Patterns of cervical lymph node involvement in mono-focal papillary thyroid carcinoma patients with different capsular status: A multi-center analysis.

OBJECTIVE: The characteristics of cervical lymph node involvement in papillary thyroid carcinoma (PTC) patients with different degree of capsular invasion remains unclear, especially for those with mono-focal lesion who have traditionally been considered as low neck metastasis risk subgroup. STUDY DESIGN: Retrospective cohort study. SETTING: Three academic teaching hospital. METHODS: A total of 1276 mono-focal PTC patients were retrospectively analyzed. RESULTS: Mono-focal PTC patients with extrathyroidal extension (ETE) showed significantly higher central lymph node metastasis (CLNM) rate than those without. For patients with no gross ETE (gETE), those with minimal ETE (mETE) also showed more commonly CLNM than those with encapsulated lesions. However, the lateral lymph node metastasis (LLNM) rates of patients with mETE and encapsulated tumors were comparable, both lower than that of patients with gETE. Age ≥40, male, and MTD ≥0.5 cm were identified as independent risk factors of CLNM for those with encapsulated tumors and were enrolled for creating a prediction model. In terms of LLNM, only MTD ≥1.0 cm was confirmed as independent risk factors of LLNM for patients with positive gETE. CONCLUSIONS: The presence and degree of ETE may have different effects on the risk of central and lateral lymph node metastasis. gETE demonstrates a strong correlation with both CLNM and LLNM while mETE is only associated with CLNM in mono-focal PTC patients. A comprehensive model is established in the aim of predicting neck involvement according to the capsular status and the corresponding stratified risk factors, which may aid clinical decision-making for the management of neck regions.

Reg4 deficiency aggravates pancreatitis by increasing mitochondrial cell death and fibrosis.

Regenerating gene family member 4 (Reg4) has been implicated in acute pancreatitis, but its precise functions and involved mechanisms have remained unclear. Herein, we sought to investigate the contribution of Reg4 to the pathogenesis of pancreatitis and evaluate its therapeutic effects in experimental pancreatitis. In acute pancreatitis, Reg4 deletion increases inflammatory infiltrates and mitochondrial cell death and decreases autophagy recovery, which are rescued by the administration of recombinant Reg4 (rReg4) protein. In chronic pancreatitis, Reg4 deficiency aggravates inflammation and fibrosis and inhibits compensatory cell proliferation. Moreover, C-X-C motif ligand 12 (CXCL12)/C-X-C motif receptor 4 (CXCR4) axis is sustained and activated in Reg4-deficient pancreas. The detrimental effects of Reg4 deletion are attenuated by the administration of the approved CXCR4 antagonist plerixafor (AMD3100). Mechanistically, Reg4 mediates its function in pancreatitis potentially via binding its receptor exostosin-like glycosyltransferase 3 (Extl3). In conclusion, our findings suggest that Reg4 exerts a therapeutic effect during pancreatitis by limiting inflammation and fibrosis and improving cellular regeneration.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy.

OBJECTIVES: To investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features. MATERIALS AND METHODS: One hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were used to evaluate the predictive performance of the scoring system. RESULTS: Multivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001). CONCLUSION: ECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach. CRITICAL RELEVANCE STATEMENT: The scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis. KEY POINTS: Predicting the progression of LAPC in patients receiving IORT is important. Our ECV-based scoring system can risk stratifying patients with initial SD. Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.

Parathyroidectomy for solitary parathyroid adenoma via trans-areola single site endoscopic approach: Results of a case-match study.

BACKGROUND: This study aimed to establish the standardized procedure of trans-areola single site endoscopic parathyroidectomy (TASSEP), and to compare the performance of TASSEP with that of conventional open parathyroidectomy (COP). METHODS: This study enrolled 40 patients with primary hyperparathyroidism (PHPT) who underwent TASSEP, and included 40 of 176 PHPT patients who underwent COP based on propensity score matching. The retrospective analysis was conducted based on prospectively collected data. Perioperative outcomes, including surgical profile, surgical burden and cosmetic results and follow-up were reported. The learning curve was described using a cumulative sum (CUSUM) analysis. RESULTS: 40 TASSEPs were completed successfully without conversions or severe complications. There was no statistically significant difference in operation time between TASSEP and COP groups (80.83 ± 11.95 vs. 76.95 ± 7.30 min, p = 0.084). Experience of 17 cases was necessitated to reach the learning curve of TASSEP. Postoperative pain score and traumatic index (C-reactive protein and erythrocyte sedimentation rate) in TASSEP were apparently lower than those in COP group (p < 0.05). During the proliferation and stabilization phases, TASSEP was associated with significantly better incision recovery and cosmetic scores. Postoperative serum calcium and PTH levels throughout the follow-up period indicated satisfactory surgical qualities in both groups. CONCLUSION: Based on precise preoperative localization and intraoperative planning facilitated by three-dimensional (3D) virtual modeling, TASSEP can be feasibly performed on selected patients with satisfactory success rates and low complication rates, providing preferable cosmetic results and alleviating the surgical burden to a certain extent.

Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer.

BACKGROUND: The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors. METHODS: The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT. RESULTS: After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2 = 0.319, P = 0.037, and BMD was also positively correlated with pectoral muscle density, R2 = 0.329, P = 0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism. CONCLUSION: Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.

Phosphine-Catalyzed Domino Annulation of γ-Vinyl Allenoates: Synthesis of Tetrahydrofuro[3,2-c]quinoline Derivatives.

A novel phosphine-catalyzed domino annulation reaction of γ-vinyl allenoates and o-aminotrifluoacetophenones for the construction of terahydrofuro[3,2-c]quinoline derivatives has been developed. In this domino reaction, two kinds of terahydrofuro[3,2-c]quinoline compounds containing CF3 groups were obtained with good yields under mild conditions, three new C-N, C-C, and C-O bonds can be built in one step, and the reaction selectivity is achieved by adjusting the reaction conditions. Furthermore, preliminary studies on an asymmetric variant of this reaction proceeded with moderate enantioselectivity.

Liver Transplantation for Diffuse Form of Caroli Disease with Chronic Hepatitis B: A Case Report.

Caroli disease (CD) is a congenital disease of the intrahepatic biliary system, which manifests as cystic dilatation of the intrahepatic bile ducts. The disease has a low incidence and atypical clinical manifestations; therefore, it can be easily misdiagnosed. Hepatitis B infection is a viral infection that affects liver cells, leading to degeneration, necrosis, and regeneration of the cells and formation of false lobules, and ultimately nodular cirrhosis, which can lead to liver dysfunction and liver failure. Herein, we report a case of decompensated liver cirrhosis because of a diffuse form of CD, which was misdiagnosed because of long-term hepatitis B virus (HBV) infection. Finally, orthotopic liver transplantation (OLT) was performed, and the patient was cured. We believe that this congenital factor combined with HBV infection accelerated cirrhosis progression in this patient. This transplant was carried out in accordance with the Helsinki Congress and the Declaration of Istanbul.

A modified dual-knife fistulotomy for achieving challenging biliary cannulation in type 3 papilla.

Video 1A modified dual-knife fistulotomy for achieving challenging biliary cannulation in type 3 papilla.

Flexible and Energy-Efficient Synaptic Transistor with Quasi-Linear Weight Update Protocol by Inkjet Printing of Orientated Polar-Electret/High-k Oxide Composite Dielectric.

Inkjet printing artificial synapse is cost-effective but challenging in emulating synaptic dynamics with a sufficient number of effective weight states under ultralow voltage spiking operation. A synaptic transistor gated by inkjet-printed composite dielectric of polar-electret polyvinylpyrrolidone (PVP) and high-k zirconia oxide (ZrOx) is proposed and thus synthesized to solve this issue. Quasi-linear weight update with a large variation margin is obtained through the coupling effect and the facilitation of dipole orientation, which can be attributed to the orderly arranged molecule chains induced by the carefully designed microfluidic flows. Crucial features of biological synapses including long-term plasticity, spike-timing-dependence-plasticity (STDP), "Learning-Experience" behavior, and ultralow energy consumption (<10 fJ/pulse) are successfully implemented on the device. Simulation results exhibit an excellent image recognition accuracy (97.1%) after 15 training epochs, which is the highest for printed synaptic transistors. Moreover, the device sustained excellent endurance against bending tests with radius down to 8 mm. This work presents a very viable solution for constructing the futuristic flexible and low-cost neural systems.

Biomimetic Multifunctional Graphene-Based Coating for Thermal Management, Solar De-Icing, and Fire Safety: Inspired from the Antireflection Nanostructure of Compound Eyes.

