High Expression Rate Research Articles

Testicular Neoplasms: Primary Tumour Size Is Closely Interrelated with Histology, Clinical Staging, and Tumour Marker Expression Rates-A Comprehensive Statistical Analysis.

The role of primary tumour size (TS) in the clinical course of testicular tumours is incompletely understood. We retrospectively evaluated 641 consecutive patients with testicular neoplasms with regard to TS, histology, clinical stage (CS), serum tumour marker (STM) expression and patient age using descriptive statistical methods. TS ≤ 10 mm was encountered in 13.6% of cases. Median TS of 10 mm, 30 mm, 35 mm, and 53 mm were found in benign tumours, seminomas, nonseminomas, and other malignant tumours, respectively. In cases with TS ≤ 10 mm, 50.6% had benign tumours. Upon receiver operating characteristics analysis, TS of > 16 mm revealed 81.5% sensitivity and 81.0% specificity for detecting malignancy. In subcentimeter germ cell tumours (GCTs), 97.7% of cases had CS1, and CS1 frequency dropped with increasing TS. Expression rates of all STMs significantly increased with TS. MicroRNA-371a-3p (M371) serum levels had higher expression rates than classical STMs, with a rate of 44.1% in subcentimeter GCTs. In all, TS is a biologically relevant factor owing to its significant associations with CS, STM expression rates and histology. Importantly, 50% of subcentimeter testicular neoplasms are of benign nature, and M371 outperforms the classical markers even in subcentimeter tumours.

Glucose-Regulated Protein 94 Expression in Patients with Non- Small Cell Lung Cancer and Prognostic Significance

The researchers aimed to study the correlations of expression of glucose-regulated protein 94 (GRP94) with clinicopathological characteristics and prognosis of patients with non-small cell lung cancer (NSCLC). NSCLC tissue specimens were collected from January 2016 to January 2018. The prognostic factors of NSCLC patients were analyzed. Survival curves were plotted. Logistic multivariate regression analysis was performed to explore the factors influencing prognosis. GRP94 protein was mainly expressed in the nucleus in NSCLC and para-carcinoma tissues. The high expression rates of GRP94 in NSCLC tissues were significantly different in patients with and without tumor metastasis after surgery (P<0.05). GRP94-positive NSCLC patients had significantly longer mean survival time than GRP94-negative ones (P<0.01). Positive GRP94 expression, maximum diameter of tumor, pathological type, lymph node metastasis, T stage and postoperative TNM stage were independent risk factors affecting prognosis. GRP94 is an independent factor influencing the prognosis of NSCLC, as a potential target for treatment.

Preliminary study on angiogenesis and functional evaluation of benign adrenal pheochromocytoma vessels

Objective: To study the relationship between the pheochromacytomas’ MVD and VEGF expression which are two indexes of angiogenesis, and analyze the difference of MVD and VEGF expression in different groups of pheochromocytomas with the purpose of correlating pheochromocytoma’s function and angiogensis. Methods From June 2009 to December 2015, thirty-one patients histologically diagnosed as benign pheochromocytoma were divided into two groups according to the length of preparing time before operation(group 1≦2 weeks, group 2>2 weeks), and eight normal adrenal glands as the control group. The MVD and VEGF expression of all the pheochromocytomas and normal adrenal glands were evaluated, with the purpose of correlating the MVD and VEGF expression and analyzing the difference among of two groups of pheochromocytomas and normal adrenal glands. The tumors’ diameter, intratumoral necrosis and the patients’ urine VMA were also analyzed with MVD and VEGF expression. Results :1) The mean value of MVD in group 1 is 50.2±15.4 per HP, and less than the group 2 with the mean value 69.5±3.8 per HP(p<0.05), but more than the normal adrenal glands with the mean value 35.1±3.4 per HP(p<0.05). There is no MVD mean value difference between groups divided according to tumors’ diameter, intratumoral necrosis and the patients’ urine VMA. There is 30.8% high VEGF expression in group 1 less than group 2 with 77.8%(p<0.05), and there no high VEGF expression rate difference between groups divided according to tumors’ diameter, intratumoral necrosis and the patients’ urine VMA; The MVD correlates with VEGF expression in pheochromocytomas (r=0.545, p<0.05). Conclusion :1) The function of pheochromocytoma maybe correlate with the angiogenesis. 2) The angiogenesis of pheochromocytoma was more than that of the normal adrenal gland. 3)There are no correlation with the angiogenesis and tumor’s diameter, intratumoral necrosis and the patients’ urine VMA in this study.

