Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China / 中国当代儿科杂志

OBJECTIVE@#To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants.@*METHODS@#The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP.@*RESULTS@#The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (@*CONCLUSIONS@#A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

Association of different stages of histological chorioamnionitis with respiratory distress syndrome in preterm infants with a gestational age of < 32 weeks / 中国当代儿科杂志

OBJECTIVE@#To study the association of different stages of histological chorioamnionitis (HCA) with the incidence rate and severity of respiratory distress syndrome (RDS) in preterm infants.@*METHODS@#Related data were collected from the infants and their mothers who were treated in the Neonatal Intensive Care Unit of Qingdao Women and Children's Hospital, Qingdao University, from January 2018 to June 2020. According to the presence or absence of HCA and its stage, the infants were divided into four groups: control (@*RESULTS@#Compared with the control and late-stage HCA groups, the early-stage HCA group had a significantly lower incidence rate of placental abruption and a significantly higher rate of prenatal use of antibiotics (@*CONCLUSIONS@#Early-, middle-, and late-stage HCA can reduce the incidence rate of RDS in preterm infants. HCA stage may not be correlated with RDS severity in preterm infants, which needs to be verified by further research.

Advance in Flexible Variable Stiffness Actuator of Rehabilitation Robot (review) / 中国康复理论与实践

Flexible variable stiffness actuator is divided into four categories including elastic element, pneumatic element, electric-magnetic element and intelligent material. It is gradually applied in rehabilitation robot. It could adapt the change of patient's impedance in the upper and lower limb rehabilitation robots, ensure the safety of the wearer in the exoskeleton, and improve the biomimetics in the prosthesis. Variable stiffness driving mechanism for rehabilitation robot still has some disadvantages. It is proposed to have compact structure, low power consumption, good stiffness characteristics, high response rate and progressive output torque curve, etc.

Analysis of temporal and spatial characteristics of fluoride in drinking water in rural areas of Jinan City from 2015 to 2018 / 中华地方病学杂志

Objective:To understand the temporal and spatial characteristics of fluoride in rural drinking water in Jinan City.Methods:From 2015 to 2018, the factory water and terminal water samples of centralized rural water supply system were collected from all townships (streets) in 7 agriculture-related districts (counties) in Jinan City during dry season and high water season. Water samples were collected, stored, transported and tested in accordance with the "Standard Examination Methods for Drinking Water" (GB/T 5750-2006). The time, region, endemic areas (Zhangqiu, Jiyang, Shanghe, Licheng, Changqing) and non-endemic areas (Pingyin, Tianqiao) of drinking water type fluorosis, water periods (dry season and high water season), water samples (factory water and terminal water), water sources (shallow well water, deep well water, river water and reservoir water) of water fluorine were analyzed descriptively.Results:A total of 1 638 water samples were collected from 2015 to 2018, the median of water fluorine was 0.400 mg/L, ranging from 0.002 to 2.700 mg/L. The differences in water fluorine of different year (0.400, 0.430, 0.490, 0.360 mg/L) were statistically significant ( H = 33.907, P < 0.01). Total water fluorine excess rate was 5.49% (90/1 638), there were 3 districts with water fluorine excess, namely Jiyang [26.11% (59/226)], Zhangqiu [6.12% (30/490)] and Licheng [0.53% (1/188)]. The median of water fluorine in endemic areas (1 398 samples) was 0.420 mg/L, the non-endemic areas (240 samples) was 0.320 mg/L, and the water fluorine in endemic areas was significantly higher than that in non-endemic areas ( Z =-6.490, P < 0.01). The water fluorine excess rate in endemic areas was 6.44% (90/1 398), and there was no water fluorine excess in non-endemic areas. The median of water fluorine in both dry season (819 samples) and high water season (819 samples) was 0.400 mg/L. The median of water fluorine of factory water (392 samples) was 0.320 mg/L, the terminal water (1 246 samples) was 0.450 mg/L, and the water fluorine of terminal water was significantly higher than that of factory water ( Z =-6.881, P < 0.01). The water fluorine excess rates of shallow well water and deep well water were 31.76% (47/148) and 3.82% (43/1 126), respectively, and there were no water fluorine excess in river water and reservoir water. Conclusions:Fluoride of drinking water in rural areas of Jinan City exceeds the standard, mainly concentrated in Jiyang District. The water fluorine in endemic areas is higher than that in non-endemic areas, water fluorine of terminal water is higher than that of factory water, shallow well water and deep well water as the sources of water has excessive water fluoride, and the general survey and detection of fluoride content in residents' drinking water should be continuously carried out.

