Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance.

Acquired radioresistance is the primary contributor to treatment failure of radiotherapy, with ferroptosis is identified as a significant mechanism underlying cell death during radiotherapy. Although resistance to ferroptosis has been observed in both clinical samples of radioresistant cells and cell models, its mechanism remains unidentified. Herein, our investigation revealed that radioresistant cells exhibited greater tolerance to Glutathione Peroxidase 4 (GPX4) inhibitors and, conversely, increased sensitivity to ferroptosis suppressor protein 1 (FSP1) inhibitors compared to their sensitive counterparts. This observation suggested that FSP1 might play a dominant role in the development of radioresistance. Notably, the knockout of FSP1 demonstrated considerably superior efficacy in resensitizing cells to radiotherapy compared to the knockout of GPX4. To elucidate the driving force behind this functional shift, we conducted a metabolomic assay, which revealed an upregulation of Coenzyme Q (CoQ) synthesis and a downregulation of glutathione synthesis in the acquired radioresistance cells. Mechanistically, CoQ synthesis was found to be supported by aarF domain containing kinase 3-mediated phosphorylation of CoQ synthases, while the downregulation of Solute carrier family 7 member 11 led to decreased glutathione synthesis. Remarkably, our retrospective analysis of clinical response data further validated that the additional administration of statin during radiotherapy, which could impede CoQ production, effectively resensitized radioresistant cells to radiation. In summary, our findings demonstrate a dependency shift from GPX4 to FSP1 driven by altered metabolite synthesis during the acquisition of radioresistance. Moreover, we provide a promising therapeutic strategy for reversing radioresistance by inhibiting the FSP1-CoQ pathway.

Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 µg/d + DHA 800 mg/d), FA (800 µg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow-up, scores of full intelligence quotient (ßDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated. METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status. RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group. CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease.

Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca2+ homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca2+ release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC50 = 0.162 µM) and AChE (inhibition (%) = 93.5, IC50 = 0.372 µM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD.

An investigation into the disturbance effects of coal mining on groundwater and surface ecosystems.

Coal mining disturbs surface ecosystems in coal mining subsidence areas. Based on the groundwater-surface composite ecosystem analysis, we constructed an ecological disturbance evaluation index system (18 indices) in a coal mining subsidence area using the analytic hierarchy process (AHP). Taking the Nalinhe mining area in Wushen Banner, China, in 2018-2020 as an example, the weight, ecological disturbance grade and correlation of different indicators were determined by implementing fuzzy mathematics, weighting method, and correlation analysis method. The major conclusions of this review were: (i) After two years of mining, ecological disturbance was the highest in the study area (Grade III) and the lowest in the non-mining area (Grade I). (ii) Coal mining not only directly interfered with the environment, but also strengthened the connection of different ecological indicators, forming multiple ecological disturbance chains such as "mining intensity-mining thickness-buried depth/Mining thickness", "coal mining-surface subsidence-soil chemical factors", and "natural environment-soil physical factors". The disturbance chain that controls the ecological response factors in the region remains to be determined. However, the ecological response factors are the most important factor that hinders the restoration of the ecology in a coal mining subsidence area. (iii) The ecological disturbance in the coal mining subsidence area continued increasing over two years due to coal mining. The ecological disturbance by coal mining cannot be completely mitigated by relying on the self-repair capability of the environment. This study is of great significance for ecological restoration and governance of coal mining subsidence areas.

Prevalence of vitamin A and vitamin D deficiency in hospitalized neonates in Xi'an, China.

BACKGROUND AND OBJECTIVES: To investigate the prevalence of vitamin A and vitamin D deficiency and the associated factors in hospitalized neonates in Xi'an, China. METHODS AND STUDY DESIGN: A total of 524 hospitalized neonates were collected in this study. Serum vitamin A and D concentrations were detected in neonates within two weeks of birth. RESULTS: Serum vitamin A and D concentrations of hospitalized neonates were 0.55±0.21 µmol/L and 42.0±20.6 nmol/L, respectively. They were greater in full-term neonates than in preterm neonates, greater in rural neonates than in urban, and greater in single than in twin (all p<0.001). The prevalence of vitamin A and D deficiency were 14.9% and 33.0%, the prevalence of marginal vitamin A deficiency was 64.7%, and vitamin D insufficiency was 35.1%. Neonatal serum vitamin A and D concentrations were all positively correlated with birth weight and gestational age. Neonatal serum vitamin D concentration was also positively correlated with maternal serum vitamin D concentration. Additionally, neonatal vitamin A concentration was positively correlated with neonatal serum vitamin D concentration. CONCLUSIONS: Vitamin A and vitamin D statuses are compromised in hospitalized neonates in Xi'an, especially in premature neonates, low birth weight neonates, twins, and those born in urban areas. Individualized supplementation with vitamin A and vitamin D in neonates should be a clinical consideration.

Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers.

More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-specific pattern of metastasis in 1889, now known as the "seed and soil" theory where distinct cancer types are found to metastasize to different tumor-specific sites. Our understanding of the biology of tumor metastasis and specifically the molecular mechanisms driving their formation are still limited, in particular, as it relates to the genesis of oligometastasis. In the following review, we discuss recent advances in general understanding of this metastatic behavior including the role of specific signaling pathways, various molecular features and biomarkers, as well as the interaction of carcinoma cells with their tissue microenvironments (both primary and metastatic niches). The unique features that underlie OMD provide potential targets for localized therapy. As it relates to clinical practice, OMD is emerging as treatable with surgical resection and/or other local therapy options. Strategies currently being applied in the clinical management of OMD will be discussed including surgical, radiation-based therapy, ablation procedures, and the results of emerging clinical trials involving immunotherapy.

[Isovaleric acidemia due to compound heterozygous variants of IVD gene in a case].

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 µmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION: The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.

Relationship between folate, vitamin B12, homocysteine, transaminase and mild cognitive impairment in China: a case-control study.

To explore the association between the levels of serum folate, vitamin B12, and homocysteine (Hcy), transaminase and mild cognitive impairment (MCI) in Chinese elderly. A case-control study was implemented between April and October 2016. Elderly participants aged ≥60 with and without MCI (n = 118 separately) were recruited from Community Health Center of Binhai New Area in Tianjin. Spearman's correlation analysis indicated that Hcy was significantly positively correlated with alanine transaminase (ALT) and aspartate aminotransferase (AST), and negative correlations were found among Hcy, Mini-Mental Status Examination score, Wechsler Adult Intelligence Scale-Revised by China intelligence quotient, folate and vitamin B12. The associations among MCI and folate, vitamin B12, Hcy and transaminase were assessed using multivariate logistic regression analyses. Lower folate levels and higher Hcy and ALT and AST levels were associated with MCI risk adjusted for multiple covariates. Increased ALT, AST, Hcy levels and lower folate levels were independently associated with the risk of MCI.

[Clinical phenotype and variantal analysis of a pedigree affected with hereditary coagulation factor V deficiency].

OBJECTIVE: To explore the molecular basis for a pedigree affected with coagulation factor V (FV) deficiency. METHODS: Clinical data of the patient and his family members was analyzed. Targeted capture and next-generation sequencing (NGS) and Sanger sequencing were carried out to detect potential variant of the FV gene. RESULTS: The patient presented with jaundice and prolonged prothrombin time (PT) and activated partial thromboplastic time (APTT). V factor activity measured only 0.1% of the normal level, though the patient had no sign of bleeding. A paternal heterozygous variant c.653T>C (p.F218S) and a maternal heterozygous variant c.3642_3643del (p.P1215Rfs*175) were identified in the FV gene of the patient. His elder brother was a heterozygous carrier of the c.653T>C (p.F218S) variant. c.653T>C(p.F218S) was a known pathogenic variant, while the c.3642_3643del (p.P1215Rfs*175) variant was unreported previously. CONCLUSION: Mutations of the FV gene probably underlie the hereditary coagulation factor V deficiency in this patient. NGS combined with Sanger sequencing has detected potential variant with efficiency and provided a reliable basis for clinical and prenatal diagnosis for this family.

Targeting cancer stem cells and their niche: perspectives for future therapeutic targets and strategies.

