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Alzheimer’s Disease (AD), characterized by deficits in memory and cognition and by behavioral impairment, is a progressive neurodegenerative disorder that influences more than 47 million people worldwide. Currently, no available drug is able to stop AD progression. Therefore, novel therapeutic strategies need to be investigated.
We analyzed the RNA sequencing data (RNA-seq) derived from the Gene Expression Omnibus (GEO) database to identify the differentially expressed mRNAs in AD. The AD mouse model Tg2576 was used to verify the effects of IGF-2. The Morris Water Maze was administered to test the role of IGF-2 in memory consolidation. In addition, we quantified cell apoptosis by the TUNEL assay. The levels of amyloid plaques and the levels of Aβ40 and Aβ42 in the hippocampus were also determined by immunohistochemistry and ELISA, respectively.
RNA-seq analysis revealed that IGF-2 was remarkably reduced in AD. The expression of the upstream genes PI3K and AKT and the downstream gene CREB in the PI3K signaling pathway was significantly increased in the hippocampus of Tg2576 mice cells treated with IGF-2. The Morris water maze test showed that IGF-2 improved memory consolidation in Tg2576 mice. The activity of caspase-3 was decreased in Tg2576 mice treated with IGF-2. Amyloid plaques in the hippocampus were reduced, and the levels of Aβ40 and Aβ42 were decreased. The above effects of IGF-2 on AD were blocked when the PI3K signaling pathway inhibitor wortmannin was added.
IGF-2 attenuates memory decline, oxidative stress, cell apoptosis and amyloid plaques in the AD mouse model Tg2576 by activating the PI3K/AKT/CREB signaling pathway.
There is emerging evidence that glycaemic variability (GV) plays an important role in the development of diabetic complications. The current study aimed to compare the effects of lifestyle intervention (LI) with and without partial meal replacement (MR) on GV. A total of 123 patients with newly diagnosed and untreated type 2 diabetes (T2D) were randomised to receive either LI together with breakfast replacement with a liquid formula (LI+MR) (n 62) or LI alone (n 61) for 4 weeks and completed the study. Each participant was instructed to have three main meals per d and underwent 72-h continuous glucose monitoring (CGM) both before and after intervention. Measures of GV assessed by CGM included the incremental AUC of postprandial blood glucose (AUCpp), standard deviation of blood glucose (SDBG), glucose CV and mean amplitude of glycaemic excursions (MAGE). After a 4-week intervention, the improvements in systolic blood pressure (P=0·046) and time in range (P=0·033) were more pronounced in the LI+MR group than in the LI group. Furthermore, LI+MR caused significantly greater improvements in all GV metrics including SDBG (P=0·005), CV (P=0·002), MAGE (P=0·016) and AUCpp (P<0·001) than did LI. LI+MR (v. LI) was independently associated with improvements in GV after adjustment of covariates (all P<0·05). Our study showed that LI+MR led to significantly greater improvements in GV compared with LI, suggesting that LI+MR could be an effective treatment to alleviate glucose excursions.
Evidence on the association between maternal Hb concentration and preterm birth (PTB) risk is inconclusive. This paper aimed to explore whether women with anaemia or high Hb level before pregnancy would be at higher risk of PTB. We conducted a population-based cohort study with 2 722 274 women aged 20–49 years, who participated in National Free Pre-Pregnancy Checkups Project between 2013 and 2015 and delivered a singleton before 2016 in rural China. Logistic models were used to estimate OR and 95 % CI after adjusting for confounding variables. Restricted cubic spline models were applied to evaluate the dose–response relationships. A total of 192 819 (7·08 %) women had preterm deliveries. Compared with women with Hb of 110–149 g/l, the multivariable-adjusted OR for PTB was 1·19 (95 % CI 0·98, 1·44) for women with Hb<70 g/l, 1·01 (95 % CI 0·97, 1·03) for 70–99 g/l, 0·96 (95 % CI 0·95, 0·98) for 100–109 g/l, 1·04 (95 % CI 1·01, 1·06) for 150–159 g/l, 1·11 (95 % CI 1·05, 1·17) for 160–169 g/l and 1·19 (95 % CI 1·11, 1·27) for ≥170 g/l, respectively. The multivariable-adjusted OR for very PTB (VPTB) was 1·07 (95 % CI 1·03, 1·12) and 1·06 (95 % CI 1·01, 1·12) for women with Hb <110 and ≥150 g/l, compared with those with Hb of 110–149 g/l, respectively. Our study identified a U-shaped relationship between maternal preconception Hb concentration and PTB risk. Both preconception anaemia and high Hb level can significantly increase VPTB risk. Appropriate intervention for women with abnormal Hb levels before pregnancy is very necessary.
