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As a marginal organ donor, organs from hepatitis C donors have been applied in solid organ transplantation. While effectively alleviating the shortage of organs, it also faces certain challenges, such as the spread of hepatitis C virus (HCV). With the emergence and application of direct-acting antiviral agent, the cure of hepatitis C has gradually become a reality, laying the foundation for hepatitis C patients to become organ transplant donors. At present, with adjuvant treatment using antiviral drugs, certain efficacy has been achieved in solid organ transplantation from hepatitis C donors. In this article, research progress in kidney, heart, lung and liver transplantation from hepatitis C donors, the application of hepatitis C donors in solid organ transplantation and the safety and effectiveness of antiviral drugs were reviewed, and the feasibility of hepatitis C donors in solid organ transplantation was evaluated, aiming to provide reference for expanding the donor pool of organ transplantation and shortening the waiting time for organ transplantation in patients with end-stage diseases.
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ObjectiveInferring cancer driver genes, especially rare or sample-specific cancer driver genes, is crucial for precision oncology. Considering the high inter-tumor heterogeneity, a few recent methods attempt to reveal cancer driver genes at the individual level. However, most of these methods generally integrate multi-omics data into a single biomolecular network (e.g., gene regulatory network or protein-protein interaction network) to identify cancer driver genes, which results in missing important interactions highlighted in different networks. Thus, the development of a multiplex network method is imperative in order to integrate the interactions of different biomolecular networks and facilitate the identification of cancer driver genes. MethodsA multiplex network control method called Personalized cancer Driver Genes with Multiplex biomolecular Networks (PDGMN) was proposed. Firstly, the sample-specific multiplex network, which contains protein-protein interaction layer and gene-gene association layer, was constructed based on gene expression data. Subsequently, somatic mutation data was integrated to weight the nodes in the sample-specific multiplex network. Finally, a weighted minimum vertex cover set identification algorithm was designed to find the optimal set of driver nodes, facilitating the identification of personalized cancer driver genes. ResultsThe results derived from three TCGA cancer datasets indicate that PDGMN outperforms other existing methods in identifying personalized cancer driver genes, and it can effectively identify the rare driver genes in individual patients. Particularly, the experimental results indicate that PDGMN can capture the unique characteristics of different biomolecular networks to improve cancer driver gene identification. ConclusionPDGMN can effectively identify personalized cancer driver genes and broaden our understanding of cancer driver gene identification from a multiplex network perspective. The source code and datasets used in this work are available at https://github.com/NWPU-903PR/PDGMN.
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OBJECTIVE@#To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD).@*METHODS@#This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD.@*RESULTS@#There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE.@*CONCLUSION@#Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.
Subject(s)
Pregnancy , Infant, Newborn , Female , Humans , Pregnancy Outcome , Retrospective Studies , Abortion, Spontaneous/etiology , Undifferentiated Connective Tissue Diseases , Pre-Eclampsia/epidemiology , Lupus Erythematosus, Systemic , Risk Factors , Leukopenia , Pregnancy Complications/epidemiology , Disease Progression , Connective Tissue Diseases/epidemiologyABSTRACT
Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.
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Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.
Subject(s)
Humans , Glucocorticoids/adverse effects , Quality of Life , Osteoporosis/therapy , Incidence , Rheumatology , Bone DensityABSTRACT
Objective To propose a two-way fluid-structure interaction (FSI) method based on real patients with carotid artery stenosis, and analyze the hemodynamic parameters of carotid plaques with different types at the lesion as well as deformation and stress changes of the plaque itself. Methods Three-dimensional ( 3D) modeling was performed based on computed tomography angiography ( CTA) data of patients with moderate carotid artery stenosis. The carotid artery wall model and plaque model were separated, and transient fluid structure coupling calculation was performed. The situation from early stage of carotid atherosclerosis to formation of the plaque was simulated. The plaque types were divided into thickened plaques, lipid plaques, mixed plaques and calcified plaques, among which thickened plaques were regarded as non-plaque conditions for representing the thickening of vascular intima-media. The stenotic carotid arteries with different plaque types were compared and analyzed. Results The plaques with different types had little effect on the overall blood flow, but the wall shear stress of lipid plaques at the lesion was lower than that of other plaques. With thickened plaques as a control, concurrence of the plaque would inhibit artery expansion, and lipid plaques were the most obvious. Calcified plaques had the highest average plaque structure stress, while lipid plaques had the lowest average plaque structure stress. Conclusions The method proposed in this study can analyze fluid area and solid area at the same time. The results can contribute to better understanding the influence of different plaque types on carotid artery diseases.
