MORC2 phosphorylation fine tunes its DNA compaction activity.

Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects in epigenetic regulation and DNA damage response. The C-terminal domain (CTD) of MORC2, frequently phosphorylated in DNA damage, promotes cancer progression, but its role in chromatin remodelling remains unclear. Here, we report a molecular characterisation of full-length, phosphorylated MORC2, demonstrating its preference for binding open chromatin and functioning as a DNA sliding clamp. We identified a phosphate interacting motif within the CTD that dictates ATP hydrolysis rate and cooperative DNA binding. The DNA binding impacts several structural domains within the ATPase region. We provide the first visual proof that MORC2 induces chromatin remodelling through ATP hydrolysis-dependent DNA compaction, regulated by its phosphorylation state. These findings highlight phosphorylation of MORC2 CTD as a key modulator of chromatin remodelling, presenting it as a potential therapeutic target.

Assessing the current situation and the influencing factors affecting perceived stigma among older patients after leukemia diagnosis.

BACKGROUND: Psychological problems are becoming increasingly prominent among older patients with leukemia, with patients potentially facing stigmatization after diagnosis. However, there is limited research on the stigma experienced by these patients and the factors that may contribute to it. AIM: To investigate the stigma faced by older patients after being diagnosed with leukemia and to analyze the potential influencing factors. METHODS: A retrospective analysis was conducted using clinical data obtained from questionnaire surveys, interviews, and the medical records of older patients with leukemia admitted to the Hengyang Medical School from June 2020 to June 2023. The data obtained included participants' basic demographic information, medical history, leukemia type, family history of leukemia, average monthly family income, pension, and tendency to conceal illness. The Chinese versions of the Social Impact Scale (SIS), Perceived Social Support Scale (PSSS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to assess indicators related to stigma, social support, and mental health status. We used Pearson's correlation coefficient to analyze the strength and direction of the relationship between the scores of each scale, and regression analysis to explore the factors related to the stigma of older patients with leukemia after diagnosis. RESULTS: Data from 120 patients with leukemia aged 65-80 years were analyzed. The total score on the SIS and PSSS was 43.60 ± 4.07 and 37.06 ± 2.87, respectively. The SAS score was 58.35 ± 8.32 and the SDS score was 60.58 ± 5.97. The stigma experienced by older leukemia patients was negatively correlated with social support (r = -0.691, P < 0.05) and positively correlated with anxiety and depression (r = 0.506, 0.382, P < 0.05). Age, education level, smoking status, average monthly family income, pension, and tendency to conceal illness were significantly associated with the participants' level of stigma (P < 0.05). Age, smoking status, social support, anxiety, and depression were predictive factors of stigmatization among older leukemia patients after diagnosis (all P < 0.05), with a coefficient of determination (R2) of 0.644 and an adjusted R2 of 0.607. CONCLUSION: Older patients commonly experience stigmatization after being diagnosed with leukemia. Factors such as age, smoking status, social support, and psychological well-being may influence older patients' reported experience of stigma.

Population pharmacokinetic study and application of ticagrelor and AR-C124910XX after percutaneous coronary intervention in Chinese patients with acute coronary syndrome.

OBJECTIVES: This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization. MATERIALS AND METHODS: Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology. RESULTS: The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased. CONCLUSION: The study offers key insights into ticagrelor's dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.

Female reproductive factors, exogenous hormone use, and incident chronic kidney disease and end-stage renal disease.

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

Lower plasma linoleic acids as a risk factor for gout: an integrated analysis of population-based cohort and genetic data.

