Expression and Clinical Significance of TIGIT in Primary Breast Cancer.

Purpose: The roles of T cell immunoreceptor with Ig and ITIM domains (TIGIT) in the diagnosis of primary breast cancer (PBC) are still unclear. This study was designed to investigate the expression of TIGIT in PBC patients, with an aim to analyze its diagnostic value in PBC. Patients and Methods: We first explore the expression of TIGIT in cancer patients based on TCGA database, and then we analyzed its correlation with clinicopathological features. Afterwards, we compared the protein and mRNA expressions of TIGIT in two BC cell lines (MCF-7 and MDA-MB-231) and normal breast epithelial cell line (MCF-10A). Subsequently, 56 PBC female patients admitted to the Taizhou People's Hospital from October 2018 to June 2021 were included in this study. Flow cytometry was used to detect TIGIT level on peripheral blood CD3+ T cells of PBC patients and healthy controls. TIGIT expression in PBC tissues was detected by immunohistochemistry (IHC) and immunofluorescence staining. Results: TCGA database showed that compared with adjacent tissues, TIGIT was significantly upregulated in tumor tissues. High TIGIT expression was positively correlated with tumor stage and negatively correlated with recurrence free survival (RFS) and overall survival (OS). TIGIT level in BC cell lines, peripheral blood and tumor tissues of PBC patients was significantly higher than that of control (P < 0.05). TIGIT level was correlated with age (P < 0.05), rather than tumor size, pathological type, lymph node metastasis, ER, PR, HER-2, and P53. ROC curve showed that the optimal critical value of peripheral blood TIGIT for BC screening was 23.38%. Postoperative TIGIT level in peripheral blood was significantly decreased compared to the preoperative TIGIT level (P < 0.05). Conclusion: TIGIT was upregulated in PBC and was correlated with age. It may be a potential target for the diagnosis and immunotherapy of PBC.

Enhanced electrocatalytic performance for oxygen evolution reaction via active interfaces of Co3O4arrays@FeOx/Carbon cloth heterostructure by plasma-enhanced atomic layer deposition.

Oxygen evolution reaction (OER) is a necessary procedure in various devices including water splitting and rechargeable metal-air batteries but required a higher potential to improve oxygen evolution efficiency due to its slow reaction kinetics. In order to solve this problem, a heterostructured electrocatalyst (Co3O4@FeOx/CC) is synthesized by deposition of iron oxides (FeOx) on carbon cloth (CC) via plasma-enhanced atomic layer deposition, then growth of the cobalt oxide (Co3O4) nanosheet arrays. The deposition cycle of FeOxon the CC strongly influences thein situgrowth and distribution of Co3O4nanosheets and electronic conductivity of the electrocatalyst. Owing to the high accessible and electroactive areas and improved electrical conductivity, the free-standing electrode of Co3O4@FeOx/CC with 100 deposition cycles of FeOxexhibits excellent electrocatalytic performance for OER with a low overpotential of 314.0 mV at 10 mA cm-2and a small Tafel slope of 29.2 mV dec-1in alkaline solution, which is much better than that of Co3O4/CC (448 mV), and even commercial RuO2(380 mV). This design and optimization strategy shows a promising way to synthesize ideally designed catalytic architectures for application in energy storage and conversion.

Radiologic findings that aid in the reduction of misdiagnoses of Langerhans cell histiocytosis of the bone: a retrospective study.

