Nomogram prediction of the 70-gene signature (MammaPrint) binary and quartile categorized risk using medical history, imaging features and clinicopathological data among Chinese breast cancer patients.

BACKGROUND: The 70-gene signature (70-GS, MammaPrint) test has been recommended by the main guidelines to evaluate prognosis and chemotherapy benefit of hormonal receptor positive human epidermal receptor 2 negative (HR + /Her2-) early breast cancer (BC). However, this expensive assay is not always accessible and affordable worldwide. Based on our previous study, we established nomogram models to predict the binary and quartile categorized risk of 70-GS. METHODS: We retrospectively analyzed a consecutive cohort of 150 female patients with HR + /Her2- BC and eligible 70-GS test. Comparison of 40 parameters including the patients' medical history risk factors, imaging features and clinicopathological characteristics was performed between patients with high risk (N = 62) and low risk (N = 88) of 70-GS test, whereas risk calculations from established models including Clinical Treatment Score Post-5 years (CTS5), Immunohistochemistry 3 (IHC3) and Nottingham Prognostic Index (NPI) were also compared between high vs low binary risk of 70-GS and among ultra-high (N = 12), high (N = 50), low (N = 65) and ultra-low (N = 23) quartile categorized risk of 70-GS. The data of 150 patients were randomly split by 4:1 ratio with training set of 120 patients and testing set 30 patients. Univariate analyses and multivariate logistic regression were performed to establish the two nomogram models to predict the the binary and quartile categorized risk of 70-GS. RESULTS: Compared to 70-GS low-risk patients, the high-risk patients had significantly less cardiovascular co-morbidity (p = 0.034), more grade 3 BC (p = 0.006), lower progesterone receptor (PR) positive percentage (p = 0.007), more Ki67 high BC (≥ 20%, p < 0.001) and no significant differences in all the imaging parameters of ultrasound and mammogram. The IHC3 risk and the NPI calculated score significantly correlated with both the binary and quartile categorized 70-GS risk classifications (both p < 0.001). The area under curve (AUC) of receiver-operating curve (ROC) of nomogram for binary risk prediction were 0.826 (C-index 0.903, 0.799-1.000) for training and 0.737 (C-index 0.785, 0.700-0.870) for validation dataset respectively. The AUC of ROC of nomogram for quartile risk prediction was 0.870 (C-index 0.854, 0.746-0.962) for training and 0.592 (C-index 0.769, 0.703-0.835) for testing set. The prediction accuracy of the nomogram for quartile categorized risk groups were 55.0% (likelihood ratio tests, p < 0.001) and 53.3% (p = 0.04) for training and validation, which more than double the baseline probability of 25%. CONCLUSIONS: To our knowledge, we are the first to establish easy-to-use nomograms to predict the individualized binary (high vs low) and the quartile categorized (ultra-high, high, low and ultra-low) risk classification of 70-GS test with fair performance, which might provide information for treatment choice for those who have no access to the 70-GS testing.

Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway.

BACKGROUND: Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. METHODS: We analyzed data from TCGA and METABRIC and established an immunity-related gene prognosis model for breast cancer. The SDC1 expression in tumor and cancer associated fibroblasts (CAFs) was then observed in 282 TNBC patients by immunohistochemistry. The effects of SDC1 on MDA-MB-231 proliferation, migration and invasion were evaluated. Qualitative real-time PCR and western blotting were performed to identify mRNA and protein expression, respectively. RESULTS: SDC1, as a key immunity-related gene, was significantly correlated with survival in the TCGA and METABRIC databases, while SDC1 was found to be highly expressed in TNBC in the METABRIC database. In the TNBC cohort, patients with high SDC1 expression in tumor cells and low expression in CAFs had significantly lower disease-free survival (DFS) and fewer tumor-infiltrating lymphocytes (TILs). The downregulation of SDC1 decreased the proliferation of MDA-MB-231, while promoting the migration of MDA-MB-231 cells by reducing the gene expression of E-cadherin and TGFb1 and activating p-Smad2 and p-Smad3 expression. CONCLUSION: SDC1 is a key immunity-related gene that is highly expressed TNBC patients. Patients with high SDC1 expression in tumors and low expression in CAFs had poor prognoses and low TILs. Our findings also suggest that SDC1 regulates the migration of MDA-MB-231 breast cancer cells through a TGFb1-Smad and E-cadherin-dependent mechanism.