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Objective To compare the measurement differences between the skull 3D printed model and the real specimen under different CT scan slice thicknesses, and to explore the effect of slice thickness on the accuracy of the 3D printed model. Methods Eight normal skull specimens (marked as Nos. f-8) (group N) were used for CT scanning with different slice thicknesses, specifically 0.625 mm (group A),1.25 mm (group B) , and 2.5mm (group C) ,3.75 mm (group D) , and 5 mm (group E) , and then earned out 3D reconstruction and 3D printing respectively, and compared the anatomical reduction degree of the foramen magnum diameter, anterior clinoid distance, and butterfly wing distance of the 3D printed skull model. Results The reduction degree of anatomical structure of 3D printed skull model decreased with the increase of CT slice thickness. There was no significant difference in the accuracy of 3D model among groups A, B and C (P >0.05 ) . There was a high correlation between group A, B and C and group N ( P < 0 .05 ).The size indexes and statistical values of group A, B and C were similar. Conclusion CT slice thickness has a significant effect on the accuracy and reduction of the 3D printed skull model. The 3D printed model with thin slice data (0.625 mm,1.25 mm,2.5 mm) has higher accuracy and less difference.
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OBJECTIVE@#To explore the mechanism of effects of total saponin fraction from Dioscorea Nipponica Makino (TSDN) on M1/M2 polarization of monocytes/macrophages and arachidonic acid (AA) pathway in rats with gouty arthritis (GA).@*METHODS@#Seventy-two Sprague Dawley rats were randomly divided into 4 groups (n=18 in each): normal, model, TSDN at 160 mg/kg, and celecoxib at 43.3 mg/kg. Monosodium urate crystal (MSU) was injected into the rats' ankle joints to induce an experimental GA model. Blood and tissue samples were collected on the 3rd, 5th, and 8th days of drug administration. Histopathological changes in the synovium of joints were observed via hematoxylin and eosin (HE) staining. The expression levels of arachidonic acid (AA) signaling pathway were assessed via real-time polymerase chain reaction (qPCR) and Western blot. Flow cytometry was used to determine the proportion of M1 and M2 macrophages in the peripheral blood. An enzyme-linked immunosorbent assay (ELISA) was used to detect interleukine (IL)-1 β, tumor necrosis factor-alpha (TNF-α), IL-4, IL-10, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4).@*RESULTS@#HE staining showed that TSDN improved the synovial tissue. qPCR and Western blot showed that on the 3rd, 5th and 8th days of drug administration, TSDN reduced the mRNA and protein expressions of cyclooxygenase (COX)2, microsomal prostaglandin E synthase-1 derived eicosanoids (mPGES-1), 5-lipoxygenase (5-LOX), recombinant human mothers against decapentaplegic homolog 3 (Smad3), nucleotide-binding oligomerization domain-like receptor protein 3 (NALP3), and inducible nitric oxide synthase (iNOS) in rats' ankle synovial tissues (P<0.01). TSDN decreased COX1 mRNA and protein expression on 3rd and 5th day of drug administration and raised it on the 8th day (both P<0.01). It lowered CD68 protein expression on days 3 (P<0.01), as well as mRNA and protein expression on days 5 and 8 (P<0.01). On the 3rd, 5th, and 8th days of drug administration, TSDN elevated the mRNA and protein expression of Arg1 and CD163 (P<0.01). Flow cytometry results showed that TSDN decreased the percentage of M1 macrophages while increasing the percentage of M2 in peripheral blood (P<0.05 or P<0.01). ELISA results showed that on the 3rd, 5th, and 8th days of drug administration, TSDN decreased serum levels of IL-1 β, TNF-α, and LTB4 (P<0.01), as well as PGE2 levels on days 3rd and 8th days (P<0.05 or P<0.01); on day 8 of administration, TSDN increased IL-4 serum levels and enhanced IL-10 contents on days 5 and 8 (P<0.05 or P<0.01).@*CONCLUSION@#The anti-inflammatory effect of TSDN on rats with GA may be achieved by influencing M1/M2 polarization through AA signaling pathway.
