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Background: Distinguishing between tumor recurrence and pseudoprogression (PsP) in high-grade glioma postoperatively is challenging. This study aims to enhance this differentiation using a combination of intratumoral and peritumoral radiomics., Purpose: To assess the effectiveness of intratumoral and peritumoral radiomics in improving the differentiation between high-grade glioma recurrence and pseudoprogression after surgery., Material and Methods: A total of 109 cases were randomly divided into training and validation sets, with 1316 features extracted from intratumoral and peritumoral volumes of interest (VOIs) on conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps. Feature selection was performed using the mRMR algorithm, resulting in intratumoral (100 features), peritumoral (100 features), and combined (200 features) subsets. Optimal features were then selected using PCC and RFE algorithms and modeled using LR, SVM, and LDA classifiers. Diagnostic performance was compared using area under the receiver operating characteristic curve (AUC), evaluated in the validation set. A nomogram was established using radscores from intratumoral, peritumoral, and combined models., Results: The combined model, utilizing 14 optimal features (8 peritumoral, 6 intratumoral) and LR as the best classifier, outperformed the single intratumoral and peritumoral models. In the training set, the AUC values for the combined model, intratumoral model, and peritumoral model were 0.938, 0.921, and 0.847, respectively; in the validation set, the AUC values were 0.841, 0.755, and 0.705. The nomogram model demonstrated AUCs of 0.960 (training set) and 0.850 (validation set)., Conclusion: The combination of intratumoral and peritumoral radiomics is effective in distinguishing high-grade glioma recurrence from pseudoprogression after surgery., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bitterness, as one of the most important physiological sensations in animals, is primarily recognized through the mediation of bitter taste receptors. In recent years, it has been found that these receptors are not only expressed in taste bud cells on the tongue but also in the respiratory, cardiovascular, digestive, reproductive, and nervous systems. They are involved in regulating various fundamental physiological processes and are now considered important targets for the treatment of various diseases. This paper reviewed the structure, classification, distribution, and signaling pathways of bitter taste receptors, their relationship with different diseases, and the role of bitter taste receptors agonists, aiming to provide a basis for scientific research on bitter taste receptors.

Aim: To investigate the application of the T2-weighted (T2)-fluid-attenuated inversion recovery (FLAIR) mismatch sign and machine learning-based multiparametric magnetic resonance imaging (MRI) radiomics in predicting 1p/19q non-co-deletion of lower-grade gliomas (LGGs)., Materials and Methods: One hundred and forty-six patients, who had pathologically confirmed isocitrate dehydrogenase (IDH) mutant LGGs were assigned randomly to the training cohort (n=102) and the testing cohort (n=44) at a ratio of 7:3. The T2-FLAIR mismatch sign and conventional MRI features were evaluated. Radiomics features extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), FLAIR, apparent diffusion coefficient (ADC), and contrast-enhanced T1WI images (CE-T1WI). The models that displayed the best performance of each sequence were selected, and their predicted values as well as the T2-FLAIR mismatch sign data were collected to establish a final stacking model. Receiver operating characteristic curve (ROC) analyses and area under the curve (AUC) values were applied to evaluate and compare the performance of the models., Results: The T2-FLAIR mismatch sign was more common in the IDH mutant 1p/19q non-co-deleted group (p<0.05) and the area under the curve (AUC) value was 0.692 with sensitivity 0.397, specificity 0.987, and accuracy 0.712, respectively. The stacking model showed a favourable performance with an AUC of 0.925 and accuracy of 0.882 in the training cohort and an AUC of 0.886 and accuracy of 0.864 in the testing cohort., Conclusion: The stacking model based on multiparametric MRI can serve as a supplementary tool for pathological diagnosis, offering valuable guidance for clinical practice., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: The dysregulation of TGF-β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-β signaling in glioma is currently unclear., Methods: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA., Results: In glioma, a TGF-β signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-β signaling pathway., Conclusions: A prognostic lncRNA signature of TGF-β signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Enzymatic synthesis of ursodeoxycholic acid (UDCA) catalyzed by an NADH-dependent 7β-hydroxysteroid dehydrogenase (7β-HSDH) is more economic compared with an NADPH-dependent 7β-HSDH when considering the much higher cost of NADP + /NADPH than that of NAD + /NADH. However, the poor catalytic performance of NADH-dependent 7β-HSDH significantly limits its practical applications. Herein, machine-learning-guided protein engineering was performed on an NADH-dependent Rt 7β-HSDH M0 from Ruminococcus torques . We combined random forest, Gaussian Naïve Bayes classifier, and Gaussian process regression with limited experimental data, resulting in the best variant Rt 7β-HSDH M3 (R40I/R41K/F94Y/S196A/Y253F) with improvements in specific activity and half-life (40 °C) by 4.1-fold and 8.3-fold, respectively. The preparative biotransformation using a "two stage in one pot" sequential process coupled with Rt 7β-HSDH M3 exhibited a space-time yield (STY) of 192 g L -1 d -1 , which is so far the highest productivity for the biosynthesis of UDCA from chenodeoxycholic acid (CDCA) with NAD + as a cofactor. More importantly, the cost of raw materials for the enzymatic production of UDCA employing Rt 7β-HSDH M3 decreased by 22% in contrast to that of Rt 7β-HSDH M0 , indicating the tremendous potential of the variant Rt 7β-HSDH M3 for more efficient and economic production of UDCA.

Seasonal influenza, causes hundreds of thousands of deaths annually, posing a severe threat to human health. Currently available influenza vaccines are targeted only at specific strains or conserved epitopes; however, these vaccines are not completely efficacious because influenza viruses can undergo mutation during circulation, leading to antigenic mismatch between recommended strains and circulating strains and elusion from the immune system. Therefore, developing an influenza vaccine that is quick, effective, and broadly protective has become crucial, and the integral part of hemagglutinin (HA) remains an ideal target for vaccine development. This study developed a lipid nanoparticle-encapsulated nucleoside-modified mRNA vaccine (mRNA-LNPs) encoding a consensus full-length HA sequence (H1c) and evaluated its protective efficacy and immunogenicity through in vitro and in vivo assays. Following two intramuscular immunizations (2, 10 µg, or 20 µg) at a 3-week interval in BALB/c mice, H1c-mRNA-LNP vaccine induced strong antibodies as shown in the hemagglutination-inhibition test and protective neutralizing antibodies against numerous heterologous H1N1 influenza viruses as shown in the microneutralization assay. Additionally, both Th1- and Th2-biased cellular immune responses were elicited, with the Th1-biased response being stronger. Two doses of the H1c-mRNA-LNP vaccine could neutralize a panel of heterologous H1N1 influenza viruses and could confer protection in mice. Taken together, these findings suggest that the H1c-mRNA-LNP vaccine encoding a consensus full-length HA is a feasible strategy for developing a cross-protective vaccine against a panel of heterologous H1N1 influenza viruses.

The selection of metal centers can endow donor-metal-accepter (D-M-A) type MOFs with progressive framework dimensions. 3D Cd-based MOFs with intramolecular charge transfer caused by D-M-A exhibit a satisfactory photothermal conversion efficiency of 35.7%, with the temperature rapidly rising from 25 °C to 201 °C in 7 s under 808 nm laser irradiation.

