CT-based staging and prognosis of novel coronavirus (COVID-19) pneumonia: correlation with blood glucose levels.

OBJECTIVE: Based on the latest epidemic situation and field experience, this study aims to explore the correlation of computed tomography (CT) stages and blood glucose level in patients with novel coronavirus pneumonia (COVID-19). PATIENTS AND METHODS: The clinical data of first and multiple CT imaging re-examination and blood glucose levels from 62 confirmed cases of COVID-19 were collected for a retrospective analysis to determine the correlation between glucose level and CT-based staging. RESULTS: Of the 62 COVID-19 patients, 48 cases of early stage and 14 cases of advanced stage were found in the CT data of the first diagnosis. These 62 cases were currently under follow-up (17-32 days): 18 cases in early stage-resorption stage, 25 cases in early stage-advanced stage-resorption stage, 12 cases in advanced stage-resorption stage, 5 cases in early stage -advanced stage-severe stage-resorption stage, and 2 cases in advanced stage-severe stage-resorption stage. Among them, the CT of 14 patients with advanced stage at the first diagnosis showed multiple stage lesions (advanced stage + early stage) at the same time. Patients presented with statistically significant changes in blood glucose at early stage-resorption stage, early stage-advanced stage-resorption stage, advanced stage-resorption stage, and early stage-advanced stage-severe stage-resorption stage (p<0.05). However, no statistically significant alterations were observed in the glucose level of patients with advanced stage-severe stage-resorption stage (p>0.05). CONCLUSIONS: Alteration of blood glucose is positively correlated with CT-based staging of COVID-19. Blood glucose is of great value in clinical diagnosis of COVID-19 and in determining the stage and prognosis of this disease.

The value of Gd-BOPTA- enhanced MRIs and DWI in the diagnosis of intrahepatic mass-forming cholangiocarcinoma.

The aim of this study is to explore the value of unenhanced magnetic resonance imaging (MRI), gadobenate dimeglumine injection (Gd-BOPTA)-enhanced MRI and diffusion-weighted imaging (DWI) in the diagnosis of intrahepatic mass-forming cholangiocarcinoma (IMCC). Totally 59 IMCC patients who underwent Gd-BOPTA-enhanced MRIs were recruited. The time-signal intensity curves and lesion periphery enhancement rates of the IMCC and liver parenchyma was drawn using apparent diffusion coefficient (ADC) values. The Gd-BOPTA-enhanced MRI showed that the peripheries of 30 lesions in the arterial phase exhibited irregular ring enhancement. However, lesions in the portal and delayed phases (which were gradually filled with a contrast agent), presented a patchy or latticed enhancement. Twenty-two lesions in the arterial and delayed phases exhibited uneven mild/moderate patchy enhancements with a progressive and centripetal lesion. Five lesions emerged from the arterial phase without any significant enhancement and had only gradual enhancement during the delayed phase. The remaining 2 lesions had a decreased mild enhancement, presented comparatively high signals and the lesion center had visible small spotted low signals. The DWI signals displayed a slightly high or high unevenness. Some lesion peripheries had a high signal but lesion centers displayed a relatively low or slightly low signal and irregular patches. There were significant differences between the ADC values of the lesion edge, lesion center and liver parenchyma. The IMCC detection rates of the Gd-BOPTA-enhanced MRI and DWI were higher than those of the unenhanced MRI. Our study demonstrated that both the Gd-BOPTA-enhanced MRI and DWI had higher accuracies rates than an unenhanced MRI. Furthermore, the hepatobiliary phase of IMCC plays an important role in the diagnosis and identification of IMCC constituents.

Gilbert damping in CoFeB/GaAs(001) film with enhanced in-plane uniaxial magnetic anisotropy.

A 3.5 nm amorphous CoFeB film was sputtered on GaAs (001) wafer substrate without applying magnetic field during deposition, and a significant in-plane uniaxial magnetic anisotropy (UMA) field (Hu) of about 300 Oe could be achieved. To precisely determine the intrinsic Gilbert damping constant (α) of this film, both ferromagnetic resonance (FMR) and time-resolved magneto-optical Kerr effect (TRMOKE) techniques were utilized. With good fitting of the dynamic spectra of FMR and TRMOKE, α is calculated to be 0.010 and 0.013, respectively. Obviously, the latter is 30% larger than the former, which is due to the transient heating effect during the TRMOKE measurement. In comparison with ordinary amorphous CoFeB films with negligible magnetic anisotropies, α is enhanced significantly in the CoFeB/GaAs(001) film, which may be mainly resulted from the enhanced spin-orbit coupling induced by the CoFeB/GaAs interface. However, the significant in-plane UMA plays minor role in the enhancement of α.

