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Background Immune thrombocytopenia (ITP) is an autoimmune disease characterized as a low platelet count resulting from immune-mediated platelet destruction. Dimethyl fumarate (DMF) is widely applied for the treatment of several autoimmune diseases with immunosuppressive effect. However, whether it ameliorates ITP is unclear. This study aims to evaluate whether DMF has a preventive effect on ITP in mice. Methods DMF (30, 60 or 90 mg/kg body weight) was intraperitoneally injected into mice followed by injection of rat anti-mouse integrin GPIIb/CD41antibody to induce ITP. Peripheral blood was isolated to measure platelet count and spleen mononuclear cells were extracted to measure Th1 and Treg cells along with detecting the levels of IFN-γ, and TGFβ-1 in plasma and CD68 expression in spleen by immuohistochemical staining. Additionally, macrophage cell line RAW264.7 was cultured and treated with DMF followed by analysis of cell apoptosis and cycle, and the expression of FcγRI, FcγRIIb and FcγRIV mRNA. Results DMF significantly inhibited antiplatelet antibody-induced platelet destruction, decreased Th1 cells and the expression of T-bet and IFN-γ, upregulated Treg cells and the expression of Foxp3 and TGF-β1 as well as reduced CD68 expression in the spleen of ITP mouse. DMF-treated RAW264.7 cells showed S-phase arrest, increased apoptosis and downregulated expression of FcγRI and FcγRIV. Meanwhile, in vitro treatment of DMF also decreased the expression of cyclin D1 and E2, reduced Bcl-2 level and increased Bax expression and caspase-3 activation. Conclusions In conclusion, DMF prevents antibody-mediated platelet destruction in ITP mice possibly through promoting apoptosis, indicating that it might be used as a new approach for the treatment of ITP.

Background "Diffuse midline glioma, H3 K27M-mutant" (DMG) mainly arises within the pontine, thalamic, and spinal cord regions. Because of the rarity of spinal cord gliomas, the general knowledge surrounding DMGs is mainly based on pontine and thalamic gliomas, whereas tumor location tends to influence the clinicopathological features and prognosis. Objective To determine the clinicopathological characteristics and molecular profiles of DMGs located in the spinal cord. Methods The clinical and molecular pathologic features and prognosis were comprehensively analyzed in a series of 44 patients with spinal cord DMGs. Results The median age was 36 yr, and 88.7% of patients (39/44) were adults (≥18 yr). Histopathologically, malignant grades included grade II (16 cases), grade III (20 cases), and grade IV (8 cases). Compared with patients with histological grade IV, patients with lower histological grade (grade II/III) were older (37 vs 24 yr, P = .020) and were associated with longer overall survival (24.1 vs 8.6 mo, P = .007). All 30 tested tumors were isocitrate dehydrogenase (IDH) wild type, and 96% of cases (22/23) presented with unmethylated O6-methylguanine-DNA methyltransferase. Univariate and multivariate analyses showed that histological grade and presurgery McCormick Scale scores were independent prognostic factors for overall survival, whereas extensive surgical resection and chemoradiotherapy were not significantly associated with improved survival. The most frequent anatomic locations were the cervical enlargement (C4-T1, n = 16) and conus medullaris (T12-L1, n = 13), which exhibited distinctive clinical characteristics and molecular features. Conclusion The findings provide guidelines for the evidence-based practice of the specialized management of spinal cord DMGs.

Introduction:. Scabies is an infectious skin disorder caused by the mite Sarcoptes scabiei. The diagnosis of scabies is often confirmed by microscopic detection of scabies mites, eggs, or feces. We herein describe the diagnosis of scabies in a boy with the assistance of dermoscopy and fluorescence microscopy. Case presentation:. A 16-year-old Chinese boy presented with a 2-month history of extensive papules and excoriations with intense pruritus on the trunk and limbs. Dermoscopy showed a sinuous burrow in the finger webs with a brown jet-shaped triangular structure at the end. A fluorescence microscopy revealed a hatching egg and a mite. The boy was diagnosed with scabies and treated with 5% sulfur ointment. Discussion:. The use of dermoscopy in patients with scabies reveals a sinuous burrow with a brown jet-shaped triangular structure composed of the pigmented head and anterior legs of the mite[1]. A fluorescence microscopy revealed mites and eggs with blue fluorescence after staining, allowing us to easily identify scabies. Conlcusion:. The combination of dermoscopy-guided tape testing with fluorescence staining technology may enhance the diagnostic accuracy and efficiency of scabies.

