Prediction of lymph node metastasis in patients with papillary thyroid cancer based on radiomics analysis and intraoperative frozen section analysis: A retrospective study.

INTRODUCTION: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). METHODS: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. RESULTS: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. CONCLUSION: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC.

Mucin-producing tumors of the ovary--preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Ethanol extract of Cyathulae Radix inhibits osteoclast differentiation and bone loss.

Cyathulae Radix, a traditional Chinese medicine and a common vegetable, boasts a history spanning millennia. It enhances bone density, boosts metabolism, and effectively alleviates osteoporosis-induced pain. Despite its historical use, the molecular mechanisms behind Cyathulae Radix's impact on osteoporosis remain unexplored. In this study, we investigated the effects and mechanisms of Cyathulae Radix ethanol extract (CEE) in inhibiting osteoporosis and osteoclastogenesis. Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks. Micro-computed tomography (micro-CT) assessed histomorphometric parameters, bone tissue staining observed distal femur histomorphology, and three-point bending tests evaluated tibia mechanical properties. Enzyme-linked immunosorbent assay (ELISA) measured serum estradiol (E2), receptor activator for nuclear factor B ligand (RANKL), and osteoprotegerin (OPG) levels. Osteoclastogenesis-related markers were analyzed via Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase (TRAP) staining, qRT-PCR, and WB assay. Compared with the ovariectomy (OVX) group, CEE treatment enhanced trabecular bone density, maximal load-bearing capacity, and various histomorphometric parameters. Serum E2 and OPG levels significantly increased, while Receptor activator of nuclear factor-κB (RANK) decreased in the CEE group. CEE downregulated matrix metallopeptidase 9 (MMP-9), Cathepsin K (CTSK), and TRAP gene and protein expression. In bone marrow macrophages (BMMs), CEE reduced mature osteoclasts, bone resorption pit areas, and MMP-9, CTSK, and TRAP expression during osteoclast differentiation. Compared with DMSO treatment, CEE markedly inhibited RANK, TNF receptor associated factor 6 (TRAF6), Proto-oncogene c-Fos (c-Fos), Nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expressions, and Extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), NF-kappa B-p65 (p65) phosphorylation in osteoclasts. In conclusion, CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis, potentially through modulating the Estrogen Receptor (ER)/RANK/NFATc1 signaling pathway.

Silent information regulator 2 deficiency exacerbates chronic cold exposure-induced colonic injury and p65 activation in mice.

Cold is a common stressor that threatens colonic health by affecting internal homeostasis. From the literature, Silent information regulator 2 (SIRT2) may have important roles during cold stress, but this conjecture requires investigation. To address this knowledge gap, we investigated the effects of SIRT2 on colonic injury in chronically cold-exposure mice. In a previous study, we showed that SIRT2 regulated p65 activation after cold exposure. In the current study, mice were exposed to 4 °C for 3 h/day for 3 weeks to simulate a chronic cold exposure environment. Chronic cold exposure shortened colon length, disrupted tight junctions in colonic epithelial tissue, and disordered colonic flora. Chronic cold exposure also increased p65 acetylation levels, promoted nuclear factor (NF)-κB activation, and increased the expression of its downstream pro-inflammatory factors, while SIRT2 knockdown aggravated the consequences of tissue structure disruption and increased inflammatory factors brought about by chronic cold exposure to some extent, but could alleviate the downregulation of colonic tight junction-related proteins to some extent. We also observed direct SIRT2 regulatory effects toward p65, and in Caco-2 cells treated with lipopolysaccharide (LPS), SIRT2 knockdown increased p65 acetylation levels and pro-inflammatory factor expression, while SIRT2 overexpression reversed these phenomena. Therefore, SIRT2 deletion exacerbated chronic cold exposure-induced colonic injury and p65 activation in mice. Mechanistically, p65 modification by SIRT2 via deacetylation may affect NF-κB signaling. These findings suggest that SIRT2 is a key target of colonic health maintenance under chronic cold exposure conditions.

Retraction: An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma.

Retraction of 'An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma' by Jinlong Shi et al., Nanoscale, 2017, 9, 8970-8981, https://doi.org/10.1039/C6NR08786H.

