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Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6 J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16 S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1+ (CD8+ T cell/Treg) and promoted the levels of IFN-γ+ CD8+ T cells and TNF-α+ CD8+ T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1+ (CD8+ T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.
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Flavonoids , Gastrointestinal Microbiome , Humans , Mice , Animals , Gastrointestinal Microbiome/physiology , CD8-Positive T-Lymphocytes/metabolism , Programmed Cell Death 1 Receptor , Mice, Inbred C57BL , Fatty Acids, Volatile/metabolismABSTRACT
Objective @# To investigate the role of Epac1 / CaMK Ⅱ signaling pathway in myocardial ischemia reper- fusion injury (MIRI) in mice，and to investigate the protective effect of vitexin ( VT) on acute MIRI．@*Methods@#C57 / BL mice were randomly divided into 5 groups : Sham surgery group ( Sham) ，ischemia reperfusion group ( I / R) ，and ischemia reperfusion + vitexin group ( function 3，6，12 mg / kg groups) ．Ligation of the left anterior descending coronary artery (LAD coronary artery) in mice resulted in ischemia of part of the heart tissue for 30min and reperfusion of the blood for 120min．Mouse myocardial ischemia reperfusion injury ( MIRI) model was established．In the sham operation group，only the LAD was not ligated．Serum LDH levels of mice were detected．Hema- toxylin-eosin (H＆E) staining was performed on the left ventricular myocardium of mice to observe the histopatho- logical changes．The expression level of Epac1 in myocardial tissue was observed by immunohistochemistry．The protein expressions of Epac1，Rap1，CaMK Ⅱ and ERK / p-ERK were determined by Western Blot. @*Results @# Compared with Sham group，serum LDH level of mice in I / R group was significantly increased，protein expressions of Epac1， Rap1 and CaMK Ⅱ in myocardial tissue were significantly up-regulated，and ERK1 /2 phosphorylation level was decreased．Compared with I / R group，vitexin (3，6，12 mg / kg) pretreatment group decreased serum LDH level，inhib- ited Epac1，Rap1 and CaMK Ⅱ protein expression in mouse myocardial tissue，and promoted ERK1 /2 phosphoryla- tion(P＜0. 05 or P＜0. 01) ．The histopathological results showed that the myocardial fibers in the I / R group were disordered and broken，with increased gaps and obvious inflammatory cell infiltration．In the vitexin treatment group，the myocardial fibers were arranged more neatly and inflammatory cells were infiltrated less.@*Conclusion@#Vitexin may regulate Epac1 / CaMK Ⅱ signaling pathway，down-regulate CaMK Ⅱ protein expression，increase ERK phosphorylation，and effectively reduce MIRI.
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Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft
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Objective:To investigate the progress and prognosis of cervical high-grade squamous epithelial lesion (HSIL) in pregnancy and its effects on pregnancy outcome.Methods:Eighty-five pregnant women who were complicated by cervical HSIL and accepted prenatal care and delivered in Shanghai First Maternity and Infant Hospital from January 2013 to December 2017 were retrospectively recruited as case group. Another 85 pregnant women without cervical lesions were recruited as control. The progress and outcome of cervical HSIL in the case group and the association with delivery mode were analyzed. The pregnancy outcomes were compared between the two groups by two independent sample t-test, Chi-square test or Fisher's exact test. Results:In the case group, the regression rate of cervical HSIL was 29% (25/85) with 10 cases regressing to low-grade squamous epithelial lesion or atypical squamous epithelial cells of undetermined significance and 15 to chronic cervical inflammation; the persistence rate was 64%(54/85); and the progression rate was 7%(6/85). All six progressed patients gave birth to alive babies and one case progressed to invasive cervical cancer and five to HSIL with micro-invasive cervical cancer after delivery. There was no significant difference in the progression rate [7%(4/60) vs 8%(2/25)], regression rate [32%(19/60) vs 24%(6/25)] or persistence rate [62%(37/60) vs 68%(17/25)] between vaginal delivery and cesarean delivery women ( χ2=0.509, P=0.775). The incidence of premature birth of the HSIL group was higher than that of the control group [9%(8/85) vs 1%(1/85), Fisher's exact test, P=0.017], while there were no significant differences in the incidence of other complications or adverse pregnancy outcomes such as intrauterine fetal death, preterm premature rupture of membranes, low-lying placenta, amniotic fluid contamination of Ⅱ-Ⅲ degree, placental abruption, oligohydramnios and fetal distress between the two groups (all P>0.05). Conclusions:The progression rate of HSIL during pregnancy is low. Thus, a close follow-up could be conducted if invasive carcinoma is ruled out and the postpartum treatment should base on pathological results. HSIL during pregnancy could increase the risk of preterm labor, but is not an indication of cesarean section.