Many shorebird populations are in decline along the East Asian-Australasian Flyway. The rapid loss of coastal wetlands in the Yellow Sea, which provide critical stop-over sites during migration, is believed to be the cause of the alarming trends. The Yalu Jiang coastal wetland, a protected area in the north Yellow Sea, supports the largest known migratory staging populations of Bar-tailed Godwits Limosa lapponica (menzbieri and baueri subspecies) and Great Knots Calidris tenuirostris. Monitoring of the macrozoobenthos food for these shorebirds from 2011 to 2016 showed declines of over 99% in the densities of the bivalve Potamocorbula laevis, the major food here for both Bar-tailed Godwits and Great Knots. The loss of the bivalve might be caused by any combination of, but not limited to: (1) change in hydrological conditions and sediment composition due to nearby port construction, (2) run-off of agrochemicals from the extensive shoreline sea cucumber farms, and (3) parasitic infection. Surprisingly, the numbers of birds using the Yalu Jiang coastal wetland remained stable during the study period, except for the subspecies of Bar-tailed Godwit L. l. menzbieri, which exhibited a 91% decline in peak numbers. The lack of an overall decline in the number of bird days in Great Knots and in the peak numbers of L. l. baueri, also given the published simultaneous decreases in their annual survival, implies a lack of alternative habitats that birds could relocate to. This study highlights that food declines at staging sites could be an overlooked but important factor causing population declines of shorebirds along the Flyway. Maintaining the quality of protected staging sites is as important in shorebird conservation as is the safeguarding of staging sites from land claim. Meanwhile, it calls for immediate action to restore the food base for these beleaguered migrant shorebirds at Yalu Jiang coastal wetland.
For treatment of patients diagnosed with schizophrenia, comparative
long-term effectiveness of antipsychotic drugs to reduce relapses when
minimising adverse effects is of clinical interest, hence prompting this
To evaluate the comparative long-term effectiveness of antipsychotic
We systematically searched electronic databases for reports of randomised
controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing
relapse risks in schizophrenia. We conducted network meta-analysis of 18
antipsychotics and placebo.
Studies of 10 177 patients in 56 reports were included; treatment
duration averaged 48 weeks (range 4–156). Olanzapine was significantly
more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI
0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine
decanoate was more effective than chlorpromazine (OR=0.31, 95% CI
0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol,
haloperidol decanoate and trifluoperazine produced more extrapyramidal
adverse effects than olanzapine or quetiapine; and olanzapine was
associated with more weight gain than other agents.
Except for apparent superiority of olanzapine and fluphenazine decanoate
over chlorpromazine, most agents showed intermediate efficacy for relapse
prevention and differences among them were minor. Typical antipsychotics
yielded adverse neurological effects, and olanzapine was associated with
weight gain. The findings may contribute to evidence-based treatment
selection for patients with chronic psychotic disorders.
Paragonimiasis is an important infectious disease in Chongqing, China. However, no epidemiological surveys of paragonimiasis have been carried out in Chongqing since it became a municipality in 1997. We conducted a retrospective case review of 683 patients who were referred to our laboratory and diagnosed as having paragonimiasis during 2010–2015. Patients were diagnosed with paragonimiasis based on immunodiagnostic tests in addition to clinical and laboratory findings. Patient data extracted from the epidemiologic form were analysed. The majority of patients were distributed on the east side of the Wujiang River, which belongs to the Three Gorges Reservoir region. Consumption of raw or undercooked freshwater crab or crayfish in the family Cambaridae was the main reason for infection. Notably, more than 50·0% of patients were diagnosed between March and July, indicating that serious clinical symptoms only appear approximately 6 months post-infection. Paragonimiasis remains a public health issue in Chongqing, and an epidemiological study of Paragonimus in the Three Gorges region is strongly recommended.
