Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids.

Patient-derived tumor organoids (PDOs) have emerged as a reliable in vitro model for drug discovery. However, RNA sequencing-based analysis of PDOs treated with drugs has not been realized in a high-throughput format due to the limited quantity of organoids. Here, we translated a newly developed pooled RNA-seq methodology onto a superhydrophobic microwell array chip to realize an assay of genome-wide RNA output unified with phenotypic data (Grouped-seq). Over 10-fold reduction of sample and reagent consumption together with a new ligation-based barcode synthesis method lowers the cost to ∼$2 per RNA-seq sample. Patient-derived colorectal cancer (CRC) organoids with a number of 10 organoids per microwell were treated with four anti-CRC drugs across eight doses and analyzed by the Grouped-seq. Using a phenotype-assisted pathway enrichment analysis (PAPEA) method, the mechanism of actions of the drugs were correctly derived, illustrating the great potential of Grouped-seq for pharmacological screening with tumor organoids.

Three Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer: Similarities and Differences.

Osimertinib, almonertinib and furmonertinib are third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) approved for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. This article reviews research advances in pharmacokinetics, pharmacodynamics, treatment-related adverse events, and other aspects related to the three EGFR-TKIs were systematically reviewed in order to provide references for clinical drug selection. There are differences in dosing schedule and incidence of adverse events among three drugs. Optimization of third-generation EGFR-TKIs options for individuals may produce the maximal benefits to NSCLC patients with EGFR T790M mutation.

Nocturnal dexmedetomidine alleviates post-intensive care syndrome following cardiac surgery: a prospective randomized controlled clinical trial.

BACKGROUND: Dexmedetomidine is a sedative agent that may have the potential to reduce the risk of post-intensive care syndrome (PICS). This study aimed to establish whether prophylactic nocturnal dexmedetomidine safely reduces postoperative PICS incidence and to develop an easy-to-use model for predicting the risk of PICS following cardiac surgery. METHODS: This was a single-center, double-blind, randomized, prospective, placebo-controlled trial. Patients undergoing cardiac surgery were randomly assigned (1:1) to dexmedetomidine or placebo (normal saline) groups between January 2019 and July 2020. Dexmedetomidine or a similar volume of saline was administered, with an infusion rate up to 1.2 µg/kg/h until the RASS remained between - 1 and 0. The primary study endpoint was PICS incidence at 6 months follow-up, as defined by cognitive, physical, or psychological impairments. RESULTS: We assessed 703 individuals for eligibility, of whom 508 were enrolled. Of these, there were 251 in the dexmedetomidine group and 257 in the placebo group that received the trial agent, forming a modified intention-to-treat population. PICS incidence at 6-month follow-up was significantly decreased in the dexmedetomidine group (54/251, 21.5%) relative to the placebo group (80/257, 31.1%) (odds ratio [OR] 0.793, 95% CI 0.665-0.945; p = 0.014). Psychological impairment was significantly reduced in the dexmedetomidine group relative to the placebo group (18.7% vs. 26.8%, OR 0.806, CI 0.672-0.967, p = 0.029). However, dexmedetomidine treatment was associated with a higher rate of hypotension. A nomogram revealed that age, education, a medical history of diabetes and smoking, dexmedetomidine treatment, postoperative atrial fibrillation, and sequential organ failure assessment scores at 8 h post-surgery were independent predictors of PICS. CONCLUSIONS: Prophylactic nocturnal dexmedetomidine administration significantly reduced PICS incidence by a marked reduction in psychological impairment within a 6-month follow-up period. TRIAL REGISTRATION: ChiCTR, ChiCTR1800014314 . Registered 5 January 2018, http://www.chictr.org.cn/index.aspx.

miR-302a-3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia-reoxygenation injury.