PATHOLOGIC STUDY OF UNTREATED INTRARETINAL GLIOSIS SURGICALLY EXCISED VIA PARS PLANA VITRECTOMY.

PURPOSE: To evaluate the pathologic process of intraretinal glioses by investigating mass tissues resected from untreated eyes with intraretinal glioses. METHODS: Five patients with intraretinal gliosis without previous conservative treatment were included. All patients underwent pars plana vitrectomy. The mass tissues were excised and processed for the pathologic study. RESULTS: During surgery, it was observed that the intraretinal gliosis mainly affected the neuroretina and the retinal pigment epithelium was not affected. Pathologic examination revealed that all intraretinal glioses consisted of different proportions of hyaline vessels and hyperplastic spindle-shaped glial cells. In one case, the intraretinal gliosis was mainly composed of hyaline vascular components. In another case, the intraretinal gliosis showed a predominance of glial cells. The intraretinal glioses in the other three cases had vascular and glial components. The proliferated vessels showed different amounts of collagen deposits against different backgrounds. Vascularized epiretinal membrane was found in some intraretinal glioses. CONCLUSION: Intraretinal glioses affected the inner retinal layer. Hyaline vessels were the most characteristic pathologic changes; the proportion of proliferative glial cells varied in different intraretinal glioses. The natural course of intraretinal gliosis may involve the proliferation of abnormal vessels in the early stage, which then gradually become scarred and are replaced by glial cells.

Long-term survival of screen-detected synchronous and metachronous bilateral non-palpable breast cancer among Chinese women: a hospital-based study (2003-2017).

PURPOSE: Screen-detected unilateral non-palpable breast cancer (NPBC) shows favorable prognosis, whereas bilateral breast cancer (BBC), especially synchronous BBC (SBBC) manifests worse survival than unilateral breast cancer (BC). It remains unclear whether screen-detected bilateral NPBC has compromised survival and requires intensified treatment or favorable prognosis and needs de-escalating therapy. METHODS: From 2003 to 2017, 1,075 consecutive NPBC patients were retrospectively reviewed. There were 988 patients with unilateral NPBC (UniNPBC), and 87 patients with ipsilateral NPBC + any contralateral BC [(N + AnyContra) PBC], including 32 patients with bilateral NPBC (BiNPBC) and 55 patients with ipsilateral NPBC + contralateral palpable cancer [(N + Contra) PBC]. Median follow-up time was 91 (48-227) months. Clinicopathological characteristics were compared between UniNPBC and BBC, whereas relapse-free survival (RFS) and overall survival (OS) among BBC subgroups. RFS and OS factors of BBC were identified. RESULTS: Compared to UniNPBC, patients with screen-detected bilateral BC had more invasive (85.1%, 74.8%), ER negative (26.4%, 17.1%), PR negative (36.8%, 23.5%), triple-negative (21.6%, 8.5%) BC as well as less breast conserving surgery (17.2%, 32.4%), radiotherapy (13.8%, 32.0%) and endocrine therapy (71.3%, 83.9%). 10 year RFS and OS rates of (N + AnyContra) PBC (72.8%, 81.5%), (N + Contra) PBC (60.6%, 73.9%), and synchronous (N + Contra) PBC (58.1%, 70.1%) were significantly compromised compared to UniNPBC (91.0%, 97.2%). RFS factors of BBC included pN3 (p = 0.048), lymphovascular invasion (p = 0.008) and existence of contralateral palpable interval BC (p = 0.008), while the OS relevant factor was pN3 (p = 0.018). CONCLUSION: Screen-detected bilateral NPBC including SynBiNPBC and MetaBiNPBC showed good prognosis as UniNPBC so that the therapy of BiNPBC could be de-escalated and optimized according to UniNPBC. Contrarily, screen-detected ipsilateral NPBC with contralateral palpable BC [(N + Contra) PBC] manifested unfavorable survival worse than UniNPBC and synchronous (N + Contra) PBC had the worst survival among all subgroups, implying that these were actually bilateral interval BC and required intensified treatment.

