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ObjectiveWe evaluated the difference in parathyroid visualization on 18F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at different time points, to determine the best imaging time for FCH PET/CT.MethodsThis retrospective study included 73 patients with hyperparathyroidism (HPT) who underwent 18F-FCH PET/CT imaging between December 2017 and December 2021. The diagnostic efficiency of 5- and 60-min dual time point imaging for the diagnosis of hyperparathyroidism and parathyroid adenoma and hyperplasia, were compared using visual and quantitative analyses.ResultsDual-time 18F-FCH PET/CT imaging visual analysis had diagnostic value for HPT. The receiver operating characteristic curve of PET/CT quantitative parameters for the diagnosis of HPT and lesions showed that the parathyroid/thyroid SUVmax ratio for 60-min imaging had a higher sensitivity and specificity (based on patient, sensitivity: 90.90% and specificity: 85.71%; based on focus, sensitivity: 83.06% and specificity: 85.71%) compared to that for 5-min imaging. PET/CT quantitative parameters can distinguish parathyroid adenoma and hyperplasia. The 60-min parathyroid SUVmax value had the highest diagnostic value (cutoff: 3.945; area under the curve: 0.783).ConclusionThe quantitative parameters of 60min 18F-FCH PET/CT have more advantages in aiding in the pathologica diagnosis and clinical treatment of HPT.

BackgroundFew studies have investigated the effects of repeated sessions of transcranial direct current stimulation (tDCS) combined with concurrent cognitive training on improving response inhibition, and the findings have been heterogeneous in the limited research. This study investigated the long-lasting and transfer effects of 10 consecutive sessions of multitarget anodal HD-tDCS combined with concurrent cognitive training on improving response inhibition compared with multitarget stimulation or training alone.MethodsNinety-four healthy university students aged 18–25 were randomly assigned to undergo different interventions, including real stimulation combined with stop-signal task (SST) training, real stimulation, sham stimulation combined with SST training, and sham stimulation. Each intervention lasted 20 min daily for 10 consecutive days, and the stimulation protocol targeted right inferior frontal gyrus (rIFG) and pre-supplementary motor area (pre-SMA) simultaneously with a total current intensity of 2.5 mA. Performance on SST and possible transfer effects to Stroop task, attention network test, and N-back task were measured before and 1 day and 1 month after completing the intervention course.ResultsThe main findings showed that the combined protocol and the stimulation alone significantly reduced stop-signal reaction time (SSRT) in the post-intervention and follow-up tests compared to the pre-intervention test. However, training alone only decreased SSRT in the post-test. The sham control exhibited no changes. Subgroup analysis revealed that the combined protocol and the stimulation alone induced a decrease in the SSRT of the low-performance subgroup at the post-test and follow-up test compared with the pre-test. However, only the combined protocol, but not the stimulation alone, improved the SSRT of the high-performance subgroup. The transfer effects were absent.ConclusionThis study provides supportive evidence for the synergistic effect of the combined protocol, indicating its superiority over the single intervention method. In addition, the long-term after-effects can persist for up to at least 1 month. Our findings also provide insights into the clinical application and strategy for treating response inhibition deficits.

Several trivalent and pentavalent vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands were synthesized. These vanadium complexes were identified by elemental analysis, FTIR spectrometry and NMR. Single crystals of trivalent vanadium complexes V2,...