Получение хрящеподобных структур из стволовых клеток с индуцированной плюрипотентностью

One of the approaches to cartilage tissue restoration problem relies on cellular technologies that use iPSCs, induced pluripotency stem cells that are an unlimited source of cellular material for tissue engineering with significant differentiation potential. However, there are no standardized protocols for chondrogenic differentiation of iPSCs. This study aimed to make cartilage tissue samples using 3D spheroid cultures and following four chondrogenic differentiation protocols, then compare characteristics of the cartilage samples made under different protocols and isolate the most effective way of differentiation. The iPSCs were differentiated chondrogenically, the four protocols were "long", "short", "combined" and with conditioned medium from a primary culture of autologous chondrocytes; the combinations of TGFβ1, BMP2, Chir 99021, and PK factors varied. Microwell plates were used to make spheroids. Immunocytochemical staining, real-time PCR and histological staining enabled assessment of the synthesis and expression profiles. High rates of synthesis and expression of chondrogenic markers Sox9, aggrecan, type II collagen were observed in spheroids experimented with under the "long", "combined" protocols and the conditioned medium protocol. The "combined" differentiation protocol made chondrogenesis most effective, and conditioned medium was highly efficient in inducing and supporting chondrogenic differentiation.

Effect of drought stress and inoculation treatments on nutrient uptake, essential oil and expression of genes related to monoterpenes in sage (Salvia officinalis)

To investigate the effect of inoculation of Piriformospora indica (P. indica) and Pseudomonas fluorescens (P. fluorescens) on some morphological and physiological traits, nutrient concentration, essential oil (EO) and gene expression in Salvia officinalis under drought stress (100, 70 and 40% Field Capacity (FC)) we designed a factorial experiment in a completely randomized design with three replications. The results showed that by increasing drought stress intensity, percentage of root colonization by P. indica, growth parameters, relative water content, chlorophyll index, essential oil yield, and nutrient concentration decreased. The highest and lowest values of dry herb yield (33.94 and 11.62 g pot−1), RWC (80.20 and 51.60 %), chlorophyll concentration (38.46 and 30.47), essential oil yield (0.22 and 0.20 ml pot−1) and P concentration (0.40 and 0.26 %) were observed in P. indica inoculated plants under well-watered conditions and non-inoculated plants in severe drought stress (40% FC), respectively. The Sabinene synthase (ss) gene expression rate enhanced notably under drought stress and the highest expression rate was obtained in the 40% FC in plants inoculated with P. fluorescens. In contrast, the expression of geranyl diphosphate synthase (gpps) and bornyl diphosphate synthase (bpps) decreased under drought stress. The highest amount of predominant compounds of essential oil including α-Thujone, 1,8-Cineole (36.48 and 13.26%) and Camphor (18.94%) were observed in bacterial inoculation treatment under drought level of 40% FC and non-inoculated plants in well-watered condition, respectively.

High expression of CCBE1 in adjacent tissues of tongue squamous cell carcinoma is correlated with pericancerous lymphatic vessel proliferation and poor 5-year survival outcomes

To examine the correlation of CCBE1 expression in adjacent tissues of tongue squamous cell carcinoma (TSCC) with pericancerous lymphatic vessel proliferation, cervical lymph node metastasis and survival outcomes of the patients. Lymphatic vessel density was quantified in pericancerous tissue sections of 44 cases of cT1-2N0 TSCC using D2-40 as the lymphatic vessel endothelial marker for calibration and counting of the lymphatic vessels. Of these 44 cases, 22 showed a relatively low lymphatic vessel density (group A) and the other 22 had a high lymphatic vessel density (group B), and the expression levels of CCBE1 in the adjacent tissues determined using immunohistochemistry, immunofluorescence assay and Western blotting were compared between the two groups. The expression level of CCBE1 was also measured in another 90 patients with TSCC using immunohistochemistry, and all the patients were followed up for their survival outcomes. Immunohistochemistry and Western blotting showed a significantly lower rate of high CCBE1 expression in group A than in group B (P < 0.05). Immunofluorescence assay showed co-localization of CCBE1 and D2-40 in the adjacent tissues of TSCC. In the 90 TSCC patients with complete follow-up data, a high expression of CCBE1 was found to correlate with lymph node metastasis and a poor 5-year survival outcomes of the patients (P < 0.05). A high expression of CCBE1 in the adjacent tissues of TSCC is closely related with pericancerous lymphatic vessel proliferation, cervical lymph node metastasis and a poor 5-year survival of the patients, suggesting the value of CCBE1 as a potential prognostic predictor for TSCC.

