Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease with a poor prognosis. We previously found that p62 presented a marked nuclear-cytoplasmic translocation in ESCC cells as compared that in normal esophageal epithelial cells, but its effects on ESCC cells remain unclear. This study aims to clarify the impacts of different cellular localization of p62 on the function of ESCC cells and the underlying molecular mechanisms. We here demonstrated that cytoplasmic p62 enhances the migration and invasion abilities of esophageal cancer cells, whereas nuclear p62 has no effect. We further explored the interaction protein of p62 by using GST pull-down experiment and identified EPLIN as a potential protein interacting with p62. In addition, reducing EPLIN expression significantly inhibited the migration and invasion of ESCC cells, which were rescued when EPLIN expression was restored after the p62 knockdown. At a molecular level, p62 in cytoplasm positively regulated the expression of EPLIN via enhancing its protein stability. Data from the TCGA and GEO database displayed a significant up-regulation of EPLIN mRNA expression in ESCC tissues compared with corresponding paired esophageal epithelial samples. Our findings present evidence that the nuclear-cytoplasmic translocation of p62 protein contributes to an aggressive malignancy phenotype, providing candidate molecular biomarkers and potential molecular targets for the diagnosis and treatment of ESCC.

Forensic bone age assessment of hand and wrist joint MRI images in Chinese han male adolescents based on deep convolutional neural networks.

In Chinese criminal law, the ages of 12, 14, 16, and 18 years old play a significant role in the determination of criminal responsibility. In this study, we developed an epiphyseal grading system based on magnetic resonance image (MRI) of the hand and wrist for the Chinese Han population and explored the feasibility of employing deep learning techniques for bone age assessment based on MRI of the hand and wrist. This study selected 282 Chinese Han Chinese males aged 6.0-21.0 years old. In the course of our study, we proposed a novel deep learning model for extracting and enhancing MRI hand and wrist bone features to enhance the prediction of target MRI hand and wrist bone age and achieve precise classification of the target MRI and regression of bone age. The evaluation metric for the classification model including precision, specificity, sensitivity, and accuracy, while the evaluation metrics chosen for the regression model are MAE. The epiphyseal grading was used as a supervised method, which effectively solved the problem of unbalanced sample distribution, and the two experts showed strong consistency in the epiphyseal plate grading process. In the classification results, the accuracy in distinguishing between adults and minors was 91.1%, and the lowest accuracy in the three minor classifications (12, 14, and 16 years of age) was 94.6%, 91.1% and 96.4%, respectively. The MAE of the regression results was 1.24 years. In conclusion, the deep learning model proposed enabled the age assessment of hand and wrist bones based on MRI.

Green and Efficient Extraction of Phenolic Components from Plants with Supramolecular Solvents: Experimental and Theoretical Studies.

The supramolecular solvent (SUPRAS) has garnered significant attention as an innovative, efficient, and environmentally friendly solvent for the effective extraction and separation of bioactive compounds from natural resources. However, research on the use of a SUPRAS for the extraction of phenolic compounds from plants, which are highly valued in food products due to their exceptional antioxidant properties, remains scarce. The present study developed a green, ultra-sound-assisted SUPRAS method for the simultaneous determination of three phenolic acids in Prunella vulgaris using high-performance liquid chromatography (HPLC). The experimental parameters were meticulously optimized. The efficiency and antioxidant properties of the phenolic compounds obtained using different extraction methods were also compared. Under optimal conditions, the extraction efficiency of the SUPRAS, prepared with octanoic acid reverse micelles dispersed in ethanol-water, significantly exceeded that of conventional organic solvents. Moreover, the SUPRAS method demonstrated greater antioxidant capacity. Confocal laser scanning microscopy (CLSM) images revealed the spherical droplet structure of the SUPRAS, characterized by a well-defined circular fluorescence position, which coincided with the position of the phenolic acids. The phenolic acids were encapsulated within the SUPRAS droplets, indicating their efficient extraction capacity. Furthermore, molecular dynamics simulations combined with CLSM supported the proposed method's mechanism and theoretically demonstrated the superior extraction performance of the SUPRAS. In contrast to conventional methods, the higher extraction efficiency of the SUPRAS can be attributed to the larger solvent contact surface area, the formation of more types of hydrogen bonds between the extractants and the supramolecular solvents, and stronger, more stable interaction forces. The results of the theoretical studies corroborate the experimental outcomes.

