Objective To investigate the impact of cerebral microbleeds (CMBs) on cognitive function in ischemic stroke patients.Methods A total of 268 acute ischemic stroke patients recruited in the Ningbo First Hospital from January 2014 to June 2015 were divided into CMBs group (199 patients) and non-CMBs group (69 patients) according to whether complicated with CMBs by susceptibility-weighted imaging (SWI).According to the microbleed number, CMBs group patients were divided into 2 grades: grade 1 (1-5 CMBs) and grade 2 (≥6 CMBs). Montreal Cognitive Assessment (MoCA) was used to evaluate and compare the global cognitive function and cognitive domains of the patients. Results The total MoCA score and the scores of visuospatial/executive, attention domains in CMBs group were 20.95±4.53, 2.53±1.09, 3.83±0.97, while those in non-CMBs group were 26.82±1.25, 3.16±1.24 and 4.91±0.84. The total MoCA score and the scores of visuospatial/executive, attention domains were significantly lower in CMBs group than those in non-CMBs group (t=16.59, P<0.01;t=3.75, P<0.01;t=8.83, P<0.01). The total MoCA score and the score of attention domain in grade 1 CMBs group were 21.53±4.61 and 4.11±0.91 , which were significantly lower than those in non-CMBs group (t=14.09, P<0.01;t=14.23, P<0.01). Whereas the total MoCA score and the scores of visuospatial/executive, attention, orientation domains in grade 1 CMBs group were 21.53±4.61, 2.88±1.06, 4.11±0.91, 4.96±0.40, which were significantly higher than those in grade 2 CMBs group (18.58±3.08, 2.23±0.95, 3.63±1.01, 3.85±0.39, respectively;t=2.85, P<0.01;t=2.54, P<0.05;t=5.63, P<0.01;t=2.58, P<0.01). Multivariate regression analysis showed that independent risk factors of MoCA scores in ischemic stroke patients included CMBs (OR=3.15, 95% CI 1.28-5.12, P=0.005) and the number of CMBs (OR=1.73,95% CI 1.08-2.32,P=0.031). Conclusions CMBs and the number of CMBs were independently associated with cognitive impairment in ischemic stroke patients. And with the increasing of the microbleed number, the impairments of certain cognitive domains were more obviously.

Objective To prepare the sinomenine hydrochloride multivesicular liposomes with high entrapment efficiency and sustained release character.Methods Multiple emulsion method was used to prepare the sinomenine hydrochloride multivesicular liposomes.Uniform design was applied to optimize the formulation and pharmaceutical process.The shape,the particle size,and the release charcter of the liposome were evaluated.Results The sinomenine hydrochloride multivesicular liposomes prepared were spherical and the size of majority particles was in the range of 20—30 ?m and well distributed.The encapsulation efficiency was more than 80% and its in-vitro release profile accorded well with the Higuchi model with t1/2 up to 52.7 h.Conclusion The formulation and pharmaceutical process of the sinomenine hydrochloride multivesicular liposomes are stable and feasible with the high encapsulation efficiency and good sustained-release character.

Objective To prepare sinomenine hydrochloride transfersomes and evaluate their qualities. MethodsThree different preparation methods including film dispersion, reverse phase evaporation, and ethanol injection methods were compared according to the encapsulation efficiency of transfersomes. Uniform design was applied to optimize the formulation and pharmaceutical process of reverse phase evaporation. The particle size, the appearance, the Z-potential, and the stability were also evaluated. ResultsThe transfersomes prepared by reverse-phase evaporation method possessed the highest encapsulation efficiency. The ideal combinations of preparation and formulation were: soya lecithin/sodium cholate was 200/30 mg/mg, chloroform/PBS was 5 mL/mL, pH of PBS was 6.5, added sinomenine hydrochloride was 10 mg. The transfersomes obtained were milky white translucent suspension, with a mean encapsulation efficiency of 62.2%. The shape of their particles was spherical or similar to spherical under microscope, which was smooth and disconglutinated with an average diameter of 96.4 nm, and a Z-potential of-35.93 mV. Aggregation or deposition was not observed after exposure under the temperature of 4 ℃ for 30 d. ConclusionThe preparation process of sinomenine hydrochloride transfersomes is feasible, the quality of obtained transfersomes is stable.It is expected to provide a new preparation for clinical use of sinomenine hydrochloride.