A small subpopulation of cells within the bulk of tumors share features with somatic stem cells, in that, they are capable of self-renewal, they differentiate, and are highly resistant to conventional therapy. These cells have been referred to as cancer stem cells (CSCs). Recent reports support the central importance of a cancer stem cell-like niche that appears to help foster the generation and maintenance of CSCs. In response to signals provided by this microenvironment, CSCs express the tumorigenic characteristics that can drive tumor metastasis by the induction of epithelial-mesenchymal-transition (EMT) that in turn fosters the migration and recolonization of the cells as secondary tumors within metastatic niches. We summarize here recent advances in cancer stem cell research including the characterization of their genetic and epigenetic features, metabolic specialities, and crosstalk with aging-associated processes. Potential strategies for targeting CSCs, and their niche, by regulating CSCs plasticity, or therapeutic sensitivity is discussed. Finally, it is hoped that new strategies and related therapeutic approaches as outlined here may help prevent the formation of the metastatic niche, as well as counter tumor progression and metastatic growth.

Association of Leukocyte Telomere Length with Mild Cognitive Impairment and Alzheimer's Disease: Role of Folate and Homocysteine.

BACKGROUND: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer's disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear. OBJECTIVES: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association. METHODS: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders. RESULTS: The mean LTL was 1.56 ± 0.25 in controls, 1.44 ± 0.23 in MCI, and 1.28 ± 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101-0.597) and AD (OR 0.123; 95% CI 0.044-0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level. CONCLUSIONS: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.

Effects of folic acid supplementation on cognitive function and Aß-related biomarkers in mild cognitive impairment: a randomized controlled trial.

PURPOSE: Observational studies have frequently reported that low blood folate concentrations are associated with poor cognitive performance. Our previous studies have shown the potential beneficial effect on the metabolite levels of methionine cycle and peripheral blood inflammatory cytokines from 6- and 12-month folic acid supplementation on cognitive function in mild cognitive impairment (MCI). This study aims to continue exploring the effect of 24-month folic acid supplementation on cognitive function and pathological mechanism in MCI. METHODS: 180 individuals with MCI were identified and randomly divided into intervention (folic acid 400 µg/day, n = 90) and convention (n = 90) groups. Cognitive function (WAIS-RC) and blood Aß-related biomarkers were measured at baseline and at 6, 12, 18, and 24 months. Data were analyzed using generalized estimating equation. This trial has been registered with Trial Number: ChiCTR-TRC-13003227. RESULTS: During the follow-up, scores of full scale IQ, verbal IQ, and subdomains of Information and Digit Span were significantly higher in the intervention group than those in the convention group (P < 0.05). In the intervention group, blood homocysteine, S-adenosylhomocysteine (SAH), Aß-42, and the expression of APP-mRNA were decreased (P < 0.05), while S-adenosylmethionine (SAM), SAM/SAH ratio, and the expression of DNA methyltransferase mRNA were increased (P < 0.05). CONCLUSION: Folic acid supplementation appears to improve cognitive function and reduce blood levels of Aß-related biomarkers in MCI. Larger-scale double-blind placebo-controlled randomized trials of longer duration are needed.

[Analysis of clinical characteristics and genetic mutation in a pedigree affected with Chediak-Higashi syndrome].

OBJECTIVE: To explore the genetic basis for a pedigree affected with Chediak-Higashi syndrome (CHS). METHODS: Clinical data of two CHS patients from the pedigree was collected and analyzed. Targeted next generation sequencing and Sanger sequencing were conducted to detect potential mutation of the LYST gene. RESULTS: Both patients presented immunodeficiency, oculocutaneous albinism, and acidophilic inclusion body on bone marrow and blood smears. A homozygous c.6077_6078insA (p.Tyr2026Terfs) mutation was detected in the LYST gene in both patients. CONCLUSION: Genetic testing can play an important role in the diagnosis of CHS.

Small molecule-directed specification of sclerotome-like chondroprogenitors and induction of a somitic chondrogenesis program from embryonic stem cells.