Ivabradine Alleviates Experimental Autoimmune Myocarditis-Mediated Myocardial Injury.

Ivabradine (IVA) reduces heart rate by inhibiting hyperpolarization-activated cyclic nucleotide-gated channels (HCNs), which play a role in the promotion of pacemaker activity in cardiac sinoatrial node cells. HCNs are highly expressed in neural and myocardial tissues and are involved in the modulation of inflammatory neuropathic pain. However, whether IVA exerts any effect on myocardial inflammation in the pathogenesis of heart failure is unclear. We employed single-cell RNA sequencing (scRNA-seq) in porcine cardiac myosin-induced experimental autoimmune myocarditis rat model to determine the effects and mechanisms of IVA. Lewis rats (n = 32) were randomly divided into the normal, control, high-dose-IVA, and low-dose-IVA groups. Heart rate and blood pressure were measured on days 0 and 21, respectively. Echocardiography was performed on day 22, and inflammation of the myocardium was evaluated via histopathological examination. Western blot was employed to detect the expression of HCN1-4, MinK-related protein 1 (MiRP1), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor-ß (TGF-ß). Furthermore, enzyme-linked immunosorbent assay was performed to measure serum IL-1, IL-6, and TNF-α. The relative mRNA levels of collagen I, collagen III, and α-smooth muscle actin (α-SMA) were determined via qRT-PCR. We found that IVA reduced the total number of cells infiltrated into the myocardium, particularly in the subset of fibroblasts, endocardia, and monocytes. IVA administration ameliorated cardiac inflammation and reduced collagen production. Results of the echocardiography indicated that left ventricular internal diameter at end-systole LVIDs increased whereas left ventricular ejection fraction and left ventricular fractional shortening decreased in the control group. IVA improved cardiac performance. The expression of HCN4 and MiRP1 protein and the level of serum IL-1, IL-6, and TNF-α were decreased by IVA treatment. In conclusion, HCNs and the helper proteins were increased in the profile of myocardial inflammation. HCNs may be involved in the regulation of myocardial inflammation by inhibiting immune cell infiltration. Our findings can contribute to the development of IVA-based combination therapies for the future treatment of cardiac inflammation and heart failure.

The Added Value of ADC-based Nomogram in Assessing the Depth of Myometrial Invasion of Endometrial Endometrioid Adenocarcinoma.

RATIONALE AND OBJECTIVES: To explore the potential value of the apparent diffusion coefficient (ADC)-based nomogram models in preoperatively assessing the depth of myometrial invasion of endometrial endometrioid adenocarcinoma (EEA). MATERIALS AND METHODS: Preoperative magnetic resonance imaging (MRI) of 210 EEA patients were retrospectively analyzed. ADC histogram metrics derive from the whole-tumor regions of interest. Univariate and multivariate analyses were used to screen the ADC histogram metrics and clinical characteristics for nomogram model building. The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of two radiologists without and with the assistance of models were calculated and compared. RESULTS: Two nomogram models were developed for predicting no myometrial invasion (NMI) and deep myometrial invasion (DMI) with area under the curves of 0.85 and 0.82, respectively. With the assistance of models, the overall accuracies were significantly improved [radiologist_1, 73.3% vs 86.2% (p = 0.001); radiologist_2, 80.0% vs 91.0% (p = 0.002)]. In determining NMI, the sensitivity and PPV were greatly improved but not significant for radiologist_1 (51.9% vs 77.8% and 46.7% vs 75.0%, p = 0.229 and 0.511), and under/near the significance level for radiologist_2 (59.3% vs 88.9% and 57.1% vs 82.8%, p = 0.041 and 0.065), while the specificity, accuracy, and NPV were significantly improved (all p < 0.001). In determining DMI, all sensitivity, specificity, accuracy, PPV, and NPV were significantly improved (all p < 0.001). CONCLUSION: The ADC-based nomogram models can improve the diagnostic performance of radiologist in preoperatively assessing the depth of myometrial invasion and facilitate optimizing clinical individualized treatment decisions.

Susceptibility to preoperative seizures in glioma patients with elevated homocysteine levels.

