Objective To assess the accuracy of pN staging prediction in papillary thyroid carcinoma (PTC) using ultrasound radiomics and deep neural networks (DNN). Methods A retrospective analysis was conducted on 375 patients with pathologically confirmed PTC, comprising 261 cases in the training set and 114 in the test set. Staging was categorized as pN0 (no cervical lymph node metastasis), pN1a (central neck lymph node metastasis), and pN1b (lateral neck lymph node metastasis). An ultrasound physician manually segmented the regions of interest (ROIs) for PTC, extracting 1899 radiomic features. Dimensionality reduction was performed using the least absolute shrinkage and selection operator (LASSO) regression. A DNN model for predicting PTC pN staging was developed using the H2O deep learning platform, trained on the training set, and validated on the test set to assess the accuracy of the optimal model. Results A total of 153 patients were in the pN0 stage, 131 patients in the pN1a stage, and 91 patients in the pN1b stage. LASSO regression selected 15 radiomic features for each PTC. The optimal DNN model, constructed using these 15 features, achieved accuracies of 85.82% on the training set and 81.57% on the test set. Conclusion Ultrasound radiomics of PTC demonstrates high accuracy in predicting pN staging and shows potential for automating N staging in patients.

Objective To compare the cost and utility of aflibercept and ranibizumab in the treatment of diabetic macular edema(DME),in order to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods The Markov model was established by extracting the clinical medication patterns,the survival status of the two treatment regimens within 10 years were simulated,the cost and health utilities were calculated respectively,and the incremental cost-utility ratio(ICUR)was obtained.Compared with the 2022 per capita gross domestic product(GDP)of China,which was 1 time,as the willingness to pay(WTP),the cost-utility advantage scheme was selected.Results During the simulation period,the ICUR of aflibercept compared with ranibizumab was 61 024.22 yuan/quality-adjusted life year(QALY),which was lower than that of WTP,which had obvious economic benefits.Univariate sensitivity analysis showed that the metastasis probability of visual acuity improvement with aflibercept and the number of ranibizumab injections per year were important influencing factors for ICUR.Probabilistic sensitivity analysis showed that when WTP was 1 time of the GDP,aflibercept had a significant cost-utility advantage,the economic probability was 63.7%,and the results were relatively stable.Conclusion For the treatment of DME,aflibercept has a cost-utility advantage over ranibizumab.

AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.

Objective:To investigate the effect of rumination on learning burnout of nursing undergraduate students and the mediating role of psychological capital between rumination and learning burnout of nursing undergraduate students.Methods:A total of 296 undergraduate nursing students from three medical colleges were assessed by using ruminative responses scale, learning burnout questionnaire and psychological capital scale. SPSS 20.0 was used for t-test. Pearson correlation was to analyze the relationship among psychological capital, learning burnout and ruminative thinking. AMOS 20.0 was used to construct and analyze the mediating model of psychological capital and its mediating effect was tested by Bootstrap method. Results:The average score of rumination of nursing undergraduate students was 46.60±11.40, learning burnout score was 56.18±11.25, and psychological capital scale score was 99.93±15.27. There was a significant difference among the rumination, psychological capital, and learning burnout scores in whether there was curriculum failure ( P < 0.05). The total score of rumination was positively related to the total score of learning burnout ( r = 0.39, P < 0.01), and was negatively related to the total score of psychological capital ( r = -0.53, P < 0.01). The total score of rumination was negatively related to the total score of psychological capital ( r = -0.46, P < 0.01). The psychological capital played a partial mediating role between rumination and learning burnout. The mediating effect value was 0.216, accounting for 61.521% of the total variation. Conclusion:The rumination can both directly affect the learning burnout of nursing undergraduate students and indirectly affect the learning burnout through psychological capital. Psychological capital plays a bridge role in improving rumination related to learning burnout.

