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Objective To investigate the clinical characteristics of stasis-toxin pathogenesis in patients with non-small cell lung cancer(NSCLC)of blood stasis and qi stagnation type,and to explore the interventional mechanism of adjuvant therapy with Bufei Huayu Decoction.Methods Seventy-eight patients with NSCLC of blood stasis and qi stagnation type admitted to the Department of Respiratory Medicine of Liu'an Hospital of Traditional Chinese Medicine from January 2021 to September 2022 were selected as the NSCLC group,and 71 volunteers who underwent physical examination during the same period served as the healthy control group.The clinical characteristics of stasis-toxin pathogenesis in the NSCLC group were observed,and the differences in the indicators of coagulation function were compared between NSCLC group and the healthy control group.According to the therapy,the NSCLC patients were divided into Bufei Huayu Decoction group(40 cases)and conventional treatment group(38 cases).The conventional treatment group was treated with conventional chemotherapy,while Bufei Huayu Decoction group was treated with Bufei Huayu Decoction together with conventional chemotherapy.Three weeks constituted one course of treatment,and the treatment lasted for 2 courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,coagulation function,immune function,serum nitric oxide(NO),vascular endothelial growth factor(VEGF)level in Bufei Huayu Decoction group and conventional treatment group were observed before and after treatment.Moreover,the clinical efficacy of the two groups and the occurrence of adverse reactions were compared during the treatment period.Results(1)NSCLC patients were classified into the clinical stages Ⅲ and Ⅳ and the pathological types of squamous carcinoma and adenocarcinoma,had the high proportion of KPS scores lower than 70,and were scored with high TCM syndrome scores,suggesting that the illness condition of patients with NSCLC was serious.Compared with the healthy control group,plasminogen time(PT)and thrombin time(TT)in NSCLC patients were significantly shortened,and levels of fibrinogen(FIB)and D-dimer(D-D)were significantly increased,and the differences were statistically significant(P<0.01).(2)After 6 weeks of treatment,the total effective rate and total stability rate of Bufei Huayu Decoction group were 32.50%(13/40)and 85.00%(34/40),which were significantly superior to those of the conventional treatment group[versus 13.16%(5/38)and 60.53%(23/38)],and the differences were statistically significant(P<0.05).(3)After 3 weeks of treatment,obvious improvement was presented in the scores of all the TCM symptoms of fatigue,chest distress and shortness of breath,stabbing pain in the chest,and blood stasis in the vessels and collaterals of Bufei Huayu Decoction group and in the scores of the fatigue,chest distress and shortness of breath of the conventional treatment group when compared with those before treatment(P<0.05).After 6 weeks of treatment,all of the TCM syndrome scores of the two groups were improved compared with those before treatment and after three weeks of treatment(P<0.05).The intergroup comparison showed that except for the scores of chest distress and shortness of breath after 3 weeks of treatment,the effect on improving all of the TCM syndrome scores in Bufei Huayu Decoction group was significantly superior to that in the conventional treatment group after 3 and 6 weeks of treatment(P<0.05 or P<0.01).(4)After 6 weeks of treatment,the levels of coagulation function indicators of PT,TT,FIB and D-D in the Bufei Huayu Decoction group were significantly improved compared with those before treatment(P<0.05),while only FIB and D-D in the conventional treatment group were improved compared with those before treatment(P<0.05).The intergroup comparison showed that Bufei Huayu Decoction group had stronger effect on improving the levels of PT,FIB and D-D than the conventional treatment group(P<0.05).(5)After 6 weeks of treatment,the serum NO and VEGF levels in both groups were significantly lower than those before treatment(P<0.05),and the effect on lowering serum NO and VEGF levels of the Bufei Huayu Decoction group was significantly superior to that of the conventional treatment group(P<0.01).(6)After 6 weeks of treatment,the immune function parameters of CD3+,CD4+ levels and CD4+/CD8+ ratio in the Bufei Huayu Decoction group were increased(P<0.05)and CD8+level was decreased(P<0.05)as compared with those before treatment,whereas CD3+,CD4+ levels and CD4+/CD8+ ratio in the conventional treatment group were decreased(P<0.05)and CD8+ level was increased(P<0.05).The intergroup comparison showed that the effect of Bufei Huayu Decoction group on the increase of CD3+,CD4+ levels and CD4+/CD8+ ratio and the effect on the decrease of CD8+ level were significantly superior to those of the conventional treatment group(P<0.01).(7)In terms of the quality of life,the KPS scores of patients in the two groups after 6 weeks of treatment were significantly higher than those before treatment(P<0.05),and the effect of Bufei Huayu Decoction group on the increase of KPS scores was significantly superior to that of the conventional treatment group(P<0.01).(8)During the course of treatment,the incidence of adverse reactions such as gastrointestinal reactions and alopecia in the two groups was not statistically significant(P>0.05),while the incidence of hepatic and renal impairment,bone marrow suppression,and toxicity of oral mucosa in Bufei Huayu Decoction group was significantly lower than that of the conventional treatment group(P<0.05 or P<0.01),suggesting that Bufei Huayu Decoction group reduced the adverse reactions induced by chemotherapy to a certain extent.Conclusion Patients with NSCLC of blood stasis and qi stagnation type generally have advanced disease progression and high blood coagulation,which is consistent with the stasis-toxin pathogenesis in TCM.The use of Bufei Huayu Decoction against the stasis-toxin pathogenesis can significantly improve patients'TCM syndrome scores and coagulation function,down-regulate the levels of serum NO and VEGF,and improve the immune function,which brings about the enhancement of clinical efficacy and quality of life,and the reduction of adverse reactions caused by chemotherapy,with a high safety.
