Search

Antiangiogenic therapy is an effective way to disrupt nutrient supply and starve tumors, but it is restricted by poor efficacy and negative feedback-induced tumor relapse. In this study, a neuropilin-1 (NRP-1)-targeted nanomedicine (designated as FPPT@Axi) is reported for spatiotemporal tumor suppression by combining photodynamic therapy (PDT) with antiangiogenesis. In brief, FPPT@Axi is prepared by utilizing an NRP-1-targeting chimeric peptide (Fmoc-K(PpIX)-PEG 8 -TKPRR) to encapsulate the antiangiogenic drug Axitinib (Axi). Importantly, the NRP-1-mediated targeting property enables FPPT@Axi to selectively concentrate at vascular endothelial and breast cancer cells, facilitating the production of reactive oxygen species (ROS) in situ for specific vascular disruption and enhanced cell apoptosis under light stimulation. Moreover, the codelivered Axi can further inhibit vascular endothelial growth factor receptor (VEGFR) to impair the negative feedback of PDT-induced tumor neovascularization. Consequently, FPPT@Axi spatiotemporally restrains the tumor growth through blocking angiogenesis, destroying tumor vessels, and inducing tumor apoptosis. Such an NRP-1-mediated targeting codelivery system sheds light on constructing an appealing candidate with translational potential by using clinically approved PDT and chemotherapy.

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ . Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.

Herein, a Sc(OTf) 3 -catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[ b ]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Objective: To develope a titanium specimen with good osteogenic activity through fabrication of a composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface. Methods: An ordered micro-/nanotextured structure was prepared on the surface of titanium (the control), and then hydroxyapatite was deposited on the as-prepared ordered micro-/nanotextured structure by alternative loop immersion method. The ordered micro-/nanotextured structures before and after hydroxyapatite deposition were denoted as HA and MN, respectively. Surface morphology was observed using a scanning electron microscope. Bone marrow mesenchymal stem cells (BMMSC) were seeded on the surface of three different materials. Cell morphology was observed with a scanning electron microscope. Cell adhesion and cell proliferation were evaluated using 4', 6-diamidino-2-phenylindole staining and cell counting kit-8 assay, respectively. Extracellular matrix mineralization and the expression levels of osteogenesis-related genes were evaluated by alizarin red staining and real-time quantitative PCR, respectively. Each group has three samples in every experiment. Results: After alternative loop immersing, the MN's original microholes (20 μm in diameter) were retained, and the uniform petal-like hydroxyapatite was deposited on the MN's original titania nanotubes (70 nm in diameter). Compared with the control, BMMSC on MN and HA elongated further and intersected along the micron structure with noticeable pseudopodia and pseudoplates, and the trend was more pronounced especially on HA. The number of early adherent cells on HA was remarkably larger than that on the control and MN at each time point ( P< 0.05). On day 1, the A value of cell proliferation on HA was significantly higher than that on the control and MN ( P< 0.05). The A value of cell proliferation on HA was significantly lower than that on the control and MN on day 3 ( P <0.05). On day 7, the A value of cell proliferation on HA was significantly lower than that on MN ( P <0.05), but there was no statistically significant difference in the A value of cell proliferation between HA and the control on day 7 ( P >0.05). The A value of extracellular matrix mineralization on HA (0.607±0.011) was significantly higher than that on the control and MN (0.268±0.025 and 0.522±0.022, respectively) ( t =-0.25, P <0.001; t =-0.34, P <0.001). The expression levels of bone related genes on HA were significantly higher than those on the control and MN ( P <0.05). Conclusions: HA could promote the BMMSC adhesion and osteogenic differentiation, support BMMSC proliferation, and demonstrate good osteogenic activity.

Fat emulsion is a drug commonly used clinically for parenteral nutrition support in critically ill patients.With the development of the pharmaceutical industry, fat emulsion has formed a variety of different formulations, among which different types of fat emulsion have their own metabolic and body energy supply characteristics, and the application indications are also different. In addition to providing the supply of nutrients, the role of fat emulsion in anti-toxicity, immune regulation, anti-inflammatory, anti-shock, cardiopulmonary resuscitation and other aspects has gradually been discovered. This article reviews the existing evidence-based medical evidence and expounds the mechanism and therapeutic role of fat emulsion in the treatment of critically ill patients with poisoning. Its value in the treatment of critically ill patients with poisoning was discussed, and some references were provided for the application of non-nutritional functions of fat emulsion in the future.

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP 3 R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP 3 R3. The effect of IP 3 R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP 3 R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP 3 R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP 3 R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP 3 R3, which was accompanied by a subcellular redistribution process in which IP 3 R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP 3 R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP 3 R3 are involved in promoting renal cyst development, which implies IP 3 R3 as a potential therapeutic target of ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/β-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Competing Interests: Conflicts of interest: None.

