The value of baseline Doppler ultrasonography in the prediction of treatment response with recombinant human tumor necrosis factor-α receptor Ⅱ immunoglobulin G Fc fusion protein in patients with ankylosing spondylitis / 中华风湿病学杂志

Objective:To predict the inflammatory activity of patients with ankylosing spondylitis (AS) after 12 weeks treatment with recombinant human tumor necrosis factor-α receptor Ⅱ immunoglobulinG Fc fusion protein (rhTNFR:Fc) by Doppler ultrasonography at baseline.Methods:A total of 60 patients with AS were selected, and their general clinical characteristics before and after treatment were compared. Meanwhile, Doppler ultrasonography of the sacroiliac joint was performed to compare the Doppler parameters before and after treatment, and the correlation between baseline Doppler ultrasonography and clinical characteristics was analyzed, along with its diagnostic performance. The pre-treatment and post-treatment parameters were compared to the measured data followed by paired t-test for normal distribution, and the counting data were paired with Chi- square test. Pearson correlation test was used to analyze the correlation between pretreatment ultrasound parameters and pre-treatment disease activity. All statistical tests were bilateral, with a statistically significant difference of P<0.05. Results:After treatment, the overall score [(1.4±1.0) points vs (6.0±1.8) points, t=17.80, P<0.001], night pain score [(1.6±1.2) points vs (5.7±1.5) points, t=15.80, P<0.001], back pain score [(1.9±1.3) points vs (5.5±1.2) points, t=16.39, P<0.001], morning stiffness [(12±6) min vs (38±21) min points, t=8.93, P<0.001], Bath ankylosing spondylitis disease activity index (BASDAI) [(1.1±0.6) vs (4.6±1.3), t=12.41, P<0.001], ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP) [(1.0±0.4) points vs (3.7±0.9) points, t=22.01, P<0.001] and ASDAS-erythrocyte sedimentation rate (ESR) [(1.0±0.7) points vs (4.0±0.8) points, t=20.10, P<0.001] of patients with ankylosing spondylitis were lower than those before treatment, and the differences were statistically significant ( P<0.001). Compared with AS patients before treatment, the color blood flow grading score was significantly lower after treatment [(1.7±0.8) points vs (3.9±1.1) points, t= 12.86, P<0.001). The post-treatment proportion of AS patients with bilateral sacroiliac joint blood flow signal was 67% (40/60), which was lower than 87% (52/60) before treatment, but the difference was not statistically significant ( P=0.251). After treatment, the peak systolic velocity (PSV), pulsatile index (PI) and resistance index (RI) were significantly higher than those before treatment [(30±17) cm/s vs (19±8) cm/s, t=-5.42, P<0.001; (1.55±0.69) vs (1.00±0.45), t=0.45, P<0.001; (0.81±0.11) vs (0.55±0.14), t=11.20, P<0.001)]. The end diastolic velocity (EDV) before and after treatment had no statistical significant differences [(6.7±2.5) cm/s vs (6.3±1.9) cm/s, t=0.80, P=0.428]. Baseline Doppler ultrasound parameters and pre-treatment clinical indicators showed that PI and RI were negatively correlated with BASDAI ( r=-0.49, P=0.005; r=-0.51, P<0.001) , and blood flow grades were positively correlated with BASDAI ( r=0.46, P=0.028). However, there were no significant correlation between PSV, EDV and BASDAI ( r=-0.12, P=0.176; r=0.03, P=0.756). Baseline Doppler ultrasound parameters were correlated with ASDAS-CRP ( r=-0.45, P=0.012; r=0.29, P<0.048; r=-0.52, P<0.035; r=-0.76, P<0.001; r=0.61, P<0.001). There was no correlation between EDV and ASDAS-ESR ( r=0.30, P=0.110), the other ultrasound Doppler parameters were correlated with ASDAS-ESR ( r=-0.36, P<0.001; r=-0.54, P<0.001; r=-0.61, P=0.021; r=0.41, P=0.028). The receiver operating characteristic curve was drawn with the baseline RI value as a variable. According to the ASDAS-CRP value, the diagnostic threshold for determining the presence or absence of AS activity after 12 weeks of treatment was 0.49, with an area under the curve of 0.817, sensitivity of 88.1%, specificity of 61.1%, positive predictive value of 66.7%, and negative predictive value of 86.1%. Conclusion:Baseline Doppler ultrasound correlates well with clinical indicators, among which baseline RI values is a good predictor of inflammatory activity status after rhTNFR:Fc treatment.

Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI

Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection induced more severe cell death in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection and drug discovery.

Single-Cell Analysis Reveals Macrophage-Driven T Cell Dysfunction in Severe COVID-19 Patients

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, SARS-CoV-2-specific T cells were observed in pleural effusion earlier than in peripheral blood. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.

Relationship between diabetes mellitus and hypothalamic-pituitary-adrenal axis:A systematic review / 中华内分泌代谢杂志

Objective To provide objective evidences for early screening of the hypothalamic-pituitary-adrenal(HPA)axis function in diabetic patients, the relationship between HPA axis function and diabetes mellitus was systematically reviewed. Methods PubMed, Ovid, Embase, Web of science Databases were retrieved from articles reporting the relationship between HPA axis function and diabetes mellitus. Meta-analysis were carried out by Stata 12. 0 software for heterogeneity test and data merged among articles for the inclusion and exclusion criteria. Results Our meta-analysis showed the following results: Compared with control group, the basal plasma cortisol level in total diabetes group, T1DM group, T2DM group, diabetes patients(with or without chronic complications)combined with hypertension was significantly higher. Compared with control group, postdexamethasone cortisol level was markedly higher in diabetes group. There was no significant difference in 24 h urinary free cortisol(24h UFC)and ACTH levels between diabetes group and control group. Our qualitative evaluation shows the following results: the differences of awaking salivary cortisol and cortisol awakening response(CAR)between the two groups were inconsistent among all included studies. Most studies showed that CAR was lower in diabetic patients. Conclusion The present analysis has demonstrated that HPA axis dysfunction exists along with diabetes mellitus, and diabetic comorbidity may further worsen the HPA axis dysfunction.

Three-dimensional CT liver image segmentation based on hierarchical contextual active contour / 生物医学工程学杂志

In this paper, we propose a new active contour algorithm, i. e. hierarchical contextual active contour (HCAC), and apply it to automatic liver segmentation from three-dimensional CT (3D-CT) images. HCAC is a learning-based method and can be divided into two stages. At the first stage, i.e. the training stage, given a set of abdominal 3D-CT training images and the corresponding manual liver labels, we tried to establish a mapping between automatic segmentations (in each round) and manual reference segmentations via context features, and obtained a series of self-correcting classifiers. At the second stage, i.e. the segmentation stage, we firstly used the basic active contour to segment the image and subsequently used the contextual active contour (CAC) iteratively, which combines the image information and the current shape model, to improve the segmentation result. The current shape model is produced by the corresponding self-correcting classifier (the input is the previous automatic segmentation result). The proposed method was evaluated on the datasets of MICCAI 2007 liver segmentation challenge. The experimental results showed that we would get more and more accurate segmentation results by the iterative steps and the satisfied results would be obtained after about six rounds of iterations.

Correlation of self defensive styles of isolated population and their cognition to risk with mental health / 中国组织工程研究

BACKGROUND:During the outbreak of severe acute respiratory syndrome(SARS),certain people had been isolated by various reasons and appeared a series of psychological, physical and behavioral reactions. OBJECTIVE:To understand the different defensive features in people with different level of mental health in the isolated population, and explore the relationship between defensive style and mental health. DESIGN:An in investigative study taking the isolated population during outbreak of SARS as the subjects. SETTING:A psychiatric department of a military hospital. PARTICIPANTS:Totally 187 people of different sex,age and education, who were isolated during April and May 2003 due to SARS outbreak in a city of northwest China,were selected as the subjects. INTERVENTIONS:The 187 subjects,who were isolated due to SARS outbreak,were evaluated by using the symptom checklist(SCL 90) and defense style questionnaire(DSQ). RESULTS:About 36.4% people of this population had distinct mental or physical health problems that were characterized by anxiety,horror,depression,hostility and compulsion.There was difference in defensive styles between the high symptom group and low symptom group,among which the score of DSQ factors in the immature type of high and low symptom groups were 5.72± 1.56 and 4.35± 0.96 respectively while the scores in the intermediate type defense were 4.98± 1.44 and 3.72± 0.89 respectively(P< 0.01).Mental health problem was positively correlated with the application of immature defensive style,but had negative correlation with application of mature defensive means. CONCLUSION:There is difference in the defensive styles among the isolated people with different mental health status,and their defensive strategies are closely related to the mental health.