The enhanced release of inflammatory cytokines mediated by high mobility group box1 (HMGB1) leads to pain sensation, and has been implicated in the etiology of inflammatory pain. Paeonol (PAE), a major active phenolic component in Cortex Moutan, provides neuroprotective efficacy via exerting anti-inflammatory effect. However, the role and mechanism of PAE in inflammatory pain remain to be fully clarified. In this study, we showed that PAE treatment significantly ameliorated mechanical and thermal hyperalgesia of mice induced by complete Freund's adjuvant (CFA). The analgesic effect of PAE administration was associated with suppressing the enhanced expression of HMGB1 as well as the downstream signaling molecules including toll-like receptor 4 (TLR4), the nuclear NF-κB p65, TNF-α and IL-1β after CFA insult in the anterior cingulate cortex (ACC), a key brain region responsible for pain processing. Furthermore, inhibition of HMGB1 activity by glycyrrhizin (GLY), an HMGB1 inhibitor, alleviated CFA-induced pain and also facilitated PAE-mediated analgesic effect in mice along with the decreased expression of TLR4, NF-κB p65, TNF-α and IL-1β upon CFA injury. Collectively, we showed PAE exerted analgesic effect through inhibiting the HMGB1/TLR4/NF-κB p65 pathway and subsequent generation of cytokines TNF-α and IL-1β in the ACC.

Background Due to their rarity, the clinicopathological characteristics and prognostic factors of spinal cord gliomas are still unclear. Here, we aimed to clarify these issues in a cohort of 108 spinal cord astrocytomas. Methods We characterized the clinicopathological characteristics, including 2016 World Health Organization (WHO) grade, age, sex, location, segment length, resection, pre‐ and postsurgery, Modified McCormick Scale (MMS), radio‐ and chemotherapy, and Ki‐67 and H3 K27M mutations, in 108 spinal cord astrocytomas through heatmaps. The Cox regression analysis and Kaplan‐Meier curves were used to study the prognostic value of these clinicopathological features. Results There are a total 38 H3 K27M‐mutant tumors, including 31 cases with histological grade II/III tumors. The age of low‐grade astrocytoma patients (WHO grade I/II, n = 54) was significantly younger (27.0 vs 35.5 years, P = .001) than those with high‐grade tumors (WHO grade III/IV, n = 54). All patients underwent surgical resection with neurophysiological monitoring, and the surgery did not result in significant changes in MMS. The presurgery MMS was associated with overall survival in the high‐grade subgroup (P = .008) but not in the low‐grade subgroup (P = .312). While, the high content of resection improved the survival of only patients with low‐grade astrocytomas (P = .016) but not those with high‐grade astrocytomas (P = .475). Both the low‐grade and high‐grade astrocytomas had no obvious benefit from neither adjuvant chemotherapy nor radiotherapy (all P > .05). Conclusions We characterized the clinicopathological characteristics and their prognostic values in 108 spinal cord astrocytomas, which could help with evidence‐based management of spinal cord astrocytomas., We characterized the clinicopathological characteristics and their prognostic values in 108 spinal cord astrocytomas, which could help with evidence‐based management of spinal cord astrocytomas.

The present study compared the expression levels of limb-bud and heart (LBH) between gastric intestinal-type adenocarcinoma (GITA) and healthy gastric tissues; with the aim of investigating the possible effect of LBH on the prognosis of patients with GITA and to analyze the associated signaling pathways in GITA. Three Oncomine gastric datasets were utilized for the preliminary prediction of the expression levels of LBH mRNA in GITA and healthy gastric tissues. Gene expression and corresponding clinical data of 163 patients with GITA were downloaded from The Cancer Genome Atlas. Wilcoxon signed rank-sum test was used to distinguish the clinical value of LBH expression in the various clinicopathological features. Subsequently, Kaplan-Meier univariate and Cox multivariate survival analyses were performed to determine the prognostic significance of LBH expression in patients with GITA. Function enrichment analysis was conducted for the co-expression gene of LBH, defined as correlation coefficient r>0.06 and P

Background. Helicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP. Methods. We searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I2) statistic. Results. A total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29–0.47). The combined estimate is I2 = 57% (P