NEW FINDINGS: What is the central question of this study? How does miR-302a-3p play a role in hypoxia-reoxygenation-induced pyroptosis of renal tubular epithelial cells? What is the main finding and its importance? Hypoxia-reoxygenation treatment upregulated the expression of miR-302a-3p in HK-2 cells, and then inhibited the transcription of FMRP translational regulator 1 (FMR1), so as to promote the activation of the NLRP3 inflammasome and aggravate the pyroptosis of HK-2 cells. miR-302a-3p was used as a molecular target in this study, which provides a new theoretical basis for the treatment of renal failure. ABSTRACT: Hypoxia-reoxygenation (H/R) induction can affect miRNA expression and then control NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis. This study investigated the mechanism of miR-302a-3p in H/R-induced renal tubular epithelial cell (RTEC) pyroptosis. Human HK-2 RTECs were induced by H/R. Lactate dehydrogenase content, cell activity and pyroptosis, and levels of NLRP3, GSDMD-N, caspase-1, interleukin (IL)-1ß, IL-18, superoxide dismutase, and malondialdehyde were detected to verify the effect of H/R on HK-2 cells. The NLRP3 inflammasome action was evaluated after H/R-induced HK-2 cells were treated with BAY11-7082, an inflammasome inhibitor. After inhibiting miR-302a-3p expression, the changes of pyroptosis were observed. The binding relation between miR-302a-3p and FMRP translational regulator 1 (FMR1) was verified. A function-rescue experiment verified the role of FMR1 in the regulation of pyroptosis. H/R-induced HK-2 cells showed significant pyroptosis injury, and the NLRP3 inflammasome was activated. After inhibiting the NLRP3 inflammasome, H/R-induced apoptosis was inhibited. After H/R treatment, miR-302a-3p in HK-2 cells was increased, and miR-302a-3p downregulation limited H/R-induced NLRP3 inflammasome-mediated pyroptosis. FMR1 is the target of miR-302a-3p. Inhibition of FMR1 alleviated the inhibition of H/R-induced HK-2 cell pyroptosis by miR-302a-3p inhibitor. Collectively, inhibiting miR-302a-3p can weaken its targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 inflammasomes and reducing caspase-1-dependent pyroptosis in HK-2 cells.

Establishment and validation of a prediction model for the probability of malignancy in solid solitary pulmonary nodules in northwest China.

BACKGROUND AND OBJECTIVES: To construct a prediction model of solitary pulmonary nodules (SPNs), to predict the possibility of malignant SPNs in patients aged 15-85 years in northwest China for clinical diagnostic and therapeutic decision-making. METHODS: The features of SPNs were assessed by multivariate logistic regression, followed by visualization using a nomogram. Hosmer lemeshow was applied to evaluate the fitting degree of the model. The area under the receiver operating characteristic (ROC) curve was identified to determine the discriminative ability of the model. RESULTS: Lobulation, spiculation, pleural-tag, carcinoembryonic antigen, neuron-specific enolase, and total serum protein were independent predictors of malignant pulmonary nodules (p < .05). Lobulation (100 points) scored the highest in the nomogram, and the Hosmer-Lemeshow goodness-of-fit statistic was 0.805 (p > .05). The area under curve (AUC) of the modeling and validation groups using logistic regression were 0.859 (95% CI, 0.805-0.903) and 0.823 (95% CI, 0.738-0.890), respectively. Moreover, the AUC of our model was higher than that of the Mayo model, VA model, and Peking University (AUC 0.823 vs. 0.655 vs. 0.603 vs. 0.521). CONCLUSION: Our prediction model is more suitable for predicting the possibility of malignant SPNs in northwest China, and can be calculated using a nomogram to determine further treatments.

Anxiety Administrated by Dexmedetomidine to Prevent New-Onset of Postoperative Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Graft.

This study aims to evaluate the effect of dexmedetomidine (DEX) sedation for relieving anxiety and the incidence of atrial fibrillation (AF) after off-pump coronary artery bypass graft (OPCABG).This randomized, double-blind, controlled trial was conducted on 196 patients who underwent OPCABG in Shandong Provincial Hospital from July 2017 to June 2018. The patients were randomly assigned to two groups, intervention of DEX group and Propofol (PROP) group. Episodes of postoperative AF (POAF) were identified within 5 days after OPCABG. Perioperative anxiety status was assessed using Zung's Self-Rating Anxiety Scale (SAS). The baseline demographic and surgical characteristics of the population and other outcome variables were evaluated.We analyzed 62 patients in the DEX group and 61 patients in the PROP group. There was no significant difference in SAS anxiety scores between two groups before surgery (P = 0.104), while SAS had significantly after surgery (P = 0.018). The incidence of POAF in the DEX group was lower than that of the PROP group (16.1% versus 32.8%, P = 0.037), and a total of 30 patients (30/123, 24.4%) manifested POAF after OPCABG. Some univariable predictors of POAF were detected. The conceptual model of mediator analyses showed DEX was not only directly related to POAF but was also indirectly related through the independent effect of anxiety level.The findings indicated that patients receiving DEX were more likely to have less incidence of POAF, also uniquely showed DEX administration and POAF processes as a function of anxiety status.

