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Objective:To observe the clinical efficacy and adverse reactions of rituximab in the treatment of systemic sclerosis (SSc).Methods:Eight SSc patients who received rituximab treatment in the Department of Rheumatology of Shanghai Ruijin Hospital from November 2016 to May 2020 were treated with rituximab at week 0, week 2, week 4, week 24 and week 48. The clinical symptoms and laboratory parameters were evaluated at baseline, week 4, week 24 and week 48 respectively. All data were analyzed by Wilcoxon test.Results:All the patients were diagnosed as diffuse SSc, including seven females and one male, with a median disease course of 2.5 years. At week 0, week 24 and week 48, the modified Rodnon skin scores (MRss) were 16.5 (11.8, 29.5) , 14.5 (9.5, 27) ( Z=0.841) and 10.5 (7, 24.3) ( Z=0.420) respectively, which were significantly improved as compared with the baseline ( P<0.05). The patients' self-scores were 60(50, 77.5), 52.5(41.3, 67.5)( Z=0.113) and 47.5(36.3, 57.5)( Z=0.474) respectively, which were significantly improved at week 24 and week 48, and the High Resolution CT (HRCT) scores at baseline and week 48 were 2.7(1.02, 3.7) and 1.6(0.65, 2.95)( Z=0.964) respectively, significantly improved after treatment ( P<0.05). The pulmonary aterial hypertension (PAH) values were 48(41, 58.5) mmHg and 47(38.5, 57) mmHg ( Z=0.315) respectively. There was no significant difference between the two groups. Clinical observation showed that the condition was improved and no adverse reaction occurred at the same time period. Conclusion:The improvement of skin sclerosis, pulmonary interstitial lesion and pulmonary artery pressure can be observed during the treatment with rituximab, which may be a new choice for the treatment of SSc. There is no serious adverse reaction during the treatment, and the patients are well tolerated and safe.
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Objective To explore and compare the prognostic ability of the serum level of M2BPGi and MRI imaging technology for hepatic fibrosis. Methods 118 patients who were diagnosed as hepatitis C were enrolled from March 2014 to March 2015 in our hospital.Their baseline data were recorded,and they were texted by imaging examination of MRI.Then all patients were followed-up 2 years.The patients were divided into hepatic fibrosis group and control group according to the follow-up results.Univariate analysis and Cox model were used to show that the prognostic factors influencing the prognosis of hepatic fibrosis in patients;meanwhile,the statistical significance factors were calculated by ROC curve.Results The serological markers of IV-C,HA and serum level of M2BPGi in hepatic fibrosis group were higher than those in control group,but its ADC values of liver was lower than those in control group,and the difference was statistically significant(P < 0.05). COX regression analysis showed that the difference of M2BPGi(RR = 4.282,P = 0.003)and ADC values(RR = 0.654,P = 0.004). The ROC analysis of the hepatic fibrosis group and the control group showed that the AUC of the combination was 0.865,the sensitivity and specificity were 95.2%,60.5%,respectively.Conclusion The clinical value the com-bined prognostic of them is of high prognostic efficacy,which is hopeful to be used as an auxiliary prognostic meth-od in clinic.
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Epilepsy with mental retardation limited to females (EFMR) is a syndrome characterized by early onset heat-sensitive epilepsy of infancy or early childhood and generally limited to females,which previously reported that the cadherin gene superfamily subtype protocadherin 19 (PCDH19)gene is its pathogenic gene.We retrospectively analyzed the clinical data for 2 cases of EFMR patients with PCDH19 mutation diagnosed by Department of Pediatric Neurology of Xiangya Hospital,Central South University in 2015.Literature on PubMed,OMIM and HGMD relevant to this syndrome was reviewed,and the clinical characteristics were summarized accordingly.The 2 cases are consistent with the typical clinical manifestations of EFMR caused by PCDH19 mutations.Their seizures are heat sensitive,with or without screaming,and expressed in various forms.Cognitive impairment or autism-like performance were often identified in these patients,hematuria metabolic diseases screening was normal,no abnormal MRI imaging of the head,and de novo PCDH19 gene mutations were found in their epilepsy gene chip sequencing.It is noteworthy that this disease is very similar to the clinical manifestations of the Dravet syndrome due to the mutations of the neurotype sodium channel αl subunit SCN1A.Therefore,in female patients whose clinical manifestations resemble to Dravet syndrome but SCN1A gene test were negative,EFMR with PCDH19 mutation should be taken into consideration.Early PCDH19 gene testingis of great significance because it not only helps clinicians to understand and analyze the prognosis of this disease,but also offers genetic counseling to the parents.