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Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.
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OBJECTIVE To explore the possible role and mechanism of vitamin D on the pathogenesis of allergic rhinitis by adjuvant therapy with vitamin D3. METHODS A total of 60 allergic rhinitis patients and 30 healthy subjects were selected as the combination therapy group, standard treatment group and control group. Vitamin D3 nasal drops to nasal cavity and oral Desloratadine Citrate Disodium at the same time 8.8 mg once a day were given in combined treatment group patients. Standard treatment group patients received oral Desloratadine Citrate Disodium 8.8 mg once a day. The total course of treatment was 4 weeks and then to assess the changes of serum 25(OH)D concentration, eosinophils, IL-4 levels and the therapeutic effect before and after treatment. RESULTS The serum 25(OH)D levels before and after treatment in combination therapy group were(23.67±4.47)ng/ml and (47.57±2.83)ng/ml, the IL-4 levels were (14.576 ± 4.472)pg/ml and (10.381 ± 3.41l)pg/ml, and the eosinophils of peripheral blood counts were (0.71±0.14)× 109/L and (0.34 ± 0.09)×109/L. The total effective rate was 97％. The serum 25(OH)D levels before and after treatment in standard treatment group were (23.42±3.83)ng/ml and(31.51 ±2.95)ng/ml, the IL-4 levels were (15.187±5.144)pg/ml and (12.794 ±5.396)pg/ml, and the eosinophils of peripheral blood counts were (0.67±0.12)×109/L and (0.41 ±0.10)×109/L. The total effective rate was 84％. CONCLUSION Nasal vitamin D3 drops combined with antihistamines for allergic rhinitis can effectively improve the clinical symptoms and reduce the related inflammatory markers.
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Objective To study the clinical characteristics and potential influencing factors of rehabilitation of cognition in post-stroke patients with aphasia.methods Forty-one patients with aphasia after ischemic stroke,admitted to Nanfang hospital and Nanfang Yanling Hospital from June 2015 to November 2016 were included.Their primary clinical information and NIHSS scores were registered.In acute phase,Aphasia Battery of Chinese and Boston Diagnostic Aphasia Examination was used to evaluate language ability and classify the aphasia type.Non-language-based Cognitive assessment (NLCA) was used to assess patients' nonlinguistic cognition.Besides,the assessment of post-stroke depression and dependence degree of daily living activities were performed.3 months later,patients were evaluated again.A total of 30 aphasia patients completed the final follow-up.Result s(1) Compared with the baseline in patients with aphasia after stoke,all domains of language ability were significantly improved after 3 months(P<0.05).(2)Every nonlinguistic cognitive score was significantly increased within 3 months(total NLCA score(65.83±13.02 vs 48.00±25.11),memory(17.23±2.49 vs 13.30±5.42),visual spatial ability(10.67±2.43 vs 8.07±3.75),logical reasoning ability(6.53±1.48 vs 4.97±2.43),attention(25.57±5.79 vs 17.43±12.33),executive function(5.77±3.47 vs 4.20±4.23),all P<0.01).(3)The NLCA total score (62.40±14.23 vs 72.70±6.34)and scores in visual spatial (9.95±2.67 vs 12.10±0.74)and abstract reasoning(6.05±1.54 vs 7.50±0.71) of persisting aphasia patients were significantly lower than that of aphasia recovered group(all P<0.05).(4) Multivariate regression showed that initial NLCA score had a negative predictive effect on cognitive function improvement of aphasia patients 3 months after stroke(β=-0.603,P<0.01).Conclusion The rehabilitation of cognitive function in patients with aphasia after stroke is similar to that of language function.Patients with persisting aphasia may have worse performance on nonlinguistic cognition and ability of daily living,even with more serious depressive emotion.Evaluation of nonlinguistic cognition in post-stroke aphasia patients in acute phase is necessary and the score seems to be an important predicting factor of 3-month cognition.