Subject(s)
Rats , Humans , Animals , Arthritis, Gouty/drug therapy , Monocytes/pathology , Interleukin-10/metabolism , Arachidonic Acid/pharmacology , Dioscorea/chemistry , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism , Saponins/therapeutic use , Interleukin-4/metabolism , Leukotriene B4/pharmacology , Rats, Sprague-Dawley , Macrophages , Signal Transduction , RNA, Messenger/metabolismABSTRACT
OBJECTIVE@#To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).@*METHODS@#From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.@*RESULTS@#In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.@*CONCLUSIONS@#GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).
Subject(s)
Humans , Percutaneous Coronary Intervention/adverse effects , Quality of Life , Depression , Coronary Disease/drug therapy , Drugs, Chinese Herbal/therapeutic use , Angina Pectoris/drug therapy , Prognosis , Anxiety , Treatment Outcome , Double-Blind MethodABSTRACT
OBJECTIVE@#To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro.@*METHODS@#In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA).@*RESULTS@#GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil.@*CONCLUSIONS@#GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.
Subject(s)
Mice , Rabbits , Animals , Antidiarrheals/adverse effects , Jejunum , Glycyrrhiza uralensis , Castor Oil/adverse effects , Calcium Chloride/adverse effects , Diarrhea/drug therapy , Plant Extracts/adverse effects , Verapamil/adverse effects , Muscle ContractionABSTRACT
At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.
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Objective: To compare the short-term efficacy and long-term prognosis of laparoscopic and laparotomy radical resection for gallbladder cancer(GBC). Methods: From January 2010 to December 2020,the clinical data and survival information for 133 patients who underwent radical resection of GBC at the Department of Hepatopancreatobiliary Surgery,Zhejiang Provincial People's Hospital,were retrospectively collected. Eighty patients(23 males and 57 females) underwent laparoscopic radical resection and had a median age(M(IQR)) of 66.0(12.8)years(range:28.0 to 82.0 years). Fifty-three patients(45 males and 8 females) who received laparotomy were 63.0(6.0)years old(range:45.0 to 80.0 years old). There were no significant differences in age,gender,body mass index,preoperative albumin,preoperative total bilirubin,N stages,vascular invasion,peri-neural invasion or tumor differentiation between the laparoscopic and laparotomy group(all P>0.05). But there were significant differences in preoperative CA19-9(Z=-2.955, P=0.003), preoperative ALT level(Z=-2.801,P=0.031) and T stage (χ2=19.110,P=0.007) between the two groups. A non-parametric test was used for quantitative data. χ2 test or Fisher exact probability method was used for count data. Results: Patients in the laparoscopic group did not differ from those in the laparotomy group in terms of length of operation,number of lymph node yield,number of positive lymph nodes,the incidence of intraoperative gallbladder rupture,incidence of postoperative bile leakage,abdominal bleeding or abdominal infection,30-day mortality,90-day mortality, the incidence of incision implantation or peritoneal cavity metastasis(all P>0.05). Patients in the laparoscopic group showed less intraoperative bleeding(100.0(200.0)ml vs. 400.0(250.0)ml)(Z=-5.260,P<0.01),fewer days with drainage tube indwelling(6.0(3.8)days vs. 7.0(4.0)days)(Z=-3.351, P=0.001), and fewer postoperative days in hospital(8.0(5.0)days vs. 14.0(7.5)days)(Z=-6.079,P<0.01) than those in the laparotomy group. Patients in the laparoscopic group displayed better overall survival (P<0.01) and progression-free survival (P<0.01). Subgroup analysis for GBC of T1b-T2 and T3 stages revealed comparable overall survival and progression-free survival between the laparoscopic and laparotomy groups (P>0.05). Conclusions: Laparoscopic radical resection can achieve long-term survival for GBC comparable to that with open surgery. Laparoscopic radical resection has advantages over open surgery regarding surgical trauma and postoperative recovery.
Subject(s)
Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Gallbladder Neoplasms/surgery , Laparoscopy , Laparotomy , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE@#To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis.@*METHODS@#The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma.@*RESULTS@#A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker β-human chorionic gonadotropin (β-HCG) were normal in 8 patients.The serum β-HCG was normal in 11 patients but the cerebrospinal fluid β-HCG was slightly elevated, and the serum and cerebrospinal fluid β-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement.@*CONCLUSION@#The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.
