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Vascular smooth muscle cell (VSMC) plasticity is tightly associated with the pathological process of vasculopathy. Blood vessel epicardial substance (Bves) has emerged as an important regulator of intracardiac vasculogenesis and organ homeostasis. However, the involvement and role of Bves in VSMC plasticity and neointimal lesion development remain unclear.We used an in vivo rat model of graft arteriosclerosis and in vitro PDGF-treated VSMCs and identified the novel VSMC contractile phenotype-related gene Bves using a transcriptomic analysis and literature search. In vitro knockdown and overexpression approaches were used to investigate the mechanisms underlying VSMC phenotypic plasticity. In vivo, VSMC-specific Bves overexpression in rat aortic grafts was generated to assess the physiological function of Bves in neointimal lesion development.Here, we found that Bves expression was negatively regulated in aortic allografts in vivo and PDGF-treated VSMCs in vitro. The genetic knockdown of Bves dramatically inhibited, whereas Bves overexpression markedly promoted, the VSMC contractile phenotype. Furthermore, RNA sequencing unraveled a positive correlation between Bves and dual-specificity protein phosphatase 1 (Dusp1) expression in VSMCs. We found that Bves knockdown restrained Dusp1 expression, but enhanced p38MAPK and ERK1/2 activation, resulting in the loss of the VSMC contractile phenotype. In vivo, an analysis of a rat graft model confirmed that VSMC-specific Bves and Dusp1 overexpression in aortic allografts significantly attenuated neointimal lesion formation.Bves maintains the VSMC contractile phenotype through Dusp1-dependent p38MAPK and ERK1/2 signaling, and protects against neointimal formation, underscoring the important role of Bves in preventing transplant vasculopathy.

Background The role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive. Methods Real‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78‐kDa glucose‐regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X‐box binding protein 1 (sXBP‐1), and phosphorylated eukaryotic initiation factor 2α (p‐eIF2α), in inferior turbinate tissue samples from patients with AR and non‐AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor. Results Compared to those in non‐AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non‐AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4‐PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α was significantly reduced in cultured AR‐derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants. Conclusions ER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production. Level of Evidence NA

Silicon carbide (SiC) is a high-performance structural ceramic material with excellent comprehensive properties unmatched by metals and other structural materials. In this paper, the raw SiC powder with an average grain size of 5 μm was sintered by an isothermal compression process at 5.0 GPa and 1500 °C, and the maximum hardness of the sintered samples is 31.3 GPa. Subsequently, scanning electron microscopy was used to observe the microscopic morphology of the recovered SiC samples treated in the temperature and extended pressure range of 0 - 1500 °C and 0 - 16.0 GPa, respectively. The defects and plastic deformation in SiC grains were further analyzed by transmission electron microscopy. Further, high pressure in situ synchrotron radiation x-ray diffraction was used to study the intergranular stress distribution and yield strength under non-hydrostatic compression. This study provides a new viewpoint for the sintering of pure phase micron sized SiC particles.

Background: Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. Objective: To study the role of IL-17A, CXCL13 and lymphotoxin (LT) in eLT formation in NPs. Methods: The expression of CXCL13 and LT as well as their receptors, and the phenotypes of stromal cells in NPs were studied by flow cytometry, immunostaining, and RT-PCR. Purified nasal stromal cells and polyp B cells were cultured and a murine model with nasal type 17 inflammation was established for the mechanistic study. Results: Excessive CXCL13 production was found in NPs and correlated with enhanced IL-17A expression. Stromal cells, with an expansion of CD31-Pdpn+ fibroblastic reticular cell (FRC) type, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1β2 in NPs with eLTs. CXCL13 upregulated LTα1β2 expression on polyp B cells, which in turn promoted CXCL13 production from polyp B cells and nasal stromal cells. LTα1β2 induced expansion of FRCs and CD31+Pdpn+ lymphoid endothelial cells, corresponding to the phenotypic characteristic of stromal cells in NPs with eLTs. IL-17A gene knockout, and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model. Conclusion: We identified an important role of IL-17A-induced stromal cell remodeling in the initiation, and crosstalk between B and stromal cells via CXCL13 and LTα1β2 in the enlargement of eLTs in NPs.

