Significance of plasma p-tau217 in predicting long-term dementia risk in older community residents: Insights from machine learning approaches.

INTRODUCTION: Whether plasma biomarkers play roles in predicting incident dementia among the general population is worth exploring. METHODS: A total of 1857 baseline dementia-free older adults with follow-ups up to 13.5 years were included from a community-based cohort. The Recursive Feature Elimination (RFE) algorithm aided in feature selection from 90 candidate predictors to construct logistic regression, naive Bayes, bagged trees, and random forest models. Area under the curve (AUC) was used to assess the model performance for predicting incident dementia. RESULTS: During the follow-up of 12,716 person-years, 207 participants developed dementia. Four predictive models, incorporated plasma p-tau217, age, and scores of MMSE, STICK, and AVLT, exhibited AUCs ranging from 0.79 to 0.96 in testing datasets. These models maintained robustness across various subgroups and sensitivity analyses. DISCUSSION: Plasma p-tau217 outperforms most traditional variables and may be used to preliminarily screen older individuals at high risk of dementia. HIGHLIGHTS: Plasma p-tau217 showed comparable importance with age and cognitive tests in predicting incident dementia among community older adults. Machine learning models combining plasma p-tau217, age, and cognitive tests exhibited excellent performance in predicting incident dementia. The training models demonstrated robustness in subgroup and sensitivity analysis.

Unraveling the link between hypertriglyceridemia, dampness syndrome, and chronic diseases: A comprehensive observational study.

To investigate the dampness syndrome score in hypertriglyceridemia and the correlations between hypertriglyceridemia and other chronic diseases and lifestyle factors. Data were retrospectively obtained from individuals who underwent physical examinations at Guangzhou Cadres Health Management Centre from May 2022 to May 2023. t Test, variance analysis, and chi-square test were used to compare the score of dampness syndrome and the prevalence of hypertriglyceridemia among different subgroups. Pearson, Spearman correlation analysis, and regression analysis were used to explore the correlations between hypertriglyceridemia and dampness syndrome, chronic diseases, and lifestyle factors. The prevalence of hypertriglyceridemia was 26.70%. Clinical test index and dampness syndrome score were significant differences between hypertriglyceridemia group and normal group (P < .05). Subgroup analyses as a function of the degree of triglyceridemia indicated that the dampness syndrome score increased with increasing degree of triglyceridemia (P < .05). Correlation analysis showed that hypertriglyceridemia was correlated with dampness syndrome, overweight/obesity, hypertension, diabetes, and other chronic diseases (P < .05). Multivariate logistic regression analysis showed that age, sex, marriage, education level, smoking, drinking, fruit consumption, vegetable consumption, milk and dairy product consumption, dessert or snack consumption, the degree of dampness syndrome, and engagement in exercise were associated with hypertriglyceridemia (P < .05). Hypertriglyceridemia is associated with a variety of chronic diseases and lifestyle factors, and is closely related to dampness syndrome. The score of dampness syndrome can reflect hypertriglyceridemia to a certain extent. It provides more clinical reference for the treatment of hypertriglyceridemia combined with the analysis of dampness syndrome of traditional Chinese medicine.

Natural Antioxidant Vitamin C Improves Photovoltaic Performance of Tin-Lead Mixed Perovskite Solar Cells.

The oxidation of Sn2+ can occur even after the completion of the perovskite crystallization in a low oxygen environment. Concerning this, the natural antioxidant vitamin C (VC) is introduced to the surface of Sn-Pb mixed perovskite using a postprocessing method to achieve the purpose of inhibiting Sn2+ oxidation and enhancing perovskite solar cells performance. The results indicate that the VC could effectively inhibit Sn2+ oxidation and heal the vacancy defects of the annealed perovskite film. Meanwhile, the introduction of VC significantly improves the morphology and crystalline quality of the perovskite films. After optimization, the highest power conversion efficiency of the VC-treated Sn-Pb mixed device increased to 20.44%. Moreover, the VC-treated unencapsulated device shows excellent long-term stability, retaining 75.3% of its initial efficiency after 800 h of aging in a N2 atmosphere, which is much higher than the 20.1% of the control device.

Mortality of Epilepsy in Chinese Populations: A Comprehensive Review.