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Objective To explore the clinical characteristics and related factors of cognitive impairment in elderly post-stroke aphasia (PSA) patients.Methods Eighty-two patients after stroke,admitted to our hospitals between April 2013 and November 2014,were enrolled in this study,including 62 patients with aphasia.Based on the criteria for age segmentation from World population ageing 2009 [6],these patients were divided into 3 groups with "age=60 years":PSA patients older than 60 years as experimental group (n=30),PSA patients younger than 60 years as control group Ⅰ (n=32),and non-aphasia patients older than 60 years as control group Ⅱ (n=20).The clinical data,NIHSS scores and MRI/CT results of these patients were recorded;and the assessments of language ability,post-stroke depression (PSD) and nonlinguistic cognition were performed;classification of aphasia severity of the patients was performed by Boston diagnostic aphasia examination (BDAE).Multivariate regression analysis was performed to examine relative factors of cognitive impairment in PSA patients.Results (1) Nonlinguistic cognitive scores were significantly correlated with BDAE scores (β=0.637,P=0.000),age(β=-0.392,P=0.000),SADQ-H scores(β=-0.176,P=0.035) and cortical lesions(β=-0.150,P=0.049).(2) As compared with patients of control group Ⅰ,patients of experimental group were more likely showed deficits in most nonlinguistic cognitive domains except for abstract reasoning;and the cognitive function scale scores were significantly decreased (P＜0.05);patients of experimental group had significantly increased number of nonlinguistic cognitive domains and significantly decreased cognitive function scale scores,except for visual perception and construction scores as compared with patients of control group Ⅱ (P＜0.05).(3) The prevalence of abstract reasoning impairment was significantly lower as compared with that of visual memory,attention and executive functioning in patients of experimental group (P＜0.05).(4) The frequency and severity of impaired cognitive domains in the experiment group were significantly higher than those in the control group Ⅰ and Ⅱ (P＜0.05).Conclusions Nonlinguistic cognitive impairment is extremely common in elderly PSA patients.The aphasia severity and age are most associated with cognitive impairment in PSA patients,post-stroke depression and cortical lesions also have an effect on cognitive scores.
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Objective To study the variation characteristics of cognitive impairment and its influencing factors using telephone interview for cognitive status-modified (TICS-m) in patients after cerebral ischemia,and evaluate the application value of TICS-m.Methods Ninety-five patients with cerebral ischemia,matched the criteria and admitted to our hospital from December 2014 to December 2015,were chosen.Their related information was recorded,their cognitive function was assessed by face-to-face neuropsychological tests,including Montreal Cognitive Assessment (MoCA),Hamilton Depression Rating Scale,activities of daily living (ADL) and Chinese Neuropsychiatric Inventory (CNPI),in the acute stage (10-14 d),and then,their cognitive function was assessed by TICS-m 4,12 and 18 weeks after cerebral ischemia and their rehabilitation was followed up.Results The incidence of cognitive impairment after cerebral ischemia in the acute stage was 78.9％;when cutoffs of dementia was ＜28 points and mild cognitive impairment (MCI) was 28-33 points in TICS-m,the incidences of cognitive impairment 4,12 and 18 weeks after cerebral ischemia were 69.4％ (MCI:45.8％,dementia:23.6％),57.3％ (MCI:42.6％,dementia:14.8％),44.9％ (MCI:34.7％,dementia:10.2％).And the TICS-m total scores 12 and 18 weeks after cerebral ischemia were significantly increased than that 4 weeks after cerebral ischemia,amplification reaching to 7.9％ and 10.7％ (P＜0.05);subtests analysis indicated that 12 and 18 weeks after cerebral ischemia,the memory recovered obviously:the scores were significantly increased,amplification reaching to 34.5％ and 49.0％ as compared with those 4 weeks after the cerebral ischemia (P＜0.05).Logistic regression analysis indicated that age (OR=66.615,P=0.001,95％CI:5.449-814.349),education level (OR=0.134,P=0.009,95％CI:0.029-0.608) and work type (OR=0.090,P=0.004,95％CI:0.017-0.464) were closely related to the cognitive impairment after cerebral ischemia.The follow-up visit analysis showed that most patients (91.8％) could take the drug for the secondary prevention of stroke and return to the clinic regularly,and only a small part of patients (31.8％) took the related drugs to improve their cognitive impairment;about 77.6％ patients recovered good after discharge,54.7％ patients supported and hoped the doctors continue the follow-up visit by telephone.Conclusions The incidence of cognitive impairment is high after cerebral ischemia and it declines over time,and advanced age,low education level and manual work are the important factors affect the incidence.TICS-m is an effective and convenient tool to assess the characteristic and prognosis of patients with cognitive impairment after the cerebral ischemia,and it' s suitable for clinic follow-up study and scientific research.