Artificial intelligence for histological subtype classification of breast cancer: combining multi-scale feature maps and the recurrent attention model.

AIMS: The aim of this study was to apply a two-stage deep model combining multi-scale feature maps and the recurrent attention model (RAM) to assist with the pathological diagnosis of breast cancer histological subtypes by the use of whole slide images (WSIs). METHODS AND RESULTS: In this article, we propose an integrated framework combining multi-scale feature maps from Inception V3 and the recurrent attention model to classify the six histological subtypes of breast cancer. This model was trained with 194 WSIs, and on 63 validation WSIs the model achieved accuracies of 0.9030 for patch-level classification and 0.8889 for WSI-level classification. In the testing stage, a total of 65 WSIs were used to achieve an accuracy of 0.8462 without any form of data curation. The t-distributed stochastic neighbour embedding showed that features extracted by the feature network of the RAM from WSIs of the same category can cluster together after training, and the visualization of decision steps showed that the decision-making glimpses are focused on the middle tumour area of an example from test WSIs. Finally, the false classification patches indicated that the morphological similarities between tumour tissues of different subtypes or non-tumour tissues and tumour tissues in patches might contribute to misclassification. CONCLUSIONS: This model can imitate the diagnostic process of pathologists, pay attention to a series of local features on the pathology image, and summarize related information, in order to accurately classify breast cancer into its histological subtypes, which is important for treatment and prognosis.

Prognostic significance of different molecular typing methods and immune status based on RNA sequencing in HR-positive and HER2-negative early-stage breast cancer.

BACKGROUND: This study was conducted to evaluate the prognostic significance of different molecular typing methods and immune status based on RNA sequencing (RNA-seq) in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR + /HER2-) early-stage breast cancer and develop a modified immunohistochemistry (IHC)-based surrogate for intrinsic subtype analysis. METHODS: The gene expression profiles of samples from 87 HR + /HER2- early-stage breast cancer patients were evaluated using the RNA-seq of Oncotype Dx recurrence score (RS), PAM50 risk of recurrence (ROR), and immune score. Intrinsic tumor subtypes were determined using both PAM50- and IHC-based detection of estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor, and cytokeratins 14 and 5/6. Prognostic variables were analyzed through Cox regression analysis of disease-free survival (DFS) and distant metastasis-free survival (DMFS). RESULTS: Survival analysis showed that ROR better predicted recurrence and distant metastasis compared to RS (for DFS: ROR, P = 0.000; RS, P = 0.027; for DMFS, ROR, P = 0.047; RS, P = 0.621). Patients with HR + /HER2- early-stage breast cancer was classified into the luminal A, luminal B, HER2-enriched, and basal-like subtypes by PAM50. Basal-like subgroups showed the shortest DFS and DMFS. A modified IHC-based surrogate for intrinsic subtype analysis improved the concordance with PAM50 from 66.7% to 73.6%, particularly for basal-like subtype identification. High level of TILs and high expression of immune genes predicted poor prognosis. Multi-factor Cox analysis showed that IHC-based basal-like markers were the only independent factors affecting DMFS. CONCLUSIONS: Prognosis is better evaluated by PAM50 ROR in early-stage HR + /HER2- breast cancer and significantly differs among intrinsic subtypes. The modified IHC-based subtype can improve the basal-like subtype identification of PAM50. High immunity status and IHC-based basal-like markers are negative prognostic factors.

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis.

BACKGROUND: Intercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation. METHODS: Cancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker. RESULTS: We found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641. CONCLUSION: The findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment. Video Abstract.

Prognostic significance of branched-chain amino acid transferase 1 and CD133 in triple-negative breast cancer.

