The mild cognitive impairment and vascular cognitive impairment no dementia are the early stages for Alzheimer's disease and vascular dementia proposed in recent years.They both not only have some differences,but also have many crosses and contacts in concepts,diagnostic criteria,epidemiology,pathology,neuropsychology,and biological markers,etc.This article reviews the recent progresses and problems facing in recent years.

ObjectiveTo investigate the treatment strategies and factors influencing the prognosis of patients with primary gallbladder carcinoma.MethodsThe clinical data of 135 patients with primary gallbladder cancer who were admitted to the Cancer Hospital of Tianjin Medical University from January 2000 to December 2009 were retrospectively analyzed.The survival curve was drawn by the Kaplan-Meier method,and the survival rates were analyzed by using the Log-rank test.Factors which may have influences on the prognosis were analyzed by univariate analysis and COX multivariate analysis.ResultsThe overall 1-,3-,5-year survival rates of the 135 patients were 46.7％,10.4％ and 5.2％,respectively.The 1-,3-,5-year survival rates of 74 patients who received radical resection of gallbladder cancer were 68.9％,18.9％ and 9.5％,respectively.The 1-,3-,5-year survival rates of 50 patients who received palliative treatment were 24.0％,0 and 0,respectively.The 1-,3-,5-year survival rates of 11 patients who received conservative treatment were 0,0 and 0,respectively.There was no significant difference in the survival rates among patients who received different treatment methods (x2 =5.642,P ＜ 0.05 ). Of the 9 patients with gallbladder cancer who received reoperation after laparoscopic choledochotomy,the survival time of 1 patient in stage Ⅰ and 1 of the 3 patients in stage Ⅱ who received radical surgery exceeded 5 years,while the survival time of 5 patients in stage Ⅱ who received palliative treatment was shorter than 5 years.There was a significant difference in the survival time among the 3 groups of patients ( x2 =5.642,P＜0.05).Under the condition of same TNM stages ( Ⅱ,ⅢA,ⅢB,ⅣA,ⅣB),the survival rates of patients who received radical resection of gallbladder cancer were significantly higher than those who received palliative or conservative treatment ( x2 =8.971,21.250,44.153,6.696,21.722,P ＜ 0.05 ).The results of univariate analysis showed that age,CA19-9,TNM stages and treatment methods were risk factors influencing the median survival time ( x2 =8.466,3.977,9.837,5.642,P ＜ 0.05 ).The results of multivariate analysis showed that age,TNM stages and treatment methods were the independent risk factors influencing the median survival time ( Wald=5.779,14.724,11.640,P＜0.05).ConclusionThe prognosis of primary gallbladder cancer is poor.Age,TNM stages and treatment methods are the independent factors influencing the prognosis of patients with gallbladder cancer,and patients who receive radical resection have relatively good prognosis.

Objective To verify the anti-inflammatory effects of intra-articular injection of botulinum toxin type A (BoNT/A) on adjuvant-induced arthritis using a rat model.Methods A murine model of chronic ankle arthritis was established in 90 Wistar rats by injection of 0.1 ml of complete Freund adjuvant (CFA) into the pads of their left paws.They were then randomly divided into a BoNT group (n =30) which received an intra-articular injection of 0.1 ml (20 IU) of BoNT/A,an NS group (n=30) which received intra-articular injection of0.1 ml of normal saline solution and a sham group (n =30) which were punctured without any injection.In addition,30 normal rats formed a control group.Infrared thermal imaging was performed and an index of arthritis was evaluated every three days.The infrared thermal imaging revealed the expression of interleukin-1β (IL-1β) through hematoxy-eosin (HE) staining.Results The arthritis index began to increase 3 days after the injection of CFA and it had increased significantly after 10 days,reaching a peak value of 18,24 days after the injection.The infrared thermal imaging showed that the temperature in the right paw increased greatly after the injection.Following the development of arthritis,the temperature declined gradually,arriving at a steady temperature of between 37.5 and 38.0 ℃ in both ankles 20 days after the injection.The average temperature in both paws of the BoNT group had decreased significantly more by 7 and 14 days after the injection than in the NS and sham groups.The expression of IL-1β in the synovium of the ankle joint also had decreased significantly more in the BoNT group after 7 and 14 days.HE scoring showed an obvious histopathologic change in the hypertrophic synovium,inflamnatory cell infiltration,cartilage destruction and exposure of subchondral bone after 7 and 14 days compared with right after the injection in all groups except the control group.Moreover,the average HE scores of the BoNT group rats after 7 and 14 days were significantly lower than those seen in the NS and sham groups at the same time points.Conclusion Intra-articular injection of botulinum toxin type A has an anti-inflammatory effect on arthritis induced by complete Freund adjuvant,at least in rats.

Objective:To explore the application of failure mode and effects analysis (FMEA) in low-energy X-ray intraoperative radiotherapy (IORT), analyze its potential risks in IORT, and preliminarily explore the feasibility of FMEA in optimizing IORT management and reducing the occurrence of potential risks.Methods:An FMEA working group was established by the IORT team (1 radiologist, 1 radiology physicist, 2 surgeons, and 2 nurses) to apply the FMEA methodology to conduct a systematic risk assessment. The process modules were established, the potential failure modes and causes for each module were analyzed, the severity (SR), frequency of occurrence (OR) and likelihood of detection (DR) of failure modes were scored and the risk priority number (RPN) was calculated: RPN= SR × OR × DR. The possible errors and potential clinical impact of each part of the radiotherapy process were prospectively analyzed and understood, the causes and current measures were analyzed for each failure mode and preventive measures were proposed and risk management measures were taken accordingly.Results:The IORT process was divided into 8 modules with 14 failure modes. The highest OR value was unsatisfactory target area confirmation (7 points), the highest SR value was equipment failure to discharge the beam (10 points), the highest DR value was wrong key entry after dose calculation (7 points), the highest RPN values were unsatisfactory target area confirmation (210 points) and ineffective protection of endangered organs (180 points). Weaknesses were corrected according to priorities, workflows were optimized and more effective management methods were developed.Conclusion:FMEA is an effective method of IORT management and contributes to reducing the occurrence of potential risks.