BACKGROUND: This study aimed to identify the characteristic radiological signs for the diagnosis of Langerhans cell histiocytosis (LCH) of the bone. METHODS: We retrospectively studied 82 cases of LCH with bone lesions confirmed by pathology. Clinical and radiological features of the patients were analyzed. RESULTS: A total of 64 and 18 patients had single and multiple bone lesions, respectively. With regard to LCH with single bone lesions, 37.5% (24/64) of lesions were located in the skull and presented as bone destruction with or without soft tissue mass. The correct diagnosis rate of these lesions was 60.0% (9/15) in children and adolescents, but was only 22.2% (2/9) in adults. A total of 26.5% (17/64) of the solitary lesions were found in the spine. Of these, 88.2% (15/17) were located in the vertebral body and appeared to have different degrees of collapse, and 66.7% (10/15) of these lesions were correctly diagnosed. Of the unifocal lesions, 21.8% (14/64) were located in other flat and irregular bones and manifested as osteolysis. Only 21.4% (3/14) of these cases were correctly diagnosed. In total, 14.1% (9/64) of the isolated bone LCH lesions were located in the long bones. Of these, 77.8% (7/9) were located in the diaphysis and presented as central bone destruction with or without fusiform periosteal reaction and extensive peripheral edema, of which 42.9% (3/7) were correctly diagnosed before surgery or biopsy. With regard to LCH with multiple bony destructive lesions, 71.4% (10/14) of cases in children and adolescents were correctly diagnosed; however, all four cases among adults were misdiagnosed. CONCLUSION: In all age groups, isolated diaphyseal destruction of the long bone with fusiform periosteal reaction and extensive peripheral edema, vertebra plana of the spine, and bevelled edge of skull defects accompanied by soft tissue masses strongly suggest LCH diagnosis. Moreover, the multiple bone osteolytic destruction in children and adolescents strongly suggests LCH diagnosis. Familiarity with these typical radiological signs of LCH is necessary to decrease misdiagnoses.

Calculation Method of Permanent Deformation of Asphalt Mixture Based on Interval Number.

There are great uncertainties in road design parameters, and the traditional point numerical calculation results cannot reflect the complexity of the actual project well. Additionally, the calculation method of road design theory based on interval analysis is more difficult in the use of uncertain design parameters. In order to simplify the calculation process of the interval parameters in the road design theory, the asphalt pavement design is taken as the analysis object, and the permanent deformation of the asphalt mixture is simplified by combining the interval analysis theory. Considering the uncertainty of the design parameters, the data with boundaries but uncertain size are expressed in intervals, and then the interval calculation formula for the permanent deformation of the asphalt mixture is derived, and the interval results are obtained. In order to avoid the dependence of interval calculation on the computer code, according to the interval calculation rule, the interval calculation method with the upper and lower end point values as point operations is proposed. In order to overcome the contradiction between interval expansion results and engineering applications, by splitting the multi-interval variable formulas, the interval variable weights are reasonably given, and the synthesis of each single interval result realizes a simplified calculation based on interval variable weight assignment. The analysis results show that the interval calculation method based on the point operation rule is accurate and reliable, and the simplified method based on the interval variable weight assignment is effective and feasible. The simplified interval calculation method proposed in this paper provides a reference for the interval application of road design theory.

Machine learning based adaptive optics for doughnut-shaped beam.

The doughnut-shaped beam has been widely applied in the field of super-resolution microscopic imaging, micro-nanostructure lithography, ultra-high-density storage, and laser trapping. However, how to maintain the doughnut-shaped focus inside the scattering medium becomes a challenge, due to the wavefront aberrations. Here we demonstrate a machine learning based adaptive optics method to recover the doughnut-shaped focus with high speed. In our method, the relationship between the distorted doughnut-shaped intensity point spread function and the coefficients of the first 15 Zernike modes for phase correction is established. Experimental results show that the wavefront aberration with 101,784 optical control elements can be predicted within ~17 ms even using a personal computer, and 97.5% correction accuracy can be achieved in 200 repeated tests. Besides, we successfully apply this method in the scanning microscopy theoretically. With a large number of optical control elements and fast operation speed, our method may pave the way for many important applications in bioimaging, such as deep tissue stimulated emission depletion (STED) microscopy.

Glucuronidated bilirubin: Significantly increased in hepatic encephalopathy.

Bilirubin is produced by the breakdown of hemoglobin in senescent erythrocytes by macrophages and carried by albumin from blood circulation to the liver for removal in normal physiology. Glucuronic acid modification of bilirubin by UDP-glucuronyltransferase in the liver is the key event for its subsequent elimination from human body. Conditions that accelerate the breakdown of erythrocytes may cause an elevated blood level of unconjugated bilirubin whereas the factors affect the glucuronidated bilirubin formation and subsequent elimination may cause decreased or increased blood level of glucuronidated bilirubin, the water soluble "direct bilirubin" measured by clinical blood test. Studies showed that increased total serum bilirubin has a protective effect on cardiovascular and other related diseases, but it is unknown how direct bilirubin levels were related to different diseases. By taking advantage of the data collected in the clinical laboratory of our hospital, the direct bilirubin data from 192,535 patients with 72 clinically defined diseases were compared to that of healthy controls (10,497). Based on the mean, median, and p values, we found that patients with hepatic encephalopathy had the highest serum direct bilirubin level, which resembled acute hepatic encephalopathy caused by increased serum direct bilirubin level in neonates. In contrast, patients with uremia, nephrotic syndrome, and preeclampsia had significantly lower levels of serum direct bilirubin. Taken together, our data revealed that serum direct bilirubin levels were either increased or decreased in a disease-dependent manner. The possible molecular mechanisms of increased direct bilirubin levels in patients suffering hepatic encephalopathy are discussed.