Anxiety leads to a global decline in quality of life and increase in social burden. However, treatments are limited, because the molecular mechanisms underlying complex emotional disorders are poorly understood. We explored the anxiolytic effects of 8-O-acetyl shanzhiside methylester (8-OaS), an active component in Lamiophlomis rotata (L. rotata; Benth.) or Kudo, a traditional herb that has been shown to be effective in the clinical treatment of chronic pain syndromes in China. Two mouse anxiety models were used: forced swimming stress (FSS)–induced anxiety and complete Freund’s adjuvant (CFA)–induced chronic inflammatory pain. All animal behaviors were analyzed on the elevated plus maze and in the open-field test. 8-OaS significantly ameliorated anxiety-like behaviors in both anxiety models and inhibited the translation enhancement of GluN2A, GluN2B, and PSD95. Moreover, a reduction in GABA receptors disrupted the excitatory/inhibitory (E/I) balance in the basolateral amygdala (BLA), indicated by increased excitatory and decreased inhibitory presynaptic release. 8-OaS also blocked microglia activation and reduced the phosphorylation of p38, c-Jun N-terminal kinase (JNK), NF-κB p65, and tumor necrosis factor alpha (TNF-α) in the BLA of anxiety mice. 8-OaS exhibits obvious anxiolytic effects by regulating the excitatory/inhibitory (E/I) synaptic transmission and attenuating inflammatory responses in the BLA.

A 46-year-female presented with a one-week history of multiple erythema and blisters with pruritus on the extremities. She had received both doses of the SARS-CoV-2 vaccine (CoronaVac developed by Sinovac Life Sciences, Beijing, China) which is an inactivated vaccine. She had no adverse reactions after the first dose.

Given the large amount of food waste coming from households, reducing household food waste is essential to the mitigation of overall food waste and the provision of multi-faceted benefits for both people and the planet. This study identifies factors and management strategies for the reduction of household food waste in the Taiwanese household setting. Using snowball sampling, semi-structured interviews are conducted to collect data from 27 household food providers in Taipei. The research findings identify four critical motivators and four barriers to minimizing household food waste in Taiwan. The most frequently mentioned motivator for the reduction of food waste is a convenient shopping environment, and the most important barrier is lack of knowledge for assessing the edibility of food. Additionally, four major prevention strategies are identified to help reduce household food waste: (1) planned purchase schedule, (2) skills to keep food fresh and longer, (3) understanding family preferences and leftover management, and (4) sharing additional food and co-procurement and cooking. The results of this study not only help improve the understanding and application of Chinese household food waste reduction, but also demonstrate the significance of its socio-cultural impacts in future studies.

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction, leading to lower platelet count. Thalidomide is considered as a novel immunomodulatory drug for treating several autoimmune diseases. Whether thalidomide can ameliorate ITP remains unclear. This study aims to evaluate the effect of thalidomide on ITP mouse model. ITP mouse model was established through intraperitoneal injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin. Thalidomide (10, 20 or 50 mg/kg body weight) was intraperitoneally injected into mice followed by antibody injection. Then, peripheral blood and plasma was isolated for analysis of platelet count and the level of IFN-γ and IL-17 in plasma. Meanwhile, spleen was extracted to measure the expression of CD68, a macrophage marker. In addition, macrophage cell line RAW264.7 was cultured and treated with thalidomide followed by analysis of cell viability, apoptosis as well as cell cycle. Thalidomide prevented antiplatelet antibody-mediated platelet destruction in ITP mouse model. Compared with vehicle (phosphate-buffered saline), thalidomide significantly inhibited the secretion of IFN-γ and IL-17 in ITP mouse and reduced the expression of CD68 in spleen. After thalidomide treatment, the cell viability of RAW264.7 cell was significantly reduced and the cell number in S phase was also significantly decreased. In addition, the expression of cyclin E2 was significantly reduced. In conclusion, thalidomide prevents antiplatelet antibody-mediated platelet destruction in ITP mouse possibly through reducing the number of macrophages, suggesting that it might be a novel approach for treating ITP.

To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP). A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events. Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P

A stochastic micromechanical framework is proposed to quantitatively characterize the probabilistic behavior of the saturated concrete healed by the electrochemical deposition method (EDM). Multiphase micromechanical representation for the healed saturated concrete is presented based on the material’s microstructures. Differential scheme-based multilevel homogenization procedures are proposed to quantitatively predict the effective properties of the repaired concrete. The material microstructures are characterized by the non-stationary random process and random variables. The probabilistic behavior for the repaired concrete is reached with high computational efficiency by incorporating the dimensional decomposition method and Newton interpolations. The predictions obtained by the proposed stochastic micromechanical framework are then compared with the available experimental data, existing models, and direct Monte Carlo simulations, which indicates that the presented stochastic micromechanical framework is computationally efficient and capable of characterizing for the probabilistic behavior of saturated concrete repaired by EDM considering the inherent randomness. Finally, the influences of the deposition products and healing degrees on the probabilistic behavior of repaired concrete are discussed based on the proposed models.

