Application of metagenomic next-generation sequencing in prevention and control of infection in solid organ transplantation / 器官移植

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study.

PURPOSE: To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). METHODS: Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. RESULTS: MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. CONCLUSION: MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.

Circ_TNFRSF21 promotes cSCC metastasis and M2 macrophage polarization via miR-214-3p/CHI3L1.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a highly invasive disease with the potential to metastasize and cause fatality. Therefore, it is crucial to understand the mechanism behind cSCC in order to devise effective strategies to combat this disease. OBJECTIVE: We investigated the function of circ_TNFRSF21/miR-214-3p/CHI3L1 axis in cSCC. METHODS: The features of circ_TNFRSF21 was characterized using Sanger sequencing, and RNase R/actinomycin D treatment. Genes and M1/M2 markers levels were assessed by qRT-PCR and IHC. The proliferation, migration, and invasion of cells were evaluated by CCK-8, colony formation, EdU incorporation, and transwell assays. Tumor growth and metastasis in vivo were evaluated by nude mouse xenograft model. Interactions of circ_TNFRSF21/miR-214-3p and miR-214-3p/CHI3L1 were validated by RNA immunoprecipitation and dual luciferase assay. RESULTS: Circ_TNFRSF21 and CHI3L1 expression were elevated in both human cSCC tissues and cells, whereas miR-214-3p was reduced. Circ_TNFRSF21 silencing or miR-214-3p overexpression suppressed cSCC cell proliferation, migration, invasion, and M2 macrophage polarization. Circ_TNFRSF21 functioned as a sponge for miR-214-3p while miR-214-3p directly targeted CHI3L1. Knockdown of miR-214-3p reversed the effects of circ_TNFRSF21 knockdown on cSCC development, while CHI3L1 upregulation reversed the effects of miR-214-3p overexpression. Furthermore, knockdown of circ_TNFRSF21 inhibited cSCC tumor growth and metastasis in vivo. CONCLUSION: Circ_TNFRSF21 plays a significant role in cSCC progression by enhancing cell proliferation, migration, invasion, and M2 macrophage polarization through inhibiting miR-214-3p and subsequent disinhibition of CHI3L1. These findings deepen our understanding of the molecular mechanism of cSCC and propose the circ_TNFRSF21/miR-214-3p/CHI3L1 axis as promising diagnosis markers or therapeutic targets for cSCC.

Value of CT radiomic features in differential diagnosis of lung metastases / 国际肿瘤学杂志

Objective:To distinguish lung metastases of different origin by constructing a classification model according to CT radiomics features.Methods:A total of 226 patients with lung metastases of gastric cancer, breast cancer and kidney cancer attending Chongqing Red Cross Hospital from January 2015 to July 2020, with a total of 402 metastases, were randomly divided into a training cohort (training set, 136 patients, 280 metastases) and a validation cohort (validation set, 90 patients, 122 metastases) by the hold-out method. In addition, 68 patients with lung metastases (138 lung metastases in total) attending Chongqing Red Cross Hospital from August 2020 to April 2022 were matched as an external test cohort (test set). Region of interest segmentation was performed by two experienced radiologists independently and manually without clinical information to construct the model by using LASSO screening for the best radiomic features. Support vector machine (SVM) and random forest (RF) were selected to build dichotomous and trichotomous models respectively. The receiver operating characteristic curve was used to evaluate the classification efficiency of both models.Results:There were no statistically significant differences in age ( t=-0.06, P=0.534), gender ( χ2<0.01, P=0.961) and number of lung metastases ( χ2=0.71, P=0.703) between the validation and test sets. A total of 792 radiomic features were extracted, 703 of which had good agreement (intraclass correlation coefficient≥0.75), while 89 features being excluded for having poor agreement (intraclass correlation coefficient<0.75). The dichotomous model (SVM) screened 28 (lung metastases from gastric cancer vs. lung metastases from breast cancer), 25 (lung metastases from gastric cancer vs. lung metastases from kidney cancer) and 34 (lung metastases from kidney cancer vs. lung metastases from breast cancer) features, respectively; the trichotomous model (RF) screened 20 features (three types of lung metastases), in which Short Run Emphasis and Inverse Variance were significantly higher in lung metastases from kidney cancer than in the other two types, correlation was higher in lung metastases from gastric cancer than in the other two types, and there was no significant difference in the sphericity of the three lung metastases. For the dichotomous model, in the validation set, the area under the curve (AUC) of the 28 features selected to distinguish gastric cancer lung metastases from breast cancer lung metastases was 0.81, the AUC of the 25 features distinguishing gastric cancer lung metastases from kidney cancer lung metastases was 0.86, and the AUC of the 34 features distinguishing kidney cancer lung metastases from breast cancer lung metastases was 0.92, and the AUCs of the test set were 0.80, 0.79 and 0.86 respectively. For the trichotomous model, the AUC for predicting lung metastases from gastric cancer, breast cancer and kidney cancer in the validation set were 0.85, 0.82 and 0.91 respectively, and both macroscopic and microscopic AUC were 0.85; In the test set, the AUC for predicting lung metastases from gastric cancer, breast cancer, and kidney cancer were 0.77, 0.86 and 0.84 respectively, and both macroscopic and microscopic AUC were 0.81. Conclusion:The SVM and RF models based on CT radiomic features are helpful in distinguishing lung metastases derived from gastric cancer, breast cancer and kidney cancer.