Proteoglycans as miscommunication biomarkers for cancer diagnosis.

Cancer cells reside in a microenvironment comprising of fibroblasts, endothelial cells, pericytes, macrophages, and other immune cells. All these cells coevolve with the cancer cells into a clinically manifested tumor. The immune system of the host should eliminate the tumor but fails to do so until it develops into a deadly disease. Based on these facts, cancer is a system disorder caused by miscommunications among cancer cells, its microenvironment, and host immune system. Therefore, identifying communication-related biomarkers will be important for cancer diagnosis and treatment. Proteoglycans are important communication molecules made by all types of mammalian cells and present both at cell surfaces and in extracellular matrix. Proteoglycans consist of a core protein to which one or more glycosaminoglycan (GAG) chains are covalently attached. GAGs are long linear anionic polysaccharides. They interact with hundreds of growth factors, chemokines, cytokines, proteases, protease inhibitors, and facilitate many signaling transduction pathways in a GAG composition and/or sequence-specific manner. When the GAG network goes awry, the problem cannot be defined by conventional genomic or proteomic approaches because GAGs are assembled without a genetic template. This review will summarize all GAG- and proteoglycan-related cancer biomarkers as well as GAG modification enzymes including sulfotransferase-, heparanase-, hyaluronidase-, and sulfatase-based biomarkers identified during the past 20 years. The published data demonstrate that the proteoglycan- and GAG-related cancer biomarkers are not produced by cancer cells alone, and they are indicators of a miscommunicated system during cancer development.

Temporal Data-Driven Sleep Scheduling and Spatial Data-Driven Anomaly Detection for Clustered Wireless Sensor Networks.

The spatial-temporal correlation is an important feature of sensor data in wireless sensor networks (WSNs). Most of the existing works based on the spatial-temporal correlation can be divided into two parts: redundancy reduction and anomaly detection. These two parts are pursued separately in existing works. In this work, the combination of temporal data-driven sleep scheduling (TDSS) and spatial data-driven anomaly detection is proposed, where TDSS can reduce data redundancy. The TDSS model is inspired by transmission control protocol (TCP) congestion control. Based on long and linear cluster structure in the tunnel monitoring system, cooperative TDSS and spatial data-driven anomaly detection are then proposed. To realize synchronous acquisition in the same ring for analyzing the situation of every ring, TDSS is implemented in a cooperative way in the cluster. To keep the precision of sensor data, spatial data-driven anomaly detection based on the spatial correlation and Kriging method is realized to generate an anomaly indicator. The experiment results show that cooperative TDSS can realize non-uniform sensing effectively to reduce the energy consumption. In addition, spatial data-driven anomaly detection is quite significant for maintaining and improving the precision of sensor data.

Recombinant human thyrotropin stimulated 131I treatment for multinodular goiter.

The aim of the study was to investigate the effects of rhTSH stimulation before 131I treatment in patients with MNG. METHODS: Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS database (all until January 2016). Randomized controlled trials (RCTs) that assessed the efficacy of rhTSH-stimulated 131I treatment compared to placebo or 131I treatment alone were collected. Two authors performed the data extraction independently. RESULTS: Six RCTs involving 294 patients with MNG were included in this review. Altogether 168 patients were randomized to rhTSH-stimulated 131I therapy, and 126 to either placebo and 131I or 131I alone. rhTSH-stimulated 131I vs placebo and 131I or 131I alone for MNG showed no statistically significant difference in quality of life and all-cause mortality. rhTSH- (at a dose of 0.03 mg and above) stimulated 131I treatment for MNG showed significant benefits in thyroid volume reduction. 131I treatment with rhTSH stimulation at high doses (0.03 mg, 0.1 mg, 0.3 mg and 0.45 mg) for MNG caused significantly higher adverse effects and hypothyroidism. CONCLUSIONS: The overall results indicated that using rhTSH at high doses of 0.03-0.45 mg before 131I therapy resulted in a greater TVR than 131I therapy alone for patients with non-toxic MNG. However, an increased incidence of adverse effects and hypothyroidism was observed in patients receiving high-dose of rhTSH pretreatment than in patients who received low-dose rhTSH pretreatment. Therefore, a dose of 0.03 mg rhTSH pretreatment before 131I therapy may be more potent than 131I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.