The electrochemical CO2 reduction reaction (CO2RR) is a promising technology for converting waste CO2 into chemicals which could be used as feedstock for the chemical industry or as synthetic fuels...

This paper presents a new location detection technology to find the bar code under complex background. Firstly, the contour of the grayscale image is extracted by the optimized Sobel operator and differential algorithm, and then we use the morphological algorithm to make extracted contours more complete and clear. Secondly, we select the area where the bar code may exist, with the area of contours as a standard. Then the paper uses the Hough transform to detect and filter the contour edges that meet the requirements. Then aiming at the area where the edge of the selected contour was located, we calculate the gradient in the relevant direction and statistic results. Furthermore, based on statistics, we filtered out the area where the bar code is located. Experiments show that the bar code location detection algorithm proposed in the paper is not only superior to the traditional gradient detection and morphological detection methods, but also has the advantage such as good robustness, small amount of processed data, fast processing speed, and high accuracy, which is fit for the image larger than 4 million pixels.

China's economy has achieved rapid growth, but the change has also brought about serious environmental degradation, which is the main factor endangering human health. This study empirically investigates the impact of the population health environmental index on the promotion of provincial governors using an ordered probit model. The sample of the study consists of regions where provincial governors, municipal mayors, and autonomous region chairmen were stationed from 1995 to 2015. The results show that the population health environmental index had a significant and positive impact on governors' promotions, especially in the eastern region. The reformation of the population health environmental index assessment system for government officials was the initial factor that brought about these effects.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

The authors have requested that this preprint be removed from Research Square.

Purpose Clodronate-liposomes (Clod-Lip) is an effective candidate drug for treating chronic myelomonocytic leukemia, autoimmune hemolytic anemia and immune thrombocytopenic purpura in mice experiments. But its role in hematopoietic recovery after acute myelosuppression is still unknown. We aim to explore the function and underlining mechanisms of Clod-Lip on hematopoietic reconstitution after sublethal dose irradiation in mice. Materials and methods Mice at 8-10 weeks received a total-body sublethal dose γ-irradiation (TBI) and injected with Clod-Lip or PBS-Liposomes (PBS-Lip) every 4 days after TBI. The survival rate of each group was recorded. Flow cytometry was used to analyze changes in hematopoietic stem cells and their progenies in bone marrow. ELISA and RT-qPCR were used for the analysis of hematopoietic regulatory factors. Regarding IL-1β inhibition, 25 mg/kg diacerein or an equal volume of DMSO was intraperitoneally injected into mice every day after TBI. Results In sublethal dose-irradiated mice, Clod-Lip reduced the survival rate, the total number of bone marrow and hematopoietic stem cells, delayed peripheral blood recovery of red blood cells and platelets. However, it could increase the number of CMP, MEP and myeloid cells, which suggested that Clod-Lip could induce HSC to myeloid differentiation in vivo. We further verified that Clod-Lip may induce myeloid differentiation by bone marrow microenvironmental factor IL-1β. Conclusions In summary, this study suggested that Clod-Lip may aggravate inhibitor effect of hematopoietic function and promote myeloid differentiation in myelosuppression mice model.

Background There has been limited research on the comparison of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of cervical cancer and that lack of information may have significant bearing on the treatment of patients. We compared survival outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer patients and examined factors related to the prognosis of cervical cancer. Methods We identified 4131 patients with stage IB2-IVA cervical cancer patients diagnosed between 2010 and 2015 by using the Surveillance, Epidemiology, and End Results (SEER) database. Variables related to the prognosis of cervical cancer were compared using both univariate and multivariate Cox models and log-rank method before and after propensity score matching. We compared the efficacy of radiotherapy alone to radiotherapy combined with chemotherapy or/and surgery in overall survival of SCC and AC. Results Our sample included 3385 patients with SCC (81.9%) and 746 patients with AC (18.1%). The 5-year overall survival on comparing the squamous cell carcinoma group and adenocarcinoma group was not significant (P > 0.05). Using propensity score matching, 676 pairs of patients were selected. The 5-year overall survival of matched patients did not differ significantly (P > 0.05). Histology was not independently associated with overall survival in multivariate Cox model (P > 0.05). Factors affecting overall survival included FIGO stage IVA (P P Conclusions The OS in AC of the cervix is similar to that SCC in when treated with radiotherapy combined with chemotherapy and/or surgery but better when treated with radiation alone.

