Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Cognition ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Monocytes/pathology* ; Polysaccharides/therapeutic use* ; Proteoglycans

Alzheimer Disease/diagnosis* ; Cognitive Dysfunction ; Disease Progression ; Humans ; Neuroimaging

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

Objective To investigate the relationship between hemoglobin and blood pressure of pregnant women in Zhoushan islands, so as to provide scientific evidence for the etiological study of gestational hypertension. Methods A retrospective study was conducted among 1 383 pregnant women who received perinatal care in Zhoushan Maternal and Child Health Hospital of Zhejiang Province from January 2017 to June 2018. Pregnant women were monitored for hemoglobin content and blood pressure in the early, middle and late pregnancy. The multivariate linear regression was used to analyze the relationship between hemoglobin content and blood pressure in different pregnancy. Results The incidence of anemia in early, middle and late pregnancy was 7.74%, 25.45% and 15.76% respectively. The multivariate linear regression showed that hemoglobin levels during pregnancy had effects on systolic blood pressure in early, middle and late pregnancy, and the earlier hemoglobin levels were monitored, the more obvious the effect on systolic blood pressure was.With the increase of hemoglobin level, systolic blood pressure increased, such as the effect of hemoglobin on systolic blood pressure in early pregnancy, mid-pregnancy and late pregnancy. Hemoglobin of first trimster had the greatest effect (β=0.10, P<0.001), Hemoglobin of second trimester had no obvious effect, and that of third trimester had the second effect (β=0.04, P=0.027).Hemoglobin levels and diastolic blood pressure levels were similar to their relationship with systolic blood pressure. Conclusions Hemoglobin levels during pregnancy have significant effects on systolic and diastolic blood pressure in first, second and third trimsters of pregnancy. Regular measurement of hemoglobin levels during pregnancy can improve the health of pregnant women.

Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Alzheimer Disease ; diagnosis ; physiopathology ; therapy ; Animals ; Biomarkers ; blood ; Biomedical Research ; methods ; Disease Progression ; Humans ; Magnetic Resonance Imaging

OBJECTIVETo explore the mental health status of residents scattered living in Anxian after Wenchuan earthquake so as to provide scientific basis for further mental health intervention.

METHODSA face to face interview was conducted among the scattered residents with designed questionnaire, which had three parts of the physical and emotional reaction, the relax methods and the social care and supports expected. Two-stage probability proportional to size (PPS) sample method was performed to sample 2184 from 0.44 million scattered residents in Anxian. On the basis of statistical description, mental health of different characteristics groups was compared.

RESULTSThree main symptoms of posttraumatic stress disorders in 2184 residents (11.23+/-3.44) were higher than the 103 fire victims in Hunan in 2003 (10.06+/-3.26), three factor scores of SCL-90 (5.76+/-1.74) were higher than normal in 1998 repair mode (n=23 891) (4.72+/-1.44), and the statistical difference was observed (t=10.77, P<0.05; t=706.04, P<0.05). Comparing the mental health of different groups, some significant differences were found by age, gender and education background.

CONCLUSIONThe earthquake disaster brought prevalent physical and emotional reaction. Elderly people, female, junior students need mental intervention immediately. Therefore, strengthen the mental education and assistance (especially in high risk groups) would be of more significance.

Adolescent ; Adult ; Child ; Child, Preschool ; Disasters ; Earthquakes ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mental Health ; Middle Aged ; Sampling Studies ; Stress Disorders, Post-Traumatic ; epidemiology ; psychology ; Surveys and Questionnaires ; Young Adult

OBJECTIVETo explore the public health situation and needs in Anxian after Wenchuan earthquake so as to make an effective strategy for disease control and prevention.

METHODS69 concentrated settlements with 100 residents were investigated. Probability proportion to size was adopted for sampling of 2200 residents from 687 scattered households (about 440 000 scattered residents). The content of this survey included drinking water, food hygiene, environment sanitation, planning immunity and medical health service, disease surveillance and so on. SPSS 16.0 was used for data analysis, and statistical interpretation was used to describe the results.

RESULTS90.9% (31/66) resettled residents in Anxian lived in tents, 7.6% (5/66) lived in the movable-plate house, 93.3% (621/666) scattered households lived in tents and 71.9% (446/621) of them lived in tents which were built by residents themselves; the rate of drinking water disinfection in resettlement sites and scattered households were 97.1% (66/68) and 94.6% (650/687); 12.8% scattered residents had mouldy or food; 50% of resettlement sites raised animals; 43.6% (17/39) medical station didn't have bacterin inoculation service; 66.7% (10/15) lacked sufficient disinfection equipment; register rate was 50.0% (33/66) and report rate of symptoms and infectious diseases was 56.1% (37/66).

CONCLUSIONThere was still some risk of enteric and vector-borne diseases in Anxian, therefore, some tailored measures should be very important.

Disasters ; Earthquakes ; Environmental Monitoring ; Health Care Surveys ; Health Services ; Health Services Needs and Demand ; Humans ; Water Supply

OBJECTIVE: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of opiates in biological samples according to the emerging problem in drugs abuse. METHODS: Opiates such as heroin, 6-acetylmorphine, morphine, codeine, acetylcodeine, hydrocodone and hydromorphone were isolated from human blood, urine, oral fluid and hair using a simple extraction and consequently analyzed using LC-MS/MS. The method was evaluated by real cases. RESULTS: The mobile phase give the optimum separation for opiates. The detection limit of morphine in urine with dilution and liquid-liquid extraction and in hair is 10ng/mL, 0.01 ng/mL and 0.01 ng/mg, respectively. CONCLUSION The method is simple and rapid, offering superior sensitivity and selectivity for opiates. The target compounds comprising hydrocodone and hydromorphone enlarge the applied area.
Chromatography, Liquid ; Codeine/analysis* ; Forensic Medicine/methods* ; Hair/chemistry* ; Humans ; Hydrocodone/analysis* ; Hydromorphone/analysis* ; Morphine/analysis* ; Narcotics/analysis* ; Reproducibility of Results ; Saliva/chemistry* ; Substance Abuse Detection/methods* ; Tandem Mass Spectrometry