Exosomal MEF2C's Association With the Progression of CRC in Regulating CD36 Transcription.

Context: Exosomes are biologically active, extracellular vesicles that are involved in tumor-related processes, including activating tumors, facilitating tumor growth, and promoting inflammation. Objective: The study intended to investigate microRNAs (miRNAs) in exosomes that are associated with colorectal cancer (CRC). Design: The research team performed bioinformatics analysis, extracting RNA-sequencing (RNA-seq) datasets from the Cancer Genome Atlas (TCGA); ExoRBase, a database of different types of RNA information that scientists have extracted from human exosomes; and the Gene Expression Omnibus (GEO) databases, and analyzed the data. Setting: The study took place at the Department of Colorectal Surgery at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China. Participants: From October 2020 to March 2021, a total of 28 CRC patients who underwent curative resection at the National Cancer Center were enrolled. Tumor samples and tumor-adjacent normal sample were obtained from these CRC patients. Postoperative pathological characteristics all shown adenocarcinoma. The research team recruited participants from the hospitals connected with CAMS and PUMC and obtained written informed consent from them for publication of a case report and any accompanying images. The Ethics Committee of the Cancer Institute (Hospital), CAMS & PUMC has officially recognized the study (NCC 2017-YZ-026). Outcome Measures: The research team: (1) extracted RNA-seq datasets from the TCGA, exoRBase and GEO and analyzed the differentially expressed genes (DEGs); (2) performed a cluster analysis of variant genes using weighted gene co-expression network analysis (WGCNA);(3) verified expression of myocyte enhancer factor 2C-genecards (MEF2C) and cluster of differentiation 36 (CD36) in CRC tissues; (4) explored the biological function of the MEF2C by performing proliferation, migration, and invasion assays; and (5) used a chromatin immunoprecipitation (ChIP) experiment to analyze mechanisms to reveal CD36 transcription regulated by exosomal MEF2C. Results: A significant mean difference in exosomal MEF2C existed between normal and tumor tissues. By performing a correlation analysis, the research team found 609 potential target points of exosomal MEF2C (r > 0.5, P < .05). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network analysis indicated that CD36 may be the target of exosomal MEF2C. Univariate, multivariate, and Kaplan-Meier analyses showed that CD36 was closely related to the overall survival (OS) of CRC patients. Obvious differences existed in the expression levels of MEF2C and CD36 in CRC and normal tissues according to qPCR and immunohistochemical assays. Functional-experiments analysis in vitro showed that exosomal-MEF2C could be considered as an antioncogene. Mechanistically, ChIP assays showed that MEF2C regulated the transcriptional level of CD 36; thus, the expression of CD36 increased significantly. Conclusion: MEF2C is a potential biomarker of a favorable prognosis in CRC and is related to the progression of CRC. Moreover, the MEF2C-CD36 pathway may reveal the tumor regulation mechanism in CRC. The exosomal MEF2C was the hub gene in exosomes, with CD36 was identified as the potential target. Exosomal MEF2C may be a promising molecular biomarker for predicting a good prognosis and may have potential as a medical target for CRC.

The Value of VR-PVEP in Objective Evaluation of Monocular Refractive Visual Impairment.

