A study on combination of non-ablative local RFA with PD-1 and angiogenesis blocking to prolong survival through improvement of immune microenvironment in advanced Hepatocellular Carcinoma.

Radiofrequency ablation (RFA), an effective local treatment method for early-stage Hepatocellular Carcinoma (HCC), combined with PD-1 blocking and anti-angiogenic therapy is being extensively explored in advanced HCC, however, the definite results and underlying mechanisms still remain to be elucidated. Therefore, whether non-ablative RFA-based combined therapy can play a synergistic anti-tumor effect through improving tumor immune microenvironment was investigated by us in HCC mouse models. Our results showed that non-ablative RFA could regulate multilayered immunity, such as inducing immunogenic death of tumor cells, upregulating the secretion of inflammatory cytokines, mainly IFN-γ, TNF-α, and IL-10, and subsequently promoting the infiltration of CD8 + T cells. As a result, a significant synergistic anti-tumor effect was demonstrated in the combination therapy group. Similarly, in the real-world setting, non-curative RFA combined with PD-1 blocking and Lenvatinib for 12 patients with Barcelona Clinic Liver Cancer (BCLC) stage C achieve promising results, with 6.9 months (95 % CI: 3.23-15.73) median progression-free survival (mPFS) and 12.7 months (95 % CI: 7.40-19.73) median overall survival (mOS). The common treatment-related adverse reactions were pneumonia and thyroiditis with low prevalence, both less than grade 3 and manageable by symptomatic treatment. Summarily, local non-ablative RFA should be a clinically preferred strategy in combination with PD-1 blocking and anti-angiogenic therapy, because this more flexible scheme abandons its historical concept of tumor eradication, but fully utilizes the immune regulatory function by inducing immunogenic tumor death and has higher-level of safety. Therefore, this is a two-pronged and highly balanced approach to achieved favorable treatment outcomes, while conclusive evidence is still pending, it can be attempted in the real world anyway.

A metabolic mechanism analysis of Gentiana radix and wine-processed Gentiana radix effects on damp-heat jaundice syndrome in Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana radix (GR) and wine-processed Gentiana radix (WGR) are commonly used in folk medicine for the treatment of bile or liver disorders, including jaundice, hepatitis, swelling or inflammation for thousands of years. However, the therapeutic effects of gentian root (GR) and wine-made gentian root (WGR) treatment on damp-heat jaundice syndrome (DHJS) have not been studied in animal experiments. AIM OF THE STUDY: This study aimed to investigate the protective effects and mechanisms of GR and WGR on DHJS in rats. MATERIALS AND METHODS: In a high-fat and high-sugar diet in a humidified hot environment, hepatic injury induced by giving of alpha-naphthalene isothiocyanate (ANIT) in rats were used as a DHJS model. Histological analysis, enzyme-linked immunosorbent assay (ELISA), PCR analysis, and metabolomics were used to elucidate the mechanism of GR and WGR for DHJS. RESULTS: The results indicated that GR and WGR affected DHJS by inhibiting the release of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (D-BIL), total bilirubin (TBIL), total bile acid (TBA), malondialdehyde (MDA), glutathione S-transferase (GST) (P < 0.05). In addition, they significantly reduced the gene expression levels of Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BESP), multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) (P < 0.05). The WGR group improved the above function indicators better than the GR group. GR and WGR could restore 11 potential biomarkers in rats with DHJS tended to return to normal levels, these biomarkers were involved in arachidonic acid metabolism, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, porphyrin and chlorophyll metabolism, retinol metabolism, arginine biosynthesis. The results of the metabolic pathway showed that WGR was significantly better than GR in the improvement of porphyrin and chlorophyll metabolism. CONCLUSIONS: These findings suggest that treatment with GR and WGR has a beneficial effect on DHJS in rats, the major mechanisms may be involved in improving functional indicators of the body and endogenous metabolism, and WGR is more effective than GR. It provides important evidence for the clinical application of GR and WGR in the treatment of DHJS.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG- events.

Introduction: This study assessed incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG) as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. Methods: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. Results: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient cost of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001.Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively.Conclusions: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over 3 times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm­a muscle that helps with breathing­becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specially for patients who also have a heart, blood, and blood vessels disease; patients who have a mental illness; and patients who have MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight stays in a hospital. Patients with gMG also had 4 times more overnight hospital stays and 2 times more hospital day visits, when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors need to also control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.

Women's experiences with Centering-Based Group Care in Zhejiang China: A pilot study.

