Tracking the hologenome dynamics in aquatic invertebrates by the holo-2bRAD approach.

The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.

Case Report: Four cases of SARS-CoV-2-associated Guillain-Barré Syndrome with SARS-CoV-2-positive cerebrospinal fluid detected by metagenomic next-generation sequencing: a retrospective case series from China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often absent or at low levels in the cerebrospinal fluid (CSF) of patients with previous SARS-CoV-2-associated Guillain-Barré syndrome (GBS). This has led to speculation that SARS-CoV-2-associated GBS is more likely mediated by post-infectious immunity or a parainfection. This understanding has influenced the development of treatment regimens for SARS-CoV-2-associated GBS. This paper reports our experience with four Chinese patients with SARS-CoV-2-associated GBS who tested positive for SARS-CoV-2 RNA in the CSF. They developed symptoms of peripheral nerve damage 4-15 days after fever and confirmed SARS-CoV-2 infection, all of whom presented with progressive weakness of both lower limbs; three with autonomic nerve function impairment such as constipation and urination disorder; and one with polycranial neuritis and Miller-Fisher syndrome. Three patients were tested for anti-ganglioside antibodies, and one tested positive for GD1a-IgG. Four patients recovered well after treatment with anti-viral drugs combined with intravenous immunoglobulin. The present results showed that SARS-CoV-2 RNA can be detected via mNGS in the CSF of some patients with SARS-CoV-2-associated GBS, suggesting that SARS-CoV-2-associated GBS may have multiple pathogeneses.

A novel self-assembled nanoplatform based on retrofitting poloxamer 188 for triple-negative breast cancer targeting treatment.

Poloxamer 188 is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (< 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, docetaxel (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.

Application of Virtual Sample Generation and Screening in Process Parameter Optimization of Botanical Medicinal Materials.

BACKGROUND: The small sample problem widely exists in the fields of the chemical industry, chemistry, biology, medicine, and food industry. It has been a problem in process modeling and system optimization. The aim of this study is to focus on the problems of small sample size in modeling, the process parameters in the ultrasonic extraction of botanical medicinal materials can be obtained by optimizing the extraction rate model. However, difficulty in data acquisition results in problem of small sample size in modeling, which eventually reduces the accuracy of modeling prediction. METHODS: A virtual sample generation method based on full factorial design (FFD) is proposed to solve the problem ofa small sample size. The experiments are first conducted according to the Box- Behnken Design (BBD) to obtain small-size samples, and the response surface function is established accordingly. Then, virtual sample inputs are obtained by the FFD, and the corresponding virtual sample outputs are calculated by the response surface function. Furthermore, a screening method of virtual samples is proposed based on an extreme learning machine (ELM). The connection weights of ELM are used for further optimization and screening of the generated virtual samples. RESULT: The results show that virtual sample data can effectively expand the sample size. The precision of the model trained on semi-synthetic samples (small-size experimental simples and virtual samples) is higher than the model trained merely on small-size experimental samples. CONCLUSION: The virtual sample generation and screening methods proposed in this paper can effectively solve the modeling problem of small samples. The reliable process parameters can be obtained by optimizing the model trained by the semi-synthetic samples.

Association of Red Blood Cell Distribution Width with Stroke Prognosis Among Patients with Small Artery Occlusion: A Hospital-Based Prospective Follow-Up Study.

Objective: Stroke is the leading cause of mortality and disability worldwide. However, there is no study on the relationship between red blood cell distribution width and the prognosis of small artery occlusion, which is a stroke subtype. This study aimed to assess the association of red blood cell distribution width at admission with outcomes among patients with small artery occlusion. Methods: In this hospital-based follow-up study, all included patients were diagnosed with small artery occlusion. Outcomes included death, recurrence, and dependency at 3, 12, and 36 months after stroke onset. Multivariate analysis was performed to explore the association of red blood cell distribution width with stroke outcomes. Results: This study included 1576 patients with small artery occlusion who were followed up at 3, 12, and 36 months. For every unit increase in red blood cell distribution width, the risk of stroke recurrence and dependency increased by 5.1% (95% CI 1.002-1.102, P=0.039) at 3 months after stroke onset. At the 12-month follow-up, for every unit increase in red blood cell distribution width, the risk of stroke recurrence increased by 3.4% (95% CI 1.000-1.069, P=0.047). However, the relationship between red blood cell distribution width and mortality rate was not significant at 36 months after stroke onset after adjustment of covariates. Conclusion: Red blood cell distribution width is an important hematological index of small artery occlusion. It may be used to predict the recurrence of acute ischemic stroke in small artery occlusion. Therefore, patients with higher baseline values of red blood cell distribution width may need more risk factor control to reduce recurrence and dependency.