Peony seed phospholipids (PPLs), a kind of multifunctional plant-like phospholipids were extracted from peony seed meal. We investigated the functional properties of PPLs and compared their emulsification performance in corn oil-peony seed oil o/w emulsion systems with that of soy lecithin (DPLs). The PPLs were characterized with the higher content of phosphatidylcholine (PC) (416 ± 28 mg/g) and lyso-phosphatidylcholine (LPC) (43 ± 14 mg/g) fractions, and lower content of phosphatidylethanolamine (PE) (71 ± 13 mg/g). The polyunsaturated fatty acids showed higher content (83.25%), with the highest content of linoleic acid (46.05%) in PPLs. PPLs-emulsions showed smaller average particle size and higher loaded peony seed oil content at pH 5, temperature 50 °C, and about 60% corn oil content. PPLs-emulsions imparted better hydroxyl radical scavenging efficiency and reducing power than DPLs. Our results suggest that PPLs can be used as emulsifiers with improved antioxidant properties., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs., Materials and Methods: Eighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected., Results: In total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb + ) and CDAb-negative (CDAb - ) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa&#95;circ&#95;0004564 in the CDAb + group significantly decreased (CDAb + vs. CDAb - :1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10 -6 ), while the expression of hsa&#95;circ&#95;0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb + vs. CDAb - :1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa&#95;circ&#95;0004564 and CD3 + cells was validated in children with T1D after adjustments for CDAbs ( p = 0.029), while there were no correlations between hsa&#95;circ&#95;0004564 and clinical characteristics or other immune cell subsets (i.e., CD4 + T cells, CD8 + T cells, and natural killer cells)., Conclusion: This study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa&#95;circ&#95;0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wang, Xu, Zhang, Zhang, Lu, Gu, Dong, Xiao and Xia.)

Anemarrhenae Rhizoma (AR) has multiple pharmacological activities to prevent and treat Alzheimer's disease (AD). However, the effect and its molecular mechanism are not elucidated clear. This study aims to evaluate AR's therapeutic effect and mechanism on AD model rats induced by D -galactose and AlCl 3 with serum metabolomics. Behavior study, histopathological observations, and biochemical analyses were applied in the AD model assessment. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-QTOF/MS) were combined with multivariate statistical analysis to identify potential biomarkers of AD and evaluate the therapeutic effect of AR on AD from the perspective of metabolomics. A total of 49 biomarkers associated with the AD model were identified by metabolomics, and pathway analysis was performed to obtain the metabolic pathways closely related to the model. With the pre-treatment of AR, 32 metabolites in the serum of AD model rats were significantly affected by AR compared with the AD model group. The regulated metabolites affected by AR were involved in the pathway of arginine biosynthesis, arginine and proline metabolism, ether lipid metabolism, glutathione metabolism, primary bile acid biosynthesis, and steroid biosynthesis. These multi-platform metabolomics analyses were in accord with the results of behavior study, histopathological observations, and biochemical analyses. This study explored the therapeutic mechanism of AR based on multi-platform metabolomics analyses and provided a scientific basis for the application of AR in the prevention and treatment of AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AL declared a shared affiliation, with the authors to the handling editor at the time of the review., (Copyright © 2022 Wang, Dai, He, Xia, Chen, Hong and Chai.)

Background: Lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), causes high mortality around the world. Previous studies have suggested that the metabolic pattern of tumor is associated with tumor response to immunotherapy and patient's survival outcome. Yet, this relationship in LUAD is still unknown., Methods: Therefore, in this study, we identified the immune landscape in different tumor subtypes classified by metabolism-related genes expression with a large-scale dataset (tumor samples, n = 2181; normal samples, n = 419). We comprehensively correlated metabolism-related phenotypes with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in LUAD patients., Results: And we confirmed tumors with activated lipid metabolism tend to have higher immunocytes infiltration and better response to checkpoint immunotherapy. This work highlights the connection between the metabolic pattern of tumor and tumor immune infiltration in LUAD. A scoring system based on metabolism-related gene expression is not only able to predict prognosis of patient with LUAD but also applied to pan-cancer. LUAD response to checkpoint immunotherapy can also be predicted by this scoring system., Conclusions: This work revealed the significant connection between metabolic pattern of tumor and tumor immune infiltration, regulating LUAD patients' response to immunotherapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To compare the clinical effects of cervical decompression first, lumbar decompression first, or simultaneous decompression of both lesions in the treatment of tandem spinal stenosis (TSS)., Methods: This is a retrospective analysis. From January 2013 to December 2018, 51 TSS patients underwent our surgery and postoperative investigation. Among the 51 subjects, 27 females and 24 males, aged 49-77 years with an average age of 66.3 ± 6.8, were selected. According to the different operation sequences, all patients were divided into three groups. In simultaneous operation group, five patients underwent cervical and lumbar vertebrae surgery at the same time. In first cervical surgery group, 28 patients underwent cervical vertebra surgery first, followed by lumbar spine surgery after a period of recovery. And in first lumbar surgery group, 18 patients underwent lumbar vertebrae surgery first. The choice for neck surgery is posterior cervical single-door vertebroplasty, the surgery of lumber is plate excision and decompression needle-rod system internal fixation. The outcome measures are visual analogue scale (VAS), Japanese Orthopaedic Association cervical (JOA-C) and lumbar (JOA-L) scores, which were assessed at 3 months and 1 year after the operation by telephone interview. In addition, operative time, estimated blood loss, and hospital stay were also recorded., Results: All the patients in the study had surgery performed successfully by the same group of orthopaedic surgeons. The preoperative VAS scores of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 8.00 ± 1.00, 8.36 ± 0.68, and 8.17 ± 0.71 (P > 0.05). The preoperative JOA-C scores were 7.00 ± 2.35, 6.54 ± 1.53, and 7.83 ± 1.04 (P < 0.05). And the preoperative JOA-L scores were 7.20 ± 2.17, 4.64 ± 2.36, and 5.78 ± 1.22 respectively (P < 0.05). During the final 1-year follow-up, the JOA-C improvement rates of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 85.68% ± 5.44%, 84.27% ± 5.02%, and 83.34% ± 10.25%, respectively (P > 0.05), and the JOA-L improvement rates were 80.04% ± 3.35%, 81.65% ± 3.74%, and 80.21% ± 4.76% (P > 0.05). The difference among them was not statistically significant. In addition, operation time (OP), blood loss (BL), and hospital stay (HS) in the simultaneous operation group were 245.00 ± 5.00 min, 480.00 ± 27.39 mL, and 16.60 ± 0.55 days, respectively. While those parameters in the first cervical surgery group were 342.50 ± 18.18 min, 528.21 ± 43.97 mL, and 22.75 ± 2.15 days, and in the first lumbar surgery group they were 346.11 ± 24.77 min, 519.44 ± 43.99 mL, and 22.89 ± 1.64 days. The average blood loss in simultaneous operation group was less (P > 0.05); meanwhile, the operation time and hospital stay time were significantly shorter in the simultaneous operation group than in the first cervical surgery group and first lumbar surgery group (P < 0.05). Only one case of fat liquefaction occurred in first cervical surgery group, which healed spontaneously after a regular change of dressing for 1 month., Conclusions: Under the condition of ensuring the surgical effect, the choice of staged surgery or concurrent surgery according to the patients' own symptoms of cervical and lumbar symptoms could both obtain satisfactory results, and the damage of simultaneous surgery was less than that of staged surgery., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To analyze the clinical characteristics and pathogenesis of refractory gastroesophageal reflux disease(RGERD). Methods: The patients with acid regurgitation, heartburn and extraesophageal symptoms were enrolled in the study from November 2015 to September 2017 at Peking University Third Hospital. All the subjects filled the informed consent.Questionnaire, SCL-90, SAS and SDS scales were recorded. A 24 hour pH-impedance monitoring and esophageal high resonance manometry were carried out. According to the response to proton pump inhibitor(PPI), the patients were divided into RGERD and non-RGERD(NRGERD)groups. The clinical characteristics were compared between these two groups. Logistic regression was used to analyze the risk factors of RGERD. Results: One hundred and nineteen patients were finally enrolled in the study including 61 RGERD (51.3%) and 58 NRGERD patients (48.7%).The body mass index (BMI) and rates of, typical GER symptoms including acid regurgitation in RGERD patients were significantly lower than those in NRGERD patients ( P <0.05).While the atypical GER symptoms such as poststernal discomfort or chest pain were more common in RGERD group ( P <0.05).RGERD patients presented less acid reflux events and lower proximal segment reflux ratio than NRGERD patients. No obvious differences were found in the manometry metrics between these two groups. The scores of somatization, depression and hostility in RGERD patients by SCL-90 scales were significantly higher than those in NRGERD patients ( P <0.05), and depression score was an independent risk factor for RGERD [ OR =3.915 (95% CI 1.464-10.466), P =0.007]. Conclusions: RGERD patients present more atypical symptoms and pathological non-acid reflux.Depression is an independent risk factor for RGERD.