Background In this study we aimed to identify inflammatory patterns and predictors associated with clinical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients with different blood and tissue eosinophilia. Methods A total of 535 CRSwNP patients were enrolled, and the expression of 35 biomarkers, together with eosinophil and neutrophil counts in nasal polyps, were analyzed in a subset of 249 patients. Patients were stratified on the basis of blood (≥0.5 × 109 /L) and tissue (>10%) eosinophilia. Logistic regression models were applied to identify predictors of uncontrolled disease at least 1 year after surgery. Uncontrolled disease was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Results Among 535 patients, 38.5% showed inconsistent blood and tissue eosinophilia. In 249 CRSwNP patients, subjects with concomitant blood and tissue eosinophilia (group 1) showed marked mucosal type 2 inflammation, characterized by high levels of interleukin (IL)-5, IL-13, and eotaxin-1, whereas subjects with normal blood and tissue eosinophil levels (group 4) demonstrated significant local neutrophilic inflammation with high expression of granulocyte colony-stimulating factor and subjects with selective tissue eosinophilia (group 2) showed intermediate and mixed eosinophilic and neutrophilic inflammation. Subjects with isolated blood eosinophilia (group 3) showed low expression of vascular endothelial growth factor and IL-10. Asthma, prior sinus surgery, and blood eosinophilia were the top 3 predictors for postsurgical uncontrolled disease. For subgroup analysis, sex in group 1, asthma in group 2, tissue IL-10 and immunoglobulin E in group 3, and prior sinus surgery in group 4 were the strongest predictors of uncontrolled disease, respectively. Conclusion Different blood and tissue eosinophilia revealed distinct tissue inflammatory patterns in CRSwNP patients.

Ectopic lymphoid tissues (eLTs) characterized by B cell aggregation contribute to the local immunoglobulin production in nasal polyps (NPs). B cell-activating factor (BAFF) is vital for B cell survival, proliferation, and maturation. The purpose of this study is to investigate whether BAFF is involved in the B cell survival and eLT formation in NPs. The mRNA and protein levels of BAFF in NP tissues with and without eLTs were detected by PCR and ELISA assay, respectively. The cellular sources of BAFF and active caspase-3-positive B cells in NPs were studied by immunofluorescence staining. B cells purified from NP tissues were stimulated with BAFF and were analyzed by flow cytometry. Stromal cells purified from NP tissues were stimulated with lymphotoxin (LT) α1β2, and BAFF levels in culture supernatants were analyzed by ELISA. Compared with those in control tissues and NPs without eLTs, the BAFF levels were elevated in NPs with eLTs. Abundant BAFF-positive cells and few active caspase-3-positive apoptotic B cells were found in NPs with eLTs, in contrast to those in NPs without eLTs. There was a negative correlation between the numbers of BAFF-positive cells and frequencies of apoptotic B cells in total B cells in NP tissues. BAFF protected nasal polyp B cells from apoptosis in vitro. Stromal cells were an important cellular source of BAFF in NPs with eLTs. LTα1β2 induced BAFF production from nasal stromal cells in vitro. We propose that BAFF contribute to eLT formation in NPs by promoting B cell survival.

