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To clarify the characteristics and origin of the cellular components in atherosclerosis, carotid atherosclerotic plaques (CAPs) of four patients were studied by light microscopy using hematoxylin-eosin, Congo red and alpha-smooth-muscle actin stains, and by transmission electron microscopy of different regions of CAPs. By light microscopy, CAPs were composed of 1) a fibrous cap; 2) an atherosclerotic core presenting focal fibrosis, neovascularization, hemorrhage, necrosis, chondrification and ossification; and 3) a basal band composed of a hyperplasic pseudo-media and affected tunica media. Ultrastructurally, the CAPs contained a diversity of cells including fibroblasts, myofibroblasts, osteochondrocytes, vascular smooth-muscle cells, foam cells and other myoid cells characterized by varied features of the above mentioned cells. The results indicated that CAPs were derived from a proliferation of multipotential mesenchymal stem cells, leading to the presence of degenerated foam cells and lipid-laden cells.

Jiale Duan,1,* Yanping Yang,1,* Lei Yin,1 Xue Zhang,2 Yi Tang,1 Shuxian Zhang,1 Hanjuan Gong,1 Ming Xiao,1 Ming Li,1 Qingshu Li,1 Xian Li,1 Lian Yang,1 Qi Fan,2 Yalan Wang1 1Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2School of Pharmacy, Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yalan WangDepartment of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaEmail wangyalan@cqmu.edu.cnIntroduction: In metastatic colorectal cancer (mCRC), the B-type Raf kinase (BRAF)V600E mutation is a molecular biomarker of poor prognosis and is of great importance to drug target. Currently, the commonly used methods for detecting BRAFV600E mutation include immunohistochemistry (IHC) and gene sequencing, but both present certain limitations. Near-infrared (NIR) spectroscopy is a spectroscopy technology that takes advantage of the electromagnetic wavelength between visible light and mid-infrared light.Methods: IHC was used to detect the expression of BRAFV600E protein with the BRAFV600E (VE1) antibody in 42 cases of paraffin-embedded (FFPE) mCRC tissue sections. The NIR-discriminant analysis model (NIRS-DA) was established using 6 cases of wild-type and 6 cases of mutant-type BRAF specimens.Results: IHC detection results revealed 13 cases of weakly positive (+), 1 case of moderately positive (++), and 28 cases of negative (−) CRC. Compared with the next-generation sequencing (NGS) results, the positive rate was 66.7%. The classification accuracy of calibration (CAC) was 100% compared with the results of NGS, demonstrating that the BRAFV600E mutant NIRS-DA model, verified by 2 cases of wild-type and 2 cases of mutant-type CRC samples was established. The NIRS-DA model was used to predict gene mutation in the CRC samples, 7 cases were positive (+), and 35 cases were negative (−), and the classification accuracy of prediction (CAP) was 83.3% (35/42).Discussion: The NIRS-DA model-predicted results were in high agreement with the detection results of NGS, and the difference in IHC is not statistically significant (P> 0.05). However, this study is a preliminary discussion on a methodology due to its small sample size.Keywords: colorectal cancer, BRAFV600E mutant, near-infrared spectroscopy, next-generation sequencing, immunohistochemistry

Supplemental material, sj-pdf-3-jcb-10.1177_0271678X221109997 for High-resolution 3D demonstration of regional heterogeneity in the glymphatic system by Xu-Zhong He, Xin Li, Zhen-Hua Li, Jing-Cai Meng, Rui-Ting Mao, Xue-Ke Zhang, Rong-Ting Zhang, Huai-Liang Huang, Qian Gui, Guang-Yin Xu and Lin-Hui Wang in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221074223 for Validation of external and internal exposome of the findings associated to cerebral small vessel disease: A Mendelian randomization study by Xue-Qing Zhang, Yu-Xiang Yang, Can Zhang, Xin-Yi Leng, Shi-Dong Chen, Ya-Nan Ou, Kevin Kuo, Xin Cheng, Xiang Han, Mei Cui, Lan Tan, Lei Feng, John Suckling, Qiang Dong and Jin-Tai Yu: the OPTIMAS investigators in Journal of Cerebral Blood Flow & Metabolism