Additional file 1: Appendix 1.0. Study design and subjects. Appendix 2.0. Assessment of risk factors. Appendix 3.0. Definition of GC cases. Table S1. Results of univariate Cox regression analysis in the CKB cohort. Table S2. Results of multivariate Cox regression model and corresponding risk points in sensitivity analysis 1: excluding weak variables in the simplified model. Table S3. Results of multivariate Cox regression model and corresponding risk points in sensitivity analysis 2: integrating lifestyle factors as an index. Table S4. Results of multivariate Cox regression model and corresponding risk points in sensitivity analysis 3: excluding participants who had GC diagnosis within the first year after recruitment. Table S5. Results of multivariate Cox regression model and corresponding risk points in sensitivity analysis 4: excluding participants who had cancer at baseline. Table S6. Results and corresponding risk points in sensitivity analysis 5: competing risk model by considering death as a competing event. Table S7. Risk categories by deciles of the GCRS in the CKB cohort. Table S8. Internal validation of the GCRS in different regions of CKB. Table S9. Harrell’s C-index of the GCRS from ten-fold cross validation in the CKB cohort. Table S10. Risk categories of the GCRS in the Changzhou cohort. Table S11. Risk categories and associated 3-year, 5-year, and 10-year risk of incident GC derived from CKB. Table S12. Risk categories of different gastric lesions in the Yangzhou screening program. Table S13. Performance of the GCRS across different predicted risk cutoffs in the Yangzhou screening program. Table S14. Risk categories of different gastric lesions in the Yangzhou screening program in sensitivity analysis 1: excluding weak variables in the simplified model. Table S15. Risk categories of different gastric lesions in the Yangzhou screening program in sensitivity analysis 2: integrating lifestyle factors as an index. Table S16. Risk categories of different gastric lesions in the Yangzhou screening program in sensitivity analysis 3: excluding participants who had GC diagnosis within the first year after recruitment. Table S17. Risk categories of different gastric lesions in the Yangzhou screening program in sensitivity analysis 4: excluding participants who had cancer at baseline. Table S18. Risk categories of different gastric lesions in the Yangzhou screening program in sensitivity analysis 5: competing risk model. Table S19. The GCRS and corresponding 3-year, 5-year, and 10-year risk of incident GC derived from the CKB cohort. Fig. S1. Study design and eligible participants’ selection procedures in three studies. Fig. S2. The relationship of the GCRS with incident GC risk in the CKB cohort. Fig. S3. The relationship of the GCRS with incident GC risk in the Changzhou cohort. Fig. S4. Calibration and discrimination of the GCRS in sensitivity analysis 1: excluding weak variables in the simplified model. Fig. S5. Calibration and discrimination of the GCRS in sensitivity analysis 2: integrating lifestyle factors as an index. Fig. S6. Calibration and discrimination of the GCRS in sensitivity analysis 3: excluding participants who had GC diagnosis within the first year after recruitment. Fig. S7. Calibration and discrimination of the GCRS in sensitivity analysis 4: excluding participants who had cancer at baseline. Fig. S8. Calibration and discrimination of the GCRS in sensitivity analysis 5: competing risk model.

Thiopurine dose optimization by thiopurine-S-methyltransferase (TPMT) or nudix hydrolase-15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although laboratory monitoring of 6-thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA-thioguanine nucleotides (DNA-TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA-TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells

The vast majority of traditional vulcanized rubber products are insoluble and infusible, which is difficult to reprocess and biodegrade, resulting in black pollution. In addition, although most rubber materials based on covalent adaptive networks (CANs) can achieve structural reconstruction, the lack of traditional vulcanization system leads to a decline in strength. In this study, biobased vanillin derivatives (PV) were synthesized to cross-link the commercially available 1,2-polybutadiene rubber precursor to construct imine-based CANs, thereby fabricating a resource-renewable, recyclable, and degradable high-performance rubber material. Due to the rigid tripod structure of the PV, the tensile strength of the material can achieve as high as 16.24 MPa, ranking among the best in the field of recyclable polybutadiene-based materials. Benefiting from the dynamic imine unit, the "dynamic covalent bridge" can be re-established to repair the damaged network and endow the material with excellent weldability. And, shape memory faculty of the material was proved and depicted. Moreover, this material displayed excellent antibacterial property originates from the introduced Schiff-base structure. By mixing with graphene, the application of action sensors can also be achieved.

Purpose Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine. Methods In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities. Results Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions. Conclusion tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.

Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1–2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.