Objective: To explore the mechanism of moxibustion for rheumatoid arthritis (RA) by observing the metabolite changes in urine using liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis. Methods: Twenty-four rats were randomly divided into a control group, a model group, and a moxibustion group. Rats in the model and moxibustion groups were established as collagen-induced arthritis (CIA) models. The control and model groups did not receive any intervention; rats in the moxibustion group received moxibustion at Shenshu (BL23) and Zusanli (ST36). After three weeks of intervention, ankle joint, serum, and urine samples were collected for pathological examinations and metabolomic tests. Results: After moxibustion treatment, the CIA rats showed increased body mass, reduced swelling of the hind paws and arthritis score, decreased serum cytokine levels, and improved histopathological evaluation of the ankle joint. Twenty-four significantly altered metabolites were found, mainly involved in alanine metabolism, taurine and hypotaurine metabolism, tricarboxylic acid cycle, phenylalanine metabolism, tyrosine metabolism, and primary bile acid biosynthesis. These metabolites may serve as potential biomarkers for RA. Conclusion: Moxibustion can effectively resist inflammation in CIA rats. The potential biomarkers and the abnormal metabolic pathways of RA can be identified by LC-MS-based metabolomics. Metabolomics may be an effective way to explain the mechanism of moxibustion in treating RA.

OBJECTIVE To find the infla mmation bio markers induced by coke oven e missions (COE),we investigated the changes of T helper 17 (Th17 )cytokines in hu man bronchial epithelial (16HBE)cells.METHODS 16HBE cells were exposed to organic extracts of COE collected fro m co-king plant at the concentrations of 5,10 and 20 mg·L -1 for 24 h or 5 d to establish short-term and long-term cell models,respectively.Cell viability was measured by MTT assay and infla mmatory da mage was assessed by lactate dehydrogenase assay (LDH).The cytokines in culture supernatant sa mples was detected by co mmercial hu man Th17 cytokine panel kit.RESULTS COE Can induce infla mmation in COE 20 mg·L -1 group and no expression on IL-17 F and IL-1 β.The concentration of IL-10 was 1 .25 ± 0.54,1 .39 ±0.13 and (1 .90 ±0.73)pg·mL -1 in COE 5,10 and 20 mg·L -1 group showing good con-centration-effect relationship (r=0.98,P <0.05 ).IL-23 expression was found only higher at 10 and 20 mg·L -1 and the concentrations were 3.38 ±3.90 and (1 .74 ±2.00 )pg·mL -1 ,respectively.In 16HBE cells treated by COE for 5 d,elevated expression of IL-17A was found in COE 5 and 10 mg·L -1 group,and there was statistically sigificant difference between COE 10 mg·L -1 and DMSO group (P<0.05).Elevated concentration of IL-17F of 10.2 ±1 1 .78 and (6.79 ±7.84)pg·mL -1 was found in COE 5 and 10 mg·L -1 group.The concentration of IL-10 was 1 .71 ±0.02,1 .49 ±0.25 and (2.82 ± 0.33)pg·mL -1 in COE 5,10 and 20 mg·L -1 group,respectively.We found increased IL-1 βexpression with concentration of 2.72 ±0.62,2.25 ±0.33 and (0.93 ±0.21 )pg·mL -1 in COE 5,10 and 20 mg·L -1 group with negative dose-response relationship.We also found more elevated TNF-αlevels in the 5 d than in the 24 h model with no COE specific relationship.CONCLUSION COE induces expression changes of Th17 cytokines profile in 16HBE cells,including IL-23 and IL-1 βfor early and long-term infla mmation,respectively.IL-10 may be a candidate marker for population study on COE induced infla mmatory injury.