Objective: To summarize the clinical characteristics and treatment effect of patients with acute oral 84 disinfectant poisoning, so as to improve the understanding, diagnosis and treatment of the disease. Methods: In January 2022, 25 hospitalized patients with acute oral 84 disinfectant poisoning admitted to our department from March 2016 to August 2021 were selected as the research objects, and their general conditions, poisoning reasons, poisoning time, dose of poisoning, clinical manifestations, blood routine and biochemical indicators, diagnosis, treatment and prognosis were selected. Results: A retrospective analysis was performed. Among the 25 patients, there were 4 males and 21 females, aged from 20 to 91 years, and M ( Q (1), Q (3)) was 38.7 (27, 46) years; The poisoning time (from exposure to poison to treatment) was 1~72 h, and M ( Q (1), Q (3)) was 10.5 (3, 11.5) h. The length of stay was 1~20 days, and M ( Q (1), Q (3)) was 5.72 (2, 7) days.The dose was 40-500 ml, and the M ( Q (1), Q (3)) was 219.6 (100, 330) ml. Chest CT showed exudative changes in both lungs in 4 patients, excessive decreased permeability in 1 case and pleural effusion in 1 case. Gastroscope showed 2 cases of erosive inflammation of gastric body and antrum, 1 case of esophageal ulcer and cardiac ulcer, 1 case of corrosive gastritis, gastric fundus ulcer and esophageal stenosis. Abdominal X-ray showed 1 case of abdominal intestinal dilatation and pneumatosis with multiple gas-liquid planes.There were 1 case of type I respiratory failure, 6 cases of gastrointestinal bleeding and 1 case of incomplete intestinal obstruction. There were 19 cases of nausea and vomiting, 9 cases of abdominal pain, 6 cases of pharyngeal pain and 6 cases of retrosternal burning pain, 1 case of cough and 2 cases of fatigue. Conclusion: Acute oral 84 disinfectant will cause varying degrees of damage to the human digestive tract and lungs. In severe cases, gastrointestinal bleeding, intestinal obstruction, hypoxemia, etc, and even life-threatening, should be paid attention to clinically. The treatment is mainly symptomatic support treatment, such as protecting gastrointestinal mucosa, controlling acute inflammatory reaction, protecting the functions of liver and kidney and other important organs.

Background: Misuse of disinfectants during the coronavirus disease 2019 pandemic has led to several poisoning incidents. However, there are few clinical case reports on poisoning caused by improper mixing of household disinfectants., Aim: To summarize the clinical characteristics and treatment effects of chlorine poisoning caused by improper mixing of hypochlorite bleach with acidic cleaning agents., METHODSWe retrospectively analyzed baseline and clinical data, clinical symptoms, and treatment methods of seven patients with chlorine poisoning who were admitted to the National Army Poisoning Treatment Center., Results: Among the seven patients, the average poisoning time (exposure to admission) was 57 h (4-240 h). All patients were involved in cleaning bathrooms. Chest computed tomography scans revealed bilateral lung effusions or inflammatory changes in five patients. The partial pressure of oxygen decreased in six patients, and respiratory failure occurred in one. Five patients had different degrees of increase in white blood cell count. Humidified oxygen therapy, non-invasive mechanical ventilation, anti-inflammatory corticosteroids, antioxidants, and antibiotics were administered for treatment. The average length of hospital stay was 7 d (4-9 d). All seven patients recovered and were discharged., Conclusion: Improper mixing of household disinfectants may cause damage to the respiratory system due to chlorine poisoning. Corticosteroids may improve lung exudation in severe cases, and symptomatic supportive treatment should be performed early., Competing Interests: Conflict-of-interest statement: All authors declare that they have no competing interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations&apos; safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present., Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments., Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies., Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect., Competing Interests: The authors disclose no conflicts., (Copyright © 2022 Li-Hua Liu et al.)

Competing Interests: Conflicts of interests: All authors declared no conflicts of interests.

Dearomatization of indole is a useful strategy to access indolimines: a motif widely exists in biologically active molecules and natural products. Herein, an efficient method for the dearomatization of 2,3-disubstituted indoles to generate diverse indolimines with tetrasubstituted allenes is described. This work accomplishes dearomatization of 2,3-disubstituted indoles through 1,8-addition of (aza)- para -quinone methides, which are generated in situ from propargylic alcohols. A series of synthetically useful indolimines containing quaternary carbon centers and tetrasubstituted allenes can be accessed in good yields (up to 99%). Additionally, the separability of product isomers, diversified product transformations, and easy scale-up of the reaction demonstrate the potential application of this method.

A novel Brønsted acid catalyzed 1,8-addition mediated (3 + 4)-annulation of in situ generated propargylic p -quinone methides with 2-indolylmethanols is described. This method provides a convenient and mild approach to structurally interesting and synthetically important polysubstituted indole-fused oxepines in high yields. Moreover, 2-indolylmethanols as four-atom synthons in the (3 + 4)-annulations under Brønsted acid conditions have been explored for the first time.

Herein, we describe a highly effective 1,8-conjugate-addition-mediated formal (3+3)-annulation of (aza)- para -quinone methides in situ generated from propargylic alcohols with 4-hydroxycoumarins and 1,3-dicarbonyl compounds under the catalysis of a Brønsted acid. This methodology affords efficient and practical access to synthetically important and highly functionalized pyranocoumarins and pyrans in excellent yields under mild conditions. Importantly, these products exhibit impressive inhibitory activity toward α-glucosidase.