Background: Gout is a nutrition-related, highly prevalent inflammatory arthritis with undesirable effects on the quality of life. The relationships between circulating fatty acids (FAs) and gout remain poorly understood. Method: We included 268 174 participants with plasma FAs measured using nuclear magnetic resonance at the baseline (2006-2010) from the UK Biobank, of which 15 194 participants had repeated measures of FAs between 2012 and 2013. Cox proportional hazards models were used to assess the association of the baseline and longitudinal changes in relative levels of plasma FAs (% total FAs) with incident gout. Mendelian randomization (MR) analyses were conducted to assess the potential causality of the examined association. Results: Over a median follow-up of 12.8 years, 5160 incident cases of gout occurred. Baseline polyunsaturated fatty acids (PUFAs), n-6 PUFAs, and linoleic acids (LAs) were inversely associated with incident gout (all P-trend values < 0.0001). Baseline monounsaturated fatty acids (MUFAs), n-3 PUFAs, and docosahexaenoic acids (DHAs) were positively associated with incident gout (all P-trend values < 0.0001). Longitudinal increments of n-6 PUFAs and LAs were associated with a lower risk of subsequent gout, whereas an increment of n-3 PUFAs was associated with a higher risk. In two-sample MR analyses, genetically determined higher levels of PUFAs, n-6 PUFAs, and LAs were associated with a decreased risk of gout (all P values < 0.05). Conclusions: Our findings consistently indicate a causal relationship of elevated levels of n-6 PUFAs, especially LAs, with a reduced risk of gout.

TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Personal mastery and quality of life in patients with atrial fibrillation after radiofrequency ablation: The mediating role of health promoting behavior.

BACKGROUND: Improving quality of life is vital for patients with atrial fibrillation (AF) after radiofrequency ablation. Quality of life can be affected not only by personal mastery but also by health promoting behavior as previously studied. However, it remains unclear whether health promoting behavior mediates the relationship between personal mastery and quality of life. OBJECTIVES: To explore whether health promoting behavior mediates the relationship between personal mastery and quality of life in patients with AF after radiofrequency ablation. METHODS: A cross-sectional design and convenience sampling were conducted at a tertiary hospital in China. Self-reported questionnaires were used to assess personal mastery, health promoting behavior and quality of life. SPSS and AMOS software were used for statistical analysis. RESULTS: A total of 202 patients with AF after radiofrequency ablation were enrolled (mean age 58.28 ± 12.70 years). The scores for personal mastery and quality of life were 22.52 ± 2.53 points and 62.58 ± 8.59 points, respectively, indicating a limited level. The health promoting behavior exhibited a moderate level, with scores averaging 103.82 ± 8.47 points. There was a positive correlation between the three variables (all P < 0.05). Health promoting behavior played a partial mediating role in the relationship between personal mastery and quality of life in patients with AF after radiofrequency ablation, accounting for 44.79 % of the total effect. CONCLUSIONS: In order to improve quality of life and prognosis, it is necessary to consider enhancing personal mastery and increasing patient compliance with health promoting behavior, which are important ways to improve their quality of life.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.

Relationship of microvascular complications and healthy lifestyle with all-cause and cardiovascular mortality in women compared with men with type 2 diabetes.