This paper is mainly aimed at the development requirement of infrared seeker precision guided weapon system. The infrared sensor of seeker is modeled and simulated, and the image sequence is output. The imaging simulation quality of infrared seeker sensor and the adaptability of terminal guidance algorithm based on simulation real-time graph are evaluated from the perspectives of multi-granularity similarity parameter index system construction, multi-saliency fusion feature consistency and bio-visual feature similarity evaluation. At the same time, the analytic hierarchy process (AHP) model is applied to the process of similarity evaluation to solve the comprehensive decision-making problem in multi-index similarity evaluation, and to evaluate the performance of the simulation system from the perspective of the combination of human-computer intelligence, so as to guide the improvement of the simulation system. Based on the above research results, a set of mature and reliable simulation similarity evaluation software is formed. The research results are of great significance to the development and standardization of the whole infrared simulation technology.

We study the nonreciprocal properties of transmitted photons in a chiral waveguide quantum electrodynamics (QED) system, including single- and two-photon transmissions and second-order correlations. For the single-photon transmission, the nonreciprocity is induced by the effects of chiral coupling and atomic dissipation in the weak coupling region. It vanishes in the strong coupling regime when the effect of atomic dissipation becomes ignorable. In the case of two-photon transmission, there exist two ways of going through the emitter: independently as plane waves and formation of bound state. Besides the nonreciprocal behavior of plane waves, the bound state that differs in two directions also alters transmission probabilities. In addition, the second-order correlation of transmitted photons depends on the interference between plane wave and bound state. The destructive interference leads to the strong antibunching in the weak coupling region, while the effective formation of bound state leads to the strong bunching in the intermediate coupling region. However, the negligible interactions for left-propagating photons hardly change the statistics of the input coherent state.

As the key component of glutathione peroxidase with unique antioxidant properties, selenium has been considered to play an important part on lipid metabolism. However, the associations of serum selenium concentrations with lipid concentrations and dyslipidemia are still controversial.We analyzed cross-sectional data including serum selenium levels, lipid concentrations and other related indexes of 8198 rural Chinese. Serum selenium was measured by inductively coupled plasma mass spectrometry, and total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and low density lipoprotein-cholesterol (LDL-c) of serum were measured with kits.Overall, mean serum selenium was 120 μg/l. Multivariate liner regression revealed that selenium concentrations were positively correlated with TC (P 0.001), HDL-c (P 0.001), TG (P 0.001) and LDL-c (P 0.001). Compared with the lowest quintile of serum selenium, participants in quintile 3, 4 and 5 had higher risks of High-TC dyslipidemia (P ≤ 0.02) and High-LDLC dyslipidemia (P 0.02) after adjusting for covariates. In the stratified analyses, we found that the selenium-dyslipidemia associations were significantly stronger in post-menopausal women (OR: 2.72; 95% CI: 1.97, 4.17) and diabetics (OR: 9.40; 95% CI: 3.02, 29.26).Elevated serum selenium levels were correlated with the increased concentrations of TC, LDL-c, HDL-c and TG, and increased the risk of High-TC and High-LDLC dyslipidemia among rural Chinese. However, the real associations between serum selenium and lipid profile should be verified in specifically designed randomized trials in future.

Although selenium, which is a necessary trace element for the human body, has been considered to be beneficial to the cardiovascular system and helpful to lower blood pressure, more and more evidence shows that high amounts of selenium are a risk factor for hypertension. A random multistage sampling which included the cluster method was performed; a total of 9076 urban and rural residents between 18 and 80 years old in the Shandong province of China were investigated by questionnaire, physical examination, and laboratory tests. The prevalence of hypertension was 42.1% in males and 35.3% in females. The mean (standard deviation) selenium concentration was 124.68 (36.32) μg/l in males and 119.54 (31.88) μg/l in females. After adjusting for potential confounders, logistic regression analysis showed that the highest selenium levels were associated with a risk of hypertension (OR = 1.192; 95% CI 1.009-1.407) in females, while there was no significant difference in males (OR = 1.043; 95% CI 0.864-1.259). Our findings suggest that high selenium levels in females are more likely to increase the risk of hypertension compared to similar levels in males. More attention should be paid to the metabolic mechanisms and physiological effects of selenium in females.