Due to the ubiquitous and inexhaustible solar source, photothermal materials have gained considerable attention for their potential in heating and de-icing. Nevertheless, traditional photothermal materials, exemplified by graphene, frequently encounter challenges emanating from their elevated reflectance. Inspired by ocular structures, this study uses the Fresnel equation to enhance the photo-thermal conversion efficiency of graphene by introducing a polydimethylsiloxane (PDMS)/silicon dioxide (SiO2) coating, which reduces the light reflectance (≈20%) through destructive interference. The designed coating achieves an equilibrium temperature of ≈77 °C at one sun and a quick de-icing in ≈65 s, all with a thickness of 5 µm. Simulations demonstrate that applying this coating to high-rise buildings results in energy savings of ≈31% in winter heating. Furthermore, the combination of PDMS/SiO2 and graphene confers a notable enhancement in thermal stability through a synergistic flame-retardant mechanism, effectively safeguarding polyurethane against high temperatures and conflagrations, leading to marked reduction of 58% and 28% in heat release rate and total heat release. This innovative design enhances the photo-thermal conversion, de-icing function, and flame retardancy of graphene, thereby advancing its applications in outdoor equipment, high-rise buildings, and aerospace vessels.

Identification and validation of a novel anoikis-related prognostic model for prostate cancer.

BACKGROUND: Anoikis resistance is a hallmark characteristic of oncogenic transformation, which is crucial for tumor progression and metastasis. The aim of this study was to identify and validate a novel anoikis-related prognostic model for prostate cancer (PCa). METHODS: We collected a gene expression profile, single nucleotide polymorphism mutation and copy number variation (CNV) data of 495 PCa patients from the TCGA database and 140 PCa samples from the MSKCC dataset. We extracted 434 anoikis-related genes and unsupervised consensus cluster analysis was used to identify molecular subtypes. The immune infiltration, molecular function, and genome alteration of subtypes were evaluated. A risk signature was developed using Cox regression analysis and validated with the MSKCC dataset. We also identify potential drugs for high-risk group patients. RESULTS: Two subtypes were identified. C1 exhibited a higher level of CNV amplification, immune score, stromal score, aneuploidy score, homologous recombination deficiency, intratumor heterogeneity, single-nucleotide variant neoantigens, and tumor mutational burden compared to C2. C2 showed a better survival outcome and had a high level of gamma delta T cell and activated B cell infiltration. The risk signature consisting of four genes (HELLS, ZWINT, ABCC5, and TPSB2) was developed (area under the curve = 0.780) and was found to be an independent prognostic factor for overall survival in PCa patients. Four CTRP-derived and four PRISM-derived compounds were identified for high-risk patients. CONCLUSIONS: The anoikis-related prognostic model developed in this study could be a useful tool for clinical decision-making. This study may provide a new perspective for the treatment of anoikis-related PCa.

Single-double-band switchable optical circular polarizers based on surface plasmon resonance: publisher's note.

This publisher's note reports a correction in Appl. Opt.63, 1153 (2024)APOPAI0003-693510.1364/AO.513837.

Network pharmacology and molecular docking reveal the mechanisms of curcumin activity against esophageal squamous cell carcinoma.

Background: Curcumin (CUR), an effective traditional Chinese medicinal extract, displays good anti-cancer activity against various cancers. Nevertheless, the impacts and fundamental mechanisms of CUR to treat esophageal squamous cell carcinoma (ESCC) yet to be comprehensively clarified. This study examined the suppressive impacts of CUR on ESCC. Methods: For a comprehensive understanding of the effect of CUR in ESCC. The CUR targets and ESCC-related genes were identified respectively, and the intersection targets between CUR and ESCC were acquired. Then, we examined the intersection targets and discovered genes that were expressed differently in ESCC. Using DAVID, enrichment analyses were conducted on the targets of CUR-ESCC. The STRING database and Cytoscape v.3.9.1 were utilized to build networks for protein-protein interaction (PPI) and drug-target-pathway. Furthermore, the interactions between CUR and its core targets were confirmed by molecular docking studies. To confirm the effects of CUR on ESCC cells, in vitro experiments were finally conducted. Results: Overall, 47 potential CUR targets for ESCC treatment were identified. The KEGG pathway enrichment analysis identified 61 signaling pathways, primarily associated with the FoxO signaling, the cell cycle, cellular senescence, the IL-17 signaling pathway which play important roles in ESCC progression. In the PPI network and the docking results identified CHEK1 and CDK6 as the core targets that positively associated with ESCC survival. CUR arrested ESCC cells at the G2/M and S phases, as shown by flow cytometry. Colony formation and CCK8 assays showed that CUR can inhibit the proliferative ability of ESCC cells. The Transwell invasion results validated that CUR can significantly inhibit the invasion rates of ESCC cells. Conclusion: Collectively, these findings indicate that CUR exhibits pharmacological effects on multiple targets and pathways in ESCC.