Porcine pseudorabies virus (PRV) infection is a major disease in swine. It is challenging to eradicate the virus entirely after it has invaded Chinese farms, resulting in significant economic losses. This study aimed to explore the histopathological correlation of brain regions in PRV-infected pigs. Twenty pigs were randomly divided into two experimental groups (the PRV-infected and sham-inoculated groups; n = 10 per group). The pigs were then observed for clinical signs at specified time points. Brain tissue samples were collected for histopathological examination on days 3, 10, and 14. The correlation analysis was based on clinical observation, lesion characterization, and pathogen location. Clinical observation showed that the severity of clinical neurological signs increased with time. Pathological dissection and microscopic observation revealed gross pathological changes such as degeneration and necrosis of nerve cells, increase in microglia, eosinophilic inclusion body, lymphocyte infiltration, and loose cortical tissue structure. Immunohistochemistry showed that the virus was mainly localized in neurons, microglia, nerve fibers, cerebellar granular layer, and Purkinje cell layer. The virus invasion route was from the cerebrum to the cerebellum and eventually to the brainstem, and the severity of brain damage increased with time. The route of virus infection was from the olfactory bulb to the hippocampus and eventually to the medulla oblongata, and the viral expression increased with time. Of note, brain injury, viral expression, and clinical neurological signs were positively correlated with the infection period; similarly, the severity and degrees of their changes were positively correlated.

Chinese herbal formulas including the lung-cleaning and toxicity-excluding (LCTE) soup have played an important role in treating the ongoing COVID-19 pandemic (caused by SARS-CoV-2) in China. Applying LCTE outside of China may prove challenging due to the unfamiliar rationale behind its application in terms of Traditional Chinese Medicine. To overcome this barrier, a biochemical understanding of the clinical effects of LCTE is needed. Here, we explore the chemical compounds present in the reported LCTE ingredients and the proteins targeted by these compounds via a network pharmacology analysis. Our results indicate that LCTE contains compounds with the potential to directly inhibit SARS-CoV-2 and inflammation, and that the compound targets proteins highly related to COVID-19’s main symptoms. We predict the general effect of LCTE is to affect the pathways involved in viral and other microbial infections, inflammation/cytokine response, and lung diseases. Our work provides a biochemical basis for using LCTE to treat COVID-19 and its main symptoms., Deng-hai Zhang et al. report a network pharmacology analysis of the Traditional Chinese Medicine (TCM) lung-cleaning and toxicity-excluding (LCTE) soup. By exploring the chemical compounds that make up LCTE and the likely pathways and proteins that they target, the authors show that LCTE may have the potential to directly inhibit the SARS-CoV-2 virus and relieve inflammatory symptoms.

OBJECTIVE To investigate the inhibitory effect of Jinghua Weikang capsule (JWC) on gastric inflammation induced by Helicobacter pylori (H. pylori) via the nuclear factor-kappa B (NF-κB) signaling pathway in Kunming mice. METHODS We investigated the anti-inflammation potential of JWC extract in vivo in a H. pylori-induced gastritis mouse model. The expression of inflammation-related molecules was evaluated by Western blotting, and the concentrations of in vivo inflammatory markers were measured by enzyme-linked immunosorbent assay. Inflammatory cell infiltration was evaluated by histopathological examination, and mRNA levels of related genes were evaluated by quantitative reverse transcription polymerase chain reaction. RESULTS JWC had a dose-dependent protective effect against H. pylori-induced gastritis by protecting gastric epithelial cells and inhibiting inflammatory cell infiltration. Mechanistically, JWC decreased the protein levels of phosphorylated IκBα and NF-κB p65, mRNA levels of NF-κB pathway molecules, and plasma levels of tumor necrosis factor-α and interleukin 1 beta. CONCLUSION An important finding of our study is that JWC attenuated gastrointestinal inflammation and ulceration and exerted a protective effect against gastric injury via inhibition of inflammation reactions and regulating the canonical NF-κB signaling pathway in vivo.

Three new anthraquinones, 1-methyl-2,4-dimethoxy-3-hydroxyanthraquinone (6), 1-methoxy-3-hydroxy-2-ethoxymethylanthraquinone (7), and 2-methyl-3-O-β-D-primeveroside (14), together with 15 known compounds, including seven anthraquinones, one iridoid glucoside, three phenolic compounds, three flavone glucosides, and one flavone, were isolated from Paederia scandens. The isolated compounds were elucidated by extensive spectroscopic methods. To the best of our knowledge, six known anthraquinones (1, 2, 5, 9, 10, and 13) and two known phenolic acids (4, 11) were isolated from this plant for the first time.