Background Although subsequent anti-inflammatory treatments are indispensable for patients with chronic rhinosinusitis (CRS) undergoing sinus surgery, few studies have explored the factors influencing the efficacy of postoperative anti-inflammatory treatment. Objective We aimed to develop prediction models for the response to glucocorticoid- and macrolide-based postoperative therapy in CRS patients. Methods We performed a post-hoc analysis of our previous study comparing the efficacy of fluticasone propionate and clarithromycin in the postoperative treatment of CRS patients. Clinical characteristics and treatment outcome information were collected. In addition, diseased sinonasal mucosal tissues obtained during surgery were processed for Bio-Plex analysis of protein levels of 34 biomarkers. Classification trees were built to predict refractory CRS based on clinical characteristics and biological markers for patients treated with fluticasone propionate or clarithromycin. A random forest algorithm was used to confirm the discriminating factors that formed the classification trees. Results One year after surgery, 22.7% of the patients (17/75) treated with fluticasone propionate, and 24.3% of those (18/74) treated with clarithromycin were diagnosed with refractory CRS. Nasal tissue IL-8 and IgG3 levels and headache VAS scores in the fluticasone propionate group, and nasal tissue IgG4 levels and overall burden of symptoms VAS scores in the clarithromycin group, were identified as discriminating factors forming the classification tree to predict refractory CRS. The overall predictive accuracy of the model was 89.3% and 87.8% for fluticasone propionate- and clarithromycin-based postsurgical treatment, respectively. Conclusions Classification trees built using clinical and biological parameters could be helpful in identifying patients with poor response to fluticasone propionate- and clarithromycin-based postoperative treatment.

Background: Gastric cancer (GC) is among the malignant tumors of highest morbidity and mortality in the world, and has a profile of high lymph node metastasis rate. Lymph node clearance is a critical part of gastric cancer surgery, however, the extent of lymph node clearance, for example, whether to perform abdominal aortic lymph node dissection, remains considerably controversial. In this study, we performed a systematic review and meta-analysis to assess the effects of D2 plus para-aortic lymphadenectomy (PALD) on survival and postoperative complications in patients with GC.Methods: An electronic search was conducted through PubMed, Embase and cochrane library. The Q test and I2 were used to assess heterogeneity. The publication bias was evaluated via funnel plots. All statistical analyses were performed using STATA 14.0 (STATA, College Station, TX).Results: 908 studies were retrieved via literature search and eight studies were finally included. There was no significant difference between D2 and D2+PALD in the 5-year survival rate after surgery (HR: 1.00, 95% CI: 0.97-1.03, P = 0.897; I2 = 64.9%). Besides, the 30-day mortality (RR: 1.17, 95% CI: 0.66-2.10, P = 0.590; I2 = 0.0%) and the overall risk of postoperative complications (RR: 1.15, 95% CI: 0.83-1.59, P = 0.411; I2 = 35.5%) were comparable between D2 and D2+PALD.Conclusion: Based on current literature body, compared with D2, D2+PALD does not prevail in terms of long-term survival or perioperative outcomes.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of “cough for 11 days and once fever 8 days ago” on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19. Electronic supplementary material The online version of this article (10.1007/s42058-020-00045-z) contains supplementary material, which is available to authorized users.

Background Emerging evidence shows that the deregulation of tripartite motif (TRIM) family proteins have various functions in cellular processes and play important role in innate immunity, nervous system diseases, protein quality control and carcinogenesis. However, the precise biological function and molecular mechanism of TRIM family proteins in ovarian cancer chemo-resistance remain unclear. Methods The protein and mRNA expression of TRIM37 in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot and IHC respectively. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM37 in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37 promotes chemoresistance in ovarian cancer cells. Results Herein, we found that the protein and mRNA expression of TRIM37 were markedly overexpressed in ovarian cancer tissues which shown partially responded to cisplatin chemotherapy. Moreover, TRIM37 expression was inversely correlated with patient survival in our cohort HCC tissue samples and public HCC database. Overexpression of TRIM37 confers cisplatin resistance on ovarian cancer cells; but, inhibition of TRIM37 sensitized ovarian cancer cell lines to cisplatin cytotoxicity both in vitro and in vivo. Additionally, TRIM37 upregulated the levels of nuclear β-catenin, thereby activating canonical wnt/β-catenin signaling. Conclusions our results demonstrate that targeting TRIM37/β-catenin axis may represent a promising strategy to enhance cisplatin response in patients with chemo-resistant ovarian cancer.

