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Objective:To investigate the application of endothelial glycocalyx degradation products in assessing the severity of pulmonary edema in patients with acute respiratory distress syndrome (ARDS).Methods:A prospective study was conducted to select patients diagnosed with ARDS at Wuxi People's Hospital from July 1, 2018 to December 31, 2019. The extravascular lung water index (EVLWI) was recorded within 2 h after admission by continuous cardiac output with pulse indicator. The indexes of glycocalyx degradation products syndecan-1 (SDC-1), heparan sulfate (HS), hyaluronic acid (HA) and the concentrations of inflammatory factors [blood tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-10] were measured by enzyme-linked immunosorbent assay. Pearson correlation method was adopted to analyze the correlation of glycocalyx degradation products with EVLWI and inflammatory factors in ARDS patients. The patients were divided into the mild pulmonary edema group and severe pulmonary edema group according to EVLWI at the cut-off value of 10 mL/kg, and the differences of glycocalyx degradation products and inflammatory factors between the two groups were compared. Receiver operating characteristic (ROC) curve of the subjects were plotted to analyze the value of glycocalyx degradation products in determining the severity of pulmonary edema.Results:A total of 85 ARDS patients were enrolled. Pearson correlation analysis showed that SDC-1, HS, and HA were all positively correlated with IL-6, TNF-α, EVLWI (all P<0.05), but did not correlate with IL-10 (all P>0.05). Comparison of indicators between the mild pulmonary edema group (39 cases) and the severe pulmonary edema group (46 cases) showed that: IL-6[(33.63±3.43) ng/L vs. (39.99±4.64) ng/L], TNF-α[(43.38±6.05) ng/L vs. (50.79±7.35) ng/L], SDC-1[(494.13±47.23) ng/L vs. (563.50±56.36) ng/L], HS[(114.02±18.39) ng/mL vs. (138.93±17.02) ng/mL], and HA[(441.44±62.52) ng/mL vs. (546.23±85.24) ng/mL] were statistically different between the two groups(all P<0.05). Whereas, IL-10 [(24.37±10.11) ng/L vs. (28.75±11.98) ng/L] was not statistically different between the two groups ( P>0.05). ROC curve analysis showed that the combined prediction of SDC-1, HA and HS indicators was superior to the single indicator. The area under the ROC curve combining the three indicators was 0.928 (95% CI: 0.872-1.000), with a sensitivity and specificity of 87.5% and 86.7%, respectively. Conclusions:There is a positive correlation between glycocalyx degradation products SDC-1, HS, HA and EVLWI in ARDS patients. The application of these three glycocalyx degradation products can be used as a reliable indicators for judging the severity of pulmonary edema in ARDS patients.
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Ovarian cancer is characterized by insidious onset and poor prognosis, and among gynecological malignancies, its mortality rate ranks first, which poses a serious threat to women's health worldwide. In recent years, increasing evidence has suggested that modifiable lifestyle factors, particularly dietary factors, played important roles in the prognosis of ovarian cancer. As important nutrients, dietary fats and fatty acids can affect various vital physiological functions in human beings. However, the association of dietary fat and fatty acid intake with the prognosis of ovarian cancer remains unclear. Therefore, this review aims to analyze the existing epidemiological evidence between the two variables by searching the literature to provide dietary suggestions for ovarian cancer patients.
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In this study, alkali-soluble polysaccharide was extracted from Poria residue, and the structure of alkali-soluble polysaccharide was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The physical morphology of alkali-soluble polysaccharide and ethyl cellulose (EC) was investigated by scanning electron microscopy (SEM), and the focus on angle of repose, bulk density, tapped density, Carr index, interparticle porosity, cohesion index, Hausner ratio, etc. The physical fingerprints were drawn, and the powder properties were evaluated by multivariate analysis. Diclofenac sodium extended-release tablets were prepared by direct compression method using alkali-soluble polysaccharide and EC as insoluble backbone materials to evaluate the basic properties of the extended-release tablets, investigate the in vitro drug release behavior and study the release mechanism. The results showed that alkali-soluble polysaccharide is a semi-crystalline polymer with smooth lamellar structure, and its stacking and compressibility are stronger than EC. The in vitro release experiments showed that the slow release performance of alkali-soluble polysaccharide is stronger than EC, and the release behavior of the prepared slow release tablets is in accordance with the Higuchi model. The pore structure is formed inside the tablets during the release process, and the release mode is pore diffusion release. The results of this study are of great significance for the development of new slow-release materials and the rational use of resources.