lncRNA HCG11 regulates cell progression by targeting miR-543 and regulating AKT/mTOR pathway in prostate cancer.

Prostate cancer (PCa) is a common cancer worldwide, which mostly occurs in males over the age of 50. Accumulating evidence have determined that long non-coding RNA/microRNA (lncRNA/miRNA) axis plays a critical role in cell progression of cancers, including PCa. However, the pathogenesis of PCa has not been fully indicated. In this study, quantitative real-time polymerase chain reaction was used to detect the expression of HCG11 and miR-543. Western blot was applied to measure the protein expression of proliferating cell nuclear antigen, cleavage-caspase 3 (cle-caspase 3), N-cadherin, E-cadherin, GAPDH, P-AKT, AKT, p-mTOR, and mTOR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell invasion, and transwell migration assay were used to detect cell proliferation, invasion, and migration, respectively. The function and mechanism of lncRNA HCG11 were confirmed in PCa cell and xenograft mice models. Luciferase assay indicated that miR-543 was a target miRNA of HCG11. Further investigation revealed that overexpression of HCG11 inhibited cell proliferation, invasion, and migration, whereas induced cell apoptosis by regulating miR-543 expression in vitro and in vivo. More than that, lncRNA HCG11 inhibited phosphoinositide-3 kinase/protein kinaseB (PI3K/AKT) signaling pathway to suppress PCa progression. Our data showed the overexpression of HGC11-inhibited PI3K/AKT signaling pathway by downregulating miR-543 expression, resulting in the suppression of cell growth in PCa. This finding proved a new regulatory network in PCa and provided a novel therapeutic target of PCa.

Understanding the textural enhancement of low-salt myofibrillar protein gels filled with pea protein pre-emulsions through interfacial behavior: Effects of structural modification and oil phase polarity.

This study investigated the effects of pea protein pre-emulsions containing triglyceride- or diglyceride-oil on the emulsifying and gelling properties of low-salt myofibrillar protein (MP). Pea protein isolates treated with pH12-shifting (PPIpH) or ultrasonication (PPIU) demonstrated superior initial interfacial adsorption and higher final interfacial pressure than native pea protein. Within MP/PPI blends, an increased ratio of MP led to a decrease in interfacial pressure, while simultaneously enhancing film elasticity at both polar and non-polar interfaces. Polar diglyceride promoted protein adsorption and fostered interfacial interactions between modified pea proteins and MP, enhancing the cross-linking of transglutaminase (TG) in the composite emulsion gels. Combining diglyceride-type PPIU and PPIpH emulsions with TG increased gel strength to 0.58 N and 0.63 N, respectively, from an initial 0.33 N, yielding a denser protein network with uniformly dispersed oil droplets. Therefore, the utilization of diglyceride and modified PPI can serve as structural enhancers in comminuted meat products.

Research of nuclide identification method based on background comparison method.

Radioactive material inspection in public is important to nuclear safety, and it is also the key security for holding large-scale events, while fast and efficient means of detecting radioactive materials are an important technical guarantee for nuclear safety. In this paper, energy and time distribution characteristics information of the natural background and target nuclide gamma particles are used to improve the sequential background comparison method. By using those energy and time distribution characteristics information, with the half-life and characteristic gamma-ray energy and branching ratio information of the nuclide, the response time and the identification accuracy of extremely low radioactive nuclides detected under natural-radiation background can be improved. Based on the theoretical research, the particle event acquisition device with the LaBr3(Ce) detector was used to carry out the experimental verification, and the results show that, this method can identify 137Cs (characteristic energy of 0.662 MeV，8700 Bq，the position relative to the detector is 30 cm) in 6.2 s, and identify 60Co (characteristic energy of 1.173 MeV and 1.332 MeV, 4500 Bq, the position relative to the detector is 15 cm) in 5.9 s. Experiments prove that the improved background comparison-based sequential Bayesian method can identify low radioactivity radionuclides under natural-radiation background rapidly.