Depinning of domain walls in permalloy nanowires with asymmetric notches.

Effective control of the domain wall (DW) motion along the magnetic nanowires is of great importance for fundamental research and potential application in spintronic devices. In this work, a series of permalloy nanowires with an asymmetric notch in the middle were fabricated with only varying the width (d) of the right arm from 200 nm to 1000 nm. The detailed pinning and depinning processes of DWs in these nanowires have been studied by using focused magneto-optic Kerr effect (FMOKE) magnetometer, magnetic force microscopy (MFM) and micromagnetic simulation. The experimental results unambiguously exhibit the presence of a DW pinned at the notch in a typical sample with d equal to 500 nm. At a certain range of 200 nm < d < 500 nm, both the experimental and simulated results show that the DW can maintain or change its chirality randomly during passing through the notch, resulting in two DW depinning fields. Those two depinning fields have opposite d dependences, which may be originated from different potential well/barrier generated by the asymmetric notch with varying d.

The PPARalpha ligand fenofibrate: meeting multiple targets in diabetic nephropathy.

Fibrate peroxisome proliferator-activated receptor (PPAR)-alpha ligands are mainly used as hypolipidemic drugs. But this commentary highlights their potential in treating insulin resistance, dyslipidemia, and hypertension and in preventing diabetic nephropathy, inflammation, and cardiovascular disease. Because diabetes is a major contributor to chronic kidney disease and cardiovascular disease, PPAR-alpha agonists may provide greater opportunities for hitting multiple targets in this complex metabolic disease.

Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10.

Cytokines are important mediators of inflammatory and proliferative responses in disease states including atherosclerosis. Genetic variations in cytokine production could potentially influence the outcome of these responses. The aim of this study was to determine whether cytokine gene polymorphism might influence the development of atherosclerotic renal artery stenosis. Sixty-six patients with atherosclerotic renal artery stenosis and 100 normal healthy individuals were genotyped for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-2 promoter region polymorphism. TNF-a, TNF-d, and IL-10 microsatellite polymorphisms were also analyzed. The frequency of the anti-inflammatory cytokine IL-10 promoter (-1082 A positive) GA and AA genotypes which are associated with low production were higher in the patient group when compared to the control group. The AA-TT-AA homozygous genotype combination of three single-nucleotide polymorphisms at -1082, -819, and -592 in the IL-10 gene was also observed at a higher frequency in the patient group compared to the controls. The frequency of TNF-alpha, IL-6, and IL-2 polymorphisms did not show any significant difference between the patient and control groups. To correlate IL-10 genotypes with differences in IL-10 protein expression, in vitro mRNA and protein levels were analyzed in lipopolysaccharide-stimulated peripheral blood mononuclear cells from 22 patients with renal artery stenosis and 33 controls. Individuals genotyped as A positive at position -1082 produced lower levels of IL-10 protein and had lower copy numbers of mRNA when compared to individuals genotyped as A negative in both patient and control groups. The increased frequency of the low producer IL-10 promoter, -1082 A-positive genotype in patients with renal artery stenosis, suggests that IL-10 may protect against the development of atherosclerotic renovascular disease.

Regulation of lipoprotein trafficking in the kidney: role of inflammatory mediators and transcription factors.