Integrated mRNA and miRNA Transcriptome Analysis Suggests a Regulatory Network for UV-B-Controlled Terpenoid Synthesis in Fragrant Woodfern (Dryopteris fragrans).

Fragrant woodfern (Dryopteris fragrans) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting DfSPL and DfARF, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.

Novel detection of mutation in the TECPR2 gene in a Chinese hereditary spastic paraplegia 49 patient: a case report.

BACKGROUND: Hereditary spastic paraplegia 49 (HSP49) is an autosomal recessive genetic disease first discovered in 2012; and which the mutation primarily affects Bukharian Jewish patients. CASE PRESENTATION: The present case reports the first instance of HSP49 detected in China. The patient had normal mental development and good athletic ability before 10 years old and presented with instable temperature, mental retardation, spastic ataxia, and paroxysmal convulsions. Genetic diagnosis was based on detection of whole exons and two heterozygous variants in the exon region of the TECPR2 gene: c.1729C > T and c.4189G > A. Mutations at these two sites have not been previously reported. CONCLUSIONS: This case expands the gene mutation spectrum and clinical phenotypic characteristics of autosomal recessive HSP in China; moreover, it indicates differences in the clinical phenotype of HSP49 in different ethnicities. In addition, this reported provides further evidence regarding the effectiveness of targeted next-generation sequencing technology in improving the efficiency and diagnostic rate of genetic diagnosis of HSP.

Analysis of Shared Genetic Regulatory Networks for Alzheimer's Disease and Epilepsy.

Alzheimer's disease (AD) and epilepsy are neurological disorders that affect a large cohort of people worldwide. Although both of the two diseases could be influenced by genetic factors, the shared genetic mechanism underlying the pathogenesis of them is still unclear. In this study, we aimed to identify the shared genetic networks and corresponding hub genes for AD and epilepsy. Firstly, the gene coexpression modules (GCMs) were constructed by weighted gene coexpression network analysis (WGCNA), and 16 GCMs were identified. Through further integration of GCMs, genome-wide association studies (GWASs), and expression quantitative trait loci (eQTLs), 4 shared GCMs of AD and epilepsy were identified. Functional enrichment analysis was performed to analyze the shared biological processes of these GCMs and explore the functional overlaps between these two diseases. The results showed that the genes in shared GCMs were significantly enriched in nervous system-related pathways, such as Alzheimer's disease and neuroactive ligand-receptor interaction pathways. Furthermore, the hub genes of AD- and epilepsy-associated GCMs were captured by weighted key driver analysis (wKDA), including TRPC1, C2ORF40, NR3C1, KIAA0368, MMT00043109, STEAP1, MSX1, KL, and CLIC6. The shared GCMs and hub genes might provide novel therapeutic targets for AD and epilepsy.

Factors associated with prognosis after small-vessel occlusion among young and middle-aged patients: a hospital-based follow-up study.

Objective: Small-vessel occlusions are the most common causes of mild strokes and, in China, account for approximately 27.3% of ischemic stroke cases. However, the factors associated with short- and long-term outcomes appear contradictory. Thus, we assessed the factors related to outcomes 3 years after small-vessel occlusion among patients aged 18 to 55 years.Methods: Between 2007 and 2014, we recruited patients who experienced small-vessel occlusion (according to Trial of Org 10,172 in Acute Stroke Treatment [TOAST] classification) aged 18 to 55 years and conducted a hospital-based follow-up study. The assessed outcomes were mortality, recurrence, and dependency within 3 years after the initial stroke. The outcome determinants were assessed using a multivariate logistic regression analysis.Results: A total of 276 patients (men, 76.09%) with small-vessel occlusions were enrolled in this study. In addition, 85.1% of the patients had strokes between the ages of 45 and 55 years. The risk of recurrence within 3 years was higher for patients who had moderate strokes than for those who had mild events (relative risk [RR], 3.09; 95% confidence interval [CI], 1.14-8.34; P < 0.05). Further, the risk of dependency within 3 years was 2.61 times higher in obese patients than in non-obese patients (RR, 2.61; 95% CI, 1.00-6.79; P < 0.05). The risks of recurrence and dependency within 3 years increased by 17% and 18%, respectively, for each 1-unit increase in fasting plasma glucose levels (RR, 1.17; 95% CI, 1.05-1.30 and RR, 1.18; 95% CI, 1.06-1.32, respectively; both P < 0.05).Conclusion: Our findings suggest that small-vessel occlusions cause the heaviest disease burden in patients aged 45 to 55 years. To reduce stroke recurrence, young and middle-aged patients with small-vessel occlusions should control their fasting plasma glucose levels and manage their weight.