OBJECTIVES: To study the virtual reality-pattern visual evoked potential (VR-PVEP) P100 waveform characteristics of monocular visual impairment with different impaired degrees under simultaneous binocular perception and monocular stimulations. METHODS: A total of 55 young volunteers with normal vision (using decimal recording method, far vision ≥0.8 and near vision ≥0.5) were selected to simulate three groups of monocular refractive visual impairment by interpolation method. The sum of near and far vision ≤0.2 was Group A, the severe visual impairment group; the sum of near and far vision <0.8 was Group B, the moderate visual impairment group; and the sum of near and far vision ≥0.8 was Group C, the mild visual impairment group. The volunteers' binocular normal visions were set as the control group. The VR-PVEP P100 peak times measured by simultaneous binocular perception and monocular stimulation were compared at four spatial frequencies 16×16, 24×24, 32×32 and 64×64. RESULTS: In Group A, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 24×24, 32×32 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group B, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 16×16, 24×24 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group C, there was no significant difference between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at all spatial frequencies (P>0.05). There was no significant difference in the P100 peak times measured at all spatial frequencies between simulant visual impairment eyes and simultaneous binocular perception in the control group (P>0.05). CONCLUSIONS: VR-PVEP can be used for visual acuity evaluation of patients with severe and moderate monocular visual impairment, which can reflect the visual impairment degree caused by ametropia. VR-PVEP has application value in the objective evaluation of visual function and forensic clinical identification.

Research Progress of Age Estimation in the Living by Knee Joint MRI.

Bone development shows certain regularity with age. The regularity can be used to infer age and serve many fields such as justice, medicine, archaeology, etc. As a non-invasive evaluation method of the epiphyseal development stage, MRI is widely used in living age estimation. In recent years, the rapid development of machine learning has significantly improved the effectiveness and reliability of living age estimation, which is one of the main development directions of current research. This paper summarizes the analysis methods of age estimation by knee joint MRI, introduces the current research trends, and future application trend.

Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis.

BACKGROUND: Recently, Zika virus (ZIKV) re-emerged in India and was potentially associated with microcephaly. However, the molecular mechanisms underlying ZIKV pathogenesis remain to be explored. RESULTS: Herein, we performed a comprehensive RNA-sequencing analysis on ZIKV-infected JEG-3, U-251 MG, and HK-2 cells versus corresponding uninfected controls. Combined with a series of functional analyses, including gene annotation, pathway enrichment, and protein-protein interaction (PPI) network analysis, we defined the molecular characteristics induced by ZIKV infection in different tissues and invasion time points. Data showed that ZIKV infection and replication in each susceptible organ commonly stimulated interferon production and down-regulated metabolic-related processes. Also, tissue-specific immune responses or biological processes (BPs) were induced after ZIKV infection, including GnRH signaling pathway in JEG-3 cells, MAPK signaling pathway in U-251 MG cells, and PPAR signaling pathway in HK-2 cells. Of note, ZIKV infection induced delayed antiviral interferon responses in the placenta-derived cell lines, which potentially explains the molecular mechanism by which ZIKV replicates rapidly in the placenta and subsequential vertical transmission occurs. CONCLUSIONS: Together, these data may provide a systemic insight into the pathogenesis of ZIKV infection in distinct human tissue-derived cell lines, which is likely to help develop prophylactic and therapeutic strategies against ZIKV infection.

Evaluate Short-Term Outcomes of abciximab in ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials.

Objectives: This meta-analysis was to verify the short-time efficacy and safety of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Background: Abciximab has long-term efficacy in patients with STEMI undergoing PCI, but the short-term efficacy is still controversial. Methods: We conducted a systematic review and meta-analysis compared with or without abciximab in patients with STEMI undergoing PCI. The relevant randomized controlled trials were included by searching PubMed, EMBASE, Cochrane Library, and Web of Science databases and other sources. The relative risk (RR) and 95% confidence intervals (CI) of outcomes were calculated by the fixed-effects model. Results: Ten randomized controlled trials with 5008 patients met inclusion criteria. There were no significant differences in risk of all-cause death at 30-day (RR 0.79, CI 0.55-1.12, P=0.18), major bleeding (1.37, 0.93-2.03, P=0.11), and transfusion (1.23, 0.94-1.61, P=0.13) between the two groups. However, there were significant differences in risk of all-cause death at 6 months (0.57, 0.36-0.90, P=0.02), recurrent myocardial infarction (0.55, 0.33-0.92, P=0.02), repeat revascularization (0.58, 0.43-0.78, P=0.0004), final TIMI flow <3 (0.77, 0.62-0.96, P=0.02), minor bleeding (1.29, 1.02-1.63, P=0.04), and thrombocytopenia (2.04, 1.40-2.97, P=0.0002). Conclusions: The application of abciximab can lead to a lower risk of reinfarction, revascularization, and all-cause death at 6 months, but a higher risk of minor bleeding, and thrombocytopenia.

