Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents.

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Comprehensive investigation of malignant epithelial cell-related genes in clear cell renal cell carcinoma: development of a prognostic signature and exploration of tumor microenvironment interactions.

Clear cell renal cell carcinoma (ccRCC) is a prevalent malignancy with complex heterogeneity within epithelial cells, which plays a crucial role in tumor progression and immune regulation. Yet, the clinical importance of the malignant epithelial cell-related genes (MECRGs) in ccRCC remains insufficiently understood. This research aims to undertake a comprehensive investigation into the functions and clinical relevance of malignant epithelial cell-related genes in ccRCC, providing valuable understanding of the molecular mechanisms and offering potential targets for treatment strategies. Using data from single-cell sequencing, we successfully identified 219 MECRGs and established a prognostic model MECRGS (MECRGs' signature) by synergistically analyzing 101 machine-learning models using 10 different algorithms. Remarkably, the MECRGS demonstrated superior predictive performance compared to traditional clinical features and 92 previously published signatures across six cohorts, showcasing its independence and accuracy. Upon stratifying patients into high- and low-MECRGS subgroups using the specified cut-off threshold, we noted that patients with elevated MECRGS scores displayed characteristics of an immune suppressive tumor microenvironment (TME) and showed worse outcomes after immunotherapy. Additionally, we discovered a distinct ccRCC tumor cell subtype characterized by the high expressions of PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) and SAA1 (Serum Amyloid A1), which we further validated in the Renji tissue microarray (TMA) cohort. Lastly, 'Cellchat' revealed potential crosstalk patterns between these cells and other cell types, indicating their potential role in recruiting CD163 + macrophages and regulatory T cells (Tregs), thereby establishing an immunosuppressive TME. PLOD2 + SAA1 + cancer cells with intricate crosstalk patterns indeed show promise for potential therapeutic interventions.

Parkinson's disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins.

OBJECTIVE: This study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson's disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups. METHODS: A total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups. RESULTS: The frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aß1-42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum. CONCLUSIONS: The frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.

The Development and Validation of Multi-dimensional Resilience Scale for People Living with HIV in China.

The study aimed to provide a measurement tool for the assessment of resilience among people living with HIV (PLHIV) in China. The study period was from April 2019 to October 2020: first, 14 PLHIV were interviewed to build an item pool; 15 experts were invited to evaluate the scale items. The test-retest reliability of the scale was carried out with 29 PLHIV. Online and field investigation were used, and convenience sampling was conducted in Luzhou and Zigong. A pool of 31 items was formed and the Scale-Level Content Validity Index average was 0.96, while the that intra-class correlation coefficient for test-retest reliability was 0.816. From the exploratory factor analysis, four factors (Acceptance; Disease Management; Emotion Regulation; and Reconstruction) with 19 items were extracted. The Cronbach's alpha value of the Resilience Scale was 0.88. This scale could prove useful as a measuring tool for evaluating the level of resilience for PLHIV.

RESUMEN: El estudio tuvo como objetivo proporcionar una herramienta de medición para la evaluación de la resiliencia entre las personas que viven con el VIH (PVVIH) en China. El período de estudio fue de abril de 2019 a octubre de 2020: primero, se entrevistó a 14 PVVIH para construir un grupo de artículos; 15 expertos fueron invitados a evaluar los ítems de la escala. La confiabilidad test­retest de la escala se realizó con 29 PVVIH. Se utilizaron investigaciones en línea y de campo, y se realizó un muestreo de conveniencia en Luzhou y Zigong. Se formó un conjunto de 31 ítems y el índice de validez de contenido a nivel de escala promedio fue de 0,96, mientras que el coeficiente de correlación intraclase para la confiabilidad test­retest fue de 0,816. Del análisis factorial exploratorio se extrajeron cuatro factores (Aceptación; Manejo de la Enfermedad; Regulación de las Emociones y Reconstrucción) con 19 ítems. El valor alfa de Cronbach de la Escala de Resiliencia fue de 0,88. Esta escala podría resultar útil como herramienta de medición para evaluar el nivel de resiliencia de las PVVIH.