Atazanavir sulphate, an antiretroviral protease inhibitor, has been used to treat HIV/AIDS, but its ability to serve as an antipulmonary fibrosis (PF) agent remains unknown. In this study, the effects of atazanavir sulphate on various aspects of PF were examined and CoCl2 was used to induce the hypoxia-mimicking condition in vitro, including epithelial-mesenchymal transition (EMT) in A549 cells, endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells (HPMECs), proliferation in human lung fibroblasts (HLF-1) and potential protective effects in human type I alveolar epithelial cells (AT I). Additionally, the effects of atazanavir sulphate were examined using a bleomycin (BLM)-induced pulmonary fibrosis model. After atazanavir sulphate treatment, in A549 cells and HPMECs, the expression of vimentin, HMGB1, Toll-like receptor 4 (TLR-4) and p-NF-κB decreased, while the expression of E-cadherin and VE-cadherin increased. In AT I cells, the expression of aquaporin 5 and RAGE were increased after atazanavir treatment. Proliferation of HLF-1 was reduced after atazanavir treatment, meanwhile the expression of hypoxia-inducible factor-1α (HIF-1α), prolyl hydroxylase domain protein 2 (PHD-2), HMGB1, TLR-9, p-NF-κB, collagen I and collagen III was decreased. In the BLM-induced pulmonary fibrosis rat model, atazanavir sulphate ameliorated PF by reducing pathological score, collagen deposition and the expression of α-SMA, HIF-1α, PHD-2, HMGB1, TLR-4, TLR-9 and p-NF-κB. In summary, our study supports the proposal that atazanavir sulphate may have a therapeutic potential in reducing the progression of pulmonary fibrosis by suppressing HMGB1/TLR signalling.

Background Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) with active proliferative lesions show a good response to immunosuppressive treatment. Study Design Multicenter, prospective, randomized, controlled trial. Setting & Participants 176 patients with IgAN with active proliferative lesions (cellular and fibrocellular crescents, endocapillary hypercellularity, or necrosis), proteinuria with protein excretion ≥ 1.0g/24h, and estimated glomerular filtration rate > 30mL/min/1.73m2. Intervention Mycophenolate mofetil (MMF) group: MMF, 1.5g/d, for 6 months and prednisone, 0.4 to 0.6mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months; prednisone group: prednisone, 0.8 to 1.0mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months. All patients were followed up for another 6 months. Outcomes The primary end point was complete remission rate at 6 and 12 months. Results At baseline, median estimated glomerular filtration rates were 90.2 and 94.3mL/min/1.73m2 and mean proteinuria was protein excretion of 2.37 and 2.47g/24h in the MMF and prednisone groups, respectively. At 6 months, complete remission rates were 37% (32 of 86 patients) and 38% (33 of 88 patients); the between-group difference was not statistically significant (P=0.9). At 12 months, complete remission rates were 48% (35 of 73 patients) and 53% (38 of 72 patients) in the MMF and prednisone groups, respectively; the between-group difference was not statistically significant (P=0.6). Incidences of Cushing syndrome and newly diagnosed diabetes mellitus were lower in the MMF group than in the prednisone group. Limitations Not all participants were treated with renin-angiotensin system blockers, relatively short follow-up. Conclusions MMF plus prednisone versus full-dose prednisone did not differ in reducing proteinuria, but patients treated with the former had fewer adverse events in patients with IgAN with active proliferative lesions.