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ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis (UC) through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS, and 56 BALB/c male mice were randomly divided into model group, AMPK inhibitor group (20 mg·kg-1), paeoniflorin (50 mg·kg-1) + inhibitor (20 mg·kg-1) group, and high dose (50 mg·kg-1), medium dose (25 mg·kg-1), and low dose (12.5 mg·kg-1) paeoniflorin groups. After seven days of drug intervention, the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight, disease activity index (DAI) changes, and Hematoxylin-eosin (HE) staining results. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum of mice in each group, and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 (LC3) content in the colon, AMPK, mTOR proteins, and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot, and the mRNA expression levels of AMPK, mTOR, Beclin1, LC3, and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the blank group, the model group showed a decrease in body mass, an increase in DAI score, and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum (P<0.01), while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue, and those of p-mTOR/mTOR were up-regulated (P<0.01). The mRNA expression levels of AMPK and LC3 were down-regulated, while the mRNA expression levels of mTOR and p62 were up-regulated (P<0.01). Compared with the model group and the paeoniflorin + inhibitor group, the mice treated with paeoniflorin showed an increase in body mass, a decrease in DAI score, a reduction in pathological damage to colon tissue, and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum (P<0.05). The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated, while the protein levels of p-mTOR/mTOR were down-regulated (P<0.01). The mRNA expression levels of AMPK, Beclin1, and LC3 were up-regulated, while the mRNA expression of mTOR and p62 were down-regulated (P<0.01). The colon tissue of the inhibitor group was severely damaged, and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.
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BACKGROUND@#Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia.@*METHODS@#In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared.@*RESULTS@#A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05).@*CONCLUSIONS@#The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.
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Humans , Retrospective Studies , Pneumonia/diagnostic imaging , Analysis of Variance , Tomography, X-Ray Computed , Lymphoma/diagnostic imagingABSTRACT
OBJECTIVE@#To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF).@*METHODS@#The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events.@*RESULTS@#A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor.@*CONCLUSION@#Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.
Subject(s)
Humans , Biomarkers , Drug Combinations , Drugs, Chinese Herbal , Follow-Up Studies , Heart Failure/drug therapy , Natriuretic Peptide, Brain , Peptide Fragments , Prognosis , Retrospective Studies , Stroke Volume , Ventricular Function, LeftABSTRACT
Objective:To explore the MRI features of fetal coronal cleft vertebrae, and to compare the efficacy of MRI and ultrasound in the diagnosis of fetal coronal cleft vertebrae, and to analyze the outcome of fetal coronal cleft vertebrae.Methods:From September 2019 to June 2021, 40 fetuses suspected of fetal vertebral deformities by ultrasound were retrospectively collected in Shandong Provincial Hospital Affiliated to Shandong University, who were diagnosed as coronal cleft vertebrae after MRI examination. Five cases of induced labor and 14 cases lost to follow-up were excluded, and 21 fetuses who underwent MRI after delivery were finally included. The gestational weeks were 25-34 (29.1±2.6) weeks, and there were 19 males and 2 females. Fetal spine MRI includes susceptibility weighted imaging (SWI) and T 2-true fast imaging with steady-state (True-FISP). The MRI features and outcome of fetal coronal cleft vertebrae were explored. The image quality scores of SWI, T 2-True-FISP and ultrasound were compared with Friedman test and Wilcoxon signed-rank test. The diagnostic accuracy of fetal coronal cleft vertebrae of SWI, T 2-True-FISP and ultrasound was calculated. Cochran test was used to compare the efficiency of 3 kinds of images, and the modified McNemar test was used for pairwise comparison between groups. Results:There were 10 cases of single and 11 cases of multiple fetal coronal cleft vertebrae, 16 cases of simple lumbar vertebrae, 2 cases of simple thoracic vertebrae, and 3 cases of thoracolumbar vertebrae. The common SWI features of 21 cases show longitudinal strip or dot high signal on the sagittal plane, and transverse fissure like high signal on axial plane. Anterior part of vertebral body was larger than posterior part in 19 cases of them. The image quality scores of SWI, T 2-True-FISP and ultrasound were 4 (3, 4), 2 (2, 2), 2 (2, 2), and the difference was statistically significant in general (χ2=34.24, P<0.001). Pairwise comparison showed that the image quality of SWI was better than those of T 2-True-FISP and ultrasound ( Z=-4.04, P<0.001; Z=-4.11, P<0.001), and there was no statistically significant difference between T 2-True-FISP and ultrasound ( Z=-0.58, P=0.388). The diagnostic accuracy of SWI, T 2-True-FISP and ultrasound was 100% (21/21), 66.7% (14/21), 47.6% (10/21). The diagnostic accuracy of SWI was better than those of T 2-True-FISP and ultrasound (χ2=5.14, P=0.008; χ2=9.09, P<0.001), and there was no statistically significant difference between T 2-True-FISP and ultrasound (χ2=0.75, P=0.194). MRI showed that coronal cleft vertebrae disappeared in all 21 fetuses after birth, including 1 case of syringomyelia and 1 case of fatty filum terminal. Conclusions:MRI, especially SWI, plays an important role in the diagnosis of fetal coronal cleft vertebrae. Fetal coronal cleft vertebrae disappeared in the follow-up after birth, which proved to be a normal physiological variation from the radiographic perspective.