3, 14, 19-Triacetyl Andrographolide alleviates the cognitive dysfunction of 3 × Tg-AD mice by inducing initiation and promoting degradation process of autophagy.

The present study aims to investigate the cognition-enhancing effect of 3, 14, 19-Triacetyl andrographolide (ADA) on learning and memory deficits in 3 × Tg-AD mice and to explore its underlying mechanism. Eight-month-old 3 × Tg-AD mice and C57BL/6J mice were randomly divided into three groups, namely wild-type group, 3 × Tg-AD group, and 3 × Tg-AD+ADA group (5 mg/kg, for 21 days, i.p.). We found that ADA significantly improved learning and cognition impairment, inhibited the loss of Nissl body, and reduced Aß load in the brains of 3 × Tg-AD mice. In addition, ADA enhanced the levels of PSD95 and SYP, which were closely associated with synaptic plasticity. Accumulated autophagosomes, LC3II, and P62 in hippocampus and cortex of 3 × Tg-AD mice were decreased by ADA treatment. Furthermore, ADA administration further down-regulated the expressions of p-AKT and p-mTOR, reduced the level of CTSB, and increased the co-localization of LC3 and LAMP1 in the brains of 3 × Tg-AD mice, implying that ADA-induced autophagy initiation and also promoted the degradation process. In Aß25-35 -induced HT22 cells, ADA displayed similar effects on autophagy flux as observed in 3 × Tg-AD mice. Our finding verified that ADA could improve synaptic plasticity and cognitive function, which is mainly attributed to the key roles of ADA in autophagy induction and degradation.

Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation.

Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg-1 · d-1, ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1ß, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.

The mean age of menarche among Chinese schoolgirls declined by 6 months from 2005 to 2014.

AIM: This study assessed the trends in the age at menarche in Chinese schoolgirls from the majority Han group and 21 ethnic minorities from 2005 to 2014. We also compared the group differences during the study period. METHODS: A total of 344 230 girls aged 9-18 years were extracted from the 2005, 2010 and 2014 Chinese National Survey on Students' Constitution and Health. The age at menarche for each subgroup was estimated by probit analysis. The chi-square test and Z-test were used to compare the differences between the groups. RESULTS: The overall average age at menarche in Chinese schoolgirls decreased from 12.8 years in 2005 to 12.3 years in 2014. The Han girls and girls from 17 ethnic minorities showed decreasing trends in the age at menarche, while four ethnic minorities demonstrated fluctuating increasing trends over time. The gaps in age at menarche between the Han group and 14 of the ethnic minorities became smaller over the study period and were similar by 2014. CONCLUSION: The overall findings were a decrease in the age at menarche in China and smaller gaps between the majority Han group and ethnic minority groups. Ethnic-specific public health policies are urgently needed on issues such as contraception.

Gender differences in self-harm and drinking behaviors among high school students in Beijing, China.

BACKGROUND: Self-harm and drinking are both serious problems in adolescents and many studies presented evidence of their association. However, gender differences in this association are seldom deeply discussed. Our study aimed to evaluate the prevalence of self-harm and explore its association with drinking behaviors by gender and investigate the extent to which the gender differences exist in the association between self-harm and drinking. METHODS: A total of 32,362 students in grades 7 to 12 in Beijing, China were anonymously surveyed and included in our study using two-stage, stratified probability proportion sampling. Self-harm, drinking behaviors and other basic information were obtained from an anonymous questionnaire. Demographic variables, self-harm and drinking behaviors were analyzed using the Chi-square test and the Gamma test between genders and the gender differences in this association were analyzed by Log-binomial regression. RESULTS: The total prevalence of self-harm was 13.7% with no significant gender difference (χ2 =0.352, P = 0.553). The prevalence of self-harm in girls decreased with age (G = -0.163, P < 0.001). Self-harm was associated with drinking behaviors in both boys and girls. The Log-binomial regression demonstrated that girls in the 16-19 years old group were at lower risk of self-harm than girls in the 12-15 years old group while this association was weaker in boys (1.493 vs 1.128). The higher OR for self-harm was found among girls with early drinking experiences compared with boys (2.565 vs 1.863). Girls who had previously drunk (i.e. drunk at least once) (2.211 vs 1.636), were currently drinking (3.400 vs 2.122) and performed binge drinking (6.357 vs 3.924) were at greater risk of self-harm than boys. CONCLUSION: Among high school students, self-harm has a significant positive association with drinking and girls with drinking behaviors are at higher risk of suffering self-harm. Identifying adolescents' drinking behaviors is of vital importance to self-harm prevention and special attention should be focused on younger girls.