Objective: To analyze the causes of the esophagogastric junction outlet obstruction (EGJOO) patients, to discuss the differences of the clinical manifestation and esophageal motility characteristics between the anatomic EGJOO (A-EGJOO) and functional EGJOO (F-EGJOO) subgroups, and to search the diagnostic values of the specific metrics for differentiating the subgroups of EGJOO patients., Methods: For the current retrospective study, all the patients who underwent the esophageal high resonance manometry test were retrospectively analyzed from Jan 2012 to Oct 2018 in Peking University Third Hospital. The EGJOO patients were enrolled in the following research. The clinical characteristics, such as symptoms and causes of the patients were studied. Then the patients were divided into two subgroups as A-EGJOO subgroup and F-EGJOO subgroup. The clinical symptoms and the main manometry metrics were compared between these two subgroups. The significant different metrics between the two groups were selected to draw receiver operating characteristic (ROC) curves and the diagnostic values were analyzed in differentiating the A-EGJOO and F-EGJOO subgroups., Results: The most common symptom of EGJOO was chest pain or chest discomfort (30.63%), then the dysphagia (29.73%), and acid regurgitation/heartburn (27.03%). Non-erosive reflux disease (36.04%) was the most popular cause for EGJOO, then the reflux esophagitis (17.12%). Besides the intra-EGJOO and extra-EGJOO lesions, the connective tissue disease (6.31%) and central nervous diseases (2.70%) were found to be the etiology of EGJOO. The causes of the rest 19 EGJOO were unknown. A-EGJOO patients presented significantly higher intra bolus pressure (IBP) than that of F-EGJOO [6.80 (5.20, 9.20) mmHg vs. 5.10 (3.10, 7.60) mmHg, P =0.016]. The area under curve of IBP was 0.637. When IBP≥5.15 mmHg, the sensitivity was 78.60% and specificity 50.70% to differentiate A- or F-EGJOO., Conclusion: Chest pain or chest discomfort was the most common symptom in EGJOO patients. Besides the intraluminal structural disorders, the extra-luminal causes were found in EGJOO patients. A-EGJOO presented higher IBP than that of F-EGJOO patients. The cutoff value of IBP to differentiate A-EGJOO from EGJOO was 5.15 mmHg with sensitivity 78.06% and specificity 50.70%. However for the low area under curve, the diagnostic value of IBP was limited.

Background: Patients diagnosed with schizophrenia were found having lower risks to develop cancers, including glioma. Based on this epidemiology, we hypothesized that there were gene profiles playing opposite roles in pathogenesis of schizophrenia and glioma., Methods: Based on GEO datasets and TCGA, key genes of schizophrenia genes on the opposite development of glioma were screened by different expressed genes (DEGs) screening, weighted gene coexpression network analysis (WGCNA), disease-specific survival (DSS), and glioma grading and verified by gene set enrichment analysis (GSEA)., Results: First, 612 DEGs were screened from schizophrenia and control brain samples. Second, 134 key genes more specific to schizophrenia were left by WGCNA, with 93 key genes having annotations in TCGA. Third, DSS of glioma helped to find 42 key gene expressions of schizophrenia oppositely associated with survival of glioma. Finally, 24 key genes showed opposite expression trends in schizophrenia and different glioma grading, i.e., the upregulated key genes in schizophrenia expressed increasingly in higher grade glioma, and vice versa. CAMK2D and MPC2 were taken as the examples and evaluated by GSEA, which indeed showed opposite trends in the same pathways of schizophrenia and glioma., Conclusion: This workflow of selecting novel targeted genes which may have opposite roles in pathogenesis of two diseases was firstly and innovatively generated by our team. Some filtered key genes were indeed found by their potential effects in several mechanism studies, indicating our process could be effective to generate novel targeted genes. These 24 key genes may provide potential directions for future biochemical and pharmacotherapeutic research studies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Ya-Dan Wen et al.)

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

Because the study population with gliosarcoma (GSM) is limited, the understanding of this disease is insufficient. In this study, the authors aimed to determine the clinical characteristics and independent prognostic factors influencing the prognosis of GSM patients and to develop a nomogram to predict the prognosis of GSM patients after craniotomy. A total of 498 patients diagnosed with primary GSM between 2004 and 2015 were extracted from the 18 Registries Research Data of the Surveillance, Epidemiology, and End Results (SEER) database. The median disease-specific survival (DSS) was 12.0 months, and the postoperative 0.5-, 1-, and 3-year DSS rates were 71.4%, 46.4% and 9.8%, respectively. We applied both the Cox proportional hazards model and the decision tree model to determine the prognostic factors of primary GSM. The Cox proportional hazards model demonstrated that age at presentation, tumour size, metastasis state and adjuvant chemotherapy (CT) were independent prognostic factors for DSS. The decision tree model suggested that age <71 years and adjuvant CT were associated with a better prognosis for GSM patients. The nomogram generated via the Cox proportional hazards model was developed by applying the rms package in R version 3.5.0. The C-index of internal validation for DSS prediction was 0.67 (95% confidence interval (CI), 0.63 to 0.70). The calibration curve at one year suggested that there was good consistency between the predicted DSS and the actual DSS probability. This study was the first to develop a disease-specific nomogram for predicting the prognosis of primary GSM patients after craniotomy, which can help clinicians immediately and accurately predict patient prognosis and conduct further treatment.

Background: Specific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear., Methods: We employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 in regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation. The levels of cytokines and expressions of relative signaling molecules were measured by ELISA, western blot, and qPCR, respectively. Frequency of CD4 + IL-17A + , CD4 + IL-6R + , and CD4 + IL-23R + cells was analyzed by FCM. The interaction between HO-1 and signaling pathway-related proteins was determined by co-immunoprecipitation and western blot., Results: Here, we show that hemin-induced HO-1 overexpression is required to mediate this process. Specifically, HO-1 decreased STAT3 phosphorylation but not IL-6R/IL-23R expression or JAK1/JAK2 activation in CD4 + T cells. The effect was accompanied by co-inhibition of SOCS3, a negative feedback factor of STAT3 activation. HO-1 bound to three domains on STAT3 (DNA-binding, linker, and transactivation domains) to directly regulate STAT3 activation. Conversely, either forced expression of a constitutively active STAT3 mutant or application of small-interfering RNA (siRNA) for HO-1 reversed these effects., Conclusions: Our data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Outcomes of coiling embolization versus clipping for patients with high-grade aneurysmal subarachnoid hemorrhage (aSAH) have not been previously compared. We reviewed current evidence regarding the safety and efficacy of clipping versus coiling for high-grade aSAH., Methods: We conducted a meta-analysis of studies that compared clipping with coiling in patients with high-grade aSAH published from January 1999 to February 2016 in Medline, Embase, and Cochrane databases based on PRISMA inclusion and exclusion criteria. Binary outcome comparisons between clipping and coiling were described using odds ratios (ORs)., Results: Three randomized controlled trials (RCTs) and 16 observational studies were included. There was no statistical difference in good outcome rates between the clipping and coiling groups (OR, 1.44; 95% confidence interval [CI], 0.97-2.13). Subgroup analysis showed no significant difference between the 2 treatments in non-RCTs (OR, 1.49; 95% CI, 0.95-2.36) and RCTs (OR, 1.15; 95% CI, 0.59-2.25). Coiling was associated with higher mortality (OR, 0.55; 95% CI, 0.41-0.75). Lower mortality was associated with clipping in non-RCTs (OR, 0.54; 95% CI, 0.40-0.74), but there was no difference in the RCTs (OR, 0.79; 95% CI, 0.19-3.39). Coiling was not associated with lower rates of complications including rebleeding (OR, 0.62; 95% CI, 0.30-1.29), ischemic infarct (OR, 0.89; 95% CI, 0.53-1.49), symptomatic vasospasm (OR, 0.76; 95% CI, 0.45-1.29), or shunt-dependent hydrocephalus (OR, 1.33; 95% CI, 0.52-3.40)., Conclusion: The outcome with coiling is not superior to clipping in patients with high-grade aSAH; moreover, coiling has a greater risk of mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: It is gradually accepted that solid bolus swallow needs to be added to the procedure of manometry. The motility differences in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES) were not well described. Sierra Scientific Instruments solid-state high-resolution manometry (HRM) system, the most popular HRM system in China, lacks the Chinese normative values for both liquid and solid bolus swallow parameters., Methods: The esophageal HRM data of 88 healthy volunteers were analyzed. The parameters of both sphincters in resting stage were summarized and those during solid and liquid swallows were compared., Key Results: Normative HRM values of sphincter parameters in solid and liquid bolus swallows in China were established. The UES residual pressure of solid bolus swallows was lower than that of liquid bolus (0.3±5.5 mm Hg vs 4.8±5.9 mm Hg, P=.000). The time parameters of UES relaxation between two types of bolus swallows were similar. In solid bolus swallows, the intrabolus pressure (IBP) (13.8±5.1 mm Hg vs 10.9±5.7 mm Hg, P=.000) and LES relaxation time (11.0±2.1 seconds vs 8.7±1.3 seconds, P=.000) were higher. The 4-second integrated relaxation pressure between both bolus swallows was similar., Conclusions & Inferences: The function of the UES and LES between solid and liquid bolus swallows is different. Chinese HRM parameters are different from the Chicago Classification (http://www.chictr.org.cn, Number ChiCTR-EOC-15007147)., (© 2016 John Wiley & Sons Ltd.)