Background M2 macrophages are characterized by high interleukin-10 (IL-10) expression and are critical for resolving inflammation. Although increased accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly the eosinophilic type, their functional relevance in CRSwNP remains poorly understood. Methods M1 and M2 macrophages and IL-10 expression in sinonasal tissues were detected by double-immunofluorescence staining. THP-1 cells, a human monocytic leukemia cell line, were stimulated with various cytokines to study macrophage polarization and IL-10 expression. Polyp size, computed tomography (CT) scans, and symptom severity were scored. Results Compared with numbers in control tissues, the numbers of total CD68+ macrophages, interferon regulatory factor 5-positive and CD68+ M1 macrophages, and CD163+ CD68+ and CD206+ CD68+ M2 macrophages were increased in both eosinophilic and non-eosinophilic polyps. However, compared with non-eosinophilic polyps, eosinophilic polyps contained fewer M1 macrophages and more M2 macrophages. Consistent with this, the M1/M2 macrophage ratio was increased in non-eosinophilic polyps, whereas it decreased in eosinophilic polyps. Strikingly, the numbers of IL-10+ CD68+ macrophages and the percentage of IL-10+ CD68+ macrophages relative to the total number of macrophages were decreased in eosinophilic polyps, despite the upregulation of M2 macrophages in this type of polyp. The number of IL-10+ CD68+ M2 macrophages correlated negatively with total symptoms scores, polyp sizes, total CT scores, and the total number of inflammatory cells in patients with eosinophilic CRSwNP. Poly I:C downregulated IL-10 expression in M2 macrophages differentiated from THP-1 cells in vitro. Conclusion Impaired IL-10 production by M2 macrophages may contribute to sustained inflammation in eosinophilic CRSwNP.vv.

Background This study aimed to study the osteo-preservative effects of captopril, an inhibitor on angiotensin-converting enzyme (ACE), on bone mass, micro-architecture and histomorphology as well as the modulation of captopril on skeletal renin-angiotensin system (RAS) and regulators for bone metabolism in mice with bilateral orchidectomy. Methods The orchidectomized (ORX) mice were orally administered with vehicle or captopril at low dose (10 mg/kg) and high dose (50 mg/kg) for six weeks. The distal femoral end, the proximal tibial head and the lumbar vertebra (LV) were stained by hematoxylin and eosin, Safranin O/Fast Green and masson-trichrome. Micro-computed tomography was performed to measure bone mineral density (BMD). Results Treatment with captopril increased trabecular bone area at distal metaphysis of femur, proximal metaphysis of tibia and LV-4, moreover, high dose of captopril significantly elevated trabecular BMD of LV-2 and LV-5. The mRNA expressions of renin receptor, angiotensinogen, carbonic anhydrase II, matrix metalloproteinase-9, and tumor necrosis factor-alpha were significantly decreased in tibia of ORX mice following treatment with captopril. The administration with captopril enhanced the ratio of OPG/RANKL mRNA expression, the mRNA expression of transforming growth factor-beta and the protein expression of bradykinin receptor-1. Conclusions The inhibition on ACE by captopril exerts beneficial effects on trabecular bone of ORX mice. The therapeutic efficacy may be attributed to the regulation of captopril on local RAS and cytokines in bone.

BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disorder characterized by exaggerated local immune responses. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a novel protein with potential immune modulating function. The expression and function of TIPE2 in human airway diseases are unclear. METHODS The expression of TIPE2 in sinonasal mucosal samples was assessed by means of quantitative reverse transcript-polymerse chain reaction, immunohistochemistry, and Western blotting. The human monocytic/macrophage cell line, THP-1 cells, was stimulated with various cytokines. Computed tomography (CT) scan images, endoscopic findings, and symptoms were scored. RESULTS Compared with non-eosinophilic polyps and control mucosa, the mRNA and protein expression of TIPE2 was significantly upregulated in eosinophilic polyps, with a further increase in those with asthma. The number of CD68+ CD163+ alternatively activated (M2) macrophages was increased in eosinophilic polyps. TIPE2 was mainly expressed by M2 macrophages in sinonasal mucosa and its expression was upregulated in M2 macrophages in eosinophilic polyps. Interleukin (IL)-4 and IL-13, but not interferon (IFN)-γ or IL-17A, induced TIPE2 expression in differentiated THP-1 cells. The mRNA levels of IL-4 and IL-13 correlated with the mRNA levels of TIPE2 and M2 macrophage markers in sinonasal mucosa. Importantly, the number of TIPE2+ cells, particularly TIPE2+ CD163+ CD68+ M2 macrophages, correlated positively with the number of eosinophils and total inflammatory cells in sinonasal mucosa, as well as disease duration, CT scores, hyposmia scores, and polyp size in CRSwNP. CONCLUSION The T-helper 2 milieu is able to induce TIPE2 expression in macrophages. TIPE2-positive M2 macrophages potentially contribute to eosinophilic inflammation and disease progression in CRSwNP.