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Objective To investigate the clinical features and influencing factors of somatic symptoms in patients with acute stroke.Methods Patients with acute stroke were enrolled in the study.Using the scores of symptom checklist 90 (SCL-90)-somatization factor part,the patients were divided into either a somatic symptom group (≥24) or a control group (＜24).Their age,gender,economic level,education level,underlying diseases,Hamilton Anxiety Scale (HAMA),Hamilton Depression Scale (HAMD),NEO Five-Factor Inventory scores,Social Support Rating Scale scores-simplified Chinese version,Mini-Mental StateExamination (MMSE) scores,National Institute of Health Stroke Scale (NIHSS) scores were documented and analyzed.Results A total of 70 patients with acute stroke were enrolled,and 33 (47.1％) of them had somatic symptoms.There were no significant differences in demographic characteristics,education level,family income,occupation,marital status,living alone,residence,medical expenses payment methods and social support scores between the somatic symptom group and the control group.There were also no significant differences in the types of stroke,lesion side,baseline NIHSS score,MMSE score,and NEO Five-Factor Inventory score between the 2 groups.There was significant difference in lesion side between the somatic symptom group and the control group (x2 =0.161,P=0.006).The comparison of neuropsychological test results showed that the proportion of patients with an anxiety state of the somatic symptom group was significantly higher than that of the control group (24.2％ vs.5.4％;x2 =5.055,P =0.025),but there was no significant difference in the proportion of patients with depression status;after excluding the cases who met the anxiety and depression criteria,HAMA (8.08 ± 3.12 vs.5.58 ± 3.06;t =-3.059,P =0.003) and HAMD (10.80 ± 4.81 vs.7.73 ± 3.88;t =-2.694,P =0.009) scores of the somatic symptom group (n =25) were significantly higher than those of the control group (n =33).The number of somatic symptoms of the somatic symptom group was significantly more than that of the control group (Z =-5.817,P ＜ 0.001),and was more likely to have pain symptoms (97.0％ vs.73.0％;x2 =7.584,P =0.006).The correlation analysis showed that there was a significant positive correlation in the 12-item scores of the SCL-90 somatic factors and HAMA (r =0.494,P ＜0.001) and HAMD (r=0.369,P=0.002) scores in patients.Multivariate logistic regression analysis showed that HAMA score was an independent risk factor for somatic symptoms after stroke.(odds ratio 1.286,95％ confidence interval 1.060-1.560;P=0.011).Conclusions The incidence of somatic symptoms is high after acute stroke,especially in patients with cortical stroke.The somatic patients after stroke are prone to have pain-related symptoms.The patients with anxiety and depression status after stroke are prone to have somatic symptoms after stroke;HAMA score is an independent risk factor for having somatic symptoms after stroke.