Objectives: To compare the clinical features and high-resolution esophageal motility-impedance characteristics among esophagogastric junction outflow obstruction (Eoo) patients, type Ⅱ achalasia (Ach) patients and healthy controls (Con), in order to explore the values of esophageal high-resolution manometry (HRM) in diagnosis and treatment of Eoo patients., Methods: Patients with dysphagia were enrolled from December 2011 to December 2014 at the outpatient department of Peking University Third Hospital, so were age-matched healthy volunteers. All the patients with organic obstruction were excluded. All the participants were tested with high-resolution esophageal motility-impedance measurement, the patients were diagnosed as Eoo or Ach according to the Chicago classification criteria. Clinical features and esophageal motility characteristics of Eoo, Ach and Con were analyzed., Results: A total of 23 Eoo, 24 Ach and 20 Con were enrolled, whose gender ratios, average ages and body mass indexes were of no significant differences(all P>0.05). (1) The Eoo group had higher percentage of food reflux[21.7% (5/23) vs 0(0/24), P=0.005]and belching[17.4% (4/23) vs 0 (0/24), P=0.013], but lower percentage of dysphagia[47.8% (11/23) vs 79.2% (19/24), P=0.025]and vomiting[0(0/23) vs 12.5%(3/24), P=0.040]compared with the Ach group, with no significant differences in other symptoms(all P>0.05). Besides, the Eoo group had lower Eckardt scores than the Ach group[1(1, 2) vs 3 (2, 5), P<0.001]. (2) The lower esophageal sphincter (LES) basal pressure-minimum in the Eoo was higher than the Con[(26.73±2.77) vs (17.16±1.76) mmHg, P<0.05]. The mean LES basal pressure; and the LES integrated relaxation pressure (IRP), IRP-maximum, and LES relaxation percentage were significantly different among Eoo, Ach and Con[(19.80±1.25) vs (35.95±2.36), (8.43±0.72) mmHg, both P<0.05; (23.22±2.02) vs (48.37±3.71), (12.32±1.29) mmHg, bothP<0.05; 38.61%±3.10% vs 12.42%±5.66%, 64.00%±3.85%, both P<0.05]. (3) There were significant differences in velocity, amplitude, and duration of esophageal peristaltic wave and intrabolus pressure (all P<0.05) among Eoo, Ach and Con; and failed contraction percentage, panesophageal pressurization percentage, premature contraction percentage, and rapid contraction percentage of Eoo were lower than Ach (all P<0.05) while complete contraction percentage of Eoo was high compared with Ach (P<0.001), but no significant differences between Eoo and Con. (4) The Eoo had significantly less incomplete bolus clearance[0.00% (0.00%, 20.00%) vs 100.00% (90.00%, 100.00%), P<0.001]and shorter bolus transit time[(5.44±0.29) s vs (24.13±1.69) s, P<0.001]than Ach, but there were no significant differences between Eoo and Con in these two indexes[0.00% (0.00%, 20.00%) vs 0.00% (0.00%, 9.75%); (5.44±0.29) s vs (5.30±0.19) s; both P>0.05]., Conclusions: The clinical manifestations and esophageal HRM characteristics of Eoo appear to be between Ach and Con, which suggests that Eoo may be an early-stage of Ach. Further study of the pathophysiological characteristics of Eoo patients may provide more evidence to elucidate the pathogenesis of achalasia.

Objective: To study the role of esophagogastric junction contractile index (EGJ-CI) in evaluating the function of anti-reflux barrier, and in differentiating patients with gastroesophageal reflux disease (GERD) from those with functional heartburn (FH)., Methods: A total of 115 patients presenting heartburn were enrolled in the study from January 2012 to June 2015.All subjects had completed Gerd-Q questionnaire and undergone gastroscopy, 24-hour pH-impedance monitoring and esophageal high-resolution manometry. GERD patients were divided into as reflux esophagitis, acid-nonerosive reflux disease (NERD) and weakly acid-NERD groups. Patients with normal esophageal mucosa, normal acid exposure and negative proton pump inhibitor test were enrolled in FH group. EGJ-CI (mmHg·cm) as well as EGJ rest pressure and 4s integrated relaxation pressure (IRP 4s) were measured., Results: Among the 115 patients, 18 were reflux esophagitis [(49.0±18.9) years, M∶F=10∶8], 25 were acid-NERD [(48.7±14.4) years, M∶F=13∶12], 37 were weakly acid-NERD [(52.0±14.8) years, M∶F=15∶22] and 35 were FH [(53.6±14.8), M∶F=8∶27]. No differences of Gerd-Q scores were noticed between the four groups. (1)Negative correlations were demonstrated between EGJ-CI and esophageal acid exposure time (r=-0.283, P=0.002), EGJ-CI and acid reflux events (r=-0.233, P=0.012), EGJ-CI and weakly acid reflux events (r=-0.213, P=0.022), EGJ-CI and non-acid reflux events (r=-0.200, P=0.032). (2)The value of EGJ-CI was significantly higher in FH patients than in the three subgroups of GERD(all P<0.01). EGJ rest pressure of FH group was higher than that of acid-NERD (P<0.01). IRP 4s in acid-NERD group was lower than that of FH and weakly acid-NERD (P<0.05). (3)The area under curve (AUC) of EGJ-CI was higher than that of EGJ-CIT, EGJ rest pressure or IRP 4s(0.686 vs 0.678, 0.641 and 0.578). The cut-off value of EGJ-CI to differentiate GERD from FH was 9.74 mmHg·cm with sensitivity 82.86% and specificity 51.52%., Conclusions: The EGJ-CI values are negatively correlated with esophageal acid exposure time, weakly acid reflux events and non-acid reflux events. Thus it might be used as a metric to reflect the anti-reflux function of EGJ. According to the cut-off value of EGJ-CI 9.74 mmHg·cm, patients with GERD can be sensitively differentiated from patients with FH.