BACKGROUND: Previous studies have shown that branched-chain amino acid transferase 1 (BCAT1) is associated with tumour progression in triple-negative breast cancer (TNBC). Furthermore, CD133 has emerged as a novel cancer stem cell marker for indicating tumour progression. However, the prognostic significance of these two markers remains to be verified. This study was conducted to investigate the correlation between BCAT1 and CD133 expression and clinicopathological features, as well as the prognosis of patients with TNBC. METHODS: The study cohort included 291 patients with TNBC. Tissue microarrays were constructed for both cancer and normal tissues. The expression of BCAT1 and CD133 was detected by immunohistochemical staining, and the levels were evaluated using an H-scoring system. Cut-off points for BCAT1 and CD133 expression were determined using receiver operating characteristic curves. RESULTS: The median follow-up time for the study participants was 68.73 months (range: 1.37-103.6 months). The 5-year disease-free survival (DFS) and overall survival (OS) rates of the 291 patients with TNBC were 72.51 and 82.47%, respectively. Higher levels of BCAT1 and CD133 expression independently indicated shorter DFS and OS. High levels of both BCAT1 and CD133 expression were detected in 36 (12.37%) patients, who had significantly shorter DFS and OS (both P < 0.001) compared to other patients. CONCLUSION: BCAT1 and CD133 can be considered as biomarkers with prognostic significance for TNBC.

Granular cell tumor presenting as an intraocular mass: a case report.

BACKGROUND: Granular cell tumor (GCT) can arise in any location in the body and present as a solitary, slow-growing, painless mass. However, GCT rarely affects the orbit. We report a Chinese girl who presented with an intraocular mass, and in whom a biopsy led to a diagnosis of GCT. CASE PRESENTATION: A 5-year-old Chinese girl exhibited exotropia in her right eye for 2 years and had been losing her vision for 6 months. The visual acuity in the right eye revealed no light perception. A fundus examination showed a large, yellowish-white, elevated, subretinal mass lesion in front of and inferior to the disc, with hemi-inferior-quadrant retinal detachment. The retina was greyish-yellow with scattered yellow spots. A vitrectomy with neoplasm resection was performed. A histopathologic examination revealed a GCT. The tumor cells were positive for CD68, NSE, S-100, and CD163 expression but negative for GFAP, Syn, and CD123 expression. The Ki-67 index was 1%. The right eye remained stable with visual acuity of no light perception at a 2-years follow-up. CONCLUSION: Intraocular GCT can present as a yellow-white solid mass with no calcification. Although intraocular GCT is very rare, it can lead to devastating visual loss. Intraocular GCT should be kept in mind and considered in clinical practice.

Evaluating differences in forest fragmentation and restoration between western natural forests and southeastern plantation forests in the United States.

Changes in forest ecosystem structure and functions are considered some of the research issues in landscape ecology. In this study, advancing Forman's theory, we considered five spatially explicit processes associated with fragmentation, including perforation, dissection, subdivision, shrinkage, and attrition, and two processes associated with restoration, i.e., increment and expansion processes. Following this theory, a forest fragmentation and restoration process model that can detect the spatially explicit processes and ecological consequences of forest landscape change was developed and tested in the current analysis. Using the National Land Cover Databases (2001, 2006 and 2011), the forest fragmentation and restoration process model was applied to US western natural forests and southeastern plantation forests to quantify and classify forest patch losses into one of the four fragmentation processes (the dissection process was merged into the subdivision process) and to classify the newly gained forest patches based on the two restoration processes. At the same time, the spatio-temporal differences in fragmentation and restoration patterns and trends between natural forests and plantations were further compared. Then, through overlaying the forest fragmentation/restoration processes maps with targeting year land cover data and land ownership vectors, the results from forest fragmentation and the contributors to forest restoration in federal and nonfederal lands were identified. Results showed that, in natural forests, the forest change patches concentrated around the urban/forest, cultivated/forest, and shrubland/forest interfaces, while the patterns of plantation change patches were scattered sparsely and irregularly. The shrinkage process was the most common type in forest fragmentation, and the average size was the smallest. Expansion, the most common restoration process, was observed in both natural forests and plantations and often occurred around the previous expansion or covered the previous subdivision or shrinkage processes. The overall temporal fragmentation pattern of natural forests had a "perforation-subdivision/shrinkage-attrition" pathway, which corresponded to Forman's landscape fragmentation rule, while the plantation forests did not follow the rule strictly. The main land cover types resulted from forest fragmentation in natural forests and plantation forests were shrubland and herbaceous, mainly through subdivision and shrinkages process. The processes and effects of restoration of plantation forests were more diverse and efficient, compared to the natural forest, which were simpler with a lower regrowth rate. The fragmentation mostly occurred in nonfederal lands. In natural forests, forest fragmentation pattern differed in different land tenures, yet plantations remained the same in federal and nonfederal lands.

c-Met and ERß expression differences in basal-like and non-basal-like triple-negative breast cancer.