The associations of economic growth and anaemia for school-aged children in China.

Economic growth has brought improvements in many areas of child health, but its effects on anaemia among school-aged children remain unknown. However, this is important because iron deficiency anaemia is common and is the main cause of disability-adjusted life years for school-aged children. In this study, we included 429,222 Chinese children aged 7-17 years from five consecutive national cross-sectional surveys during 1995-2014. Using altitude-adjusted haemoglobin concentration measured from capillary blood samples, we defined anaemia status according to World Health Organization's recommendation. We used logistic regressions weighted by provincial population to examine the association between provincial gross domestic product (GDP) per capita and anaemia, adjusting for sex, age, urban-rural location, regional socio-economic status (SES), fixed effect of province, and clustering of schools. We used generalised additive mixed models to evaluate a potentially non-linear relationship. For each 100% growth in GDP per capita, there was a 40% (odds ratio [OR] = 0.60; 95% confidence interval [CI; 0.56, 0.65]) reduction in anaemia. However, the association was weaker for girls and in cities with a lower SES. The association was weaker across 2005-2014 (OR = 0.75, 95% CI [0.62, 0.90]) compared with 1995-2005 (OR = 0.52; 95% CI [0.44, 0.61]), reflecting a weaker association when GDP per capita reaches around $2,000. The results were similar for moderate-to-severe anaemia. We concluded that economic growth has been associated with reductions in anaemia among school-aged children in China but with fewer benefits for girls and those in poorer settings. Further economic development in China is unlikely to bring similar reductions in anaemia, suggesting that additional population level and targeted interventions will be needed.

Theoretical Investigations of the Photophysical Properties of Star-Shaped π-Conjugated Molecules with Triarylboron Unit for Organic Light-Emitting Diodes Applications.

The density functional theory (DFT) and time-dependent DFT (TD-DFT) methodologies have been applied to explore on a series of star-shaped π-conjugated organoboron systems for organic light-emitting diode (OLED) materials. The compounds under investigation consist of benzene as π-bridge and different core units and triarylboron end groups. Their geometry structures, frontier molecular orbital (FMO) energies, absorption and fluorescence spectra, and charge transport properties have been investigated systematically. It turned out that the FMO energy levels, the band gaps, and reorganization energies optical are affected by the introduction of different core units and triarylboron end groups. The results suggest that the designed compounds are expected to be promising candidates for luminescent materials. Furthermore, they can also serve as hole and/or electron transport materials for OLEDs.

Effects of bisphenol A on the development of central immune organs of specific-pathogen-free chick embryos.

Bisphenol A (BPA) is a chemical estrogen widely used in the food packaging industry, especially in baby bottles. Its toxicity for the fetus has become a great concern in recent years. In the present study, the effects of BPA on the development of central immune organs in chick embryos were investigated. A total of 30 specific-pathogen-free (SPF) chick embryos were divided into BPA, control, and vehicle group. Chick embryos were exposed to BPA (250 µg per egg), saline (control), or corn oil (vehicle) on embryonic day 9 (ED9) by injection into the allantoic cavity. Thymuses and bursae of Fabricius were collected on ED22. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of thymus and the bursa of Fabricius morphology under light and scanning electron microscopes (SEM). In the BPA group, the weight index of the bursae of Fabricius was significantly reduced (p < 0.01); the number of lymphatic follicles in the bursae of Fabricius was remarkably decreased (p < 0.01); and the thickness of the thymus cortex and medulla was reduced (p < 0.01). Light microscope and SEM examinations further showed that the lymphatic follicles and epithelial cells of the bursa of Fabricius and thymus were damaged by BPA. Our study confirms a direct toxicity of BPA at a very low-dose level on the development of the central immune organs of SPF chick embryos. However, more studies are necessary to elucidate the underlying mechanisms.