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Objective To investigate whether folate deficiency cause high expression level of interferon gamma (IFN-γ) resulted from IFN-γ gene ( IFNG) hypomethylation and then promote the pathogenesis and development of ulcerative colitis (UC ) in a dextran sulfate sodium (DSS )-induced experimental colitis model in mice .Methods A total of 24 female BALB/c mice were divided into four groups ,six mice in each group , including folate deficient/DSS+ group , standard diet/DSS+ group , standard diet/DSS - group and folate deficient/DSS- group .At the beginning of the sixth week since fed , the mice of model groups were treated with 5% DSS to establish experimental colitis .By the end of the sixth week ,disease activity index (DAI) of colitis and histological changes were evaluated .The folate level of peripheral blood serum of mice were detected by enzyme-linked immunosorbent assay (ELISA ) . The expression of IFN-γ in colonic mucosa of mice was examined by immunohistochemistry . The methylation level of CpG island in the promoter region of IFNG was determined by methylation specific polymerase chain reaction (MSP) .The t test was used for measurement data .Chi square test was performed for comparison between groups of count data . Spearman correlation analysis was used for correlation analysis .Results The folate levels of peripheral blood serum of folate deficiency/DSS+ group and folate deficiency/DSS- group ((2 .70 ± 0 .19) and (2 .80 ± 0 .25)μg/L) were significantly lower than those of standard diet/DSS+ group and standard diet/DSS- group ((13 .62 ± 0 .38 ) and (13 .52 ± 0 .77)μg/L ,t= -63 .33、32 .27 ,both P< 0 .05) ,resepectively .The expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group and standard diet/DSS+ group were significantly higher than those of folate deficiency/DSS- group and standard diet/DSS- group (χ2 = 22 .18 ,P< 0 .05 ) . And the expression of IFN-γ in colonic mucosa of folate deficiency/DSS+ group was also higher than that of standard diet/DSS+ group (χ2 = 12 .00 ,P< 0 .05) .The expression level of IFN-γ of folate deficiency/DSS+ group and standard diet/DSS+ group was positively correlated with (r=0 .998、0 .953 ,both P<0 .01) .The folate levels of peripheral blood serum of folate deficiency/DSS+ group was negatively correlated with IFN-γexpression level and DAI (r= -0 .880 and -0 .926 ,both P<0 .05) .No abnormal methylation was detected in IFNG promoter CpG island in colonic mucosa tissues of mice of each group . Conclusion In the mice model of DSS induced acute experimental colitis ,folate deficiency may increace the expression of inflammatory factor IFN-γand enhance the inflammation activity of colonic mucosa .