Nectin-4 is widely expressed in head and neck squamous cell carcinoma.

Purpose: Nectin-4 has been successfully established as a target molecule in locally advanced and metastatic bladder cancer. An antibody-drug conjugate (enfortumab-vedotin) directed against nectin-4 has shown marked tumor remission rates in this tumor type, which is known for high expression rates of nectin-4. As head and neck cancer and urothelial carcinomas share morphological and molecular similarities, we aimed to evaluate Nectin-4 expression in head and neck squamous cell carcinoma (HNSCC).Material and Methods: A previously described and clinically characterized cohort of HNSCC (n = 159) was analyzed by immunohistochemistry for Nectin-4 expression. The expression data was correlated to clinico-pathological parameters including patient outcome.Results: Nectin-4 was found in 86.2% of HNSCC, with medium/high expression seen in 32.7% of cases. Non smokers and p16 positive HNSCC showed a higher expression of Nectin-4 (p < 0.005). There was no correlation of Nectin-4 with grading or tumor stage. Nectin-4 positive tumors showed a significant better survival (log rank p = 0.006).Conclusions: Similar to urothelial carcinoma, Nectin-4 is found in the majority of HNSCC, which clearly warrants further studies to clarify if HNSCC also respond to targeted therapy with enfortumab-vedotin. Moreover, expression of Nectin-4 is associated with HPV infection and may serve as a prognostic marker in HNSCC.

Differential gene expression of SARS-CoV-2 transcriptome provides insight into the design of more sensitive diagnostic tests

The Coronavirus disease 2019 (COVID-19) pandemic is being addressed through RT-PCR, a frontline diagnostic technique. We evaluated gene expression patterns to improve the accuracy and sensitivity of current diagnostic tests. We downloaded relevant next-generation sequencing (NGS) data from the Sequence Read Archive (SRA) database, checked for quality, and mapped them onto the target reference sequence. It was determined that ORF1ab, N, S, and ORF8 genes are mainly expressed based on the results of the quantitative evaluation after normalization by HPRT and elimination of insufficient expression data. ORF8, ORF3a, and M genes were found to have higher expression values than the E gene as a routine RT-PCR detector gene (p*0.05). M gene expression values are also close to ORF8 values. Taking into account the importance of differential expression of genes in the design of diagnostic kits as well as the findings of from this study, it is likely that the M gene is worth further investigation due to its high expression and low mutation rate.

Evaluation of hCG as gonadotropic support to timed embryo transfer protocol in beef cattle