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In order to solve the problem of poor robustness of the traditional method of calculating torque in the mechanical model of 7-DOF picking manipulator, this paper proposes a control strategy of calculating torque plus fuzzy compensation by using adaptive fuzzy logic system to compensate the uncertain part of the mechanical model of 7-DOF picking manipulator. By using Lagrange method, the dynamic model of 7-DOF manipulator is established, and the relationship between joint motion and applied torque (force) is obtained. Using ADAMS and MATLAB to establish a co-simulation platform, the manipulator and trajectory tracking control system are simulated. The results show that the trajectory tracking error of each joint in the algorithm is obviously reduced and the convergence trend is obvious. The average trajectory tracking accuracy of joint 1 to joint 7 was improved by 70.22%, 94.78%, 0.62%, 74.23%, 89.78%, 86.45%, and 67.15%, respectively. In this control scheme, the control force (moment) of each joint changes regularly, and the output force (moment) does not appear chattering and mutation when the disturbance signal is added. The research results can provide support for the further study of picking manipulator trajectory tracking control system.
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Robotics , Algorithms , Computer Simulation , Fuzzy Logic , Motion , Robotics/methodsABSTRACT
Objective To investigate the relationship between the expressions of iron transport related proteins and the dysregulation of iron homeostasis in the spinal cord of amyotrophic lateral sclerosis (ALS) transgenic mice. Methods The hSOD1
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Objective:To evaluate the feasibility and the application values of quantitative susceptibility mapping (QSM) for the assessment of meniscal injury and in distinguishing meniscus degeneration and tears.Methods:The clinical and imaging data of 70 patients suspected of meniscus injury and scheduled for arthroscopy in Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University from November 2019 to June 2020 were analyzed retrospectively. Thirty age-and sex-matched healthy subjects were also examined as controls. All subjects received knee joint QSM and routine MR imaging. According to the results of arthroscopy, the patients was divided into meniscus degeneration and meniscus tear groups, respectively. The conventional MR was evaluated by two radiologists. The meniscus injury area was delineated on the original QSM magnitude images (the central area of the posterior corner of the lateral meniscus was selected in the healthy controls) and mapped to the corresponding QSM maps, and the magnetic susceptibility values were measured. Kruskal-Wallis H test was used to analyze the magnetic sensitivity values of meniscal degeneration, meniscal tear and healthy control groups; and Bonferroni was used to correct the pairwise comparison. ROC curve was established to evaluate the threshold and efficacy of magnetic susceptibility value in the diagnosis of meniscal tear. The results were compared with those of conventional MRI. Results:The magnetic susceptibility values of meniscus of healthy controls, meniscal degeneration and meniscal tear groups were (0.035±0.016)ppm, -0.031(-0.040,-0.005)ppm, and(-0.122±0.115)ppm, respectively, with significant difference found among the three groups (χ2=44.419, P<0.05). The magnetic susceptibility values of meniscus of healthy controls was significantly higher than those of meniscus degeneration patients and meniscus tear patients (χ2=-23.843, -48.253, P<0.05). The magnetic susceptibility values of meniscus of meniscus tear group was significant lower than those of meniscus degeneration group (χ2=-24.410, P<0.05). Taking magnetic susceptibility values of -0.062 5 ppm as threshold, the area under the ROC curve for the diagnosis of meniscal tears was 0.949, with the sensitivity as 87% and the specificity as 100%. The sensitivity and specificity of conventional MRI in the diagnosis of meniscal tears were 86.8% and 87.5%, respectively. Conclusion:QSM can quantitatively evaluate meniscus injury and can be used as an effective supplement method to conventional MRI, which is helpful to improve the diagnosis of meniscus tear.