OBJECTIVE: To explore the genetic basis for a patient with episodic ataxia and pyramidal tract signs. METHODS: The patient was subjected to high-throughput sequencing, Sanger sequencing and analysis of dynamic variant site associated with spinocerebellar ataxias (SCA). RESULTS: The patient was an adolescent male presenting with episodic ataxia, bilateral knee hyper-reflexia and ankle clonus. By genetic testing, he was found to harbor a c.1159-1162dupAAGT variant of PDHA1 gene. The same variant was not found in his parents and elder sister. No abnormalities were found by SCA dynamic variant screening. The patient was diagnosed as pyruvate dehydrogenase E1alpha deficiency due to variant of the PDHA1 gene. CONCLUSION The de novo c.1159-1162dupAAGT variant of the PDHA1 gene probably underlies the disease in the proband. Patients with pyruvate dehydrogenase E1alpha deficiency have complex phenotypes and very few have pyramidal tract involvement, which may be attributed to abnormal early neuronal development.

Exosomes are vesicles with a double globular membrane of lipids that can be secreted by a variety of cells, including stem cells. Exosomes have unique biological characteristics and irreplaceable powerful functions which play an important role in intercellular communication. The various cytokines, signal proteins, lipids and regulatory nucleic acids contained in stem cell exosomes can play a protective role against the injury of kidney, liver, heart, blood vessels and nerves. Stem cell exosomes delay the process of intervertebral disc degeneration by inhibiting the apoptosis of nucleus pulposus cells and increasing the synthesis of extracellular matrix, etc. The mechanism of its role is mainly through miRNA and related signaling pathways. Exosomes contain complex components. Although the mechanism of action of exosomes in intervertebral discs has been preliminarily explored, the components contained in exosomes are complex and the specific situation has not been fully understood, which still needs further study. In this review, the characteristics and functions of stem cell exosomes, extraction, identification and storage methods, the impacttovarious other tissues, as well as the effects on intervertebral discs and their mechanisms were elaborated in order to provide a basis for the study of intervertebral disc degenerative diseases.

Objective To investigate the electrophysiological characteristics of hamster primary cortical neurons by using the whole-cell patch-clamp recordings in a Mg2+-free cell model of epilepsy.Methods The cerebral cortex were isolated for primary neuron culture from neonatal Syrian hamsters 1-2 days after birth.After 12 days,primary neurons were exposed to normal external(Mg2+group)or Mg2+-free external(Mg2+-free group)respectively for 3 hours,followed by a 24-hour incubation in normal culture medium.Excitatory postsynaptic currents(EPSC)and excitatory postsynaptic potentials(EPSP)were recorded in voltage clamp mode and current clamp mode using whole-cell patch-clamp recordings,respectively.Results Compared to Mg2+group,the frequency of EPSC[(124.38±75.15)Hz vs.(33.93±22.32)Hz,P<0.001](P<0.001)and EPSP[(37.05±38.37)Hz vs.(5.63±9.52)Hz,P<0.01]in primary cortical neurons from the Mg2+-free group increased significantly.Meanwhile,there were no statistically significant differences in the amplitude,area under the curve and half-width of EPSC and EPSP between the two groups(P>0.05).Conclusion The present study demonstrates an increase in excitability of primary hamsters cortical neurons after Mg2+depletion,suggesting that these neurons can be utilized to use to create cell models of epilepsy.

OBJECTIVE To optimize β-cyclodextrin(β-CD)inclusion process of Cinnamomi Ramulus Formula Granules vola-tile constituents by orthogonal test,based on standard relation and information entropy method.METHODS On the basis of single factor experiments,the ratio of β-CD to aromatic aqueous solution,the inclusion temperature,and the inclusion time were selected as the investigating factors;the inclusion rate,drug loading,and standard relation of cinnamic aldehyde in inclusion complex were used as the evaluation index.The information entropy method was used to determine the weight coefficient of each index,then the comprehen-sive score was calculated,the inclusion process conditions were optimized by orthogonal experiment.The inclusion complex was charac-terized by thin layer chromatography,ultraviolet absorption spectroscopy,Fourier infrared spectroscopy,and X-ray diffraction.RE-SULTS The best inclusion process was that the ratio of β-CD to aromatic aqueous solution was 3∶100(g·mL-1),the inclusion temperature was 50℃,and the inclusion time was 1 h.The average inclusion rate of the obtained inclusion compound was 80.84%,the drug loading was 8.63%,and the standard relation was 0.91.The results of thin-layer chromatography,ultraviolet,infrared spec-troscopy and other characterization experiments showed that the volatile components in the aromatic aqueous solution successfully en-tered the β-CD cavity,and the inclusion complex was successfully prepared.CONCLUSION The optimum inclusion process is sta-ble and feasible,which can provide references for the preparation process of Cinnamomi Ramulus Formula Granules.