Background: Some pulmonary nodules are not suitable for computed tomography-guided percutaneous localization. This study aimed to investigate the feasibility and safety of real-time localization for these non-palpable pulmonary nodules using watershed analysis of the target pulmonary artery during thoracoscopic wedge resection., Methods: Watershed analysis is a novel technique that can be used to create a specific area on the lung surface for nodule localization. This analysis is performed by temporarily blocking the target pulmonary artery and using indocyanine green fluorescence during surgery. In our study, the surgery was simulated and evaluated preoperatively using a high-precision three-dimensional reconstruction model obtained by multidetector spiral computed tomography. The lung was observed using an infrared thoracoscopy system after an intravenous injection of indocyanine green (2.5 mg/mL), and the white-to-blue transitional zone was marked using electrocautery, after which a wedge resection was performed., Results: A total of 25 out of 26 patients underwent successful wedge resection. The mean tumor size and depth based on computed tomography scans were 13.2±6.4 and 12.2±7.8 mm, respectively. The mean operation duration was 142.6±52.8 min. The mean bleeding volume during surgery was 12.9±9.7 mL. The mean drainage tube indwelling time was 35.6±20.0 h, and the median length of postoperative stay was 3 days (range, 2-6 days)., Conclusions: Our experience showed that the watershed analysis of the target pulmonary artery for nodule localization was safe and feasible. It may become an effective and attractive alternative method for localizing non-palpable pulmonary nodules in selected patients undergoing thoracoscopic wedge resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1281). YLW serves as an unpaid Honorary Editor-in-Chief of Translational Lung Cancer Research from Jan 2015 to Jan 2021. WZZ serves as an unpaid Associate Editor-in-Chief of Translational Lung Cancer Research from Jan 2015 to Jan 2021. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Ephedrine (EPH) is an alkaloid commonly used to relieve nasal congestion caused by colds, allergic rhinitis, rhinitis, and sinusitis, and to control bronchial asthma. It is also be used as a raw material in the manufacture of methamphetamine. Although the distribution of EPH in surface waters has been widely studied, its uptake, internal distribution, and toxicokinetic processing in exposed organisms have not been well investigated. In this study, we investigated the uptake, disposition, and toxicokinetics of EPH in zebrafish ( Danio rerio ) in a semi-static exposure system. EPH was consistently detected in zebrafish biological samples, with the highest concentrations of 84.97 ng·g -1 detected in the brain tissue of fish in the high treatment group. Over the 14-d exposure period, the relative abundance of mean concentrations of EPH in biological samples generally followed the order of brain > ovary > liver > intestine > muscle. The uptake rate constants ( K u ), elimination rate constants ( K e ), and half-lives of EPH in the biological tissues were in the ranges 0.23-570.31 L·(kg·d) -1 , 1.22-6.11 d -1 , and 0.12-0.57 d, respectively. The observed bioconcentration factor (BCF o ) and kinetically-derived bioconcentration factor (BCF k ) were similar, ranging 0.24-337.33 L·kg -1 and 0.13-316.43 L·kg -1 , respectively. These results are helpful for understanding the behavior of psychoactive substances in aquatic organisms and have directive significance for studying their toxicity and ecological risks to aquatic organisms.

Herein, we report an efficient Brønsted acid-catalyzed formal (3+3)-annulation of (aza)- para -quinone methides generated in situ from propargylic alcohols with naphthol derivatives, which involves a 1,8-conjugate addition/6-endo annulation process. This protocol provides an effective method for preparing important functionalized pyranocoumarins under mild conditions.

Background: Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis‑related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC., Methods: Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets., Results: Seventeen prognostic GRGPs (HMMR&#95;PFKFB1, CHST1&#95;GYS2, MERTK&#95;GYS2, GPC1&#95;GYS2, LDHA&#95;GOT2, IDUA&#95;GNPDA1, IDUA&#95;ME2, IDUA&#95;G6PD, IDUA&#95;GPC1, MPI&#95;GPC1, SDC2&#95;LDHA, PRPS1&#95;PLOD2, GALK1&#95;IER3, MET&#95;PLOD2, GUSB&#95;IGFBP3, IL13RA1&#95;IGFBP3 and CYB5A&#95;IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e-14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e-02, and Asian: P = 6.342e-08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets., Conclusion: The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC., Competing Interests: The authors declare that they have no competing interests., (© 2020 Zhou et al.)

An efficient and straightforward Lewis-acid-mediated stereoselective (4 + 3)-cyclization of indole-substituted alkylidene malonates and donor-acceptor cyclopropanes has been developed involving the Friedel-Crafts/Michael addition cyclization cascade. This reaction provides a mild and effective method for the construction of synthetically and structurally interesting functionalized cycloheptannelated indoles.

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P< 0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group ( P< 0.01), and Roxithromycin inhibited the high expression of these cytokines ( P< 0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P< 0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P< 0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group ( P< 0.01), and Roxithromycin up-regulated its expression ( P< 0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE ( r= 0.706, P< 0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 ( r= -0.775, P< 0.01), and between the expression of Caveolin-1 and RAGE ( r= -0.919, P< 0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.

Objective: Ulcerative colitis (UC), one of the most stubborn diseases, is mainly treated by aminosalicylic acid (ASA). However, the side effects of ASA include vomiting, nausea, rash, diarrhea, headache, etc, which seriously affect life-quality of UC patients. Probiotics such as bifid triple viable (BTV) could reduce drug-induced adverse reactions and has a good clinical effect on UC. Therefore, we aimed to evaluate the clinical efficacy and safety of BTV plus ASA in treating UC., Methods: PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang databases were searched from the inception dates to October 12, 2018. Randomized controlled trials (RCTs) were included by comparing BTV plus ASA programs with ASA alone in patients with UC. Methodological quality was assessed by 2 independent researchers according to the inclusion criteria and exclusion criteria. Meta-analysis was performed by using the Review Manager 5.3 Software. Risk ratios (RRs), 95% confidence interval (CI), and standardized mean difference were calculated., Results: Sixty RCTs involving 4954 participants were selected for final review. Compared with ASA, BTV plus ASA significantly improved the clinical effect rate [RR = 1.23, 95% CI (1.20, 1.26), P < .00001]; reduced the relapse rate [RR = 0.34, 95% CI (0.18, 0.62), P = .0005]; and adverse effect rate [RR = 0.66, 95% CI (0.53, 0.82), P = .0002]. Compared with the controls, levels of tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, C-reactive protein (CRP), hypersensitive CRP, erythrocyte sedimentation rate, and malondialdehyde were reduced; levels of IL-10, CD3+, CD4+, and superoxide dismutase were increased in BTV plus ASA group., Conclusions: BTV plus ASA has positive therapeutic effects on UC, and it might be a safe way to treat UC. However, comprehensive clinical trials are needed to obtain high level of clinical evidence.