Research of a Wearable Lower Extremity Assisted Exoskeleton Robot System / 中国康复理论与实践

Objective:To propose a new type of lightweight wearable lower extremity exoskeleton assisted robot system, and explore the feasibility of walking and posture change rehabilitation training for patients with gait disorder and with paraplegia under T4 spinal cord injury (exclusion of lower extremity muscle spasm and obvious pain). Methods:The active and passive hybrid wearable lower extremity exoskeleton assisted robot structure of the hip joint with two-motor active drive and the knee joint passive four-link simulating the instantaneous movement of the human body was designed. Based on modular control, the STM32F767IGT6 and peripheral circuits, attitude acquisition, power supply and crutches module control system were proposed. The exoskeleton robot was worn by a normal person to perform the experiment of leveling, slope and posture transformation and analyze hip/knee /ankle joint angles during exercise, and compare the myoelectric signals of the lateral femoral and medial femoral muscles. Results:The wearer could realize the sitting-standing posture change and the flat/slope walking only based on the exoskeleton robot system, and the hip/knee/ankle angles were basically consistent with the normal walking and the electromyographic signals of the lateral femoral, medial femoral muscle significantly decreased when the robot was worn while walking. Conclusion:The active-passive hybrid lower exoskeleton assisted robot system can still achieve the rehabilitation of walking and posture change while reducing the weight. This verified the feasibility of the assisted robot system with the active dual-motor of the hip joint and the passive four-link structure of the knee joint to help the patients with paraplegia and gait disorder to walk and recover.

Report of three death cases of imported falciparum malaria in Wenzhou City / 中国血吸虫病防治杂志

The three death cases of falciparum malaria in Wenzhou City were all imported from Africa. One patient died on 10 January 2007 because of severe clinical symptoms after hospitalization. The second case was initially misdiagnosed as influen-za in primary health and medical institution. The patient's condition quickly worsened and died of Plasmodium falciparum infec-tion on 5 March 2011. The third patient belonged to"non-identity"person,and there were no detailed information and epidemio-logical history on admission,which resulted in the delayed diagnosis,disease exacerbation and death. In conclusion,the health education should be provided to the people who return from Africa and also to medical workers in order to reduce the mortality of falciparum malaria.

Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71.</p><p><b>METHODS</b>A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children.</p><p><b>RESULTS</b>The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01).</p><p><b>CONCLUSIONS</b>T allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.</p>

Value of serum S100B protein and neuron-specific enolase levels in predicting the severity of hand, foot and mouth disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the value of serum S100B protein and neuron-specific enolase (NSE) levels in predicting the severity of hand, foot and mouth disease (HFMD).</p><p><b>METHODS</b>Ninety children with HFMD were classified into three groups: common type, severe type, and critical type (n=30 each). Thirty healthy children were randomly selected as the control group. ELISA was used to measure serum levels of S100B protein and NSE before and at 7 days after treatment. The receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of S100B protein and NSE for the severity of HFMD.</p><p><b>RESULTS</b>The critical type group had significant increases in the serum levels of S100B protein and NSE compared with the other three groups (P<0.01). The severe type group had significant increases in serum levels of S100B protein and NSE compared with the common type and control groups (P<0.01). The critical type and severe type groups had significant reductions in serum levels of S100B protein and NSE after treatment (P<0.05). Serum S100B protein had the highest Youden value of 0.611 at the cut-off value of 0.445 μg/L, with a sensitivity of 61% and a specificity of 100%, in the prediction of serious HFMD (including severe type and critical type HFMD). Serum NSE had the highest Youden value of 0.533 at the cut-off value of 5.905 μg/L, with a sensitivity of 80% and a specificity of 73%, in the prediction of serious HFMD. Combined measurements of these two parameters had a sensitivity of 86% and a specificity of 73% and had the highest predictive value for serious HFMD.</p><p><b>CONCLUSIONS</b>The serum levels of S100B protein and NSE help to predict the severity and treatment outcomes of HFMD. Combined measurements of these two parameters has a higher predictive value for serious HFMD.</p>

Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.</p><p><b>METHODS</b>All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.</p><p><b>RESULTS</b>A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.</p><p><b>CONCLUSIONS</b>Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.</p>

Differences in the Levels of Gastric Cancer Risk Factors Between Nanjing and Minqing Counties, China / 예방의학회지

OBJECTIVES: In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. METHODS: We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. RESULTS: Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. CONCLUSIONS: The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