OBJECTIVE: Seizures are a common clinical presentation in patients with glioma and substantially impact patients' quality of life. Hyperhomocysteinemia is defined as abnormally high serum levels of homocysteine (Hcy) and is reportedly linked to susceptibility to various nervous system diseases. However, it remains unclear whether and how hyperhomocysteinemia and its associated genetic polymorphisms promote seizures in glioma patients. METHODS: We retrospectively reviewed all medical data from 127 patients with malignant gliomas, who underwent initial tumor resection by our team between July 2019 and June 2021 and had preoperative measurements of serum Hcy levels. According to whether they had at least one seizure before surgery, they were divided into the seizure and nonseizure groups. We also detected polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and measured intratumoral Hcy levels in these patients. RESULTS: Hyperhomocysteinemia was a susceptibility factor for preoperative seizures in glioma patients according to both univariate analyses (P < 0.001) and multivariate logistic regression analyses (OR 1.239, 95% CI 1.062-1.445, P = 0.007). Patients with the MTHFR C677T variant exhibited elevated serum Hcy levels (P = 0.027) and an increased prevalence of preoperative seizures (P = 0.019). Intratumoral Hcy levels were positively correlated with serum Hcy levels (R = 0.231, P = 0.046) and were elevated in patients with hyperhomocysteinemia (P = 0.031), the MTHFR C677T variant (P = 0.002) and preoperative seizures (P = 0.003). High intratumoral Hcy levels, rather than hyperhomocysteinemia or the MTHFR C677T variant, emerged as an independent risk factor for preoperative seizures (OR 1.303, 95% CI 1.015-1.673, P = 0.038). Furthermore, the effects of hyperhomocysteinemia on epileptic susceptibility were reduced to nonsignificance when intratumoral Hcy was controlled to the same level between groups. SIGNIFICANCE: Glioma patients with hyperhomocysteinemia and the MTHFR C677T variant were susceptible to preoperative seizures, suggesting their potential as biomarkers for the management of seizures in glioma patients. The elevation of intratumoral Hcy is a possible mechanism underlying this susceptibility.

A rare case of intracranial solitary fibrous tumor that is still alive after multiple surgical resections: a case report and review of the literature.

A Solitary Fibrous Tumor (SFT) is a rare, aggressive, and metastasis- and recurrence- prone mesenchymal tumor. In this case report and review, we describe a rare instance of intracranial SFT, discovered for the first time. It was discovered in 2008 and following total surgical removal, the pathology was categorized as hemangiopericytoma cell tumor (HPC) at the time by WHO tumor criteria. An imaging review 8 months after surgery revealed a tumor recurrence: combined radiation and gamma-knife therapy was continued throughout this time. The tumor did not metastasis until June 2018 when it presented in the pancreas with ruptured bleeding and a postoperative pathology was suggestive of SFT. Fortunately, the patient is still alive nearly 3 years after the 2020 surgery, after staged surgical resection and combined multimedia therapy, with no imaging or clinical evidence of a recurrent intracranial primary lesions. To our knowledge, there is no previous record of using a combined treatment modality for Intracranial Solitary Fibrous Tumor (ISFT). Combined with an account of the patient's experience, we empirically describe a combined approach with a preference for gross-total resection (GTR), supplemented by multimodal assistance with stereotactic (radiotherapy), gamma knife (GK), molecular targeting, and immunization for patients admitted acutely, with accurate preoperative identification and aggressive management after intraoperative case response to maximize treatment of recurrent ISFT and improve prognosis. We recommend multimodal management for SFT with prolonged-term recurrence and metastases, both for the control benefits of GTR, RT, or GK for local recurrence and for the positive prognosis of targeted and immune metastases.

Effectiveness of oncology nurse navigator on the incidence of postoperative pulmonary complications in gastric cancer patients undergoing radical gastrectomy.