BACKGROUND: Sex differences exist in the prevalence of microvascular disease (MVD) and healthy-lifestyle adherence. Whether MVD and healthy lifestyles are associated with mortality risk similarly for women and men who have type 2 diabetes mellitus (T2DM) remains unknown. METHODS: The present study included 9992 women and 15,860 men with T2DM from the UK Biobank. MVDs included retinopathy, peripheral neuropathy, and chronic kidney disease. Healthy lifestyle factors consisted of ideal BMI, nonsmoking, healthy diet, regular exercise, and appropriate sleep duration. Sex-specific hazard ratios (HRs) of mortality associated with the MVDs or healthy lifestyles were calculated and women-to-men ratio of HRs (RHR) were further estimated, after multivariable adjustment for potential confounders. RESULTS: During a median of 12.7 years of follow-up, 4346 (1202 in women) all-cause and 1207 (254 in women) CVD deaths were recorded. The adjusted HRs (95% CI) of all-cause mortality for 1 additional increment of the MVDs were 1.71 (1.55, 1.88) for women and 1.48 (1.39, 1.57) for men, with an RHR of 1.16 (1.03, 1.30). The corresponding RHR was 1.36 (1.09, 1.69) for cardiovascular mortality. Adhering to a healthy lifestyle (≥4 vs. ≤1 lifestyle factor) was associated with an approximately 60%-70% lower risk of all-cause and cardiovascular mortality without sex differences (P-interaction >0.70). Furthermore, as compared with having no MVD and an unfavorable lifestyle, having ≥2 MVDs but a favorable lifestyle was not associated with a higher risk of all-cause mortality either in women (HR = 0.88; 95% CI: 0.49, 1.60) or in men (HR = 0.95; 95% CI: 0.64, 1.40), similarly when considering cardiovascular mortality. CONCLUSIONS: In T2DM, while MVDs are more strongly associated with mortality risk in women than in men, adhering to a favorable lifestyle is associated with a substantially lower risk of mortality and may eliminate the detrimental impact of MVDs in both sexes.

Microvascular disease, modifiable risk factor profiles and incident arrhythmias in type 2 diabetes.

BACKGROUND: To assess the roles of diabetic microvascular disease and modifiable risk factors and their combination in the development of arrhythmias. METHODS: We included participants with type 2 diabetes (T2D) who were free of arrhythmias during recruitment in the UK Biobank study. The associations of microvascular disease states (defined by the presence of retinopathy, peripheral neuropathy or chronic kidney disease), four modifiable arrhythmic risk factors (body mass index, smoking, systolic blood pressure and glycosylated haemoglobin) and their joint associations with incident arrhythmias were examined. RESULTS: Among the 25 632 participants with T2D, 1705 (20.1%) of the 8482 with microvascular disease and 2017 (11.8%) of the 17 150 without microvascular disease developed arrhythmias during a median follow-up of 12.3 years. Having any of the three microvascular diseases was associated with a 48% increase in the hazard of developing arrhythmias. Incorporating microvascular disease states into a model alongside 11 traditional risk factors significantly enhanced arrhythmia prediction. Furthermore, individuals with microvascular disease who had optimal levels of zero to one, two, three or four arrhythmic risk factors showed an HR of 2.05 (95% CI 1.85, 2.27), 1.67 (95% CI 1.53, 1.83), 1.35 (95% CI 1.22, 1.50) and 0.91 (95% CI 0.73, 1.13), respectively, compared with those without microvascular disease. CONCLUSIONS: Although microvascular disease, a non-traditional risk factor, was associated with incident arrhythmias in individuals with T2D, having optimal levels of risk factors may mitigate this risk.

Studies on adsorption properties of magnetic composite prepared by one-pot method for Cd(II), Pb(II), Hg(II), and As(III): Mechanism and practical application in food.

A one-pot synthesis afforded a magnetic, crosslinked polymer adsorbent (m-P6) with a variety of functional groups to realize simultaneous adsorption of Cd2+, Pb2+, Hg2+, and As3+. The material was characterized by TEM-EDS, XRD, FT-IR, VSM, and XPS. Kinetic and isothermal analyses suggested mainly chemisorption processes of heavy metal ions that form multiple layers on heterogeneous surfaces. Theoretical adsorption capacities calculated by a pseudo-2nd-order kinetic model and the Sips isothermal model were 282.88 mg/g for Cd2+, 326.18 mg/g for Pb2+, 117.85 mg/g for Hg2+, and 320.29 mg/g for As3+. m-P6 not only can efficiently adsorb divalent heavy metals (Cd2+, Pb2+, Hg2+), but also demonstrate a process of adsorption-driven catalytic oxidation by single-electron transfer (SET) from As3+ to As5+. In application, in addition to adsorption in water, m-P6 is capable of minimizing matrix interference, and extracting trace heavy metals in a complex environment (cereal) through easy operations for improving the detection accuracy, as well as it is potential for application in detection of trace heavy metals in foodstuffs. m-P6 can be readily regenerated and efficiently recycled for 5 cycles using eluent E12 and dilute acid.