Cell reprogramming in a predictable manner on the superhydrophobic microwell array chip.

Reprogramming of somatic cells into the pluripotent state is stochastic and inefficient using the conventional culture plates. Novel micro-culture systems employing precisely controlled biophysical cues can improve the reprogramming efficiencies dramatically. Here we perform iPSC induction on our previously developed superhydrophobic microwell array chip (SMAR-chip) where cells undergo distinctive morphology change, switching from 2D monolayers to 3D clumps, and develop into bona fide colonies in more than 90% of the microwells. The PDMS substrate, together with the microwell structure and the superhydrophobic layer constitute a well-controlled microenvironment favorable for the morphogenesis and pluripotency induction. Investigation of the molecular roadmap demonstrates that the SMAR-chip promotes the transition from the initiation phase to the maturation phase and overcomes the roadblocks for reprogramming. In addition, the SMAR-chip also promotes the reprogramming of human cells, opening our method for translational applications. In summary, our study provides a novel platform for efficient cell reprogramming and emphasizes the advantages of employing the insoluble microenvironmental cues for the precise control of cell fate conversion.

Coexistence of ferromagnetism and superconductivity in YBCO nanoparticles.

Nanoparticles of superconducting YBa(2)Cu(3)O(7-δ) were synthesized via a citrate pyrolysis technique. Room temperature ferromagnetism was revealed in the samples by a vibrating sample magnetometer. Electron spin resonance spectra at selected temperatures indicated that there is a transition from the normal to the superconducting state at temperatures below 100 K. The M-T curves with various applied magnetic fields showed that the superconducting transition temperatures are 92 K and 55 K for the air-annealed and the post-annealed samples, respectively. Compared to the air-annealed sample, the saturation magnetization of the sample by reheating the air-annealed one in argon atmosphere is enhanced but its superconductivity is weakened, which implies that the ferromagnetism maybe originates from the surface oxygen defects. By superconducting quantum interference device measurements, we further confirmed the ferromagnetic behavior at high temperatures and interesting upturns in field cooling magnetization curves within the superconducting region are found. We attributed the upturn phenomena to the coexistence of ferromagnetism and superconductivity at low temperatures. Room temperature ferromagnetism of superconducting YBa(2)Cu(3)O(7-δ) nanoparticles has been observed in some previous related studies, but the issue of the coexistence of ferromagnetism and superconductivity within the superconducting region is still unclear. In the present work, it will be addressed in detail. The cooperation phenomena found in the spin-singlet superconductors will help us to understand the nature of superconductivity and ferromagnetism in more depth.

Identification of Prostate Cancer Risk Genetics Biomarkers Based on Intergraded Bioinformatics Analysis.

Background: Prostate cancer (PCa) is one of the most popular cancer types in men. Nevertheless, the pathogenic mechanisms of PCa are poorly understood. Hence, we aimed to identify the potential genetic biomarker of PCa in the present study. Methods: High-throughput data set GSE46602 was obtained from the comprehensive gene expression database (GEO) for screening differentially expressed genes (DEGs). The common DEGs were further screened out using The Cancer Genome Atlas (TCGA) dataset. Functional enrichment analysis includes Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to study related mechanisms. The Cox and Lasso regression analyses were carried out to compress the target genes and construct the high-risk and low-risk gene model. Survival analyses were performed based on the gene risk signature model. The CIBERSORT algorithm was performed to clarify the correlation of the high- and low-risk gene model in risk and infiltration of immune cells in PCa. Results: A total of 385 common DEGs were obtained. The results of functional enrichment analysis show that common DEGs play an important role in PCa. A three-gene signature model (KCNK3, AK5, and ARHGEF38) was established, and the model was significantly associated with cancer-related pathways, overall survival (OS), and tumor microenvironment (TME)-related immune cells in PCa. Conclusion: This new risk model may contribute to further investigation in the immune-related pathogenesis in progression of PCa.