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Anthocyanidin reductase (ANR) is one of the key enzyme in the flavonoid biosynthetic pathway, and its catalytic activity is important for the synthesis of plant anthocyanin. In this study, specific primers were designed according to the transcriptome data of Lonicera japonica Thunb., and the CDS, gDNA and promoter sequences of ANR genes from Lonicera japonica Thunb. and Lonicera japonica Thunb. var. chinensis (Wats.) Bak. were cloned. The results showed that the CDS sequences of LjANR and rLjANR were 1 002 bp, the gDNA sequences were 2 017 and 2 026 bp respectively, and the promoter sequences were 1 170 and 1 164 bp respectively. LjANR and rLjANR both contain 6 exons and 5 introns, which have the same length of exons and large differences in introns. The promoter sequences both contain a large number of light response, hormone response and abiotic stress response elements. Bioinformatics analysis showed that both LjANR and rLjANR encoded 333 amino acids and were predicted to be stable hydrophobic proteins without transmembrane segments and signal peptides. The secondary structures of LjANR and rLjANR were predicted to be mainly consisted of α-helix and random coil. Sequence alignment and phylogenetic analysis showed that LjANR and rLjANR had high homology with Actinidia chinensis var. chinensis, Camellia sinensis and Camellia oleifera, and were closely related to them. The expression levels of LjANR and rLjANR were the highest in flower buds and the lowest in roots. The expression patterns at different flowering stages were similar, with higher expression levels in S1 and S2 stages and then gradually decreased until reaching the lowest level in S4 stage, after a slow increase in S5 stage, the expression levels decreased again. The expression levels of ANR genes in the two varieties showed significant differences in roots, S2 and S5 stages, while the differences in stems, flower buds, S1, S3 and S6 stages were extremely significant. The prokaryotic expression vector pET-32a-LjANR was constructed for protein expression. The target protein was successfully expressed of about 59 kD. This study lays a foundation for further study on the function of ANR gene and provides theoretical guidance for breeding new varieties of Lonicera japonica Thunb.
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Social isolation represents the development of a certain level, either partial or complete, of deprivation of socialization and may have adverse effects in many aspects for the elderly, which can be physiological, psychological and social.Meanwhile, during the course of human life, aging becomes an inevitable process and brings about changes in cognitive ability, which become an important focus of our attention.This paper reviews the research progress on the relationship between social isolation and cognitive ability in the elderly, in order to provide a new perspective for future research on social isolation and cognitive ability in the elderly and also to offer new insight on how to construct a model of intervention and health management for the elderly population with social isolation.
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Objective:To assess the long-term follow-up results of intensity-modulated radiotherapy (IMRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitor (TKI) in patients with hepatocellular carcinoma (HCC) showing macrovascular invasion (MVI).Methods:A retrospective analysis was conducted for 63 patients with HCC showing MVI without distant metastasis treated in Peking University Cancer Hospital from October 2015 to October 2018. Among them 28 patients were treated with IMRT combined with TACE and sorafenib (Group A) and 35 patients were treated with IMRT combined with TACE (Group B). Propensity score matching (PSM) was applied to assess the progression-free survival (PFS) and the overall survival (OS) of both groups.Results:The median follow-up time was 62 months. Before PSM, the median OS of group A and B were 19.0 months and 15.2 months ( χ2=3.15, P=0.076), respectively, and the median PFS of groups A (10.7 months) was longer than that of group B (8.6 months; χ2=3.99, P=0.046). After PSM, the median OS of group A (30.6 months) was significantly longer than that of group B (15.2 months; χ2=5.34, P=0.023), and the PFS of groups A (12.5 months) was still longer than that of group B (8.3 months; χ2=4.79, P=0.026). In the whole group, 10 patients (15.9%) suffered from grade-3 hematologic toxicity, and seven patients (11.1%) experienced grade-3 hepatic toxicity. The incidence of skin reactions, hand-foot syndrome, and diarrhea in group A was higher than that in group B, but all these adverse events were grade 1-2. Moreover, no grade-4 adverse events, radiation-induced liver disease, and treatment-related mortality occurred in both groups. Conclusions:As demonstrated by the long-term follow-up result, IMRT combined with TACE and TKI could improve both the PFS and the OS of patients with HCC showing MVI after PSM.