BACKGROUND: Management of postoperative pulmonary complications (PPCs) can be challenging in gastric cancer patients undergoing radical gastrectomy and is always associated with poor prognosis. Even though oncology nurse navigator (ONN) provide effective and critical individualized care to patients, little is known about their impact on the occurrence of PPCs in gastric cancer patients. This study aimed to determine whether ONN decreases the incidence of PPCs in gastric cancer patients. METHODS: This was a retrospective review in which data for gastric cancer patients at one centre was evaluated before and after an ONN hired. An ONN was introduced to patients at their initial visit to manage pulmonary complications throughout treatment. The research was conducted from 1 August 2020 to 31 January 2022. The study participants were divided into the non-ONN group (from 1 August 2020 to 31 January 2021) and the ONN group (from 1 August 2021 to 31 January 2022). The incidence and severity of PPCs between the groups were then compared. RESULTS: ONN significantly decreased the incidence of PPCs (15.0% vs. 9.8%) (OR = 2.532(95% CI: 1.087-3.378, P = 0.045)), but there was no significant difference in the components of PPCs including pleural effusion, atelectasis, respiratory infection, and pneumothorax. The severity of PPCs was also significantly higher in the non-ONN group (p = 0.020). No significant statistical difference was observed for the major pulmonary complications ([Formula: see text] 3) between the two groups (p = 0.286). CONCLUSIONS: Role of ONN significantly decrease the incidence of PPCs in gastric cancer patients undergoing radical gastrectomy.

Mechanism of lnRNA-ICL involved in lung cancer development in COPD patients through modulating microRNA-19-3p/NKRF/NF-κB axis.

The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.

Clinical and Pathological Features of Hydroa Vacciniforme-Like Lymphoproliferative Disorder Along with Risk Factors Indicating Poor Prognosis.

Purpose: To examine the clinical and pathological features, laboratory markers, therapeutic options and risk factors indicating poor prognosis of hydroa vacciniforme-like lymphoproliferative disorder (HVLPD). Patients and Methods: Seven patients with HVLPD had their clinical and pathological data collected. Immunohistochemical staining, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization experiments, T-cell receptor (TCR) gene rearrangement, RT-PCR tests and the Elisa assay were carried out. Results: The main clinical manifestations were papulovesicular lesions and ulcers on the face, neck, or trunk. Five cases had systemic symptoms. Three of the deceased patients had significant facial edema, deep body necrosis, and ulceration. The pathological results demonstrated that lymphocytes infiltrated blood vessels and sweat glands in addition to the dermis and subcutaneous tissues. All patients tested positive for CD3 and EBER. Six cases tested positive for TCRßF1, but none tested positive for TCRδ. TCRγ monoclonal rearrangement, strongly positive expression of TIA-1 and a Ki67 proliferation index of 40% occurred in 3 fatal cases. When compared to the survival group, the plasma EBV DNA in the deceased group was considerably higher (P<0.05). IFN-γ and TNF-α cytokine levels in patients were higher than in the control group, particularly in the deceased group (P<0.05). The skin lesions on all patients recovered quickly underwent conservative care. Nonetheless, 3 patients passed away as the disease progressed in its latter stages. Conclusion: In our cases, the main infiltrating cells were T cells and the dominant lymphocyte subclass was αßT cells. A significant increase in lgE level, plasma EBV DNA, IFN-γ, and TNF-α cytokine levels, decreased hemoglobin level, strongly positive expression of TIA-1, high Ki67 proliferation index, and positive TCR gene rearrangement are all indicators of a poor prognosis.

Ferrous sulfate reverses cerebral metabolic abnormality induced by minimal hepatic encephalopathy.

Orally administered ferrous iron was previously reported to significantly improve the cognition and locomotion of patients with minimal hepatic encephalopathy (MHE). However, the metabolic mechanisms of the therapeutic effect of ferrous iron are unknown. In this study, MHE was induced in rats by partial portal vein ligation (PPVL), and was treated with ferrous sulfate. The Morris water maze was used to evaluate the cognitive condition of the rats. The metabolites observed by NMR and validated by liquid chromatography-mass spectrometry were defined as the key affected metabolites. The enzyme activities and trace element contents in the rat brains were also investigated. The Mn content was found to be increased but the ferrous iron content decreased in the cortex and striatum in MHE. Decreased oxoglutarate dehydrogenase activity and increased glutamine synthetase (GS) and pyruvate carboxylase (PC) activity were observed in the cortex of MHE rats. Decreased pyruvate dehydrogenase activity and increased GS and PC activity were observed in the striatum of MHE rats. The levels of BCAAs and taurine were significantly decreased, and the contents of GABA, lactate, arginine, aspartate, carnosine, citrulline, cysteine, glutamate, glutamine, glycine, methionine, ornithine, proline, threonine and tyrosine were significantly increased. These metabolic abnormalities described above were restored after treatment with ferrous sulfate. Pathway enrichment analysis suggested that urea cycle, aspartate metabolism, arginine and proline metabolism, glycine and serine metabolism, and glutamate metabolism were the major metabolic abnormalities in MHE rats, but these processes could be restored and cognitive impairment could be improved by ferrous sulfate administration.