Development of a Nomogram Model Based on Lactate-To-Albumin Ratio for Prognostic Prediction in Hospitalized Patients with Intracerebral Hemorrhage.

OBJECTIVE: This study aims to develop a nomogram model incorporating lactate-to-albumin ratio (LAR) to predict the prognosis of hospitalized patients with intracerebral hemorrhage (ICH) and demonstrate its excellent predictive performance. METHODS: A total of 226 patients with ICH from the Medical information mart for intensive care III (MIMIC Ⅲ) database were randomly split into 8:2 ratio training and experimental groups, and 38 patients from the eICU-CRD for external validation. Univariate and multivariate Cox proportional hazards regression analysis was performed to identify independent factors associated with ICH, and multivariate Cox regression was used to construct nomograms for 7-day and 14-day overall survival (OS). The performance of nomogram was verified by the calibration curves, decision curves, and receiver operating characteristic (ROC) curves. RESULTS: Our study identified LAR, glucose, mean blood pressure, sodium, and ethnicity as independent factors influencing in-hospital prognosis. The predictive performance of our nomogram model for predicting 7-day and 14 -day OS (AUCs: 0.845 and 0.830 respectively) are both superior to Oxford Acute Severity of Illness Score, Simplified acute physiology score II, and SIRS (AUCs: 0.617, 0.620 and 0.591 and AUCs: 0.709, 0.715 and 0.640, respectively) in internal validation, and also demonstrate favorable predictive performance in external validation (AUCs: 0.778 and 0.778 respectively). CONCLUSIONS: LAR as a novel biomarker is closely associated with an increased risk of in-hospital mortality of patients with ICH. The nomogram model incorporating LAR along with glucose, mean blood pressure, sodium, and ethnicity demonstrate excellent predictive performance for predicting the prognosis of 7- and 14-day OS of hospitalized patients with ICH.

3D printed high-precision porous scaffolds prepared by fused deposition modeling induce macrophage polarization to promote bone regeneration.

Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay for cytokine secretion levels.In vitroosteogenic capacity was determined through alkaline phosphatase and alizarin red staining. Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells, exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.

Non-covalent binding of chlorogenic acid to myofibrillar protein improved its bio-functionality properties and metabolic fate.

As natural antioxidants added to meat products, polyphenols can interact with proteins, and the acid-base environment influenced the extent of non-covalent and covalent interactions between them. This study compared the bio-functional characteristics and metabolic outcomes of the myofibrillar protein-chlorogenic acid (MP-CGA) complexes binding in different environments (pH 6.0 and 8.5). The results showed that CGA bound with MP significantly enhanced its antioxidant activity and inhibitory effect on metabolism enzymes. CGA bound deeply into the MP structure hydrophobic cavity at pH 6.0, which reduced its degradation by digestive enzymes, thus increasing its bio-accessibility from 59.5% to 71.6%. The digestion products of the two complexes exhibited significant differences, with the non-covalent MP-CGA complexes formed at pH 6.0 showing significantly higher concentrations of rhetsinine and piplartine, two well-known compounds to modulate diabetes. This study demonstrated that non-covalent binding between protein and polyphenol in the acidic environment held greater promising prospects for improving health.

Association between nutritional status and gait performance in Alzheimer's disease.