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Objective:To investigate the influence of bacterial outer membrane vesicles (OMVs) tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer. Methods:The experimental study was conducted. The ovalbumin (OVA) lentivirus vector plasmid pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro was used to construct the mouse pancreatic cancer Pan02-OVA cells. The ClyA-Catchers-OMVs (CC-OMVs) originated from Escherichia coli and labeled antigenic peptide SpyTag-OVA were used to construct the OMVs tumor vaccine. Mouse CD8 + T cells were stimulated by OMVs tumor vaccine, and the effects of OMVs tumor vaccine on inhibiting pancreatic cancer cells proliferation and stimulating CD8 + T cell infiltration were analy-zed by in vitro cell killing assay, including the OMVs tumor vaccine stimulated T cell group and the control T cell group, subcutaneous pancreatic cancer model, including the OMVs tumor vaccine group and the control group, and immunohistochemical staining. Observation indicators: (1) identification of mouse pancreatic cancer Pan02-OVA cells; (2) morphological observation of CC-OMVs; (3) inhibi-tion of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells; (4) inhibi-tion of mouse pancreatic cancer by OMVs tumor vaccine; (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages. Results:(1) Identification of mouse pancreatic cancer Pan02-OVA cells. Results of laser scanning confocal microscopy showed that the mNeongreen fluorescence was expressed in Pan02-OVA cells infected with the OVA lentivirus vector plasmid of pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro. Results of Flow cytometry showed that using the mouse pancreatic cancer Pan02 cells as references, the protein expression rate of Flag on the Pan02-OVA cells was 90.7%. (2) Morphological observation of CC-OMVs. Results of transmission electron microscopy analysis showed that the CC-OMVs were in spherical shape, with a diameter <50 nm. (3) Inhibition of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells. Results of cell proliferation toxicity test showed that the absorbance at 450 nm of mouse pancreatic cancer Pan02-OVA cells was 0.41±0.12 and 1.05±0.15 in the OMVs tumor vaccine-stimulated T cell group and the control T cell group, respectively, showing a significant difference between the two groups ( t=9.54, P<0.05). (4) Inhibition of mouse pancreatic cancer by OMVs tumor vaccine. The weight of subcutaneous tumor tissue in the back of mouse was (81±10)g and (153±17)g in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.26, P<0.05). (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Results of immuno-histochemical staining showed that the numbers of CD8 + T cells staining in the mouse back subcu-taneous tumor tissues was 28.7±3.5 and 9.3±1.5 in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.74, P<0.05). Conclusion:Bacterial OMVs tumor vaccine can inhibit proliferation of pancreatic cancer cells and increase the numbers of CD8 + T cells infiltrated in pancreatic cancer tissue of mouse.
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Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).
Subject(s)
Atractylodes/chemistry , Drugs, Chinese Herbal/chemistry , Rhizome/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Sterol Regulatory Element Binding Proteins/antagonists & inhibitorsABSTRACT
8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
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Dimethylallyltranstransferase/metabolism , Flavonoids/metabolism , Molecular Docking Simulation , Prenylation , Saccharomyces cerevisiae/metabolism , Sophora/metabolismABSTRACT
Objective: To investigate the clinical phenotype, treatment and prevention of Van der Hoeve syndrome, and analyze the variation characteristics of its related gene COL1A1. Methods: Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People's Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed. The variation of the COL1A1 gene and return visits to traceable patients and families were summarized, the disease progress and clinical treatment effects were analyzed, and the prevention strategies were discussed. Results: A total of 7 patients with COL1A1 gene mutation underwent clinical intervention. The mutation sites were c.1342A>T (p.Lys448*), c.124C>T (p.Gln42*), c.249insG(p.Ala84*), c.668insC(p.Gly224*), c.2829+1G>C, c.1081C>T (p.Arg361*), c.1792C>T (p.Arg598*), of which c.1081C>T and c.1792C>T had been previously reported, and the remaining 5 were novo mutations that have not been reported. All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance. Conclusions: Van der Hoeve syndrome belongs to osteogenesis imperfecta type Ⅰ. The disease has high penetrance. Timely surgical intervention for hearing loss can improve the life quality in patients. Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.