Effect of the type of brewing water on the sensory and physicochemical properties of light-scented and strong-scented Tieguanyin oolong teas.

Variations in the quality of brewing water profoundly impact tea flavor. This study systematically investigated the effects of four common water sources, including pure water (PW), mountain spring water (MSW), mineral water (MW) and natural water (NW) on the flavor of Tieguanyin tea infusion. Brewing with MW resulted in a flat taste and turbid aroma, mainly due to the low leaching of tea flavor components and complex interactions with mineral ions (mainly Ca2+, Mg2+). Tea infusions brewed with NW exhibited the highest relative contents of total volatile compounds, while those brewed with PW had the lowest. NW and MSW, with moderate mineralization, were conducive to improving the aroma quality of tea infusion and were more suitable for brewing both aroma types of Tieguanyin. These findings offer valuable insights into the effect of brewing water on the sensory and physicochemical properties of oolong teas.

Predictors for non-attainment of meropenem target concentrations when treating infections in critically ill patients
.

BACKGROUND: Failure to achieve target concentrations of ß-lactam antibiotics is not uncommon despite administration of high doses. The objective of this study was to identify risk factors predicting non-attainment of ß-lactams target concentration in critically ill patients receiving meropenem as an intravenous infusion. MATERIALS AND METHODS: The retrospective study included adult patients receiving meropenem by intravenous infusion and undergoing therapeutic drug monitoring (TDM) in the intensive care units (ICU) at Nanjing First Hospital. Blood samples were analyzed using UPLC-MS. Potential risk factors were evaluated by correlating them with meropenem trough concentrations (Cmin) lower than the targeted concentration (the minimum inhibitory concentration (MIC)). RESULTS: Non-attainment of target concentrations was observed in 41 patients (19.5%) of the 210 patients examined. Predictors for non-attainment using multivariate logistic regression analysis were: age (p = 0.013), dosage (p = 0.042), augmented renal clearance (ARC), (p = 0.041). CONCLUSION: In addition to the expected risk factors (age and dosage), ARC was a predictor for non-attainment of the target concentration. The risk of non-attainment of target concentrations increased with an increase in creatinine clearance. Attention should be given to ARC and creatinine clearance when administering meropenem by intravenous infusion.

Moisture content of tea dhool for the scenting process affects the aroma quality and volatile compounds of osmanthus black tea.

To improve the quality of osmanthus black tea, samples produced with different scenting methods were prepared. The sensory quality was assessed and the characteristic aromatic components were explored using solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry. According to the results, osmanthus black tea obtained by adding osmanthus scenting in the fermentation process had the strongest floral aroma. The major contributors to the aroma of osmanthus black tea were identified as ß-ionone, dihydro-ß-ionone, benzeneacetaldehyde, citral, geraniol, and linalool by calculating their relative odor activity values. An analysis of the causes revealed that the moisture content of tea dhool significantly affected the adsorption of fresh flower aroma by tea. The experimental results showed that osmanthus black tea produced using tea dhool containing 30% moisture content had the highest content of crucial aroma components, suggesting the tea dhool under this condition had the strongest adsorption capacity for osmanthus aroma.

Disease trajectories in older adults with non-AD pathologic change and comparison with Alzheimer's disease pathophysiology: A longitudinal study.

Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models. We found that compared to individuals with A-T-N-, those with abnormal tauopathy or neurodegeneration biomarkers (A-T + N-, A-T-N + , and A-T + N + ) had a faster rate of cognitive decline and disease progression. Individuals with A-T + N + had a faster rate of decline than those with A-T + N-. Additionally, in individuals with the same baseline tauopathy and neurodegeneration biomarker status, the presence of baseline amyloid could accelerate cognitive decline and clinical progression. These findings provide a foundation for future studies on non-AD pathologic change and its comparison with AD pathophysiology.