BACKGROUND: The group prenatal care model, which caters to women with low medical needs but high support needs, has become a highly prevalent and innovative approach implemented globally. For Centering-Based Group Care (CBGC) to remain effective, women's evaluations of the quality of care and perspectives about the model are crucial. AIM: This study aimed to describe women's appraisal of CBGC quality and explore the experiences of women in the mixed-methods pilot study conducted in Zhejiang, China. METHODS: From August 2021 to December 2022, 20 women provided complete quantitative data using the Quality of Prenatal Care Questionnaire before hospital discharge. Semi-structured interviews were conducted at 6 months postpartum. Qualitative data were analysed using Colaizzi's method. FINDINGS: The mean (standard deviation) total score (of the 5) of the questionnaire was 4.43 (0.1) with a good quality of CBGC. Qualitative research identified five themes: motivations and concerns for participation, the appeal of interactive learning, the development of community ties and social support, healing from psychological trauma with CBGC, and suggestions for CBGC enhancement. DISCUSSION: Women rated CBGC quality as good and benefited significantly from it in the study. As a new alternative option, the women's accounts suggested that CBGC performed excellently in enhancing knowledge, strengthening social bonds, and providing psychological support. CONCLUSION: CBGC quality cannot be determined based on limited the sample size. This pilot study provides evidence regarding the beneficial effects of knowledge, socialization, and psychological healing on CBGC. Further research is suggested to measure CBGC effectiveness and quality.

Long-term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-based Study.

INTRODUCTION: Health care costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and pre-existing (PE) MG in Sweden. METHODS: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥ 24-month follow-up during the period 1/1/2010 to 12/31/2017 were included. RESULTS: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years and 52.3% were female. In first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs 83.9%), corticosteroids (59.6% vs 45.8%), thymectomy (12.1% vs 0.7%) and plasma exchange (3.8% vs 0.6%); had higher all-cause (70.9% vs 35.8%) and MG-related (62.5% vs 18.4%) hospitalization rates with 11 more hospitalization days (all p<0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred €7302 (p<0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p<0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ~55% for ND MG from year 1 and were comparable with PE MG. CONCLUSION: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis.

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results.Abbreviation: 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Försterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green™ SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.

Differences in physiology and behavior between male winner and loser mice in the tube test.

Social hierarchy is a crucial element for survival, reproduction, fitness, and the maintenance of a stable social group in social animals. This study aimed to investigate the physiological indicators, nociception, unfamiliar female mice preference, spatial learning memory, and contextual fear memory of male mice with different social status in the same cage. Our findings revealed significant differences in the trunk temperature and contextual fear memory between winner and loser mice. However, there were no major discrepancies in body weight, random and fasting blood glucose levels, whisker number, frontal and perianal temperature, spleen size, mechanical and thermal pain thresholds, preference for unfamiliar female mice, and spatial memory. In conclusion, social status can affect mice in multiple ways, and, therefore, its influence should be considered when conducting studies using these animals.

The chemerin-CMKLR1 axis in keratinocytes impairs innate host defense against cutaneous Staphylococcus aureus infection.

The skin is the most common site of Staphylococcus aureus infection, which can lead to various diseases, including invasive and life-threatening infections, through evasion of host defense. However, little is known about the host factors that facilitate the innate immune evasion of S. aureus in the skin. Chemerin, which is abundantly expressed in the skin and can be activated by proteases derived from S. aureus, has both direct bacteria-killing activity and immunomodulatory effects via interactions with its receptor CMKLR1. Here, we demonstrate that a lack of the chemerin/CMKLR1 axis increases the neutrophil-mediated host defense against S. aureus in a mouse model of cutaneous infection, whereas chemerin overexpression, which mimics high levels of chemerin in obese individuals, exacerbates S. aureus cutaneous infection. Mechanistically, we identified keratinocytes that express CMKLR1 as the main target of chemerin to suppress S. aureus-induced IL-33 expression, leading to impaired skin neutrophilia and bacterial clearance. CMKLR1 signaling specifically inhibits IL-33 expression induced by cell wall components but not secreted proteins of S. aureus by inhibiting Akt activation in mouse keratinocytes. Thus, our study revealed that the immunomodulatory effect of the chemerin/CMKLR1 axis mediates innate immune evasion of S. aureus in vivo and likely increases susceptibility to S. aureus infection in obese individuals.

Comprehensive Study and Design of Graphene Transistor.