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Humans , Hearing , Hearing Tests , Osteogenesis Imperfecta , Retrospective Studies , StapesABSTRACT
Cryo-electron microscopy (cryo-EM) imaging has the unique potential to bridge the gap between cellular and molecular biology. Therefore, cryo-EM three-dimensional (3D) reconstruction has been rapidly developed in recent several years and applied widely in life science research to reveal the structures of large macromolecular assemblies and cellular complexes, which is critical to understanding their functions at all scales. Although the technical breakthrough in recent years, for example, the introduction of the direct detection device (DDD) camera and the development of cryo-EM software tools, made the three cryo-EM pioneers share the 2017 Nobel Prize, several bottleneck problems still exist that hamper the further increase of the resolution of single-particle reconstruction and hold back the application of in situ subnanometer structure determination by cryo-tomography. Radiation damage is still the key limiting factor in cryo-EM. In order to minimize the radiation damage and preserve as much resolution as possible, the imaging conditions of a low dose and weak contrast make cryo-EM images extremely noisy with very low signal-to-noise ratios (SNR), generally about 0.1. The high noise will obscure the fine details in cryo-EM images or reconstructed maps. Thus, a method to reduce the level of noise and improve the resolution has become an important issue. In this paper, we systematically reviewed and compared some robust filters in the cryo-EM field of two aspects, single-particle analysis (SPA) and cryo-electron tomography (cryo-ET), and especially studied their applications, such as, 3D reconstruction, visualization, structural analysis, and interpretation. Conventional approaches to noise reduction in cryo-EM imaging include the use of Gaussian, median, and bilateral filters, among other means. A Gaussian filter selects an appropriate filter kernel to conduct spatial convolution with a noisy image. Although noise with larger standard deviations in cryo-EM images can be suppressed and satisfactory performance is achieved in certain cases, this filter also blurs the images and over-smooths small-scale image features. This is especially detrimental when precise quantitative information needs to be extracted. Unlike a Gaussian filter, a median filter is based on the order statistics of the image and selects the median intensity in a window of the adjacent pixels to denoise the image. Although this filter is robust to outliers, it suffers from aliasing problems that possibly result in incorrect information for cryo-EM structure interpretation. A bilateral filter is a nonlinear filter that performs spatial weighted averaging and is more selective in the pixels allowing to contribute to the weighted sum, excluding the high frequency noise from the smoothing process. Thus, this filter can be used to smooth out noise while maintaining the edge details, which is similar to an anisotropic diffusion filter, and distinct from a Gaussian filter but its utility will be limited when the SNR of a cryo-EM image is very low. Generally, spatial filtering methods have the disadvantage of losing image resolution when reducing noise. A wavelet transform can exploit the wavelet's natural ability to separate a signal from noise at multiple image scales to allow for joint resolution in both the spatial and frequency domains, and thus has the potential to outperform existing methods. The modified wavelet shrinkage filter we developed can offer a remarkable improvement in image quality with a good compromise between detail preservation and noise smoothing. We expect that our review study on different filters can provide benefits to cryo-EM applications and the interpretation of biological structures.
