ABSTRACT
Chinese materia medica has a wide range of clinical applications， but it has many active ingredients with different physicochemical properties， and the target organs， action pathways and mechanisms for different ingredients to exert their efficacy are not the same. Therefore， it is difficult to design and develop a co-delivery system loading multiple components of Chinese materia medica to maximize the synergistic therapeutic efficiency. Based on the characteristics of effectiveness and functionality of active ingredients， the strategies for multi-component co-delivery of Chinese materia medica can be categorized into two types：firstly， based on the effectiveness of active ingredients， new carriers such as liposomes， nanoparticles can be constructed to load multi-components of Chinese materia medica. secondly， based on the functionality of some active ingredients of Chinese materia medica， they are employed in the construction of co-delivery system， which can give play to the dual characteristics of their own efficacy and preparation functions. In this paper， we summarized the relevant research progress of the above two types of multi-component co-delivery strategies， and mainly discussed the pharmaceutical functions of the active ingredients in co-delivery systems， in order to find a more suitable multi-component co-delivery strategy， promoting the design and development of new delivery systems of Chinese materia medica.
ABSTRACT
Intestinal flora imbalance and abnormal glucose and lipid metabolism are important risk factors and pathological mechanisms of colorectal polyps. "Spleen deficiency and dampness accumulation" is the core pathogenesis of colorectal polyps. The imbalance of intestinal flora is related to spleen deficiency, and the application of Chinese herbs for invigorating spleen is helpful to the recovery of intestinal flora balance. Abnormal glucose and lipid metabolism is related to dampness accumulation, and it is effective to treat it with bitter and spicy herbs or spleen-invigorating and dampness-eliminating herbs. The interaction between intestinal flora imbalance and abnormal glucose and lipid metabolism changes intestinal microenvironment, damages intestinal epithelial cells, causes abnormal proliferation of intestinal stem cells and leads to colorectal polyps, which is consistent with the pathogenesis of spleen deficiency and dampness accumulation in Traditional Chinese Medicine. Thus, we tried to explore the biological connotation of the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps from the perspective of the interaction of intestinal flora and glucose and lipid metabolism, in order to provide reference for identifying high-risk population and analyzing the therapeutic mechanism of compound prescription for invigorating spleen and removing dampness.
ABSTRACT
ObjectiveTo picture the trajectory of changes in glucose and lipid metabolism among schizophrenic patients in long-term hospitalization. MethodsA total of 109 inpatients of Shenzhen Kangning Hospital from 2014 to 2022， who were diagnosed with schizophrenia based on the International Classification of Diseases， tenth edition （ICD-10） criteria， were recruited as subjects. Real-world follow-up data on longitudinal glucose metabolism （fasting blood glucose， glycosylated hemoglobin， C-peptide） and lipid metabolism （triglycerides， low density lipoprotein， high density lipoprotein， total cholesterol） were observed. The frequency of visit was once a year， with a total of 9 visits over 8 years. ResultsIn terms of glucose metabolism parameters， fasting blood glucose level decreased to 4.87 mmol/L at the 7th visit， lower than the baseline level （P<0.01）. Glycated hemoglobin level was 6.08% at the 9th visit， higher than the baseline level （P<0.05）. C-peptide level was 3.14 ng/mL at the 7th visit， higher than the baseline level （P<0.01）. As for the trajectory of lipid metabolism parameters， high-density lipoprotein level were significantly lower than baseline level at the second visit （P<0.01） and stayed basically stable thereafter. Total cholesterol levels at the last three visits were 4.06， 4.07 and 3.95 mmol/L， respectively， all lower than the baseline level （P<0.01）. ConclusionThe changes of glycolipid metabolism parameters in long-term inpatients with schizophrenia were generally smooth during the 8-year follow-up period.
ABSTRACT
Cholestatic liver diseases (CLD) are a series of diseases due to impaired bile flow and accumulation of bile acid in the liver and/or systemic circulation caused by immune, genetic, and environmental factors. The pathogenesis of CLD remains unclear and CLD is difficult to treat. As a substitute for human diseases, animal models can provide a platform for exploring the etiology and pathogenesis of the disease and finding appropriate therapeutic targets. This article reviews the current research advances in the animal models of CLD.