Parkinson protein 7 (PARK7)/DJ-1 (DJ-1) is a redox sensitive molecular and stabilizer of nuclear factor erythroid 2-related factor 2 (Nrf-2). Nrf-2 regulates the downstream antioxidant defense system and exerts a significant function in patients with chronic obstructive pulmonary disease (COPD). Vitamin D receptor (VDR) is the nuclear receptor that regulates the downstream target genes. This study aimed to analyze the associations among pulmonary function, DJ-1, VDR and Nrf-2 in COPD patients. Serum was collected from 180 COPD patients and control subjects. Thirty-five lung tissues were obtained. DJ-1 was measured using ELISA and western blotting. Nrf-2 and VDR were detected by immunohistochemistry. Serum and pulmonary DJ-1 levels were lower in COPD patients than those in control subjects. Pulmonary VDR-positive nuclei were reduced in COPD patients. Nrf-2-positive nuclei were reduced in lung tissues of COPD patients. On the contrary, Nrf-2-related downstream target proteins were elevated in COPD patients. Further correlation analysis indicated that forced expiratory volume in 1 second (FEV1) was positively associated with pulmonary DJ-1, VDR and Nrf-2 in patients with COPD. In addition, there were positive correlations among DJ-1, VDR and Nrf-2 in lung tissues of COPD patients. In conclusion, DJ-1, VDR and Nrf-2 were decreased in COPD patients compared with control subjects. The reduction of DJ-1 and VDR associating with Nrf-2 downregulation may be involved in the process of COPD.

In this work, a series of oxovanadium complexes bearing the ligands (S,E)-(+)-2, 6-dialkyl-N-(2-((2-(4-isopropyl-4,5-dihydrooxazole-2-yl)phenyl)amino)benzylidene)aniline (dialkyl = dimethyl (V1), diethyl (V2), and isopropyl (V3)) have been synthesized and characterized by FTIR spectroscopy and elemental analysis. Moreover, the molecular structures of complexes V2 and V3 were defined by X-ray diffraction. On activation with ethylaluminium sesquichloride (Al2Et3Cl3), these complexes exhibited high activity towards ethylene polymerization (up to 1.39 × 107 g molv−1 h−1) and showed excellent thermal stability (up to 60 °C). The obtained polyethylene had a moderate molecular weight (21.9 × 104 to 66.4 × 104 g mol−1) and exhibited narrow distribution (1.91 to 2.86) and unimodal features. The effect of the substituents on the ligands was also investigated in detail. The compound bearing the diisopropyl group showed the highest activity toward ethylene polymerization as the bimolecular deactivation of the catalyst can be effectively inhibited by the steric hindrance of the ortho-substituent on aniline. The complex V2 with moderate steric hindrance was also evaluated as a catalyst for the copolymerization of ethylene with norbornene and showed moderate to high activity.

Additional file 2: Table S1. Characteristics of the population finished vaccination.

Additional file 5. Checklist for the appropriate reporting statement: STROBE.

Additional file 1 : Supplementary Figure 1. Flow cytometry analysis on the anti-CD7 CAR T-cells. Supplementary Figure 2. Cytotoxicity analysis of the anti-CD7 CAR T-cells. Supplementary Figure 3. Timeline of treatments and responses. Supplementary Figure 4. T-cell fractions in the PB post CAR T-cells infusion. Supplementary Table 1. Baseline clinical characteristics of the patient. Supplementary Table 2. A panel of 222 genes detected by next generation sequencing.

Numerous studies demonstrated that bleomycin (BLM) caused acute lung injury (ALI). This study explored the role of mitochondrial reactive oxygen species (ROS) on BLM-induced ALI and pulmonary epithelial ferroptosis. Male C57BL/6J mice were intratracheally injected with BLM (3.0 mg/kg). BEAS-2B cells, human bronchial epithelial cells, were cultured with BLM (10 μg/ml). Pulmonary MDA and 4-HNE, two markers of lipid peroxidation, were elevated in BLM-exposed mice. Oxidized lipids were upregulated in BLM-exposed BEAS-2B cells. Ferroptosis-characteristic ultrastructure, mainly disappearance of mitochondrial bilayer membrane structure and cristae, was observed in BLM-exposed pulmonary epithelium. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated BLM-evoked pulmonary lipid peroxidation, ferroptosis-characteristic mitochondrial ultrastructure and pulmonary epithelial death. The in vitro experiments showed that mitochondrial membrane potentials (MMPs) were decreased and mitochondrial ROS were increased in BLM-exposed BEAS-2B cells. Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, prevented BLM-induced MMP reduction and mitochondrial ROS elevation in BEAS-2B cells. The in vivo experiment found that MitoQ attenuated BLM-evoked GSH depletion and lipid peroxidation in mouse lungs. Moreover, MitoQ prevented BLM-induced ferroptosis-characteristic mitochondrial changes, pulmonary epithelial death and ALI. In conclusion, mitochondrial ROS are an initiator of BLM-induced pulmonary epithelial ferroptosis. Mitochondria-targeted antioxidants may be used as potential therapeutic agents for BLM-induced ALI.