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Algorithms , Cryoelectron Microscopy , Image Processing, Computer-Assisted , Normal Distribution , Signal-To-Noise Ratio , Tomography, X-Ray ComputedABSTRACT
Objective:To investigate the value of plasma syndecan-1 (SDC-1) combined with lung ultrasonography in evaluating the degree of extravascular lung water in patients with acute respiratory distress syndrome (ARDS).Methods:From July 2018 to July 2019, 50 patients with ARDS admitted to the department of intensive care unit of Wuxi People's Hospital Affiliated to Nanjing Medical University were enrolled. After admission, pulse indicator continuous cardiac output (PiCCO) catheter was established for all patients. PiCCO indexes, including extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were monitored by one doctor. Another doctor performed lung ultrasound examination, and calculated the sum of the number of B-lines under 10 ultrasound sections of upper blue point, lower blue point, diaphragm point, Plaps point and rear blue point of both lungs. Then the level of plasma SDC-1 was detected by enzyme linked immunosorbent assay (ELISA). Pearson correlation method was used to analyze the correlation between the number of ultrasonic B-lines, plasma SDC-1 level and EVLWI and PVPI. Taking 10 mL/kg EVLWI as the boundary value, the degree of pulmonary edema in patients with ARDS was divided into mild pulmonary edema and severe pulmonary edema. The receiver operator characteristic curve (ROC curve) was drawn, and the number of B-lines, SDC-1 and the predictive value of the combination of the above two indicators on the severity of pulmonary edema in patients with ARDS were analyzed.Results:The cardiac index (CI) and central venous pressure (CVP) of 50 patients with ARDS were (46.84±6.00) mL·s -1·m -2 and (8.12±1.80) mmHg (1 mmHg = 0.133 kPa), cardiogenic pulmonary edema was excluded. In 50 patients with ARDS, EVLWI was (10.82±2.92) mL/kg, PVPI was 3.02±0.69, the number of ultrasound B-lines was 40.90±13.05, and plasma SDC-1 was (568.25±118.14) μg/L. Pearson correlation analysis showed that the number of ultrasound B-lines in patients with ARDS was significantly positively correlated with EVLWI and PVPI ( r1 = 0.802, r2 = 0.799, both P < 0.01). Plasma SDC-1 was also positively correlated with EVLWI and PVPI ( r1 = 0.732, r2 = 0.576, both P < 0.01). ROC curve analysis showed that the number of B-lines and SDC-1 had good predictive value for the severity of pulmonary edema in patients with ARDS. The area under ROC curve (AUC) and 95% confidence interval (95% CI) were 0.891 (0.803-0.979) and 0.875 (0.772-0.978), respectively. When the cut-off of B-lines was 40.50, the sensitivity and specificity were 82.1% and 86.4%, respectively. When the cut-off of SDC-1 was 559.37 μg/L, the sensitivity and specificity were 85.7% and 81.8%, respectively. Combining the number of B-lines with SDC-1 could further improve the predictive value of pulmonary water in patients with ARDS. The AUC (95% CI) was 0.958 (0.890-1.000), and the sensitivity and specificity were 92.9% and 91.8%, respectively. Conclusions:The level of plasma SDC-1 and the number of pulmonary ultrasonic B-lines have a good correlation with the degree of extravascular lung water in patients with ARDS. The combined application of the two noninvasive indexes can be used to evaluate the degree of extravascular lung water in patients with ARDS.