Objective: To observe the expression of the Receptor of Advanced glycation end products (RAGE) in asthmatic rats, and explore the intervention of Roxithromycin. Methods: A total of 18 Specific Pathogen Free-class Brown Norway male rats were randomly divided into control group, asthma model group and Roxithromycin group, with 6 rats in each group. The asthmatic model was sensitized by intraperitoneal injection of Ovalbumin (OVA)+Al(OH)(3), and challenged with OVA. Rats in Roxithromycin group were given Roxithromycin 30 mg/kg 30 minutes before each challenge. Rats in control group and asthma model group were treated with equal volume of saline. The concentrations of RAGE and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent (ELISA); the pathological changes of lung tissues were observed by HE-staining; the thickness of airway wall and airway smooth muscle were measured by Image-Pro Plus; the relative expression of RAGE in lung tissues were detected by Western blot. Results: In asthma model group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously higher than those in control group [(494±32) vs (327±45) ng/L; (32.4±5.8) vs (13.1±2.9) ng/L; (553±38) vs (399±56) ng/L; (37.8±3.4) vs (19.4±2.5) ng/L] (all P< 0.01); in Roxithromycin group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously lower than those in asthma model group [(438±18) vs (494±32) ng/L; (22.8±6.0) vs (32.4±5.8) ng/L; (444±42) vs (553±38) ng/L; (25.6±4.5) vs (37.8±3.4) ng/L] (all P< 0.05). In asthma model group, the bronchial wall was thickened, the lumen was narrow, the mucosal wrinkles were significantly increased, edema appeared under the mucosa, and a large number of inflammatory cells infiltrated and aggregated in the bronchi, perivascular and alveolar spaces; the thickness of airway wall and airway smooth muscle were significantly increased than those in control group ( P< 0.01); in Roxithromycin group, airway inflammation and remodeling were alleviated compared with those in asthma model group ( P< 0.05). In asthma model group, the expression of RAGE in lung tissues were significantly increased than those in control group ( P< 0.01); in Roxithromycin group, the expression of RAGE were significantly decreased than those in asthma model group ( P< 0.01). There were positive correlations between the expression of RAGE and IL-4 in BALF and serum ( r= 0.782, 0.804, all P< 0.01); there were positive correlations between RAGE and total white cell counts, eosinophil counts, smooth muscle thickness ( r= 0.897, 0.927, 0.860, all P< 0.01). Conclusions: The increasing of RAGE in asthmatic rats are positively correlated with airway inflammation and airway remodeling. Roxithromycin may inhibit the development of asthma by reducing the expression of RAGE.

Tremendous amount of whole-genome sequencing data have been provided by large consortium projects such as TCGA (The Cancer Genome Atlas), COSMIC and so on, which creates incredible opportunities for functional gene research and cancer associated mechanism uncovering. While the existing web servers are valuable and widely used, many whole genome analysis functions urgently needed by experimental biologists are still not adequately addressed. A cloud-based platform, named CG (ClickGene), therefore, was developed for DIY analyzing of user's private in-house data or public genome data without any requirement of software installation or system configuration. CG platform provides key interactive and customized functions including Bee-swarm plot, linear regression analyses, Mountain plot, Directional Manhattan plot, Deflection plot and Volcano plot. Using these tools, global profiling or individual gene distributions for expression and copy number variation (CNV) analyses can be generated by only mouse button clicking. The easy accessibility of such comprehensive pan-cancer genome analysis greatly facilitates data mining in wide research areas, such as therapeutic discovery process. Therefore, it fills in the gaps between big cancer genomics data and the delivery of integrated knowledge to end-users, thus helping unleash the value of the current data resources. More importantly, unlike other R-based web platforms, Dubbo, a cloud distributed service governance framework for 'big data' stream global transferring, was used to develop CG platform. After being developed, CG is run on an independent cloud-server, which ensures its steady global accessibility. More than 2 years running history of CG proved that advanced plots for hundreds of whole-genome data can be created through it within seconds by end-users anytime and anywhere. CG is available at http://www.clickgenome.org/., Competing Interests: Competing interestsThe 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.

Greenhouse gas monitoring instruments (GMI) are spatial heterodyne spectroscopy (SHS) sensors that monitor greenhouse gases (GHG) from space. Due to several kinds of polarization-sensitive optical elements in GMIs, to some extent, the instrument becomes a polarization-sensitive sensor. Its polarization sensitivity will reduce the radiometric accuracy and spectral inversion accuracy of GHG column concentration. Theoretical radiation response models for analyzing the polarization sensitivity of a GMI, which is mainly affected by a scanning mirror beam splitter and diffraction gratings, are presented in this paper. Based on these models and the polarization performance testing, the theoretical and experimental results of the main spectral band of a GMI, covering the wavelength range of 1.568-1.583 μm for carbon dioxide (CO 2 ) detection, have been given. The result shows that the linear polarization sensitivity is less than 0.65% and 1.32% in the nadir (45°, 0°) and in the oblique view direction (45±20°, ±31°), respectively, and that it meets the qualification requirement for an absolute radiometric calibration accuracy better than 5%. The absolute radiometric calibration accuracy directly affects the accuracy of GHG concentration retrieval.