Gestational arsenic (As) exposure has been associated with adverse developmental outcomes. The purpose of this study was to explore the impacts of As exposure in different periods on susceptibility to allergic asthma. In model 1, dams were administered with NaAsO

Major depression is a serious and chronic mental illness. However, its etiology is poorly understood. Although glial cells have been increasingly implicated in the pathogenesis of depression, the specific role of microglia and astrocytes in stress-induced depression remains unclear. Translocator protein (TSPO) has long been considered a marker of neuroinflammation and microglial activation. However, this protein is also present on astrocytes. Thus, it is necessary to explore the relationships between TSPO, microglia, and astrocytes in the context of depression. In this study, C57BL/6J male mice were subjected to chronic unpredictable stress (CUS) for 5 weeks. Subsequently, sucrose preference and tail suspension tests (TSTs) were performed to assess anhedonia and despair in these mice. [

Background Autosomal trisomy is a relatively rare abnormality observed in AML, occurring singly or as a secondary event in association with other karyotypic changes, and associated with prognosis. The molecular genetic and clinical characterizations of acute myeloid leukemia (AML) with isolated trisomy 4, 11, or 21 have been poorly investigated. Materials and methods Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for 41 chromosomal gene translocations/fusion genes, and next-generation sequencing (NGS) were performed on 29 AML patients with trisomy 4, 11, or 21 as the sole chromosomal anomaly. Results Of the 29 patients, one or more mutations were detected in 93.1% of patients. CEBPA had the highest mutation frequency, followed by TET2, NPM1, DNMT3A, and FLT3-ITD. The sole +11 AML patients exhibited more mutations in FLT3-ITD (P = .031) than the sole +21 AML patients, while CEBPA mutation was more frequently found in the sole +21 AML patients than that in the sole +11 AML patients(P = .07). The median overall survival (OS) and disease-free survival (DFS) for patients with +11 were shorter than those with +4(P = .015, 0.046) or +21 (0.057, 0.064), but no difference was found between +4 patients and +21 patients. In the whole cohort, only the FLT3-ITD mutation was significantly associated with inferior OS (18 vs. 35 months, P = .023) and DFS (12 months vs. NR, P = .046). There were no significant differences in OS and DFS according to the gene mutation status of CEBPA, TET2, NPM1, DNMT3A, and IDH1/2. Conclusion There was a significantly different mutation profile among the sole +4, +11, +21 AML patients. Our research provided new insight into the molecular characteristics of AML with isolated trisomy.

Within the transport model evaluation project (TMEP) of simulations for heavy-ion collisions, the mean-field response is examined here. Specifically, zero-sound propagation is considered for neutron-proton symmetric matter enclosed in a periodic box, at zero temperature and around normal density. The results of several transport codes belonging to two families (BUU-like and QMD-like) are compared among each other and to exact calculations. For BUU-like codes, employing the test particle method, the results depend on the combination of the number of test particles and the spread of the profile functions that weight integration over space. These parameters can be properly adapted to give a good reproduction of the analytical zero-sound features. QMD-like codes, using molecular dynamics methods, are characterized by large damping effects, attributable to the fluctuations inherent in their phase-space representation. Moreover, for a given nuclear effective interaction, they generally lead to slower density oscillations, as compared to BUU-like codes. The latter problem is mitigated in the more recent lattice formulation of some of the QMD codes. The significance of these results for the description of real heavy-ion collisions is discussed.

Benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon, exists widely in automobile emissions and polluted atmosphere. The current study aimed to describe pulmonary inflammation during BaP-induced acute lung injury (ALI). All mice except controls were intratracheally instilled with a single dose of BaP (90 μg per mouse). The alveolar structure was damaged, accompanied by numerous inflammatory cell infiltration around pulmonary interstitium and small airway. Airway wall area and mean linear intercept were reduced in BaP-exposed mouse lungs. By contrast, airway wall thickness and destructive index were elevated in BaP-exposed mouse lungs. Several inflammatory genes, such as Tnf-α, Il-1β, Il-6, Mip-2, Kc, and Mcp-1, were upregulated in mouse lungs. Phosphorylated IκBα was elevated in BaP-exposed mouse lungs. Nuclear translocation of NF-κB p65 and p50 was accordingly observed in BaP-exposed mouse lungs. Several molecules of the MAPK pathway, including JNK, ERK1/2, and p38, were activated in mouse lungs. Of interest, pretreatment with N-acetylcysteine (NAC), an antioxidant, alleviated BaP-induced ALI. Moreover, NAC attenuated BaP-induced inflammatory cell infiltration in mouse lungs and inflammatory gene upregulation in A549 cells. In addition, NAC attenuated BaP-induced NF-κB activation in A549 cells and mouse lungs. These results suggest that NAC alleviates pulmonary inflammatory response during BaP-evoked ALI.

Additional file 1. The experimental protocol.

A steel pipe-rubber friction damper (FRD) is proposed for the purpose of achieving greater cost-efficiency. The theoretical calculation formula of yield load was deduced based on generalized Hooke's law, and in order to investigate the behaviour of the proposed damper quasi-static cyclic tests were carried out on 7 specimens. Besides, a numerical finite element analysis (FEA) was carried out on ten dampers. Furthermore the mechanical property of FRD was proposed. Tests and finite element analysis results show that: Hysteretic curve of the steel pipe-rubber friction damper is slippery. The seismic energy dissipation capability is stable which related to load amplitude rather than loading rate. The results of finite element analysis fit well with the test curve. The differences of yield load between the theoretical value, FEA value and experimental data are small. The simulating hysteretic curve with ideal elastoplastic model is identical to the test data, and it is feasible to adopt the ideal elastoplastic model to simulate the damper element in the analysis of a structure with the steel pipe-rubber friction damper.

Multivariate time-series forecasting plays a crucial role in many real-world applications. It is a challenging problem as one needs to consider both intra-series temporal correlations and inter-series correlations simultaneously. Recently, there have been multiple works trying to capture both correlations, but most, if not all of them only capture temporal correlations in the time domain and resort to pre-defined priors as inter-series relationships. In this paper, we propose Spectral Temporal Graph Neural Network (StemGNN) to further improve the accuracy of multivariate time-series forecasting. StemGNN captures inter-series correlations and temporal dependencies \textit{jointly} in the \textit{spectral domain}. It combines Graph Fourier Transform (GFT) which models inter-series correlations and Discrete Fourier Transform (DFT) which models temporal dependencies in an end-to-end framework. After passing through GFT and DFT, the spectral representations hold clear patterns and can be predicted effectively by convolution and sequential learning modules. Moreover, StemGNN learns inter-series correlations automatically from the data without using pre-defined priors. We conduct extensive experiments on ten real-world datasets to demonstrate the effectiveness of StemGNN. Code is available at https://github.com/microsoft/StemGNN/, Comment: Accepted by NeurIPS 2020. 20 pages, 7 figures

1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 μg/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-β wasn't altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis.