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Objective:To investigate the main postoperative complications, causes of death and the risk factors for survival in patient with benign end-stage lung diseases within 1 year after lung transplantation.Methods:A retrospective analysis was conducted to collect the clinical data of 200 patients with benign end-stage lung disease who underwent lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from May 2017 to October 2018. The main postoperative complications, survival and causes of death within 1 year after operation were analyzed. The Kaplan-Meier method was used to plot survival curves, and the Log-Rank test was used to compare the influence of factors, including recipient's gender, use of marginal donor lung, primary disease, preoperative combination of moderate to severe pulmonary hypertension (PAH), intraoperative extracorporeal membrane oxygenation (ECMO) support, surgical methods, intraoperative massive blood loss, postoperative complications [infection, primary graft dysfunction (PGD), acute rejection], on 1-year survival in patients who underwent lung transplantation. The multivariate Cox proportional hazards regression model was used to evaluate the risk factors of death within 1 year after lung transplantation.Results:Two hundred patients underwent successful lung transplantation. The major postoperative complications within 1 year after transplantation included infection in 131 patients, PGD in 20 patients, acute rejection in 57 patients, anastomotic complication in 26 patients and others (new onset diabetes, osteoporosis, etc.) in 53 patients. The 3-month, 6-month, and 1-year postoperative cumulative survival rates were 81.5%, 80.0% and 77.5%, respectively. Forty-five patients died during 1 year after operation, among whom 14 died of infection, 7 died of PGD, 8 died of acute rejection, 4 died of anastomotic complication, 3 died of cardio-cerebrovascular accident, 3 died of multiple organ failure, 2 died of respiratory failure and 4 died of other causes (traffic accident, etc.). The Kaplan-Meier survival analysis showed that recipient's gender, idiopathic pulmonary fibrosis (IPF) as the primary disease, preoperative combination of moderate and severe PAH, intraoperative ECMO support, intraoperative massive blood loss, postoperative complications (infection, PGD, acute rejection) were influencing factors for postoperative 1-year survival rate. The multivariate Cox regression model showed that male was the protective factor [hazard ratio ( HR) = 0.481, 95% confidence interval (95% CI) was 0.244-0.947, P = 0.034], IPF as the primary disease ( HR = 2.667, 95% CI was 1.222-5.848, P = 0.014), intraoperative use of ECMO support ( HR = 1.538, 95% CI was 0.787-3.012, P = 0.028), massive blood loss during surgery ( HR = 2.026, 95% CI was 0.976-4.205, P = 0.045) and postoperative infection ( HR = 3.138, 95% CI was 1.294-7.608, P = 0.011), PGD ( HR = 1.604, 95% CI was 0.464-5.539, P = 0.004), and acute rejection ( HR = 1.897, 95% CI was 0.791-4.552, P = 0.015) were the independent risk factors for death within 1 year after transplantation. Conclusions:One-year survival rates after lung transplantation are affected by recipient's gender, primary disease, preoperative combination of moderate and severe PAH, intraoperative ECMO support, intraoperative massive blood loss, and postoperative complications (infection, PGD, acute rejection). The male is the protective factor, while IPF as the primary disease, intraoperative ECMO support, massive blood loss during surgery and postoperative complications (infection, PGD, acute rejection) are independent risk factors for death within 1 year after lung transplantation.
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Objective:To explore the clinical value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) combined with neutrophil extracellular traps (NETs) in predicting liver injury in patients with sepsis.Methods:A prospective observational study was conducted. The patients who met the diagnostic criteria for sepsis 3.0 admitted to the Department of Intensive Care Unit in Wuxi People’s Hospital Affiliated to Nanjing Medical University from March 2019 to June 2020 were selected as the research objects. The basic informations of the patients were recorded. NLR based on blood routine at admission was calculated. PicoGreen fluorescence quantitative detection kit was used to detect the quantitative level of free DNA (cf-DNA/NETs) in the peripheral plasma of patients at admission. According to whether liver injury occurred, the patients were divided into the sepsis without liver injury group and sepsis with liver injury group. Binary Logistics regression analysis was used to predict the risk factors of sepsis with liver injury. The receiver operating characteristic (ROC) curve was drawn. The value of NLR, NETs, NLR combined with NETs in predicting liver injury in patients with sepsis was analyzed.Results:A total of 122 patients with sepsis were enrolled, of which 45 patients suffered from septic liver injury, with an incidence rate of 36.89%. The NLR of the sepsis wth liver injury group was (21.63 ± 4.71), the NLR of the sepsis without injury injury group was (15.03 ± 4.71), and the NETs level of the sepsis with liver injury group was (505.86 ± 250.05) μg/L, the level of NETs in the sepsis without liver injury group was (179.27 ± 67.20) μg/L, and the differences between the two groups were statistically significant (all P<0.05). Binary logistic regression analysis found that NLR ( OR=1.470, 95% CI: 1.121-1.926, P<0.05) and NETs ( OR=1.018, 95% CI: 1.005-1.030, P<0.05) at admission were the independent risk factors for liver injury in patients with sepsis. The best cut-off value of NLR was 16.68, and the best cut-off value of NETs was 317 μg/L. The sensitivity of combined application of NLR and NETs to predict liver injury in patients with sepsis was 77.78%, specificity was 98.70%, the area under the curve was 0.930, and the Youden Index was 0.765. Conclusions:The peripheral blood NLR and NETs levels are independent risk factors for liver injury in patients with sepsis. The combined application of NLR and NETs has a certain predictive value for liver injury in patients with sepsis. Taking NLR of 16.68 and NETs of 317 μg/L as the cut-off values, they can be used as early warning indicators to predict liver injury in patients with sepsis.