A case report of cerebral venous sinus thrombosis presenting with rapidly progressive dementia.

Background: Cerebral venous sinus thrombosis (CVST) is a rare but serious and treatable cause of neurologic symptoms. Due to the variable clinical presentation, CVST was often misdiagnosed. According to published case reports, common clinical manifestations of CVST include headache, focal neurological deficit, epilepsy, papilledema, etc. It is rare, nevertheless, to mention cases of rapidly progressive dementia (RPD). Case presentation: We reported a case of a 62-year-old retired male accountant, a Han Chinese from eastern China, who initially presented with slow response and memory decline. Until 2 months later, his memory declined and slow response deteriorated significantly, and he could not even complete simple tasks like brushing his teeth, washing his face, washing his feet, and dressing himself, and sometimes developed fecal incontinence. His neuropsychological test demonstrated severe cognitive decline. The cerebrospinal fluid (CSF) studies revealed markedly high opening pressure (260 mm of water), and coagulation tests indicated a mild elevation of D-Dimer of 1.19 mg/L. The magnetic resonance venography (MRV) showed thrombosis of the left transverse sinus, sigmoid sinus, and jugular venous bulb and was diagnosed as CVST. He switched from subcutaneous low molecular weight heparin (LMWH) and transitioned to oral anticoagulants at the time of discharge. The repeated CSF studies revealed normal opening pressure. After 5 days of anticoagulant treatment, his symptoms considerably improved, and a 1-month follow-up revealed that he had fully healed with no signs of recurrence. Conclusion: This case demonstrated the clinical heterogeneity of CVST, which should be taken into account for differential diagnosis of RPD. This case study also offered fresh data for the categorization of the clinical traits and the diagnosis of CVST.

Elevated Red Blood Cell Distribution Width Levels at Admission Predicts Depression After Acute Ischemic Stroke: A 3-Month Follow-Up Study.

Purpose: Red blood cell distribution width (RDW) is closely related to inflammatory-related disease markers. The present study aimed to investigate the association between the red blood cell distribution width (RDW) and post-stroke depression (PSD). Patients and Methods: A total of 414 patients with acute ischemic stroke (AIS) admitted to our hospital from June 2018 to July 2021 were consecutively enrolled and received 3 months' follow-up. According to the 17-item Hamilton Depression Scale (HAMD) assessment, they were divided into PSD group and non-PSD group. Diagnosis of PSD was made in accordance with DSM-IV. RDW was recorded within 24 hours of admission. Results: Among the included 414 patients, 95 (22.95%) patients were diagnosed as having PSD at 3 months after stroke. The results showed significantly higher level of RDW in patients with depression (13.69 (IQR13.24-13.88) vs. 13.56 (IQR 12.67-13.77), P<0.001) at admission than patients without depression. After adjustment for potential confounding factors, the odds ratio of PSD was 5.707 (95% CI, 2.717-11.989) for the highest tertile of RDW compared with the lowest tertile. Moreover, based on the receiver operating characteristic (ROC) curve, the optimal cutoff of RDW levels as an indicator for the prediction of PSD was projected as 13.01, which yielded a sensitivity of 83% and a specificity of 41.0%, with an area under the curve (AUC) of 0.643 (95% CI, 0.585-0.701; P = 0.012). Conclusion: Higher RDW levels at admission were found to be correlated with PSD 3 months after stroke.

Circular RNA circSDHC (hsa_circ_0015004) regulates tumor growth and angiogenesis via regulating centrosomal protein 55 expression in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the main aggressive subtype of kidney cancer. Circular RNAs have been shown to exert critical roles in RCC. However, little is known about the regulatory mechanism of hsa_circ_0015004 (circSDHC) in RCC. METHODS: 35 patients with RCC were recruited in the research. Expression changes of circSDHC were determined by real-time quantitative polymerase chain reaction (RT-qPCR). The effects of circSDHC inhibition on cell proliferation, apoptosis, angiogenesis, migration, and invasion were analyzed. The regulation mechanism of circSDHC was surveyed by bioinformatics analysis. The effect of circSDHC on tumorigenesis was validated by xenograft assay. RESULTS: We observed an observable elevation in circSDHC expression in RCC tissues and cell lines. Functionally, circSDHC silencing decreased xenograft tumor growth and induced RCC cell apoptosis, repressed RCC cell proliferation, angiogenesis, migration, and invasion in vitro. Mechanically, circSDHC modulated centrosomal protein 55 (CEP55) expression by functioning as a miR-130a-3p sponge. Also, miR-130a-3p silencing offset circSDHC knockdown-mediated impacts on malignant phenotypes and angiogenesis of RCC cells. Furthermore, exogenetic expression of CEP55 counteracted miR-130a-3p overexpression-mediated effects on malignant phenotypes and angiogenesis of RCC cells. CONCLUSION: Silencing of circSDHC restrained cell malignant phenotypes and angiogenesis via reducing CEP55 expression by releasing miR-130a-3p in RCC, providing a new mechanism for understanding the progression of RCC.