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Objeetive To investigate the clinical efficacy of treating stomach cance belonging to spleen and stomach deficient cold type with self-designed formula and chemotherapy.Methods 100 patients of stomach cancer belonging to stomach and spleen deficient cold were randomly grouped into a control group and a treatment group,with 50 cases in each group.The control group was only treated with chemotherapy,and the treatment group was additionally treated with self-designed Chinese formula on the basis of the control group.After 3 months' treatment,the curative effect,the improvement of life quality,the changes of body weight,the improvement of peripheral blood and immune function,and the occurrence of adverse reaction were observed.The survival rate of patients after 1,3 and 5 years' treatment was investigated.Results ① Short term curative effect:the total effectiveness of the control group and the treatment group was 60.0％ (30/50) and 30.0％ (15/50) respectively,with the treatment group being better than the control group(Z=-2.100,P＜0.05);② life quality:theimprovement rate of life quality in the treatment group and the control group was 64.0％ (32/50) and 20.0％ (10/50) respectively,with the treatment group being better than the control group (Z=-3.259,P＜0.05); ③ body weight:the improvement rate of body weight in the treatment group and the control group was 24.0％ and 16.0％ respectively,and there was no significant difference (Z=-1.815,P＞0.05) ; ④ peripheral blood:the peripheral blood abnormality rates of treatment group was obviously lower than the control group (Z=-4.286,P＜0.05) ;⑤ immune function changes:CD4+、CD8+、and the activity of NK cell of two groups after the treatment [the treatment group was (40.8 ± 4.1)％,(26.1-3.2)％,(83.57-2.52)％ respectively; the control group was (31.7±2.9)％、(33.8±3.0)％、(92.88±3.83)％ respectively] wasobviously improved compared with the same group before the treatment [the treatment group was (34.2±3.5)％,(31.0±2.0)％,(85.01±2.92)％ respectively; the control group was (34.0±3.2)％,(30.9±2.2)％,(85.02± 3.48) ％ respectively].The immune indexes (CD4+、CD8++、CD4+/CDg+and the activity of NK cell)in the treatment group presented significant difference (P＜0.01) than the control group after the treatment.⑥adverse reaction:compared with the control group,the occurrence rate of adverse reaction of the treatment group was obviously lower than the control group,and there was significant difference (Z=-5.297,P＜0.05).⑦survival rate:the survival rate of patients after 1,3 and 5 years' treatment in the treatment group was better than the control group,and there was significant difference (x2=5.263,12.96,7.895,P＜0.05).Conclusion The combination of self-designed Chinese formula and chemotherapy could effectively relieve the clinical symptoms,improve the immunity,reduce the occurrence of adverse reaction,and improve the life quality of patients with stomach cancer belonging to stomach and spleen deficient cold type.
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Objective To investigate the effects of recombinant tissue plasminogen activator (rt-PA)intravenous thrombolysis on blood-brain barrier (BBB) permeability,the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats.Methods A total of 40 adult male Sprague-Dawley rats were allocated into 3 groups:Sham operation group (n =10),middle cerebral artery occlusion (MCAO) group (n =18),and rt-PA thrombolysis group (n =18).A MCAO model was established by using autologous thromboembolism.The sham operation group did not inject any thromboembolus,the MCAO group only made MCAO,and the rt-PA thrombolysis group received intravenous thrombolysis with rt-PA at 3 hours after MCAO.Brain infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride staining BBB permeability was measured by Evans blue dye leakage.The activities and the expressions of MMP-2 and MMP-9 in brain tissue were detected by Gelatin zymography and Western blot,respectively.Results Compared to the MCAO group,the neurological function was improved significantly in the rt-PA thrombolysis group,and the infarct volume was also reduced significantly (t =7.365,P =0.005).However,the hemorrhage score (t =-3.286,P =0.017) and BBB permeability (t =-3.947,P =0.029) were increased significantly.The activities and the expressions of MMP-2 and MMP-9 in the sham operation group were lower.The activities and the expressions of MMP-2 (t =-45.121,P =0.000; t =-11.624,P=0.000) and MMP-9 (t=-71.849,P=0.000; t=-8.992,P=0.000) in the MCAO group were increased and upregulated significantly.Compared to the MCAO group,the activities and the expressions of MMP-2 (t =-28.792,P =0.000; t =-3.809,P =0.013) and MMP-9 (t =-53.506,P =0.000; t =-2.640,P =0.046) in the rt-PA thrombolysis group were increased and upregulated significantly.Conclusions After rt-PA intravenous thrombolytic therapy,the BBB permeability was increased.The activities and the expressions of MMP-2 and MMP-9 were increased and upregulated.MMP-2 and MMP-9 might participate in the increased BBB permeability,and thus inducing hemorrhagic transformation after rt-PA intravenous thrombolytic therapy in rats with cerebral ischemia.