Change mode and effects analysis (CMEA) is a powerful technique for measuring product flexibility toward future changes and diminishing the cost of redesign as well as shortening time to market. As a systematic methodology, it provides an in-depth view for the investigation of potential changes, causes, and effects in designs, products, and processes. Traditional CMEA determines the risk priorities of change modes by using change potential number, which requires the risk factors of design flexibility, occurrence, and readiness to be precisely evaluated. However, this is not always possible in real applications due to the uncertainty and subjectivity involved in the early design stages. It has been criticized much for its deficiencies in criteria weighting of the risk factors, change potential number calculation, and risk priorities determination of the change modes. This paper presents a systematic evaluation approach for determining a more rational rank of change modes by combining with the entropy weight method, rough number, and grey relational analysis. In this study, the entropy weight method is adopted to calculate the relative importance of risk factors. Rough number is presented to aggregate individual weights and preferences, and to manipulate the vagueness in the evaluation process. Then a rough number enhanced grey relational analysis is proposed to evaluate the risk ranking of change modes. Finally, a practical example is put forward to validate the performance of the proposed method. The result shows that the proposed change mode evaluation method can effectively overcome the shortcomings of traditional CMEA and strengthen the objectivity of product flexibility measurement.
The new Vancouver Chest Pain (VCP) Rule recommends early discharge for chest pain patients who are at low risk of developing acute coronary syndrome (ACS), and thus can be discharged within 2 hours of arrival at the emergency department (ED). This study aimed to assess the performance of the new VCP Rule for Asian patients presenting with chest pain at the ED.
This prospective cohort study involved patients attended to at the ED of a large urban centre. Patients of at least 25 years old, presenting with stable chest pain and a non-diagnostic ECG, and with no history of active coronary artery disease were included in the study. The main outcome measures were cardiac events, angioplasty, or coronary artery bypass within 30 days of enrolment.
The study included 1690 patients from 27 August 2000 to 1 May 2002, with 661 patients fulfilling the VCP criteria. Of those for early discharge, 24 had cardiac events and 13 had angioplasty or bypass at 30 days, compared to 91 and 41, respectively, for those unsuitable for discharge. This gave the rule a sensitivity of 78.1% for cardiac events, including angioplasty and bypass. Specificity was 41.0%, and negative predictive value (NPV) was 94.4%.
We found the new VCP Rule to have moderate sensitivity and poor specificity for adverse cardiac events in our population. With an NPV of less than 100%, this means that a small proportion of patients sent home with early discharge would still have adverse cardiac events.
We report here first results on the bulk soil organic carbon (SOC), apparent radiocarbon ages and δ13C characteristics of the tropical and subtropical forest soil in Dinghushan Biosphere Reserve (DHSBR). The forest oxisol in Dinghushan has developed during the Holocene. The δ13C variation curves in all three profiles may be divided into two sections. The upper section from 0 to 40 cm has δ13C values varying from −27.4 to −24.1‰, −27.5 to −22.2‰, and −24.4 to −20.1‰. in the Wukesong, Qingyunsi and Kengkou profiles, respectively. The lower section, including the 40–160 cm horizons, has a uniform δ13C. The mean δ13C values of the soil organic carbon could be used not only to discriminate between C3 and C4 plants, but also to distinguish between coniferous and broad-leaf plants.
Objectives: Effective formulary management in healthcare institutions safeguards rational drug use and optimizes health outcomes. We implemented a formulary management program integrating the principles of health technology assessment (HTA) to improve the safe, appropriate, and cost-effective use of medicine in Singapore.
Methods: A 3-year formulary management program was initiated in 2011 in five public healthcare institutions. This program was managed by a project team comprising HTA researchers. The project team worked with institutional pharmacy and therapeutics (P&T) committees to: (i) develop tools for formulary drug review and decision making; (ii) enhance the HTA knowledge and skills of formulary pharmacists and members of P&T committees; (iii) devise a prioritization framework to overcome resource constraints and time pressure; and (iv) conceptualize and implement a framework to review existing formulary.
Results: Tools that facilitate drug request submission, drug review, and decision making were developed for formulary drug inclusion. A systematic framework to review existing formulary was also developed and tested in selected institutions. A competency development plan was rolled out over 2 years to enhance formulary pharmacists’ proficiency in systematic literature search and review, meta-analysis, and pharmacoeconomic evaluation. The plan comprised training workshops and on-the-job knowledge transfer between the project team and institutional formulary pharmacists through collaborating on selected drug reviews. A resource guide that consolidated the tools and templates was published to encourage the adoption of best practices in formulary management.