To investigate the mechanisms of anti-apoptosis and immune evasion in drug-resistant leukemia cells mediated by STAT3, further to explore the possible mechanism of leukemia relapse caused by minimal residual.Drug-resistance leukemia cell line was established by transfecting pcDNA3.1-STAT3 into K562 cells (K562/STAT3). The expression of STAT3, BAX and NKG2D ligands (MICA and ULBP1) in K562/-cells, K562/STAT3 were detected by Western blot and/or RQ-PCR. Cells apoptosis and the killing effect of NK cells on leukemia cells were detected by flow cytometry.The expression of the total STAT3, STAT3 phosphorylation in K562/STAT3 was significantly increased, and P-gp mRNA expression was increased also significantly (P0.005). In K562/STAT3 cells, the expression of pro-apoptotic BAX (P=0.005) was significantly lower, and the number of apoptotic cells (P=0.002) induced by adriamycin was significantly decreased as compared with those in K562/- cells. After K562/STAT3 cells were treated by STAT3 inhibitor (SH-4-54), the expression of BAX mRNA (P=0.017) was significantly higher and the number of apoptotic cells (P=0.005) was significantly increased. The MICA and ULBP1 mRNA expression in K562/STAT3 cells was significantly lower than that in K562/- cells, and also for MICA and ULBP1 protein (MICA and ULPB1 mRNA: P0.0001, MICA protein: P=0.001, ULPB1 protein: P=0.022). After K562/STAT3 cells were treated with STAT3 inhibitor (SH-4-54), the expression of MICA mRNA and protein was increased (mRNA: P=0.001, protein: P=0.002), but ULBP1 mRNA and protein showed no significantly change (mRNA: P=0.137, protein: P=0.1905). The cytotoxicity of NK cells to K562/STAT3 cells was susceptible as compared with K562/- (P=0.002), but the cytotoxicity of K562/STAT3 cells to NK cell could be recovered by STAT3 inhibitor (P=0.006).STAT3 phosphorylation can inhibits cell apoptosis and promotes cell immune escape. STAT3 inhibitors can promote the apoptosis of leukemia cells and increase their sensitivity to NK cells.STAT3介导耐药白血病细胞抗凋亡和免疫逃逸机制的研究.研究STAT3在耐药白血病细胞凋亡及免疫逃逸中的作用，并探讨白血病微小残留病引起的白血病复发的可能机制.用pcDNA3.1-STAT3质粒转染K562细胞，建立耐药白血病细胞株K562/STAT3细胞。RQ-PCR和（或）Western blot检测空载质粒转染的对照细胞株K562/-细胞和K562/STAT3细胞中STAT3、BAX以及NKG2D配体的表达。流式细胞术检测K562/-细胞和K562/STAT3细胞的凋亡情况及NK细胞对K562/-细胞和K562/STAT3细胞的杀伤作用.K562/STAT3细胞中总STAT3和STAT3磷酸化水平均明显升高，而且其耐药蛋白P-gp mRNA的表达明显升高（P0.005）。与K562/-细胞相比，K562/STAT3细胞促凋亡基因BAX mRNA的表达水平明显下降（P=0.005），且多柔比星引起的K562/STAT3细胞凋亡明显减少（P=0.002）；用STAT3抑制剂（SH-4-54）处理K562/STAT3细胞后，促凋亡基因BAX mRNA的表达水平明显升高（P=0.017），同时细胞凋亡也明显增加（P=0.005）。与K562/-细胞相比，K562/STAT3细胞NKG2D配体（MICA和ULBP1）mRNA的表达水平明显下降（P0.0001），MICA和ULBP1蛋白的表达水平亦明显下降（MICA：P=0.001，ULBP1：P=0.022）；用STAT3抑制剂（SH-4-54）处理K562/STAT3细胞后，MICA mRNA和蛋白表达水平升高（mRNA：P=0.001，蛋白：P=0.002），但ULBP1 mRNA和蛋白无明显改变（mRNA：P=0.137，蛋白：P=0.1905）。NK细胞对耐药K562/STAT3细胞的杀伤能力较K562/-细胞下降（P=0.002），但是STAT3抑制剂恢复了K562/STAT3细胞对NK细胞的杀伤敏感性（P=0.006）.STAT3磷酸化介导了耐药白血病细胞抗凋亡，降低其对NK细胞的杀伤敏感性。STAT3抑制剂可以促进耐药白血病细胞凋亡并增加其对NK细胞的杀伤敏感性.