A class of novel 2-aryl-3-(1,3,4-thiadiazolyl)-6(8)-methyl-1,3-benzoxazines was prepared by reactions of 2-methyl-6-((1,3,4-thiadiazolylamino)methyl)phenols or 4-methyl-2-((1,3,4-thiadiazolylamino)methyl)phenols and 2- or 4-nitrobenzaldehyde in the presence of TMSCl in refluxing toluene. The electron-donating methyl group on the benzene ring played an essential role on the reactivity of the substituted phenols, which was proved by DFT calculation. The fungicidal activity of the resultant products were also preliminarily evaluated, most of which displayed moderate to good fungicidal activity. Especially, compound 6f showed 98.0% activity against Sclerotonia sclerotiorum and Botrytis cinerea at concentration of 25μg/mL., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The novel neutron spectrometer TOFED (Time of Flight Enhanced Diagnostics), comprising 90 individual photomultiplier tubes coupled with 85 plastic scintillation detectors through light guides, has been constructed and installed at Experimental Advanced Superconducting Tokamak. A dedicated magnetic shielding system has been constructed for TOFED, and is designed to guarantee the normal operation of photomultiplier tubes in the stray magnetic field leaking from the tokamak device. Experimental measurements and numerical simulations carried out employing the finite element method are combined to optimize the design of the magnetic shielding system. The system allows detectors to work properly in an external magnetic field of 200 G.

Linear regularization has been applied to the HL-2A infrared imaging bolometer to reconstruct local plasma emission with one-dimensional (1D) and three-dimensional (3D) modeling under the assumption of toroidal symmetry. In the 3D modeling, a new method to calculate the detector point response function is introduced. This method can be adapted to an arbitrarily shaped pinhole. With the full 3D treatment of the detector geometry, up to 50% of the mean-squared error is reduced compared with the 1D modeling. This is attributed to the effects of finite detector size being taken into account in the 3D modeling. Meanwhile, the number of the bolometer pixels has been optimized to 20 × 20 by making a trade-off between the number of bolometer pixels and the sensitivity of the system. The plasma radiated power density distributions have been calculated as a demonstration using 1D modeling and 3D modeling, respectively.

An infrared imaging bolometer diagnostic has been developed recently for the HL-2A tokamak to measure the temporal and spatial distribution of plasma radiation. The three-dimensional tomography, reduced to a two-dimensional problem by the assumption of plasma radiation toroidal symmetry, has been performed. A three-dimensional geometry matrix is calculated with the one-dimensional pencil beam approximation. The solid angles viewed by the detector elements are taken into account in defining the chord brightness. And the local plasma emission is obtained by inverting the measured brightness with the minimum Fisher regularization method. A typical HL-2A plasma radiation model was chosen to optimize a regularization parameter on the criterion of generalized cross validation. Finally, this method was applied to HL-2A experiments, demonstrating the plasma radiated power density distribution in limiter and divertor discharges.

Objective: To investigate the discrepancy of anorectal function in patients of Parkinson's disease (PD) with constipation and functional constipation (FC)., Methods: Fifteen consecutive male PD patients with constipation and 45 male FC patients were recruited for the study. All subjects underwent colonoscopy or barium enema in order to exclude organic colon diseases. Every patient underwent anorectal manometry and was categorized into subgroups of either dyssynergia defecation (F3a) or inadequate defecatory propulsion (F3b)., Results: The ages of PD with constipation and FC patients were (70 ± 11) and (68 ± 11) years old respectively. The rectal resting pressure in PD with constipation was higher than that in FC group without statistical significance [9.0(4.0, 15.0) mm Hg vs 6.0(3.0, 9.5) mm Hg, P = 0.082, 1 mm Hg = 0.133 kPa]. The anal resting pressure in PD group was not different from FC group [(51.2 ± 17.2) mm Hg vs (59.7 ± 20.4) mm Hg, P = 0.152]. During anal squeezing, the maximal contraction pressure and area under the squeeze curve in PD with constipation group were both significantly lower than FC patients [maximal contraction pressure: (136.9 ± 43.8) mm Hg vs (183.0 ± 62.1) mm Hg, P = 0.010; area under the squeeze curve: (823.5 ± 635.7) mm Hg·s vs (1392.4 ± 939.9) mm Hg·s, P = 0.033]. During forced defecation, both of the defecation rectal pressure and defecation anal pressure in PD with constipation group were significantly lower than that of FC patients [22.0(15.0, 30.0) vs 42.0(31.0, 55.0) mm Hg, P = 0.000; and (46.3 ± 23.3) vs (77.9 ± 35.1) mm Hg, P = 0.002]. The proportions of F3a subtype were 10/15 and 46.7% (21/45) in PD with constipation and FC patients respectively. There was no significant difference in the constituent ratio (P = 0.120). Initial rectal sensory volumes were (91.3 ± 56.9) ml and (67.2 ± 38.9) ml in PD with constipation and FC patients respectively. Even both volumes were higher than the normal controls, there was no significant difference between the two groups (P = 0.074)., Conclusions: Both PD with constipation and FC patients have abnormal anorectal motility and sensation comparing to the FC group, the parameters of anal contraction and defecation are significantly lower, F3b is dominant, and rectal sensory threshold is higher in PD with constipation patients. These parameters could possibly characterize the anorectal manometry for PD with constipation patients, which is helpful to understand the pathogenesis of PD and differentiate from other diseases.

Background: To compare the characteristics between 22-channel water-perfusion manometry (WPM) and solid-state manometry (SSM) with 36 sensors of the pressure measurements, as well as patients' discomfort indices in nose and pharynx, the preparation and operation time of the manometry., Methods: 12 volunteers were included in the study. Each of the volunteers underwent esophageal manometry by both 22-channel water-perfusion catheter (WPC) and solid-state catheter (SSC) with 36 sensors in random order, and separated by 30 min. The subjects gave a VAS score soon after each test. Non-parametric tests were used to analyze the differences and Bland-Altman plots were used to assess the consistency of the two systems., Results: During the wet swallows, there were significant differences between the two systems in three measurements of location of lower esophageal sphincter (LES) upper margin (Z = -2.11, P = 0.035), LES relax ratio (Z = -2.20, P = 0.028) and IRP4s (Z = -2.05, P = 0.041). During the jelly pocket swallows, LES relax ratio measurements of the two systems showed significant differences (Z = -2.805, P = 0.005). Further Bland-Altman plots analysis presented good agreement between the two systems measurements of location of LES upper margin, LES relax ratio and IRP4s. The discomfort indices of subjects' nasal sensation were higher when inserting the solid-state catheter [5(3.75-5)] than water-perfusion one (2.5(2-4)) (Z = -2.471, P = 0.013), as well as the discomfort indices of pharyngeal sensation (7.5(4.75-9) vs. 4.5(3.75-6.5)), (Z = -2.354, P = 0.019). The preparation time for WPC was 40(39-41) minutes, which was much longer than that for SSC 32.5(31.75-33) minutes, (Z = -3.087, P = 0.002). And the nurses reported it's much easier to insert WPC (Z = -3.126, P = 0.002)., Conclusions: In conclusion, most pressure measurements were consistent between WPM and SSM. Patients tolerated better with WPC, while for operators, the SSC presented more convenient.

Ladar range images have attracted considerable attention in automatic target recognition fields. In this paper, Zernike moments (ZMs) are applied to classify the target of the range image from an arbitrary azimuth angle. However, ZMs suffer from high computational costs. To improve the performance of target recognition based on small samples, even-order ZMs with serial-parallel backpropagation neural networks (BPNNs) are applied to recognize the target of the range image. It is found that the rotation invariance and classified performance of the even-order ZMs are both better than for odd-order moments and for moments compressed by principal component analysis. The experimental results demonstrate that combining the even-order ZMs with serial-parallel BPNNs can significantly improve the recognition rate for small samples.

A new neutral particle analyzer diagnostic has been developed for HuanLiuqi-2A (commonly referred to as HL-2A), which can provide the neutral particle flux measurement along 11 separate sightlines, simultaneously, within a wider energy range (1-70 keV). It is an electrostatic type analyzer with a removable pinhole and special-shape condenser. The energy analysis can be flexibly achieved by controlling a preset stepwise high voltage on the condenser. It is compact and its field of view covers HL-2A cross section from -33 cm to 33 cm without "cross-talk." The energy spectra and ion temperature profile have been obtained during its commissioning.