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Objective To investigate the oxidative stress and cytoskeleton protein carbonylation in rat brains after different severities of traumatic brain injury (TBI).Methods Fluid percussion percussion device was used to establish the mild,severe and sham-operated Sprague-Dawley rat models (n=15);24 h after that,enzyme linked immunosorbent assay was used to detect the levels of malondialdehyde (MDA) and glutathione (GSH),and Western blotting was employed to detect the cytoskeletal proteins (β-actin,β-tublin and glial fibrillary acidic [GFAP]) carbonylation levels;phosphorylated tau (p-tau) protein expressions were examined by Western blotting.Results The expression levels of MDA in mild TBI group and severe TBI group were (389.62±29.95) μmol/g and (642.50±37.56) μmol/g,respectively,which was significantly increased as compared with the MDA level ([233.94±25.08] μmol/g) in sham-operated group (P＜0.05).The expression level of GSH in mild TBI group and severe TBI group was (352.10±37.75) μmol/g and (153.27 ±43.49) μmol/g,respectively,which was significantly decreased as compared with the GSH level ([492.48 ±41.43] μmol/g) in sham-operated group (P＜0.05).The β-actin,β-tublin and GFAP proteincarbonylation levels (0.099± 0.104,0.194±0.114 and 0.643±0.037;0.142±0.017,0.290±0.029 and 0.902±0.021) and p-tau level (0.289±0.014 and 0.373±0.012) in mild TBI group and severe TBI group were significantly higher than those in sham-operated group (0.068±0.017,0.108±0.016 and 0.673±0.032;0.185±0.009;P＜0.05).Conclusions The oxidative stress and carbonylation of cytoskeleton proteins are significantly increased after TBI,and the expression levels are correlated with the severity of TBI.The carbonylation of cytoskeleton protein aggravates the axonal injury after TBI.
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Objective To study the effects of Liensinine on apoptosis of 5637 cells, and its mechanism thereof. Meth?ods CCK-8 method and the colony formation test were used to detect cell viabilities, and then inhibition rates were calcu?lated. Flow cytometry was used to detect the effects of Liensinine on apoptosis of 5637 cells. Western blot assay was used to detect Caspase-7 protein expression. Results CCK-8 assay and colony formation test indicated that Liensinine inhibited the cell proliferation significantly. Results of flow cytometry indicated that Liensinine induced early apoptosis of 5637 cells. Western blot assay showed that Liensinine improved the expression of Caspase-7 and enhanced the activation of Caspase-7 in 5637 cells. Conclusion Liensinine could inhibit the proliferation of 5637 cells, induce early apoptosis, which may be re?lated with the enhanced expression of Caspase-7 and its activation.
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Objective To explore the value of SOD activity in diagnosis of central nervous system leukemia (CNSL )by detec-ting SOD activity of cerebrospinal fluid of patients with CNSL .Methods The cerebrospinal fluid of 55 patients from department of hematology of Nanfang hospital of southern medical university were collected from January 2008 to January 2009 ,in which 30 pa-tients suffered with central nervous system leukemia (CNSL group) ,the other 25 patients suffered with acute leucemia without im-paired central nervous system(control group) .The SOD activity of cerebrospinal fluid was detected by the xanthine oxidase meth-od ,while the routine test ,biochemistry test and cell smear of cerebrospinal fluid was detected .Results There were statistics differ-ence in the level of white cell and protein in cerebrospinal fluid between CNSL and control group (P0 .05) .There was statistics difference in the level of SOD activity between CNSL and control group(P<0 .05) .The white cell quantity and the protein level in cerebrospinal fluid had negative corre-lation with the activity of SOD ,(r=0 .871 ,P=0 .000 ;r=0 .518 ,P=0 .003) .The activity of SOD in the cerebrospinal fluid had sta-tistics difference before and after intrathecal chemotherapy (P<0 .05) .The activity of SOD in the cerebrospinal fluid whose under 45 year-old (755 .64 ± 345 .77) ,which was significant lower than that of the paitents whose equal with or above 45 year-old (1 420 .49 ± 307 .69)(P<0 .05) .Conclusion The changes of the SOD activity in the cerebrospinal fluid had relation with central nervous system leukemia ,and the SOD activity might be a auxiliary diagnosis index used in central nervous system leukemia by revi-sing age factor .
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Objective To analyze the characteristics of the non-language-based cognitive function in patients with aphasia after stroke.Methods Thirty patients of the first infarction with aphasia and thirty stroke patients without aphasia were recruited.The aphasia deficits in patients were evaluated using the Aphasia Battery of Chinese(ABC).The non-language-based cognitive assessment scale (NLCA) was applied to analyze the cognitive function in the two groups.The stroke aphasic depression questionnaire hospital version (SADQ-H)was applied to analyze the depression in the two groups.Results The score in NLCA of the aphasia group was significantly lower than that of control group((50.01± 14.01)vs(66.13±5.95),P＜0.01).There was high correlation between the total and sub-scores of NLCA and ABC in both groups(P＜0.01,P＜0.05).The score in SADQ-H of the aphasia group was significantly higher than that of control group((21.83±7.37)vs(16.13±5.84),P＜0.01).The total score for the aphasia patients shown by the SADQ-H was negatively related with the total score of the NLCA(r=-0.468,P＜0.05).Conclusion There is non-language-based cognitive dysfunction in patients with aphasia after stroke,and the severity of depression affects cognitive function.