BACKGROUND: Premature mortality is a significant part of the epilepsy burden and may vary across populations, especially between high-income and lower- and middle-income countries. People with epilepsy in China are approximately a fifth of the global population with epilepsy. Previous studies were unlikely to represent the situation in China due to limitations in design, methods, sample size, follow-up time, and other inherent population heterogeneity. SUMMARY: By summarising the evidence on the mortality characteristics in Chinese populations with epilepsy in the last 6 decades, we found a median mortality rate of 14.7 (6.8-74.4)/1,000 person-years and a median standardised mortality ratio (SMR) of 4.4 (2.6-12.9) in population-based studies, and a median mortality rate of 12.3 (9.5-101.5)/1,000 person-years and a median SMR of 3.0 (1.5-5.1) in hospital-based studies. Vascular diseases, complications of diabetes, and accidental injuries were the leading causes of death. Risk factors for mortality were reported as older age, male, longer duration, and higher frequency of seizures. Case fatality ratios of status epilepticus in adults were higher than in children, and both increased with follow-up time. Mortality in people with symptomatic epilepsy was high and varied across different primary diseases. KEY MESSAGES: The highest mortality rate and sudden unexpected death in epilepsy (SUDEP) incidence were reported from the least developed areas in China. Accidental injuries were the most common causes of epilepsy-related deaths, while the incidence of SUDEP may be underestimated in Chinese populations. Further research is warranted to improve the understanding of premature mortality risk so that preventative measures can be introduced to improve the situation.

Joint effect of testosterone and neurofilament light chain on cognitive decline in men: The Shanghai Aging Study.

INTRODUCTION: The association of testosterone and cognitive decline is inconclusive, and its joint effect with neurofilaments light chain (NfL) remains largely unknown. METHODS: A total of 581 non-demented older men in the Shanghai Aging Study were included. Blood total testosterone (TT), free testosterone (FT), and NfL were measured at baseline. The relationships between TT, FT, TT/FT-NfL, and cognitive decline were explored by Cox regression models. RESULTS: During a median follow-up of 6.7 years, there was an inverse association between TT/FT and cognitive decline (TT, trend p = 0.004, Q1 vs Q4, hazard ratio [HR] = 4.39, 95% confidence interval [CI] = 1.60 to 12.04; FT, trend p = 0.002, Q1 vs Q4, HR = 5.29, 95% CI = 1.50 to 16.89). Compared to participants with high TT/FT-low NfL, those with low TT/FT-high NfL had significantly higher risks of cognitive decline (TT, HR = 5.10, 95% CI = 1.11 to 23.40; FT, HR = 6.14, 95% CI = 1.34 to 28.06). DISCUSSION: Our findings suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive insights into future cognitive decline. HIGHLIGHTS: Testosterone is inversely associated with cognitive decline in older men. There is a joint effect of testosterone and NfL on cognitive decline. Sex hormone and neurodegeneration may synergistically contribute to cognitive deterioration.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Dynamic contrast-enhanced MR imaging in identifying active anal fistula after surgery.

BACKGROUND: It is challenging to identify residual or recurrent fistulas from the surgical region, while MR imaging is feasible. The aim was to use dynamic contrast-enhanced MR imaging (DCE-MRI) technology to distinguish between active anal fistula and postoperative healing (granulation) tissue. METHODS: Thirty-six patients following idiopathic anal fistula underwent DCE-MRI. Subjects were divided into Group I (active fistula) and Group IV (postoperative healing tissue), with the latter divided into Group II (≤ 75 days) and Group III (> 75 days) according to the 75-day interval from surgery to postoperative MRI reexamination. MRI classification and quantitative analysis were performed. Correlation between postoperative time intervals and parameters was analyzed. The difference of parameters between the four groups was analyzed, and diagnostic efficiency was tested by receiver operating characteristic curve. RESULTS: Wash-in rate (WI) and peak enhancement intensity (PEI) were significantly higher in Group I than in Group II (p = 0.003, p = 0.040), while wash-out rate (WO), time to peak (TTP), and normalized signal intensity (NSI) were opposite (p = 0.031, p = 0.007, p = 0.010). Area under curves for discriminating active fistula from healing tissue within 75 days were 0.810 in WI, 0.708 in PEI, 0.719 in WO, 0.783 in TTP, 0.779 in NSI. All MRI parameters were significantly different between Group I and Group IV, but not between Group II and Group III, and not related to time intervals. CONCLUSION: In early postoperative period, DCE-MRI can be used to identify active anal fistula in the surgical area. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033072.

Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy.

Aside from antibodies, peptides show great potential as immune checkpoint inhibitors (ICIs) due to several advantages, such as better tumor penetration and lower cost. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Here, we found that LAG-3 expression was higher than programmed cell death protein 1 (PD-1) in multiple human cancers by TCGA databases, and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning, which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II. Subsequently, d-amino acids were introduced to substitute the N- and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1, which restores T cell function in vitro and inhibits tumor growth in vivo. Further, a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1 blocking peptide OPBP-1(8-12), which activates T cell with enhanced proliferation and IFN-γ production. More importantly, LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response. In conclusion, we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function, and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.

Dual targeting of TIGIT and PD-1 with a novel small molecule for cancer immunotherapy.