Basal-like breast cancer (BLBC) and triple-negative breast cancer (TNBC) are two entities of breast cancer that share similar poor prognosis. Even though both cancers have overlaps, there are still some differences between those two types. It has been reported that the c-Met high expression was associated with poor prognosis not only in breast cancer but also in many other cancers. The role of ERß in pathogenesis and treatment of breast cancer has remained controversial. In this study, we firstly distinguished basal-like from nonbasal-like cancer patients in TNBC patients using CK5/6 and EGFR as markers and next determined the relationship of basal-like breast cancer with c-Met or ERß expression levels and prognosis in TNBC patients. One hundred twenty-seven patients who had been diagnosed with TNBC were enrolled. The clinical and pathological characteristics of the patients were recorded. The expression of EGFR, CK5/6, ERß, and c-Met were evaluated with immunohistochemical methods using paraffin blocks. The median age of patients was 50.7 years. CK5/6 immunopositivity was 31.5 % (40/127), and EGFR was 40.2 % (51/127). Of the TNBC cases, 55.1 % (71/127) were positive for either CK5/6 or EGFR and were thus classified as basal-like breast cancer. C-Met (P < 0.001) and ERß (P = 0.002) overexpression, small tumor sizes, a ductal subtype, and high-grade tumor were significantly correlated with BLBC. High c-Met expression was detected in 43.3 % patients. Metastatic lymph nodes and tumor size (>5 cm), which were both important prognostic predictors, were significantly associated with recurrence and mortality. BLBC typically demonstrates a unique profile. CK5/6 and EGFR expression combination indicates a higher basal-like phenotype possibility. The expression of c-Met and ERß were significantly related to the basal-like phenotype. The classical markers, lymph node metastasis, and tumor size were found to have important prognostic value. However, high c-Met expression and basal-like phenotypes did not show a direct correlation with poor prognosis.

IgG4-related kidney disease from the renal pelvis that mimicked urothelial carcinoma: a case report.

BACKGROUND: IgG4-related kidney disease is a comprehensive term for renal lesions associated with IgG4-related disease, which mainly manifests as plasma cell-rich tubulointerstitial nephritis with increased IgG4+ plasma cells and fibrosis. IgG4-related kidney disease in the renal pelvis is rare. CASE PRESENTATION: We describe a 53-year-old Asian woman who was referred to our hospital with a space-occupying renal lesion discovered by medical examination. A physical examination and laboratory evaluation revealed no significant abnormalities. Computed tomography scans showed a soft-tissue mass with an irregular border and mild homogeneous enhancement in the right renal pelvis and calyces. A positron emission tomography/computed tomography scan revealed soft-tissue density shadows with increased radionuclide uptake. To investigate a suspected pelvic carcinoma, a right ureteronephrectomy was performed. A pathologic examination of the renal sections showed a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, with fibrosis beneath the urothelial epithelium of the renal pelvis. Postoperatively, the serum IgG4 level was significantly elevated. The patient was diagnosed with IgG4-related kidney disease. CONCLUSION: We present a case of IgG4-related kidney disease mimicking urothelial carcinoma in the renal pelvis. When a buried and solitary hypovascular tumor is detected in the kidney, we must consider IgG4-related kidney disease as a differential diagnosis. Accordingly, elevated serum IgG4, radiologic findings, and pathologic examination may improve the diagnosis.

Photosynthetic and Self-Draining Biohybrid Dressing for Accelerating Healing of Diabetic Wound.