Nicotine effects on muscarinic receptor-mediated free Ca[Formula: see text] level changes in the facial nucleus following facial nerve injury.

It was suggested that muscarinic, and nicotinic receptors increase free Ca[Formula: see text] levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca[Formula: see text] overload can trigger either necrotic or apoptotic cell death. It is assumed that, following facial nerve injury, the interactions of nicotinic and muscarinic acetylcholine receptors in facial nerve nucleus may negatively regulate free Ca[Formula: see text] concentrations in the facial nerve nucleus, which provide important information for the repair and regeneration of the facial nerve. The present study investigated the regulatory effects of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus in a rat model of facial nerve injury at 7, 30, and 90 days following facial nerve injury using laser confocal microscopy. The dose-dependent regulation of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus may decrease the range of free Ca[Formula: see text] increases following facial nerve injury, which is important for nerve cell regeneration. It is concluded that the negative effects of nicotine on muscarinic receptors are related to the [Formula: see text] subtype of nicotinic receptors.

rhTSH-aided low-activity versus high-activity regimens of radioiodine in residual ablation for differentiated thyroid cancer: a meta-analysis.

The effects of low-activity versus high-activity radioiodine regimens in thyroid remnant ablation for patients with differentiated thyroid carcinoma (DTC) under recombinant human thyrotropin (rhTSH) stimulation have been widely quoted but there has been no systematic review of the evidence. We undertook a systematic review of randomized controlled trials to assess the effects of low-activity radioiodine in thyroid remnant ablation in patients with DTC under rhTSH stimulation compared with high-activity radioiodine. Studies were obtained from computerized searches of MEDLINE, EMBASE, and the Cochrane Library (all until September 2012). Randomized controlled trials were included. Altogether, 637 patients with DTC who participated in three trials for residual ablation were included. Overall, studies had a low risk of bias. We found no statistically significant differences between low-activity (1.11/1.85 GBq) and high-activity (3.7 GBq) radioiodine treatment aided by rhTSH in terms of successful ablation rates on the basis of diagnostic scans [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.49-1.47, P=0.56], thyroglobulin levels (OR 0.66, 95% CI 0.38-1.15, P=0.14), and health-related quality of life (mean difference 0.07, 95% CI -0.96 to 1.09, P=0.9). In addition, the subgroup analysis of 1.11 versus 3.7 GBq (OR 0.83, 95% CI 0.46-1.49, P=0.53) and 1.85 versus 3.7 GBq (OR 1, 95% CI 0.23-4.35, P=1) also showed no significant differences. The lower activity of 1.11 GBq showed significant benefit in terms of reduction in adverse events including neck pain, radiation gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI 0.42-0.93, P=0.02). Limited data from three randomized controlled trials suggested that an rhTSH-aided low radioiodine activity level of as low as 1.115 GBq may be sufficient for thyroid remnant ablation when compared with 3.7 GBq, with fewer common adverse effects in patients with metastasis-free DTC. Further evidence is needed to confirm the effects of low-activity radioiodine for thyroid remnant ablation. Radioiodine treatment of 1.11 GBq showed significant benefit in terms of reduction in adverse events including neck pain, radiation gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI 0.42-0.93, P=0.02). rhTSH-aided low radioiodine activity levels of 1.11 and 1.85 GBq are sufficient for thyroid remnant ablation as compared with 3.7 GBq, with fewer common adverse effects in patients with metastasis-free DTC. A well-designed study that compares low-activity with high-activity radioiodine ablation is needed to fully understand the long-term adverse effects and relapse or metastases.

Primary endodermal sinus tumor in the posterior cranial fossa: clinical analysis of 7 cases.