This study compared the reproductive performance of embryo recipients treated with a timed embryo transfer (TET) protocol using human chorionic gonadotropin (hCG) or equine chorionic gonadotropin (eCG). On a random day of the estrous cycle (Day −10) indicus-taurus recipients (n = 341; 194 nulliparous and 147 multiparous cows) with a body condition score between 3.0 and 4.0, were submitted to the TET protocol consisting of an intramuscular (i.m.) injection of 2.0 mg estradiol benzoate (EB) and the insertion of intravaginal progesterone (P4) device that remained until Day −2.5. On the same day (−2.5), the recipients received i.m. 150 mg D-cloprostenol and 1 mg estradiol cypionate and were randomly divided into two groups: the eCG group (n = 179), in which females received i.m. 300 IU eCG and the hCG group (n = 162), in which females received 150 IU hCG. Then, estrus intensity and the diameter of the dominant follicle (DF) were monitored on D0 and the quality of the corpus luteum (CL) (B mode and color Doppler) was assessed on D7 to select recipients eligible for receiving the transfer of an embryo produced in vitro. Pregnancy diagnosis was assessed 23 days after the transfer. Continuous data were analyzed by ANOVA using a mixed-effects model and Tukey's test. The rates were analyzed using a logistic regression model. The diameter of the DF on day 0 of the TET protocol was influenced by the interaction between gonadotropic treatment and category (P = 0.01), and nulliparous recipients treated with hCG had the smallest diameter. Treatment with hCG and eCG resulted in a high rate of estrus expression; however, the proportion of females with a high-intensity of estrus was higher in the hCG group (79.84 vs. 68.61%, respectively; P = 0.03). The utilization rate (recipients with CL) showed a tendency (P = 0.06) to be influenced by the interaction between gonadotropic treatment and category, wherein nulliparous recipients treated with hCG exhibited a lower utilization rate than the other groups. The diameter, perimeter, and area of the CL were similar (P > 0.1) in all groups. However, the hCG group resulted in CL with a better Doppler evaluation score (P = 0.04), central blood flow (P = 0.03), and tendency towards greater peripheral blood flow (P = 0.08). The rates of conception (32.00% hCG vs. 35.10% eCG; P = 0.46) and pregnancy (24.69% hCG vs. 29.61% eCG; P = 0.20) were similar between the hCG and eCG groups. However, an interaction between the gonadotropic treatment and category revealed lower conception (P = 0.01) and pregnancy rates (P = 0.001) in nulliparous recipients treated with hCG. Treatment with hCG resulted in a greater intensity of estrus expression and CL with a higher Doppler score, which determined rates of utilization, conception, and pregnancy similar to conventional protocols using eCG. However, nulliparous recipients treated with hCG exhibited a lower overall reproductive rate.

Influence of a Calcium Phosphate Coating (BONIT®) on the Proliferation and Differentiation Potential of Human Mesenchymal Stroma Cells in the Early Phase of Bone Healing.

When implanting osteosynthetic materials or orthopedic implants, the surface condition plays a decisive role for mid- to long-term osseointegration. BONIT®, an electrochemically produced calcium phosphate (CaP) coating, has been used in the surface refinement of implants since 1995. More than 3.5 million coated implants have been successfully placed so far. BONIT® has thus been able to demonstrate clinical success. However, due to its surface properties and solubility, and the resulting difficulty in culturing cells, there are no in vitro studies investigating its influence at the molecular level, particularly on bone metabolism. In a first step, the cells from a total of ten donors were seeded separately on four different surfaces: 1. a pure corundum-blasted titanium surface (CELLTex®, CT), 2. CT with additional BONIT® coating (CT + B), 3. a hydroxyapatite-blasted titanium surface (DUOTex®, DT), 4. DT with additional BONIT® coating (DT + B). In a second step, the cells were grown for 48 h. The proliferation behavior and differentiation potential of hMSCs were investigated at three consecutive time points (12 h, 24 h and 48 h) by quantifying the mRNA expression of ten important differentiation markers using quantitative real-time polymerase chain reaction (qRT-PCR). We were able to show that BONIT® has an influence on the early proliferation and differentiation behavior of hMSCs in patients of all age groups. The additional BONIT® coating on CELLTex® or DUOTex® led to a defined mRNA expression pattern for the investigated factors: a tendency towards a higher expression rate with coating present could be found for bone morphogenetic protein 2 (BMP2), osteopontin (OPN), osteocalcin (OC), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). A similar or lower expression rate was detected for runt-related transcription factor 2 (RUNX2), alpha-1 type I collagen (COL1A1), alkaline phosphatase (AP), osteonectin (ON) and insulin-like growth factor I (IGF1). We have developed a new method that allows the cultivation of human mesenchymal stromal cells (hMSCs) on the soluble coating BONIT® for gene expression analysis. BONIT® has a significant influence on the proliferation and differentiation behavior of human mesenchymal stroma cells. This study describes a defined gene expression pattern of bone metabolism that may help to understand the influence of this CaP coating on the early phase of implant osseointegration.