Immune thrombocytopenia (ITP) is an autoimmune disease, which is characterized by abnormal of T immunity. A disintegrin and metalloproteinase (ADAM) 10, a member of proteinase family, has been demonstrated to regulate T cell proliferation and effector function. Considering the closely association of dysregulation of T cell function with ITP, whether ADAM10 involves in the pathogenesis of ITP remains unclear. In this study, 54 active ITP patients, 18 ITP in remission and 24 age and gender matched healthy control were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and control for isolation of RNA and plasma which were used to measure mRNA level of ADAM10 and tissue inhibitor of metalloproteinase 3 (TIMP3) by quantitative real-time PCR and soluble level of FasL and lymphocyte activation gene-3 (LAG-3) in plasma by ELISA. Meanwhile, T cell activation was measured by flow cytometry. Our results showed significantly higher expression of ADAM10 and lower expression of TIMP3 in active ITP patients compared with control, which were all restored into normal level in remission patients. Consistent with the expression profile of ADAM10, increased soluble plasma level of FasL and LAG-3 were observed in active ITP patients and reduced to normal level in patients in remission. Furthermore, increased T cell activation as demonstrated by higher expression of HLA-DR and CD69 were found in active ITP patients. In conclusion, elevated expression of ADAM10 was associated with the pathogenesis and development of ITP and therapeutically targeting it might be a novel approach for the treatment of ITP.

Pretreatment before transplantation initiates an inflammatory response. Inflammasomes are key regulators of immune and inflammatory responses, but their role in regulating hematopoiesis is unclear. Our study intended to assess the role and mechanism of nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 1 (NLRP1) in the bone marrow microenvironment on hematopoiesis regulation. To explore the effects of an absence of NLRP1 on hematopoietic reconstitution, we established a hematopoietic cell transplantation model by infusing bone marrow mononuclear cells of wild-type C57BL/6 mice into either NLRP1 knockout (NLRP1-KO) or wild-type C57BL/6 mice. Using the transplantation model, the role of NLRP1 in the bone marrow microenvironment was determined by flow cytometry, hemacytometry, and hematoxylin and eosin staining. As the major component of the bone marrow microenvironment, mesenchymal stem cells (MSCs) were isolated to analyze the effects of NLRP1 on them by osteogenic and adipogenic induction. Endothelial cells (ECs) were isolated and sorted by magnetic beads. The expression of adhesion molecules and their relationship with nuclear factor kappa B (NF-κB) were measured by immunofluorescence, enzyme-linked immunosorbent assay, and western blot. Finally, the effect of NLRP1-deleted MSCs or ECs on hematopoietic stem and progenitor cells (HSPCs) was examined by establishing co-culture models. Compared with C57BL/6 recipients, reduced inflammatory cell infiltration, decreased levels of proinflammatory cytokines interleukin (IL)-18, IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), together with reduced pathological injury of bone marrow, were observed in NLRP1-KO recipients after transplantation. However, increased HSPC engraftment and hematopoietic reconstitution were detected in NLRP1-KO recipients after transplantation. Furthermore, MSCs isolated from NLRP1-KO mice had decreased osteogenic and adipogenic differentiation and increased proliferation and differentiation of HSPCs. The expression of adhesion molecules in ECs from NLRP1-KO mice was increased due to the promotion of nuclear translocation of NF-κB; these adhesion molecules are critical for hematopoietic stem cell homing. Knockout of NLRP1 in the bone marrow microenvironment could significantly relieve bone marrow inflammatory response and promote hematopoietic reconstitution, perhaps by regulating MSCs and ECs, indicating that NLRP1 might be a target for the treatment of delayed hematopoietic and immune recovery in patients after hematopoietic stem cell transplantation.

This paper proposes an optimal 4H-silicon carbide trench MOS barrier Schottky (TMBS) Rectifier. The optimal structure of this rectifier is achieved by adding an N− wrapping region at the P+ shielding of the conventional TMBS structure, which significantly reduces the depletion region formed by the P+ shielding region. As a result, the proposed structure provides a lower ON-resistance comparing with the conventional P+ shielding structure. Moreover, we study the electric characteristics of the proposed structure via numerical simulation. Such a structure improves the specific ON-resistance and figure of merit of the conventional P+ shielding TMBS by 32.2% and 48.4%, respectively, and offers a high breakdown voltage, i.e., up to 1908 V.

Wide bandwidth, wide tunable phase range, and a compact circuit size are always desired for the tunable phase shifter utilized in the modern wireless communication system. However, the existing reflection-type phase shifter configurations cannot satisfy all these requirements simultaneously. To resolve these problems, the reflection load consisting of two tunable capacitors and a quarter wavelength transmission line is utilized on a vertically installed planar structure to implement a new reflection-type phase shifter. For demonstration, a reflection-type phase shifter is designed, fabricated, and measured. A wide bandwidth of 66.7% defined by 10-dB return loss had been achieved. Over the same band, a wide phase shift range up to 407° can be observed. Meanwhile, the fabricated circuit occupies a compact circuit size of ${0.26\lambda _{g} *0.37\lambda _{g}}$ .