AIMS: This study aimed to comprehensively explore the nutrition and gait of AD patients at different stages and the relationship between them. METHODS: A total of 85 AD patients were consecutively enrolled in this cross-sectional study and divided into the mild cognitive impairment (MCI) due to AD (AD-MCI) and the dementia due to AD (AD-D) groups. Demographic information, nutritional status, and gait performance were compared between the two groups, and the correlation between nutritional status and gait performance was subsequently analyzed by Pearson and Spearman correlation analyses. RESULTS: The AD-D group had lower scores on Mini-Nutritional Assessment (MNA) and MNAm scales, lower levels of urea nitrogen, folic acid, and vitamin B12 in blood, and higher homocysteine level than those in the AD-MCI group (all p < 0.05). The AD-D group had slower step speed, shorter step length, and shorter stride length than those in the AD-MCI group (all p < 0.05). AD patients with decreased scores of MNA and MNAm scales, and declined levels of urea nitrogen and vitamin B12 in blood had reduced gait speed and gait cadence, and prolonged step length time and stride length time, whereas homocysteine showed the almost opposite results (all p < 0.05). In the AD-MCI group, the score of scale was negatively correlated with the coefficient of variation (CV) of stride length, and the folic acid level was negatively correlated with the CV of stride length and cadence (all p < 0.05). CONCLUSIONS: AD patients at the dementia stage had worse nutritional status and gait performance than those at the MCI stage, which was associated with worse global cognition and activities of daily living. Poorer nutritional status was associated with higher gait variability in patients at the MCI stage and with poorer gait performance in patients at the dementia stage. Early identification and intervention of patients with nutritional risk or malnutrition may improve gait performance, thus reducing the risk of falling and cognitive decline, as well as the mortality.

The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease.

AIMS: To explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients. METHODS: AD patients were divided into the APOE ε4 carrier and the APOE ε4 non-carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently analyzed. RESULTS: ß amyloid protein (Aß)1-42 level from the APOE ε4 carrier group was significantly lower than that from the non-carrier group (p = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non-carrier group (p = 0.016), which was significantly and positively correlated with the Trail Making Test (TMT)-A-time (r = 0.21, p = 0.026) and TMT-B-time (r = 0.38, p < 0.01). CONCLUSION: APOE ε4 is associated with poorer cognition, particularly the early symptoms of memory, language, and attention. APOE ε4 is associated with lower Aß1-42 level, and the more numbers of APOE ε4 are carried, the lower level of Aß1-42 is measured. APOE ε4 is associated with elevated NO level, which is linked to the impaired attention and executive function.

Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4.

AIMS: To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4. METHODS: Totals of 173 patients with AD were divided into APOE ε4 carrier and non-carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition. RESULTS: Global cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 carrier group was lower than that in the non-carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE ε4 and Animal Fluency Test score (ß, -0.45; 95% CI [-0.96, -0.07]; p < 0.001) and Trail Making Test-A (time) (ß, 0.15; 95% CI [0.01, 0.33]; p < 0.001). CONCLUSION: APOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4-associated cognitive impairment.

An investigation into the potential association between nutrition and Alzheimer's disease.

Background: Malnutrition is the most common nutritional issue in Alzheimer's disease (AD) patients, but there is still a lack of a comprehensive evaluation of the nutritional status in AD patients. This study aimed to determine the potential association of various nutritional indices with AD at different stages. Methods: Subjects, including individuals with normal cognition (NC) and patients diagnosed with AD, were consecutively enrolled in this cross-sectional study. Demographics, body composition, dietary patterns, nutritional assessment scales and nutrition-related laboratory variables were collected. Binary logistics regression analyses and receiver operating characteristic (ROC) curves were used to indicate the association between nutrition-related variables and AD at different stages. Results: Totals of 266 subjects, including 73 subjects with NC, 72 subjects with mild cognitive impairment due to AD (AD-MCI) and 121 subjects with dementia due to AD (AD-D) were included. There was no significant difference in dietary patterns, including Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet between the three groups. Lower BMI value, smaller hip and calf circumferences, lower Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) scores, and lower levels of total protein, albumin, globulin, and apolipoprotein A1 were associated with AD (all p < 0.05). Total protein and albumin levels had the greatest ability to distinguish AD from non-AD (AUC 0.80, 95% CI 0.74-0.84, p < 0.001), increased by combining calf circumference, MNA score and albumin level (AUC 0.83, 95% CI 0.77-0.88, p < 0.001). Albumin level had the greatest ability to distinguish NC from AD-MCI (AUC 0.75, 95% CI 0.67-0.82, p < 0.001), and MNA score greatest ability to distinguish AD-MCI from AD-D (AUC 0.72, 95% CI 0.65-0.78, p < 0.001). Conclusion: Nutritional status of AD patients is significantly compromised compared with normal controls, and tends to be worsened with AD progresses. Early identification and intervention of individuals with nutritional risk or malnutrition may be significantly beneficial for reducing the risk, development, and progression of AD.