Aims and Background: To investigate the changing pattern of adenocarcinoma of the esophagogastric junction subtypes and its time trend relationship with that of reflux esophagitis over 10 years at a tertiary medical center in China., Methods and Study Design: . The medical records of all patients who underwent gastroscopy from 2000 to 2009 were reviewed. Subtypes of adenocarcinoma of the esophagogastric junction according to Siewert's classification, gastric non-cardiac adenocarcinoma, esophageal squamous cell carcinoma, reflux esophagitis and Helicobacter pylori infection were diagnosed according to the results of gastroscopy and mucosal histopathology. All the patients were divided into three cohorts (cohort A [2000-2003], cohort B [2004-2006]), cohort C [2007-2009]), and the proportion of adenocarcinoma of the esophagogastric junction and its subtypes in all upper gastrointestinal tumors (adenocarcinoma of the esophagogastric junction, gastric non-cardiac adenocarcinoma and esophageal squamous cell carcinoma) in each cohort were compared. The annual percentages of adenocarcinoma of the esophagogastric junction, reflux esophagitis and H pylori in all patients were also compared., Results: 70,073 patients (cohort A, n = 20298, cohort B, n = 20443, cohort C, n = 29332) who underwent gastroscopy were reviewed. Totally there were 279 patients with adenocarcinoma of the esophagogastric junction (0.398%, M:F = 5.6:1), 794 gastric non-cardiac adenocarcinoma patients (1.133%, M:F = 2:1), 366 esophageal squamous cell carcinoma patients (0.522%, M:F = 3.4:1) and 4681 reflux esophagitis patients. Among the three subtypes of adenocarcinoma of the esophagogastric junction, only type I adenocarcinoma of the esophagogastric junction in upper GI tumors exhibited increasing trend over time (1.86%, 3.39% and 4.94% for cohort A, B and C, respectively, P = 0.009). According to the WHO classification of histological types, the tubular types of adenocarcinoma of the esophagogastric junction have decreased (P = 0.008), whereas papillary type (P = 0.001) increased. The annual detection rate of type I adenocarcinoma of the esophagogastric junction appeared to be positively correlated with reflux esophagitis (r = 0.846, P = 0.002) and negatively with H pylori infection (r = -0.785, P = 0.007) in time trend., Conclusions: Over a recent 10-year period, the three subtypes of adenocarcinoma of the esophagogastric junction showed different changing trends, suggesting heterogeneous characteristics of the three Siewert types of adenocarcinoma of the esophagogastric junction.

By using 15N pool dilution technique in combining with in situ soil cultivation, this paper studied the effects of nitrification inhibitors dicyandiamide (DCD) and 3,4-dimethylpyrazole phosphate (DMPP) on the gross nitrogen (N) mineralization and nitrification rates in a saline-alkali cinnamon soil in North China. The experiment was carried out in a maize-wheat rotation field in Yuncheng City of Shanxi Province, and three treatments were installed, i.e., urea, urea + DCD, and urea + DMPP. In the first two weeks after fertilization, DCD and DMPP made the gross N mineralization rate and gross N nitrification rate decreased by 25.5% and 7.3%, and by 60.3% and 59.1%, respectively, with a significant difference in the gross N mineralization rate but less difference in the gross N nitrification rate between the effects of DCD and DMPP. However, significant difference was observed in the gross N nitrification rate between the effects of DCD and DMPP after seven weeks of fertilization. The gross N mineralization and nitrification rates and the NH4+ and NO3-consumption rates after two weeks of fertilization were 7.2-10.0, 5.5-21.5, 9.1-12.2, and 5.1-8.4 times of those before fertilization, respectively, possibly due to the stimulating effect of N fertilization. DCD and DMPP made the fertilizer urea N more maintained in NH(4+)-N form and less accumulated in NO(3-)-N form in soil. The decreases of the gross N mineralization and nitrifications rate in the test soil due to the effects of the inhibitors would benefit the reduction of N2O emission from the soil.

The formation of a transient internal transport barrier (ITB) is observed after the electron-cyclotron-resonance-heating (ECRH) switch-off in the HL-2A plasmas, characterized by transient increase of central electron temperature. The newly developed correlation reflectometer provided direct measurements showing reduction of turbulence in the region of steepened gradients for the period of ITB formation triggered by the ECRH switch-off. Furthermore, the reduction of core turbulence is correlated in time with the appearance of a low-frequency mode with a spectrally broad poloidal structure that peaks near zero frequency in the core region. These structures have low poloidal mode number, high poloidal correlation, and short radial correlation and are strongly coupled with high-frequency ambient turbulence. Observation indicates that these structures play important roles in the reduction of the core turbulence and in improvements of the core transport after the off-axis ECRH is turned off.

Objective: To compare the diagnostic values of GerdQ questionnaire, 24-h pH monitoring and 24-h impedance-pH monitoring for gastroesophageal reflux disease (GERD) and to analyze the reflux patterns of Barrett's esophagus (BE), reflux esophagitis (RE) and non-erosive disease (NERD)., Methods: From June 1, 2009 to September 30, 2010, 205 GERD patients were included according to the Montreal consensus. All were surveyed by a GerdQ questionnaire and underwent 24-h impedance-pH monitoring. The diagnostic sensitivities of GerdQ, 24-h pH-DeM and 24-h IMP-pH were compared and the reflux pattern of BE, RE and NERD analyzed., Results: A total of 205 GERD patients including 10 BE, 28 RE and 167 NERD were recruited. (1) The diagnostic rate of 24-h IMP-pH was 74.1%. It was significantly higher than that of GerdQ (51.7%) and 24-h pH-DeM (29.2%). (2) The diagnostic sensitivities of GerdQ and 24-h pH-DeM for BE and RE were higher than that for NERD. But there were no significant differences of 24-h IMP-pH for three types of GERD (70.0%, 82.1% and 73.1%). (3) There were positive correlations among the scores of GerdQ, pH-DeM scores and acid scores in IMP-pH (r = 0.242, P = 0.000; r = 0.182, P = 0.009 and r = 0.632, P = 0.000). (4) Added diagnostic values of IMP-pH were 58.5% and 74.5% respectively in patients who would have been missed by GerdQ and pH-DeM. (5) The detection rate and score of acid reflux in RE patients were higher than that of NERD [53.6% vs 23.4%, P < 0.05; 45.6 (35.0 - 67.5) vs 23.1 (9.3 - 35.0), P < 0.05]. But gas score and separate acid reflux were lower than that in NERD [17 (0 - 194) vs 30 (0 - 500), P < 0.05; 57.4% vs 28.6%, P < 0.05]., Conclusions: Acid reflux plays an important role in RE. The value of GerdQ and 24-h pH-DeM and 24-h IMP-pH monitoring were similar for the diagnosis of RE. Weak acid may be more important for BE and NERD patients than separate acid reflux. And 24-h IMP-pH monitoring has a distinct advantage in diagnosing these two types.

Objective: To investigate the clinical characteristic and prognosis of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin associated peptic ulcer bleeding., Method: All patients with peptic ulcer bleeding were studied by the same researcher after admission and discharge., Results: Fifty-one cases with NSAIDs and aspirin medication of the total peptic ulcer bleeding patients (147 cases) were included (34.7%). Compared with patients not associated with NSAIDs and aspirin medication, they are older [(41.2 ± 1.9) years vs (59.4 ± 2.2) years, P < 0.001], more commonly associated with hypertension (10.4% vs 39.2%, P < 0.001), coronary heart disease (10.4% vs 17.6%, P < 0.001), diabetes (4.2% vs 19.6%, P = 0.005); and had more severe anemia (7.3% vs 23.5%, P = 0.008). Fewer patients in NSAIDs group had epigastric pain (61.5% vs 27.5%, P < 0.001), while there was more re-bleeding (9.4% vs 15.7%, P = 0.034). In all bleeding patients, factors associated with re-bleeding, surgical intervention and death included NSAIDs and aspirin medication, and low platelet count. In patients with NSAIDs and aspirin medication, re-bleeding was associated with previous ulcer history (P < 0.05)., Conclusion: Peptic ulcer bleeding patients with NSAIDs and aspirin medication were more severe ill, and less likely to present with epigastric pain.