Wound healing is a well-orchestrated progress associated with angiogenesis, epithelialization, inflammatory status, and infection control, whereas these processes are seriously disturbed in diabetic wounds. In this study, a biohybrid dressing integrating the inherent ability of Bromeliad leaf (photosynthesis and self-draining) with the therapeutic effect of artificial materials (glucose-degrading and ROS-scavenging) is presented. The dressing consists of double-layered structures as follows: 1) Outer layer, a Bromeliad leaf substrate full of alginate hydrogel-immobilized glucose oxidase (GOx@Alg@Bromeliad substrate, abbreviated as BGA), can generate oxygen to guarantee the GOx-catalyzed glucose oxidation by photosynthesis, reducing local hyperglycemia to stabilize hypoxia inducible factor-1 alpha (HIF-1α) for angiogenesis and producing hydrogen peroxide for killing bacteria on the surface of wound tissue. The sophisticated structure of the leaf drains excessive exudate away via transpiration-mimicking, preventing skin maceration and impeding bacterial growth. 2) Inner layer, microneedles containing catalase (CAT-HA MNs, abbreviated as CHM), reduces excessive oxidative stress in the tissue to promote the proliferation of fibroblasts and inhibits proinflammatory polarization of macrophages, improving re-epithelialization of diabetic wounds. Together, the biohybrid dressing (BGA-CHM, abbreviated as BCHM) can enhance angiogenesis, strengthen re-epithelialization, alleviate chronic inflammation, and suppress bacterial infection, providing a promising strategy for diabetic wound therapy.

Improvement of physicochemical properties and quercetin delivery ability of fermentation-induced soy protein isolate emulsion gel processed by ultrasound.

This study aimed to investigate the effects of ultrasonic treatment at different powers on the physicochemical properties, microstructure and quercetin delivery capacity of fermentation-induced soy protein isolate emulsion gel (FSEG). The FSEG was prepared by subjecting soy protein isolate (SPI) emulsion to ultrasonic treatment at various powers (0, 100, 200, 300, and 400 W), followed by lactic acid bacteria fermentation. Compared with the control group (0 W), the FSEG treated with ultrasound had higher hardness, water holding capacity (WHC) and rheological parameters. Particularly, at an ultrasonic power of 300 W, the FSEG had the highest hardness (101.69 ± 4.67 g) and WHC (75.20 ± 1.07%) (p < 0.05). Analysis of frequency sweep and strain scanning revealed that the storage modulus (G') and yield strains of FSEG increased after 300 W ultrasonic treatment. Additionally, the recovery rate after creep recovery test significantly increased from 18.70 ± 0.49% (0 W) to 58.05 ± 0.54% (300 W) (p < 0.05). Ultrasound treatment also resulted in an increased ß-sheet content and the formation of a more compact micro-network structure. This led to a more uniform distribution of oil droplets and reduced mobility of water within the gel. Moreover, ultrasonic treatment significantly enhanced the encapsulation efficiency of quercetin in FSEG from 81.25 ± 0.62 % (0 W) to 90.04 ± 1.54% (300 W). The bioaccessibility of quercetin also increased significantly from 28.90 ± 0.40% (0 W) to 42.58 ± 1.60% (300 W) (p < 0.05). This study enriches the induction method of soy protein emulsion gels and provides some references for the preparation of fermented emulsion gels loaded with active substances.

Quantifying spatial CXCL9 distribution with image analysis predicts improved prognosis of triple-negative breast cancer.

Background: The C-X-C motif chemokine ligand 9 (CXCL9) plays a pivotal role in tumor immunity by recruiting and activating immune cells. However, the relationship between CXCL9 expression and prognosis in triple-negative breast cancer (TNBC) is unclear. Methods: We investigated CXCL9 mRNA expression, clinicopathological features, and prognosis in TNBC patients. We also used computational image analysis to quantify and assess the distribution of CXCL9 protein in the tumor core (TC) and invasive margin (IM). Results: CXCL9 mRNA expression was significantly higher in TNBC tumors compared to normal tissue (p < 0.001) and was associated with smaller tumors (p = 0.022) and earlier stages (p = 0.033). High CXCL9 mRNA expression was correlated with improved overall survival (OS) in three independent cohorts (all p < 0.05). In a separate analysis, low CXCL9 protein expression was associated with increased lymph node metastasis (p = 0.018 and p = 0.036). High CXCL9 protein expression in the TC, IM, or both was associated with prolonged OS (all p < 0.001). Conclusion: High CXCL9 expression, at both the mRNA and protein levels, is associated with improved prognosis in TNBC patients. CXCL9 expression in the TC and/or IM may be an independent prognostic factor.

The relationship of peripheral blood lncRNA-PVT1 and miR-146a levels with Th17/Treg cytokines in patients with Hashimoto's thyroiditis and their clinical significance.