Roxadustat is the first orally administered, small-molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that has been submitted for FDA regulatory approval to treat anemia secondary to chronic kidney diseases. Its usage has also been suggested for pulmonary fibrosis; however, the corresponding therapeutic effects remain to be investigated. The in vitro effects of roxadustat on cobalt chloride (CoCl2)-stimulated pulmonary fibrosis with L929 mouse fibroblasts as well as on an in vivo pulmonary fibrosismice model induced with bleomycin (BLM; intraperitoneal injection, 50 mg/kg twice a week for 4 continuous weeks) were investigated. It found that the proliferation of L929 cells was inhibited and the production of collagen I, collagen III, prolyl hydroxylase domain protein 2 (PHD2), HIF-1α, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1) and p-Smad3 were reduced relative to that in the CoCl2 or BLM group after roxadustat treatment. Roxadustat ameliorated pulmonary fibrosis by reducing the pathology score and collagen deposition as well as decreasing the expression of collagen I, collagen III, PHD2, HIF-1α, α-SMA, CTGF, TGF-β1 and p-Smad3/Smad3. Our cumulative results demonstrate that roxadustat administration can attenuate experimental pulmonary fibrosis via the inhibition of TGF-β1/Smad activation.

Delayed diarrhea is a common side effect of irinotecan administration, leading to a reduction in dose and thus a delay in anticancer therapy. Ganciclovir (GCV), an antiretroviral drug, is used to treat cytomegalovirus (CMV) infection. It is unclear whether GCV exhibits protective effects against irinotecan-induced intestinal dysfunction. Intraperitoneal administration of irinotecan with or without GCV for 4 days induced intestinal toxicity in mice to analyze diarrhea; beta-glucuronidase (β-GLU) activity; fecal occult blood; hepatic function in blood samples, histopathological changes; and NOD-like receptor 3 (NLRP3), toll-like receptor 4 (TLR4), high-mobility group box 1 protein (HMGB1), phosphorylated nuclear factor kappa B (p-NF-κB), occludin, and zonular occludens (ZO-1) expression in colonic and ileal tissues. In addition, an irinotecan-treated mouse model was constructed and analyzed based on survival time. Expression levels of NLRP3, TLR4, HMGB1, p-NF-κB, occludin, and ZO-1 in normal colonic epithelial cells (NCM460 cells) stimulated with SN-38 were analyzed. GCV treatment reduced various indicators of irinotecan-induced intestinal dysfunction, including delayed-onset diarrhea, pathomorphological changes indicating hepatotoxicity, and proteins related to the HMGB1/TLR4 pathway that induced inflammation; the results were increased body weight, food intake, and expression of the protective proteins occludin and ZO-1. No changes in β-GLU activity were observed. Changes in the expression of proteins related to the HMGB1/TLR4 pathway, occludin, and ZO-1 in SN-38-stimulated NCM460 cells were similar to changes in these proteins in vivo. In addition, administration of GCV improved mouse survival, indicating that the drug had long-term efficacy. Furthermore, GCV + irinotecan did not decrease the anti-tumor effect of irinotecan in vivo. In summary, GCV had intestine-protective and anti-inflammatory properties that possibly reduced irinotecan-induced intestinal dysfunction.

Raltegravir, an inhibitor of human immunodeficiency virus-1 (HIV-1) integrase, has been used to treat HIV/acquired immunodeficiency syndrome; however, its therapeutic effects on pulmonary fibrosis have not been investigated. In this study, the in vitro effects of raltegravir (RAV) on transforming growth factor beta 1 (TGF-β1)-induced pulmonary fibrosis on L929 mouse fibroblasts were investigated. In addition, the effects of RAV on an in vivo pulmonary fibrosis model induced by intratracheal instillation of bleomycin were investigated. The proliferation of L929 cells was inhibited after RAV treatment. Meanwhile, the in vitro and in vivo protein expression of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), prolyl hydroxylase domain protein 2, phosphorylated nuclear factor-κB (p-NF-κB), hypoxia-inducible factor-1α (HIF-1α), collagens I and III was reduced relative to TGF-β1 or the bleomycin group. Raltegravir ameliorated pulmonary fibrosis by reducing the pathology score, collagen deposition, and expression of α-smooth muscle actin, NLRP3, HMGB1, TLR4, inhibitor of kappa B, p-NF-κB, HIF-1α, collagen I, and collagen III. The results of this study demonstrate that RAV attenuated experimental attenuates pulmonary fibrosis by inhibiting NLRP3 activation.