Subject(s)
Child , Female , Humans , Male , Atrophy/pathology , Basal Ganglia/pathology , Biomarkers, Tumor , Brain Neoplasms/diagnostic imaging , Chorionic Gonadotropin, beta Subunit, Human , Germinoma/pathology , Magnetic Resonance Imaging , Neoplasms, Germ Cell and Embryonal , Retrospective StudiesABSTRACT
Objective:To explore the clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the direction of head and foot.Methods:Twenty-eight patients who presented Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from January 2017 to June 2019 were collected. All patients who underwent one-step CT angiography of the deep veins of the lower extremities to the pulmonary artery were randomly divided into two groups, A or B, and scanned from the entrance of the thorax to 10 cm below the knee joint. Group A was foot-head direction group with delayed time scanning according to empirical method. Group B was the head-foot direction group with a single point triggered automatic tracing scan at the level of the main pulmonary artery trunk. The independent sample t-test was used to compare the scan time, dose length product (DLP), and mean CT value of enhancement of the pulmonary artery opening between the two groups. Results:The average scanning time of the foot-head scanning group was (36.4±1.2)s, the average DLP was (684.4±37.8) mGy·cm, and the average enhanced CT value of pulmonary artery image was (181.3±15.5) HU. The average scanning time of the head foot scanning group was (16.4±0.3) s, the average DLP was (441.8±34.4) mGy·cm, and the average enhanced CT value of the pulmonary artery image was (257.9±24.5) HU. Scanning time, mean DLP, and pulmonary artery level enhancement values were significantly different between the two groups ( t=17.92, 4.71, 2.44, P<0.05). Conclusions:The clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the head-foot direction is significantly better than that in the head-foot direction. It can significantly shorten the scanning time, reduce the radiation dose, and increase the enhancement value of pulmonary artery to improve the detection of pulmonary embolism.
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Objective:To investigate the values of CT angiography (CTA) and color Doppler ultrasound in the diagnosis and etiological screening of varicocele (VC).Methods:Ninety-seven patients with VC diagnosed by the Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital from May 2016 to December 2017 were retrospectively included. The CTA and color Doppler ultrasonographic data of 194 spermatic veins (including 116 varicocele veins) were analyzed. Paired t test was used to compare the mean diameter of spermatic veins at the root of scrotum measured by CTA and color Doppler ultrasound. McNemar test was used to compare the sensitivity and specificity of CTA and color Doppler examination for VC, and χ 2 or Fisher exact probability was used to compare the detection rate of CTA and color Doppler examination in screening the etiology of VC. Results:The average diameters of scrotal root of spermatic veins by CTA and color Doppler ultrasonography were (2.9±0.6) and (3.0±0.6) mm for VC cases, with no significant difference found( t=0.885, P=0.381). According to the diagnostic VC standard of color Doppler ultrasound (diameter>2 mm), no significant difference was found between CTA and color Doppler ultrasound in the sensitivity [95.69%(111/116) vs. 100%(116/116)] and specificity [100%(78/78) vs. 100%(78/78)] in the diagnosis of VC. The etiological detection rate of CTA in 97 patients with VC was significantly higher than that of color Doppler ultrasound ( P<0.05). Conclusions:Both CTA and color Doppler ultrasound have high sensitivity and specificity in the diagnosis of VC. CTA has a higher etiological detection rate in etiological screening of VC than color Doppler ultrasound.
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Background@#Pseudorabies virus (PRV) infection leads to high mortality in swine. Despite extensive efforts, effective treatments against PRV infection are limited. Furthermore, the inflammatory response induced by PRV strain GXLB-2013 is unclear. @*Objectives@#Our study aimed to investigate the inflammatory response induced by PRV strain GXLB-2013, establish an inflammation model to elucidate the pathogenesis of PRV infection further, and develop effective drugs against PRV infection. @*Methods@#Kunming mice were infected intramuscularly with medium, LPS, and different doses of PRV-GXLB-2013. Viral spread and histopathological damage to brain, spleen, and lung were determined at 7 days post-infection (dpi). Immune organ indices, levels of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines, as well as levels of activity of COX-2 and iNOS were determined at 4, 7, and 14 dpi. @*Results@#At 105 –106 TCID50 PRV produced obviously neurological symptoms and 100% mortality in mice. Viral antigens were detectable in kidney, heart, lung, liver, spleen, and brain. In addition, inflammatory injuries were apparent in brain, spleen, and lung of PRVinfected mice. Moreover, PRV induced increases in immune organ indices, ROS and NO levels, activity of COX-2 and iNOS, and the content of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ and MCP-1. Among the tested doses, 10 2 TCID 50 of PRV produced a significant inflammatory mediator increase. @*Conclusions@#An inflammatory model induced by PRV infection was established in mice, and 102 TCID50 PRV was considered as the best concentration for the establishment of the model.