Expression of Twist 1 in bone marrow and extramedullary lesions of patients with myeloma and its prognostic significance

In patients with multiple myeloma (MM) extramedullary (EM) lesions could be a possible indicator of poor prognosis. Twist 1, an EMT related transcription factor, is known to play an important role in embryonic development and also in the process of tumor cell proliferation, apoptosis, metastasis etc. The Twist 1 protein expression hence has prognostic significance in MM. This study investigates expression of Twist-1 in MM patients with extramedullary lesions and its relationship with clinicopathological data and prognosis, so as to elucidate the clinical significance of Twist-1 expression. Patients with MM complicated with EM lesions were selected retrospectively, including 35 cases in the bone marrow group (MM complicated with extramedullary lesions) and 80 cases in the extramedullary group (MM combined with extramedullary lesions). The expression of Twist 1 protein was detected by immunohistochemistry. The relationship between Twist 1 protein expression and general clinicopathological data was analyzed by statistics. The relationship between Twist 1 protein expression and prognosis was analyzed by COX single factor and multivariate regression analysis. Immunohistochemical staining showed that the expression level of Twist-1 protein in the nucleus of myeloma cells in the extramedullary group was significantly higher than that of the bone marrow group. However, in the cytoplasm of myeloma cells, there was no significant difference in the expression level of Twist-1 protein between the extramedullary group and the bone marrow group. The expression level of Twist-1 protein in extramedullary tissue was not related to sex, age, D-S stage, ISS stage, immunoglobulin type, creatinine and hemoglobin. The expression level of β2-microglobulin in Twist-1 high expression group was significantly higher than that of Twist-1 low expression group. Follow-up findings discovered that overall survival (OS) of Twist 1 high expression group was significantly lower than that of Twist 1 low expression group. COX multivariate analysis showed that Twist 1 protein and International Staging System (ISS) stage were independent risk factors affecting OS for 3 years. The high expression rate of Twist 1 protein in extramedullary lesions of MM patients with extramedullary lesions is significantly higher than that in bone marrow tissues of patients with extramedullary lesions. The results suggest that high expression of Twist 1 protein is an independent risk factor affecting the prognosis of MM patients with extramedullary lesions.

Fucoxanthin induces apoptosis and reverses epithelial-mesenchymal transition via inhibiting Wnt/β-catenin pathway in lung adenocarcinoma

BackgroundInvasion and metastasis are hallmark characteristics of cancer and the main causes of death in cancer patients. Studies have shown that epithelial-mesenchymal transition (EMT) plays significant role in tumor invasion and metastasis. Fucoxanthin, a carotenoid found in seaweeds, has been proved to have anti-tumor effects. Our study aimed to research the role of fucoxanthin on proliferation, apoptosis, migration and EMT of two types of LUAD cells.MethodsCell migration and invasion were examined by Wound-healing and Transwell assays. Western blot assay was used to detect the expression levels of apoptosis-related proteins, EMT-related proteins and β-catenin. Immunohistochemistry was used to detect the expression of β-catenin in human lung adenocarcinoma tissues and corresponding para-cancerous tissues.ResultsOur results revealed that fucoxanthin depressed the proliferation and induced apoptosis in A549 and NCI-H1299 cells. Moreover, fucoxanthin reversed TGF-β1-induced EMT and cell motility. Meanwhile, we disclosed that fucoxanthin and XAV939 had similar effect on β-catenin, EMT protein and cell motility. What is more, immunohistochemical results revealed that the high expression rate and abnormal expression rate of β-catenin in cancer tissues was significantly higher than that in para-cancerous tissues.ConclusionTaken together, the findings of our research highlight a novel role for fucoxanthin in NSCLC cells, which might be a potentially effective anti-tumor agent for the treatment of LUAD patients.