ABSTRACT
Objective:To investigate the efficacy of 3D-printed quantitative bone implants assisting second-stage Masquelet technique for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures.Methods:A retrospective case series analysis was made on 26 patients with long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures treated in Wuxi Ninth People′s Hospital from July 2015 to December 2020, including 20 males and 6 females; aged 19-63 years [(46.5±4.5)years]. Gustilo classification was type IIIB in 23 patients and type IIIC in 3. In the first stage, all patients had thoroughly emergent debridement, removal of all free bone pieces, restoration of the length and force line plus externally fixion, and vacuum sealing drainage (VSD) of the residual wound. After 2-7 days, the external fixation was removed and replaced by internal fixation, with the bone cement filling in the defect area and the free flap covering the wound. The length of tibial bone defect was 5-14 cm [(6.3±0.4)cm], and the tibial defect volume was 12.2-73.1 cm 3 [(33.6±9.2)cm 3]. In the second stage (6-19 weeks after injury), the bone cement was removed, followed by autologous bone grafting. Prior to bone grafting, digital technology was used to accurately calculate the bone defect volume, and an equal volume of bone harvesting area was designe to produce the 3D printed osteotomy template. Bone grafting was conducted after bone removal according to the osteotomy template during operation. The success rate of one-time iliac bone extraction, bone harvesting time, and bleeding volume were recorded. Pain in the bone extraction area was evaluated by visual analogue score (VAS) at 1 day and 1 month after operation and at the last follow-up. Wound healing, complications, and bone healing were observed. Life quality was evaluated by health survey brief form (SF-36) including scores of physical component summary (PCS) and mental component summary (MCS) before bone grafting and at the last follow-up. Results:All the patients were followed up for 13-53 months [(32.3±12.5)months]. One-time iliac bone extraction was successful in all the patients. Bone harvesting time was 15-30 minutes [(21.0±2.5)minutes]. The bleeding volume was 50-120 ml [(62.3±29.0)ml]. The VAS was 1-4 points [(1.2±0.9)points] at 1 day after operation, higher than these (0.0±0.0)points at 1 month after operation and at the last follow-up (all P<0.01). Totally, 25 patients obtained wound healing after operation, except for 1 patient with superficial wound infection after bone grafting that was healed by dressing change. There was 1 patient with bone infection after 3 months of bone grafting that was healed by repeated surgery with Masquelet technique in the first and second stage. Besides, 2 patients had symptoms of cutaneous nerve injury in the iliac donor area. The time of bone healing was 4-7 months [(5.8±0.8)months]. The scores of PCS and MCS in SF-36 at the last follow-up were (73.6±12.8)points and (83.6±13.2)points, significantly higher than those before bone grafting [(46.8±0.5)points, (60.7±2.0)points] (all P<0.01). Conclusion:Second-stage Masquelet technique with 3D printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures is associated with shortened bone harvesting time, attenuated pain, reduced complications, accelerated bone healing and improved function.
ABSTRACT
OBJECTIVE To investigate the improve-ment functions of flavonoid compounds on temozolomide(TMZ)-,aging-or AD model-induced dysregulation of hip-pocampal NSC lineage progression,retardancy of den-dritic spine maturation in new-born neurons,as well as impairment of hippocampal-related learning and memory.METHODS We applied 30-week-old neural stem cell(NSC)specific promoter Nestin-GFP and NestinCreERT2:Rosa26-LSL-tdTomato transgenic mice and 16-week-old AD model 5XFAD transgenic mice,together with hippo-campal microinjection(ih),endogenous fluorescence trac-ing and immunofluorescent staining.RESULTS Both fla-vonoid compound A and its functional derivative flavo-noid compound B dose-dependently improved TMZ-,aging-or AD-induced defects of hippocampal NSC lin-eage progression and the maturation of dendritic spines of newborn neurons,thereby improving hippocampus related learning and memory.CONCLUSION This paper provides a new idea and treatment strategy for the devel-opment of new flavonoids that can promote neurogene-sis for neurodegenerative diseases and aging.