With matrine(MAT) as the model drug, to prepare nano graphene oxide(NGO)-based MAT in situ gel(MAT-NGO-gel), a kind of drug for tumor treatment in combination with phototheraphy, and investigate the physicochemical properties and anti-tumor effects in vivo of MAT-NGO-gel. First, HPLC method was established to measure the content of MAT in the gel. The ultrasonic method was used to load MAT onto the surface of NGO, and then poloxamer 188 and poloxamer 407 were chosen as the main materials to prepare MAT-NGO-gel. The optimum prescription was selected with the gelation temperature as the index. Finally, the drug loading rate, micromorphology, phototherrmal conversion characteristics and drug release in vitro of MAT-NGO-gel were characterized. In the optimized prescription, the concentration of poloxamer 188 and poloxamer 407 was 2% and 20% respectively, and the mass ratio of NGO and MAT was 1∶1. The gelation temperature and drug loading rate of MAT-NGO-gel prepared by the optimal prescription process was 37.5 ℃ and 16.7%. Under 808 nm laser irradiation, MAT-NGO-gel showed obvious concentration-and time-dependent photothermal conversion characteristics. In vitro release experiments showed that MAT-NGO-gel had temperature-dependent release characteristics. The pharmacodynamics of MAT solution, NGO-gel and MAT-NGO-gel were studied by using S180 tumor-bearing mice and 808 nm laser. The relative tumor volume and body weight of the tumor-bearing mice were plotted over time. After the experiment, the tumor tissues of each group were taken and the histopathological changes were observed by HE staining. The results of pharmacodynamic studies demonstrated that when compared with NS group and NGO-gel group, the body weights of mice in MAT-NGO-gel group and MAT-NGO-gel + laser group were higher, and the relative tumor volume growth was slower. The results of HE stained pathological sections showed that the tumor cells count for the mice in MAT-NGO-gel group and MAT-NGO-gel + laser group was significantly reduced, with obvious nuclear fragmentation and nucleolysis in these two groups. These results suggested that MAT-NGO-gel, especially combined with 808 nm laser, had stronger anti-tumor activity in vivo. The prescription process of MAT-NGO-gel in this experiment was stable and feasible. As compared with MAT solution, MAT-NGO-gel showed obvious sustained and temperature-dependent drug release characteristics. MAT-NGO-gel had much more obvious anti-tumor activity in vivo when combined with 808 nm laser irradiation. This study could provide certain theoretical basis for the therapy of malignant tumor with multiple mechanisms.

Coronavirus disease 2019 (COVID-19) is a newly emerged infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been pandemic all over the world. This study described acute kidney injury (AKI) at early stage of COVID-19 and its clinical significance. Three-hundred and fifty-five COVID-19 patients with were recruited and clinical data were collected from electronic medical records. Patient’s prognosis was tracked and risk factors of AKI was analyzed. Of 355 COVID-19 patients, common, severe and critical ill cases accounted for 63.1%, 16.9% and 20.0%, respectively. On admission, 56 (15.8%) patients were with AKI. Although AKI was more common in critical ill patients with COVID-19, there was no significant association between oxygenation index and renal functional indices among COVID-19 patients with AKI. By multivariate logistic regression, male, older age and comorbidity with diabetes were three important independent risk factors predicting AKI among COVID-19 patients. Among 56 COVID-19 patients with AKI, 33.9% were died on mean 10.9 day after hospitalization. Fatality rate was obviously higher among COVID-+19 patients with AKI than those without AKI (RR=7.08,P

BackgroundCoronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients.MethodsTwo hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient’s prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed.ResultsOf 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities, including diabetes, hypertension, hepatic disease, cardiac disease, chronic pulmonary disease and others. Among all patients, critical cases, defined as oxygenation index lower than 200, accounted for 26.2%. Severe cases, oxygenation index from 200 to 300, were 29.7%. Besides, common cases, oxygenation index higher than 300, accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT and TBIL, two indexes of hepatic injury, AST, myoglobin and LDH, AST/ALT ratio, several markers of myocardial injury, creatinine, urea nitrogen and uric acid, three indexes of renal injury, were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients.ConclusionOlder age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators. Early hospitalization is of great significance to prevent multiple organ damage and improve the survival of COVID-19 patients.SummaryIn this hospital-based case-cohort study, we found that serum urea nitrogen, TBIL, LDH and AST/ALT ratio, several markers of extrapulmonary organ injuries, were positively correlated with death risk of COVID-19 patients. We provide evidence for the first time that multiple organ damage on admission influences the prognosis of COVID-19 patients. Early hospitalization is beneficial for elevating the survival rate of COVID-19 patients especially critical ill patients.

