With the continuous development of China's aging society and the prevalence of unhealthy lifestyles, the incidence of cardiovascular disease in China has been increasing in recent years. Among them, atrial fibrillation (AF) is the most common arrhythmia disease. In recent years, pulsed field ablation (PFA) has been continuously applied to AF treatment as a novel treatment. This paper first introduces the principle of PFA applied to AF treatment, and introduces the research progress of PFA in different directions, such as the comparison of different ablation methods, the study of physical parameters, the study of ablation area, the study of tissue specificity and clinical research. Then, the clinical prior research of PFA is discussed, including the use of simulation software to obtain the simulation effect of different parameters, the evaluation of ablation effect during animal research, and finally the current AF treatment. Various prior studies and clinical studies are summarized, and suggestions are made for the shortcomings found in the study of AF treatment and the future research direction is prospected.

Objective To evaluate the application of three deep learning algorithms in automatic segmentation of clinical target volumes (CTVs) in high-dose-rate brachytherapy after surgery for endometrial carcinoma. Methods A dataset comprising computed tomography scans from 306 post-surgery patients with endometrial carcinoma was divided into three subsets: 246 cases for training, 30 cases for validation, and 30 cases for testing. Three deep convolutional neural network models, 3D U-Net, 3D Res U-Net, and V-Net, were compared for CTV segmentation. Several commonly used quantitative metrics were employed, i.e., Dice similarity coefficient, Hausdorff distance, 95th percentile of Hausdorff distance, and Intersection over Union. Results During the testing phase, CTV segmentation with 3D U-Net, 3D Res U-Net, and V-Net showed a mean Dice similarity coefficient of 0.90 ± 0.07, 0.95 ± 0.06, and 0.95 ± 0.06, a mean Hausdorff distance of 2.51 ± 1.70, 0.96 ± 1.01, and 0.98 ± 0.95 mm, a mean 95th percentile of Hausdorff distance of 1.33 ± 1.02, 0.65 ± 0.91, and 0.40 ± 0.72 mm, and a mean Intersection over Union of 0.85 ± 0.11, 0.91 ± 0.09, and 0.92 ± 0.09, respectively. Segmentation based on V-Net was similarly to that performed by experienced radiation oncologists. The CTV segmentation time was < 3.2 s, which could save the work time of clinicians. Conclusion V-Net is better than other models in CTV segmentation as indicated by quantitative metrics and clinician assessment. Additionally, the method is highly consistent with the ground truth, reducing inter-doctor variability and treatment time.

Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis（PNAC）in extremely/ultra-low birth weight infants，and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020，using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software，and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included，with a median gestational age of 29.14（28.00，30.86）weeks and a median birth weight of 1　170（1　000,1　300）g.Among them，26（12.81%）cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition（ OR=1.015 ，95% CI 1.003-1.034），the cumulative amount of glucose（ OR=1.014 ，95% CI 1.001-1.028），small for gestational age（ OR=3.455 ，95% CI 1.127-10.589），and neonatal sepsis（ OR=3.142 ，95% CI 1.039-9.503）were independent risk factors for PNAC（ P＜0.05）；The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model，the area under the receiver operating characteristic curve was 0.835（95% CI 0.842-0.731），and the results of the Hosmer Limeshow goodness of fit test show that：χ 2=5.34，degree of freedom=8， P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate，with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition，glucose accumulation，small for gestational age infants，and neonatal sepsis exhibits high predictive ability，and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants

Introduction::Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.Methods::In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 –8). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR–Egger, and weighted median regression) were used to ensure that our results more reliable. Results::All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30–1.58, P = 2.51 × 10 -13). The results of MR–Egger and weighted median regression exhibited similar trends (MR–Egger OR = 1.40 [95% CI, 1.08–1.81], P = 1.61 × 10 -2; weighted median OR = 1.39 [95% CI, 1.21–1.61], P = 1.62 × 10 -6). MR–Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. Conclusions::Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