Regeneration and developmental enhancers are differentially compatible with minimal promoters

Enhancers and promoters are cis-regulatory elements that control gene expression. Enhancers are activated in a cell type-, tissue-, and condition-specific manner to stimulate promoter function and transcription. Zebrafish have emerged as a powerful animal model for examining the activities of enhancers derived from various species through transgenic enhancer assays, in which an enhancer is coupled with a minimal promoter. However, the efficiency of minimal promoters and their compatibility with multiple developmental and regeneration enhancers have not been systematically tested in zebrafish. Thus, we assessed the efficiency of six minimal promoters and comprehensively interrogated the compatibility of the promoters with developmental and regeneration enhancers. We found that the fos minimal promoter and Drosophila synthetic core promoter (DSCP) yielded high rates of leaky expression that may complicate the interpretation of enhancer assays. Notably, the adenovirus E1b promoter, the zebrafish lepb 0.8-kb (P0.8) and lepb 2-kb (P2) promoters, and a new zebrafish synthetic promoter (ZSP) that combines elements of the E1b and P0.8 promoters drove little or no ectopic expression, making them suitable for transgenic assays. We also found significant differences in compatibility among specific combinations of promoters and enhancers, indicating the importance of promoters as key regulatory elements determining the specificity of gene expression. Our study provides guidelines for transgenic enhancer assays in zebrafish to aid in the discovery of functional enhancers regulating development and regeneration.

Peripheral Nerve Regeneration-Adipose-Tissue-Derived Stem Cells Differentiated by a Three-Step Protocol Promote Neurite Elongation via NGF Secretion.

The lack of supportive Schwann cells in segmental nerve lesions seems to be one cornerstone for the problem of insufficient nerve regeneration. Lately, adipose-tissue-derived stem cells (ASCs) differentiated towards SC (Schwann cell)-like cells seem to fulfill some of the needs for ameliorated nerve recovery. In this study, three differentiation protocols were investigated for their ability to differentiate ASCs from rats into specialized SC phenotypes. The differentiated ASCs (dASCs) were compared for their expressions of neurotrophins (NGF, GDNF, BDNF), myelin markers (MBP, P0), as well as glial-marker proteins (S100, GFAP) by RT-PCR, ELISA, and Western blot. Additionally, the influence of the medium conditioned by dASCs on a neuron-like cell line was evaluated. The dASCs were highly diverse in their expression profiles. One protocol yielded relatively high expression rates of neurotrophins, whereas another protocol induced myelin-marker expression. These results were reproducible when the ASCs were differentiated on surfaces potentially used for nerve guidance conduits. The NGF secretion affected the neurite outgrowth significantly. It remains uncertain what features of these SC-like cells contribute the most to adequate functional recovery during the different phases of nerve recovery. Nevertheless, therapeutic applications should consider these diverse phenotypes as a potential approach for stem-cell-based nerve-injury treatment.

Correlation between PD-L1 expression and radiomic features in early-stage lung adenocarcinomas manifesting as ground-glass nodules.

BackgroundImmunotherapy might be a promising auxiliary or alternative systemic treatment for early-stage lung adenocarcinomas manifesting as ground-glass nodules (GGNs). This study intended to investigate the PD-L1 expression in these patients, and to explore the non-invasive prediction model of PD-L1 expression based on radiomics.MethodsWe retrospectively analyzed the PD-L1 expression of patients with postoperative pathological diagnosis of lung adenocarcinomas and with imaging manifestation of GGNs, and divided patients into positive group and negative group according to whether PD-L1 expression ≥1%. Then, CT-based radiomic features were extracted semi-automatically, and feature dimensions were reduced by univariate analysis and LASSO in the randomly selected training cohort (70%). Finally, we used logistic regression algorithm to establish the radiomic models and the clinical-radiomic combined models for PD-L1 expression prediction, and evaluated the prediction efficiency of the models with the receiver operating characteristic (ROC) curves.ResultsA total of 839 “GGN-like lung adenocarcinoma” patients were included, of which 226 (26.9%) showed positive PD-L1 expression. 779 radiomic features were extracted, and 9 of them were found to be highly corelated with PD-L1 expression. The area under the curve (AUC) values of the radiomic models were 0.653 and 0.583 in the training cohort and test cohort respectively. After adding clinically significant and statistically significant clinical features, the efficacy of the combined model was slightly improved, and the AUC values were 0.693 and 0.598 respectively.ConclusionsGGN-like lung adenocarcinoma had a fairly high positive PD-L1 expression rate. Radiomics was a hopeful noninvasive method for predicting PD-L1 expression, with better predictive efficacy in combination with clinical features.