Incidence and risk factors of dementia and the primary subtypes in northern rural China.

ABSTRACT: This study was carried out to estimate the incidence and to determine socio-demographic risk factors for dementia among individuals residing in rural northern China.The current prospective, population-based study was conducted between 2011 and 2016. Follow-up interviews were conducted annually from 2014 to 2016. The study involved 1511 dementia-free individuals aged 60 years or above from rural China. Standard criteria were used to make diagnoses for dementia and Alzheimer disease (AD).At least one follow up survey was completed with 1181 study participants. At the 5-year follow-up, 127 individuals had developed dementia, 75 had developed AD, and 32 had developed vascular dementia (VaD). With a total of 5649.2 risk years for the sample, the estimated incidence rates per 1000 person-years were 22.48 (95% CI: 18.62, 26.35) for dementia and 13.28 (95% CI: 10.29, 16.26) for AD. Incidence rates for dementia and AD increased with age across the 10-year age groups. Poor education (illiteracy) was an independent risk factor for both AD and VaD. Being engaged in social activities was an independent protective factor for VaD.The incidence of dementia in rural China was found to be higher than previously reported. Incidence of dementia increased with age, and AD was the most frequent type of dementia. Poor education was associated with a higher risk of VaD and AD. Engagement in social activities was an independent protective factor for VaD.

Albicanol Alleviates D-Galactose-Induced Aging and Improves Behavioral Ability Via by Alleviating Oxidative Stress-Induced Damage.

Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.

Hydrogen sulfide of air induces macrophage extracellular traps to aggravate inflammatory injury via the regulation of miR-15b-5p on MAPK and insulin signals in trachea of chickens.

Hydrogen sulfide (H2S) is an environmental contaminant to cause the airway damage. The release of macrophage extracellular traps (METs) is the mechanism of immune protection to harmful stimulation via microRNAs, but excessive METs cause the injury. However, few studies have attempted to interpret the mechanism of an organism injury due to H2S via METs in chickens. Here, we investigated the transcriptome profiles, pathological morphologic changes and METs release from chicken trachea after H2S exposure. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 10 differentially expressed genes were related to the METs release, the MAPK and insulin signaling pathways. Morphological and immunofluorescence analysis showed that H2S caused airway injury and MET release. H2S activated the targeting effect of miRNA-15b-5p on activating transcription factor 2 (ATF2). Western blotting and real time quantitative PCR results showed that H2S down-regulated the levels of dual specificity protein phosophatase1 (DUSP1) but up-regulated p38 MAP Kinase (p38) in the MAPK signal pathway. And the expression of phosphoinositide-dependent protein kinase 1 (PDK1), serine/threonine kinase (Akt), and protein kinase ζ subtypes (PKCζ) in the insulin signal pathway were increased after H2S exposure. These promoted the release of myeloperoxidase (MPO) and degradation histone 4 (H4) to induce the release of METs. Taken together, miR-15b-5p targeted ATF2 to mediate METs release, which triggered trachea inflammatory injury via MAPK and insulin signals after H2S exposure. These results will provide new insights into the toxicological mechanisms of H2S and environmental ecotoxicology.

Albicanol antagonizes Cd-induced apoptosis through a NO/iNOS-regulated mitochondrial pathway in chicken liver cells.