Dual Antiplatelet Therapy After Drug-Eluting Stents Implantation in East Asians: A Network Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Dual antiplatelet therapy (DAPT) is essential to prevent the risk of ischemia events, but it is difficult to avoid concurrent bleeding events. East Asians are associated with a higher tendency of bleeding than Caucasians, which may affect the DAPT duration. Therefore, this network meta-analysis to explore optimum DAPT duration for East Asians. The related randomized controlled trials that compared the different DAPT duration in East Asian patients were included by searching PubMed, EMBASE, and Cochrane Library database. The outcomes included myocardial infarction, stent thrombosis, all-cause death, stroke, and major bleeding. In addition, net adverse cardiac and cardiovascular events was defined as a composite outcome in this study. We calculated the odds ratio (OR) and 95% confidence intervals for end point events by the fixed effects model in the Bayesian's network frame. We included a total of 12 randomized controlled trials with 30,640 patients. Compared with 12-month DAPT, 1- to 3-month DAPT is effective in myocardial infarction (OR 0.72, 0.46-1.08), stents thrombosis (OR 1.27, 0.59-2.84), all-cause death (OR 0.91, 0.65-1.28), and stroke (OR 0.89, 0.57-1.39). The 1- to 3-month DAPT was associated with a lower risk of major bleeding compared with 12-month DAPT (OR 0.55, 0.4-0.76), 6-month DAPT (OR 0.54, 0.31-0.94), and >12-month DAPT (OR 0.43, 0.28-0.65). In addition, more than 12 months of DAPT did not reduce the incidence of myocardial infarction (OR 0.75, 0.51-1.11) and increased the risk of major bleeding (OR 1.28, 0.88-1.87) compared with 12-month DAPT. The 1- to 3-month DAPT was more secure and effective than the other 3 DAPT strategies. Although East Asians have a higher risk of bleeding, more than 12 months of DAPT does not increase this incidence of major bleeding.

Efficacy and Safety of Proton Pump Inhibitors in Patients With Coronary Artery Diseases Receiving Oral Antiplatelet Agents and/or Anticoagulants: A Systematic Review and Meta-Analysis.

ABSTRACT: The purpose of this meta-analysis was to evaluate the efficacy and safety of proton pump inhibitors (PPIs) plus antithrombotic strategy in patients with coronary artery diseases compared with antithrombotic strategy alone. We searched PubMed, EMBASE, Cochrane Library, and Chinese Biomedical Medical Literature databases to retrieve randomized controlled trials investigating PPIs combined with antithrombotic strategy in coronary artery diseases. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety outcome was gastrointestinal events. Secondary outcomes included all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, significant bleeding from gastroduodenal lesions, and gastroduodenal ulcer. Overall, 43,943 patients were enrolled from 19 trials. The incidence of MACCE [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.15], all-cause death (RR 0.84; 95% CI 0.69-1.01), cardiovascular death (RR 0.88; 95% CI 0.69-1.12), myocardial infarction (RR 0.98; 95% CI 0.88-1.09), stent thrombosis (RR 1.01; 95% CI 0.76-1.34), and gastroduodenal ulcer (RR 0.40; 95% CI 0.13-1.29) did not increase significantly in patients receiving PPIs compared with patients without those. There were significant differences in the risk of gastrointestinal events (RR 0.34; 95% CI 0.21-0.54) and significant bleeding from gastroduodenal lesions (RR 0.09; 95% CI 0.03-0.28) between the 2 groups. In patients with coronary artery diseases, PPIs plus antithrombotic strategy could reduce the risk of gastrointestinal events and significant bleeding from gastroduodenal lesions but may not affect the incidence of MACCE, all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, and gastroduodenal ulcer (PROSPERO: CRD42021277899, date of registration October 10, 2021).