Pluripotent embryonic stem cells (ESCs) generate rostral paraxial mesoderm-like progeny in 5-6 days of differentiation induced by Wnt3a and Noggin (Nog). We report that canonical Wnt signaling introduced either by forced expression of activated ß-catenin, or the small-molecule inhibitor of Gsk3, CHIR99021, satisfied the need for Wnt3a signaling, and that the small-molecule inhibitor of BMP type I receptors, LDN193189, was able to replace Nog. Mesodermal progeny generated using such small molecules were chondrogenic in vitro, and expressed trunk paraxial mesoderm markers such as Tcf15 and Meox1, and somite markers such as Uncx, but failed to express sclerotome markers such as Pax1. Induction of the osteochondrogenically committed sclerotome from somite requires sonic hedgehog and Nog. Consistently, Pax1 and Bapx1 expression was induced when the isolated paraxial mesodermal progeny were treated with SAG1 (a hedgehog receptor agonist) and LDN193189, then Sox9 expression was induced, leading to cartilaginous nodules and particles in the presence of BMP, indicative of chondrogenesis via sclerotome specification. By contrast, treatment with TGFß also supported chondrogenesis and stimulated Sox9 expression, but failed to induce the expression of Pax1 and Bapx1. On ectopic transplantation to immunocompromised mice, the cartilage particles developed under either condition became similarly mineralized and formed pieces of bone with marrow. Thus, the use of small molecules led to the effective generation from ESCs of paraxial mesodermal progeny, and to their further differentiation in vitro through sclerotome specification into growth plate-like chondrocytes, a mechanism resembling in vivo somitic chondrogenesis that is not recapitulated with TGFß.

[Effects of siRNAs targeting CD97 immune epitopes on biological behavior in breast cancer cell line MDA-MB231].

OBJECTIVE: To investigate the effects of siRNAs targeting CD97 immune epitopes on proliferation, infiltration, apoptosis and cell cycle of breast cancer cells. METHODS: siRNA sequences targeting CD97EGF and CD97Stalk immune epitopes were designed according to Gene Bank NM_001025160.2 with smart siCatchTM siRNA design software. CD97siRNAs were transfected into MDA-MB231 cells in which CD97 was highly expressed. Highest sensitive CD97EGF and CD97Stalk siRNA were screened by Western blotting. Inverted microscope was used to observe the growth of CD97siRNAs-transfected MDA-MB231 cells; the proliferation activity of MDA-MB231 cells was detected by MTT method; the wound healing assay and Transwell migration test were performed to examine the migration and infiltration ability of CD97EGF and CD97Stalk siRNA-transfected MDA-MB231 cells; the effects of CD97EGF siRNA and CD97Stalk siRNA on cell apoptosis and cell cycle of MDA-MB231 cells were detected by TUNEL and flow cytometry. RESULTS: The growth and proliferation activity of CD97siRNAs-transfected MDA-MB231 cells were significantly lower than those in the control groups, and such differences were more significant in CD97Stalk siRNA-transfected group (all P<0.05); scratch test showed that the wound healing rate was lower in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); Transwell migration showed that the number of MDA-MB231 cells crossing through chambers were less in CD97siRNAs-transfected groups, especially in CD97Stalk siRNA-transfected group (all P<0.05); no significant difference in cell apoptosis was observed between CD97siRNAs-transfected groups and control groups; cell cycle detection showed that CD97siRNAs-transfected groups had less cells in G0/G1 phase and more cells in S phase compared with the control groups, and such effect on cell cycle was more marked in CD97Stalk siRNA-transfected group (all P<0.05). CONCLUSIONS: CD97 plays an important role in the cell growth, proliferation, migration and invasion of breast cancer MDA-MB231 cells, and compared with CD97EGF, CD97Stalk may have more effective inhibitory effects on cellular malignant behaviors.

Prevalence of Mild Cognitive Impairment and Its Subtypes among Chinese Older Adults: Role of Vascular Risk Factors.