Ticagrelor Steady-State Trough Concentration in Chinese Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVE: Platelets play a pivotal role in thrombotic events associated with acute coronary syndrome (ACS), making oral antiplatelet therapy a cornerstone in antithrombotic strategies. The dosing regimen for the oral antiplatelet drug ticagrelor warrants evaluation to ensure its appropriateness in clinical practice. Therefore, this study aimed to investigate the real-world clinical application of ticagrelor by determining the optimal therapeutic concentration of ticagrelor in Chinese patients undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled a cohort of 912 patients who underwent PCI with drug-eluting stent implantation for the treatment of ACS. We measured steady-state plasma drug concentrations using high-performance liquid chromatography-tandem mass spectrometry. The therapeutic drug concentration range at steady state was established on the basis of clinical pharmacodynamic indices, with verification of reliability through concentration-effect analysis and receiver operating characteristic curve assessment. RESULTS: Analysis of plasma samples from the 912 patients revealed significant variations in the steady-state trough concentration of ticagrelor associated with factors such as gender, age, hypertension, and hyperlipidemia. On the basis of this analysis, the optimal therapeutic range for steady-state trough concentration was determined to be 240.65-335.83 ng/mL. Furthermore, the upper limit values for steady-state concentration were established at 439.97 ng/mL for male patients and 347.06 ng/mL for female patients. CONCLUSIONS: This study provides robust and reliable insights into the optimal therapeutic steady-state trough concentrations of ticagrelor in Chinese patients with post-percutaneous coronary intervention. These findings have significant implications for guiding the rational use of antiplatelet drugs and facilitating precise drug administration in Chinese patients undergoing percutaneous coronary intervention.

Preparation methods, structural characteristics, and biological activity of polysaccharides from Platycodon grandiflorus.

Platycodon grandiflorus (P. grandiflorus), a traditional Chinese medicinal herb used for both medicine and food, has a long history of treating respiratory infections, bronchitis, pneumonia, and other lung-related diseases. The therapeutic effects of P. grandiflorus are attributed to its chemical components, including polysaccharides. Among these components, Platycodon grandiflorus polysaccharides (PGP) are recognized as one of the most important and abundant active ingredients, exhibiting various biological activities such as prebiotic, antioxidant, antiviral, anticancer, antiangiogenic, and immune regulatory properties. Incorporating the principles of traditional Chinese medicine, carrier concepts, and modern targeted drug delivery technologies, PGP can influence the target sites and therapeutic effects of other drugs while also serving as a drug carrier for targeted and precise treatments. Therefore, it is essential to provide a comprehensive review of the extraction, separation, purification, physicochemical properties, and biological activities of PGP. In the future, by integrating new concepts, technologies, and processes, further references and guidance can be provided for the comprehensive development of PGP. This will contribute to the advancement of P. grandiflorus in various fields such as pharmaceuticals, health products, and food.

Development and evaluation of serological screening based on one dried plasma spot for HIV, syphilis, and HCV.