Predicting the risk of nodular thyroid disease in coal miners based on different machine learning models.

Background: Nodular thyroid disease is by far the most common thyroid disease and is closely associated with the development of thyroid cancer. Coal miners with chronic coal dust exposure are at higher risk of developing nodular thyroid disease. There are few studies that use machine learning models to predict the occurrence of nodular thyroid disease in coal miners. The aim of this study was to predict the high risk of nodular thyroid disease in coal miners based on five different Machine learning (ML) models. Methods: This is a retrospective clinical study in which 1,708 coal miners who were examined at the Huaihe Energy Occupational Disease Control Hospital in Anhui Province in April 2021 were selected and their clinical physical examination data, including general information, laboratory tests and imaging findings, were collected. A synthetic minority oversampling technique (SMOTE) was used for sample balancing, and the data set was randomly split into a training and Test dataset in a ratio of 8:2. Lasso regression and correlation heat map were used to screen the predictors of the models, and five ML models, including Extreme Gradient Augmentation (XGBoost), Logistic Classification (LR), Gaussian Parsimonious Bayesian Classification (GNB), Neural Network Classification (MLP), and Complementary Parsimonious Bayesian Classification (CNB) for their predictive efficacy, and the model with the highest AUC was selected as the optimal model for predicting the occurrence of nodular thyroid disease in coal miners. Result: Lasso regression analysis showed Age, H-DLC, HCT, MCH, PLT, and GGT as predictor variables for the ML models; in addition, heat maps showed no significant correlation between the six variables. In the prediction of nodular thyroid disease, the AUC results of the five ML models, XGBoost (0.892), LR (0.577), GNB (0.603), MLP (0.601), and CNB (0.543), with the XGBoost model having the largest AUC, the model can be applied in clinical practice. Conclusion: In this research, all five ML models were found to predict the risk of nodular thyroid disease in coal miners, with the XGBoost model having the best overall predictive performance. The model can assist clinicians in quickly and accurately predicting the occurrence of nodular thyroid disease in coal miners, and in adopting individualized clinical prevention and treatment strategies.

Comparison of Ultrasound-Guided Core Needle Biopsy Under the Assistance of Hydrodissection With Fine Needle Aspiration in the Diagnosis of High-Risk Cervical Lymph Nodes: A Randomized Controlled Trial.

A randomized comparison of ultrasound (US)-guided core needle biopsy (CNB) under the assistance of hydrodissection with fine needle aspiration (FNA) was performed to evaluate the feasibility, safety and effectiveness for the diagnosis of high-risk cervical lymph nodes. Patients from December 2018 to May 2020 were randomly assigned to the CNB group and the FNA group at a ratio of 1:1. This study protocol was approved by the Ethics Committee of our hospital and registered in the Chinese Clinical Trial Registry (ChiCTR1800019370). The feasibility of CNB for high-risk cervical lymph nodes was evaluated by observing and recording the separation success rate (SSR) and technical success rate (TSR) of the CNB group. Safety was evaluated by comparing the incidence of major complications in the two groups. The diagnostic efficacy was evaluated by comparing the diagnostic accuracy, sensitivity, and specificity of the two groups. A total of 84 patients (84 lymph nodes) were randomized into the CNB (n = 42) and FNA (n = 42) groups. All patients in the CNB group achieved successful hydrodissection and biopsy. The SSR and TSR were both 100% in the CNB group. There were no major complications during or after the process in the two groups. Compared with the FNA group, the CNB group was significantly superior in terms of diagnostic accuracy and sensitivity (100% vs. 81.0%, P = 0.009; 100% vs. 79.2%, P = 0.035, respectively). The specificity of the two groups was 100%, and there was no significant difference. Compared with FNA, CNB under the assistance of hydrodissection is a feasible and safe method but is more effective for the diagnosis of high-risk cervical lymph nodes. CLINICAL TRIAL REGISTRATION: http://www.medresman.org, ChiCTR1800019370.