Purpose: Mycophenolate mofetil (MMF) is a pro-drug that is hydrolyzed to release mycophenolic acid (MPA). Subsequently MPA is extensively metabolized to phenyl mycophenolic acid glucuronide (MPAG) and MPA acyl glucuronide (AcMPAG). It was presumed that the closest association is between plasma AcMPAG concentrations and the incidence of diarrhea. This study aimed to investigate the correlation between pharmacokinetics of MPA, MPAG, and AcMPAG and diarrhea in liver transplant recipients on MMF with tacrolimus., Methods: Sixty-seven patients receiving liver transplantation were included. The pharmacokinetics of MPA and its metabolites were monitored repeatedly in the early stage (within 2 weeks) and in the late stage after transplant. The plasma concentrations of MPA, MPAG, and AcMPAG were determined by the HPLC method., Results: Twenty-two patients (32.8%) suffered from episodes of diarrhea. Compared with the data from the early stage, AUC(0-12h) of MPA, MPAG, and AcMPAG increased significantly in both groups in the later stage. AUC(0-12h) of MPA, MPAG, and AcMPAG were not different significantly between the group with diarrhea and the group without diarrhea, either in the early stage or in the late stage (P > 0.05)., Conclusion: These results suggest that systemic exposures to MPA and its metabolites are not associated with the incidence of diarrhea in liver transplant recipients.

Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 A, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 A, and the standard bond angle deviation was 1.3 degrees . The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored approximately 90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis.

Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of ferroheme metabolic pathway, which has the functions of anti-oxidation, anti-inflammatory, anti-apoptosis and anti-smooth muscle hyperplasia. Furthermore, HO-1 exerts a protective action in the diseases mediated by effector T lymphocytes such as T helper (Th) 1, Th2 and Th17. In addition, regulatory T cells (Treg) control the activity of CD4+CD25- effector cells in a suppressive manner. Numerous studies indicate that the protective action of HO-1 in diseases is through CD4+CD25+ Treg. This paper will review the current research and understanding of HO-1's role in T cells-mediated immunoregulation.

Cumulative evidence suggests the up-regulation of interleukin (IL)-10 and T-regulatory (Treg) cells is implicated in anti-inflammatory effect of heme oxygenase-1 (HO-1). Thus, we postulated that induction of HO-1 could augment IL-10 and transforming growth factor (TGF)-beta production and foxp3+CD4+CD25+ Treg cell function, thereby leading to attenuation of airway inflammation. In this study, CD4+CD25+ Treg cells isolated from mouse spleen were either transfected with a HO-1 expression vector (pcDNA3HO-1) or treated with a HO-1 inducer (hemin). Up-regulation of HO-1 enhanced foxp3 expression and IL-10 secretion in the Treg cells in vitro. Next, BALB/c, C57/B6.129, and IL-10-deficient B6.129P2-Il10tm1Cgn/J mice were challenged by ovalbumin to induce airway inflammation. Consistent with in vitro findings, hemin treatment resulted in induction of HO-1 and foxp3 and production of IL-10 and membrane-bound TGF-beta1 in vivo. This was further correlated with decrease of ovalbumin-specific immunoglobulin E level and eosinophil infiltration in bronchial alveolar lavage fluid from the asthmatic mice. Furthermore, hemin significantly enhanced the biological activity of CD4+CD25+ Treg cells. This protective effect was specifically blocked by Sn-protoporphyrin, a HO-1 enzymatic inhibitor. Finally, hemin failed to up-regulate the function of CD4+CD25+ Treg cells from IL-10-deficient mice. Our study indicates that HO-1 exerts its protective effect on asthma through a mechanism mediated by foxp3+CD4+CD25+ Treg cells, IL-10, and membrane-bound TGF-beta1.

Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage.

Heme oxygenase-1 (HO-1) has anti-inflammatory effects in asthma. CD4+CD25(high) regulatory T cells (Treg) are a potent immunoregulator that suppresses the immune response. We studied the effects of HO-1-mediated CD4+CD25(high) Treg on suppression of allergic airway inflammation by comparing mice treated with hemin, OVA, Sn-protoporphyrin (SnPP), and hemin plus SnPP. Airway responsiveness, airway eosinophil infiltration, the level of OVA-specific IgE, and the numbers of cells in general and eosinophils in particular in bronchial alveolar lavage fluid were lower in the hemin group than in the OVA, SnPP, and hemin plus SnPP groups. The expressions of HO-1 mRNA and protein in the lung were increased by repeated administrations of hemin and SnPP. However, the activity of HO-1 was highest in hemin mice. The percentage and suppressive function of CD4+CD25(high) Treg and the expression of Foxp3 mRNA were obviously enhanced after treatment with hemin. This increase was diminished by the administration of SnPP. The concentration of serum IL-10 was higher in the hemin group than in the other groups, whereas the level of serum TGF-beta did not significantly differ across groups. Furthermore, the ratio of IFN-gamma/IL-4 mRNA in the lung was higher in hemin-treated mice than in OVA and SnPP mice. The suppressive capacity of CD4+CD25(high) Treg was not enhanced in the IL-10-deficient mice treated with hemin. In conclusion, our experiments in the animal model demonstrated that HO-1 has anti-inflammatory effects, probably via enhancement of the secretion of IL-10 and promotion of the percentage of CD4+CD25(high) Treg.

Objective: Comparing the infection rates and density of Helicobacter pylori (H. pylori) and the patterns of gastritis in reflux esophagitis (RE) and non-erosive reflux disease (NERD) patients to investigate the role of H. pylori in the pathogenesis of RE., Methods: Two hundred and twenty-three out-patients with typical gastroesophageal reflux symptoms who consecutively visited the hospital underwent ambulatory 24-hour pH monitoring and gastroscopy, and biopsy of the gastric mucosa. RE and NERD were diagnosed based on the presentation of endoscopy. Gastritis was divided into four different patterns: chronic non-atrophic antritis (CNAA); chronic non-atrophic pan-gastritis (CNAG); chronic atrophic antritis (CAA); and chronic atrophic pan-gastritis (CAG). H. pylori infection was evaluated by Warthin-Starry staining. DeMeester score > or = 15 was considered as pathological acid reflux., Results: Sixty-two patients (27.8%) were found to have RE, 161 (72.2%) were found to have NERD. Totally, 67 patients had H. pylori infection (30.0%). There was no significant difference in H. pylori infection rate between the RE and NERD groups (25.8% vs. 31.5%, P > 0.05). 45 of the 223 patients were diagnosed as with CNAA (20.2%), 88 (39.5%) with CNAG, 65 (29.2%) with CAA, and 25 (11.2%) with CAG. The CAG rates in the RE and NERD groups were 6.5% and 13.0% respectively (P > 0.05). There were no differences in abnormal pH monitoring rate and DeMeester score among the different patterns of gastritis. In the sixty-seven H. pylori-positive GERD patients, the 24 h pH monitoring positive rate of the moderate-severe H. pylori colonization density group was 46.4%, significantly higher than that of the mild H. pylori colonization density group (73.5%, P < 0.05); and the mean intra-gastric pH value during 24 hours of the moderate-severe H. pylori colonization density group was 2.3 +/- 0.8, significantly higher than that of the mild H. pylori colonization density group (2.0 +/- 1.1, P < 0.05)., Conclusion: H. pylori infection is associated with the pattern of gastritis, but shows no relationship to the incidence of RE. High density of H. pylori colonization in gastric corpus may reduce the esophageal acid exposure. Diffuse atrophic gastritis may protect the patients from RE.