Relationships between physical activity, fundamental motor skills, and body mass index in preschool children.

Purpose: To investigate whether there is a potential relationship between physical activity (PA), fundamental motor skills (FMS), and Body Mass Index (BMI) in preschool children and to further explore the differences in PA and FMS between normal-weight and overweight/obese preschool children. Method: Participants were 366 preschool children aged 3 to 6 years; 358 completed all tests (194 boys and 164 girls). PA, FMS, body weight, and height were measured by triaxial accelerometer, the Test of Gross Motor Development, Second Edition (TGMD-2), and anthropometry measurement, respectively. Result: The overall rate of overweight/obesity was 17.0%, with no significant gender difference (χ 2 = 0.628, p = 0.428). Older children perform significantly better in both object control skills and locomotor skills. Independent samples t-tests were used to examine the difference between genders on FMS and PA: girls in the 5-year-old group display better locomotor skills (p = 0.012) than boys. Boys spent more time on moderate-to-vigorous physical activity (MVPA) and less time on sedentary activity when compared to girls. Results of partial correlation analysis showed that PA was significantly and positively correlated with both locomotor skills and object control skills in preschool children (p < 0.01), while there was no correlation between FMS, PA level, and BMI. Results of ANCOVA revealed no significant difference in FMS between normal-weight and overweight or obese preschool children; normal-weight girls had significantly longer MPA and MVPA duration and significantly shorter sedentary periods than overweight or obese girls (p < 0.05). Conclusion: Overweight/obesity in preschool children requires effective measures. PA is positively associated with FMS, while BMI is not potentially related to FMS or PA in preschool years. Overweight or obese girls should develop healthier weight status by increasing MVPA hours and reducing sedentary time.

Association of lactate-to-albumin ratio with in-hospital and intensive care unit mortality in patients with intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a severe stroke subtype with a high mortality rate; the lactate-to-albumin ratio (LAR) is a new biomarker for predicting clinical outcomes in patients with ICH. However, the relationship between LAR and mortality in patients with ICH treated in the intensive care unit (ICU) remains controversial. Therefore, in this study, we aimed to investigate the association between LAR and in-hospital and ICU mortality in patients with ICH. Methods: Patients with ICH were selected from the Medical Information Mart for Intensive Care III (MIMIC-III) database; their clinical information, including baseline characteristics, vital signs, comorbidities, laboratory test results, and scoring systems, was extracted. Univariate and multivariate Cox proportional hazards analyses were used to investigate the association of LAR with in-hospital and ICU mortality. The maximum selection statistical method and subgroup analysis were used to investigate these relationships further. Kaplan-Meier (KM) analysis was used to draw survival curves. Results: This study enrolled 237 patients with ICH whose lactate and albumin levels, with median values of 1.975 and 3.6 mg/dl, respectively, were measured within the first 24 h after ICU admission. LAR had an association with increased risk of in-hospital mortality [unadjusted hazards ratio (HR), 1.79; 95% confidence interval (CI), 1.32-2.42; p < 0.001] and ICU mortality (unadjusted HR, 1.88; 95% CI, 1.38-2.55; p < 0.001). A cut-off value of 0.963 mg/dl was used to classify patients into high LAR (≥0.963) and low LAR (<0.963) groups, and survival curves suggested that those two groups had significant survival differences (p = 0.0058 and 0.0048, respectively). Furthermore, the high LAR group with ICH had a significantly increased risk of in-hospital and ICU mortality compared to the low LAR group. Conclusion: Our study suggests that a high LAR is associated with an increased risk of in-hospital and ICU mortality in patients with ICH. Thus, the LAR is a useful prognostic predictor of clinical outcomes in patients with ICH.