Cadmium (Cd) induces hepatocyte injury by oxidative stress. Albicanol is a sesquiterpenoid extracted from the medicinal plant Dryopteris fragrans that has previously been shown to exhibit anti-aging and antioxidant activity. In this study, we explored the mechanism of albicanol inhibition of the Cd-induced apoptosis of chicken hepatoma cells (LMH) by treating these cells with CdCl2 (25 µM) and/or albicanol (2.5 × 10-5 µg mL-1) for 24 h. Under Cd treatment, the research results showed that the apoptosis rate markedly increased in LMH cells. In addition, the iNOS activity and NO content increased significantly, which promoted the expressions of genes associated with the mitochondrial apoptosis pathway (Bax, CytC, Caspase-3 and Caspase-9) and inhibited the expression of Bcl-2 in this pathway. However, Cd + albicanol co-treatment significantly reduced the apoptosis rate and the expressions of iNOS and genes associated with the mitochondrial apoptosis pathway (Bax, CytC, Caspase-3 and Caspase-9), and promoted the expression of Bcl-2 in this pathway. In addition, molecular docking supported a link between the albicanol ligand and the iNOS receptor. These results indicated that albicanol can inhibit Cd-induced apoptosis by regulating the NO/iNOS-mediated mitochondrial pathway.

Anti-N-methyl-D-aspartate-receptor antibody encephalitis combined with syphilis: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations. The pathogenesis of the disease is unclear. Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms. There are few reports of anti-NMDAR encephalitis with syphilis, and the association between them is unknown; both diseases are related to immune system damage. We report a case of anti-NMDAR encephalitis with syphilis. CASE SUMMARY: A 32-year-old man was admitted to our hospital with complaints of cognitive decline, diplopia, and walking instability during the previous 6 mo. He developed dysarthria, difficulty swallowing, and involuntary shaking of his head, neck, and limbs during the month prior to presentation. Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons, midbrain, and bilateral basal ganglia, and inflammatory demyelination was considered. The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test. He was given anti-syphilis treatment, but the above symptoms gradually worsened. Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum. Due to the cerebrospinal fluid findings, anti-NMDAR encephalitis was a consideration. According to the patient's weight, he was treated with intravenous methylprednisolone 1 g QD for 5 d, with the dose gradually decreased for 6 mo, and immunoglobulin 25 g QD for 5 d; his symptoms improved after treatment. CONCLUSION: This case shows that anti-NMDAR encephalitis may be combined with syphilis, which should be recognized to avoid misdiagnosis and treatment delay.

Recurrence Rate and Relevant Associated Factors of Stroke among Patients with Small Artery Occlusion in Northern China.

Small artery occlusion (SAO) is responsible for 31.3% of all ischemic strokes in China. However, reports regarding the recurrence rate of SAO in China are rare. We aimed to assess the recurrence rate and factors associated with SAO in China. All consecutive patients with SAO hospitalized at Tianjin Huanhu Hospital from 2005 to 2014 were recruited. We assessed the association between stroke subtype, severity, and disease history with recurrence at 3, 12, and 36 months of onset using multivariate logistic regression analysis. A total of 2,524 SAO patients were included in this study, including 1696 (67.2%) men and 828 (32.8%) women. The recurrence rates were 3.1% at 3 months, 12.7% at 12 months, and 36.5% at 36 months. Compared with women, men had a higher risk of recurrence at 3 months after SAO (P = 0.003). Old age and severity of stroke were also associated with a higher risk of recurrence (P < 0.05). Patients with an elevated C-reactive protein had a higher risk of recurrence at 12 months (P = 0.003). On the other hand, the risk of recurrence at 12 months was 39% lower in patients who consumed alcohol than in those who did not (P = 0.037). Hypertension, atrial fibrillation, and obesity were independent risk factors of recurrence at 36 months. These findings suggest that modification of risk factors in patients with SAO, particularly men, is essential for reducing the rate of recurrence and the overall burden of stroke in China.

Comparative analysis of cognitive impairment prevalence and its etiological subtypes in a rural area of northern China between 2010 and 2015.

The purpose of this study was to evaluate changes in the prevalence and risk factors of cognitive impairment (CI) by analyzing and comparing two cross-sectional epidemiological surveys of CI and its subtypes were performed in a rural area of northern China between 2010 and 2015. Residents aged ≥60 years were drawn in northern China. The Mini Mental State Examination (MMSE) is recommended to test for CI. Dementia was further categorised into Alzheimer's disease (AD), vascular dementia (VaD), and dementia caused by other diseases (ODs). Mild cognitive impairment (MCI) was classified into MCI caused by AD (MCI-A), MCI caused by VaD (MCI-VD), and MCI caused by ODs (MCI-O). The prevalence of CI increased in China. The prevalence of all-cause CI was 30·5% (22.9% MCI and 7.6% dementia) in 2010. The prevalence of all-cause CI was 38.3% (27.8% MCI and 10.5% dementia) in 2015. Similar increases were observed for the prevalence of subtypes of dementia and MCI. These findings suggest an increasing prevalence of CI and its subtypes in China, which may be related to alterations in sociodemographic factors, vascular risk factors and lifestyle changes over time in these cohorts.