Differences in the Levels of Gastric Cancer Risk Factors Between Nanjing and Minqing Counties, China / 예방의학회지

OBJECTIVES: In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. METHODS: We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. RESULTS: Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. CONCLUSIONS: The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

Effects of inhaled nitric oxide in neonatal hypoxemic respiratory failure from a multicenter controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation.</p><p><b>METHODS</b>A non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index > 15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group).</p><p><b>RESULTS</b>Compared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P = 0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P = 0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (< 5%) or postnatal corticosteroids (< 10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups.</p><p><b>CONCLUSIONS</b>With relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.</p>

Expressions of nucleoside diphosphate kinase (nm23) in tumor tissues are related with metastasis and length of survival of patients with hepatocellular carcinoma / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the relationship of expressions of nucleoside diphosphate kinase (nm23) and proliferating cell nuclear antigen (PCNA), as well as apoptosis, with the prognosis of HCC patients by analyzing their pathological and clinical data.</p><p><b>METHODS</b>The expressions of nm23 and PCNA were analyzed by immunohistochemistry and the apoptotic phenomena were detected by TUNEL technique in the liver samples from 43 HCC tissues, 39 para-neoplastic tissues, and 10 normal tissues. The mean apoptosis index (AI) and proliferative index (PI) in individual sample were calculated.</p><p><b>RESULTS</b>As shown by the detection, 32.6% of carcinomas had negative nm23 signal in tumor tissues, whereas all para-neoplastic and normal tissues had positive nm23. The AI in nm23 positive HCC was significantly higher than that in nm23 negative one, with statistical difference (P<0.05). Furthermore, the expressions of nm23, and the values of AI and PI were contrastively analyzed with some main pathological and clinical data of HCC. It revealed that HCC with extrahepatic metastasis showed remarkable correlation with the negative nm23 (P=0.013) and higher PI values of HCC (P=0.015). The disease-free survival in HCC patients with negative nm23 expression was significantly poorer than that in patients with positive nm23 expression.</p><p><b>CONCLUSIONS</b>These data suggest that expressions of nm23 protein in tumor tissues are correlated with occurrences of metastasis and length of survival of the HCC patients, which may be an indicator for their prognosis.</p>

Comorbidities in patients with cerebral palsy and their relationship with neurologic subtypes and Gross Motor Function Classification System levels / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the comorbidities in patients with cerebral palsy (CP) from two perspectives as neurologic subtype and gross motor functions, and find their correlations.</p><p><b>METHODS</b>Children with cerebral palsy treated in the rehabilitation center from January 2007 to June 2009 received the following examinations: intelligence capacity test, ophthalmologic consultation, language-speech test, brainstem auditory evoked potential and electroencephalogram. They were stratified according to both neurologic subtype and gross motor functions to detect the occurrence of comorbidities.</p><p><b>RESULTS</b>Of all the 354 cases, 166 (46.89%) had mental retardation, 15 (4.24%) auditory limitations, 138 (38.98%) visual disorder, 216 (61.02%) language-speech disorder and 82 (23.16%) epilepsy. The frequency of individual comorbidities were distributed disproportionately between the different neurologic subtypes. Correlation analysis showed that there was a significant correlation between the spastic diplegia and the visual disorder (correlation coefficient = 0.26), between spastic hemiplegia and epilepsy (correlation coefficient = 0.17), between spastic quadriplegia and epilepsy and mental retardation (the correlation coefficient was 0.38 and 0.11, respectively) and between both dyskinetic and mixed children and language-speech disorder (the correlation coefficient was 0.24 and 0.27, respectively). The frequency of individual comorbidities was distributed disproportionately between the different neurologic subtypes and between the different GMFCS levels (P < 0.05), except for the frequency of visual disorders (chi(2) = 1.90, P > 0.05); and with the increase of the GMFCS levels, the burden of the comorbidities were more heavy and the incidence of the comorbidities was higher. Multi-comorbidities were relatively infrequently encountered in those with spastic hemiplegic or spastic diplegic children or patients whose GMFCS levels were I-III, while these entities occurred at a frequent level for those with spastic quadriplegic, dyskinetic, or mixed or children whose GMFCS levels were IV and V, and the differences were significant (P < 0.05). The mean GMFCS levels of children with spastic quadriplegic, dyskinetic or mixed CP were higher than level III, most of them had no ability of ambulation;while the mean GMFCS levels of spastic hemiplegic or spastic diplegic children were below level III, most of them could walk independently.</p><p><b>CONCLUSIONS</b>There are correlations between the occurrence of the comorbidities such as mental retardation, auditory or visual impairments, language-speech disorders, epilepsy and the cerebral palsy subtype and the gross motor function levels. Clinicians should have a full recognition of these comorbidities, and we should have a cooperation between the different subjects to have an overall evaluation and rehabilitation and to improve the prognosis.</p>