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Objective:To evaluate the feasibility of high resolution MRI for the measurement of anterior cartilaginous acetabulum-head-index (A-CAHI) and the value of A-CAHI for predicting hip clinical function after treatment in developmental dysplasia of the hip (DDH).Methods:The imaging data of 92 hips from 61 children with treated DDH were retrospectively reviewed in Shandong Medical Imaging Research Institute from January 2019 to January 2020. All children underwent conservative treatments or surgical interventions 3 years ago. Hip function after treatment was evaluated clinically based on the modified MacKay criteria. The hips were divided into satisfactory clinical function group (McKay rating excellent or good, n=46) and unsatisfactory group (McKay rating fair or poor, n=46). All patients were imaged with conventional MRI, high resolution fat suppressed proton density weighted image (FS-PDWI) of the unilateral hip joint in oblique sagittal view, and anteroposterior hip radiographs. A-CAHI and lateral cartilaginous acetabulum-head-index (L-CAHI) were measured respectively on high-resolution oblique sagittal PDWI and conventional coronal T 1WI. Acetabulum head index (AHI) was also measured on anteroposterior hip radiograph. Mann-Whitney U test or independent-samples t test was used to compare the difference of A-CAHI, L-CAHI and AHI between satisfactory and unsatisfactory clinical function groups. The diagnostic value using A-CAHI, L-CAHI, AHI, or A-CAHI combined with L-CAHI for unsatisfactory clinical function were investigated by the ROC curve. The area under the curve (AUC) and the Z statistic were used to compare diagnostic performance. Results:The values of A-CAHI, L-CAHI and AHI were significantly higher in satisfactory clinical function group compared with the unsatisfactory group ( Z=-7.746, -7.735, t=-7.199, all P<0.001).A-CAHI combined with L-CAHI had the significant highest diagnostic accuracy compared with A-CAHI, L-CAHI and AHI (AUC were 0.994, 0.969, 0.968, 0.861, respectively), with significant differences ( Z=1.975, 2.006, 3.553, P=0.048, 0.051,<0.001). The sensitivity and specificity of A-CAHI combined with L-CAHI for the diagnosis of prognosis were 95.7% and 97.8%, respectively. Conclusions:A-CAHI measured by high resolution MRI was found to have the highest diagnostic accuracy for prediction of hip clinical function in the treated DDH, and combined with L-CAHI can improve the diagnostic accuracy significantly.
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To observe the effect of shikonin on the proliferation, migration, adhesion and invasion of rheumatoid arthritis(RA) fibroblast like synoviocytes induced by tumor necrosis factor-α(TNF-α), and to explore its mechanism of action from aspects of protein kinase B(Akt) and mitogen activated protein kinase(MAPK) signaling pathways. TNF-α(20 ng·mL~(-1)) was used in this experiment to induce human RA fibroblast like synovial cell line(MH7 A). After addition of different concentrations of shikonin(0.025, 0.05, 0.1 pmol·L~(-1)), the proliferation, migration, adhesion and invasion ability of MH7 A cells were detected by MTT test, scratch test, adhesion test, Transwell invasion test, respectively. Protein expression of Akt and MAPK signaling pathway molecules in MH7 A cells was detected by Western blot. The results showed that as compared with the control group, TNF-α could significantly induce the proliferation, migration, adhesion and invasion of MH7 A cells, and increase the phosphorylation level of Akt, JNK, p38 and extracellular regulatory protein kinase(ERK). As compared with the TNF-α group, shikonin had no significant effect on TNF-α-induced proliferation of MH7 A cells after 24 h treatment, and it could reduce the TNF-α-induced proliferation of MH7 A cells in a concentration dependent manner after 48 h treatment. Shikonin also significantly reduced the TNF-α-induced migration, adhesion, invasion and phosphorylation levels of Akt, JNK, p38, ERK in MH7 A cells within 24 h. These results suggested that shikonin could reduce the proliferation, migration, adhesion and invasion ability of MH7 A cells induced by TNF-α, and its mechanism may be related to the down-regulation of Akt and MAPK signaling pathway activation.
Subject(s)
Arthritis, Rheumatoid , Synoviocytes , Arthritis, Rheumatoid/drug therapy , Cell Movement , Cell Proliferation , Cells, Cultured , Fibroblasts , Humans , Naphthoquinones , Synovial Membrane , Tumor Necrosis Factor-alpha/geneticsABSTRACT
The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.