Background: While tobacco exposure is the cause of the vast majority of lung cancers, an important percentage arise in lifetime never smokers. Documenting the precise extent of tobacco induced molecular changes may be of importance. Also, the contribution of environmental tobacco smoke (ETS) is difficult to assess., Methods: We developed and validated a quantitative method to assess the extent of tobacco related molecular damage by combing the most characteristic changes associated with tobacco smoke, the tumor mutation burden (TMB) and type of molecular changes present in lung cancers. Using maximum entropy (MaxEnt) as a classifier, we developed a F score. F score values >0 were considered to show evidence of tobacco related molecular damage, while values ≤0 were considered to lack evidence of tobacco related molecular damage. Compared to the stated patient tobacco exposure histories, the F scores had sensitivity, specificity and accuracy values of 85-87%. Using this method, we analyzed public data sets of lung adenocarcinoma (LUAD), lung squamous cell (LUSC) and small cell lung cancer (SCLC)., Results: Less than 10% of LUSCs and SCLCs had negative F scores, while 27% to 35% of LUADs had positive scores. The F score showed a highly significant downward trend when LUADs were subdivided into the following categories: ever, reformed ≤15 years, reformed >15 years and never smokers. Most of the examined bronchial carcinoids (a lung cancer type not associated with smoke exposure) had negative F scores. In addition, most LUADs with EGFR mutations had negative F scores, while almost all with KRAS mutations had positive scores., Conclusions: We have established and validated a quantitative assay that will be of use in assessing the presence and degree of smoke associated molecular damage in lung cancers arising in ever and never smokers., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: To systematically evaluate the clinical efficacy and safety of Kangfuxin liquid (KFXL) combined with aminosalicylic acid (ASA) in treating ulcerative colitis (UC)., Methods: The PubMed, Cochrane Library, Embase, CBM, Wan fang, the Chinese Scientific Journal Database (VIP), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized controlled trials of KFXL combined with ASA for UC from the inception dates to March 3, 2017. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality according to the inclusion criteria. The meta-analysis was performed using Review Manager software (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), and the risk of bias was assessed using the Cochrane Collaboration Tool., Results: A total of 39 randomized controlled trials (RCTs) involving 3204 patients fulfilled the inclusion criteria. Compared with ASA alone, KFXL combined with ASA significantly improved the clinical effectiveness rate [RR = 1.19, 95% CI: (1.16, 1.23), P < .00001], reduced the relapse rate [RR = 0.26, 95% CI: (0.18, 0.38), P < .00001], reduced the inflammation factor levels of TNF-a, IL-1, IL-6, IL-8, and C-reactive protein, reduced the coagulation index of fibrinogen, increased the coagulation index of prothrombin time, and mean platelet volume, and reduced the clinical symptoms of abdominal pain, diarrhoea, pus and bloody stool, and tenesmus. However, KFXL combined with ASA did not increase the adverse event incidence [RR = 0.74, 95% CI (0.42, 1.32), P = .31], and no severe adverse events were reported., Conclusion: KFXL combined with ASA has good therapeutic effect for UC and might be a safe approach in managing UC. More high-quality, multicenter randomized, double-blind trials with a large sample size are required to generate a high level of clinical evidence.

Maggot extract (ME) accelerates rat skin wound healing, however its effect on cell maintenance in wound tissues remains unclear. B‑cell lymphoma (Bcl) 2‑associated athanogene (BAG)3 inhibits apoptosis and promotes autophagy by associating with Bcl‑2 or Beclin 1. Bcl‑2, the downstream effector of signal transducer and activator of transcription 3 signaling, is enhanced in ME‑treated wound tissues, which may reinforce the Bcl‑2 anti‑apoptotic activity and/or cooperate with Beclin 1 to regulate autophagy during wound healing. The present study investigated expression levels of BAG3, Bcl‑2, Beclin 1 and light chain (LC)3 levels in rat skin wound tissues in the presence and absence of ME treatment. The results revealed frequent TUNEL‑negative cell death in the wound tissues in the early three days following injury, irrespective to ME treatment. TUNEL‑positive cells appeared in the wound tissues following 4 days of injury and 150 µg/ml ME efficiently reduced apoptotic rate and enhanced BAG3 and Bcl‑2 expression. Elevated Beclin 1 and LC3 levels and an increased LC3 II ratio were revealed in the ME‑treated tissues during the wound healing. The results of the present study demonstrate the anti‑apoptotic effects of BAG3 and Bcl‑2 in ME‑promoted wound healing. Beclin 1/LC3 mediated autophagy may be favorable in maintaining cell survival in the damaged tissues and ME‑upregulated BAG3 may enhance its activity.

Thyroid cancer (TC) is the most common endocrine malignancy without reliable preventive agent. Resveratrol possesses in vitro anti-TC activities; while its effect(s) on thyroid tumorigenesis remains unknown. This study aims to address this issue using DEN/MNU/DHPN-induced rat carcinogenesis model. 50 male Sprague-Dawley rats were separated into four groups as Group-1 (5 rats); normally fed; Group-2 (15 rats); DEN/MNU/DHPN treatment only; Group-3 (15 rats) and -4 (15 rats); DEN/MNU/DHPN treatment; followed by resveratrol intragastric (IG) injection and intraperitoneal (IP) injection; respectively; in two-day intervals for 30 weeks. The results revealed that the average resveratrol concentration in thyroid tissues was 1.278 ± 0.419 nmol/g in IG group and 1.752 ± 0.398 nmol/g in IP group. The final body weights of Group-3 and Group-4 were lighter than that ( p > 0.05) of Group-1; but heavier than Group-2 ( p < 0.05). TC-related lesions (hyperplasia and adenomas) were found in 53.3% of Group-2; 33.3% Group-3 and 26.7% Group-4. Lower serum carcino-embryonic antigen (CEA) and thyroglobulin (Tg) levels; down-regulated expression of IL-6 and cyclooxygenase-2 (COX-2); reduction of NF-κB/p65 nuclear translocation; and elevated IkB α expression were found in the thyroid tissues of Group-3 and Group-4 in comparison with that of Group-2. These results demonstrate that IG and IP administered resveratrol efficiently reduces the frequency and severity of DEN/MNU/DHPN-caused TC-related lesions and would be of values in thyroid tumor prevention., Competing Interests: The authors declare no conflicts of interest.

Four new species of cockroach genus Balta Tepper, 1893 are described and illustrated: B. crena sp. n. , B. maculata sp. n. , B. tangi sp. n. , and B. yaoi sp. n. Balta picea (Bey-Bienko, 1958) is now regarded as a new synonym of Balta hwangorum (Bey-Bienko, 1958), which is redescribed and illustrated. Two new combinations are proposed: B. nodigera (Bey-Bienko, 1958), comb. n. and B. valida (Bey-Bienko, 1958), comb. n. , and both species are redescribed and illustrated. A key to all species from China is provided.

