduction pathway research; (3) assessment of the efficacy of stem cells from different sources and administration methods in the treatment of acute myocardial infarction, myocardial hypertrophy, and heart failure; and (4) exosomes and extracellular vesicles research. Tissue research is the hotspot and frontier in this field. CONCLUSION: MSC research has presented a gradual upward trend in the cardiovascular field. Multidisciplinary intersection is a characteristic of this field. Engineering and materials disciplines are particularly valued and have received attention from researchers. The progress in multidisciplinary research will provide motivation and technical support for the development of this field.

Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function.

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague-Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1ß, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.