This paper proposes a sensitive, sample preparation-free, rapid, and low-cost method for the detection of the B-rapidly accelerated fibrosarcoma (BRAF) gene mutation involving a substitution of valine to glutamic acid at codon 600 (V600E) in colorectal cancer (CRC) by near-infrared (NIR) spectroscopy in conjunction with counter propagation artificial neural network (CP-ANN). The NIR spectral data from 104 paraffin-embedded CRC tissue samples consisting of an equal number of the BRAF V600E mutant and wild-type ones calibrated and validated the CP-ANN model. As a result, the CP-ANN model had the classification accuracy of calibration (CAC) 98.0%, cross-validation (CACV) 95.0% and validation (CAV) 94.4%. When used to detect the BRAF V600E mutation in CRC, the model showed a diagnostic sensitivity of 100.0%, a diagnostic specificity of 87.5%, and a diagnostic accuracy of 93.8%. Moreover, this method was proven to distinguish the BRAF V600E mutant from the wild type based on intrinsic differences by using a total of 312 CRC tissue samples paraffin-embedded, deparaffinized, and stained. The novel method can be used for the auxiliary diagnosis of the BRAF V600E mutation in CRC. This work can expand the application of NIR spectroscopy in the auxiliary diagnosis of gene mutation in human cancer.

Background Breast cancer (BRCA) is one of the most common malignancies in women. To reveal the molecular mechanism of the BRCA, the core genes associated with BRCA was studied by the integrated bioinformatics methods in the current study. Results A total of 1181 DEGs, 84 DEGs, and 190 DEGs were detected in GSE7904, GSE10797, and GSE103512, respectively. In addition, 7 hub genes overlapped from 3 datasets were selected, and ANNXA1, MYH11, IGFBP6, FOS, FOSB, KIT, and WLS might be the core genes of BRCA. The Go function analysis showed that the DEGs were enriched in chromosome segregation, gland development, leukocyte migration, extracellular structure organization and so on. The KEGG pathway analysis showed that the most DEGs were enriched in Pathways in cancer, Focal adhesion, ECM-receptor interaction, PPAR signaling pathway, etc. Additionally, ANXA1 was associated with worse overall survival, and the other 6 hub genes were associated with better overall survival. Conclusions ANNXA1, MYH11, IGFBP6, FOS, FOSB, KIT, and WLS might be the core genes of BRCA. WLS, IGFBP6, and FOSB might be a new biomarker of the breast tumor and potential new drug targets. This study provided new evidence for the future genomic individualized treatment of BRCA.

Porcine circovirus type 2 (PCV2) is widespread throughout Chinese farms, and the infection rate of porcine pseudorabies virus (PRV) is very high. The emergence of mixed infection involving PCV2 and PRV has been difficult to prevent and control and has caused considerable economic loss. The present study investigated lung and brain damage caused by PRV in piglets with PCV2 infection. Twenty piglets were divided randomly into two experiment groups (PRV group and PRV + PCV2 group; n = 10 per group). The pigs were observed for clinical signs at specified times. At necropsy, lung and brain tissue samples were collected for histopathological examination, and tissue virus load was determined using quantitative polymerase chain reaction. Severe pathogenicity due to PRV was evident in two-month-old piglets. PCV2 and PRV co-infection led to more severe neurological and respiratory symptoms and a higher mortality rate in the piglets. In addition, the pathological damage to the lung and brain was also aggravated. The co-infection was associated with a significant increase in the content of PRV in the brain and lung tissue. In conclusion, PCV2 and PRV co-infection could cause severe and irreversible damage to piglets.

Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP. Key words: Antihypertensive Treatment; Hypertension; Randomized Controlled Trials; Renal Denervation; Subgroup Meta-analysis

Abiotic stresses restrict the productivity and quality of agricultural crops. Glutathione S-transferase (GST) utilizes glutathione to scavenge reactive oxygen species (ROS) that result from abiotic stresses. This study aimed to determine the expression pattern of the MsGSTU8 gene and its effects on saline-alkali tolerance. MsGSTU8, from alfalfa (Medicago sativa ‘Zhaodong’), was transformed into transgenic tobacco (Nicotiana tabacum) and overexpressed to determine its effects on saline-alkali tolerance. The gene products in alfalfa localized to the cytoplasm and the transcript levels were higher in the leaves than the roots and stems. Expression was strongly induced by cold, drought, salt and saline-alkali stresses as well as abscisic acid (ABA) treatments. The transgenic tobacco lines had significantly higher transcription levels of the abiotic stress-related genes and higher GST activity than the wild types. Transgenic tobacco lines with saline-alkali treatments maintained their chlorophyll content, showed improved antioxidant enzyme activity and soluble sugar levels, reduced ion leakage, O2.−, H2O2 accumulation and malondialdehyde content. Our results indicate that overexpression of MsGSTU8 could improve resistance to saline-alkali stresses by decreasing the accumulation of ROS and increasing the levels of antioxidant enzymes. Furthermore, they suggest that MsGSTU8 could be utilized for transgenic crop plant breeding., Summary: The glutathione S-transferase gene of Medicago sativa can effectively alleviate osmotic and oxidative damage induced by saline-alkali stress in transgenic tobacco.