The accurate classification of non-small cell lung carcinoma (NSCLC) into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is essential for both clinical practice and lung cancer research. Although the standard WHO diagnosis of NSCLC on biopsy material is rapid and economic, more than 13% of NSCLC tumors in the USA are not further classified. The purpose of this study was to analyze the genome-wide pattern differences in copy number variations (CNVs) and to develop a CNV signature as an adjunct test for the routine histopathologic classification of NSCLCs. We investigated the genome-wide CNV differences between these two tumor types using three independent patient datasets. Approximately half of the genes examined exhibited significant differences between LUAD and LUSC tumors and the corresponding non-malignant tissues. A new classifier was developed to identify signature genes out of 20 000 genes. Thirty-three genes were identified as a CNV signature of NSCLC. Using only their CNV values, the classification model separated the LUADs from the LUSCs with an accuracy of 0.88 and 0.84, respectively, in the training and validation datasets. The same signature also classified NSCLC tumors from their corresponding non-malignant samples with an accuracy of 0.96 and 0.98, respectively. We also compared the CNV patterns of NSCLC tumors with those of histologically similar tumors arising at other sites, such as the breast, head, and neck, and four additional tumors. Of greater importance, the significant differences between these tumors may offer the possibility of identifying the origin of tumors whose origin is unknown., (© 2017 Wiley Periodicals, Inc.)

Hepatocyte growth factor (HGF) is a crucial factor associated with development, progression and metastasis of colorectal cancer (CRC). However, its prognostic value remains unclear. Thus studies referring to the correlation between HGF and CRC patients' prognosis were included to explore the role of HGF in CRC. At last nine articles were included. The results showed that the over-expression of HGF was associated with a poor prognosis, presented through overall survival (OS, Hazard ratio (HR) = 2.50, 95% confidence interval (CI): 2.12-2.96) and disease-free survival (DFS, HR = 1.99, 95% CI: 1.59-2.50). Subgroup analysis indicated that no significant difference was found between the Asian countries (OS: HR = 2.37; DFS: HR = 2.02) and the non-Asian countries (OS: HR = 3.15; DFS: HR = 1.87), between the studies that used univariate analyses (OS: HR = 2.51; DFS: HR = 2.07) and those that used multivariate analyses (OS: HR = 2.65; DFS: HR = 1.78), and between metastatic CRC (OS: HR = 2.26; DFS: HR = 2.06) and stage I-IV CRC (OS: HR = 3.08; DFS: HR = 0.70). Our meta-analysis has shown that the over-expression of HGF is valuable in CRC prognosis evaluation. This conclusion should be further confirmed by large-sample cohort studies.

SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergic mice. Blockade of SHP2 function by SHP2 inhibitor PHPS-1 or conditional shp2 knockdown by adenovirus-inhibited bone-marrow-derived eosinophil differentiation in vitro, with no detectable effects on the apoptosis of eosinophils. Furthermore, SHP2 induced eosinophil differentiation via regulation of the extracellular signal-regulated kinase pathway. Myeloid shp2 conditional knockout mice (LysM(cre)shp2(flox/flox)) failed to induce eosinophilia as well as airway hyper-responsiveness. The SHP2 inhibitor PHPS-1 also alleviated eosinophilic airway inflammation and airway hyper-responsiveness, accompanied by significantly reduced levels of systemic eosinophils and eosinophil lineage-committed progenitors in allergic mice. We demonstrate that inhibition of eosinophil development is SHP2-dependent and SHP2 is sufficient to promote eosinophil formation in vivo. Our data reveal SHP2 as a critical regulator of eosinophil differentiation, and inhibition of SHP2 specifically in myeloid cells alleviates allergic airway inflammation.

As an attractive technique for the improvement of biomaterials, Plasma immersion ion implantation (PIII) has been applied to modifying the titanium material for dental implant application. The present study investigated the cytocompatibility and early osseointegration of fluoride-ion-implanted titanium (F-Ti) surface and implants, both characterizing in their composition of titanium oxide and titanium fluoride. The cytocompatibility of F-Ti was evaluated in vitro by using scanning electron microscope, Cell Counting Kit-8 assay, alkaline phosphatase activity assay, and quantitative real-time polymerase chain reaction. The results showed that the F-Ti weakened the effects that Porphyromonas gingivalis exerted on the MG-63 cells in terms of morphology, proliferation, differentiation, and genetic expression when MG-63 cells and Porphyromonas gingivalis were co-cultured on the surface of F-Ti. Meanwhile, the osteogenic activity of F-Ti implants was assessed in vivo via evaluating the histological morphology and estimating histomorphometric parameters. The analysis of toluidine blue staining indicated that the new bone was more mature in subjects with F-Ti group, which exhibited the Haversian system, and the mean bone-implant contact value of F-Ti group was slightly higher than that of cp-Ti group (p>0.05). Fluorescence bands were wider and brighter in the F-Ti group, and the intensity of fluorochromes deposited at the sites of mineralized bone formation was significantly higher for F-Ti surfaces than for cp-Ti surfaces, within the 2nd, 3rd and 4th weeks (p<0.05). An indication is that the fluoride modified titanium can promote cytocompatibility and early osseointegration, thus providing a promising alternative for clinical use., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Chemiresistive gas sensors with low power consumption, fast response, and reliable fabrication process for a specific target gas have been now created for many applications. They require both sensitive nanomaterials and an efficient substrate chip for heating and electrical addressing. Herein, a near room working temperature and fast response triethylamine (TEA) gas sensor has been fabricated successfully by designing gold (Au)-loaded ZnO/SnO2 core-shell nanorods. ZnO nanorods grew directly on Al2O3 flat electrodes with a cost-effective hydrothermal process. By employing pulsed laser deposition (PLD) and DC-sputtering methods, the construction of Au nanoparticle-loaded ZnO/SnO2 core/shell nanorod heterostructure is highly controllable and reproducible. In comparison with pristine ZnO, SnO2, and Au-loaded ZnO, SnO2 sensors, Au-ZnO/SnO2 nanorod sensors exhibit a remarkably high and fast response to TEA gas at working temperatures as low as 40 °C. The enhanced sensing property of the Au-ZnO/SnO2 sensor is also discussed with the semiconductor depletion layer model introduced by Au-SnO2 Schottky contact and ZnO/SnO2 N-N heterojunction.