Efficacy and Safety of De-escalation of Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Meta-Analysis of Randomized Clinical Trials.

ABSTRACT: Considering that there is no definite conclusion on the efficacy and safety of switching from potent P2Y 12 inhibitors to clopidogrel, we conducted a systematic review and meta-analysis of patients with acute coronary syndromes undergoing percutaneous coronary intervention and compared the efficacy and safety of de-escalation or not of antiplatelet therapy. The relevant randomized controlled trials were included by searching several databases. Net adverse clinical events were identified as the composite end point, which was defined as a composite of cardiovascular death, myocardial infarction, revascularization, stroke, and bleeding at 12 months after acute coronary syndromes. The efficacy end points were cardiovascular death, myocardial infarction, revascularization, stroke, all-cause death, and stent thrombosis. Bleeding was designed as the safety end point. The risk ratio and 95% confidence intervals of end point events were calculated by the fixed-effects model. Six randomized controlled trials with 7627 patients met inclusion criteria. There were significant differences in the risk of net adverse clinical events (RR, 0.67, CI, 0.58-0.78, P < 0.00001) and bleeding end point (0.61, 0.52-0.71, P < 0.00001) between the 2 groups. However, there were no significant differences in the risk of all efficacy end points. In general, the strategy of de-escalation from prasugrel or ticagrelor to clopidogrel can reduce the incidence of net adverse clinical events and bleeding events in patients with ACS undergoing percutaneous coronary intervention.

Comparison of Ticagrelor With Clopidogrel in East Asian Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

ABSTRACT: The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33-1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15-2.12; P = 0.004), and dyspnea (RR 2.60; 1.68-4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19-0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64-1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79-7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60-0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65-1.23; P = 0.49), and stroke (RR 0.84; 0.47-1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).

Efficacy of intravascular imaging-guided drug-eluting stent implantation: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Traditional angiography only displays two-dimensional images of the coronary arteries during stent implantation. However, intravascular imaging can show the structure of the vascular wall, plaque characteristics. This article aims to evaluate the efficacy of intravascular imaging-guided drug-eluting stent (DES) implantation. METHOD: We conducted a systematic review and meta-analysis of randomized controlled trials of intravascular imaging-guided, including patients with DES implantation guided by intravascular ultrasound or optical coherence tomography and traditional angiography. The databases of PubMed, EMBASE, web of science, and Cochrane Library were searched. The primary outcome was target lesion revascularization (TLR). The secondary outcomes included the target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), cardiac death, all-cause death, and the major adverse cardiac events (MACE) during the 6-24 months follow-up. The fixed-effects model was used to calculate the relative risk (RR) and 95% confidence interval of the outcome event. Meanwhile, the trial sequence analysis was employed to evaluate the results. RESULT: This meta-analysis included fourteen randomized controlled trials with 7307 patients. Compared with angiography-guided, intravascular imaging-guided DES implantation can significantly reduce the risk of TLR (RR 0.63, 0.49-0.82, P = 0.0004), TVR (RR 0.66, 0.52-0.85, P = 0.001), cardiac death (RR 0.58; 0.38-0.89; P = 0.01), MACE (RR 0.67, 0.57-0.79; P < 0.00001) and ST (RR 0.43, 0.24-0.78; P = 0.005). While there was no significant difference regarding MI (RR 0.77, 0.57-1.05, P = 0.10) and all-cause death (RR 0.87, 0.58-1.30, P = 0.50). CONCLUSIONS: Compared with angiography, intravascular imaging-guided DES implantation is associated with better clinical outcomes in patients with coronary artery disease, especially complex lesions (Registered by PROSPERO, CRD 42021289205).