The plasma levels of homocysteine (Hcy),vitamin B12 and folic acid were measured in a total of 101 patients with herpes zoster (observation group) before treatment and 100 healthy controls (control group).And the plasma level of Hcy was also measured in observation group after treatment.There was a significant increase of Hcy level in observation group versus control group (P ＜0.01).And the levels of VitB12 and folic acid did not fluctuate (P ＞ 0.05).The occurrence rate of hyperhomocysteinemia and the level of Hcy differed in age group,onset site and pain severity (P ＜ 0.05).No significant differences existed between gender or onset site (P ＞ 0.05).The level of Hcy significantly decreased after treatment versus before treatment (P ＜0.01).Plasma Hcy significantly increased in patients with herpes zoster.And it was correlated with age,lesion extent and pain severity.However,there was no correlation with gender,onset site or levels of vitamin B12 and folic acid.

Objective:To study the protective effects of Danhong injection ( DH) on myocardial damage induced by doxorubicin ( DOX) in Lewis tumor bearing mice. Methods:The model of Lewis lung cancer in mice was established by underarm injecting tumor cells, and then randomly divided into four groups:the model control group, DOX group, DH group and DH+DOX group. After the experiment, myocardial and tumor tissue were separated from Lewis tumor bearing mice, and the excised tumors were weighted. The activities of lactate dehydrogenase ( LDH) , creatine kinase ( CK) , manganese superoxide dismutase ( SOD) , catalase ( CAT) and glu-tathione peroxidase ( GPx) , and the content of malondialdehyde ( MDA) were determined by a colorimetric method. Flow cytometry was used to determine the levels of apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (△Ψm). Re-sults:Compared with that in the model control group, a significant decrease of tumor weight was shown in both DOX group and DH+DOX group (P<0. 01). DH had no significant influence on the anticancer function of DOX. The activity of LDH and CK, and the ap-optosis in myocardium cells significantly increased (P<0. 01). Compared with DOX group, the activities of LDH and CK, and the ap-optosis significantly decreased in DH+DOX group (P<0. 01). The activities of △Ψm, SOD, CAT and GPx significantly increased (P<0.05orP<0.01). ThecontentofMDAandROSgenerationbothdecreased(P<0.01).Conclusion:DHhasnosignificantin-fluence on the antitumor effect of DOX. The combination of DH and DOX shows cadioprotective effect on the myocardial damage through improving mitochondrial antioxidant defense capacity, ameliorating oxidative stress and maintaining △Ψm homeostasis.

Objective To explore the differences between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) accompanied with or without community-acquired pneumonia (CAP).Methods We collected 141 patients with COPD who met the admission criteria and had multiple acute exacerbation hospitalization history.Among them,40 patients with AECOPD accompanied with or without acute exacerbation of hospitalization of CAP (group A),38 patients with AECOPD accompanied with acute exacerbation of hospitalization of CAP (group B) and 63 patients with AECOPD but without acute exacerbation of hospitalization of CAP (group C).The demographic differences of age,sex and smoking status were analyzed and compared.The clinical symptoms and blood-related inflammatory indicators of pa tients in group A were analyzed and compared under the acute aggravation of CAP.The number of acute hospitalizations in 12 months before onset and 12 months after discharge were tracked.Results The age,smoking rate,COPD-GOLD classification,dyspnea index,anxiety and depression score in group A were higher than those in group B and C,while the percentage of forced expiratory volume in the first second (FEV1) in predicted value was lower than that in group B and C.The proportion of patients who cooperated or needed long-term home oxygen therapy and drug therapy was higher than that in group B and C,with statistical significance (P ＜ 0.05),but there was no statistical difference in each index between group B and C (P ＞ 0.05).The clinical symptoms of cough,expectoration,fever and other blood-related inflammatory indicators were aggravated in group A when accompanied with CAP.The number of acute hospitalizations in 12 months after discharge of AECOPD without CAP was significantly higher than that of COPD with CAP (P ＜ 0.05),while there was no significant difference in blood gas analysis indicators between the two cases (P ＞ 0.05).The number of hospitalizations in 12 months after discharge,percentage of neutrophils (N)and the level of interleukin (IL)-17 were independent clinical predictors of COPD with CAP.Conclusions Patients with AECOPD accompanied with or without CAP (group A) had poor lung function,worse illness conditions,greater support of home oxygen therapy and drug therapy and poor quality of life.Patients with AECOPD accompanied with CAP had more symptoms and higher levels of inflammatory indicators,but less risk of re-hospitalization in 12 months after cure than AECOPD patients without CAP.The number of hospitalization in 12 month after discharge,the percentage of neutrophils (N),and IL-17 level were helpful in screening the patients with CAP from the AECOPD patients.