Graphene, renowned for its exceptional electrical, optical, and mechanical properties, takes center stage in the realm of next-generation electronics. In this paper, we provide a thorough investigation into the comprehensive fabrication process of graphene field-effect transistors. Recognizing the pivotal role graphene quality plays in determining device performance, we explore many techniques and metrological methods to assess and ensure the superior quality of graphene layers. In addition, we delve into the intricate nuances of doping graphene and examine its effects on electronic properties. We uncover the transformative impact these dopants have on the charge carrier concentration, bandgap, and overall device performance. By amalgamating these critical facets of graphene field-effect transistors fabrication and analysis, this study offers a holistic understanding for researchers and engineers aiming to optimize the performance of graphene-based electronic devices.

Application of Platysma Myocutaneous Flap in Surgical Repair after T2-3 Glottic Carcinoma Resection.

OBJECTIVE: Numerous methods and materials are available for vertical partial laryngectomy. In this study, the reparative effects of the platysma myocutaneous flap (PMF) and ribbon myocutaneous flap (RMF) on the postoperative voice quality of patients were compared to provide a reference for selecting a method conducive to improving postoperative voice quality. METHODS: A retrospective analysis was performed on patients with unilateral T2-3 glottic carcinoma. Following vertical partial laryngectomy, the defect was repaired with a PMF or simple RMF. Twelve months after surgery, voice quality was assessed according to voice acoustics, aerodynamics, and subjective perceptual evaluation, and glottic morphology was recorded using a laryngeal stroboscopy. RESULTS: A total of 70 patients were identified, including 54 in the PMF group and 16 in the RMF group. The PMF group was superior to the RMF group in terms of voice quality assessed by voice acoustics, aerodynamics, and subjective perceptual evaluation. In the PMF group, 72.2% of patients performed phonation with their vocal cords, and approximately 27.8% of patients were affected by supraglottic compression. In the RMF group, 81.3% of patients were affected by supraglottic compression. No significant difference was found in the 5-year survival rate between the two groups. CONCLUSION: For defect repair following vertical partial laryngectomy, a PMF can allow better postoperative voice quality to be achieved than an RMF because a PMF can provide more tissue (including strap muscle under the flap) for padding, which enables the glottic portion corresponding to the vocal cord to close well. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Intelligent method to predict intensive care unit admission after drainage operation in patients with deep neck space abscess: A multicenter retrospective study.

BACKGROUNDS: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA. METHODS: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models. RESULTS: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935. CONCLUSION: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.

The effect of in-hospital breast milk intake on the gut microbiota of preterm infants.

OBJECTIVE: The aim of this study was to explore the effect of in-hospital breast milk intake on the development of early gut microbiota in preterm infants in two dimensions: longitudinal over time and cross-sectional between groups. METHODS: Researchers collected preterm infants' general data baseline characteristics, recorded their daily breast milk intake, probiotics, and antibiotics use, and collected their stool specimens at 1st week, 2 nd week, 3rd week and 4th week after birth. The researchers analyzed the effect of breast milk on gut microbiota of preterm infants by bioinformatics methods of intra-group longitudinal variation of gut microbiota structure and diversity in preterm infants and cross-sectional differences between >70 % in-hospital breast milk intake (BM) group and ≤70 % (PF) group. RESULTS: A total of 60 preterm infants were included in this study, and a total of 213 stool specimens were retained. BM had statistically different Shannon and Simpson indices between the first and fourth week after admission (P < 0.05), both of them showed a lower diversity in the later week than in the previous week. The Shannon index and Simpson index of BM from week 3 onwards were statistically different from PF (P < 0.05), and the Shannon index and Simpson index of BM were lower than those of PF. Significantly statistical differences (P < 0.05) were found in the beta diversity of gut microbiota in preterm infants as time progressed, and both showed a lower beta diversity in the later week than in the preceding week. The dominant taxa of PF in the first postnatal week were Bifidobacterium animalis, etc., the dominant taxa of BM in the third postnatal week were Clostridium_sensu_stricto _1, etc. CONCLUSIONS: The development and evolution of gut microbiota in preterm infants' in-hospital period was a continuous, non-random process, and similar trends in species composition and changes in gut microbes emerged in preterm infants with different ratio of breast milk intake. In the NICU setting, alpha diversity was lower in preterm infants in the >70 % breast milk intake group than in the ≤70 % group when compared between groups at the same time, which may be related to delayed maturation of gut microbes and represents a more developmental gut time window.

Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neurons.

