Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Objective:To study on performance comparison between clinic digital memory assessment and previously used assessments in dementia risk screening.To compare the performance comparison between Beijing Aging Brain Rejuvenation Initiative(BABRI)Brain Health System's Clinic Digital Memory Detection as study and Alzheimer Disease-8(AD8)and the Brief Community Screening Instrument for Dementia(BCSID)as controls, We calculated and evaluated the accuracy, sensitivity and specificity of screening Mild cognitive impairment(MCI)among these tests.Furthermore, BABRI Brain Health System was used to conduct a large sample brain health examination and early dementia screening to test the validity, adaptability and stability of the evaluation results by BABRI Brain Health System'Clinic Digital Memory Detection.Methods:Dataset 1 contained 669 elderly subjects from five communities in Beijing were recruited according to inclusion and exclusion standard.The diagnosis of MCI was based on the full set of neuropsychological scale and Petersen standard.Dataset 1 was used to compare the discriminant effect of BABRI Brain Health System'Clinic Digital Memory Detection as study versus AD8 and BCSID as controls.The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of each measurement tool were calculated.Then, the receiver operator characteristic(ROC)curve was prepared to compare the discrimination ability of MCI between each measurement tool.While the area under the curve(AUC)of different tools was compared by Wald χ2 test.Dataset 2 contained 284 103 subjects from 16 communities in Beijing, which were used to test the applicability of large sample screening in BABRI Brain Health System. Results:77 patients with MCI were found among 666 people, and incidence rate was 11.56% using the full set of neuropsychological scales in dataset 1.Compared with the results of other tests, the sensitivity of BABRI Brain Health System to correctly distinguish MCI was 0.753, which was close to BCSID, and better than AD8.In addition, BABRI Brain Health System's Youden's index was 0.741 and AUC was 0.905, which suggested that the specificity, positive predictive value, negative predictive value and cognitive domain coverage of MCI screening were generally better in BABRI Brain Health System than in AD8 and BCSID.Finally, the Brain Health Examination results of 284, 000 people in dataset 2 showed that the high-risk detection rate of MCI(8.65%)of the tool for people over 50 years old under a large sample was quite close to the results of dataset 1(8.67%), indicating that the BABRI Brain Health System had high stability.Conclusions:BABRI Brain Health System has not only high sensitivity and specificity, but also wide cognitive field coverage and high stability.BABRI Brain Health System is suitable for large-scale brain health examination and dementia risk screening in grass-roots communities, and is worthy of popularization.

Objective:To analyze the epidemiological characteristics of human brucellosis (HB), evolution and origin feature of Brucella strains in Tongliao city, Inner Mongolia Autonomous Region during 2004-2018, and to provide evidence for strategy development against the disease. Methods:Data from the reports on HB in Tongliao during 2004-2018 were extracted from the China Information System for Disease Control and Prevention before being analyzed with software Excel 2016. Epidemiologic feature was described, using the number of cases, constituent ratio and related rates. Conventional biotypes methods were used for identification of species/biovars strains while species of six Brucella strains were further verified by AMOS-PCR. Cluster analyze on six Brucella strains were performed with Bio-Numerics 5.0 software and for examining and revealing the genetic characteristics of the related strains. Results:During 2004-2018, a total of 16 704 HB cases were reported, with the incidence rate as 35.41/100 000. The incidence rates appeared as 110.51/100 000 in Jarud Banner and 67.84/100 000 in Kulun flag, which were both higher than the other areas. Most of the cases were reported in the 40 -54 year olds, which accounted for 48.75% (8 143/16 704). The number of HB in farmers appeared as 14 873, which counted for 89.04% (14 873/16 704) of all the cases. Male to female ratio of incidence was 2.40∶1. Most of the reported cases appeared between March to May, which accounted for 56.30% (9 405/16 704). Peak of the disease was seen in April. Using the conventional identification method, results showed that the available six strains all belonged to B. melitensis, including three of them as B. melitensis bv.1 and others three strains as B. melitensis bv. 3. Results from the amplified AMOS-PCR showed that all the strains were B. melitensis. The six strains clustered in two MLVA-11 genotypes (111 and 116) and all belonged to the Eastern Mediterranean lineage. Based on the MLVA-16 cluster analysis, results suggested that strains from this study were having close genetic relationship with B. melitensis strains that were from Jilin and Heilongjiang provinces. Conclusions:Human brucellosis identified in Tongliao area was with greater risk in spreading the disease to the vicinity. Our findings indicated that the programs on detection and control of the disease should be strengthened.