Background and Objective: Nuclear erythroid 2 p45-related factor-2 (Nrf2) is known to play important roles in airway disorders, whereas little has been investigated about its direct role in airway mucus hypersecretion. The aim of this study is to determine whether this factor could protect pulmonary epithelium and mouse airway from cigarette-induced mucus overproduction., Methods: Using genetic approaches, the role of Nrf2 on cigarette smoking extracts (CSE) induced MUC5AC expression was investigated in lung A549 cells. Nrf2 deficiency mice were smoked for various periods, and the airway inflammation and mucus production was characterized., Results: Acute smoking exposure induced expression of MUC5AC and Nrf2 in both A549 cells and mouse lungs. Genetic ablation of Nrf2 augmented, whereas overexpression of this molecule ameliorated CSE-induced expression of MUC5AC. Nrf2 knockout mice, after exposure to cigarette smoking, displayed enhanced airway inflammation and mucus production., Conclusion: Nrf2 negatively regulated smoking-induced mucus production in vitro and in vivo, suggesting therapeutic potentials of this factor in airway diseases with hypersecreted mucus., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week-old or 5-month-old with atRA had no effect on the prevention of tumorigenesis or cure of developed nodules in liver. These events imply that the depletion of 9cRA and atRA and the inhibition of RXRα function in hepatic tumors involve more complex mechanisms besides the activation of RAS/ERK pathway., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: To translate and validate the Chinese version of the Quality Of Life Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N), a disease-specific scale to measure quality of life (QOL) for patients with head and neck cancer (HNC) who received radiotherapy., Methods: The QOL-RTI/H&N was translated and validated according to the standard process: a translation and back-translation procedure, pilot testing and a validation study. HNC patients were enrolled from the Cancer Center of Sun Yat-sen University and assessed using the QOL-RTI/H&N, QLQ-C30 and QLQ-H&N35. Reliability (internal consistency reliability, split-half reliability and test-retest reliability), validity (content validity, construct validity, criterion validity and discriminant validity), and responsiveness analysis were performed to evaluate the psychometric characteristics of the QOL-RTI/H&N., Results: A total of 238 patients (99.2%) completed the questionnaire. Item RTI23 had 16.0% missing data. Other items had low percentages of missing data (0.4% or 0.8%) or no missing data. The average time to finish the scale was 9.8 minutes. Cronbach's alpha of the domains ranged from 0.41 to 0.77. The split-half reliability coefficients ranged from 0.43 to 0.77. All of the intra-class correlation coefficients were equal to or greater than 0.8. All of the item-own domain correlation coefficients were greater than those of the item-other domain. Confirmatory factor analysis showed that Comparative Fit Index, Normed Fit Index and Non-Normed Fit Index were equal to 1.00. Root Mean Square Error of Approximation was 0.01, with 90% CI (0.00, 0.10). The domain scores of the QOL-RTI/H&N were significantly correlated with those of the QLQ-C30 or QLQ-H&N3. All domain scores of patients in different radiotherapy stages were statistically significant (P < 0.05), apart from the speech domain., Conclusions: The Chinese version of the QOL-RTI/H&N is a valid, reliable and responsive scale to measure QOL in HNC patients and can be used to assess the effects of radiotherapy treatment on these patients.

Objective: The aim of this study was to investigate the effect of Magnesium Isoglycyrrhizinate (MgIG) on intercellular adhesion moledule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) in rats with Paraquat (PQ) poisoning and its potential mechanism., Materials and Methods: 30 male Sprague Dawley rats were randomly divided into five groups, including normal control group, poisoned control group, low-dose MgIG group, medium-dose MgIG group and high-dose MgIG group. Each group was treated with corresponding dose of MgIG once on daily basis by intraperitoneal injection 24 hours later, and the normal control group and poisoned control group were injected with physiological saline. All the animals were killed 14 days after poisoning, the contents of ICAM-1 and matrix MMP-9 were determined. HE staining and Masson staining were performed, the hydroxyproline (HYP) content in the lung tissue was also determined, and the expressions of ICAM-1 and MMP-9 were detected by immunohistochemical test., Results: The contents of ICAM-1 and MMP-9 in the rat serum for all treatment groups were significantly decreased compared with those of the poisoned control group (p < 0.05, or < 0.01), and the expressions of the two proteins were significantly down-regulated, especially for the medium dose group., Conclusions: There is an improvement effect of ICAM-1 and MMP-9 in rats with Paraquat poisoning for the medium dose of MgIG, capable of slowing down the process of pulmonary fibrosis to certain extent.