Differential Analysis of Macular Structure and Microcirculation in Both Eyes of Patients With Myopic Anisometropia / 中国医学科学院学报

Objective To compare the macular structure and microcirculation in both eyes of the patients with myopic anisometropia.Methods Optical coherence tomography angiography(OCTA)was employed to scan the macular areas in both eyes of 44 patients with myopic anisometropia.The patients were assigned into high and low groups based on the refractive diopter,and the parameters such as retinal thickness,choroidal thickness,vascular density,and perfusion density in the macular areas of both eyes were compared between the two groups.Results Other macular areas except the central and external nasal areas and the choroid of the fovea in the high group were thinner than those in the low group(all P<0.05).There was no statistically significant difference in retinal vascular density or perfusion density in different areas between the two groups(all P>0.05).Conclusion In the patients with myopic anisometropia,most areas of the retina in the case of high myopia is thinner than that in the case of low myopia,while there is no difference in retinal vascular density or perfusion density in both eyes.

Identification the key factor of pulmonary fibrosis following silica nanoparticles exposure based on bioinformatics analysis / 中华劳动卫生职业病杂志

Objective: To investigate the main mechanisms of pulmonary fibrosis following silica nanoparticles (SiNPs) exposure through constructing the macrophage-fibroblast model in vitro, which simulated the process of pulmonary fibrosis. Methods: In January 2021, human mononuclear leukemia cells (THP-1) were treated with 0, 25, 50, 100 μg/ml SiNPs for 24 h. The supernatant of THP-1 cells was collected and applied to human embryonic lung fibroblast cells (MRC-5) which divided into control and low, medium and high dose groups at the logarithmic growth stage for 24 h. MRC-5 cell viability was detected by CCK8. The hydroxyproline (Hyp), interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) expression were detected in the supernatants of MRC-5. The changed proteins were detected by liquid-phase mass spectrometry in high dose group. GeneCard database were applied to identity the differential pulmonary fibrosis proteins in high dose group. Gene Ontology (GO) was performed to identity the key biological process in differential pulmonary fibrosis proteins of high dose group. The String database was used to construct the protein-protein interactions (PPI) network of differential pulmonary fibrosis proteins. The APP of CytoHubba was applied to calculate the key protein of differential pulmonary fibrosis proteins in PPI network. Correlation coefficients between key differential pulmonary fibrosis proteins were calculated using Pearson correlation analysis. Western blotting was applied to detect the expression of key proteins of differential pulmonary fibrosis proteins in different groups. Results: CCK8 results showed that MRC-5 cell viability was increasing in low, medium and high dose groups compared with control group (P<0.05). The expression levels of Hyp and IL-1β in different group were increased compared with control group, the expression levels of IL-6 and TNF-α were increased in high dose group compared with control group (P<0.05). GeneCard database identified 26 differential pulmonary fibrosis proteins, which were mainly involved in extracellular matrix hydrolysis, cell inflammatory response, tissue repair, cell proliferation, inflammation response by GO analysis. The APP of CytoHubba was calculated that matrix metalloproteinase 9 (MMP9) and tissue inhibitor metalloproteinase 1 (TIMP1) played an important role in PPI network. The results of correlation analysis showed that MMP9 was correlated with the expression of matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3), TIMP1 and epidermal growth factor receptor (EGFR) (r=0.97, 0.98, 0.94, 0.93, P<0.05). Western blotting results showed that TIMP1 protein expression was increased in low, medium and high dose groups, while MMP9 protein expression was increased only in high dose group (P<0.05) . Conclusion: Differential expression proteins related with pulmonary fibrosis in MRC-5 cells mainly regulate biological processes of extracellular matrix hydrolysis, tissue repair, and cellular inflammation response following SiNPs exposure. MMP9 and TIMP1 may be the key proteins, which affected the fibrosis process in vitro pulmonary fibrosis model.