Objective: Bronchial asthma is a chronic inflammatory disorder. Long-term inflammation leads to varying degrees of structural changes in the airway wall known as airway reconstruction or remodeling. These structural changes are found in the airways of most patients with prolonged disease. After remodeling, the airway walls show the submucous membrane becomes thick with collagen deposition, and the smooth muscle cells show hyperplasia and hypertrophy. Smooth muscle cells are a vital component of the airway wall, and a major effector cell involved in the course of bronchial contraction. Smooth muscle cell hyperplasia and hypertrophy are important pathological changes in airway remodeling. This study investigated the expression of markers of human airway smooth muscle cells (ASMCs) phenotypic change, which were matrix Gla protein (MGP) and major fibrosis proteins, after in vitro treatment with transforming growth factor-beta(1) (TGF-beta(1))., Methods: Human ASMCs were subjected to primary culture in vitro. Ten groups of cells were treated with 100 microg/ml of TGF-beta(1), while the cells in the control groups were treated with 10% fetal bovine serum. After being cultured for 7 d, the cells of both groups were harvested. MGP mRNA expression was detected by RT-PCR. Protein levels of collagen I, III and V were determined by Western blot analysis., Results: Treated with TGF-beta(1), airway smooth muscle cells expressed MGP mRNA greater than controls [(62.3 +/- 13.1)% vs (27.4 +/- 11.4)%, P < 0.01]. Also, airway smooth muscle cells stimulated by TGF-beta(1) produced more collagen I, III and V than the control group (P < 0.01)., Conclusions: TGF-beta(1) induced expression of collagen III and V, which are early markers of the switch from a contractile to a synthetic phenotype in ASMCs. This induction is an indication that ASMCs have the potential to make this switch and that TGF-beta(1) is involved in airway remodeling.

Objective: To compare the differences in the psychological scale scoring among different subgroups reflux esophagitis (RE) and non-erosive reflux disease (NERD) and to explore the influence of mental factors on the pathogenesis of RE and NERD., Methods: Two hundred and six patients with typical heartburn and acid regurgitation underwent endoscopy and esophageal pH monitoring and then were divided into 4 groups: RE+ group (n = 35, 24.3%) with RE and positive pH monitoring results, RH- group (n = 15, 30.0%) with RE and negative pH monitoring results, NERD+ group (n = 77, 40%), with NERD and positive pH monitoring results, and NERD- group (n = 79, 50.6%) with NERD and negative pH monitoring results that was re-divided into 2 subgroups according to the symptom index (SI): NERD-SI+ group (n = 18, 22.8%) with positive symptom index and NERD-SI- group (n = 61, 77.2%) with negative SI. The demographic data and body mass index (BMI) were investigated. The psychological questionnaires: Symptom Checklist 90 (SCL-90), and Hospital Anxiety and Depression Scale (HAD) were used., Results: (1) Male patients were dominant in the RE group and RE+ subgroup, while female patients were dominant in the NERD group and NERD+ subgroup. The values of BMI of the RE group and RE+ subgroup were significantly higher than those of the NERD group and NERD+ subgroup. (2) The abnormal pH monitoring rate of the RE group was 70.0%, significantly higher than that of the NERD group (49.4%). The average DeMeester's score of the RE group was 39.3 (96.5), significantly higher than that of the NERD group 13.8 (33.6). The average DeMeester's score of the RE+ group was 68.1 (95.2), significantly higher than that of the NERD+ group 40.1 (64.4). (3) 44.6% (29/65) of the patients presented depression and 36.9% (24/65) had anxiety, most of them were in mild or moderate degree. The scores of most items of each mental scale were significantly higher in the NERD- patients than in the NERD+ patients, especially in the NERD-SI- subgroup., Conclusion: The symptoms of RE+ and NERD+ patients are associated with esophageal acid exposure and the acid reflux in the RE patients is much severer than that in the NERD patients. Anxiety and depression are related to the symptoms of patients without objective evidence of esophageal mucosal injury and acid reflux (NERD-), especially in the symptom index negative subgroup. Visceral hypersensitivity and stress play an important role in the pathogenesis of gastroesophageal reflux.

Xenograft rejection are due to the activation of endothelial cells and the expression of a series of proinflammatory genes encoding adhesion molecules, cytokines/chemokines and procoagulant molecules,leading to endothelial cell injury and apoptosis. HO-1 which acts as a cytoprotective gene can suppress a variety of inflammatory responses to prevent graft rejection. In this study, The plasmid containing HO-1 cDNA was constructed and transfected into human vascular endothelial cells (HUVEC) for expression using DOTAP lipsomal transfection reagents. Cells were homogenized in cell culture lysis reagent (CCLR) and the activity of HO-1 was measured. The apoptosis of HUVEC induced by tumor necrosis factor (TNF)-alpha was analyzed by flow cytometry. Meanwhile, Heme and Sn-protoporphyrin (SnPP) were added respectively to evaluate the apoptosis rate of HUVEC. The results showed that the expression of HO-1 gene can be significantly up-regulated in HUVEC transfected with pcDNA3HO1. The apoptosis rate of cells treated with Heme was less than 20% but significantly increased when cells treated with SnPP, the maximum arrived at 95%. The apoptosis rate in heme induced cells was 5-20 times lower than that in SnPP inhibited cells. The apoptosis rate was a negative relation to HO-1 expression. HO-1 protein can inhibit apoptosis in HUVEC. The results provide evidence to support the essential role of HO-1 in the cytoprotective function.

Objectives: Comparing the esophageal acid exposure characteristics between reflux oesophagitis (RE) and non-erosive reflux disease (NERD) patients to identify the NERD subgroups., Methods: One hundred and twenty-eight patients with heartburn and acid regurgitation were evaluated. Esophageal mucosa injury was assessed by gastroscopy. The extent of esophageal acid exposure was determined by ambulatory 24 h esophageal pH monitoring. DeMeester point >/= 15 was taken as positive., Results: Thirty-seven patients were found to have RE (28.9%), 91 were diagnosed as NERD. There was no difference at DeMeester point between RE and NERD (P > 0.05). Patients with RE have more long reflux episodes than NERD patients (8.16 +/- 10.27 vs 3.96 +/- 6.87; P = 0.004). Among NERD patients, 46 (50.5%) had an abnormal pH monitoring (NERD+); another 45 were normal (NERD-). Patients with NERD+ were more likely to demonstrate at positive symptom index (SI > 50%) than those with NERD- (43.5% vs 15.6%; P < 0.001). In NERD- group, patients with a positive SI (NERD-SI+) have more reflux episodes than those with a negative SI (NERD-SI-) (55.29 +/- 24.68 vs 34.87 +/- 24.06; P < 0.05), as well as the fraction time of 24 h that pH < 4 in upright (4.16 +/- 2.98 vs 1.88 +/- 1.60; P < 0.05). Twenty-five RE patients have an abnormal pH monitoring (RE+, 67.6%), another 12 were normal (RE-). RE- patients have a higher median of intra-esophageal and gastric pH than RE+ patients respectively (6.75 +/- 0.42 vs 5.18 +/- 1.32; 2.69 +/- 2.59 vs 1.49 +/- 0.66; P < 0.05)., Conclusions: RE patients have longer reflux episodes than NERD. The symptoms of most gastroesophageal reflux disease patients associate with acid reflux. Acid reflux characteristics and symptom patterns suggest subgroups of NERD patients. The bile or mixed reflux may be involved in the pathogenesis of RE- group.

Human Heme Oxygenase-1 (hHO-1) is the rate-limiting enzyme in the catabolism reaction of heme, which directly regulates the concentration of bilirubin in human body. The mutant structure was simulated by Swiss-pdbviewer procedure, which showed that the structure of active pocket was changed distinctly after Ala25 substituted for His25 in active domain, but the mutated enzyme still binded with heme. On the basis of the results, the expression vectors, pBHO-1 and pBHO-1(M), were constructed, induced by IPTG and expressed in E. coli DH5alpha strain. The expression products were purified with 30%-60% saturation (NH4)2SO4 and Q-Sepharose Fast Flow column chromatography. The concentration of hHO-1 in 30%-60% saturation (NH4)2SO4 components and in fractions through twice column chromatography was 3.6-fold and 30-fold higher than that in initial product, respectively. The activity of wild hHO-1 (whHO-1) and mutant hHO-1 (deltahHO-1) showed that the activity of deltahHO-1 was reduced 91.21% compared with that of whHO-1. The study shows that His25 is of importance for the mechanism of hHO-1, and provides the possibility for effectively regulating the activity to exert biological function.