Studies on heredity rule of the first genealogy regarding fatal familial insomnia in Henan province / 中华流行病学杂志

Objective To investigate the epidemiological,genealogic characteristic,familial history of the families with fatal familial insomnia,its clinical and pathological features as well as the heredity rule of related genes.Methods 135 familial members of 7 eras were studied.Vein blood samples from patients as well as from some familial members were collected.PRNP gene was studied with PCR,its serial was determined and then authenticated with Nsp I.Brain tissue was obtained for neuropathological test and PrPSc test with Western blot method.Results Clinical symptoms of the 2 diagnosed cases were typical.11 familial members died of similar neural disease.32 samples of their familial members,codon at D178N of PRNP of 11 members was mutated,with mutation rate as 34.38% while D129N showed as methionine.Brain tissue of both probands denaturalized into spongiform and the nerve fiber was absent but PrPSc protein was identified.Conclusion Genealogy was described in the family with fatal familial insomnia since the patients had typical clinical symptoms and pathological characteristics.It seemed necessary to confirm cases of fatal familial insomnia and their genealogy with epidemiological data and to investigate its gene characteristics as well as with neuropathological and Western blot tests.

Curcumin attenuates left ventricular dysfunction and remodeling in rabbits with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of Curcumin on rabbits with chronic heart failure.</p><p><b>METHODS</b>Heart failure was induced by combined aortic regurgitation and aortic stenosis in 20 New Zealand rabbits and treated with placebo (HF, n = 10) and Curcumin (Cur, 100 mgxkg(-1)xd(-1), n = 10) for 8 weeks, 10 sham operated rabbits served as controls (Con). Echocardiography was performed in all rabbits at baseline and 8 weeks later. Aortic diameter (AO), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic dimension (LVDs), left ventricular end-diastolic dimension (LVDd), left ventricular posterior wall thickness (LVPW) and interventricular septum thickness (IVS) were measured. Myocardial matrix metalloproteinase (MMP)-2 and MMP-9 expressions and fibrosis were determined by immunohistochemistry and Masson staining respectively.</p><p><b>RESULTS</b>Compared to baseline, LVEF and LVFS were significantly decreased, AO, LVDs, LVDd, LVPW, and IVS significantly increased at 8 weeks after operation in HF group while these changes could be significantly attenuated in Curcumin treated rabbits. The protein expressions of MMP-2 and MMP-9 were significantly down-regulated in HF group and could be significantly up-regulated by Curcumin treatment. The increased collagen deposition in HF group was also significantly reduced by Curcumin treatment.</p><p><b>CONCLUSION</b>Curcumin attenuated left ventricular dysfunction and remodeling by up-regulating MMPs expressions and reducing myocardial fibrosis.</p>

Influence of congenital asymptomatic cytomegalovirus infection on development of infants / 中华儿科杂志