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Objective To study the effect of liensinine on the proliferation of human bladder cancer T24 cells.Methods T24 cells were treated with different concentrations of liensinine.Its influence on the cell proliferation was detected by the CCK-8 exper-iment and the clonogenic experiment.After staining of T24 cells,the influence of liensinine on the cell cycle was examined by the flow cytometry.The mRNA change of p2 1 gene was determined by real-time quantitative PCR.Results Compared with the con-trol,liensinine significantly inhibited the proliferation of T24 cells in different doses groups(1.562 5,3.125 0,6.250 0,12.500 0, 25.000 0μg/mL),the differences had statistical significance and showed the dose-dependence;the cell cycle detection results re-vealed that liensinine arrested the T24 cells at the S phase;the real-time quantitative PCR detection results showed that liensinine increased mRNA of p21 gene in T24 cells.Conclusion Liensinine inhibits the proliferation of T24 bladder cancer cells and arrests the T24 cells at S phase,its mechanism may be related with the upregulation of p21 expression.
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<p><b>OBJECTIVE</b>To screen the hepatocyte proteins that interact with hepatitis B virus X protein (HBx).</p><p><b>METHODS</b>The recombinant plasmid pSos-HBx was constructed by inserting Sos-HBx fragment into the bait vector, and after sequence verification the plasmid was transformed into competent yeast cells. The expression and self-activation of Sos-HBx protein was detected in the yeast cells. The hepatocyte proteins interacting with the bait protein was screened with CytoTrap yeast two-hybrid technique.</p><p><b>RESULTS</b>The reconstructed plasmid harboring HBx gene expressed Sos-HBx protein in the yeast cells without self-activation of the protein. CytoTrap yeast two-hybrid system identified 6 hepatocyte proteins that interacted with HBx, including fibronectin 1, translationally controlled tumor protein, IQ motif and WD repeats 1, follistatin, orosomucoid 1, and disulfide isomerase family A member 3.</p><p><b>CONCLUSION</b>Six HBx-binding hepatocyte proteins have been identified using the CytoTrap yeast two-hybrid system, which provides clues for further investigation of the role of HBx protein in hepatitis and liver cancer.</p>
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Humans , Genetic Vectors , Hepatocytes , Metabolism , Plasmids , Protein Interaction Domains and Motifs , Proteins , Metabolism , Trans-Activators , Metabolism , Two-Hybrid System TechniquesABSTRACT
<p><b>OBJECTIVE</b>To analyze the neurolinguistic features of a Chinese patient with pure alexia in acute and convalescent stages.</p><p><b>METHODS</b>We assessed the reading and writing abilities of the patient with the Aphasia Battery of Chinese (ABC), the reading examination of Chinese characters (1999, Lin) and the Chinese agraphia battery (CAB).</p><p><b>RESULTS</b>In the ABC examination in the acute phase, the patient performed well in oral expression and comprehension, and the prominent linguistic abnormalities were alexia and merging agraphia; in the convalescent phase, the recovery of alexia was better than that of agraphia. In reading examination of Chinese characters, shape errors were the main reading disorders in the acute phase with a few semantic errors, regularization errors and mistakes in pronunciation, but only shape errors reappeared in the recovery period. CAB examination showed impairment of writing for pictures and dictation abilities in the recovery period but recovery of other writing abilities. The writing disorder was manifested as aphasic agraphia, with obvious dysorthography and lexical errors; the patient was capable of spontaneous writing only after spontaneous speech, and was able to read the written words.</p><p><b>CONCLUSION</b>The linguistic components of the Chinese patient with pure alexia showed different patterns of damage and recovery, suggesting the difference in their respective neuropsychological pathways.</p>
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Humans , Male , Middle Aged , Alexia, Pure , Psychology , Rehabilitation , Neuropsychological Tests , Recovery of Function , SpeechABSTRACT