Safety and efficacy of anti-inflammatory therapy in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: The inflammation hypothesis of atherosclerosis has been put forward for more than 20 years. Although many animal experiments have suggested that anti-inflammatory therapy can inhibit the atherosclerotic process, the efficacy of anti-inflammatory therapy for patients with coronary artery disease (CAD) is still controversial. Therefore, this study aims to evaluate the safety and efficacy of anti-inflammatory drugs in patients with CAD. METHOD: We conducted this systematic review and meta-analysis of randomized controlled trials by searching PubMed, EMBASE, web of science, and Cochrane Library database. The primary outcome was a composite outcome of cardiovascular death, myocardial infarction (MI), or stroke. The secondary outcomes included individual MI, coronary revascularization, cardiovascular death, all-cause death, and stroke. The relative risk (RR) and 95% confidence intervals (CI) for outcome events were calculated by the fixed effects model, and trial sequential analysis was applied to assess the results. RESULT: A total of ten randomized controlled trials and 60,782 patients with CAD was included. Compared with patients receiving placebo, anti-inflammatory therapy significantly reduced the incidence of the primary outcome in patients with CAD (RR 0.93, 0.89-0.98, P = 0.007). In addition, the anti-inflammatory therapy can also reduce the risk of MI (RR 0.90, 0.84-0.96, P = 0.002) and coronary revascularization (RR 0.74, 0.66-0.84, P < 0.00001) remarkably. However, there was no significant difference in the incidence of cardiovascular death (RR 0.94, 0.86-1.02, P = 0.14), all-cause death (RR 1.00, 0.94-1.07, P = 0.98) and stroke (RR 0.96, 0.85-1.09, P = 0.51) between two groups. CONCLUSIONS: Anti-inflammatory therapy can reduce the incidence of the primary outcome in patients with CAD, especially the risk of MI and coronary revascularization. However, anti-inflammatory therapy increases the risk of infection. (Registered by PROSPERO, CRD 420212291032).

Aberrant functional connectivity in insular subregions in somatic depression: a resting-state fMRI study.

BACKGROUND: Somatic depression (SD) is different from non-somatic depression (NSD), and insular subregions have been associated with somatic symptoms. However, the pattern of damage in the insular subregions in SD remains unclear. The aim of this study was to use functional connectivity (FC) analyses to explore the bilateral ventral anterior insula (vAI), bilateral dorsal anterior insula (dAI), and bilateral posterior insula (PI) brain circuits in SD patients. METHODS: The study included 28 SD patients, 30 NSD patients, and 30 matched healthy control (HC) subjects. All participants underwent 3.0 T resting state functional magnetic resonance imaging. FC analyses were used to explore synchronization between insular subregions and the whole brain in the context of depression with somatic symptoms. Pearson correlation analyses were performed to assess relationships between FC values in brain regions showing significant differences and the total and factor scores on the 17-item Hamilton Rating Scale for Depression (HAMD17). RESULTS: Compared with the NSD group, the SD group showed significantly decreased FC between the left vAI and the right rectus gyrus, right fusiform gyrus, and right angular gyrus; between the right vAI and the right middle cingulate cortex, right precuneus, and right superior frontal gyrus; between the left dAI and the left fusiform gyrus; and between the right dAI and the left postcentral gyrus. Relative to the NSD group, the SD group exhibited increased FC between the left dAI and the left fusiform gyrus. There were no differences in FC between bilateral PI and any brain regions among the SD, NSD, and HC groups. Within the SD group, FC values between the left vAI and right rectus gyrus were positively correlated with cognitive impairment scores on the HAMD17; FC values between the right vAI and right superior frontal gyrus were positively related to the total scores and cognitive impairment scores on the HAMD17 (p < 0.05, uncorrected). CONCLUSIONS: Aberrant FC between the anterior insula and the frontal and limbic cortices may be one possible mechanism underlying SD.

NEFL promotes invasion and migration of esophageal squamous carcinoma cells via the EGFR/AKT/S6 pathway.