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease. We investigated the relationship of peripheral blood long noncoding RNA-plasmacytoma variant translocation 1 (lncRNA-PVT1) and microRNA (miR)-146a levels with Th17/Treg-related cytokines in HT patients and their clinical significance. Correlations of lncRNA-PVT1 and miR-146a with Th17/Treg-related cytokines were analyzed, and its clinical value in diagnosing HT was assessed. Results showed reduced lncRNA-PVT1 and interleukin (IL)-10 levels and increased miR-146a and IL-17 levels in HT patients. lncRNA-PVT1 negatively interrelated with miR-146a, IL-17, IL-23 and IL-6, and positively interrelated with IL-10; miR-146a positively correlated with IL-17, IL-23 and IL-6, but negatively correlated with IL-10 in HT patients. The area under the curve (AUC) of lncRNA-PVT1 and miR-146a levels for diagnosing HT were 0.822 and 0.844, respectively (sensitivity 88.73% and 86.62%, specificity 67.02% and 69.15%, cut-off values 0.76 and 2.73), with their combined detections yielding a higher AUC. Patients with poorly expressed lncRNA-PVT1 and highly expressed miR-146a had elevated HT incidence. lncRNA-PVT1 and miR-146a levels were also found to be an independent influencing factor for HT occurrence. Our findings suggest that HT patients have low peripheral blood lncRNA-PVT1 expression and high miR-146a expression. lncRNA-PVT1 and miR-146a level changes were correlated with Th17/Treg cytokine imbalance and could be a potential diagnostic tool and independent influencing factor for HT.

Trash into Treasure: Nano-coating of Catheter Utilizes Urine to Deprive H2S Against Persister and Rip Biofilm Matrix.

Bacteria-derived hydrogen sulfide (H2S) often contributes to the emergence of antibiotic-recalcitrant bacteria, especially persister (a sub-population of dormant bacteria), thus causing the treatment failure of Catheter-associated urinary tract infection (CAUTI). Here, an H2S harvester nanosystem to prevent the generation of persister bacteria and disrupt the dense biofilm matrix by the self-adaptive ability of shape-morphing is prepared. The nanosystem possesses a core-shell structure that is composed of liquid metal nanoparticle (LM NP), AgNPs, and immobilized urease. The nanosystem decomposes urea contained in urine to generate ammonia for eliminating bacteria-derived H2S. Depending on the oxidative layer of liquid metal, the nanosystem also constitutes a long-lasting reservoir for temporarily storing bacteria-derived H2S, when urease transiently overloads or in the absence of urine in a catheter. Depriving H2S can prevent the emergence of persistent bacteria, enhancing the bacteria-killing efficiency of Ga3+ and Ag+ ions. Even when the biofilm has formed, the urine flow provides heat to trigger shape morphing of the LM NP, tearing the biofilm matrix. Collectively, this strategy can turn trash (urea) into treasure (H2S scavengers and biofilm rippers), and provides a new direction for the antibacterial materials application in the medical field.

TraInterSim: Adaptive and Planning-Aware Hybrid-Driven Traffic Intersection Simulation.

Traffic intersections are important scenes that can be seen almost everywhere in the traffic system. Currently, most simulation methods perform well at highways and urban traffic networks. In intersection scenarios, the challenge lies in the lack of clearly defined lanes, where agents with various motion plannings converge in the central area from different directions. Traditional model-based methods are difficult to drive agents to move realistically at intersections without enough predefined lanes, while data-driven methods often require a large amount of high-quality input data. Simultaneously, tedious parameter tuning is inevitable involved to obtain the desired simulation results. In this paper, we present a novel adaptive and planning-aware hybrid-driven method (TraInterSim) to simulate traffic intersection scenarios. Our hybrid-driven method combines an optimization-based data-driven scheme with a velocity continuity model. It guides the agent's movements using real-world data and can generate those behaviors not present in the input data. Our optimization method fully considers velocity continuity, desired speed, direction guidance, and planning-aware collision avoidance. Agents can perceive others' motion plannings and relative distances to avoid possible collisions. To preserve the individual flexibility of different agents, the parameters in our method are automatically adjusted during the simulation. TraInterSim can generate realistic behaviors of heterogeneous agents in different traffic intersection scenarios in interactive rates. Through extensive experiments as well as user studies, we validate the effectiveness and rationality of the proposed simulation method.