ABSTRACT
Objective:To develop the interpersonal emotion regulation questionnaire for healthcare workers and examine its reliability and validity.Methods:Based on the theory of social regulatory cycle (SRC), literatures review and semi-structured interview were used to form the item pool of the scale.Through expert consultation, project analysis and the exploratory factor analysis, the scale items were screened, and the interpersonal emotion regulation questionnaire for healthcare workers was initially formed.The convenient sampling method was adopted to select 619 healthcare workers from multiple hospitals in Anhui province to conduct the formal survey to test the reliability and validity of the questionnaire and confirmatory factor analysis (CFA) using the SPSS 24.0 and Mplus 8.0 software.Results:There were 18 items and four dimensions including emotion identification, motivation, regulation strategy and implementation strategy process in the interpersonal emotion regulation questionnaire for healthcare workers.The results of CFA showed that the questionnaire fitted the data with well construct validity.The correlation coefficients between each dimension and the scale were 0.830-0.932.The Cronbach’s α coefficient of the overall questionnaire was 0.962, the split-half reliability was 0.880 and the test-retest reliability was 0.786.The score of total questionnaire was significantly positively correlated with the score of emotional intelligence ( r=0.680, P<0.001) and empathic ability ( r=0.554, P<0.001), and was significantly negatively correlated with the doctor-patient relationship ( r=-0.353, P<0.001). Conclusion:The interpersonal emotion regulation questionnaire for healthcare workers has satisfactory reliability and validity, which can be used to measure the ability of interpersonal emotion regulation in healthcare workers.
ABSTRACT
Objective:To investigate the value of 18F-FDG total-body PET/CT dynamic imaging in evaluating the efficacy of early radiotherapy for MDA-MB-231 breast cancer bearing nude mice. Methods:MDA-MB-231 breast cancer bearing nude mice were established and divided into control group and radiotherapy group based on the random number table method ( n=10 for each group). 18F-FDG total-body PET/CT dynamic imaging was performed before and after the radiotherapy. The SUV max and the maximum tracer uptake net influx constant ( Kimax) of tumors, and the target-to-background ratio (TBR) were calculated. The change of tumor volume was recorded. The value of 18F-FDG total-body PET/CT dynamic imaging in evaluating the efficacy of radiotherapy was accessed using pathological findings as the reference. Paired t test, independent-sample t test and Pearson correlation analysis were used for data analysis. Results:After radiotherapy, SUV max and Kimax(4.66±0.46 and 0.14±0.03) were reduced in the radiotherapy group compared with those before radiotherapy (5.30±0.52 and 0.19±0.03; t values: 4.61, 8.31, P values: 0.001, <0.001), while the SUV max (5.94±0.74 vs 5.24±0.50) and Kimax (0.23±0.03 vs 0.19±0.02) were increased compared with baseline in the control group ( t values: 4.77, 6.87, P values: 0.001, <0.001). TBR Ki was significantly higher than TBR suv based on all images of the 2 groups (14.11±5.58 vs 5.91±1.60; t=8.92, P<0.001). The tumor volume in the radiotherapy group decreased compared with that before radiotherapy, but the difference was not statistically significant ((0.74±0.12) vs (0.81±0.08) cm 3; t=2.24, P=0.052). The results of immunohistochemistry showed that glucose transport protein (Glut)1 was highly expressed in tumors, and the Glut1 positive cell percentage of the radiotherapy group was significantly lower than that of the control group ((38.30±6.18)% vs (69.78±5.37)%; t=12.17, P<0.001). The expression of Glut1 was significantly positively correlated with SUV max and Kimax(the control group: rsuv=0.75, P=0.012; rKi=0.77, P=0.010; the radiotherapy group: rsuv=0.67, P=0.035; rKi=0.77, P=0.010). The apoptosis index (AI) of tumor cells in the radiotherapy group was higher than that in the control group ((24.15±4.00)% vs (10.15±3.05)%; t=8.85, P<0.001). Conclusion:18F-FDG total-body PET/CT dynamic imaging can sensitively monitor the effect of early radiotherapy in MDA-MB-231 breast cancer bearing nude mice.
ABSTRACT
OBJECTIVE To establish a comprehensive and rapid m ethod for the a nalysis of chemical constituents as phthalides and organic acids in Angelica sinensis ，and to provide scientific reference for the quality evaluation and pharmacodynamic substance research of A. sinensis . METHODS The 70％ ethanol extract of A. sinensis was analyzed by ultra high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF/MS）. The determination was performed on ACQUITY UPLC BEH-C 18 column with mobile phase consisted of 0.1％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃，and sample size was 2 µL. The ion source was an electrospray ion source ，using positive ion scanning mode ，and the mass scanning range was m/z 50-1 000. Capillary voltage was 4 000 V； atomizer pressure was 35 psi；cracking voltage was 135 V and the taper hole voltage was 65 V；the temperature of dry gas was 320 ℃；the flow of dry gas was 10 L/min and the flow of sheath gas was 11 L/min；collision energy were 20 and 40 V. Qualitative Analysis 10.0 software was used to obtain the retention time of compounds ，the accurate mass number of excimer ion peaks and secondary fragments. The compounds were analyzed by comparing with the mass spectra of the reference substance ，combined with relevant literature ，mass spectrometry cleavage law and database such as Chemspider ，MassBank，PubChem. RESULTS A total of 72 compounds were identified or deduced from A. sinensis ，including 55 phthalides，13 organic acids and 4 other constituents. CONCLUSIONS The established method is rapid and accurate for the identification of chemical constituents from A. sinensis ，such as organic acids and phthalides ，which provides an efficient and rapid analytical method for the comprehensive characterization of its chemical constituents.