Background The role of IL-37, an immunosuppressive cytokine, in patients with inflammatory diseases is unclear. Objective We sought to explore the expression and pathogenic function of IL-37 in patients with chronic rhinosinusitis (CRS). Methods Expression levels of IL-37, IL-18 receptor α, IL-1 receptor 8, Mex3 RNA binding family member B (Mex3B), and thymic stromal lymphopoietin (TSLP) in nasal samples were studied by using quantitative RT-PCR, immunohistochemistry, Western blotting, and ELISA. Human nasal epithelial cells (HNECs) and the BEAS-2B cell line were stimulated with various cytokines and Toll-like receptor (TLR) agonists. In some experiments BEAS-2B cells were transfected with Mex3B small interfering RNA or overexpressing lentiviruses. Genes regulated by IL-37b in HNECs were studied by using RNA sequencing analysis. IL-37b function was confirmed in mice in vivo. Results Compared with control subjects, although mRNA and protein expression of IL-37 were upregulated in diseased tissues, especially in nasal epithelial cells, in patients with CRS without nasal polyps or in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), IL-37 levels in nasal secretions were reduced in patients with eosinophilic CRSwNP. Type 2 cytokines inhibited IL-37 secretion from HNECs. HNECs expressed IL-37 receptors, IL-18 receptor α, and IL-1 receptor 8. IL-37b downregulated the expression of Mex3B, a TLR3 coreceptor, in HNECs. IL-37b suppressed polyinosinic-polycytidylic acid–induced TSLP production in HNECs in vitro and in murine nasal epithelial cells in vivo. Knocking down or overexpressing Mex3B in BEAS-2B cells abolished the inhibitory effect of IL-37b. Secreted IL-37 levels negatively correlated with Mex3B and TSLP levels and eosinophil numbers in patients with eosinophilic CRSwNP. Conclusions The suppressed IL-37 secretion caused by a type 2 milieu can enhance Mex3B-mediated TLR3 activation and subsequent TSLP production in nasal epithelial cells and therefore promotes eosinophilic inflammation in patients with CRSwNP.

Bubali cornu (water buffalo horn) has been used as the substitute for Cornu rhinoceri asiatici (rhino horn) in clinical applications, and is the essential ingredient of Angong Niuhuang Wan. In recent years, there are a number of adulterants on the commercial herbal medicine markets. An efficient tool is required for species identification. In this study, 155 Bubali cornu samples have been taken from original animals and collected from commercial herbal medicine markets. 153 COI sequences have been successfully obtained from 155 samples through DNA extraction, PCR amplification, bidirectional sequencing and assembly. 93 COI sequences have been added to the DNA barcoding database of traditional Chinese animal medicine after validation using DNA barcoding GAP and tree-based methods. The species identification of the 62 commercial Bubali cornu medicines has been accomplished on the DNA barcoding system for identifying herbal medicine using the updated animal medicine database (www.tcmbarcode.cn). Except two samples failed to obtain COI sequences, 54.8% of the commercial Bubali cornu medicines were water buffalo horns and 29% were yak horns. Our results showed that yak horn was the major adulterant of Bubali cornu and the DNA barcoding method may accurately discriminate Bubali cornu and their adulterants. Therefore, we recommend that supervision on the herbal medicine markets should be strengthened with this new method to warren the effectiveness of herbal medicines.