Folic Acid Functionalized AQ4N/Gd@PDA Nanoplatform with Real-Time Monitoring of Hypoxia Relief and Enhanced Synergistic Chemo/Photothermal Therapy in Glioma.

Purpose: Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored. Methods: AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line. Moreover, the effectiveness of AGPF NPs in alleviating hypoxia was explored in tumor-bearing mice through photoacoustic imaging. In addition, the diagnosis and treatment effect of AGPF NPs were evaluated by magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) on orthotopic glioma mice respectively. Results: In vitro experiments showed that AGPF NPs had good dispersion, stability, and controlled release. AGPF NPs were internalized by cells through endocytosis, and could significantly reduce the survival rate of U87 cells and increase apoptosis under irradiation. In addition, we monitored blood oxygen saturation at the tumor site in real-time through photoacoustic imaging (PAI), and the results showed that synergistic mild-photothermal therapy/chemotherapy effectively alleviated tumor hypoxia. Finally, in vivo anti-tumor experiments have shown that synergistic therapy can effectively alleviate hypoxia and inhibit the growth of orthotopic gliomas. Conclusion: This work not only provides an effective means for real-time monitoring of the dynamic feedback between tumor hypoxia relief and therapeutic efficacy, but also offers a potential approach for the clinical treatment of gliomas.

A therapeutic ERCP in an only 5.9 kg infant with obstruction jaundice using JF-260V duodenoscope.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. CASE PRESENTATION: This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. CONCLUSIONS: In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Isthmin-1 promotes growth and progression of colorectal cancer through the interaction with EGFR and YBX-1.

While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis.

Synergistically Optimized Thermoelectric and Mechanical Properties of Mg3.2Bi1.5Sb0.5-SiC Composites.

Motivated by the surging demand for low-temperature waste heat harvesting, materials with both prominent thermoelectric and good mechanical properties are preferred in practical applications. In this present work, the composite exploration of Te-doped Mg3.2Bi1.5Sb0.5-x vol % nanosized SiC (x = 0, 0.05, 0.1, 0.2, and 0.5) was carried out, where nanosized SiC is physically dispersed in the matrix in the form of a second phase. SiC second phase compositing further optimized the matrix carrier concentration, resulting in a higher power factor in the service temperature range (the highest value from 28.9 to 31.7 µW cm-1 K-2), and the (ZT)ave from 0.91 to 0.96 compared with the matrix sample. In addition, the SiC second phase effectively enhanced the mechanical properties of composite materials, including flexural strength, microhardness, and modulus. Because of the simultaneous optimization of thermoelectric and mechanical properties, the overall performance of Te-doped Mg3.2Bi1.5Sb0.5-0.05 vol % SiC composite is leveraged to meet special requirements of power generation. It is expected that the addition of SiC should be broadly applicable to address the physical performance in other thermoelectric systems.

Association Between Liver Fibrosis Score and Diabetic Kidney Disease: A Retrospective Cross-Sectional Study of Hospitalized Patients.

OBJECTIVES: To investigate the association between liver fibrosis score and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). METHODS: A total of 897 hospitalized patients with T2DM were included in this study. Each patient completed DKD screening. Logistic regression analysis was used to assess the predictive value of non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) for the occurrence of DKD and risk for DKD progression, respectively. RESULTS: The prevalence of DKD and risk for its progression significantly increased with increasing NAFLD-FS risk category. DKD prevalence also increased with increasing FIB-4 risk category. Multivariate logistic regression analysis showed that the "high-risk" NAFLD-FS had a significantly higher risk of DKD (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.16-3.08) and risk for DKD progression (OR: 2.88, 95% CI: 1.23-6.78), and the "intermediate-risk" FIB-4 had a significantly higher risk of DKD (OR: 1.41, 95% CI: 1.00-1.98). Subgroup analysis showed that the association between NAFLD-FS and FIB-4 and DKD was significant in the female subgroup, whereas the association between the "high-risk" NAFLD-FS and risk for DKD progression was significant in the male subgroup. CONCLUSIONS: NAFLD-FS and FIB-4 are strongly associated with DKD and risk for DKD progression in patients with T2DM. Additionally, sexual dimorphism exists in this association.