OBJECTIVE: To analyze the clinical characteristics and genetic basis of a child affected with Glass syndrome. METHODS: Clinical manifestations and auxiliary examination results of the child were analyzed. Potential mutation was detected with next generation sequencing and validated by Sanger sequencing. RESULTS: The child has featured growth and mental retardation, delayed speech, cleft palate, crowding of teeth, and downslanting palpebral fissures. DNA sequencing revealed a de novo heterozygous missense mutation c.1166G>A (p.R389H) in exon 8 of the SATB2 gene in the child. CONCLUSION The heterozygous mutation c.1166G>A (p.R389H) of the SATB2 gene probably account for the Glass syndrome in the patient.
Abnormalities, Multiple ; genetics ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 2 ; Humans ; Intellectual Disability ; genetics ; Matrix Attachment Region Binding Proteins ; genetics ; Mutation ; Transcription Factors ; genetics

Objective To investigate the regulation of SIRT1 on ovarian granulosa cell in women with poor ovarian response.Methods A total of 60 women who underwent IVF/ICSI-ET were included in this study,30 women in poor ovarian response(POR)group and 30 women in normal ovarian response(NOR)group.The granulosa cells in follicular fluid were isolated and purified by density gradient centrifugation.The granulosa cells of POR group were treated with SIRT1 agonist resveratrol(RESV)or inhibitor EX527,respectively,and the control group was granulosa cells treated without drugs.mRNA levels of SIRT1 and key enzymes of steroid hormone synthesis(StAR,CYP19,CYP17)in granulosa cells were detected by qPCR.The levels of SIRT1,steroid hormone synthesis key enzymes protein and apoptosis-related protein(Bcl-2,Caspase-3)in granulosa cells were detected by Western blot.The apoptosis rate of granulosa cells was detected by TUNEL method.Determination of estradiol in granulosa cell culture medium by chemiluminescence.Results The mRNA and protein levels of SIRT1 in granulosa cells in POR group were lower than those in NOR group(P = 0.003,P<0.001).RESV up-regulated SIRT1 mRNA and protein levels(P<0.001),up-regulated mRNA and protein levels of steroid hormone synthesis key enzyme(P<0.05).EX527 down-regulated SIRT1 mRNA and protein levels(P = 0.023,0.001),down-regulated mRNA and protein levels of steroid hormone synthesis key enzymes(P<0.05).After RESV treatment,the apoptosis rate of granulosa cells was decreased(P<0.001),the Bcl-2 protein level was increased(P<0.001),and the Caspase-3 protein level was decreased(P<0.001).After EX527 treatment,the apoptosis rate of granulosa cells was increased(P<0.001),the Bcl-2 protein level was decreased(P = 0.003),and the Caspase-3 protein level was increased(P<0.001).Conclusion The SIRT1 level in granulosa cells of POR women was lower than that of NOR women.RESV up-regulated SIRT1 expression in granulosa cells.SIRT1 inhibited granulosa cell apoptosis,increased the level of steroid hormone synthesis key enzyme,and promoted estradiol synthesis in granulosa cell.Therefore,SIRT1 activators such as RESV may be a therapeutic agent to improve ovarian reactivity and increase the number of oocytes obtained in women with POR.