Biglycan (BGN), a key member of the small leucine-rich proteoglycan family, is an important component of the extracellular matrix. Clinical studies have demonstrated that upregulation of BGN is associated with poor prognosis in patients with various types of solid cancer. The present study analyzed the mRNA expression levels of BGN in various types of solid cancer when compared with that in normal tissues via the Oncomine database. The UALCAN, OncoLnc and Kaplan-Meier Plotter databases were additionally used to evaluate the prognostic values of BGN in patients with solid cancer and co-expression gene analysis was conducted using the protein-protein interaction networks of BGN. The present study observed that the mRNA expression levels of BGN were increased in bladder, brain and central nervous system, breast, colorectal, esophageal, gastric, head and neck, lung, ovarian and 28 subtypes of cancer compared with normal tissues. The increased expression of BGN was identified to be associated with a poor outcome in ovarian and gastric cancer. Based on the co-expression network, BGN was identified as the key gene in a 43-gene network. The present findings of increased expression of BGN in solid tumors and its positive association with poor outcome on patient survival indicate that BGN may serve as a prognostic marker and as a target for novel therapeutics for multiple types of cancer.

Brain tumor is resulting from the development of abnormal cells in the brain, probably leading to headache, vision or mental problems. Currently, surgery is the most effective solution to remove the tumor cells as possible. However, it is difficult to determine the safe margin during brain surgery. In this study, we implement optical coherence tomography (OCT) and OCT angiography (OCTA) to in vivo observe the growth of brain tumor and to evaluate the difference between normal and cancerous brain tissue. A swept-source OCT (SS-OCT) with a center wavelength of 1060 nm was developed for the study of brain tumor on the animal model and the angiographic algorithm was also demonstrated for simultaneously acquiring brain microcirculation. From the results, the change in the morphology of brain tissue during tumor growth can be identified. Moreover, the angiogenesis resulting from tumor growth can be observed. Moreover, the texture of OCT images and the angiogenesis are quantitatively evaluated. It can be noted that OCT/OCTA could be a potential tool for in vivo identification of brain tumor during brain surgery or treatments.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by lower platelet count resulting from immune cells-mediated platelet clearance. Tacrolimus is an immunosuppressive agent which selectively inhibits T cell activation. Whether tacrolimus plays a role in ITP remains unclear. This study aimed to investigate the effect of tacrolimus on ITP in mice. An ITP mouse model was established by injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin and treated with tacrolimus followed by isolation of peripheral blood mononuclear cells and plasma. The mRNA expression of T-bet, GATA3, and Foxp3 was measured by RT-PCR, and level of IFN-γ, IL-12p70, IL-4, IL-13, and TGF-β in plasma was measured by ELISA. Tacrolimus inhibited antiplatelet antibody-mediated platelet clearance in ITP mouse model. Meanwhile, tacrolimus-treated ITP mice displayed a significant decrease in the mRNA expression of T-bet and plasma level of IFN-γ and IL-12p70 compared with ITP mice but without differences when compared with normal mice. Furthermore, the expression of GATA3, Foxp3, and plasma level of IL-4 and TGF-β were upregulated in tacrolimus-treated ITP mice without significant differences to normal mice (except TGF-β). Tacrolimus prevents antiplatelet antibody-mediated thrombocytopenia in ITP mice possibly through regulating T cell differentiations, suggesting it might be a novel approach for preventing ITP.

To evaluate the effectiveness of diphenhydramine, an antihistamine with anti-muscarinic properties, for prevention of postoperative catheter-related bladder discomfort (CRBD).Ninety-six ASA physical status I and II adult female patients (20-60 years) scheduled for elective gynecologic laparoscopic surgery were included. Patients were randomized into two groups of 48 patients each. All patients received a detailed preoperative explanation of the possible consequences of CRBD. The control group received normal saline 2 ml, whereas the diphenhydramine group received diphenhydramine 30 mg intravenously after induction of general anesthesia. Then, all patients were catheterized with a 14F Foley catheter and the balloon was inflated with 10 ml of distilled water. All patients who complained of CRBD in the postoperative room were appeased with nursing. Ketorolac 30 mg was used as the rescue drug on patients' request or when the patient was evaluated as having moderate or severe CRBD. Bladder discomfort and its severity were assessed at 1, 2 and 6 h postoperatively. The severity of CRBD was graded as none, mild, moderate and severe. Adverse effects of diphenhydramine such as sedation, dry mouth or GI upset were recorded.The incidence of CRBD was lower in the diphenhydramine group compared with the control group at 2 h (34.8 vs. 58.7%, p = 0.02) and 6 h (23.9 vs. 56.5%, p 0.01) postoperatively. Diphenhydramine treatment also reduced the severity of CRBD at 6 h postoperatively (p = 0.01). Moreover, the request for rescue for CRBD was lower in diphenhydramine group at 2 h (8.7 vs. 26.1%, p = 0.03). There were no significant differences in side effects, such as sedation, dry mouth or gastrointestinal upset between the two groups (p 0.05).Prophylactic diphenhydramine 30 mg at induction of general anesthesia reduced the incidence and severity of postoperative bladder discomfort without significant side effects in patients receiving gynecologic laparoscopic surgery.