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Objective:To evaluate alterations of periventricular pseudocysts (PVPC) on MRI before and after birth, and to assess the prognosis.Methods:We retrospectively analyzed the data of 67 cases that were diagnosed with PVPC on prenatal MRI, of which 24 cases were lost to follow-up, 2 died after birth. A total of 41 surviving fetuses were included in this prognosis study. The gestational ages in this group were between 23 and 39 weeks, with an average of (33±3) weeks.All the subjects underwent brain MRI examinations and Gesell Developmental Scale (GDS) testing between 0-3 years of age. According to the location of cysts and with or without other intracranial and extracranial malformations (dilated ventricles orcerebella medulla, hypoxic-ischemic encephalopathy, TORCH virus infection, corporal hypoplasia, chromosomal malformations and nodular sclerosis) , the patients were divided into four groups: isolated connatal cysts, connatal cysts with additional findings,isolated subependymal pseudocysts, and subependymal pseudocysts with additional findings.The MR images were independently reviewed by two radiologists blinded to the clinical information. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two reviewers.Chi-square test was used to compare the location of cysts (single/bilateral), the number of cyst cavities (single/multi-chamber), and other abnormalities in the connatal cyst group and subependymal cyst group. The mean anteroposterior diameter and mean height of cysts between the connatal cyst group and subependymal cyst group were compared by independent sample t-test.The ANOVA test was used to compare the differences in GDS outcomes among the groups. Multiple comparisons were conducted using the LSD test. Results:Inter-observer agreements between the two radiologists were good for the collected data (all ICC>0.75). Eleven isolated connatal cysts and 7 connatal cysts with additional findings became smaller or disappeared, and all had good prognosis. Of the 14 isolated subependymal cysts, 12 became smaller or disappeared, 2 had no change in size, and 13 had good prognosis. The subependymal cysts with additional findings group included 9 cases: 6 became smaller or disappeared, only 3 showed no apparent changes, and 7 had an abnormal outcome. Subependymal cysts with additional findings were significantly reduced and patients demonstrated significant differences compared with the those with isolated subependymal cysts in the development quotients (DQ) of adaptability, large movements, fine movements, personal social interaction, and language DQ ( P all<0.05). DQ between patients with isolated connatal cysts and isolated subependymal cysts was comparable ( P all>0.05). When associated with additional findings, connatal cysts and subependymal cysts could induce significant different DQ outcome ( P all<0.05). Conclusions:Isolated PVPC usually become smaller or disappeared and have a benign presentation after birth, whereas patients with subependymal cysts with additional findings usually have a poor prognosis. Connatal cysts usually have a good prognosis.
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Objective:To discuss the feasibility of prenatal MRI in evaluating fetal auricle developmental malformation and atresia of external auditory canal.Methods:Fifteen pregnant women (aged from 22 to 40 years old, mean age 31.3±5.2 years old) with fetal external ear developmental malformation suspected by ultrasound underwent MR scanning between November 2017 and May 2019. All of them were singleton. The gestational age ranged from 23 weeks to 35 weeks, with an average of (27.5±3.5) weeks. The sensitivity, specificity and accuracy of MRI and ultrasound in the diagnosis of fetal auricle malformation and atresia of external auditory canal were calculated and compared, using postnatal follow-up as the gold standard. Fisher exact test was used to compare the efficacy of MRI and ultrasound in diagnosing atresia of external auditory canal.Results:A total of 30 fetal external ears were detected in 15 fetuses, without auricle absence. Totally 19 external ears with developmental malformation were confirmed by postnatal follow-up, including 19 ears with auricle malformation and 15 ears with external auditory canal atresia. The accuracy of MRI and ultrasound in the diagnosis of auricle malformation was both 100% (19/19). For the diagnosis of external auditory canal atresia, the sensitivity, specificity and accuracy of MRI and ultrasound were 93.3% (14/15), 75.0% (3/4), 89.5% (17/19) and 33.3% (5/15), 25.0% (1/4), 31.6% (6/19), respectively. The sensitivity and accuracy of MRI in the diagnosis of atresia of external auditory canal were significantly higher than those of ultrasound, with statistically significant difference ( P=0.004, 0.001). Conclusion:MRI plays an important role in the diagnosis of fetal external ear developmental malformation, which can be used as an effective supplement to ultrasound, especially for the diagnosis of external auditory atresia.