The paper reported a case of a young male patient, with graft-versus-host disease (GVHD) multi-organ involvement lesions after allo-hematopoietic stem cell transplantation. The patient had diverse clinical manifestations, and overlapping acute and chronic disease processes. Acute GVHD were mainly hyperbilirubinemia, with or without elevated transaminase, bloody watery stools; chronic GVHD were highlighted by extensive skin depigmentation, oral mucosal ulcer, sick nails, etc., and chronic signs, such as membranous nephropathy, polyserositis and pulmonary restrictive ventilatory insufficiency. The diagnosis of chronic GVHD mainly relies on medical history combined with clinical manifestations, and it's needed to exclude infections, drugs and tumors. Besides, the rate of missed diagnosis and misdiagnose is high, and it requires multidisciplinary diagnosis and treatment. Combined with the literature review, it indicates that there is a greater risk of GVHD in the male recipient with female donor, and peripheral blood stem cell transplant patients have a higher incidence than bone marrow transplant patients after hematopoietic stem cell transplantation, but the effect of the graft-versus-leukemia exists. Currently, glucocorticoids therapy with or without calcineurin inhibitors are the first-line treatment for GVHD, but the overall prognosis is poor.

OBJECTIVE: The medicinal mushroom Sanghuangporus vaninii produces pharmaceutically valuable hispidin polyphenols in natural habitats. However, due to the slow growth in nature, S. vaninii grown in the field (sclerotia) is not reliable for pharmaceutical purposes. Although higher biomass of fungal mycelia can be obtained in submerged cultures, the accumulation of hispidin polyphenols is rare. METHODS: In this study, the polyunsaturated fatty acids (PUFAs), linoleic acid (LA), linolenic acid (ALA), and methyl jasmonate (MeJa) were employed as the stimulant agents to coordinate the accumulation of biomass and hispidin polyphenols in its submerged cultures. RESULTS: The addition of LA and ALA promoted the mycelial accumulation, while the addition of MeJa inhibited the growth of S. vaninii concomitant with reduced total polyphenols. UPLC-Triple-TOF-MS analysis revealed an increased production of hispidin, phellinstatin, pinnilidine, and its derivatives upon the addition of LA and ALA, and hypholomine B and its isomer, 3,14'-bihispidinyl, and phelligridin E upon the addition of MeJa on day 13. Intriguingly, total polyphenols from the MeJa-supplementing cultures harbored a high capacity in scavenging free radicals. Chemical structural analysis showed that hispidin polyphenols had higher antioxidant activity due to more hispidin moieties induced by MeJa. CONCLUSION The supplement of PUFAs affects the synthesis and composition of hispidin polyphenols in S. vaninii. Our results provide a possibility to coordinate the production of hispidin polyphenols via submerged cultures of S. vaninii.

OBJECTIVE: To investigate the causal relationship between neutrophil extracellular trap (NET) and sepsis based on Mendelian randomization analysis. METHODS: The genome wide association study (GWAS) dataset for the NET biomarker myeloperoxidase (MPO)-DNA complex based on Donkel et al. 's Rotterdam study (RS) and GWAS dataset for identifying sepsis from the UK biobank were selected to screen single nucleotide polymorphisms (SNPS) associated with MPO-DNA complex as instrumental variable (IV) for genetic variation, using MPO-DNA complex as exposure factor. Potential causal associations between MPO-DNA complex and the risk of occurrence of sepsis, 28-day death from sepsis, need for intensive care due to sepsis, and 28-day death from sepsis requiring intensive care were analyzed using a two-sample, one-way Mendelian randomization analysis primary analysis method of inverse analysis of variance (IVW). Potential pleiotropy was assessed using the MR Egger regression intercept test. Sensitivity analysis was performed using the "leave one out" test. RESULTS: The GWAS data were obtained from a European population of both sexes, and the screening criteria was based on the three main assumptions of Mendelian randomization, resulting in 22 SNP entering the Mendelian randomization analysis. The results of the Mendelian randomization causal association effect analysis using the IVW method showed that for every standard deviation increase in the level of the MPO-DNA complex, the risk of sepsis increased by approximately 18% [odds ratio (OR) = 1.18, 95% confidence interval (95%CI) was 1.07-1.29, P < 0.001], the risk of 28-day death from sepsis increased by approximately 51% (OR = 1.51, 95%CI was 1.27-1.81, P < 0.001), an increase of approximately 38% in the risk of occurrence of needing intensive care due to sepsis (OR = 1.38, 95%CI was 1.12-1.70, P = 0.002), and an increase of approximately 125% in the risk of 28-day death from sepsis requiring intensive care (OR = 2.25, 95%CI was 1.21-4.18, P = 0.01). MR Egger regression intercept test suggested that there was no horizontal pleiotropy in the included SNP, and the MR-PRESSO test did not find outliers. Sensitivity analysis suggested that the results of Mendelian randomization were robust. CONCLUSIONS Rising NET can increase the risk of sepsis onset, progression and death as derived from Mendelian randomization analysis.
Female ; Male ; Humans ; Extracellular Traps ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Sepsis/genetics* ; Nonoxynol ; DNA