Inflammation and dyslipidaemia both play important roles in the development of glomerular atherosclerosis in renal diseases. We have demonstrated that inflammatory mediators induced Scr (scavenger receptor) expression and the formation of foam cells, and that AP-1 (activator protein 1)/ets were necessary transcriptional factors for Scr induction in HMCs (human kidney mesangial cells). Most cells are protected from excessive native LDL (low-density lipoprotein) accumulation by tight feedback regulation of the LDLr (LDL receptor). However, we observed that HMCs formed foam cells via the LDLr pathway when incubated with IL-1beta (interleukin-1beta; 5 ng/ml) and unmodified LDL (200 microg/ml), suggesting that inflammatory mediators may disrupt the cholesterol-mediated feedback regulation. This feedback involves cholesterol-mediated down-regulation of LDLr controlled by SCAP [SREBP (sterol responsive element-binding protein) cleavage-activating protein]. We have also demonstrated that both tumour necrosis factor alpha and IL-1beta increased nuclear SREBP-1 levels by increasing SCAP mRNA expression, even in the presence of a high concentration of LDL. Since intracellular lipid content is governed by both influx and efflux mechanisms, we set out to examine the impact of inflammatory cytokines on cholesterol efflux, a process mediated by the protein ABCA1 (ATP binding cassette A1). IL-1beta inhibited [(3)H]cholesterol efflux from HMCs by inhibition of the peroxisome-proliferator-activated receptor/LXR (liver X receptor)/ABCA1 pathway. Taken together, our results suggest that inflammatory mediators increase lipid accumulation in HMCs not only by promoting increased lipoprotein uptake by Scr and LDLr, but also by inhibiting ABCA1-mediated cholesterol efflux to high-density lipoprotein.

Effects of L-arginine on the proliferation of human renal mesangial cells and production of extracellular matrix.

AIM: To investigate the effect of L-arginine (L-arg) on the proliferation of human mesangial cells and production of collagen. METHODS: The influence of L-arg on the cell proliferation was determined by MTT assay, immunocytochemical detection of expression of proliferative cell nuclear antigen (PCNA), and flow cytometrical analysis of cell cycle. Procollagen III and total collagen level in the supernatant and expression of collagen IV mRNA in human mesangial cells were determined by radioimmunoassay, hydroxyproline colorimetric assay, and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: L-Arg induced inhibition of human mesangial cell lines (HMCL) in a concentration- and time-dependent manner. Immunocytochemical study for PCNA showed the number of cells was decreased, though the percentage of PCNA positive cells was increased in L-arg-treated group. Flow cytometrical analysis showed that cells in S and G2/-M phases were markedly increased in L-arg-treated group compared with those in control group. Furthermore, L-arg significantly inhibited the production of procollagen III and total collagen in the supernatants determined by radioimmunoassay and hydroxyproline colorimetric assay (P < 0.05 and 0.01, respectively) and inhibited the expression of collagen IV mRNA determined by RT-PCR (P < 0.01). CONCLUSION: L-arg could exert an inhibitory effect on the proliferation of human mesangial cells and production of extracellular components, which strongly suggested its potential therapeutic role in the chronic renal scarring.

Dysregulation of LDL receptor under the influence of inflammatory cytokines: a new pathway for foam cell formation.

BACKGROUND: Lipid-mediated renal injury is an important component of glomerulosclerosis and its similarity to atherosclerosis is well described. This study focused on the relationship between lipid-mediated injury and inflammation by examining the role of inflammatory cytokines in the regulation of human mesangial cell low-density lipoprotein (LDL) receptors. METHODS: A human mesangial cell line (HMCL) was used to study the effects of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on the regulation of LDL receptor mRNA and protein in the presence of a high concentration of native LDL (250 microg/mL). RESULTS: Native LDL caused foam cell formation in HMCL in the presence of antioxidants, TNF-alpha and IL-1beta. Both cytokines overrode LDL receptor suppression induced by a high concentration of LDL and increased LDL uptake by enhancing receptor expression. These cytokines also caused increased expression of SCAP [sterol responsive element binding protein (SREBP) cleavage activation protein], and an increase in the nuclear translocation of SREBP, which induces LDL receptor expression. CONCLUSION: These observations demonstrate that inflammatory cytokines can modify cholesterol-mediated LDL receptor regulation in mesangial cells, permitting unregulated intracellular accumulation of unmodified LDL and causing foam cell formation. These findings suggest that inflammatory cytokines contribute to lipid-mediated renal damage, and also may have wider implications for the study of inflammation in the atherosclerotic process.

Human mesangial cells express inducible macrophage scavenger receptor.