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Objective:To investigate the correlation of age with diffusion tensor imaging (DTI) values as fractional anisotropy (FA), apparent diffusion coefficient (ADC) and contrast to noise ratio (CNR) of three-dimensional nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation imaging (3D SHINKEI) of the brachial plexus in normal adults.Methods:A total of 54 adult healthy volunteers and 6 patients with Guillain-Barre syndrome were prospectively enrolled from October 2018 to April 2019. Healthy volunteers were divided into 3 groups according to age as 21-40 years old group ( n=20), 41-60 years old group ( n=20), and ≥61 years old group ( n=14). All of them underwent MRI examination of the brachial plexus, including DTI and 3D SHINKEI sequences. The average FA and ADC values of the brachial plexus were measured and calculated through the fusion of DTI and 3D SHINKEI by 2 physicians independently. The contrast to noise ratio (CNR) of brachial plexus nerve was measured in 3D SHINKEI sequence images. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two physicians. A simple linear regression model and Pearson correlation analysis were used to detect the correlation between FA, ADC, CNR and age. One-way analysis of variance was used to compare the differences of FA, ADC and CNR in different age groups. The FA and ADC values in different genders were compared by independent sample t-test. Results:Inter-observer agreements of the 2 physicians were good for FA and ADC values with ICC values of 0.811 and 0.901, respectively. For different groups, FA values were 0.397±0.023, 0.368±0.023, and 0.334±0.018 and ADC values were (1.376±0.072) × 10 -3 mm 2/s, (1.466±0.086) × 10 -3 mm 2/s, (1.486±0.080) × 10 -3 mm 2/s, for 21-40, 41-60, and ≥61 years old groups, respectively with statistical significant difference ( F=25.311, P<0.001; F=9.948, P<0.001). The CNR of the brachial plexus were 510.583±192.846, 502.581±128.821, and 426.782±113.648 for 21-40, 41-60, and ≥61 years old group without statistical difference ( F=1.429, P=0.249). The FA value of brachial plexus was highly negatively correlated with age ( r=-0.745, P<0.001), while the ADC value was moderately positively correlated with age ( r=0.596, P<0.001). The CNR of 3D SHINKEI sequence was negatively correlated with age ( r=-0.292, P=0.033). There was no statistically significant difference in brachial plexus FA and ADC values between male and female subjects ( t=1.496, P=0.141; t=-1.557, P=0.126). The FA value of Guillain-Barre syndrome patients was lower than that of healthy volanteers in the same age group ( t=6.129, P<0.001), and the ADC value had no statistical diference ( t=-1.335, P=0.186). Conclusion:The values of FA, ADC and CNR of brachial plexus in normal adults change with age. Among them, FA value is more significant.
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Objective To investigate the effect of glycogen synthase kinase 3β (GSK3β) on the decreased expression of Bmal1 induced by amyloid-beta protein 31-35 (Aβ31-35) in HT22 cells.Methods HT22 mouse hippocampal cells were divided into control group,Aβ31-35 group and LiCl+Aβ 31-35 group by random number table method in the present study.Cells were synchronized to G0/G1 phase by 1% serum starvation for 1 hour (circadian time 0 (CT0)).Cell viability was detected by the cell counting kit-8 assay.The mRNA expression of clock gene Bmal1 was examined by real-time PCR at different CT times.The expression of GSK3β and BMAL1 protein was detected by Western blotting.Results Compared with the control group,Aβ31-35 induced the decreased expression of Bmal1 mRNA;The expression of both Bmal1 mRNA and BMAL1 protein was decreased significantly at CT20 (Bmal1 mRNA:0.38±0.06 vs 0.83±0.08,t=4.549,P=0.001;BMAL1 protein:0.67±0.04 vs 1.00±0.04,t=5.943,P<0.001).In the Aβ31-35group,GSK3β activity was increased and the ratio of phosphorylated GSK3βS9 to GSK3β was decreased compared to the control group (0.66±0.08 vs 1.02±0.14,t=2.217,P=0.025).Aβ31-35 decreased the viability of HT22 cells (71.85%±6.20% in the Aβ31-35 group vs 98.14%±2.68% in the control group,t=3.891,P=0.006),and the GSK3β inhibitor LiC1 pretreatment effectively reversed the decline of the viability induced by Aβ31-35 (90.74%±5.74% in the LiCl+Aβ31-35 group vs 71.85%±6.20% in the Aβ31-35 group,t=3.412,P=0.010).LiCl (in the LiCl+Aβ31-35 group) increased the expression of Bmal1 mRNA and BMAL1 protein significantly at CT20 compared with the Aβ31-35 group (Bmal1 mRNA:0.72±0.05 vs 0.38±0.06,t=4.378,P=0.001;BMAL1 protein:0.90±0.04 vs 0.67±0.04,t=4.052,P=0.002).Conclusion Increased GSK3β activity involved in the decreased expression of Bmal 1 induced by Aβ31-35 in HT22 cells.