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Objective To analyze the characteristics of high-risk maternal patients and evaluate the multidisciplinary medical care system we established correspondingly. Method We collected and analyzed the medical records of high-risk maternal patients who received medical care from January 1,2017 to December 31,2020 in Peking Union Medical College Hospital. Results Ninety-eight high-risk maternal patients were included in this study,and 84.7%(83/98)of them were combined with different severe systemic diseases.Under the multidisciplinary medical care system,91 patients showed improved conditions and were discharged,and the other 7 cases had poor prognosis. Conclusions General tertiary hospitals in Beijing are receiving maternal patients with more high-risk complications.Considering the high risk and diverse diseases of maternal patients admitted to our hospital,we established a medical care system composed of a multidisciplinary panel of experts for high-risk maternal patients to improve the medical care and prognosis of the patients with high efficiency.
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Humans , Hospitalization , Hospitals, General , Prognosis , Retrospective Studies , Tertiary Care CentersABSTRACT
(2S)-taxifolin is an important flavonoid that has anti-inflammatory and anti-oxidation effects. It is widely used in pharmaceutical and nutraceutical industries. Flavone 3-hydroxylase (F3H) can catalyze the synthesis of (2S)-taxifolin and other 3-hydroxylated flavonoids from (2S)-eriodictyol. Due to the low catalytic efficiency of F3H, the titer of many 3-hydroxyflavones, such as taxifolin, synthesized by microbial method is relatively low. In this study, a SmF3H was identified from the transcriptome of Silybum marianum (L.) Gaertn. The results of fermentation showed that SmF3H can catalyze the flavone 3-hydroxylation reaction, and its catalytic efficiency was significantly higher than that of commonly used SlF3H from Solanum lycopersicum. Six promoters with different transcription strength were selected to optimize the synthesis pathway from the flavonoid precursor (2S)-naringenin to (2S)-taxifolin. The results showed that the highest titer of (2S)-taxifolin (695.90 mg/L in shake flask) could be obtained when the P(GAL7) promoter was used to control the expression of SmF3H. The titer of (2S)-taxifolin was further improved to 3.54 g/L in a 5-L fermenter, which is the highest titer according to current available literatures.
Subject(s)
Antioxidants , Flavonoids , Milk Thistle , Quercetin/analogs & derivativesABSTRACT
Objective:The purpose of this study was to explore new method for evaluating the severity of extravascular lung water in patients after bilateral lung transplantation.Methods:The study was performed in 50 patients after bilateral lung transplantation in our hospital from 2017 to 2018. Picco were implanted during the operation .Two hours after the operation, a doctor monitored the index of EVLWI and PVPI.At the same time, another doctor carried out examination of lung ultrasonography and Calculated the numbers of B line. After ultrasonography, the doctor used ELISA to determine the level of SDC-1.Results:EVLWI were significantly correlated with the number of B-line and the level of SDC-1 ( RS=0.833, RS=0.747, P<0.05), PVPI were significantly correlated with the number of B-line and the level of SDC-1 ( RS=0.738, RS=0.626, P<0.05). Conclusion:The number of B-line and the level of SDC-1 have a good correlation with extravascular lung water. The combination of the two indicators might be used as a reliable index for evaluating the degree of extravascular lung water after bilateral lung transplantation.