PRMT5/FGFR3/AKT Signaling Axis Facilitates Lung Cancer Cell Metastasis.

Objectives: This study aims to investigate the function of the protein arginine methyltransferase 5 (PRMT5) and fibroblast growth factor receptor 3 (FGFR3)/Akt signaling axis in the epithelial-mesenchymal transition (EMT) of human lung cancer. Methods: The mRNA and protein expression levels of PRMT5, FGFR3, p-Akt, and EMT markers are determined by quantitative real-time PCR and Western blotting, respectively; the expression and localization of PRMT5, p-Akt, and proliferating cell nuclear antigen are detected by immunofluorescence; the human lung cancer cell proliferation is measured by MTS assay. Results: PRMT5 and FGFR3 are highly expressed in human lung cancer tissues and are closely related to lymphatic metastasis. Moreover, down-regulation of PRMT5 by lentivirus-mediated shRNAs or inhibition of PRMT5 by specific inhibitors attenuates FGFR3 expression, Akt phosphorylation, and lung cancer cell proliferation. Further studies show that silencing PRMT5 impairs EMT-related markers, including vimentin, collagen I, and ß-catenin. Conversely, ectopic expression of PRMT5 increases FGFR3 expression, Akt phosphorylation, and EMT-related markers, suggesting that PRMT5 regulates metastasis probably through the FGFR3/Akt signaling axis. Conclusion: PRMT5/FGFR3/Akt signaling axis controls human lung cancer progression and metastasis and also implies that PRMT5 may serve as a prognostic biomarker and therapeutic candidate for treating lung cancer.

Impaired long-term anti-HBs responses in choronic hepatitis C patients: Results from a five-year follow-up study with healthy control.

Although hepatitis B virus (HBV) vaccination is recommended for hepatitis C virus (HCV)-infected individuals to avoid HBV superinfection, the persistence of their humoral and cell-mediated immunity responses to HBV vaccination is still under investigation. Patients with chronic hepatitis C (CHC) and matched healthy controls, who completed three doses of hepatitis B vaccine (HepB) in 2014, were followed up five years later. One booster dose of HepB was given to those with antibody against hepatitis B surface antigen (anti-HBs) lower than 10mIU/mL. Anti-HBs was tested at follow-up and on the 14th day after the booster dose, as well as HBsAg specific spot-forming cells of interferon γ and interleukin (IL) 2, 4, 5, and 6. At five years, only 56.58% of the CHC patients had sero-protective titers (≥10mIU/mL) of anti-HBs, compared to 70.83% in the controls (P < .05). Similarly, the geometric mean concentration (GMC) of anti-HBs in CHC patients was significantly lower than that in controls (16.95 vs 37.34 mIU/mL, P < .05). After the booster, both GMC and the rate of anamnestic response increased to a very high level in the two groups and the difference between them disappeared (P > .05). Multivariable analysis showed that HCV infection was an independent predictor factor to anti-HBs level at follow-up. HBsAg specific IL-6 was stronger in the CHC patients compared to the controls (P < .05). The data indicate that the durability of protective anti-HBs is poorer in CHC patients compared to healthy individuals, and impaired long-term anti-HBs responses might be associated with the increased HBsAg specific IL-6 responses.

Development of a prediction model for gross residual in high-grade serous ovarian cancer by combining preoperative assessments of abdominal and pelvic metastases and multiparametric MRI.