BACKGROUND: Type A scavenger receptors (Scr) mediate the uptake of modified low-density lipoproteins by macrophages. The accumulation of lipids via this process is thought to lead to foam cell formation in atherosclerotic plaques. Human mesangial cells (HMCs) have not been previously shown to express Scr in normal culture. We therefore investigated whether there is an inducible form of Scr in a human mesangial cell line (HMCL). METHODS: Scr activity was analyzed by cellular uptake of fluorescently labeled acetylated low-density lipoprotein using a flow cytometer. Scr mRNA expression was examined using reverse transcription-polymerase chain reaction, followed by Southern blotting. To investigate the molecular mechanism of Scr expression, several reporter gene constructs were designed. The first contained a full Scr promoter, the second a part of the Scr promoter that has both AP-1 and ets transcription factor binding sites. Other constructs were identical to the second, except that they contained either AP-1 or ets motif mutations. RESULTS: Phorbol 12-Myristate 13-acetate (PMA) and angiotensin II (Ang II) increased both the percentage of Scr-positive cells and the Scr mean fluorescence intensity. PMA and Ang II also increased Scr mRNA and promoter activity in a time- and dose-responsive manner. Protein kinase C and calmodulin transduction pathways were involved in Scr up-regulation induced by PMA and Ang II. Additionally, a serine/threonine kinase was involved in PMA stimulation. Functional analysis showed that both AP-1 and ets motifs were specific response elements to PMA stimulation in HMCLs. CONCLUSIONS: This study suggests that HMCs may express an inducible Scr, by which cells can acquire lipids and convert to foam cells in developing glomerulosclerosis.

Human mesangial cells express inducible macrophage scavenger receptor: an Ap-1 and ets mediated response.

BACKGROUND: Type A scavenger (SR) mediate the uptake of modified low-density lipoproteins by macrophages. The accumulation of lipid via this process is thought to lead to foam cell formation in atherosclerotic plaques. Human mesangial cells (HMC), which can be converted to foam cells in vivo, have not previously been shown to express SR in normal culture. We investigated whether or not there was an inducible form of SR in a human mesangial cell line (HMCL). METHODS: SR activity was analyzed by cellular uptake of fluorescently labeled acetylated low-density lipoprotein using a flow cytometer. SR mRNA expression was examined using RT-PCR followed by Southern blotting. To investigate the molecular mechanism of SR expression, several reporter gene constructs were designed. The first contained a full SR promoter, the second a part of the SR promoter that has both activated protein-1 (AP-1) and ets transcriptional factor binding sites. Other constructs were identical to the second except they contained either AP-1 or ets motif mutations. RESULTS: Phorbol 12-myristate 13-acetate (PMA) increased both the percentage of SR positive cells and SR mean fluorescence intensity. PMA also increased SR mRNA and promoter activity in a time and dose responsive manner. Function analysis showed that both AP-1 and ets motifs were specific response elements to PMA stimulation in HMCL. CONCLUSIONS: The present study suggests that the combination of interaction between AP-1 and ets transcriptional factors may mediate the inducible expression of the SR gene in HMCL, which may contribute to foam cell formation.

LDL receptor gene expression in human mesangial cells under the influence of calcium channel blockers.

BACKGROUND: Intracellular transport of lipid through the regulation of LDL receptor (LDLr) may be important in the progression of renal dysfunction. METHODS: We explored LDLr gene expression in human mesangial cell line (HMCL) under influence of calcium channel blockers using cell proliferation, LDL binding, Northern blot and LDLr promoter activity assay. RESULTS: Diltiazem and verapamil increased the expression of LDLr mRNA in a dose-dependent manner. Increased LDLr mRNA paralleled LDL binding. Nifedipine did not increase the expression of LDLr mRNA and LDL binding to HMCL at 1 - 100 micromol/l. The LDLr promoter activity assay showed that treatment with 100 micromol/ of diltiazem and verapamil increased LDLr promoter activity by 126.72 +/- 10.68%, and 166.41 +/- 11.41%, respectively, at 24 hours (control as 100%), while treatment with 100 micromol/l of nifedipine had an inhibitory effect on LDLr promoter activity. High concentration of LDL (250 microg/ml) inhibited promoter activity. Diltiazem or verapamil coincubated with LDL (250 microg/ml) could not override transcriptional inhibition by LDL. CCBs inhibited the proliferation of HMCL, therefore, CCBs-induced LDLr expression did not depend on a proliferative response. Signal transduction pathway experiments showed that the calmodulin transduction pathway was involved in LDLr upregulation induced by diltiazem or verapamil. Additionally, tyrosine kinase and PKC pathways were involved in the induction of LDLr induced by verapamil. CONCLUSION: These studies show that diltiazem and verapamil increase LDLr gene transcription and expression which is independent of cell proliferation in HMCL.