To explore the expression, the roles and the underlying mechanism of neurofilament light chain (NEFL) in esophageal squamous cell carcinoma (ESCC), we firstly analyzed the NEFL mRNA and protein expression in ESCC and paired normal tissues by using Gene Expression Omnibus (GEO) database, and real-time quantitative reverse transcription PCR (qRT-PCR). The results showed that NEFL mRNA level was significantly upregulated in ESCC tissues compared with that of normal tissues. Western blot analysis revealed that NEFL protein level was also significantly upregulated in ESCC tissues. CCK8 and transwell assays were performed to analyze the effect of NEFL overexpression on the malignant phenotypes of ESCC cells, and the results showed that NEFL knockdown significantly impaired the ESCC cell invasion and migration in vitro. Xenograft assay in nude mice indicated that NEFL silencing suppressed tumor growth in vivo. At the molecular level, NEFL knockdown significantly upregulated E-cadherin and downregulated N-cadherin expression, suggesting that NEFL overexpression might influence the epithelial-mesenchymal transition (EMT) process. Furthermore, we found that NEFL knockdown significantly reduced the mRNA and protein expression of epidermal growth factor receptor (EGFR) and the phosphorylation levels of protein kinase B (PKB; also known as AKT) and ribosomal protein S6 (S6). Ectopic expression of EGFR after NEFL knockdown significantly restored the phosphorylation levels of AKT and S6 as well as the invasion and migration of ESCC cells. These data indicate that NEFL overexpression might promote the EMT process of ESCC cells via the EGFR/AKT/S6 pathway, ultimately enhancing the invasion and migration of ESCC cells.

Pelvic Injury Discriminative Model Based on Data Mining Algorithm.

OBJECTIVES: To reduce the dimension of characteristic information extracted from pelvic CT images by using principal component analysis (PCA) and partial least squares (PLS) methods. To establish a support vector machine (SVM) classification and identification model to identify if there is pelvic injury by the reduced dimension data and evaluate the feasibility of its application. METHODS: Eighty percent of 146 normal and injured pelvic CT images were randomly selected as training set for model fitting, and the remaining 20% was used as testing set to verify the accuracy of the test, respectively. Through CT image input, preprocessing, feature extraction, feature information dimension reduction, feature selection, parameter selection, model establishment and model comparison, a discriminative model of pelvic injury was established. RESULTS: The PLS dimension reduction method was better than the PCA method and the SVM model was better than the naive Bayesian classifier (NBC) model. The accuracy of the modeling set, leave-one-out cross validation and testing set of the SVM classification model based on 12 PLS factors was 100%, 100% and 93.33%, respectively. CONCLUSIONS: In the evaluation of pelvic injury, the pelvic injury data mining model based on CT images reaches high accuracy, which lays a foundation for automatic and rapid identification of pelvic injuries.

Transcriptome sequencing and metabolome analysis of food habits domestication from live prey fish to artificial diets in mandarin fish (Siniperca chuatsi).

BACKGROUND: As economical traits, food habits domestication can reduce production cost in aquaculture. However, the molecular mechanism underlying food habits domestication has remained elusive. Mandarin fish (Siniperca chuatsi) only feed on live prey fish and refuse artificial diets. In the present study, we domesticated mandarin fish to feed on artificial diets. The two groups were obtained, the fish did not eat artificial diets or ate artificial diets during all of the three domestication processes, named Group W or X, respectively. RESULTS: Using transcriptome and metabolome analysis, we investigated the differentially expressed genes and metabolites between the two groups, and found three common pathways related to food habit domestication, including retinol metabolism, glycerolipid metabolism, and biosynthesis of unsaturated fatty acids pathways. Furthermore, the western blotting and bisulfite sequencing PCR analysis were performed. The gene expression of TFIIF and histone methyltransferase ezh1 were significantly increased and decreased in the fish of Group X, respectively. The total DNA methylation levels of TFIIF gene and tri-methylation of histone H3 at lysine 27 (H3K27me3) were significantly higher and lower in the fish of Group X, respectively. CONCLUSION: It was speculated that mandarin fish which could feed on artificial diets, might be attributed to the lower expression of ezh1, resulting in the decreased level of H3K27me3 and increased level of DNA methylation of TFIIF gene. The high expression of TFIIF gene might up-regulate the expression of genes in retinol metabolism, glycerolipid metabolism and glycerophosphoric metabolism pathways. Our study indicated the relationship between the methylation of DNA and histone and food habits domestication, which might be a novel molecular mechanism of food habits domestication in animals.