Hyperphosphorylation and aggregation of microtubule-associated tau is a pathogenic hallmark of tauopathies and a defining feature of Alzheimer's disease (AD). Pathological tau is targeted by autophagy for clearance, but autophagy dysfunction is indicated in tauopathy. While mitochondrial bioenergetic failure has been shown to precede the development of tau pathology, it is unclear whether energy metabolism deficiency is involved in tauopathy-related autophagy defects. Here, we reveal that stimulation of anaplerotic metabolism restores defective oxidative phosphorylation (OXPHOS) in tauopathy which, strikingly, leads to enhanced autophagy and pronounced tau clearance. OXPHOS-induced autophagy is attributed to increased ATP-dependent phosphatidylethanolamine biosynthesis in mitochondria. Excitingly, early bioenergetic stimulation boosts autophagy activity and reduces tau pathology, thereby counteracting memory impairment in tauopathy mice. Taken together, our study sheds light on a pivotal role of bioenergetic dysfunction in tauopathy-linked autophagy defects and suggests a new therapeutic strategy to prevent toxic tau buildup in AD and other tauopathies.

Bioinformatic analysis reveals prognostic value and immunotherapy potential of Siglec-15 in laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is the ultimate common malignant head and neck cancer with dismal prognosis. The expression pattern and clinical significance of Siglec-15 (Sialic acid-binding immunoglobulin-like lectin 15) in LSCC are poorly understood. In order to lay the groundwork for future immune-related research on Siglec-15 in LSCC, we set out to study its expression and prognostic importance in the disease, as well as to use bioinformatics to investigate the immune features modulated by Siglec-15 in LSCC. Methods: ① In order to get the gene expression profile and clinical data for TCGA head and neck cancer (TCGA-HNSC), you may access the relevant data from UCSC xena and use 110 cases of laryngeal cancer as a training set. Two datasets, GSE27020 and GSE25727, were obtained from the GEO databank and utilized as validation sets. These datasets include expression profiles and clinical information. The Siglec-15 gene and immune characteristics were analyzed by bioinformatics methods. ② Retrospectively collected routine paraffin specimens from patients with pathological diagnosis of squamous cell carcinoma from December 2012 to November 2015 in Sun Yat-sen Memorial Hospital and fresh frozen tissue of patients from June 2021 to March 2022. Immunohistochemistry method, immunofluorescence technique and real-time quantitative PCR was used to examine the difference of Siglec-15 appearance in LSCC tissue and adjacent tissue, and its correlation of prognosis, clinic pathological characteristics and CD8+T lymphocyte infiltration. Using human laryngeal cancer cell line (LCC), we studied the influence of Siglec-15 in cell proliferation and invasion. Results: We identified Siglec-15 was upregulated in LSCC. The patients in Siglec-15 high expression group had a poor overall survival (OS) based on the clinical information from TGCA and 111 LSCC patients that hospitalized in Sun Yat-sen Memorial Hospital. The COX regression analysis indicated Siglec-15 as an independent predictor for poor prognosis of LSCC. Bioinformatic analysis suggested that the high expression of Siglec-15 shape an immune suppressive tumor microenvironment (TEM), leading to poor response to immunotherapy in LSCC. Siglec-15 enhanced cell invasion and proliferation, as we showed in vitro. Conclusion: Our study support Siglec-15 as a potential predictor for LSCC prognosis and an attractive target for LSCC immunotherapy.

Radiomics nomogram for predicting disease-free survival after partial resection or radical cystectomy in patients with bladder cancer.

OBJECTIVES: To create a MRI-derived radiomics nomogram that combined clinicopathological factors and radiomics signature (Rad-score) for predicting disease-free survival (DFS) in patients with bladder cancer (BCa) following partial resection (PR) or radical cystectomy (RC), including lymphadenectomy (LAE). METHODS: Finally, 80 patients with BCa after PR or RC with LAE were enrolled. Patients were randomly split into training (n = 56) and internal validation (n = 24) cohorts. Radiomic features were extracted from T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, and apparent diffusion coefficient sequence. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was applied to choose the valuable features and construct the Rad-score. The DFS prediction model was built using the Cox proportional hazards model. The relationship between the Rad-score and DFS was assessed using Kaplan-Meier analysis. A radiomics nomogram that combined the Rad-score and clinicopathological factors was created for individualized DFS estimation. RESULTS: In both the training and validation cohorts, the Rad-score was positively correlated with DFS (P < .001). In the validation cohort, the radiomics nomogram combining the Rad-score, tumour pathologic stage (pT stage), and lymphovascular invasion (LVI) achieved better performance in DFS prediction (C-index, 0.807; 95% CI, 0.713-0.901) than either the clinicopathological (C-index, 0.654; 95% CI, 0.467-0.841) or Rad-score-only model (C-index, 0.770; 95% CI, 0.702-0.837). CONCLUSION: The Rad-score was an independent predictor of DFS for patients with BCa after PR or RC with LAE, and the radiomics nomogram that combined the Rad-score, pT stage, and LVI achieved better performance in individual DFS prediction. ADVANCES IN KNOWLEDGE: This study provided a non-invasive and simple method for personalized and accurate prediction of DFS in BCa patients after PR or RC.