Objective:To investigate the clinical value of contrast-enhanced ultrasonography in the diagnosis of inflammatory hepatocellular adenoma.Methods:100 patients with inflammatory hepatocellular adenoma who received treatment in the Department of Oncology, Zhejiang Quhua Hospital, between March 2018 and March 2021, were included in this study. These patients were divided into < 5 cm group (control group, n = 65) and ≥ 5 cm group (observation group, n = 35) according to maximum tumor diameter. Routine ultrasonography and contrast-enhanced ultrasonography findings were compared between the two groups. Results:Pathological findings and immunohistochemical staining results confirmed all patients had inflammatory hepatocellular adenoma. There were 65 patients with maximum tumor diameter < 5 cm in the control group and 35 patients with maximum tumor diameter ≥ 5 cm in the observation group. Routine ultrasonography findings revealed there were no significant differences in internal echo, border, shape, and blood flow distribution between control and observation groups ( χ2 = 0.45, 0.08, 3.12, 3.54, all P > 0.05). In the control group, 56 (86.15%) patients had a uniform echo and 9 (13.85%) patients had an uneven echo. In the observation group, 19 (54.29%) patients had a uniform echo and 16 (45.71%) patients had an uneven echo. There were significant differences in the number of patients having a uniform echo or an uneven echo between the two groups ( χ2 = 12.32, P < 0.05). There were no significant differences in contrast-enhanced ultrasonography results in terms of arterial phase enhancement mode, portal phase enhancement performance, delayed phase enhancement performance, and presence of a vessel sign under the capsule between the two groups ( χ2 = 0.65, 0.40, 1.75, 2.07, all P > 0.05). In the control group, 55 (84.62%) patients had a uniformly contrast-enhanced area, and 10 (15.38%) patients had a non-uniformly contrast-enhanced area, in the arterial phase at the peak intensity. In the observation group, 16 (45.71%) patients had a uniformly contrast-enhanced area, and 19 (54.29%) patients had a non-uniformly contrast-enhanced area, in the arterial phase at the peak intensity. There was a significant difference between the two groups ( χ2 = 16.52, P < 0.05). No patients from the control group had an internal perfusion defect, and 12 (34.29%) patients from the observation group had an internal perfusion defect. There was significant difference in the number of patients having an internal perfusion defect ( χ2 = 25.32, P < 0.05). High contrast enhancement in the arterial phase appeared in two groups. Conclusion:Contrast-enhanced ultrasonography can display the imaging features of inflammatory hepatocellular adenoma, which reflects the hemodynamic differences among foci of different sizes and helps diagnose and treat inflammatory hepatocellular adenoma.

BACKGROUND: Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC. METHODS: The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues. RESULTS: The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P   <  0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P   <  0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC ( P  < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway. CONCLUSIONS Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.
Humans ; Female ; Aurora Kinase A/metabolism* ; Aurora Kinase B/metabolism* ; Prognosis ; Breast Neoplasms/genetics* ; Neoplasm Recurrence, Local ; MicroRNAs

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*