Efficacy and Safety of Short-Term Dual Antiplatelet Therapy in East Asians: A Systematic Review and a Meta-Analysis of Randomized Clinical Trials.

ABSTRACT: The optimal duration of dual antiplatelet therapy (DAPT) for patients implanted with new-generation drug-eluting stents in East Asians is currently still controversial. The purpose of this meta-analysis was to investigate the efficacy and safety of short-term DAPT in patients with those. In this study, randomized controlled trials from PubMed, EMBASE, and Cochrane Library were searched to compare the efficacy and safety of short-term DAPT (6 months or less) with long-term DAPT (12 months or more) in patients implanted with new-generation drug-eluting stents in East Asian from inception to September 2020. The primary efficacy outcome was all-cause death, the primary safety outcome was major bleeding, and the secondary outcomes included cardiovascular death, myocardial infarction, definite or possible stent thrombosis, and stroke. A total of 6 randomized controlled trials with 15,688 patients met inclusion criteria; there were no significant differences in the incidence of all-cause death [risk ratio (RR), 1.03; 0.76-1.39; P = 0.856)], cardiovascular death (RR, 0.83; 0.55-1.24; P = 0.361), myocardial infarction (RR, 0.97; 0.72-1.31; P = 0.853), definite or possible stent thrombosis (RR, 1.52; 0.83-2.78; P = 0.170), and stroke (RR, 0.90; 0.61-1.31; P = 0.574) between short-term and long-term DAPTs. However, there was a significant difference in the risk of major bleeding (RR, 0.64; 0.49-0.85; P = 0.002) between the 2 groups. Compared with long-term DAPT, the short-term DAPT can reduce the risk of major bleeding without increasing the risk of death or ischemia for East Asians (Registered by PROSPERO, CRD42020213266).

Remarkable inhibition effects of afatinib alone or combining with paclitaxel in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Chemotherapy drugs do not work well in esophageal squamous cell carcinoma (ESCC), and none of the targeted drugs have been applied in clinic. This study aims to identify effective targeted drugs and related biomarkers for the treatment of ESCC. METHODS: The effect of 40 Food and Drug Administration-approved small-molecule inhibitors was first tested in five ESCC cell lines. CCK8 assays and xenografts derived from ESCC cell lines were performed to evaluate the anti-ESCC effects of inhibitors or chemotherapeutic agents in vitro and in vivo, respectively. Immunohistochemistry was utilized to analyze the p-EGFR expression in tissues. Western blot combining with gray analysis was conducted to detect the expression of interest protein. Flow cytometry and immunofluorescence assay were used to analyze apoptosis, cell cycle, and mitotic changes after drug treatment. RESULTS: Afatinib showed remarkable effects on inhibiting ESCC cells with higher expression of p-EGFR. Results from combinatorial screening in ESCC cells expressing lower phosphorylation level of EGFR showed that paclitaxel and afatinib presented a significant synergistic inhibitory effect (P < 0.001). Molecular analysis revealed that paclitaxel sensitized afatinib by activating EGFR, and afatinib in combination with paclitaxel effectively blocked MAPK pathway and induced G2/M cell arrest and apoptosis that is an indicator of mitotic catastrophe. CONCLUSIONS: Our data demonstrate that afatinib is an effective drug for patients with ESCC expressing higher phosphorylation level of EGFR. And for patients with lower p-EGFR in tumors, paclitaxel in combination with afatinib might be a promising therapeutic strategy in ESCC.