Sex Differences in the Prevalence of and Risk Factors for Cognitive Impairment No Dementia among the Elderly in a Rural Area of Northern China: A Population-Based Cross-Sectional Study.

BACKGROUND/AIMS: The burden of dementia among women in China, especially among women from rural areas, has increased due to their longevity and lower education levels compared with that among men. Thus, we aimed to assess sex differences in the prevalence of cognitive impairment and its relevant determinants among rural residents in North China. METHODS: Adults aged 60 years and older with cognitive impairment no dementia (CIND) were recruited to this study. Demographic characteristics, traditional risk factors, and lifestyle characteristics were obtained and analyzed on the basis of sex. RESULTS: There were 1,295 individuals with CIND (489 [37.8%] men and 806 [62.2%] women). The prevalence of CIND was 23.3% overall (19.8% for men, 26.1% for women; p < 0.001). Age, education level, history of stroke, and social activity were significantly associated with CIND for both men and women. Widowed status compared to married status was an independent risk factor for CIND in men (OR [95% CI] 1.50 [1.14-1.98]; p = 0.004). CONCLUSION: These findings suggest that it is crucial to address the secondary prevention of stroke and to consider the psychological status among the elderly with low educational attainment in order to reduce the burden of CIND in China.

Changes in total homocysteine levels after acute stroke and recurrence of stroke.

It is not known how total homocysteine (tHcy) levels change during the transition from acute stroke to post-stroke convalescence or whether tHcy changes occurring after the acute period are associated with recurrence of cerebro-cardiovascular events. Levels of tHcy were measured during acute ischemia and again after three months. Patients were followed for a median of 18 (range: 12-36) months. A total of 2800 patients who had at least two tHcy measurements were enrolled between February 2012 and June 2014; 2587 patients presented with ischemic stroke and 213 presented with cerebral hemorrhage. During the follow-up period, 220 (7.9%) patients experienced another ischemic event. After adjusting for additional cardiovascular risk factors, patients with the highest levels of tHcy (fourth quartile; >15.5 µmol/L) had a 1.76-fold increased risk of a recurrence (adjusted HR: 1.76, 95%CI: 1.11-3.08) as compared to patients with the lowest levels of tHcy (lowest quartile; ≤9.65 µmol/L). Additional analysis by subgroup indicated that this correlation was only significant for patients with large-artery atherosclerosis ischemia (adjusted HR: 2.00, 95%CI: 1.13-3.55). Elevated tHcy during the convalescent phase of acute stroke was independently associated with an increased risk of recurrent ischemic stroke, especially in those patients with large-vessel atherosclerosis ischemia.

Apolipoprotein E e4 Allele Is Associated with Subjective Cognitive Decline: A Meta-Analysis.

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) is a condition associated with increased risk of Alzheimer's disease. This study performs a meta-analysis to estimate the prevalence of the Apolipoprotein E e4 (APOE e4) allele in SCD and the association of APOE e4 with SCD. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched. Meta-analyses were conducted using STATA 12.0 software. When significant heterogeneity was present (I2 >50% and p < 0.05), we conducted stratified and meta-regression analyses to explore possible reasons for heterogeneity. RESULTS: We selected a total of 28 studies that were conducted in Australia, the United States, northern Europe, middle Europe, southern Europe, and Asia. The sample size of the SCD group was 6,044. Thirteen studies included a healthy control group (total control cohort of 3,822), whereas the remaining 15 studies were single-arm studies of SCD groups. The APOE e4 allele was associated with SCD (OR 1.12 [1.00-1.25]; p = 0.04). The pooled estimate for APOE e4 carrier prevalence was 32% (95% CI 28-35). Due to the significant heterogeneity in prevalence estimates, we performed stratified and meta-regression analyses and found that age and northern European residency were significantly associated with heterogeneity. CONCLUSION: The results of this meta-analysis indicate a weak association between APOE e4 and SCD. Age and northern European residency are the critical factors that determine heterogeneity in the APOE e4-associated prevalence of SCD.

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China.

BACKGROUND AND AIMS: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. METHOD: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). RESULTS: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. CONCLUSION: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.