Objective To investigate the effectiveness of donepezil in the treatment of early post-stroke aphasia (PSA).Methods PSA patients within one month after onset were randomly assigned into either a donepezil group or a control group.On the basis of conventional medication,the donepezil group was given hydrochloride donepezil 5 mg/d.The patients were followed-up after 4 week.The efficacy was evaluated by the Aphasia Battery of Chinese (ABC),the National Institute of Health Stroke Scale (NIHSS),the Stroke Aphasic Depression Questionnaire (SADQ),Chinese version,and the Treatment Emergent Symptom Scale (TESS) before and after treatment.Results A total of 48 PSA patients were enrolled in the study.Both the donepezil group and the control group had 24 patients and they all completed the study.There were no significant differences in age,years of education,NIHSS score,SADQ score,stroke duration,as well as the proportions of male,hypertension,diabetes,hyperlipidemia,heart disease,previous stroke or history of transient ischemic attack,smoking alcohol consumption,type of stroke,and lesion site (all P ＜ 0.01).There were significant differences in each language score before and after treatment both in the donepezil group and in the control group (all P ＜0.01).The difference values of listening comprehension (47.8 ± 24.7 vs.22.0 ± 15.4; t =4.342,P =0.000)and reading comprehension (20.5 ± 14.0 vs.8.1 ± 10.5; t =3.483,P ＜0.01) scores before and after treatment in the donepezil group were significantly higher than those in the control group,while there were no significant differences in the information quantity of speech,fluency,series language,repetition,naming,and reading scores (all P ＞0.05).As compared with the control group,there were significant differences in the difference values of the SADQ scores before and after treatment in the donepezil group (6.2 ±6.0 vs.2.5 ±3.0; t =2.717,P=0.009).No serious adverse reactions were observed in both groups.Conclusions On the basis of conventional stroke treatment,using hydrochloride donepezil in the early PSA patients has promotion effect on the improvement of listening comprehension and reading comprehension of language function.
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Objective To develop the Non-Language-Based Cognitive Assessment (NLCA) applicable to patients with aphasia and to validate the reliability and validity of NLCA.Methods Seventy-three normal subjects and 32 patients with mild cognitive impairment were evaluated by the NLCA and the Mini-Mental State Examination.Forty subjects were randomly selected from the normal subject samples were assessed with the NLCA,the Auditory Verbal Learning Test,the Rey-Osterrieth Complex Figure Test (Form A),the Stroop Color-Word Interference Test,the Raven's Standard Progressive Matrices (Part A),and the WAIS Digit Span Test.Results The NLCA had high inter-rater agreement (Cronbach's α coefficient 0.836),reliability among the assessors 0.895-0.953,test-retest reliability 0.863-0.952 at at a 2-6 week interval.The years of education was significantly correlated with NLCA (r =0.852,r ＜ 0.01).When the Montreal Cognitive Assessment was used as diagnostic criteria,the area under the receiver operating characteristic curve was 0.899 (95％ confidence interval 0.827-0.972).When cutoff at 70,the NLCA had had high sensitivity,specificity,positive predictive value and negative predictive value in the identification of patients with mild cognitive impairment.Conclusions The NLCA has good reliability and validity.It is an effective cognitive function assessment that meets the basic requirements of the neuropsychological tests.
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<p><b>OBJECTIVE</b>To observe the pathological changes of axonal injury in a rat model of experimental allergic encephalomyelitis (EAE).</p><p><b>METHODS</b>With HE, luxol fast blue and Bielschowsky staining, the expression of APP, MBP, SMI-32 and MBP in the brain and spinal cord of EAE rats using double-labeling indirect immunofluorescence.</p><p><b>RESULTS</b>Extensive cuffing lesions of inflammatory cell infiltrations were found in the brain and spinal cord of the rats, accompanied by multiple lesions of demyelination, axonal disarrangement with vesicular loss. SMI-32 staining identified numerous nonphosphorylated neurofilament, indicating the presence of axonal injury. Axonal oval bodies formed by APP accumulation were found in the white matters of the spinal cord 14 days after EAE, suggesting that neuraxial damage occurred in the early stage of EAE which was not synchronous with myelin loss.</p><p><b>CONCLUSION</b>Different levels of inflammation occur in different stages of EAE, and inflammatory cell infiltration is the most obvious at the peak of EAE. Axonal injury occurs in the early stage of EAE and progresses over the entire disease course.</p>