CircSMARCA5 Facilitates the Progression of Prostate Cancer Through miR-432/PDCD10 Axis.

Background: Circular RNAs (circRNAs) have been reported to be implicated in the pathogenesis of prostate cancer (PCa). Herein, the authors explore the role and molecular mechanism of circRNA SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (circSMARCA5) in PCa. Materials and Methods: The levels of circSMARCA5, SMARCA5, miR-432, and programmed cell death 10 (PDCD10) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure and stability of circSMARCA5 were validated by qRT-PCR using Oligo dT primer, transcriptional inhibitor actinomycin D, or RNase R treatment, respectively. Cell proliferation, migration, invasion, epithelial/mesenchymal transition (EMT), and glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell migration and invasion assays, Western blot assay, and Glucose or Lactate Detection Kit, respectively. The target relationship between miR-432 and circSMARCA5 or PDCD10 was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Western blot was performed to detect the protein expression of PDCD10 in PCa cells. Results: CircSMARCA5 was aberrantly upregulated, and was a circular and stable RNA in PCa cells. CircSMARCA5 accelerated the proliferation, metastasis, and glycolysis of PCa cells. MiR-432 was a direct target of circSMARCA5, and circSMARCA5 accelerated the development of PCa through miR-432 in PCa cells. PDCD10 was a direct target of miR-432, and PDCD10 addition reversed the inhibitory effects of miR-432 accumulation on the proliferation, metastasis, and glycolysis of PCa cells. CircSMARCA5 upregulated the expression of PDCD10 through sponging miR-432 in PCa cells. Conclusion: CircSMARCA5 deteriorated PCa through the miR-432/PDCD10 axis. CircSMARCA5/miR-432/PDCD10 axis might be an underlying therapeutic target for PCa treatment.

Effect of freeze-thaw cycles on the quality of quick-frozen pork patty with different fat content by consumer assessment and instrument-based detection.

The change in quality of quick-frozen patties containing different amounts of added fat (0%, 5%, 10%, 15%, and 20%) under different freeze-thaw (F-T) cycles (a F-T cycle was performed by freezing at -18 °C and thawing at 4 °C) was evaluated. The results showed that the a*-values of samples were significantly decreased, while L*-values, b*-values, thawing loss, and cooking loss were notably increased after 3 F-T cycles. Low-field nuclear magnetic resonance (LF-NMR) results showed that the water mobility of patties was enhanced. Textural properties (hardness, springiness, cohesiveness, and chewiness) of patties were significantly decreased after 5 F-T cycles (P < 0.05). Lipid and protein oxidation were aggravated with increasing fat content and number of F-T cycles, as confirmed by the increase in lipid peroxides, TBARS, and carbonyl content. Therefore, the results from instrument-based detection and consumer scores indicated that repeated F-T cycles accelerated the quality deterioration of quick-frozen pork patties, and rendered them unacceptable after 3 F-T cycles.

Exploration of the hepatoprotective effect and mechanism of magnesium isoglycyrrhizinate in mice with arsenic trioxide­induced acute liver injury.

Arsenic trioxide (ATO)­induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti­oxidant, anti­inflammatory and anti­apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO­induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high­ and low­dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro­inflammatory cytokines, cell apoptosis and changes in Kelch­like ECH­associated protein 1/nuclear factor erythroid 2­related factor 2 (Keap1­Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro­inflammatory cytokines, including IL­1ß, IL­6 and TNF­α. Western blotting showed a decrease in Bax and caspase­3. There was decreased cleaved caspase­3 expression and increased Bcl­2 expression. MgIG notably activated ATO­mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO­induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO­induced liver injury.