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Background@#Pseudorabies virus (PRV) infection leads to high mortality in swine. Despite extensive efforts, effective treatments against PRV infection are limited. Furthermore, the inflammatory response induced by PRV strain GXLB-2013 is unclear. @*Objectives@#Our study aimed to investigate the inflammatory response induced by PRV strain GXLB-2013, establish an inflammation model to elucidate the pathogenesis of PRV infection further, and develop effective drugs against PRV infection. @*Methods@#Kunming mice were infected intramuscularly with medium, LPS, and different doses of PRV-GXLB-2013. Viral spread and histopathological damage to brain, spleen, and lung were determined at 7 days post-infection (dpi). Immune organ indices, levels of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines, as well as levels of activity of COX-2 and iNOS were determined at 4, 7, and 14 dpi. @*Results@#At 105 –106 TCID50 PRV produced obviously neurological symptoms and 100% mortality in mice. Viral antigens were detectable in kidney, heart, lung, liver, spleen, and brain. In addition, inflammatory injuries were apparent in brain, spleen, and lung of PRVinfected mice. Moreover, PRV induced increases in immune organ indices, ROS and NO levels, activity of COX-2 and iNOS, and the content of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ and MCP-1. Among the tested doses, 10 2 TCID 50 of PRV produced a significant inflammatory mediator increase. @*Conclusions@#An inflammatory model induced by PRV infection was established in mice, and 102 TCID50 PRV was considered as the best concentration for the establishment of the model.
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With the development of economic globalization and the increasingly complex international competition environment, pharmaceutical research and development has become the most powerful weapon for pharmaceutical companies to cope with the uncertainty of the competitive market. From the perspective of the pharmaceutical industry, based on the five-element theory, the article used the thinking of comparative state to carry out analogy research on the five-element theory and entrepreneur type system. Based on the entrepreneur type system and enterprise management system, the article embedded the enterprise senior management team system, and entrepreneurs were included in the system and assigned roles according to their different characteristics. Then through the analysis of the relationship between different entrepreneurs and the research and development (R&D) directors, the article expounded the influence of different types of entrepreneurs on the R&D process. The purpose of this study is to provide different types of entrepreneurs with management solutions for pharmaceutical R&D innovation and internal collaborative management, which is conducive to the analysis of advantages and disadvantages of entrepreneurs based on their own characteristics, and can effectively improve their ability of internal resource integration and independent innovation in drug R&D.
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Objective:To study the effects of FcγRIIb gene modified dendritic cells on liver function and rejection after orthotopic liver transplantation in rats.Methods:The recombinant lentivirus expression vector TRE-FcγRIIb containing Lewis rat FcγRIIb gene was constructed by gene cloning technique. TRE-FcγRIIb expression virus and TET-on regulatory virus were packaged and co-infected with immature dendritic cells derived from DA rat bone marrow. The expression of FcγRIIb was detected. Donor rats DA and recipient Lewis were paired according to body weight and then randomly divided into three groups. The control group (group A) did not receive any pretreatment. The Lewis rats in group B were treated with cyclosporin A on the 2nd day after liver TX. Immature dendritic cells derived from bone marrow of DA rats were injected intravenously one day before liver TX in FcγRIIb gene modified immature dendritic cells (1×10 6 cells)group (group C). Blood and liver tissue were biopsied 7 days after operation to detect liver function and pathological changes. Results:The abnormal liver function in FcγRIIb gene modified immature dendritic cells group (group C) was significantly lower than that of control group 7 days after operation ( P<0.05), and the liver pathological rejection of FcγRIIb gene modified immature dendritic cells group (group C) was significantly lower than that of control group 7 days after operation ( P<0.05). The average survival days of rats in the control group was 12.8 days; the average survival days of rats in the cyclosporin A group was 65.3 days; the average survival days of rats in the FcγRIIb gene-modified immature dendritic cell group was 58.5 days. Conclusion:FcγRIIb gene modified immature dendritic cells can ameliorate liver dysfunction and acute liver rejection after orthotopic liver transplantation.
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OBJECTIVE@#To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes.@*METHODS@#The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters.@*RESULTS@#PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05).@*CONCLUSION@#PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.