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Objective@#To investigate the effect of glycogen synthase kinase 3β (GSK3β) on the decreased expression of Bmal1 induced by amyloid-beta protein 31-35 (Aβ31-35) in HT22 cells.@*Methods@#HT22 mouse hippocampal cells were divided into control group, Aβ31-35 group and LiCl+Aβ 31-35 group by random number table method in the present study. Cells were synchronized to G0/G1 phase by 1% serum starvation for 1 hour (circadian time 0 (CT0)). Cell viability was detected by the cell counting kit-8 assay. The mRNA expression of clock gene Bmal1 was examined by real-time PCR at different CT times. The expression of GSK3β and BMAL1 protein was detected by Western blotting.@*Results@#Compared with the control group, Aβ31-35 induced the decreased expression of Bmal1 mRNA; The expression of both Bmal1 mRNA and BMAL1 protein was decreased significantly at CT20 (Bmal1 mRNA: 0.38±0.06 vs 0.83±0.08, t=4.549, P=0.001; BMAL1 protein: 0.67±0.04 vs 1.00±0.04, t=5.943, P<0.001). In the Aβ31-35 group, GSK3β activity was increased and the ratio of phosphorylated GSK3βS9 to GSK3β was decreased compared to the control group (0.66±0.08 vs 1.02±0.14, t=2.217, P=0.025). Aβ31-35 decreased the viability of HT22 cells (71.85%±6.20% in the Aβ31-35 group vs 98.14%±2.68% in the control group, t=3.891, P=0.006), and the GSK3β inhibitor LiCl pretreatment effectively reversed the decline of the viability induced by Aβ31-35 (90.74%±5.74% in the LiCl+Aβ31-35 group vs 71.85%±6.20% in the Aβ31-35 group, t=3.412, P=0.010). LiCl (in the LiCl+Aβ31-35 group) increased the expression of Bmal1 mRNA and BMAL1 protein significantly at CT20 compared with the Aβ31-35 group (Bmal1 mRNA: 0.72±0.05 vs 0.38±0.06, t=4.378, P=0.001; BMAL1 protein: 0.90±0.04 vs 0.67±0.04, t=4.052, P=0.002).@*Conclusion@#Increased GSK3β activity involved in the decreased expression of Bmal1 induced by Aβ31-35 in HT22 cells.
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Objective@#To investigate the effect of glycogen synthase kinase 3β (GSK3β) on the decreased expression of Bmal1 induced by amyloid-beta protein 31-35 (Aβ31-35) in HT22 cells.@*Methods@#HT22 mouse hippocampal cells were divided into control group, Aβ31-35 group and LiCl+Aβ31-35 group by random number table method in the present study. Cells were synchronized to G0/G1 phase by 1% serum starvation for 1 hour (circadian time 0 (CT0)). Cell viability was detected by the cell counting kit-8 assay. The mRNA expression of clock gene Bmal1 was examined by real-time PCR at different CT times. The expression of GSK3β and BMAL1 protein was detected by Western blotting.@*Results@#Compared with the control group, Aβ31-35 induced the decreased expression of Bmal1 mRNA; The expression of both Bmal1 mRNA and BMAL1 protein was decreased significantly at CT20 (Bmal1 mRNA: 0.38±0.06 vs 0.83±0.08, t=4.549, P=0.001; BMAL1 protein: 0.67±0.04 vs 1.00±0.04, t=5.943, P<0.001). In the Aβ31-35 group, GSK3β activity was increased and the ratio of phosphorylated GSK3βS9 to GSK3β was decreased compared to the control group (0.66±0.08 vs 1.02±0.14, t=2.217, P=0.025). Aβ31-35 decreased the viability of HT22 cells (71.85%±6.20% in the Aβ31-35 group vs 98.14%±2.68% in the control group, t=3.891, P=0.006), and the GSK3β inhibitor LiCl pretreatment effectively reversed the decline of the viability induced by Aβ31-35 (90.74%±5.74% in the LiCl+Aβ31-35 group vs 71.85%±6.20% in the Aβ31-35 group, t=3.412, P=0.010). LiCl (in the LiCl+Aβ31-35 group) increased the expression of Bmal1 mRNA and BMAL1 protein significantly at CT20 compared with the Aβ31-35 group (Bmal1 mRNA: 0.72±0.05 vs 0.38±0.06, t=4.378, P=0.001; BMAL1 protein: 0.90±0.04 vs 0.67±0.04, t=4.052, P=0.002).@*Conclusion@#Increased GSK3β activity involved in the decreased expression of Bmal1 induced by Aβ31-35 in HT22 cells.
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ObjectiveTo analyze the re-examination results of malaria cases captured from the National Notifiable Communicable Disease Reporting System in Hubei Provincial Malaria Diagnostic Reference Laboratory from 2017 to 2019, so as to pro- vide the scientific evidence for improving the malaria control capability in the province. MethodsMicroscopy and nested PCR assay were performed to re-examine the diagnosis of malaria cases registered in the National Notifiable Communicable Disease Reporting System in Hubei Provincial Malaria Diagnostic Reference Laboratory from 2017 to 2019, and the coincidences of ma- laria diagnosis and malaria parasite species were evaluated. Results A total of 410 malaria cases were reported in Hubei Province from 2017 to 2019 according to the data retrieved from the National Notifiable Communicable Disease Reporting System. Among the 407 samples re-examined by Hubei Provincial Malaria Diagnostic Reference Laboratory from 2017 to 2019, the diag- nosis 374 malaria cases were confirmed, with an overall coincidence of 91.89% (374/407) for malaria diagnosis and 89.04% (333/374) for parasite species identification. The coincidence rates of malaria diagnosis and parasite species identification were 50.00% to 100.00% and 66.67% to 100.00% in 16 cities (prefectures) of Hubei Province during the re-examinations, which both varied in regions (χ2 = 40.46 and 42.30, both P values < 0.01). The coincidence rates of Plasmodium falciparum, P. vivax, P. malariae and P. ovale identification were 95.80%, 100.00%, 58.33% and 51.92% during the re-examinations, respectively (χ2 = 76.66, P < 0.01). The consistency rate between microscopic and nested PCR results was 89.83% (362/403). Conclusions The overall diagnostic quality of malaria is high in medical institutions at all levels in Hubei Province; however, the diagnostic capability of malaria remains to be improved in some regions.