Echinococcus multilocularis is a parasite that causes a dangerous zoonosis, alveolar echinococcosis (AE). Its presence in water sources, however, has scarcely been studied heretofore. Accordingly, 222 samples of different origin including wastewater from wastewater treatment plants (WWTPs) (n = 137), slaughterhouse (n = 49) as well as water from rivers (n = 26) and a cattle farm (n = 10) were collected from Xining City and a rural area in Qinghai-Tibet Plateau (QTP), an endemic area. Material obtained after processing of 10 L volume samples was subsequently analysed using three molecular detection methods: nested PCR, real-time PCR and LAMP. E. multilocularis DNA was found in 13 (5.85%) water samples; including 8 (5.8%), 3 (6%), 2 (20%) and 0 positive samples found in WWTPs, a slaughterhouse, a cattle farm and rivers, respectively. All three (LAMP, PCR, RT-PCR) molecular tools displayed high agreement and effectiveness in their ability of detecting the parasite’s DNA in environmental material. This is the first investigation describing E. multilocularis detection in wastewater samples, using three sensitive molecular diagnostic tools. Results indicate the role of wastewater in dissemination of E. multilocularis and the risk of contamination of water sources.

Since 2013, the H7 subtype avian influenza virus (AIV-H7) has seriously endangered human life and health, and has had a serious impact on the poultry industry in China. A competitive enzyme-linked immunosorbent assay (C-ELISA) which detects the antibody for AIV-H7 was developed, basing on a monoclonal antibody (mAb) against the neutralizing epitopes on hemagglutinin (HA)gene. Twelve hybridoma cell lines were screened by cell fusion. Hemagglutination inhibition (HI) assay and indirect ELISA were used to identify the competitive effect of the mAbs. High-affinity mAb 1H11 was selected as a competitive antibody. The reaction conditions for the C-ELISA were optimized for AIV-H7 antibody detection. The cross-reactivity of the C-ELISA was determined by AIV-(H1H15), NDV, IBV and IBDV positive serum. A total of 1294 field samples (chicken (462), duck (318), goose (219), quail (203) and pigeon (92) were simultaneously detected by C-ELISA and HI assay. The C-ELISA was found to have a high specificity of 93.23% and a sensitivity of 96.24%. These results reveal a positive coincidence between C-ELISA and HI assay at a coincidence rate of 97.52%. In addition, It confirmed that this method can be used for the diagnosis of AIV-H7 antibodies from chicken, ducks, goose, quail and pigeons.

Glucocorticoid insensitivity is an important barrier to the treatment of several inflammatory diseases, including acute lung injury (ALI). Saquinavir (SQV) is an inhibitor of the human immunodeficiency virus protease, and the therapeutic effects of SQV in ALI accompanied with glucocorticoid insensitivity have not been previously investigated. In this study, the effects of SQV on lipopolysaccharide (LPS)-mediated injury in human pulmonary microvascular endothelial cells (HPMECs), human type I alveolar epithelial cells (AT I), and alveolar macrophages were determined. In addition, the effects of SQV on an LPS-induced ALI model with or without methylprednisolone (MPS) were studied. In LPS-stimulated HPMECs, SQV treatment resulted in a decrease of high mobility group box 1 (HMGB1), phospho-NF-κB (p-NF-κB), and toll-like receptor 4 (TLR4), and an increase of VE-cadherin. Compared to MPS alone, MPS plus SQV attenuated the decrease of glucocorticoid receptor alpha (GRα) and IκBα in LPS-stimulated HPMECs. HMGB1, TLR4, and p-NF-κB expression were also lessened in LPS-stimulated alveolar macrophages with SQV treatment. In addition, SQV reduced the injury in human AT I with a decrease of HMGB1 and p-NF-κB, and with an increase of aquaporin 5 (AQP 5). SQV ameliorated the lung injury caused by LPS in rats with reductions in vascular permeability, myeloperoxidase activity (MPO) and histopathological scores, and with lowered HMGB1, TLR4, and p-NF-κB expression, but with enhanced VE-cadherin expression. By comparison, SQV plus MPS increased GRα and IκBα in lung tissues of rats with ALI. This study demonstrated that SQV prevented experimental ALI and improved glucocorticoid insensitivity by modulating the HMGB1/TLR4 pathway.