ABSTRACT
Objective:To explore the effect of continuous feeding on the growth and development of premature infants.Methods:A total of 82 cases of premature infants in our hospital were selected as the research objects, whose birth time was from March 2018 to March 2019. According to different feeding methods, they were divided into control group and observation group, 41 cases in each group. The control group was fed intermittently and the observation group was fed continuously. Before and after 6 months of feeding, the levels of serum growth hormone and insulin-like growth factor-1, the mental development index(MDI) and physical development index(PDI), body mass, head circumference and height, and adverse reactions were compared.Results:The time of jaundice regression and hospitalization time in the observation group were (8.01±1.52) d, (28.41±3.57) d, shorter than (10.28±2.29) d, (36.19±6.47) d in the control group, the difference was statistically significant ( t value was 5.288, 6.741, P<0.05). There was no significant difference between the control group and the observation group in the levels of serum growth hormone and insulin-like growth factor-1 before feeding ( t value was 0.160, 0.075, P>0.05). After feeding for 6 months, the levels of serum growth hormone and insulin-like growth factor-1 in the experimental group were higher than those in the control group ( t value was 6.895, 19.537, P<0.05). Six months after feeding, the MDI and PDI of the observation group were 115.2±67.93 and 107.6±48.66 respectively, higher than 96.17±13.57, 94.52±10.89 in the control group ( t value was 7.777, 6.038, P<0.05). After feeding for 6 months,the growth level of body weight,head circumference and height in the observation group was higher than that in the control group ( t value was 7.590,10.124,15.661, P<0.05). The adverse reactions of premature infants in hospital infection, multiple apnea, gastric retention and neonatal necrotizing enterocolitis were lower than those in the control group ( χ2 value was 5.399-21.006, P<0.05). Conclusions:Continuous feeding can significantly improve the level of growth hormone and insulin-like growth factor-1 in premature infants, which is conducive to their growth and development, reduce the occurrence of adverse reactions and shorten the hospitalization time of premature infants, which has a certain clinical application value.
ABSTRACT
Objective@#To explore whether extracellular histones aggravate acute respiratory distress syndrome (ARDS) by inducing peripheral blood mononuclear cell (PBMC) pyroptosis.@*Methods@#Twenty patients with ARDS admitted to Shanghai Pulmonary Hospital, Tongji University School of Medicine from April to September in 2019 were enrolled, and 20 healthy volunteers were enrolled as controls. In vivo experiment: peripheral blood samples of patients with ARDS within 24 hours after diagnosis and healthy volunteers were collected, and the levels of plasma extracellular histone, interleukins (IL-1β and IL-18) and lactic dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay (ELISA). PBMC were harvested, the expression levels of the pyroptosis associated N terminal-gasdermin-D (GSDMD-N) protein were determined by Western Blot. In vitro experiment: PBMC isolated from healthy volunteers were divided into four groups. Blank control group without any treatment; lipopolysaccharide (LPS) group was treated with 1 mg/L LPS for 4 hours; LPS+histones group was treated with 100 mg/L exogenous histones for 24 hours after LPS treatment; LPS+histone+heparin group was treated with 200 U heparin for 24 hours after LPS and exogenous histones treatment. The GSDMD-N protein expression was determined by Western Blot, and the levels of IL-1β, IL-18 and LDH in cell supernatant were determined by ELISA. Spearman test was used to test the correlation among the parameters.