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To observe the effect of Fengshi Qutong Capsules(FSQTC) on angiogenesis of rat aortarings and in knee joint synovium of type Ⅱ collagen-induced arthritis(CIA) rats. The blood vessel of aorta rings of normal SD rats were induced by vascular endothelial growth factor(VEGF) 20 μg·L~(-1 )in vitro, and were treated with FSQTC(0.02, 0.1 and 0.5 μg·L~(-1)) continuously for 9 days. The number, length and area of neovascularization of the vascular ring were measured. SD rats were immunized to establish collagen-induced arthritis. CIA rats were treated with FSQTC(0.25, 0.5, 1 g·kg~(-1)·d~(-1)) and methotrexate(0.2 mg·kg~(-1)·d~(-1)) daily for 19 days. Histopathological examination(HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joint. Immunohistochemistry was performed to observe the expression of platelets-endothelial cell adhesion molecule(CD31), VEGF and VEGF receptor 2(VEGFR_2)in the synovium. Immunofluorescence was performed to observe the expression of CD31 and α smooth muscle actin(αSMA) in synovial membrane.TGF-β, PDGF and VEGFR_2 in serum were detected by enzyme-linked immunosorbent assay. The number, branch length and area of blood vessels of aorta rings were significantly increased induced by VEGF, and FSQTC could significantly reduce the number, branch length and area of blood vessels. Compared with the normal group, the vascular density, CD31 positive expression, CD31~+/αSMA~- immature and total vascular positive expression in the synovial membrane of the model group were significantly increased, and so as VEGF and VEGFR_2 in the synovium. The VEGFR_2, TGF-β and PDGF in sera were also significantly increased in model group. FSQTC reduced the synovial vascular density and inhibited the positive expression of CD31, CD31~+/αSMA~- immature blood vessels and total vascular. FSQTC has no significant effect on CD31~+/αSMA~+mature blood vessels. FSQTC also negatively inhibited the expression of VEGF, VEGFR_2, TGF-β and PDGF in synovial membrane and/or sera. The effect of methotrexate is similar with to the high dose group. Our results demonstrated that FSQTC could inhibit the angiogenesis of synovial tissue in CIA rats and of aortaring in rats, which is related to the reduction of angiogenesis regulatory factor.
Subject(s)
Animals , Rats , Aorta , Arthritis, Experimental , Drug Therapy , Capsules , Collagen Type II , Drugs, Chinese Herbal , Pharmacology , Neovascularization, Pathologic , Drug Therapy , Rats, Sprague-Dawley , Synovial Membrane , Vascular Endothelial Growth Factor AABSTRACT
Objective:To observe the intervention effect of Fengshi Qutong capsule on collagen-induced arthritis (CIA) in rats. Method:SD rats were randomly divided into normal group, model group, low, medium and high-dose Fengshi Qutong capsule groups (0.25, 0.5, 1 g·kg-1·d-1), and methotrexate group(0.2 mg·kg-1·d-1).Except for normal group, the other groups were immunized with type Ⅱ collagen and incomplete Freund's adjuvant to establish a CIA model. On the 1st day after the first immunization, the administration group was given intragastric administration, once a day, for 19 days; on the 8th day after the first immunization, the symptoms of joint swelling and malformation of the rats were observed, and the clinical scores and incidence of arthritis were evaluated. On the 19th day, micro-computed tomography and bone metrology were performed, and histopathological examination of inflammatory joints was performed,andsynovial inflammation,vasospasm, cartilage erosion and bone destruction by pathological severity scores, serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF),matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor kappa B ligand(RANKL)were detected by enzyme linked immunosorbent assay. Result:Fengshi Qutong capsule could improve the symptoms of inflammatory joint redness, swelling and deformity in CIA rats in a dose-dependent manner. Compared with normal group, clinical score and incidence, joint synovial inflammation, vasospasm, cartilage erosion and pathological score of bone destruction in joint group were significantly increased (PPPβ, TNF-α, VEGF, MMP-3 and RANKL in serum were increased (PPPPPPPβ, TNF-α, VEGF, MMP-3 and RANKL were significantly decreased (PPConclusion:Fengshi Qutong capsule can effectively alleviate the clinical symptoms and conditions of experimental rheumatoid arthritis in rats, reduce the incidence, and relieve the histopathology and imaging severity, while inhibiting the inflammatory cytokines.