C-X-C Motif Chemokine Ligand 9 Correlates with Favorable Prognosis in Triple-Negative Breast Cancer by Promoting Immune Cell Infiltration.

C-X-C motif chemokine ligand 9 (CXCL9) plays an important role in antitumor immunity through the recruitment, proliferation, and activation of immune cells (IC). Here, we evaluated the expression patterns of CXCL9 and programmed death-ligand 1 (PD-L1) in a cohort of 268 patients with triple-negative breast cancer (TNBC) by tissue microarray (TMA). The correlations between CXCL9 expression in ICs or tumor cells (TC) and clinicopathologic parameters, PD-L1 expression, tumor-infiltrating lymphocytes (TIL) and survival were analyzed in this cohort (n = 268). In addition, we analyzed a TNBC dataset (n = 138) from The Cancer Genome Atlas (TCGA) to identify correlation between CXCL9 expression and other immune gene expression, immune infiltration, and prognosis. The results of the TMA cohort (n = 268) showed that CXCL9 was expressed in 80.6% cases, with elevated expression levels in ICs relative to in TCs (median: 1% vs. 0%). CXCL9 expressed in ≥1% of ICs was categorized as the CXCL9-IC-positive group. CXCL9-IC expression was strongly and positively correlated with the PD-L1 expression, CD3+ TILs, CD4+ TILs, CD8+ TILs, and CD19+ TILs (all P < 0.0001). Survival analyses showed that the CXCL9-IC-positive group demonstrated prolonged disease-free survival (P = 0.038) and overall survival (P = 0.023) compared with the negative group. The analyses from TCGA cohort (n = 138) showed that elevated CXCL9 expression correlated with increased infiltration of B cells, macrophages, natural killer cells, monocytes and increased expression of immune checkpoint molecules and other CXCL family members, including CXCL10 and CXCL11. These findings confirm the regulatory role of CXCL9 in antitumor immunity and suggest a potential role in treatments involving immune checkpoint blockade.

Prognostic value of various immune cells and Immunoscore in triple-negative breast cancer.

Background: This study aimed to evaluate the expression status and prognostic role of various immunoregulatory cells and test in triple-negative breast cancer (TNBC). Methods: The expression of five markers (CD3/CD4/CD8/CD19/CD163) of tumor immune cells was evaluated retrospectively in tumor sections from 68 consecutive cases of TNBC by immunohistochemistry. Computational image analysis was used to quantify the density and distribution of each immune marker within the tumor region, tumor invasive margin, and expression hotspots. Immunoscores were calculated using an automated approach. Other clinical characteristics were also analyzed. Results: For all patients, Kaplan-Meier survival analysis showed that high CD3+ signals in the tumor region (disease-free survival (DFS), P=0.0014; overall survival (OS), P=0.0031) and total region (DFS, P=0.0014; OS, P=0.0031) were significantly associated with better survival. High CD4+ levels in the tumor region and total regions were significantly associated with better survival (P<0.05). For Hotspot analysis, CD3+ was associated with significantly better survival for all Top1, Top2, and Top3 densities (DFS and OS, P<0.05). High CD4+ levels were significantly associated with better prognosis for Top1 and Top3 densities (DFS and OS, P<0.05). For stage IIB and IIIC patients, CD3+ in the tumor region and all Top hotspots was found to be significantly correlated with survival (DFS and OS, P<0.05). CD4+ cells were significantly associated with survival in the tumor region, total region, and Top3 density (DFS, P=0.0213; OS, P=0.0728). CD8+ cells were significantly associated with survival in the invasive margin, Top2 density, and Top3 density. Spatial parameter analysis showed that high colocalization of tumor cells and immune cells (CD3+, CD4+, or CD8+) was significantly associated with patient survival. Conclusion: Computational image analysis is a reliable tool for evaluating the density and distribution of immune regulatory cells and for calculating the Immunoscore in TNBC. The Immunoscore retains its prognostic significance in TNBC later than IIB stage breast cancer. Future studies are required to confirm its potential to predict tumor responses to chemotherapy and immune therapy.