@*Results@#In vivo experiment results: compared with healthy control group, the GSDMD-N protein expression in PBMC of patients with ARDS was significantly increased [GSDMD-N/GAPDH: 0.136 (0.062, 0.246) vs. 0.026 (0.018, 0.036), P < 0.01], as well as the plasma levels of IL-1β, IL-18, LDH and extracellular histones [IL-1β (ng/L): 120.0 (94.2, 213.0) vs. 88.5 (82.3, 105.3), IL-18 (ng/L): 164.5 (70.8, 236.3) vs. 60.5 (52.0, 89.0), LDH (U/L): 30.9 (24.7, 39.5) vs. 19.8 (17.2, 21.5), extracellular histones (mg/L): 73.0 (42.8, 112.9) vs. 12.2 (9.6, 16.9), all P < 0.01], indicating that the PBMC of ARDS patients had significant pyroptosis and release of a large number of inflammatory factors. The oxygenation index (PaO2/FiO2) of ARDS patients was 135.5 (94.5, 196.0) mmHg (1 mmHg = 0.133 kPa). Correlation analysis showed that the expression of GSDMD-N protein in patients with ARDS was negatively correlated with PaO2/FiO2 (r = -0.935, P < 0.01) and positively correlated with IL-1β, IL-18, LDH and extracellular histones (r value was 0.844, 0.843, 0.887, 0.899, respectively, all P < 0.01). In vitro experiment results: compared with blank control group, the expression of GSDMD-N protein in PBMC and the levels of inflammatory mediators in the supernatant of the LPS group were significantly increased [GSDMD-N/GAPDH: 0.035±0.006 vs. 0.028±0.006, IL-1β (ng/L): 39.8±5.5 vs. 22.6±4.7, IL-18 (ng/L): 31.2±4.4 vs. 20.0±2.2, LDH (U/L): 51.2±7.3 vs. 36.6±7.6, all P < 0.05], indicating that LPS stimulation could increase PBMC pyroptosis and the release of inflammatory mediators. Compared with LPS group, the expression of GSDMD-N protein and the levels of inflammatory mediators of the LPS+histones group were further increased [GSDMD-N/GAPDH: 0.114±0.009 vs. 0.035±0.006, IL-1β (ng/L): 119.0±18.7 vs. 39.8±5.5, IL-18 (ng/L): 49.2±8.5 vs. 31.2±4.4, LDH (U/L): 127.8±19.8 vs. 51.2±7.3, all P < 0.01], indicating that the stimulation of LPS on PBMC could be significantly amplified by exogenous histone treatment, GSDMD-N protein expression could be up-regulated and inflammatory factor release could be promoted to further induce PBMC pyroptosis. These adverse effects of exogenous histones on PBMC could be abrogated by heparin, the expression of GSDMD-N protein and the levels of inflammatory mediators were significantly lower than those of LPS+histones group [GSDMD-N/GAPDH: 0.063±0.004 vs. 0.114±0.009, IL-1β (ng/L): 46.8±8.6 vs. 119.0±18.7, IL-18 (ng/L): 33.0±5.1 vs. 49.2±8.5, LDH (U/L): 65.4±11.0 vs. 127.8±19.8, all P < 0.05].@*Conclusion@#Extracellular histones in plasma may aggravate ARDS by mediating PBMC pyroptosis.
ABSTRACT
Objective@#To investigate the incidence and risk factors of extraintestinal manifestations (EIMs) in children with inflammatory bowel disease (IBD).@*Methods@#The clinical data of 161 children with IBD was collected from the electronic medical records in the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine from January 2012 to December 2017. These patients were divided into Crohn′s disease (CD) group and ulcerative colitis (UC) group, accounting for 82.0% (132 cases) and 18.0%(29 cases), respectively. The incidence of EIMs in each group was analyzed. The potential risk factors of EIMs including the IBD phenotype, gender, age, location of the CD lesion, disease activity of CD, and the presence of perianal lesion were analyzed with logistic regression model.@*Results@#Eighty-eight patients (54.7%) had EIMs. The main EIMs were immune-mediated EIMs and growth retardation, accounting for 41.0% (66/161) and 24.2% (39/161), respectively. Aphthous ulcer (39/161, 23.0%) was the most common symptom among immune-mediated EIMs, followed by arthropathy (20/161, 12.4%) and skin lesions (19/161, 11.8%). Forty-three patients (26.7%) had EIMs before being diagnosed as IBD. Fifty-eight (65.9%) patients had only one EIM during the whole course of IBD. By logistic regression analysis, CD (OR=5.536, 95%CI:1.825-16.788) and perianal disease (OR=1.969, 95%CI:1.035-3.746) were the risk factors of immune-mediated EIMs. Meanwhile, CD (OR=11.319, 95%CI: 1.487-86.179), younger than six-year-old at diagnosis (OR=8.556, 95%CI: 3.109-23.545), moderate to severe activity of CD (OR=3.447, 95%CI: 1.196-9.934) and perianal disease (OR=3.361, 95%CI: 1.720-7.793) increased the risk of growth retardation.@*Conclusions@#The children with IBD have a high incidence of EIMs, which were more common in CD than in UC. The risk factors of developing EIMs include CD, perianal diseases, younger than six-year-old at diagnosis and moderate to severe activity of CD.