Objective To study the association between white matter hyperintensities(WMH)and cognitive function in silent lacunar cerebral infarction patients and its risk factors.Methods One hundred and seventy-four silent lacunar cerebral infarction patients were included in this study. They underwent MRI to show the site and severity of their WMH,including degrees 0-3of periventricular WMH in 21,102,39,12patients respectively,and deep WMH in 19,53,86,16patients respectively.Then,their cognitive function scores were compared.Results The degree of WMH was significantly higher and the age was significantly older in silent lacunar cerebral infarction patients(P＜0.05).The situation memory,working memory and Simplified Intelligent State Scale score were significantly different in patients with different degrees of WMH in peripheral brain(P＜0.05,P＜0.01).The working memory was significantly different in patients with different degrees of WMH in deep brain(P＜0.05).Degrees 1and 2of periventricular WMH were the independent risk factors for the impaired working memory(β=-0.264,P=0.038;β=-0.325,P=0.011)while degree 3of periventricular WMH was the independent risk factor for the impaired cognitive function(β=-0.273,P=0.014).Conclusion The memory is easy to be impaired in silent lacunar cerebral infarction patients with WMH of aging brain.Periventricular WMH is the major risk factor for cognitive impairment.

Objective To optimize the method of the directional differentiation of adipose-derived stem cells into keratinocytes.Methods Adipose-derived stem cells (ADSCs),separated by collagenase digestion method,were isolated and cultured.Then the expression of surface specific markers CD34,CD44 and CD90 were detected by flow cytometer.The effect of different induced mediums cultured for two weeks on the differentiation of ADSCs into KCs was demonstrated:Group 1,the DMEM supplied with 2％ FBS and 49％ supertant of KCs;group 2,KSFM medium;group 3,DMEM medium supplied with 10％ FBS and 5 μM ATRA;10％ FBS DMEM as the control group.Immunofluorescene staining was applied to detect the expression of keratin CK14 and F-actin.Results A flattened fibroblast-like morphology was observed in cells,the positive expression rate of CD34 was 0.08％,while those of CD44 and CD90 were 99％.The cells that could differentiate into osteoblasts and chondrocytes,indicated that the cells were ADSCs.There was no significant change in the cell morphology in the group 1 under the induction medium;about 10％ of the cells in group 2 were altered;the morphological changes were obvious in group 3,and approximately 20％ of the cells showed irregular polygon.The immunofluorescene staining of the cells in group 3 indicated that the cells showed cobblestone-like phenotype and an organized cytoskeletal network with dense actin fibers at the edges;some cells were positive for CK14.Conclusions ADSCs show higher induction rate under ATRA stimulation.

OBJECTIVETo investigate the expression of long noncoding RNA linc00261 in hepatocellular carcinoma (HCC) and its correlation with the clinicopathological features and postoperative outcomes of the patients.

METHODSReal-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of linc00261 in surgical specimens of HCC and adjacent tissues from 74 patients. The correlation of the expression level of linc00261 in HCC with the clinicopathological parameters of the patients was analyzed using Chi-square test. The Cox's proportional hazards regression model was used to assess the value of linc00261 in predicting the prognosis of HCC patients after operation. The expression of linc00261 was also examined in 5 HCC cell lines using qRT-PCR. The HCC cell lines MHCC-LM3 and SNU-449 were transfected with small interfering RNAs targeting linc00261 for linc00261 knockdown, and the changes in the cell proliferation, migration and invasion abilities were observed using CCK-8 assay and Transwell assay.

RESULTSThe expression level of linc00261 in HCC was significantly correlated with AFP (=0.032), tumor size (=0.007), microscopic vascular invasion (MVI; =0.01), and TNM stage (=002). The patients with lowered expressions of linc00261 in HCC tissues had a significantly shortened tumor-free survival time ( < 0.05), and a lowered expression of linc00261 was identified as an independent risk factor affecting postoperative recurrence-free survival time of the patients ( < 0.05). In HCC cell lines MHCC-LM3 and SNU-449 cells, linc00261 knockdown obviously promoted the cell migration and invasion ( < 0.01) but did not significantly affect cell proliferation ( > 0.05).

CONCLUSIONSLinc00261 may serve as a new prognostic biomarker for predicting the postoperative outcomes of the patients with HCC.

Objective To evaluate the biomechanical effectiveness of hyaluronidase (HAase) on rabbit auricular cartilage in the early stage.Methods HAase in 3 different concentrations (75 U/ml,150 U/ml,300 U/ml) were injected subcutaneously to rabbit auricle in 3 groups,while normal saline were injected as control.For the comparison of biomechanism properties among different groups and different time,cartilages were harvested at 3rd and 7th day after injection,followed by stress-relaxation assay.Results Auricular cartilage displayed different levels in control group compared with other groups in elastic modulus (P＜0.05) and maxmum stress (P＜0.05) in 3th day as well as 7th day.While both in the same concentration group,there were also differences between the 3th and 7th day (P＜0.05).Conclusions HAase injection can cause changes in biomechanical properties of auricular cartilage.And 7 days would not be enough for the tissue recovery biomechanically.