Background The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes. Methods A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1-year postoperative follow-up. Difficult-to-treat CRS was characterized in each generated cluster. Results Seven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well-defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult-to-treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult-to-treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL-8 and high proportions of difficult-to-treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL-10 and lacked difficult-to-treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult-to-treat CRS, and low inflammation load. Finally, we found that difficult-to-treat CRS was associated with distinct clinical features and biomarkers in the different clusters. Conclusions Distinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult-to-treat CRS.

This study was performed to investigate the effect of angiotensin-converting enzyme inhibitor, captopril, on bone metabolism and histology, and the action of captopril on the components of the skeletal renin-angiotensin system (RAS) and bradykinin receptor in normal male mice. The mice were orally administered captopril (10 mg/kg) for 4 weeks with vehicle-treated mice as normal control. The histology of trabecular bone at the distal femoral end was determined by hematoxylin & eosin, Safranin O and Masson-Trichrome staining. The captopril-treated mice showed a decreased level of testosterone (p

The accuracy of ultrasonography for diagnosing meniscal injury remains controversial. The aim of the present meta-analysis was to establish the role of ultrasonography in the diagnosis of meniscal injury by analyzing the data from prospectively designed studies.A systematic review was performed by searching electronic bibliographic databases prior to November 2014. Studies with diagnostic results that fulfilled the inclusion criteria were included. The methodological quality of the studies was assessed. Sensitivity, specificity and other measures of the accuracy of ultrasonography in the diagnosis of meniscal injury were summarized. Summary receiver-operating characteristic (SROC) curves were used to summarize overall test performance. Publication bias was assessed used Deek's funnel plot asymmetry test.Seven prospective studies with 551 patients were eligible for the meta-analysis. The Quality Assessment of Diagnostic Accuracy Studies scores for the included studies ranged from 10-13. The summary estimates of the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of ultrasonography in the diagnosis of meniscal injury were 0.88 (95 % CI 0.84-0.91), 0.90 (95 % CI 0.86-0.93), 7.07 (95 % CI 4.34-11.52), 0.17 (95 % CI 0.10-0.26) and 58.13 (95 % CI 24.38-138.62), respectively. There was moderate to significant heterogeneity across the above measures (P0.05). The area under the curve of the SROC was 0.948, indicating a high overall diagnostic accuracy. No publication bias was noted across the studies (P = 0.393), which suggested little influence of publication bias on the overall results.Our results suggest that the diagnostic accuracy of ultrasonography for diagnosing meniscal injury is acceptable, with a high specificity but moderate sensitivity.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disorder characterized by exaggerated local immune responses. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a novel protein with potential immune modulating function. The expression and function of TIPE2 in human airway diseases are unclear.The expression of TIPE2 in sinonasal mucosal samples was assessed by means of quantitative reverse transcript-polymerse chain reaction, immunohistochemistry, and Western blotting. The human monocytic/macrophage cell line, THP-1 cells, was stimulated with various cytokines. Computed tomography (CT) scan images, endoscopic findings, and symptoms were scored.Compared with non-eosinophilic polyps and control mucosa, the mRNA and protein expression of TIPE2 was significantly upregulated in eosinophilic polyps, with a further increase in those with asthma. The number of CD68The T-helper 2 milieu is able to induce TIPE2 expression in macrophages. TIPE2-positive M2 macrophages potentially contribute to eosinophilic inflammation and disease progression in CRSwNP.

According to continuous cooling transformation curve of pinion steel, heat treatment simulation tests of 8 series were developed. The results show that the microstructure of pinion steel depends on the cooling rate after normalizing. Furnace cooling according to 30°C/h after normalizing can get the typical F+P organizations; Converter cooling after normalizing mixed with some bainite organizations; Furnace cooling with the break after normalizing can get clear stripped bainite organizations.

Aims This study was aimed to investigate the involvement of skeletal renin–angiotensin system (RAS) and kallikrein–kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. Methods The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. Results The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Conclusion Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment.