BACKGROUND/AIMS: The prevalence of mild cognitive impairment (MCI) and its subtypes among Chinese older adults, and the contribution of vascular risk factors (VRF) and vascular disorders to MCI remain unclear. This study aims to investigate the prevalence of MCI and its different subtypes, and clarify the role of VRF and vascular diseases in the occurrence of MCI. METHODS: A random sample of 5,214 nondementia (DSM-IV) individuals aged ≥65 years underwent neuropsychological assessments and clinical examinations. MCI, including amnestic MCI-single domain (aMCI-SD), amnestic MCI-multiple domains (aMCI-MD), nonamnestic MCI-single domain (naMCI-SD), and nonamnestic MCI-multiple domains (naMCI-MD), was defined according to modifications of the Petersen criteria. VRF (smoking, obesity, and diabetes) and vascular disorders (myocardial infarction, atrial xFB01;brillation, stroke, and hypertension) were assessed based on information through self-report and medical records. Data were analyzed using multivariate logistic regression. RESULTS: The prevalence of MCI was 11.33% (95% CI: 8.21-14.43), and that of aMCI-SD, aMCI-MD, naMCI-SD, and naMCI-MD was 4.48% (95% CI: 2.24-6.74), 2.09% (95% CI: 0.80-3.38), 4.22% (95% CI: 1.38-7.08), and 0.53% (95% CI: 0.32-0.75), respectively. The prevalence of MCI is higher in women than in men. Multivariate logistic regression analysis shows that VRF and vascular diseases were significantly related to increase the odds of MCI and its specific subtype. CONCLUSIONS: The prevalence of MCI is almost 11% among Chinese older adults. VRF and vascular disorders are associated with MCI, especially naMCI.

Relationship between plasma lipids and mild cognitive impairment in the elderly Chinese: a case-control study.

BACKGROUND: High lipid levels may constitute a more important risk factor for cognitive health in previous studies. However, the association of plasma lipids with mild cognitive impairment (MCI) among elderly people had not been studied exactly. This study aims to explore the relationship between plasma lipids/lipoproteins and the risk of MCI in elderly Chinese individuals. METHODS: CSI-MCI study was a preliminary case-control study of the association of plasma lipids/lipoproteins with MCI in 112 MCI cases and 115 cognitively normal controls. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) levels were measured in fasting blood samples. Multivariable logistic regression was used to evaluate the potential association between MCI and these factors. Statistical models were adjusted for multiple demographic and biological covariates. RESULTS: The subjects with MCI were significantly older, higher percentage of females and less educated than controls (P <0.05). As expected, subjects with MCI had lower MMSE score compared with controls (P <0.05). Multivariate logistic regression analysis showed that higher plasma TC level was associated with the risk of MCI in models adjusting for age, sex and education. However, This association was attenuated after adjusting for BMI, Type 2 diabetes mellitus, heart disease and hypertension. Plasma TG level was negatively associated with the risk of MCI. The adjusted odds ratio (OR) of MCI was significantly reduced for the highest quartile of plasma TG level (OR: 0.76, 95 % CI: 0.48-0.97), but not for the second or third quartile, compared with the lowest quartile (adjusted models). Plasma HDL level was significantly negatively associated with the risk of MCI. There was no association between plasma LDL level and the risk of MCI, adjustment for demographics, vascular disorders did not change this relation. CONCLUSIONS: Plasma TC was significantly higher in MCI subjects compared to cognitively normal controls, Elevated plasma HDL and triglyceride were associated with the occurrence of MCI. These findings need to be confirmed in further longitudinal studies.

[Measurement of S-adenosylmethionine and S-adenosylhomocysteine in mice liver with high performance liquid chromatography].

OBJECTIVE: To develop a method for determination of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) simultaneously in mice liver by reversed-phase high performance liquid chromatography (HPLC). METHODS: Mice livers were weighed, emulsified quickly by handheld homogenate, four times the volume of 0.6 mol/L HCLO4 added for ultrasonic, and the hydrolysate was adjusted to centrifuged and filtrated with a membrane. The supernatants were separatedonVenusil MP-C18 column (250 mm x 4.6 mm, 5 µm) at 30 °C with a mobile phase of 50 mmol/L NaH2PO4, 10 mmol/L C7H15NaO3S and methanol, a flow rate of 1.0 ml/min and UV detection at 254 nm. RESULTS: The SAM and SAH in the corresponding concentration range showed a good linear relation with its peak area, correlation coefficient ( r > 0. 9990 ) , recovery was 92.20%-101.38%, RSD was 2.88%-6.78%. The average within-day precision of SAM and SAH was 4.14% and 3.71%, and the average day to day precision was 7.51% and 9.54%. The content of SAM and SAH in mice liver was 3.14-6.09 mg/L (31.44-60.98 nmol/g wet weight) and 1.29-3.10 mg/L (13.38-32.17 nmol/g wet weight) respectively. CONCLUSION: The validated method is simple, rapid accurate and reliable to the determination of SAM and SAH in mice liver.