Objective To evaluate the effects of lung-protective ventilation on acute lung injury after liver transplantation.Methods Sixty patients of both sexes,aged 21-64 yr,with body mass index of 18-28 kg/m2,of American Society of Anesthesiologists physical status Ⅱ-Ⅳ,scheduled for elective orthotopic liver transplantation,were divided into 2 groups (n =30 each) using a random number table:conventional mechanical ventilation group (group CMV) and lung-protective ventilation group (group LPV).In group LPV,the patients were mechanically ventilated (tidal volume 6-8 ml/kg,respiratory rate 10-15 breaths/min,positive end-expiratory pressure 3-10 cmH2 O),and lung recruitment mnaneuver was pertormed every 2 h.Before skin incision (T1),at 3 h of preanhepatic phase (T2),at 30 min of anhepatic phase (T3) and at 2 and 4 h of neohepatic phase (T4.5),bronchoalveolar lavage fluid (BALF) was collected and blood samples from the radial artery were simultaneously collected for determination of tumor necrosis factor-alpha and interleukin-8 concentrations in BALF and serum by enzyme-linked immunosorbent assay.At 2 h after operation (T6),before tracheal extubation (T7) and at 2 days after operation (T8),blood samples from the radial artery were collected for blood gas analysis,and oxygenation index was calculated.The concentrations of serum Clara cell secretory protein 16,surfactant protein D and soluble receptor for advanced glycation end-products were determined at T1-T8 using enzyme-linked immunosorbent assay.The postoperative emergence time,extubation time,duration of intensive care unit stay and development of acute lung injury were recorded.Results Compared with group CMV,the cxtubation time was significantly shortened,serum concentrations of Clara cell secretory protein 16 at T2,T3,T6 and T7,serum surfactant protein D concentrations at T5 and serum concentrations of soluable receptor for advanced glycation endproducts at T5 and T6 were decreased (P＜0.05),and no significant change was found in tunor necrosis factor-alpha and interleukin-8 concentrations in serum and BALF at each time point or postoperative incidence of acute lung injury,oxygenation index,emergence time and duration of intensive care unit stay in group LPV (P＞0.05).Conclusion Although lung-protective ventilation dose not decrease the development of acute lung injury after liver transplantation,it attenuates lung tissue injury to some extent.

BACKGROUNDMyotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease caused by abnormal expansion of cytosine-thymine-guanine (CTG) repeats in the myotonic dystrophy protein kinase gene. The clinical manifestations of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations, which make molecular methods essential for the diagnosis. So far, very few studies about molecular diagnosis in Chinese patients with DM1 have been reported. Therefore, we carried out a study using two different methods in molecular diagnosis to verify the validity in detecting CTG expansion in Chinese patients showing DM signs.

METHODSA total of 97 Chinese individuals were referred for molecular diagnosis of DM1 using conventional polymerase chain reaction (PCR) accompanied by Southern blotting and triplet primed PCR (TP-PCR). We evaluated the sensitivity and limitation of each method using percentage.

RESULTSBy conventional PCR 65 samples showed only one fragment corresponding to the normal allele and 62 out of them were correctly diagnosed as DM1 by TP-PCR and three homologous non-DM1 samples were ruled out; Southern blotting analysis successfully made 13 out of 16 correct diagnoses with a more sensitivity using α-(32)P-labeled probes than dig-labeled probes.

CONCLUSIONMolecular analysis is necessary for the diagnosis of DM1 and TP-PCR is a reliable, sensitive, and easily performed method in molecular diagnosis which is worthy to be popularized.

Adult ; Aged ; Blotting, Southern ; Female ; Humans ; Male ; Middle Aged ; Molecular Diagnostic Techniques ; methods ; Myotonic Dystrophy ; diagnosis ; genetics ; Polymerase Chain Reaction ; Sensitivity and Specificity ; Young Adult

Objective To discuss the indication for kidney-sparing surgery (KSS) on primary urothelial carcinoma of the distal ureter.MethodsClinical data of 108 patients with primary urothelial carcinoma of the distal ureter in our hospital from 2001 to 2009 were analyzed retrospectively.There were 75 males and 33 females with mean age of 62 ( range from 42 to 85 ) years old in this study.The patients were divided into KSS group and RNU group according to the operation methods.The recurrence rate of radical nephroureterectomy (RNU) and KSS were evaluated.Results The recurrence was seen none with T,stage,1 (12.5％) with T1 stage,4 (36.4％) with T2 stage and 4 (80％) with T3 stage in KSS group.In RNU group,there was none with Ta stage,4 ( 15.4％ ) with T1 stage,10 (33.3％) with T2 stage and 7 (36.8％) with T3 stage recurred.There was no difference between patients with Ta to T2 stages in KSS and RNU group (P ＞0.05 ) on recurrence,but there was a significant difference between patients with T3 stage (P＜0.05).There was 1 (33.3％) case with G1 grade,3 (18.8％) with G2 grade and 5 (62.5％) with G3 grade recurred in KSS group,while 2 (22.2％) cases with G1 grade,9 (20％) with G2 grade and 10 (37.0％) with G3 grade recurred in RNU group.There was no difference between patients with G1 to G2 grades in KSS and RNU group (P＞0.05),but there was a significant difference between patients with G3 stage in the two groups ( P ＜ 0.05 ).Conclusion KSS seems to be safe for patients with low stage and low grade primary urothelial carcinoma of the distal ureter.