M2 macrophage facilitated angiogenesis in cutaneous squamous cell carcinoma via circ_TNFRSF21/miR-3619-5p/ROCK axis.

In recent years, the role of circular RNA in cancer cells has been studied broadly; however, the functional significance of circular RNA in the regulation of the tumor microenvironment (TME) is not fully understood. In this study, we aimed to reveal the role of circ_TNFRSF21 in M2 macrophage-induced cutaneous squamous cell carcinoma (cSCC) angiogenesis. Quantitative polymerase chain reaction and Western blotting were performed to determine the levels of the indicated genes. Direct binding between circ_TNFRSF21 and miR-3619-5p, miR-3619-5p, and ROCK2 was verified by dual-luciferase activity. The migration and invasion of human umbilical vein endothelial cells were evaluated by wound healing and transwell assays. Tube formation was performed to detect in vitro angiogenesis. Circ_TNFRSF21 and ROCK2 were upregulated in cSCC tissue, while miR-3619-5p was downregulated. Circ_TNFRSF21 negatively regulated the expression of miR-3619-5p, while miR-3619-5p negatively regulated the expression of ROCK2. miR-3619-5p suppressed tube formation by inhibiting ROCK signaling. M2 macrophages facilitated tube formation via the circ_TNFRSF21/miR-3619-5p/ROCK2 axis. Our present study revealed that circ_TNFRSF21 was elevated in M2 macrophages and mediated M2 macrophage-induced tube formation in vitro.

Characterizing Sensorimotor-Related Area Abnormalities in Amyotrophic Lateral Sclerosis: An Intravoxel Incoherent Motion Magnetic Resonance Imaging Study.

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

An injectable hydrogel/staple fiber composite for sustained release of CA4P and doxorubicin for combined chemotherapy of xenografted breast tumor in mice / 南方医科大学学报

OBJECTIVE@#To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection.@*METHODS@#DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments.@*RESULTS@#The average length of FDOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX.@*CONCLUSION@#As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.

Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease / 中国医学科学杂志(英文版)

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.

White matter microstructural impairments in amyotrophic lateral sclerosis: A mean apparent propagator MRI study.

BACKGROUND: White matter (WM) impairment is a hallmark of amyotrophic lateral sclerosis (ALS). This study evaluated the capacity of mean apparent propagator magnetic resonance imaging (MAP-MRI) for detecting ALS-related WM alterations. METHODS: Diffusion images were obtained from 52 ALS patients and 51 controls. MAP-derived indices [return-to-origin/-axis/-plane probability (RTOP/RTAP/RTPP) and non-Gaussianity (NG)/perpendicular/parallel NG (NG⊥/NG||)] were computed. Measures from diffusion tensor/kurtosis imaging (DTI/DKI) and neurite orientation dispersion and density imaging (NODDI) were also obtained. Voxel-wise analysis (VBA) was performed to determine differences in these parameters. Relationship between MAP parameters and disease severity (assessed by the revised ALS Functional Rating Scale (ALSFRS-R)) was evaluated by Pearson's correlation analysis in a voxel-wise way. ALS patients were further divided into two subgroups: 29 with limb-only involvement and 23 with both bulbar and limb involvement. Subgroup analysis was then conducted to investigate diffusion parameter differences related to bulbar impairment. RESULTS: The VBA (with threshold of P < 0.05 after family-wise error correction (FWE)) showed that ALS patients had significantly decreased RTOP/RTAP/RTPP and NG/ NG⊥/NG|| in a set of WM areas, including the bilateral precentral gyrus, corona radiata, posterior limb of internal capsule, midbrain, middle corpus callosum, anterior corpus callosum, parahippocampal gyrus, and medulla. MAP-MRI had the capacity to capture WM damage in ALS, which was higher than DTI and similar to DKI/NODDI. RTOP/RTAP/NG/NG⊥/NG|| parameters, especially in the bilateral posterior limb of internal capsule and middle corpus callosum, were significantly correlated with ALSFRS-R (with threshold of FWE-corrected P < 0.05). The VBA (with FWE-corrected P < 0.05) revealed the significant RTAP reduction in subgroup with both bulbar and limb involvement, compared with those with limb-only involvement. CONCLUSIONS: Microstructural impairments in corticospinal tract and corpus callosum represent the consistent characteristic of ALS. MAP-MRI could provide alternative measures depicting ALS-related WM alterations, complementary to the common diffusion imaging methods.