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Objective To establish and validate a modified rat thromboembolic stroke model.Methods After taking femoral arterial blood and mixing it with thrombin,they were injected into PE-50 catheter for preparing in vitro thrombosis in 60 Sprague-Dawley rats.A thromboembolic cerebral ischemia model induced by catheterization of the right external carotid artery and the small blood clot emboli were injected into the internal carotid arteries.Thirty rats were randomly divided into a large number of emboli group (n =10 with 12 emboli),a median number of emboli group (n =10 with 10 emboli) and a small number of emboli group (n =10 with 8 emboli).Two hours after embolus injection,the neurological deficit score was performed and the success rate of the model was compared in all groups.Twenty-four hours after embolus injection,the rats were sacrificed and the brains were removed for 2,3,5-triphenyltetrazolium chloride staining.The hemorrhage,infarct volume,bleeding incidence and mortality after cerebral infarction were evaluated.The high success rates of the modeling in the emboli groups were selected and they were randomly divided into either a normal saline group (n =12) or a recombinant tissue-type plasminogen activator (rtPA) group (n =12).The rats were given normal saline and rtPA at 3 hours after embolus injection.Before embolus injection and 2,6,12 and 24 hours after embolus injection,the neurological scores were performed respectively; 24 hours after embolus injection,the rats were sacrificed and the brains were removed for 2,3,5-triphenyltetrazolium chloride staining.The hemorrhage rate,infarction size,degree of cerebral edema,and blood-brain barrier permeability were evaluated.Results Only 40％ of rats had neurological deficits in the small number of emboli group,and the infarct volume was only 10.54 ± 2.82％.The success rates in the median and large number of emboli groups were 80％ and 100％ respectively.They were all significantly higher than those in the small number of emboli group (P =0.011 ).The infarct volume was also significantly greater than that in the small number of emboli group (F =40.897,P =0.000).After administration of rtPA,the mean survival time of the rats in the large number of emboli group was less than 24 hours,so the median number of emboli group was selected to study the thrombolytic effect of rtPA.The infarct volume and neurological function score in the rtPA group were improved significantly compared to the normal saline group (t =7.728,P =0.000),while there were no significant differences in the hemorrhage rate,degree of brain edema and blood-brain barrier permeability between the 2 groups.Conclusions The stability and reproducibility were good in the modified thromboembolic cerebral ischemia model injected with 10 emboli,the neurological function was improved significantly after thrombolysis,and it was applicable to the experimental study of pathophysiology of cerebral ischemia and thrombolytic therapy.
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Objective To study the effects caused by novel antipsychotics quetiapine and aripiprazole on concentrations of platelet 5-HT in patients with schizophrenia,and to explore the relationships among the change of platelet 5-HT concentrations, psychiatric symptoms and the sensitivity of therapy. Methods Sixty-eight patients with schizophrenia meeting International Classification of Diseases-10 (ICD-10) were enrolled in the study. They were divided into quetiapine group(n=34) and aripiprazole group(n=34) according to the sequence of admis-sion. The platelet 5-HT concentrations were measured with high performance liquid chromatography method(HPLC-ECD). The positive and negative syndrome scale (PANSS) was used to evaluate the psychopathology. Treatment emergent symptom scale (TESS) was used to evaluate the side effects. PANSS,TESS were used at pre-treatment,the end of 4th and 8th week of treatment. Results The platelet 5-HT concentrations in two groups were higher af-ter 8 weeks treatment,but had no statistically significant difference (P>0.05). In quetiapine group, the platelet 5-HT concentration was (458.89±233.36) ng/10~9 at the pre-treatment, and (554.31±313.22) ng/10~9 at the end of treatment (t=1.709, P=0.099). In aripiprazole group, the platelet 5-HT concentration was (409.83±149.32)ng/10~9 at the pretreatment, and (421.27±245.96)ng/10~9 at the end of treatment (t=0.321, P=0.819). There was no difference between two groups(P>0.05). Stepwise regression analysis showed the changing rate of platelet 5-HT concentrations was positively correlated with the dosage of quetiapine (r=0.385, P=0.039).It was positively correlated with the decreasing rate of PANSS in aripiprazole group(r=0.391, P=0.040). Con-dusion The changes of psychiatric symptoms and the dosages of antipsychotics maybe have intimate relationships with platelet 5-HT concentrations in the course of medication.
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Approximately one-quarter of ischemic stroke occurred in vertebrobasilar artery system. Atherosclerotic vertebrobasilar artery stenosis is one of the major causes of posterior circulation stroke. In addition to the conventional medical and surgical treatment, endovascular intervention has received more and more attention, and it has become the most promising therapeutic approach.