A novel capillary electrophoresis method for simultaneous determination of Cu and Pb has been developed in this paper. Cu(II) and Pb(II) ions were reacted with ABEDTA to form complex to achieve an ideal sensitivity of heavy metal complexes. The digestion solution of Rhizoma coptidis drug sample was purified by neutral Al 2 O 3 column chromatography and the chromatographic behavior of metal–L complexes was investigated. The calibration curve was linear in the range of 5–60 μg/mL for Cu 2+ and 5–25 μg/mL for Pb 2+ with the correlation coefficients 0.9970 and 0.9972 for each ( n = 5). The average recoveries were 86.2% for Pb and 90.1% for Cu, while the relative standard deviations were 5.1% and 3.6% respectively. The method was successfully applied to determine Cu and Pb in R. coptidis drug samples.

This paper aims to study the feasibility of two solid waste which are steelmaking slag and fly ash as desulfurization and denitration absorbents by microwave. Under the optimal operating conditions, the removal efficiencies of 70.9% and 69.6% are achieved for SO2 and NOX respectively. The microstructure of before and after the adsorbent reaction are analyzed by SEM. Base on the experiment research, he mechanisms of simultaneous desulfurization and denitration are investigated in this paper. The research provides a new approach to resource recycling of steelmaking slag and fly ash. And the result has great significance to recycle solid waste and preserve the sustainable development of industrial economy and environment.

Study researches durable factors of the grain size in 18CrNiMo7-6 by heating and cooling method. Results show that alloying elements Nb and Al have a strong pining effect on the grain boundaries, Al/N ratio between 2.0-2.5 can promote the grain not to grow up for a long time, and refine grains significantly with furnace heating and after carburizing-quenching once, and can inhibit the abnormal growth of individual grains.

To gain a better understanding of differentially expressed sequence tags (ESTs) for aluminum (Al) tolerance and to investigate the molecular mechanisms of Al toxicity, cDNA subtraction libraries were generated from Al-stressed roots of alfalfa (Medicago sativa L.) compared with no Al-stressed ones, employing suppression subtractive hybridization. Using differential screening technique in which the probes were labeled with DIG, we identified 45 non-redundant ESTs in Al-stressed alfalfa root tips with significantly altered expression. Among the up-regulated ESTs, we have found genes encoding identified proteins, including malate dehydrogenase, 6-phosphogluconate dehydrogenase, peroxidase, and an ABC transporter, while the down-regulate genes included ATPase, secretory carrier membrane protein 2, pectinesterase inhibitor. In addition, two novel ESTs, EW678752 and EY976957, up- and down-regulated by Al stress were sequenced. Analyzed by real-time PCR, the expressions of EST EW678718, EW678739, EY976969 and EW678728, which encode for ABC transporter, malate dehydrogenase, peroxidase and 6-phosphogluconate dehydrogenase correspondingly, increased 1.64-, 2.75-, 3.27- and 6.54-folds, respectively, and the expression of EY976957 encoding for ATPase decreased 3.27 folds. The expression of EST EW678752 increased 34.54-fold, while that of EY976957 decreased 16.68 folds. It suggested that the two novel ESTs maybe play a significant role in the aluminum tolerance of alfalfa.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with mast cell–mediated inflammation and heightened oxidant stress. Kynurenine (KYN), an endogenous tryptophan metabolite, can promote allergen-induced mast cell activation through the aryl hydrocarbon receptor (AhR). Objectives We sought to determine the role of the KYN/AhR axis and oxidant stress in mast cell activation and the development of CRSwNP. Methods We measured the expression of indoleamine 2,3-dioxygenase 1, tryptophan 2,3-dioxygenase, KYN, and oxidized calmodulin-dependent protein kinase II (ox-CaMKII) in nasal polyps and controls. KYN-potentiated ovalbumin (OVA)-induced ROS generation, cell activation, and ox-CaMKII expression were investigated in wild-type and AhR-deficient (AhR −/− ) mast cells. The role of ox-CaMKII in mast cell activation was further investigated. Results Nasal polyps in CRSwNP showed an increased expression of indoleamine 2,3-dioxygenase 1, tryptophan2,3-dioxygenase, and KYN compared with controls. AhR was predominantly expressed in mast cells in nasal polyps. Activated mast cells and local IgE levels were substantially increased in eosinophilic polyps compared with noneosinophilic polyps and controls. Furthermore, KYN potentiated OVA-induced ROS generation, intracellular Ca 2+ levels, cell activation, and expression of ox-CaMKII in wild-type, but not in AhR −/− mast cells. Compared with noneosinophilic polyps and controls, eosinophilic polyps showed increased expression of ox-CaMKII in mast cells. Mast cells from ROS-resistant CaMKII MMVVδ mice or pretreated with CaMKII inhibitor showed protection against KYN-promoted OVA-induced mast cell activation. Conclusions These studies support a potentially critical but previously unidentified function of the KYN/AhR axis in regulating IgE-mediated mast cell activation through ROS and ox-CaMKII in CRSwNP.