Detection and Classification of Breast Lesions With Readout-Segmented Diffusion-Weighted Imaging in a Large Chinese Cohort.

Objectives: To evaluate the performance of readout-segmented echo-planar imaging DWI (rs-EPI DWI) in detecting and characterizing breast cancers in a large Chinese cohort with comparison to dynamic contrast-enhanced MRI (DCE-MRI). Methods: The institutional review board approved this retrospective study with waived written informed consent. A total of 520 women (mean age, 43.1- ± 10.5-years) were included from July 2013 to October 2019. First, the ability of rs-EPI DWI in detecting breast lesions identified by DCE-MRI was evaluated. The lesion conspicuity of rs-EPI-DWI and DCE-MRI was compared using the Wilcoxon signed rank test. With pathology as a reference, the performance of rs-EPI DWI and DCE-MRI in distinguishing breast cancers was evaluated and compared using the Chi-square test. Results: Of 520 women, 327/520 (62.9%) patients had 423 lesions confirmed by pathology with 203 benign and 220 malignant lesions. The rs-EPI DWI can detect 90.8% (659/726) (reader 1) and 90.6% (663/732) (reader 2) of lesions identified by DCE-MRI. The lesion visibility was superior for DCE-MRI than rs-EPI-DWI (all p < 0.05). With pathology as a reference, the sensitivities and specificities of rs-EPI DWI in diagnosing breast cancers were 95.9% (211/220) and 85.7% (174/203) for reader 1 and 97.7% (215/220) and 86.2% (175/203) for reader 2. No significant differences were found for the performance of DCE-MRI and rs-EPI DWI in discriminating breast cancers (all p > 0.05). Conclusions: Although with an inferior lesion visibility, rs-EPI DWI can detect about 90% of breast lesions identified by DCE-MRI and has comparable diagnostic capacity to that of DCE-MRI in identifying breast cancer.

The SARS-CoV-2 transcriptome and the dynamics of the S gene furin cleavage site in primary human airway epithelia

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the devastating ongoing coronavirus disease-2019 (COVID-19) pandemic which poses a great threat to global public health. The spike (S) polypeptide of SARS-CoV-2 consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary. The inclusion of the 4 amino acids (PRRA) at the S1/S2 boundary forms a furin cleavage site (FCS), 682RRAR{downarrow}S686, distinguishing SARS-CoV-2 from its closest relative, the SARS-CoV. Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, the virus acquired various deletions surrounding the FCS. In the present study, we studied the viral transcriptome in SARS-CoV-2 infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability at the S1/S2 boundary using RNA-seq. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the S1/S2 boundary of the S gene: one is a deletion of 12 amino acids, 678TNSPRRAR{downarrow}SVAS689, which contains the FCS, another is a deletion of 5 amino acids, 675QTQTN679, which is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions revealed that the selective pressure for the FCS maintains the S gene stability in HAE-ALI but with exceptions, in which the FCS deletions are remained at a high rate. Thus, our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is donor-dependent.