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Now syndrome study becomes the important research content in our country' TCM field,normalization of the symptoms standardization of syndromes especially becomes scientific research focal point in this field,furthermore some studies exists the conditions of symptoms short of norm and standards of syndrome differentiation discordant,as well stagnation of liver-QI with deficiency of the spleen is clinical common syndrome,so this article carried out all round analysis and investigations on the modern literature of stagnation of liver-QI with deficiency of the spleen syndrome recent ten years,to aim at analyzing the symptom characteristic and standards of syndrome differentiation on stagnation of liver-QI with deficiency of the spleen syndrome,to provide the bases of standardization and normalization of stagnation of liver-QI with deficiency of the spleen syndrome.
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The sperm DNA integrity is important for the success of natural or assisted fertilization, as well as normal development of the embryo, fetus and child. Some investigations have demonstrated that when the damaged spermatozoa DNA of the husband exceeds than 30%, the couple has very low potential of natural fertility. Several methods are available for the assessment of sperm DNA integrity, which is considered to be a better marker of male fertility potential than conventional semen parameters. Furthermore, monitering sperm DNA integrity may become an important part of the evaluation for couples seeking assisted reproductive techniques such as intracytoplasmic sperm injection (ICSI). Finally, the effects of cryopreservation and preparation techniques on sperm DNA integrity are summarized.
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Humans , Male , Chromatin , Chemistry , Cryopreservation , DNA Damage , Infertility, Male , Genetics , Reproductive Techniques , SpermatozoaABSTRACT
ObjectiveTo explore the projections of the long descending propriospinal tracts to lumbar enlargement. Method Anterograde tracing with cupric-silver staining. 10 animals were injected b biotinylated dextran in the upper cervical cord. Following survival times of 14 days, projections of the long descending propriospinal tracts were immunohistochemically demonstrated in the lumbar enlargement.Results The degenerated terminals and labeled terminals were found in the bilateral gray matter of the lumbar enlargement, but predominantly ipsilaterally. The terminals were widely distributed in laminal Ⅴ-Ⅸ, heavily Ⅶ and Ⅷ. Conclusion The long descending propriospinal tract from the upper cervical cord projects to the lumbar enlargement.
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AIM To study the characteristic of th e rapidly activating component (Ikr) and the slowly activating compone nt (Iks) of the delayed rectifier K+ current in guinea pig hypertrop hi ed ventricular myocytes induced by thyroxine. METHOD The whole c ell patch clamp techniques were used. RESULTS In hypertrophied ve ntricular myocytes, the magnitude of IKr and IKs were great ly augmented with more positive depolarizations, and the degree of increase of IKr tail and IKs were greater than that of IKr an d IKs tail, respectively. By measuring the amplitude of tail currents which reflected the degree of activation, the activation curve of IKs was shifted toward more negative potential, but that of IKr was marked ly unaffected in hypertrophied myocytes. CONCLUSION Hypertrophied ventricular myocytes induced by thyroxine obviously increased IKr and IKs.
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Objective To study whether intranasally administered transforming growth factor beta1(TGF-?1)can reach central nervous system(CNS)through the trigeminal nerve pathway.Methods Nineteen healthy male SD rats were randomly assigned into control group(n=6)and administration(IN)0.5h group(n=3),1h group(n=4),2h group(n=3)and 6h group(n=3).Rats in IN groups were given 50?l(20?g)recombinant human TGF-?1(rhTGF-?1)intranasally and were sacrificed at 0.5,1,2 or 6h after IN following blood sample collection.The cerebellum,midbrain,pon,medulla and trigeminal nerve were separated quickly and the concentration of TGF-?1 was analyzed by ELISA.Results Compared with the control group(15.01?1.50pg/mg),TGF-?1 was significantly elevated in the trigeminal nerve in all the IN groups(P0.05).TGF-?1 concentrations in plasma and other caudal CNS regions,such as cerebellum,midbrain and cervical spinal cord,were not significantly changed compared with that in control group.Conclusion TGF-?1 is likely to be absorbed by the trigeminal nerve following intranasal administration,and is subsequently delivered to some brain regions through the trigeminal nerve pathway,which may provide a potential treatment strategy for trigeminal nerve and CNS disorders.