BACKGROUND: In the effort to prevent and control HIV/AIDS, China has established a national sentinel surveillance system. However, some sentinel sites face limitations in environmental resources and accessibility, prompting the exploration of alternative sample strategies. Dried plasma spots (DPS) samples are viewed as promising alternatives to traditional plasma samples due to their advantages, including sample stability, easy storage, and convenient transport. This study aims to develop a method for screening HIV, Treponema pallidum (TP), and Hepatitis C Virus (HCV) using DPS samples and assess their performance. METHODS: Based on existing commercial assay kits, a detection method was established through the optimization of experimental parameters, including the amount of plasma on filter paper, the volume of elution solution applied to dried plasma spots, the size of dried plasma spots, elution solution volume, elution solution components, elution temperature, and elution time. A series of laboratory evaluation panels were constructed for laboratory assessments, including the laboratory basic panel, laboratory interference panel, and laboratory precision panel. Additionally, clinical samples were used for evaluation. RESULTS: Optimal conditions for DPS sample extraction were: plasma volume, 100 µL; DPS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1‰ Tween20; elution time, 2 h; elution temperature, room temperature. A total of 619 paired plasma/DPS samples were tested by both methods. The DPS-based ELISA method exhibited 100% sensitivity/specificity for HIV, 98.6%/100% for TP, and 99.6%/100% for HCV. Kappa values between the plasma samples and DPS samples were 100% for HIV, 99% for TP, and 100% for HCV. The DPS-based ELISA method failed to detect 1 HCV mono-infected sample and TP in 1 HIV/HCV/TP co-infected sample. For the HIV/HCV/TP co-infected sample, the S/CO in the plasma sample was 2.143 and in the DPS sample was 0.5. For HCV, the S/CO (sample OD/cut-off) was 3.049 in the plasma sample and 0.878 in the DPS sample. CONCLUSIONS: A single DPS, following one-time standardized processing, can be used to detect HIV, HCV, and TP. Researching and establishing laboratory testing methods better suited for China's sentinel surveillance have significant practical applications in improving HIV testing in resource-constrained environments.

Exploring the links among peripheral immunity, biomarkers, cognition, and neuroimaging in Alzheimer's disease.

INTRODUCTION: We analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)-related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD. METHODS: Peripheral immunity markers were assessed in AD, non-AD neurodegenerative disorders, and controls, examining their connections with cognition, AD-related biomarkers, and neuroimaging using multiple regression models. RESULTS: The study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lower lymphocyte-to-monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aß) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aß deposition (amyloid positron emission tomography). DISCUSSION: Peripheral immunity markers offer a non-invasive and cost-effective means of studying AD-related pathophysiological changes, providing valuable insights into its pathogenesis and treatment. Highlights: Peripheral immunity markers linked to cognitive decline and anxiety/depression.Low LMR, LYM, and high NLR linked to reduced CSF Aß, impacting cognition.High PLR, NLR, SII associated with brain atrophy and hippocampal Aß deposition.

Associations Between TREML2 Gene Variants and Alzheimer's Disease: Biomarkers, Neuroimage, and Cognition.

BACKGROUND: Recent genetic research identified a protective factor against late-onset Alzheimer's disease (AD) in Caucasians, a variant called rs3747742-C in the TREML2 gene. However, the roles of other TREML2 variants in AD have not been fully explored. OBJECTIVE: We conducted a focused analysis of 16 TREML2 variants, examining their connection to AD by studying their correlation with cerebrospinal fluid (CSF) proteins, neuroimage, and cognition in the Alzheimer's Disease Neuroimaging Initiative database (ADNI). METHODS: A multiple linear regression model was utilized to estimate potential associations between TREML2 genotypes and various endophenotypes in the entire ADNI sample at baseline, with age, gender, years of education, and APOE ɛ4 status included as covariates. To examine changes in clinical outcomes over time, linear mixed-effects models were employed. RESULTS: We found that the SNP rs17328707-A was associated with higher ADNI-VS scores, smaller ventricles, and larger middle temporal volume at baseline. The SNP rs6915083-G was linked to lower CSF t-tau and p-tau levels, and higher CSF Aß levels. The SNP rs9394766-G was associated with a smaller hippocampus and larger ventricles at baseline. In longitudinal cohorts, the rs6915083-G SNP was associated with changes in ADNI-MEM and ADNI-EF scores, as well as the rate of hippocampal and middle temporal atrophy. CONCLUSION: Our findings reveal that TREML2 gene variants have different effects on AD. Two variants are protective, while one may be a risk factor. This enhances our understanding of AD genetics and could guide future research and personalized treatments.