BLOSSoM: Improving Human Milk Provision in Preterm Infants Through Texting Support.

Introduction:Mother’s own milk (MOM) reduces complications of preterm birth. Despite high initiation rates of expression, half of preterm infants do not receive MOM at discharge. Frequent outreach and a short message service (SMS) have improved MOM provision in term dyads. We aimed to improve MOM provision rate from 61% to >80% by implementing standardized lactation education and Breastfeeding & Lactation Outreach via SMS Supporting Mothers (BLOSSoM).Methods:The baseline period was June 2019 to April 2020. A multidisciplinary team implemented PDSA cycles: education/documentation (standardized lactation education and education documentation, May 2020–April 2021), and BLOSSoM (SMS program providing educational texts/videos, reminders, 2-way communication with neonatal intensive care unit (NICU) lactation, May 2021–December 2021). The primary outcome was MOM provision at NICU discharge/transfer for infants younger than 34 weeks, as analyzed on the SPC chart. BLOSSoM participants evaluated the program using a 5-point Likert scale.Results:Demographic and clinical characteristics were unchanged among the three periods. However, the monthly MOM provision rate improved from 61% to 81%. Eighty-seven percent of BLOSSoM participants completed the evaluation with 83% rating the program most supportive, 78% rating the videos as the most helpful, followed by team check-ins (54%) and 2-way texting (24%).Conclusions:Using a multidisciplinary approach, we improved the monthly MOM provision rate at discharge/transfer for preterm infants. SMS providing educational texts/media and 2-way communication supporting lactating NICU mothers was critical to our success. Providing another method of communication through SMS was well accepted and valued by the majority.

Value of Proline, Glutamic Acid, and Leucine-Rich Protein 1 and GATA Binding Protein 3 Expression in Breast Cancer: An Immunohistochemical study

GATA binding protein 3 was more sensitive than traditional markers such as gross cystic disease fluid protein 15 and mammaglobin for identifying primary and metastatic breast carcinomas, but its significance decreased in triple-negative breast cancer. Recent studies showed a high expression rate of proline glutamic acid and leucine-rich protein in breast cancer and their superiority over GATA3 in triple-negative breast cancer. Our study provided new insights into the diagnostic and prognostic roles of PELP1 and GATA3 in primary and metastatic breast cancer. An immunohistochemical assay was carried out using PELP1 and GATA3 in 60 cases of primary breast cancer and 15 metastatic. Invasive carcinoma of no special type was the predominant type (80%). The majority of cases were grade 3 (68.3%). GATA3 expression was 83.3% positive in primary breast carcinomas and 73.5% positive in metastatic breast carcinomas. In comparison, PELP1 had a 96.7% positive expression rate in primary breast carcinomas and an 86.7% positive expression rate in metastasis. There was a statistically significant agreement between GATA3 and PELP1 in the diagnosis of the cases. PELP1 is a significantly higher proportion of both primary and metastatic breast carcinomas than GATA3. In breast cancer, there was a strong association between favorable prognostic factors and GATA3 expression, with evidence of an inverse association with Ki-67 overexpression.

Expression characteristics and diagnostic value of angiogenic molecules in intravenous leiomyomatosis