Percutaneous microwave ablation versus sclerotherapy for large hepatic hemangioma: a multi-center cohort study.

OBJECTIVE: The study aimed to compare the effectiveness and safety of ultrasound-guided microwave ablation (MWA) and percutaneous sclerotherapy (PS) for the treatment of large hepatic hemangioma (LHH). METHODS: This retrospective study included 96 patients who underwent MWA (n = 54) and PS (n = 42) as first-line treatment for LHH in three tertiary hospitals from January 2016 to December 2021. Primary outcomes were technique efficacy rate (volume reduction rate [VRR] > 50% at 12 months), symptom relief rate at 12 months and local tumor progression (LTP). Secondary outcomes included procedure time, major complications, treatment sessions, cost and one-, two-, three-year VRR. RESULTS: During a median follow-up of 36 months, the MWA group showed a higher technique efficacy rate (100% vs. 90.4%, p = .018) and symptom relief rate (100% vs. 80%, p = .123) than the PS group. The MWA group had fewer treatment sessions, higher one-, two- and three-year VRR, lower LTP rate (all p < .05), longer procedure time and higher treatment costs than the PS group (both p < .001). MWA shared a comparable major complications rate (1.8% vs. 2.4%, p = .432) with PS. After multivariate analysis, the lesion's heterogeneity and maximum diameter >8.1 cm were independent risk factors for LTP (all p < .05). In the PS group, lesions with a cumulative dose of bleomycin > 0.115 mg/cm3 had a lower risk of LTP (p = .006). CONCLUSIONS: Both MWA and PS treatments for large hepatic hemangioma are safe and effective, with MWA being superior in terms of efficacy.

A transition-metal-free azide-alkyne cycloaddition/hydroamination cascade reaction for the construction of triazole-fused piperazin-2-ones.

A time-dependent, divergent synthesis of highly functionalized [1,2,3]triazolo[1,5-a]pyrazin-4(5H)-one (reaction time: 12 h) or 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazin-4(5H)-one (reaction time: 2 h) scaffolds via a cascade azide-alkyne cycloaddition/hydroamination protocol is reported. The transformation features good functional group compatibility, broad substrate scope, high atom economy and avoidance of the use of transition-metal catalysts.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure.

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.

Aconitum coreanum alleviates cerebral ischemic stroke through the PI3K/Akt signaling pathway in gerbils model.

Cerebral ischemic stroke (CIS) is a kind of acute cerebrovascular disease with fast onset, low-cure rate, and high case-fatality rate. The application of Aconitum coreanum on CIS was recorded in many ancient books in China with it mechanism and effective components unclear. This study aimed to analyze the potential mechanism and effetvie components of A. coreanum on treating CIS. Neurological function score, cerebral infarction rate, and inflammatory indicators were applied to evaluate the efficacy of A. coreanum on gerbils with CIS. The prototype compounds in A. coreanum which were absorbed into blood was analyzed and identified by Ultra high performance liquid chromatography-Q exactive focus-Mass spectrometer (UPLC-QE-MS). And bioinformatics analysis was used to predict their potential targets or pathways of action. Western blotting and immunofluorescence were adopted to validate the targets or pathway with high relation. After treatment with A. coreanum, the neurological function status of gerbils with CIS was significantly improved, the ischemic area of the brain and the levels of inflammatory indicators significantly reduced. 22 prototype compounds in A. coreanum absorbed into blood were identified mainly including C-20 and C-19 diterpenoid alkaloids. Gene ontology (GO) function enrichment analysis illustrated that A. coreanum acted on protein phosphorylation, receptor complexes, protein kinase activity, and inflammatory response to impove CIS. The kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis results revealed that PI3K/Akt signaling pathway was a key pathway. Western blotting and immunofluorescence validated that A. coreanum acted on PI3K/Akt signaling pathway. In conclusion, A. coreanum improved the inflammantory condition in CIS by acting on PI3K/Akt signaling pathway and the effective components were the diterpenoid alkaloids in it.