Quantitative determination of triptoquinone B in Radix Folium Seu Flos Tripterygii Wilfordii and its tablets by HPLC / 中草药

Objective To establish an HPLC method for determination of triptoquinone B in Radix Folium Seu Flos Tripterygii Wilfordii(RFFTW) and its tablets.Methods An external method with HiQ siL KYA-C_(18)(250 mm?4.6 mm,5 ?m) column as fixed phase and methanol-1% acetic acid solution((66∶)34) as mobile phase was adopted.The detective wave length was 254 nm and the flow rate was 1.0 mL/min.Results The linearity range was 6.62—105.9 ?g/mL(r=0.999 9),the average recovery of T.wilfordii from Hunan Province was 97.78%,RSD was 1.09%(n=9),and the average recovery of tablet of T.hypoglaucum was 99.83%,RSD was 1.76%(n=9).Conclusion The method is accurate and sensitive.It is adoptable for quantitative analysis of triptoquinone B in RFFTW and its tablets.

Determination of tripterine in Tripterygium wilfordii and its tablets by HPLC / 中草药

Objective To determine the content of tripterine in Tripterygium wilfordii and its tablets by HPLC.Methods An external standard method by HPLC with Zorbax C_(18)column as fixed phase and methanol-1% HAc(87∶13) as mobile phase was adopted.The detection wavelength was 425 nm and the flow rate was 1.0 mL/min.Results The linear range for tripterine was 40.96～204.8 ?g/mL(r=(0.999 6).) The average recovery of Chinese medicinal materials was 98.37% and RSD was 1.01%(n=9);the average recovery of preparation sample was 98.59% and RSD was 1.18%(n=9).Conclusion The method is simple and accurate,which can be adoptable for quantitative analysis of tripterine in the plants of Tripterygium L.

Determination of triptoquinone H in Tripterygium wilfordii and its Tablet by HPLC / 中草药

Objective To develop an HPLC method for determination of triptoquinone H in Tripterygium wilfordii and its Tablet preparations. Methods An external method with Agilent Zorbax SC-C_(8)(250 mm?4.6 mm, 5 ?m) column as fixed phase and methanol-water (75∶25) as mobile phase was adopted. The detective wavelength was 258 nm and the flow rate was 1.0 mL/min. Results The linearity range of triptoquinone was 6.28 — 100.5 ?g/mL (r=0.999 7). The average recovery of T. wilfordii was 96.94%, RSD was 1.57% (n=9) and the average recovery of T. hypoglaucum Tablet was 100.02%, RSD was 1.74% (n=9). Conclusion The method is accurate and sensitive. It is adoptable for quantity analysis of triptoquinone H in T. wilfordii and its Tablet.

Perspiration on the Head, A Special Manifestation in Severely icteric Chronic Hepatitis, Report of 124 Cases, / 中医杂志

Of the 411 hepatitis with severe jaundice admitted, 124 ( 30. 17%) had head perspiration. Based on Zhang Zhongjing's etiologic - pathogenic conception, 102 cases of such patients were treated by the principle of cooling and activating blood, benefitting Qi and Yin. 89 cases had jaundice eliminated, 13 cases had residual jaundice. All 22 cases of chronic severe hepatitis survived. Of them, 9 early stage cases were all survived, 7 of the 8 cases of intermediate stage survived, only 1 out of 5 cases of late stage survived.