ABSTRACT
Objective To investigate the predictive value of CT-DRAGON score for clinical outcomes after endovascular treatment in patients with acute ischemic stroke.Methods Patients with acute ischemic stroke underwent endovascular intervention in Xuzhou Central Hospital from May 2015 to June 2019 w ere enrolled retrospectively.CT-DRAGON score w as performed before treatment,and the outcomes of patients were evaluated by the modified Rankin Scale (mRS) at 3 months after treatment,and good outcome was defined as mRS 0-2.Multivariate logistic regression analysis was used to determine the independent factors for the outcomes.The receiver operating characteristic (ROC) curve was used to analyze the predictive value of CT-DRAGON score for clinical outcome.Results A total of 67 patients were eurolled.The age was 68.69 ± 11.63 years.The median CT-DRAGON score was 5 (interquartile interval:4-7),and the baseline NIHSS score was 17.45 ±5.19.Thirty-five patients (52.2％) had a good outcome and 32 (47.8％) had a poor outcome,of which 13 (19.4％) died.Multivariate logistic regression analysis showed that higher CT-DRAGON score was an independent predictor for poor outcome (odds ratio 1.997,95％ confidence interval 1.271-3.136;P =0.003).The ROC curve analysis showed that the area under the curve of CT-DRAGON score to clinical outcome was 0.808 (95％ confidence interval 0.706-0.911;P ＜ 0.001).The optimal cutoff value was 5,the corresponding sensitivity was 65.6％,and the specificity was 80.0％.Conclusions Baseline CT-DRAGON score can effectively predict the clinical outcome of patients with acute ischemic stroke at 3 months after endovascular treatment.
ABSTRACT
To explore whether extracellular histones aggravate acute respiratory distress syndrome (ARDS) by inducing peripheral blood mononuclear cell (PBMC) pyroptosis. Methods Twenty patients with ARDS admitted to Shanghai Pulmonary Hospital, Tongji University School of Medicine from April to September in 2019 were enrolled, and 20 healthy volunteers were enrolled as controls. In vivo experiment: peripheral blood samples of patients with ARDS within 24 hours after diagnosis and healthy volunteers were collected, and the levels of plasma extracellular histone, interleukins (IL-1β and IL-18) and lactic dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay (ELISA). PBMC were harvested, the expression levels of the pyroptosis associated N terminal-gasdermin-D (GSDMD-N) protein were determined by Western Blot. In vitro experiment: PBMC isolated from healthy volunteers were divided into four groups. Blank control group without any treatment; lipopolysaccharide (LPS) group was treated with 1 mg/L LPS for 4 hours; LPS+histones group was treated with 100 mg/L exogenous histones for 24 hours after LPS treatment; LPS+histone+heparin group was treated with 200 U heparin for 24 hours after LPS and exogenous histones treatment. The GSDMD-N protein expression was determined by Western Blot, and the levels of IL-1β, IL-18 and LDH in cell supernatant were determined by ELISA. Spearman test was used to test the correlation among the parameters. Results In vivo experiment results: compared with healthy control group, the GSDMD-N protein expression in PBMC of patients with ARDS was significantly increased [GSDMD-N/GAPDH: 0.136 (0.062, 0.246) vs. 0.026 (0.018, 0.036), P < 0.01], as well as the plasma levels of IL-1β, IL-18, LDH and extracellular histones [IL-1β (ng/L): 120.0 (94.2, 213.0) vs. 88.5 (82.3, 105.3), IL-18 (ng/L): 164.5 (70.8, 236.3) vs. 60.5 (52.0, 89.0), LDH (U/L): 30.9 (24.7, 39.5) vs. 19.8 (17.2, 21.5), extracellular histones (mg/L): 73.0 (42.8, 112.9) vs. 12.2 (9.6, 16.9), all P < 0.01], indicating