Irinotecan (CPT-11) is used to treat various cancers but side effects such as delayed diarrhea restrict its use. Darunavir (DRV) is an antiretroviral drug used to treat and prevent human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), but whether DRV is protective against CPT-11-induced intestinal toxicity is unclear. An CPT-11-induced intestinal toxicity model was produced using uninterrupted CPT-11 (ip) for 4 d in mice. Enzyme-linked immuno sorbent assay (ELISA), fecal occult blood test (FOBT), Western blot, histopathological evaluation, and immunohistochemistry staining assays were used to document toxicity. DRV treatment attenuated CPT-11-induced intestinal toxicity via decreasing fecal occult blood and mitigating delayed-onset diarrhea, as well as reducing weight loss, reduced food intake, and pathomorphologic changes without inhibiting β-glucuronidase (β-GLU) activity. The high mobility group box-1 protein (HMGB1)-toll-like receptor 4 (TLR4) pathway induced inflammation and tight junction protein (occludin and zonular occluden-1) reduction in the colon was inhibited by DRV. Hepatotoxicity induced by CPT-11 was diminished after treatment with DRV, and activation of the NOD-like receptor 3 inflammasome (NLRP3) was prevented in colon tissue. In addition, DRV didn't reduce the concentration of CPT-11 and 7-ethyl-10-hydroxycamptothecin (SN-38) in plasma at the same dose of irinotecan with DRV. DRV has anti-inflammatory and intestinal-protective properties and may be used to manage CPT-11-induced intestinal toxicity.

Aims To observe the ventricular global and regional function of the patients with systemic amyloidosis using two-dimensional speckle tracking echocardiography. Methods The study enrolled 31 consecutive biopsy-proved patients with systemic amyloidosis who underwent echocardiographic examination and EF ≥ 55% and 37 age- and gender-matched healthy controls. We compared systolic strain and strain rate, diastolic strain rate, time to peak strain, peak delay time in longitudinal, radial, circumferential directions in 16 left ventricular segments. The global peak systolic longitudinal and radial strain of left ventricle, peak systolic longitudinal strain and strain rate, diastolic strain rate of right ventricular free wall were also compared. Results (1) Global peak systolic longitudinal strain (GPSLS), peak systolic longitudinal strain (PSLS) and strain rate (PSLSR), peak early diastolic longitudinal strain rate (PELSR) in 16 segments were decreased in case (P

Fourier transform infrared imaging (FTIRI) combined with chemometrics has potential to determine the molecular and chemical properties of biological tissues. In this study, FTIRI with partial least square (PLS) algorithm was used to quantitatively study the concentration distributions of two principal components (collagen and proteoglycan) in healthy and osteoarthritis (OA) articular cartilage. 10 μm-thick sections of canine tibial cartilage were imaged at 6.25 μm/pixel. The spectra extracted from the infrared images were imported into the PLS model to predict the concentrations of collagen and proteoglycan in the corresponding cartilage sections. Spectral pre-processes in this model included multiplicative scatter correction, normalization, and baseline correction, in order to reduce negative factors in the spectra. Leave-one-out cross validation was also performed in this model. The obtained coefficients of Pearson’s r (0.964) and root mean square error of calibration sample (RMSEC, 5.4%) suggest the excellent representativeness of the PLS model. The prediction results indicate that proteoglycan concentration is lower than that of collagen in both healthy and OA cartilage, and decreases in the OA cartilage, especially at superficial zone. The prediction with spatial resolution can help to understand the osteoarthritic development and demonstrate that FTIRI combined with PLS is a powerful analytical approach in biomedical research.