To investigate the mutation of RUNX1 gene in patients with myelodysplastic syndrome (MDS) and its correlation with other gene mutations and some clinical parameters.The mutations of RUNX1, DNMT3A, TET2, IDH1/2, NPM1, FLT3-ITD and C-KIT in 170 patients with MDS were detected by direct and indirect sequencing of genomic DNA-PCR amplification products.The RUNX1 mutation was found in 23 patients (13.5 %, 23/170). Among the 170 patients, other most frequent mutation was TET2 (11.2%, 19/170), followed by mutations in DNMT3A (9.4%, 16/170), NPM1 (8.2%, 14/170), IDH2 (4.1%, 7/170)、FLT3-ITD (2.9%, 5/170), IDH1 (1.7%, 3/170) and c-KIT (0.58%, 1/170). The most common coexisting mutations were TET2 (5/23). The RUNX1-mutated group showed significantly higher leukocyte levels, higher percentages of blast cells, higher incidences of leukemia transformation and lower platelet counts in comparison with RUNX1 non-mutation group (P＜0.05). whereas there were no statistically significant difference in age, MDS subtype, karyotype and hemoglobin level between 2 groups (P＞0.05). Seventeen patients harboring RUNX1 mutations were followed up and almost 47.05% (8/17) of the patients progressed into acute myeloid leukemia (AML). The rates of transformation into AML in ASXL1-mutation group was significantly higher than that in ASXLL- non-mutation group (47.05% vs 11.7%) (P=0.001).The incidence of RUNX1 mutation is high in MDS patients. The RUNX1-mutated patients have higher leukocyte level, higher percentages of blast cells, higher incidences of leukemia transformation and lower platelet count.骨髓增生异常综合症患者RUNX1基因突变分析.探讨骨髓增生异常综合症（MDS）患者中RUNX1基因突变情况，以及与其他基因突变和部分临床参数间的相关性.采用基因组DNA-PCR扩增产物直接测序法检测170例MDS患者中RUNX1、DNMT3A、TET2、IDH1/2、NPM1、FLT3-ITD、C-KIT突变情况.170例患者中RUNX1基因突变检测率为13.5%（23/170），其他基因突变率依次为：TET2（11.2%，19/170）、DNMT3A（9.4%，16/170）、NPM1（8.2%， 14/170）、IDH2（4.1%，7/170）、FLT3-ITD（2.9%，5/170）、IDH1（1.7%，3/170）、c-KIT（0.58%，1/170）。最常见的RUNX1突变共存基因为TET2（5/23）。RUNX1突变组与未突变组患者相比，具有更高的外周白细胞水平及更低的血小板水平，差异均具有统计学意义（P＜0.05）；但在中位年龄、MDS亚型、染色体核型、血红蛋白水平等方面2组间均无统计学差异。对17例RUNX1突变患者及111例未突变患者进行了有效随访，其中8例RUNX1突变的MDS患者进展为急性髓系白血病（AML），白血病转化率为47.05%（8/17），13例RUNX1未突变的MDS患者进展为AML，白血病转化率为11.7%（13/111），差异有统计学意义（P=0.001）.RUNX1突变在MDS患者中有较高的发生率，伴有该突变的MDS患者具有更高白细胞水平、更低的血小板水平、更高的骨髓原始细胞比例及白血病转化率.

Additional file 12: Table S9. The efficacy of KNN, LR, SVM, DT, MLP and XGboost in the training set of top 5 ranked features.

Background: Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely epidemi

Additional file 16: Table S11. The efficacy of KNN, LR, SVM, DT, MLP and XGboost in the test set of 5 clinical features.

Additional file 13: Table S10. The efficacy of KNN, LR, SVM, DT, MLP and XGboost in the test set of 9 SNPs features.

Additional file 4: Table S4. The sequence of 101 SNPs and their primers in multiplex PCR.

Additional file 1: Table S1. The Chinese COPD studies with basic information in international journals.

Additional file 10: Table S8. The efficacy of KNN, LR, SVM, DT, MLP and XGboost in the training set of 5 Clinical features.

Additional file 2: Table S2. Demographics of COPD patients and control subjectsin the training set.