RATIONALE AND OBJECTIVES: To preoperatively predict residual tumor (RT) in patients with high-grade serous ovarian carcinoma (HGSOC) via a radiomic-clinical nomogram. METHODS: A total of 128 patients with advanced HGSOC were enrolled (training cohort: n=106; validation cohort: n=22). Serum cancer antigen-125 (CA125), serum human epididymis protein 4 (HE-4) level, and neutrophil-to-lymphocyte ratio (NLR) were obtained from the medical records. Metastases in abdomen and pelvis (MAP) of HGSOC patients was evaluated and scored based on preoperative abdominal and pelvic enhanced CT, MRI and/or PET-CT. A volume of interest (VOI) of each tumor was manually contoured along the boundary slice-by-slice. Radiomic features were extracted from the T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) images. Univariate and multivariate analyses were used to determine the independent predictors of RT status. Least absolute shrinkage and selection operator (LASSO) logistic regression was performed to select optimal features and construct radiomic models. A radiomic-clinical nomogram incorporating radiomic signature and clinical parameters was developed and evaluated in training and validation cohorts. RESULTS: MAP score (p = 0.002), HE-4 level (p = 0.001) and NLR (p = 0.008) were independent predictors of RT status. The final radiomic-clinical nomogram showed satisfactory prediction performance in training (AUC = 0.936), cross validation (AUC = 0.906) and separate validation cohorts (AUC = 0.900), and fitted well in calibration curves (p > 0.05). Decision curve further confirmed the clinical application value of the nomogram. CONCLUSION: The proposed MRI-based radiomic-clinical nomogram achieved excellent preoperative prediction of the RT status in HGSOC.

Single-cell transcriptional profiling uncovers the association between EOMES+CD8+ T cells and acquired EGFR-TKI resistance.

Acquired resistance to tyrosine kinase inhibitors (TKIs) is reportedly inevitable in lung cancers harboring epidermal growth factor receptor (EGFR) mutations, emphasizing the need for novel approaches to predict EGFR-TKI resistance for clinical monitoring and patient management. This study identified a significant increase in eomesodermin (EOMES)+CD8+ T cells in the TKI-resistant patients, which was correlated with poor survival. The increase in EOMES+CD8+ T cells was further confirmed in both tissue samples and peripheral blood of patients with TKIs resistance. The integrated analysis of pseudotime and Gene set variation showed that the increase in EOMES+CD8+ T cells may be attributed to TRM T cell conversion and metabolic reprogramming. Overall, this work suggested an association between the increased number of EOMES+CD8+ T cells and acquired TKI drug resistance, supporting the utility of EOMES+CD8+ T cells as a biomarker for TKI treatment response.

Magnetic Resonance Imaging and Diffusion Weighted Imaging-Based Histogram in Predicting Mesenchymal Transition High-Grade Serous Ovarian Cancer.

RATIONALE AND OBJECTIVES: To investigate the value of magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) findings in predicting mesenchymal transition (MT) high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: Patients with HGSOC were enrolled from May 2017 to December 2020, who underwent pelvic MRI including DWI (b = 0,1000 s/mm2) before surgery, and were assigned to the MT HGSOC or non-MT HGSOC group according to histopathology results. Clinical characteristics and MRI features including DWI-based histogram metrics were assessed and compared between the two groups. Univariate and multivariate analyses were performed to identify the significant variables associated with MT HGSOC - these variables were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: A total of 81 consecutive patients were recruited for pelvic MRI before surgery, including 37 (45.7%) MT patients and 44 (54.3%) non-MT patients. At univariate analysis, the features significantly related to MT HGSOC were identified as absence of discrete primary ovarian mass, pouch of Douglas implants, ovarian mass size, tumor volume, mean, SD, median, and 95th percentile apparent diffusion coefficient (ADC) values (all p < 0.05). At multivariate analysis, the absence of discrete primary ovarian mass {odds ratio (OR): 46.477; p = 0.025}, mean ADC value ≤ 1.105 (OR: 1.023; p = 0.009), and median ADC value ≤ 1.038 (OR: 0.982; p = 0.034) were found to be independent risk factors associated with MT HGSOC. The combination of all independent criteria yielded the largest AUC of 0.82 with a sensitivity of 83.87% and specificity of 66.67%, superior to any of the single predictor alone (p ≤ 0.012). The predictive C-index nomogram performance of the combination was 0.82. CONCLUSION: The combination of absence of discrete primary ovarian mass, lower mean ADC value, and median ADC value may be helpful for preoperatively predicting MT HGSOC.