Background The current reports on the association of claudin-4 expression with gastric cancer outcome were inconsistent. Thus, we conducted a meta-analysis to assess the association of claudin-4 expression with the prognosis and clinical parameters more precisely. Methods Systematic searches on PubMed, Embase, and Cochrane Library prior to December 2014 were performed. The pooled hazard ratio (HR) with its 95 % confidence interval (95 %CI) was used to assess the prognostic value of claudin-4 expression with gastric cancer patients, and the pooled odds ratio (OR) with its 95 %CI was used to assess the association with clinical parameters. Results Nine studies with a total of 1265 gastric cancer patients were included. Overall, the pooled results showed that over-expression of claudin-4 was associated with a poor survival in gastric cancer patients (HR: 2.01, 95 % CI: 1.62–2.50). Over-expression of claudin-4 was also associated with advanced stage (OR: 1.96, 95 % CI: 1.08–3.56) and lymphoid node metastasis (OR: 1.72, 95 % CI: 1.05–2.81) of gastric cancer patients. No significant publication bias was found among the studies (P > 0.05). Conclusions This meta-analysis shows that over-expression of claudin-4 is associated with progress of gastric cancer and poor prognosis of gastric cancer patients.

Background Thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP, IL-25, IL-33, and their receptors in type 2 T-helper (Th) responses in chronic rhinosinusitis with nasal polyps (CRSwNPs) and their cross-regulation in human nasal epithelial cells (HNECs). Methods Immunohistochemistry, quantitative RT-PCR, ELISA, Bio-Plex assay, and flow cytometry were used to detect the expression of TSLP/common γ-like TSLP receptor (TSLPR)/IL-7 receptor α (IL-7Rα), IL-25/IL-17B receptor (IL-17RB), and IL-33/membrane-bound ST2 (ST2L)/soluble ST2 (sST2) in sinonasal mucosa and HNECs. HNECs cultured at an air–liquid interface were used to explore the expression in regulation of these cytokine systems. Results Compared with controls and noneosinophilic CRSwNP, the expression of TSLP/TSLPR/IL-7Rα and ST2L/sST2 was significantly increased in eosinophilic CRSwNP, predominantly in epithelial cells. In contrast, the expression of IL-33 and IL-25/IL-17RB was enhanced in epithelial cells in both eosinophilic and noneosinophilic CRSwNP compared to controls. The expression of TSLP, TSLPR, and ST2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRSwNP and with Th2 cytokine expression in sinonasal mucosa. The expression of ST2L was correlated with TSLP and its receptor expression. TSLP could induce ST2L expression that promoted IL-33-induced TSLP expression in HNECs. In addition, TSLP/TSLPR/IL-7Rα and ST2L could be induced by Th2 cytokines, while IL-25/IL-17RB and IL-33 could be upregulated by Th1/Th17 cytokines, in HNECs. Conclusions The positive feedback loop between TSLP, IL-33 and their receptors, and Th2 cytokines may facilitate Th2-skewed inflammation in eosinophilic CRSwNP.

We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria . Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and “domestication” by accelerated evolution of the strain upon repeated passaging.