Cytokine regulation of low-density lipoprotein receptor gene transcription in human mesangial cells.

BACKGROUND: The intracellular transport of lipids through regulation of the LDL receptor (LDLr) may be important in the progression of renal dysfunction. The present study was undertaken to investigate whether cytokines have any major effects on LDLr regulation and lipid-mediated glomerular injury in human mesangial cells (HMC). METHODS: We explored the effects of 50 ng/ml of tumour necrosis factor alpha (TNF alpha), 5 ng/ml of transforming growth factor beta (TGF beta), platelet-derived growth factor (PDGF), and interleukin-1beta (IL-1beta) on the regulation of LDLr gene transcription in a human mesangial cell line (HMCL) using cell proliferation, LDL binding, northern blot and LDLr promoter activity assays. RESULTS: TNF alpha, TGF beta, PDGF or IL-1beta did not significantly stimulate HMCL proliferation at the concentrations given above, but maximally stimulated LDLr mRNA expression and increased LDLr promoter activity by 167.48+/-23.56%, 150.47+/-24.41%, 127.71+/-24.65% and 163.01+/-31.91% respectively, at 24 h. An increased LDL binding was observed in parallel with increased LDLr mRNA. The tyrosine kinase transduction pathway was involved in LDLr upregulation induced by all four cytokines. Additionally, TGF beta involved serine/threonine kinase and G-protein pathways, and IL-1beta involved calmodulin, serine/threonine kinase and PKC pathways in upregulating LDLr. A high concentration of LDL (250 microg/ml) inhibited promoter activity, but TNF alpha, TGF beta, PDGF and IL-1beta co-incubated with LDL could override transcriptional inhibition by LDL. CONCLUSION: TNF alpha, TGF beta, PDGF and IL-1beta increased LDLr gene expression by increasing sterol-independent and mitogenesis-independent gene transcription. This process may contribute to lipid deposition and foam cell formation in HMC.

Changes of thyroid hormone levels in epileptic patients.

We measured serum T3, T4, FT3, FT4 and thyrotropin (TSH) by radioimmunoassay in 150 patients with epilepsy. Of the 150 epileptic patients, 120 cases received single antiepileptic drug, including Sod valproate (VPA), carbamazepine (CBZ), phenytoin (PHT), or MixtBrodsky (MB). Each subgroup consisted of 30 cases. The other 30 were untreated epileptics. The results suggested that there was no significant difference in serum thyroid hormone levels among healthy control group, untreated group, and hepatic non-enzyme-inducing anticonvulsant group (P < 0.05). As compared with the three groups mentioned above, the serum T3, T4, FT3, FT4 concentrations of the enzyme inducer groups were decreased, however, significant decrease was found in PHT group and CBZ group (P < 0.05, P < 0.005). All 12 patients with circulating thyroid hormone concentrations below normal reference values were given enzyme inducer. None of them revealed any clinical manifestation of hypothyroidism. There was no significant difference in serum TSH level among the above 6 groups (P < 0.05), and the serum TSH level of all patients was within normal reference limits. Our study showed that the changes of thyroid hormone in epileptics were due to the effect of some AEDs and not the disease itself. The disparity between the effect of enzyme inducer and that of non-enzyme-inducing anticonvulsants indicated that the hepatic microsomal enzyme system metabolizing thyroid hormone to be induced was the main mechanism for decreased serum thyroid hormone concentrations. Though the serum thyroid hormone levels of the enzyme inducer groups were decreased, no significant increase of the mean serum TSH concentration was found. This implies that AEDs may interfere the HPA function in some way.

Scanning electron microscopic observation on the surface ultrastructure of leucocytes in CSF.

Using scanning electron microscope (SEM), The CSF leucocytes from 3 healthy subjects and 12 patients with various NS diseases were observed. The findings were used to compare with those by optical microscope (OM) and those of human peripheral blood cells by SEM. Five types of CSF cells with particular surface structures, are emphasized in relation to both optical microscopic findings and the involved diseases.