Objective: To explore the effect of Changji'an Capsule (CA) on mRNA expressions of neuropeptide Y (NPY) in the hypothalamus and colon and serum levels of adreno-cortico-tropic hormone (ACTH) in rats of diarrhea predominant irritable bowel syndrome (IBS-D) model rats., Methods: Totally 48 SD rats were randomly divided into six groups, i.e., the normal control group, the model group, the Pinaverium Bromide group (PB, 0.018 g/kg), the high dose CA group (2.812 g/kg), the medium dose CA group (1.406 g/kg), and the low dose CA group (0.703 g/kg), 8 in each group. The IBS-D rat model was established by using separation of breast milk + stimulation of acetic acid + constraint of four limbs. Normal saline was given to rats in the normal control group and the model group. All medication lasted for 14 successive days by gastrogavage. The serum content of ACTH was detected by enzyme linked immunosorbent assay (ELISA). The expressions of NPY mRNA in the colon and the hypothalamus were detected using real-time fluorescence quantitative PCR., Results: Compared with the normal control group, the serum ACTH content significantly increased (P < 0.01), the NPY mRNA expression in the colon and the hypothalamus obviously decreased (P < 0.01) in the model control group. Compared with the model group, the serum ACTH obviously decreased in the high dose CA group, the medium dose CA group, and the PB group (P < 0.01, P < 0.05). The NPY mRNA expression in the colon and the hypothalamus were obviously up-regulated in the high dose CA group, the medium dose CA group, the low dose CA group, and the PB group (P < 0.05)., Conclusions: CA could modulate the abnormity of brain-gut axis of IBS-D rats possibly by up-regulating NPY mRNA expressions in the hypothalamus and the colon and down-regulating the ACTH content in the hypothalamic-pituitary-adrenal axis.

Background: Ulcerative colitis (UC) is associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNA (miRNA) plays an important role in the pathogenesis of UC by regulating the gene expression at the post-transcriptional level and control crucial physiological processes. This study aimed to identify aquaporin 8 (AQP8) expression and its relationship with miRNA in UC patients., Methods: Human colon samples, in this study, were obtained from 20 patients with UC and 16 healthy subjects undergoing diagnostic colonoscopy at the Chinese People's Liberation Army General Hospital between December 2009 and June 2010. We screened different genes from UC tissues and healthy subjects using genome-wide microarray, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Regulation of gene expression by miRNAs was assessed by luciferase reporter construct assays and transfection of specific miRNA mimics and inhibitor., Results: We identified that 1596 genes were increased and 1301 genes were decreased in UC patients compared to healthy subjects. Among them, we focused on the analysis of AQP8 which was decreased three folds in UC tissues (P < 0.01). The expression of AQP8 mRNA and protein were decreased in UC tissue and tumor necrosis factor (TNF)-α treated HT29 cells compared with controls (P < 0.05). We searched candidate target miRNAs of AQP8 through bioformatics and the luciferase report assay analysis indicated that miR-424, miR-195, miR-330, miR-612, and miR-16 which has complementary site in the 3-untranslated region (3'UTR) of AQP8 could decrease the relative luciferase activities by 10% - 45%., Conclusion: AQP8 and its relationship with miRNAs may be involved in the pathogenesis of UC.

Background: Transforming growth factor (TGF)-β1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-β1 production and thus a potential regulator of airway remodeling., Objectives: To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling., Methods: The airways of Shp2(flox/flox) mice were infected with recombinant adenovirus vectors expressing a Cre recombinase-green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-β1., Results: Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-β1 production by these cells correlated with the extent of shp2 gene expression., Conclusions: SHP2 activities in airway epithelial cells appear to modulate TGF-β1 production and, in turn, regulate allergic airway remodeling following allergen provocation., Clinical Implications: Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung dysfunction associated with allergen challenge. As such, SHP2 represents a potentially novel therapeutic target for the treatment of asthmatics., Capsule Summary: Airway epithelial protein tyrosine phosphatase SHP2 appears to modulate TGF-β1 activities as part of one or more cellular pathways leading to regulating the airway remodeling and lung dysfunction occurring in mouse models of allergic respiratory inflammation., (© 2012 John Wiley & Sons A/S.)

Objective: To summarise the clinical features of 18 cases with acute trichloropropane (TCP) poisoning for improving the diagnosis and treatment of the disease., Methods: Exposure history, clinical manifestations, laboratorial examinations, poisoning causes and treatment were retrospectively reviewed in 18 cases with acute TCP poisoning. The results of peripheral lymphocyte micronucleus tests were compared with the healthy control group (n = 33)., Results: The common clinical symptoms were as following: respiratory symptoms were the earlier one set, such as chest tightness in 13, dry and sore throat in 7, cough and runny nose in 2. Gastrointestinal symptoms were more common, such as abdominal pain in 18, nausea and vomit in 14. Only 1 out of 18 patients was found with liver injury. The major manifestation was the increase in ALT and AST, which was returned to normal after treatment. ALL of the 18 patients were found TCP in their serum which concentration was from 39.0 to 310.0 ng/ml, and the average was (68.9 ± 42.1) ng/ml. The symptoms of toxic peripheral neuropathy were typical in all the patients, such as fatigue and numb limb in 18, burning pain of the distal lower limbs in 14, the symmetrical sock-like sensory dysfunction of pain, touch and vibration of the lower limbs in 13, muscle strength reduced in 7, hyporeflexia knee-jerks in 4, hyporeflexia ankle-jerks in 3. The peripheral nerve conduction velocity (NCV) examinations were as followed: the (sensore-nerve conduction velocity) SCV of peroneus super nerve in 18 and the (motor-nerve conduction velocity) MCV of tibial nerve in 8 was slowed down and the distal latency in 18 was prolonged. Micronucleus were found in all 18 cases. The micronucleus rate was 10.06‰ ± 2.80‰ and 8.24‰ ± 2.67‰ in acute TCP poisoning group and healthy control group, respectively. The difference was significant (P < 0.05)., Conclusion: The common clinical manifestations of respiratory exposure of TCP poisoning patients were respiratory symptoms, gastrointestinal symptoms and the symptoms of toxic peripheral neuropathy. Liver injury in those 18 cases was not obvious. Lymphocyte micronucleus of peripheral blood were found in all 18 cases.