A review on the application of UK Biobank in neuroimaging / 生物医学工程学杂志

UK Biobank (UKB) is a forward-looking epidemiological project with over 500, 000 people aged 40 to 69, whose image extension project plans to re-invite 100, 000 participants from UKB to perform multimodal brain magnetic resonance imaging. Large-scale multimodal neuroimaging combined with large amounts of phenotypic and genetic data provides great resources to conduct brain health-related research. This article provides an in-depth overview of UKB in the field of neuroimaging. Firstly, neuroimage collection and imaging-derived phenotypes are summarized. Secondly, typical studies of UKB in neuroimaging areas are introduced, which include cardiovascular risk factors, regulatory factors, brain age prediction, normality, successful and morbid brain aging, environmental and genetic factors, cognitive ability and gender. Lastly, the open challenges and future directions of UKB are discussed. This article has the potential to open up a new research field for the prevention and treatment of neurological diseases.

Inhibitory effect of miRNA-126 on inflammatory response in mice with cerebral ischemia-reperfusion injury / 医学研究生学报

ObjectiveThe mechanism of cerebral ischemia-reperfusion injury is highly associated with the inflammatory response. MiRNA-126 plays a key role in vascular inflammation. This study aims to investigate the effect of miRNA-126 on the inflammatory response in mice accompanying cerebral ischemia-reperfusion injury through the NLRP3/NF-κB signal axis, and to explore the mechanisms involved.Methods A total of forty-eight male mice were randomly divided into four groups: the sham-operated group, cerebral ischemia-reperfusion model group, miRNA negative control group (miRNA-126 agomir NC group) and miRNA-126 overexpression group (miRNA-126 agomir group), and each group included twelve mice. The neurobehavioral score was recorded. The left-brain of the mice was sacrificed after anesthesia, and the water content of the brain tissue was measured. HE staining and light microscopy were used to identify the histopathological changes of the cerebral of the mice. The expression levels of inflammatory cytokines IL-1β and IL-6 in brain tissue and serum of mice were detected by ELISA. Western Blot method was used to determine the protein expression levels of NLRP3, ASC, caspase-1, NF-κB p65, NF-κB P50, p-NF-κB 65 and p-NF-κB 50 in brain tissues of mice in each group. RT-PCR was used to test the expression levels of miRNA126, NLRP3, ASC, caspase-1, NF-κB p65 and NF-κB P50 in brain tissue and serum of mice.ResultsIn the sham-operated group, the morphology, and structure of cerebral cortex were normal as healthy mice, being with the dense and orderly arrangement of nerve fibers, with no occurrence of impaired nerve function, and the neurobehavioral score was zero. In both of model group and the miRNA-126 agomir NC group, the ruptured cerebral cortex could be observed visually being with necrotic and disordered cells. The blurred pyknosis and interstitial edema occurred with increased water content of brain tissue. The nerve damage was observed with a significantly increased neurobehavioral score (P<0.05). Compared to the model group, the pathological morphology of the cerebral cortex in the miRNA-126 agomir group was significantly improved, and the number of necrotic cells was decreased, the arrangement of which was denser and more orderly. Reduced interstitial edema and the neurobehavioral score were identified. The significantly improved nerve injury and the decreased water content of brain tissue were observed as well (P<0.05). Compared to the sham-operated group A, the expression level of miRNA-126 mRNA in the model group and the miRNA-126 agomir NC group decreased significantly. The expression level of IL-1β and IL-6 increased, while the expression levels of NLRP3, ASC, caspase-1, NF-κB p65, NF-κB p50, p-NF-κB p65, p-NF-κB p50, and NLRP3, ASC, caspase-1, NF-κB p65, NF-κB p50 mRNA increased generally (P<0.05). Compared to the model group and the miRNA-126 agomir NC group, the expression level of miRNA-126 mRNA in the miRNA-126 agomir group increased. However, the expression level of IL-1β and IL-6 decreased, and the expression level of NLRP3/NF-κB signal axis related gene protein and mRNA decreased (P<0.05).ConclusionOverexpression of miRNA-126 can inhibit the expression of NLRP3/NF-κB signal axis related genes and the level of inflammation in brain tissue, and improve the neurological injury of cerebral ischemia-reperfusion in mice.