Erythema papulatum centrifugum (EPC), also known as erythema papulosa semicircularis recidivans (EPSR), is distinct from eczema and other well-described figurate erythemas characterised by annular erythematous lesions. We report 7 cases of EPC and propose new diagnostic criteria including the following: (i) EPC is characterised by single or multiple recurrent expanding annular or semi annular erythema with central regression, surrounded by tiny red papules; (ii) the lesions regularly relapse and resolve; (iii) the histopathologic feature shows superficial perivascular inflammation with or without mild inflammation around sweat glands in the mid dermis and (iv) patients lack other associated cutaneous or internal abnormalities.

Introduction:FANCC is reported as a novel susceptibility gene for breast cancer, however, its mutation remains unclear in Chinese population. We aimed to identify the germline mutations of FANCC in high-risk breast cancer patients in China.Methods: 255 BRCA1/2-negative Chinese familial breast and/or ovarian cancer (FBOC) patients were recruited for FANCC germline mutations screen. For whom 90 patients were detected by PCR-sequencing assay, and another 165 patients were detected by a 98-gene panel sequencing assay. The 98-gene panel sequencing assay was also used to screen other possible gene mutations for the patients with FANCC mutations detected by PCR-sequencing assay. Two hundred and fifty sporadic breast cancer (SBC) patients and 248 female non-cancer controls (FNCCs) were recruited for the genotyping analysis. Immunohistochemistry (IHC) analysis was used to evaluate the FANCC expression in patients with FANCC mutation.Results: We found one rare FANCC deleterious mutation (c.339G>A, p.W113X, 0.4%) and two novel non-synonymous variants (c.51G>C, p.Q17H, 0.4% and c.758C>A, p.A253E, 0.4%) in FBOC patients, whereas none of above mutations was identified in SBC patients or FNCCs. We also found that one novel synonymous variant (c.903A>G, p.A301A) existed in one FBOC patient. Additionally, two non-synonymous SNPs rs201407189 (c.973G>A, p.A325T) and rs1800367 (c.1345G>A, p.V449M), and two synonymous SNPs rs55719336 (c.816C>T, p.I272I) and rs79722116 (c.1407G>A, p.T469T) were identified in FBOC patients.Conclusion:FANCC deleterious mutations exist in Chinese FBOC patients and investigations on the penetrance and spectrum of FANCC mutations need to be further conducted.

We theoretically investigate the enhancement of the degree and bandwidth of squeezed states of light generated in cascaded optomechanical (OM) systems. With the obtained recursion relation of the generalized output quadratures, it is possible to realize cascaded OM systems operated simultaneously in a deamplification situation for the same quadrature with a frequency-dependent phase shift between cascaded systems. Due to the cumulative OM interaction, the degree of squeezing can be significantly improved and nearly independent of frequencies. Thus the squeezing frequency band is notably broadened. Moreover, the squeezing bandwidth can be further broadened through tuning the detunings between laser and cavity frequencies. Finally, the influence of optical losses on squeezing due to the inefficient transmission between cascaded systems is also taken into account, which degrades the squeezing via introducing uncorrelated vacuum noises. However, a better squeezed state is still achievable compared to that generated in single OM system.

It is always advantageous to include additional bandpass filtering functionality within different circuits and components in the wireless communication system, and thus, a novel circular patch loaded with vias and stubs is proposed as the basic element to achieve this function integration, as well as the performance enhancement. Owing to the introduction of a new operation mode and flexibility of the proposed patch element in locating the frequencies of different operation modes, excellent bandpass characteristics can be implemented with simplicity in structure. First, the proposed patch element is used to implement a triple-mode bandpass filter with a very wide harmonic suppression. As an extension, a novel rectifying circuit with extended input power range and bandpass filtering property is implemented based on a bandpass filtering power divider, which is also implemented using the basic patch configuration. To verify the validity of the proposed patch configurations, three different kinds of circuits have been designed, fabricated, and measured. All measured results are found to be in good agreement with the simulation results.