ABSTRACT
Guided by the theory of "component structure", we analyzed the structural characteristics of pharmacodynamical components in genuine Moutan Cortex. The compositions of organic small molecules were determined by high performance liquid chromatography(HPLC) for 20 batches of genuine Moutan Cortex and 12 batches of non-genuine Moutan Cortex. By means of similarity analysis, clustering analysis(CA), principal component analysis(PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA), the elements in structural characteristics of the pharmacodynamical components were extracted as follows: terpene glycosides components(oxidized paeoniflorin, paeoniflorin,galloyl paeoniflorin, benzoyloxy paeoniflorinand benzoyl paeoniflorin), tannin components(1,3,6-tri-O-galloside acyl glucose, pentagalloyl glucose), and phenolic acid components(methyl gallate, paeonol). The contents and quantity ratios of terpene glycoside component, tannin component and phenolic acid components in genuine Moutan Cortex were determined as 14.1, 12.5, 21.7 mg·g~(-1), 1.00∶0.89∶1.54. The contents and quantity ratios of the oxidized paeoniflorin, paeoniflorin and benzoylpaeoniflorin in the terpene glycoside components were characteristic and determined as 2.05, 7.05, 3.30 mg·g~(-1), 1.00∶3.44∶1.61. The unique structural characteristics of genuine Moutan Cortex provide scientific basis for the formulation of quality standards.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Paeonia , Principal Component AnalysisABSTRACT
In this paper, we aim to control and evaluate the quality of Liuwei Dihuang Concentrated Pill by using the model of fingerprint technique and "component structure" theory. Agilent 5 TC-C_(18) column(4.6 mm×250 mm,5 μm) was used, with 0.1% formic acid solution-acetonitrile as mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃, with detection wavelength of 242 nm and the sample volume of 10 μL. The characteristic fingerprint of Liuwei Dihuang Concentrated Pill was established by high performance liquid chromatography(HPLC) for its quality control. Seventeen common peaks were identified, and the similarity was 0.550-0.997 in 29 batches of samples, indicating that the quality difference among batches of Liuwei Dihuang Concentrated Pills was significant. The structural characteristics of the Moutan Cortex components in Liuwei Dihuang Concentrated Pills were characterized. On this basis, combined with the structural characteristics of genuine components of Moutan Cortex, the structural characteristics of components in Liuwei Dihuang Concentrated Pills were further analyzed. The results showed that there were significant differences in the contents and quantity ratios of 9 representative components(components) of Moutan Cortex in Liuwei Dihuang Concentrated Pills from different manufacturers, indicating internal quality differences among different batches of products. The fingerprint technique and the "component structure" theory established by the above research provide an analytical method and a research foundation for the quality evaluation of Liuwei Dihuang Concentrated Pills.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Quality ControlABSTRACT
Objective: To study the clinical efficacy of modified Zhenwutang combined with Zhengji technique on cold-dampness arthralgia syndrome caused by knee osteoarthritis (KOA) at episode and the effect on inflammatory factors of joint fluid. Method: One hundred and forty-eight patients were randomly divided into control group and observation group by random number table. Patients in control group got celecoxib capsules, 0.2 g/time, 1 time/day, and Zhengji technique with lumbar positioning oblique pulling and finger pressing for 12 times, 1 time for every two days, 3 times/week. Patients in observation group got modified Zhenwutang, 1 dose/day, and the same Zhengji technique. The course of treatment was 4 weeks. Before and after treatment, western Ontario and McMaster University Osteoarthritis index (WOMAC), pain and swelling, index of severity of osteoarthritis (ISOA), local signs of knee joint and cold-dampness obstruction syndrome were scored, and the score of quality of life were discussed by arthritis impact measurement scale 2 (AIMS2-SF). And levels of interleukin-1 beta (IL-1β), IL-17, tumor necrosis factor-alpha (TNF-α), substance P (SP) and calcitonin gene-related peptide (CGRP) were detected. Result: The clinical efficacy in observation group was better than that in control group (Z=2.131, PPPβ, IL-17, TNF-α, SP and CGRP were higher than those in control group (PConclusion: Modified Zhenwutang combined with Zhengji technique can relieve clinical symptoms of patients with cold-dampness arthralgia syndrome caused by knee osteoarthritis (KOA) at episode, ameliorate joint function to improve patients' quality of life, reduce the expression of proinflammatory factors and neuropeptides in synovial fluid, so as to inhibit the inflammatory response and controlling clinical symptoms.