that the PBMC of ARDS patients had significant pyroptosis and release of a large number of inflammatory factors. The oxygenation index (PaO2/FiO2) of ARDS patients was 135.5 (94.5, 196.0) mmHg (1 mmHg = 0.133 kPa). Correlation analysis showed that the expression of GSDMD-N protein in patients with ARDS was negatively correlated with PaO2/FiO2 (r = -0.935, P <0.01) and positively correlated with IL-1β, IL-18, LDH and extracellular histones (r value was 0.844, 0.843, 0.887, 0.899, respectively, all P < 0.01). In vitro experiment results: compared with blank control group, the expression of GSDMD-N protein in PBMC and the levels of inflammatory mediators in the supernatant of the LPS group were significantly increased [GSDMD-N/GAPDH: 0.035±0.006 vs. 0.028±0.006, IL-1β (ng/L): 39.8±5.5 vs. 22.6±4.7, IL-18 (ng/L): 31.2±4.4 vs. 20.0±2.2, LDH (U/L): 51.2±7.3 vs. 36.6±7.6, all P < 0.05], indicating that LPS stimulation could increase PBMC pyroptosis and the release of inflammatory mediators. Compared with LPS group, the expression of GSDMD-N protein and the levels of inflammatory mediators of the LPS+histones group were further increased [GSDMD-N/GAPDH:0.114±0.009 vs. 0.035±0.006, IL-1β (ng/L): 119.0±18.7 vs. 39.8±5.5, IL-18 (ng/L): 49.2±8.5 vs. 31.2±4.4, LDH (U/L): 127.8±19.8 vs. 51.2±7.3, all P < 0.01], indicating that the stimulation of LPS on PBMC could be significantly amplified by exogenous histone treatment, GSDMD-N protein expression could be up-regulated and inflammatory factor release could be promoted to further induce PBMC pyroptosis. These adverse effects of exogenous histones on PBMC could be abrogated by heparin, the expression of GSDMD-N protein and the levels of inflammatory mediators were significantly lower than those of LPS+histones group [GSDMD-N/GAPDH: 0.063±0.004 vs. 0.114±0.009, IL-1β (ng/L): 46.8±8.6 vs. 119.0±18.7, IL-18 (ng/L): 33.0±5.1 vs. 49.2±8.5, LDH (U/L): 65.4±11.0 vs. 127.8±19.8, all P < 0.05]. Conclusion Extracellular histones in plasma may aggravate ARDS by mediating PBMC pyroptosis.
ABSTRACT
Objective@#To investigate the predictive value of CT-DRAGON score for clinical outcomes after endovascular treatment in patients with acute ischemic stroke.@*Methods@#Patients with acute ischemic stroke underwent endovascular intervention in Xuzhou Central Hospital from May 2015 to June 2019 were enrolled retrospectively. CT-DRAGON score was performed before treatment, and the outcomes of patients were evaluated by the modified Rankin Scale (mRS) at 3 months after treatment, and good outcome was defined as mRS0-2. Multivariate logistic regression analysis was used to determine the independent factors for the outcomes. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of CT-DRAGON score for clinical outcome.@*Results@#A total of 67 patients were enrolled. The age was 68.69±11.63 years. The median CT-DRAGON score was 5 (interquartile interval: 4-7), and the baseline NIHSS score was 17.45±5.19. Thirty-five patients (52.2%) had a good outcome and 32 (47.8%) had a poor outcome, of which 13 (19.4%) died. Multivariate logistic regression analysis showed that higher CT-DRAGON score was an independent predictor for poor outcome (odds ratio 1.997, 95% confidence interval 1.271-3.136; P=0.003). The ROC curve analysis showed that the area under the curve of CT-DRAGON score to clinical outcome was 0.808 (95% confidence interval 0.706-0.911; P<0.001). The optimal cutoff value was 5, the corresponding sensitivity was 65.6%, and the specificity was 80.0%.@*Conclusions@#Baseline CT-DRAGON score can effectively predict the clinical outcome of patients with acute ischemic stroke at 3 months after endovascular treatment.