<p><b>OBJECTIVE</b>Human cytomegalovirus (HCMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection worldwide. Although 90% of the congenitally infected infants are clinically asymptomatic at birth, evidences show that these infants are at risk for audiologic, neurologic, and developmental sequelae. The aim of this study was to evaluate the outcome of children with asymptomatic congenital human cytomegalovirus infection identified from a cohort of newborn infants screened for congenital HCMV infection compared with matched uninfected control subjects.</p><p><b>METHODS</b>Between July 2003 and July 2005, eligible hospitalized infants were recruited into the cohort. Serum was collected within two weeks of birth and transported to the laboratory within 24 hours, and stored at -20 degrees C. Then Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) for the presence of HCMV DNA was used as a screening tool for the detection of congenital cytomegalovirus infection. Asymptomatic congenital HCMV infection (ACCMV) was defined as detection of HCMV during the first 2 weeks of life in the absence of any abnormal signs, symptoms, or laboratory findings. The study enrolled 41 siblings with asymptomatic congenital HCMV infection and 21 children whose neonatal screening for congenital HCMV infection showed negative results. Then they were followed up prospectively for the first years of life. A pediatric assessment, including neonatal behavioral neurological assessment (NBNA) was performed at neonatal period by a qualified pediatrician, at which time the CMV status of the infants was not yet known. At one year of age other standardised clinical evaluations were performed by the pediatrician. The Bayley scale of infant development were used to determine the intellectual and neurological development deficits, and the age-adequate neurological examinations based on the criteria by Amiel-Tison to evaluate the general movements for neurological development. Hearing screening were completed for all children to determine their hearing status. Auditory brain-stem response (ABR) and distortion product otoacoustic emission (DPOAE) have been used to accurately diagnose moderate to profound congenital sensorineural hearing loss.</p><p><b>RESULT</b>There was no significant difference between the mean NBNA score of HCMV group (38.8 +/- 2.75) and the control group (38.5 +/- 2.29) (t = 0.98, P > 0.05). Significant difference was found between the occurrence of hearing loss in infants born with asymptomatic congenital HCMV infection compared with the control group. Audiologic abnormalities (sensorineural hearing loss, SNHL) were present in 5 of 23 congenitally infected children, however, no hearing abnormalities were detected in uninfected children (chi2 = 6.94, P < 0.01). The mean Bayley score of HCMV group (MDI 106.86 +/- 10.24 and PDI 108.45 +/- 18.25) and the control group (MDI 107.49 +/- 19.31 and PDI 107.19 +/- 10.98) did not differ significantly (t = 0.33, P > 0.05, t = 0.35, P > 0.05). Otherwise, there was no significant difference in 52 Amiel-Tison neurological scale between the two groups.</p><p><b>CONCLUSION</b>These data suggest that asymptomatic congenital cytomegalovirus infection may be associated with a broad range of audiologic differences in early infancy. Continued monitoring of their hearing status in the first years of life is necessary in these children because further progression of hearing loss is possible. However, asymptomatic congenital HCMV infection is not associated with abnormalities in growth, or neurodevelopmental deficits.</p>

Establishment of a sandwich ELISA method for detection of vascular endothelial growth factor in serum samples of hepatocellular carcinoma patients / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To establish a sandwich ELISA method for detecting vascular endothelial growth factor (VEGF) in sera of population and the patients with hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Full length and two truncated human VEGF cDNA sequences were amplified from a commercial plasmid pBLAST49-hVEGF by PCR and inserted into the prokaryotic-expression plasmid pET-32a or pGEX-2T. Various VEGF proteins were expressed and purified from E. coli in His-Trx or GST fusion forms. The specific VEGF antibodies were elicited in experimental rabbits and mice by immunization of the full length VEGF fusion protein His-Trx-VEGF1-165. After purification of antibodies with chromatograph of Protein G, a sandwich ELISA technique was established. Serum VEGF levels were evaluated in 229 adults and 291 HCC patients.</p><p><b>RESULTS</b>SDS-PAGE displayed that the molecular weights of the expressed full length (His-Trx-VEGF1-165), N-terminal (His-Trx-VEGF1-100) and C-terminal (GST-VEGF100-165) human VEGF fusion proteins were about 38KD, 31KD, and 33KD, respectively. Western blots confirmed that the prepared antisera were able to recognize both prokaryoticly and eukaryoticly expressed recombinant VEGF proteins. Assays of serially diluted His-Trx-VEGF1-100 by the established sandwich ELISA method showed that the linear range of the standard curve was 0.625-320 ng/mL, with the squared correlation coefficient R2 = 0.991. Screening of a serum panel containing 291 serum samples of HCC patients and 229 health adults revealed that the average VEGF level in HCC patients was higher than that in healthy controls, with a statically significant difference.</p><p><b>CONCLUSION</b>The established sandwich ELISA reflects the level of serum VEGF and provide scientific basis for screening metastasis and recurrence of HCC using serum VEGF as an index.</p>

Establishment of an assay for PrP(Sc) detection based on streptomycin precipitation / 病毒学报

To establish a new Western blotting assay for PrP(Sc) detection, we optimized the Western blotting assay with a precipitation procedure of streptomycin sulfate. After digestion with PK, 10% scrapie infected hamster brain homogenates were incubated with 60 mmol/L streptomycin and the precipitated PrP(Sc) was recovered by centrifugation. The enrichment of PrP(Sc) by streptomycin sulfate precipitation was evaluated using Western blotting assay. The results showed streptomycin could bind to PK-treated PrP(Sc), forming high molecular masses, but not influence the glycosylated patterns on SDS-PAGE. Western blot assay revealed that the detective sensitivity of the streptomycin-precipitation PrP(Sc) was remarkably improved. As a sensitive, specific, rapid and flexible protocol for PrP(Sc), the protocol in this study has the potential utility, alone or combined with other techniques, for the detection of low level PrP(Sc) in the specimens from central nerve system, or from peripheral organs or body fluids.