Clinical characteristics of 10 patients with uremic tumoral calcinosis / 中华内科杂志

Objective:To analyze the clinical characteristics of patients with uremic tumoral calcinosis (UTC).Methods:A total of 10 patients with UTC were enrolled in this study, who were admitted in the Department of Nephrology, China-Japan Friendship Hospital and Beijing Chuiyangliu Hospital from March 2013 to February 2019.Results:The average age of 4 male and 6 female patients on regular hemodialysis was (39.90±8.57) years. The average dialysis duration was(5.90±2.57) years. Three patients presented as single lesion of one joint, the other 7 patients as involvement of multiple large joints. Serum calcium was elevated in 2 patients,both over 2.75 mmol/L. Serum hyperphosphatemia was seen in all patients with average level 2.22 (1.94,2.44) mmol/L. Serum intact parathyroid hormone (iPTH) was remarkably increased in 9 patients with average level 1 348.0(854.8,1 800.0) ng/L, while only 1 patient reported slight elevation (92.4 ng/L).High-sensitivity C-reactive protein increased in all 10 patients with average 35.81 (17.60,74.20) mg/L. The imaging findings before treatment suggested that a large number of irregular masses of calcification shadows deposited in the soft tissue adjacent to the joints. The outlines of calcification were clear without significant bone absorption. Nine patients with severe secondary hyperparathyroidism (SHPT) were treated with parathyroidectomy, resulting in lesions diminishing or even disappearing. A total of 32 parathyroid glands were resected, and pathological results showed that 7 parathyroids were diffuse hyperplasia, 11 as diffuse/nodular hyperplasia, the rest 14 as nodular hyperplasia. At least one hyperplastic parathyroid gland was seen in each patient. Only 1 patient received medical therapy yet no obvious improvement was observed.Conclusion:UTC is a rare complication in patients on regular hemodialysis, which is usually associated with severe SHPT. Parathyroid surgery may improve the clinical outcome.

Clinical and fundamental research Yinhua Miyanling Tablets in treating urinary tract infection / 中国中药杂志

As the famous Chinese patent medicine, Yinhua Miyanling Tablets, which was derived from ancient prescription denominated Bazhengsan, has not only the effects in clearing away heat and purging pathogenic fire, removing dampness and relieving stranguria, but also have the functions of detoxifying and tonifying. A great number of scientific studies have demonstrated that Yinhua Mi-yanling Tablets played significant roles in destroying harmful microbes and resisting inflammatory and diuresis. Compared with antibiotics, traditional antibacterial Chinese patent medicine Yinhua Miyanling Tablets has the advantage in bacterial resistance in long-term use. Fundamental studies about the content of pharmaceutical ingredients and the modern pharmacology of Yinhua Miyanling Tablets were collected and summarized, which conduces to indicating the active ingredients of Yinhua Miyanling Tablets with the medicinal efficacy from the molecular level and the internal mechanism of Yinhua Miyanling Tablets in the treatment of urinary tract infection(UTI) from the scientific perspective. In the field of clinical research, literatures associated with Yinhua Miyanling Tablets for the treatment of UTI were summarized and analyzed in terms of treatment type, administration mode, dosage, frequency of medication, course, efficiency, side effects and whether combined with healthy lifestyle. These literatures confirmed the medicinal values and the application prospect of Yinhua Miyanling Tablets in treating UTI, especially acute UTI, which provides a scientific theoretical foundation and a correct direction for the clinical application of Yinhua Miyanling Tablets. In conclusion, this article contributes to the standardization of Yinhua Miyanling Tablets in the treatment of UTI, in the expectation of giving the scientific guidance for clinical practice.

Anticancer effects of 10-hydroxycamptothecin induce apoptosis of human osteosarcoma through activating caspase-3, p53 and cytochrome c pathways.