OBJECTIVE: To clarify the clinical features, therapeutic method and outcomes of the primary endodermal sinus tumors (ESTs) in the posterior cranial fossa. METHODS: The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed. And a 4-year-old boy diagnosed with EST in our hospital was reported. The clinical manifestations, therapy, pathologic features, and prognosis of these cases were analyzed. RESULTS: Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review, including six cases searched from the PubMed and one case from our hospital. Six patients were boy and one patient's gender was not available from the report. Ages ranged from 1 to 5 years (mean 3.14 years). The mean tumor size in our cohort was 4.4 cm. Six cases came from East Asia. Schiller-Duval bodies were found in all seven neoplasms. All tumors were positive for alpha-fetoprotein. The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy. The mean follow-up time was 24.4 months (range 5-52 months). Six tumors were totally removed, and four of them recurred. Three cases died including one whose tumor was partially removed. CONCLUSIONS: The serum alpha-fetoprotein level is well correlated with the severity of the tumor. A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa. The prognosis of extragonadal intracranial EST is poor.

Clinicopathologic significance of slug expression in human intrahepatic cholangiocarcinoma.

AIM: To explore the expression and function of slug, a transcriptional repressor, in human intrahepatic cholangiocarcinoma (IHCC) and identify its role in IHCC progression. METHODS: Expression of slug was detected in 36 cases of IHCC and 12 cases of normal intrahepatic bile ducts and liver parenchyma by immunohistochemistry. The patients were divided into low slug expression group (< 20% of carcinoma cells stained) and high slug expression group (> or = 20% of carcinoma cells stained). Slug expression was correlated with clinicopathological parameters of IHCC patients. The patients were defined as short-term survivors if their survival time was < 12 mo and as long-term survivors if their survival time was > or = 12 mo. RESULTS: Slug was not expressed in normal liver epithelium samples, lowly expressed in 15 tissue samples (10 -, 5 +) and highly expressed in 21 tissue samples (16 ++; 5 +++) from IHCC patients. The survival rate of patients with a low slug expression was 33.3% (n = 5) and 66.7% (n = 10), respectively. The survival rate of patients with a high slug expression was 61.9% (n = 13) and 38.1% (n = 8), respectively (P = 0.02). Lymph node metastasis was found in 4 (26.7%) out of the 15 patients with a low slug expression and in 14 (66.7%) out of the 21 patients with a high slug expression, respectively. The incidence rate of lymph node metastasis increased with the increasing slug expression level (P = 0.003), and higher in patients with a high slug expression than in those with a low slug expression. Slug expression did not significantly correlate with the tumor size and stage or histologic grade, or with the gender and age of patients CONCLUSION: Slug expression is a novel prognostic marker for IHCC with lymph node metastasis.

Long-term treatment with a Chinese herbal formula, Sheng-Mai-San, improves cardiac contractile function in aged rats: the role of Ca(2+) homeostasis.

A Chinese herbal formula Sheng-Mai-Yin (SMY), the liquid dosage form of Sheng-Mai-San, has been used clinically for treating heart failure, particularly in aged patients. To investigate the effect of SMY treatment on the contractile function of aged hearts, we first examined cardiac hemodynamics in aged rats. To define the mechanism involved in the enhancement of cardiac function, we investigated the effect of SMY treatment on Ca(2+) homeostasis in ventricular cardiomyocytes isolated from aged rats. Ca(2+) release was assessed by measurements of changes in cardiac Ca(2+) transients and Ca(2+) sparks, using laser scanning confocal microscopy. The functional status of Ca(2+)-release regulators, including L-type Ca(2+) channels, sarcoplasmic reticulum (SR) Ca(2+)-adenosine triphosphatase (ATPase), and ryanodine receptors (RyRs), was also assessed. The results indicated that SMY treatment (2 g/kg per day for 30 doses within 6 weeks, intragastically) significantly improved hemodynamic parameters in aged rats. SMY treatment markedly increased the amplitude and shortened the duration of Ca(2+) transients in aged cardiomyocytes, and reversed the age-related increase in frequency, decrease in amplitude, and changes in spatiotemporal properties of Ca(2+) sparks in cardiomyocytes. In addition, SMY treatment increased the L-type Ca(2+) current density, SR Ca(2+) content, and SR Ca(2+)-ATPase expression, and decreased the sensitivity of RyRs to Ca(2+), all of which are causally related to increases in the amplitude of Ca(2+) transients and the size of Ca(2+) sparks. In conclusion, the improvement in cardiac contractile function afforded by SMY treatment in aged rats is likely mediated by an increase in Ca(2+) release from the SR through L-type Ca(2+) current-activated RyRs.