Objective To investigate the involvement of calmodulin(CaM)in the pathogenesis of Alzheimer disease(AD)and the mechanism by which CaM binds to amyloid-β(Aβ).Methods The hub genes expressed in AD and predicted to be the target proteins for AD prevention and treatment were obtained using bioinformatics methods.The GST-Aβ1-42 recombinant plasmid was constructed through genetic recombination and was then sequenced.The recombinant plasmids were identified using agarose gel electrophoresis,while the extracted and purified GST-Aβ1-42 fusion protein was confirmed using SDS-PAGE gel electrophoresis.GST pull-down assay was used to detect the interaction between GST-Aβ1-42 protein and CaM,expressed in the plasmid.Results The top 20 hub genes in degree ranking were obtained.The DNA sequencing results of the plasmid proved that the recombinant plasmid was successfully constructed.The agarose gel electrophoresis results indicated that the fragment digested by the enzyme was similar to the molecular weight of the Aβ1-42 gene seg-ments,further proving the successful construction of the recombinant plasmid.Binding of GST-Aβ1-42 protein to CaM in a concentration dependent manner was revealed through the GST pull down experiment.Conclusion The GST-Aβ1-42 recombinant plasmid is success-fully constructed and is shown to bind to CaM.

Objective:To explore the phenotype and mechanism of ferroptosis in steatosis liver ischemia reperfusion injury (IRI) and elucidate the mechanism of targeted inhibition of ferroptosis down-regulating steatosis liver IRI.Methods:First, 20 mice are divided into 2 group according to the different feeding mode: Normal chow diet(NCD group, n=10)and high fat diet(HFD group, n=10). The fatty liver constructs are successful as verified by laboratory tests for relevant indicators and oil red staining.NCD and HFD mice were randomized into two groups sham and IRI.The expression of glutathione peroxidase 4(Gpx4)in liver tissues of each group is detected by Western blot.Morphological phenotypes of mitochondria in liver tissue are observed by transmission electron microscope.Accordingly, it was determined whether ferroptosis occurred in mouse liver IRIs.NCD(n=30)and HFD(n=30)are further randomized into 3 groups: sham(n=10), IRI(n=10)and inhibitor(IRI-fer-1 group, n=10). The serum contents of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)are detected by ALT/AST kits.Hematoxylin-eosin(HE)stain is employed for detecting the degree of liver injury; immunohistochemistry(IHC)and enzyme-linked immunosorbent assay(ELISA)for detecting the levels of inflammatory factors and inflammatory cell infiltration.Similarly, primary hepatocytes from NCD/HFD mice are extracted and the occurrence of ferroptosis is verified by detecting C11-BODIPY(581/591)by fluorescent stain after hypoxia-reoxygenation(H/R).Results:As compared with NCD-IRI group, Gpx4 protein expression declined obviously in HFD-IRI group while serum ALT/AST level spiked markedly( P<0.01). IHC staining of 4-HNE is positive, mitochondrial specific damage is more pronounced and inflammatory infiltration became enhanced.As compared with IRI group, serum level of ALT/AST dropped obviously and infiltration of inflammatory cells and secretion of inflammatory factors are blunted markedly in IRI-fer-1 group( P<0.01). Conclusions:A high degree of ferroptosis and severe inflammatory response during fatty liver IR are features of distinguishing steatosis liver IRI from ordinary liver IRI.Targeted inhibition of ferroptosis lowers inflammation and damage during IR in steatosis liver.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

The genus Rosa (Rosaceae family) includes about 200 species spread in the world, and this genus shows unique advantages in medicine and food. To date, several scholars concentrated on compounds belonging to flavonoids, triterpenes, tannins, polysaccharide, phenolic acids, fatty acids, organic acids, carotenoids, and vitamins. Pharmacological effects such as antineoplastic and anti-cancer properties, anti-inflammatory, antioxidant, liver protection, regulate blood sugar, antimicrobial activity, antiviral activity, as well as nervous system protection and cardiovascular protection were wildly reported. This article reviews the chemical constituents, pharmacological effects, applications and safety evaluations of Rosa plants, which provides a reference for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of the genus Rosa.

Chronic atrophic gastritis (CAG), a common disease of digestive system, is an extremely important cause of gastric cancer (GC). The occurrence and development of CAG involves the abnormality of multiple signaling pathways. Traditional Chinese medicines (TCMs) has the advantages of mild action, multi-target and small adverse reaction, etc., which broadens the way for the treatment of the disease, and TCMs can play a therapeutic role by regulating multiple signaling pathways. In this review, based on the related experiments of TCMs and Chinese herbal compounds in recent years, the related literatures were searched and 10 kinds of signaling pathways involved were summarized, in order to provide a reference for further research on reversing or delaying the progress of CAG and preventing gastric cancer.