In order to evaluate the anticancer effect of 10-hydroxycamptothecin (HCPT) in terms of inducing the apoptosis of human osteosarcoma cells, its apoptosis-inducing molecular mechanisms were investigated. In the present study, the anticancer effects of HCPT were revealed to result in suppressed cell viability, increased cytotoxicity, the induction of apoptosis and an augmented apoptotic nucleolus of human osteosarcoma cells. MG-63 cells were cultured with HCPT (0, 20, 40 and 80 nM) for 24 and 48 h. An MTT assay and a lactate dehydrogenase assay were used to analyze the anticancer effect of HCPT on cell viability and cytotoxicity in MG-63 cells. MG-63 cell apoptosis, and caspase-9 and caspase-3 activity levels were evaluated using flow cytometry and an ELISA. Western blot analysis was used to detect the protein expression levels of p53, poly (ADP-ribose) polymerase-1 (PARP-1), cytochrome c and B cell lymphoma-2 (Bcl-2) in MG-63 cells. The anticancer effects of HCPT were demonstrated to significantly activate the protein expression of p53, PARP-1 and cytochrome c, and suppress Bcl-2 protein expression and promote the activity of caspase-9 and caspase-3 in human osteosarcoma cells. In conclusion, the anticancer effects of HCPT appear to induce the apoptosis of human osteosarcoma cells through the activation of the caspase-3, p53 and cytochrome c pathways.

MRI diagnosis of intracranial extra-encephalon cavernous angiomas / 实用放射学杂志

Objective To investigate MRI diagnosis of intracranial extra-encephalon cavernous angiomas.Methods In 9 intracranial extra-encephalon cavernous angiomas,5 masses located in the parasellar,2 masses in the lateral ventricle triangle,1 mass in the fourth ventricle and 1 mass in temporal subdural space.The MRI features of the masses were analyzed.Results 5 parasellar cavernous angiomas enclosed the ipsilateral internal carotid artery and extended the saddle.The masses showed homogeneous low intensity on T1WI,high intensity on T2WI,obvious enhancement on enhanced scan.Of 2 cavernous angiomas in the right lateral ventricle triangle, 1 mass showed homogeneous low intensity on T 1WI,high intensity on T2WI,obvious enhancement on enhanced scan;the other mass showed isointensity on T1WI,slight high intensity on T2WI,high intensity on DWI,low intensity on SWI and patchy enhancement on enhanced scan.1 cavernous angioma located in the fourth ventricular showed mixed intensity on T 1WI and T2WI,low signal rim around the mass on T2WI,inhomogeneous high intensity on DWI sequence and little enhancement on enhanced scan.1 mass located in temporal subdural space showed homogeneous low intensity on T 1WI,high intensity on T2WI,low intensity on DWI,isointensity on SWI and homogeneous obvious enhancement on enhanced scan.Conclusion The MRI findings of the intracranial extra-encephalon cavernous angiomas are characteristic.Most masses show homogeneous low intensity on T1WI,high intensity on T2WI and obvious enhancement on enhanced scan.The masses should mainly be distinguished from meningiomas.

Correlation of serum androgen levels with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou / 中华男科学杂志

<p><b>Objective</b>To investigate the relationship of the levels of serum androgens with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou.</p><p><b>METHODS</b>Using the stratified cluster sampling method, we conducted a questionnaire investigation and physical examinations among 437 men in Zunyi City. We divided the subjects into a middle-aged (40－64 ［53.20 ± 7.41］ years, n = 269) and an elderly group (=≥65 ［70.63 ± 4.66］ years, n = 168) and collected fasting elbow venous blood samples from them for measuring the levels of total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), total cholesterol (TCH), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), calculated free testosterone (cFT), free testosterone index (FTI), and testosterone secretion index (TSI).</p><p><b>RESULTS</b>Compared with the elderly group, the middle-aged males showed significantly lower SHBG, LH, HDL and LDL, and higher cFT, FTI, TSI, TG and TCH (all P < 0.05). TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, while cFT was positively correlated with TCH, and so was FTI with TG, TCH with LDL, and TSI with TCH, HDL and LDL (all P < 0.05), but LH was negatively correlated with TG, TCH and LDL (all P < 0.05). Multivariate linear regression analysis showed that TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, and so was LH with TCH, HDL and LDL (all P < 0.05).</p><p><b>CONCLUSIONS</b>In the middle-aged and elderly men in Zunyi, low concentrations of TT, SHBG and LH were associated with the increased risk of high-TCH and -LDL dyslipidemia, low concentrations of TT and SHBG with that of high-TG dyslipidemia, while high concentrations of TT, SHBG and LH with that of low-HDL dyslipidemia.</p>