Objective: This study aims to analyze the clinicopathological characteristics of patients with intravenous leiomyoma (IVL), and to explore the expression characteristics and diagnostic value of angiogenesis related molecules in IVL. Methods: The clinicopathological data of 40 patients with IVL at Women's Hospital, School of Medicine, Zhejiang University from January 2013 to April 2021 were reviewed. Log-rank test was performed to compare the difference in recurrence-free survival (RFS) rates among patients with different clinicopathological characteristics. Immunohistochemistry (IHC) staining was performed on 10 angiogenesis related molecules to analyze their expression characteristics in IVL. The sensitivity and specificity of molecules with high expression rates in the diagnosis of IVL were calculated, the receiver operating characteristic curve (ROC) was plotted and the area under ROC (AUC) was calculated to evaluate the diagnostic value. Results: Median age of the 40 patients was 47 (43, 50) years. The clinical manifestations of IVL were atypical with the diagnostic accuracy of preoperative ultrasound was 12.5% (5/40), CT and/or MRI was 26.7% (8/30), and intraoperative frozen section was 30.0% (12/40). The overall recurrence rate of IVL was 10.0% (4/40). The Log-rank test showed that the cumulative recurrence-free survival rate of IVL patients with previous cesarean section (40.9%) was lower than that of those without cesarean section (96.4%) (P<0.05); and their median RFS time was shorter than those without cesarean section (16.4 months vs 22.2 months). The overall positive rates of adrenomedullin (ADM), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 3 (VEGFR3) and angiogenin receptor tyrosine kinase receptor 1 (TIE1) were 65.0% (26/40), 75.0% (30/40), 57.5% (23/40) and 50.0% (20/40), respectively. FGFR1 expression intensity and positive rate were higher in tumors with a maximum diameter greater than 5 cm than in tumors with a maximum diameter smaller than 5 cm (P<0.05). The AUC of FGFR1 combined with ADM, VEGFR3, and TIE1 was 0.876 (95%CI: 0.788-0.964, P<0.001). Conclusions: There was no typical clinical manifestation of IVL. A history of the previous cesarean section indicated a lower cumulative recurrence-free survival rate and shorter recurrence interval. It was hard to diagnose IVL by sonography, radiography, or frozen section pathology. FGFR1, ADM, VEGFR3, and TIE1 were all highly expressed in IVL, and the efficacy of the combination of the four molecules in diagnosing IVL was higher than that of imaging and classical vascular endothelial markers, which are expected to be promising molecular diagnostic markers.

Expression patterns of uPAR, TF and EGFR and their potential as targets for molecular imaging in oropharyngeal squamous cell carcinoma.

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer-specific biomarkers. The application of three membrane-bound receptors, namely urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)-positive and 48 HPV-negative groups, the IHC-determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow-up data, overall survival (OS) and recurrence-free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log-rank test following Kaplan-Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor-specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92-4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor-specific expression pattern.

Vaccination Therapy for Acute Myeloid Leukemia: Where Do We Stand?

Simple SummaryImmunotherapy is changing the therapeutic landscape of many hematologic diseases. Nevertheless, in acute myeloid leukemia (AML) the anti CD33 antibody-drug conjugate gemtuzumab ozogamicin is the only approved drug. In this review, we aimed at reporting biological mechanisms and their clinical impact of vaccines in AML. The principal vaccination strategies have been analyzed and commented, highlighting advantages in terms of toxicity and possibility to apply in elderly patients. Nevertheless, the clinical results of this strategy in AML are still far from satisfactory. It is necessary to evaluate the best scenario for this approach, whether in a therapeutic, prophylactic, or preemptive setting, considering the poorer results in active or high-burden disease. Finally, we underlined the necessity in AML of further research to optimize immunotherapy-based strategies, among which vaccines might represent relevant actors to contribute to long-term disease control.Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. In this review, we analyze recent evidence on AML vaccines and their biological mechanisms. The principal proteins that have been exploited for vaccination strategies and have reached clinical experimental phases are Wilm’s tumor 1, proteinase 3, and RHAMM. the majority of data deals with WT1-base vaccines, given also the high expression and mutation rates of WT1 in AML cells. Stimulators of immune responses such as TLR7 agonist and interleukin-2 have also proven anti-leukemic activity both in vivo and in vitro. Lastly, cellular vaccines mainly based on autologous or allogeneic off-the-shelf dendritic cell-based vaccines showed positive results in terms of T-cell response and safety, also in elderly patients. Compared to other immunotherapeutic strategies, anti-AML vaccines have the advantage of being a less toxic and a more manageable approach, applicable also to elderly patients with poorer performance status, and may be used in combination with currently available therapies. As for the best scenario in which to use vaccination, whether in a therapeutic, prophylactic, or preemptive setting, further studies are needed, but available evidence points to poorer results in the presence of active or high-burden disease. Given the poor prognosis of relapsed/refractory or high-risk AML, further research is urgently needed to better understand the biological pathways that sustain its pathogenesis. In this setting, research on novel frontiers of immunotherapy-based agents, among which vaccines represent important actors, is warranted to develop new and efficacious strategies to obtain long-term disease control by immune patrolling.