ABSTRACT
To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI). Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests. Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) . Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Subject(s)
Humans , Amphetamine-Related Disorders , Anisotropy , Brain , Diffusion Tensor Imaging , MethamphetamineABSTRACT
Objective To analyze the expression of interleukin 16 (IL-16) in atherosclerosis (AS) patients, and to study the roles of IL-16in the pathogenesis of AS.Methods Thirty AS patients in Affiliated Hospital of Jining Medical College from August 2015to August 2016were randomly selected as the case group and twenty-nine healthy subjects were selected as the healthy control group.Peripheral blood of the subjects were collected.IL-16levels were determined with enzyme-linked immunosorbent assay (ELISA).Reverse transcriptase-polymerase chain reaction was applied to analyze IL-16mRNA level.IL-16expression in the atherosclerotic plaque samples was detected with immunohistochemical analysis.IL-16expression in aortic atherosclerotic plaque of AS patients and atherosclerotic ApoE-/-mice were analyzed by immunohistochemical staining.The aortic plaque changes of AS mice injected intraperitoneally with recombinant IL-16were detected.Results Both IL-16protein levels and IL-16mRNA levels were higher in case group than those of healthy control group, the difference was statistically significant (P＜0.05).The IL-16mRNA was highly expressed in the atherosclerotic plaque.The aortic plaque area of the mice underwent IL-16intraperitoneal injection were decreased while the plaque stability increased.Conclusion IL-16levels elevated in both AS patients and AS mice, which suggested that IL-16might play aprotective role against AS.
ABSTRACT
Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Subject(s)
Animals , Male , Acute Disease , Brain , Diagnostic Imaging , Metabolism , Brain Mapping , Disease Models, Animal , Fluorodeoxyglucose F18 , Glucose , Metabolism , Infarction, Middle Cerebral Artery , Diagnostic Imaging , Metabolism , Neural Pathways , Diagnostic Imaging , Metabolism , Positron-Emission Tomography , Radiopharmaceuticals , Random Allocation , Rats, Sprague-DawleyABSTRACT
Objective@#To investigate the risk factors and survival status of hypopharyngeal carcinoma with synchronous second primary carcinoma of the esophagus.@*Methods@#One hundred and sixty patients with newly diagnosed hypopharyngeal carcinoma from January 2009 to December 2012 were retrospectively reviewed. The clinical data, tumor-related information and follow-up results were collected and analyzed.@*Results@#Forty-three synchronous esophageal carcinomas (27%) were detected in 160 patients with hypopharyngeal carcinoma, and most patients (72%) were at an early stage. On univariate analysis, the median age of less than 55 years old (χ2=4.525, P=0.033), excessive alcohol consumption (χ2=6.942, P=0.008) and invasion site more than 3 anatomical regions (χ2=21.503, P=0.000) had a significant correlation with the occurrence of synchronous esophageal carcinomas. Multivariate analysis showed that excessive alcohol consumption (OR=4.787, P=0.029) and invasion site more than 3 anatomical regions (OR=14.391, P=0.000) were independent risk factors. The median survival time was 26 months in 43 patients with synchronous esophageal carcinomas, which was significantly lower than that (58 months) in patients without secondary primary esophageal carcinomas (χ2=11.981, P=0.001).@*Conclusions@#There is a high incidence of synchronous esophageal carcinoma in hypopharyngeal carcinoma patients, affecting the prognosis of hypopharyngeal carcinoma. Surveillance for esophageal carcinomas in patients with hypopharyngeal carcinoma, especially in excessive alcohol drinkers, is warranted.
ABSTRACT
Objective@#To investigate the expression of integrin α5β1 and fibronectin in the human aorta and coronary artery, and their effects in the development of atherosclerosis.@*Methods@#One hundred and twenty autopsy aorta and coronary artery specimens were collected, and the expression of CD68, actin, integrin α5β1 and fibronectin was detected by immunohistochemical staining. Atherosclerotic plaques were located by CD68 and actin staining, and the degree of coronary artery stenosis was determined by elastic fiber staining and NIH Scion Image(60.1) software. The coronary artery tissues were divided into groups A (0-25%); B (26%-50%); C (51%-75%) and D (76%-100%) according to the degree of stenosis.@*Results@#Integrin α5β1 showed cytoplasmic expression in endothelium, foam cells, monocytes, smooth muscle cells and adjacent tissue around calcification. In both the aorta and coronary artery, integrin α5β1 expression was stronger in the smooth muscle cells in the internal elastic lamina than in the tunica. The expression intensity in coronary artery smooth muscle decreased with increasing degree of coronary artery stenosis. Fibronectin showed cytoplasmic expression in foam cells, monocytes, smooth muscle cells of the internal elastic lamina and adjacent tissue around calcification. There was positive correlation of fibronectin and integrin α5β1 expression in smooth muscle cells and adjacent tissue around calcification.@*Conclusions@#In the development of atherosclerosis, integrin α5β1 and fibronectin may participate in the regulating the migration of smooth muscle cells to the intima, and promote the formation of local calcification of atherosclerotic plaques. But integrin α5β1 is not involved in the late stage of atherosclerosis with increasing coronary artery stenosis.