Conclusions: Based on the concepts of HTA, we implemented an evidence-based approach to optimize formulary management.
Creative conceptual design requires significant previous design knowledge. Case-based reasoning enables learning from previous design experience and has a great potential in supporting creative conceptual design by means of seeking to retrieve, reuse, and revise most appropriate cases to generate inspired solutions. However, traditional case-based reasoning based creative conceptual design models focus on design strategies research, pay little attention to defining a consistent knowledge representation model, and neglect the research to make various types of knowledge retrieval tractable. Faced with such drawbacks, the expected design knowledge cannot be retrieved properly, especially in cases where multidisciplinary knowledge is concerned or exact query terms are absent. In order to solve these issues, this paper presents a combined approach to support creative conceptual design process. First, function–behavior–structure knowledge cell is introduced as a unified consistent design knowledge representation model. Second, a hybrid similarity measure is proposed to increase the overall possibility of obtaining useful design knowledge by considering semantic understanding ability. Third, an intelligent creative conceptual design system has been developed with a case study of a novel insulin pump design to demonstrate its usage, and two experiments are conducted to evaluate the performance of the proposed approach. The results show that the proposed approach outperforms other case-based reasoning based creative conceptual design models.
To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.
An intervention trial.
Shenzhen City, Guangdong Province, China.
From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18–69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.
For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.
For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.
Uncertainty about the H+ buffering capacity in tropical rain forest limits our ability to predict the future effect of anthropogenic deposition on the streamwater chemistry. Export of major ions to the stream and the ion-fluxes via rainfall, throughfall, litter-leachate and soil-water pathways were observed to examine the source of streamwater nutrients in a small catchment in Sabah, Malaysia. The streamwater and the ion-fluxes were measured for 3.75 and 2 y, respectively, by collecting water twice a month and setting ion-exchange-resin columns. Streamwater pH ranged from 6.5 to 7.6 and was not sensitive to water discharge controlling base cations. The NO3−-N, Ca2+ and Mg2+ fluxes were low in atmospheric depositions (0.6, 0.5 and 0.3 kg ha−1 y−1, respectively) and markedly increased in the litter layer. The NO3−-N flux decreased drastically from subsoil (70 kg ha−1 y−1) to the stream (1.4 kg ha−1 y−1) whereas the Ca2+ and Mg2+ fluxes were not different between subsoil (38 and 18 kg ha−1 y−1) and stream (30 and 15 kg ha−1 y−1). Neutral pH in tropical streams was mainly due to the base cation leaching with deep chemical weathering in deeper strata, and a rapid decrease in NO3− leaching from the subsoil to the stream.
Spinal surgery is considered a high-risk surgery. To improve the accuracy, stability, and safety of such operations, we report the development of a novel six-degrees-of-freedom Robotic Spinal Surgical System that can assist surgeons in performing transpedicular surgery, one of the most common spinal surgeries. After optimization performed using Response Surface Methodology, the largest available workspace of the robot is determined and is found to easily cover the entire operation area. Cooperative control and navigation-based active control are implemented for different processes of the operation. We propose a hybrid control approach based on the speed and torque interface at the joint level. In this mode, the robot is compliant in Cartesian space, benefitting both the accuracy and efficiency of the operation. A comprehensive assessment index, combining the subjective and objective criteria in terms of positioning and operation efficiency, is proposed to compare the performance of cooperative control in speed mode, torque mode, and hybrid control mode. Active fine adjustment experiments are carried out to verify the positioning accuracy, and the results are found to satisfy the requirements of operation. As an application example, a pedicle screw insertion experiment is performed on a pig vertebral bone, demonstrating the effectiveness of our system.
Al/MoOx nanoenergetic multilayer films (nEMFs) were deposited by magnetron deposition method. The samples with bilayer thicknesses of 75 nm and 225 nm were prepared, respectively, and the total thickness is 3 μm. The as-deposited Al/MoOx nEMFs were characterized with varied analytical techniques, including SEM, XRD, XPS and DSC. Results show that the MoOx films are amorphous, and are composed of MoO3, Mo2O5 and MoO2. The values of heat release in samples are 3524 J/g and 2508 J/g, respectively, and the final products are Mo, MoO2, and Al2O3. Finally, the reaction paths and reaction kinetics of Al/MoOx exothermic reactions were discussed.