Immune checkpoint inhibitors have unveiled promising clinical prospects in cancer treatment. Nonetheless, their effectiveness remains restricted, marked by consistently low response rates and affecting only a subset of patients. The co-blockade of TIGIT with PD-1 has exhibited substantial anti-tumor effects. Notably, there is a dearth of reports on small-molecule inhibitors concurrently targeting both TIGIT and PD-1. In this study, we employed Microscale Thermophoresis (MST) to screen our laboratory's existing repository of small molecules. Our findings illuminated Gln(TrT) 's affinity for both TIGIT and PD-1, affirming its potential to effectively inhibit TIGIT/PVR and PD-1/PD-L1 pathways. In vitro co-culture experiments substantiated Gln(TrT)'s proficiency in restoring Jurkat T-cell functionality by blocking both TIGIT/PVR and PD-1/PD-L1 interactions. In the MC38 murine tumor model, Gln(TrT) emerges as a pivotal modulator, promoting the intratumoral infiltration and functional competence of CD8+ T cells. Furthermore, whether used as a monotherapy or in conjunction with radiotherapy, Gln(TrT) substantially impedes MC38 tumor progression, significantly extending the survival of murine subjects.

Quality appraisal of clinical practice guidelines addressing massage interventions using the AGREE II instrument.

OBJECTIVE: The purpose of this study was to systematically evaluate the methodological quality of massage-related clinical practice guidelines (CPGs)/consensus on massage using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument and to summarize the current status of recommendations in the CPGs. METHODS: The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP), China Biology Medicine disc (CBM), PubMed, Embase, and guideline websites (such as the Chinese Medical Ace Base, the China Association of Chinese Medicine, the World Health Organization, Guideline International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network) were searched from inception to October 31, 2022. In addition, the reference lists of relevant studies were reviewed to identify domestic and overseas massage CPGs/consensus. The search terms adopted a combination of subject words and free words, mainly including traditional Chinese medicine, complementary therapies, Tuina, massage, manipulation, chiropractic/osteopathic, spinal, acupressure, guideline, and consensus. Two researchers independently completed the eligible records and extracted the data. Before the formal research, calibrations were performed twice on AGREE II, and all reviewers completed the pilot test three times until they understood and reached an agreement on the assessment items. Three researchers appraised the methodological quality of the included guidelines using the AGREE II instrument and calculated the overall intraclass correlation coefficient (ICC) of agreement. RESULTS: The evaluation results showed that among the 49 eligible CPGs/consensus, 4 (8.2%) CPGs/consensus were considered "recommended", 15 (30.6%) CPGs/consensus were considered "recommended with modifications", and 30 (61.2%) CPGs/consensus were considered "not recommended", while the consensus was considered "not recommended". Generally, the scores in the six domains of the guidelines were all higher than the consensus. Evaluation results for the overall quality of 36 CPGs showed that 4 (11%) were "good quality", 15 (42%) were "sufficient quality" and 17 (47%) were "lower quality". The AGREE II quality scores of domains ranged from 0.30 to 0.75 ([ICC = 0.993, 95% CI (0.992, 0.995)]). The domain of scope and purpose (domain 1), with a median score of 0.75 (0.52~0.91), performed best in the guidelines with AGREE II, and stakeholder involvement (domain 2) [median 0.39 (0.31~0.56)] and application (domain 5) [median 0.30 (0.17~0.47] obtained lower scores. The consensus score of domain 1 was better at 26.0 (21.6~44.8), followed by rigor of development (domain 3) with a score of 18.0 (10.0~28.9). A total of 119 massage-related recommendations were extracted from 49 guidelines/consensuses, including "in favor" (102, 85.7%), "against" (9, 7.6%), and "did not make recommendations" (8, 6.7%). CONCLUSION: The overall quality of the included guidelines was low, and most of the guidelines were not "recommended". In future guideline updates, the existing evidence should be used, the professional composition of members of the expert group should be enriched, and patients' values and preferences should be fully considered. It is necessary to clearly propose recognizable recommendations and strengthen the rigor and standardization of guideline formulation. Thus, clear standard guidelines can be formulated to better guide clinical practice.

Discovery of a novel small molecule as CD47/SIRPα and PD-1/PD-L1 dual inhibitor for cancer immunotherapy.

BACKGROUND: Targeting the tumor microenvironment (TME) has emerged as a promising strategy in cancer treatment, particularly through the utilization of immune checkpoint blockade (ICB) agents such as PD-1/PD-L1 inhibitors. Despite partial success, the presence of tumor-associated macrophages (TAMs) contributes to an immunosuppressive TME that fosters tumor progression, and diminishes the therapeutic efficacy of ICB. Blockade of the CD47/SIRPα pathway has proven to be an effective intervention, that restores macrophage phagocytosis and yields substantial antitumor effects, especially when combined with PD-1/PD-L1 blockade. Therefore, the identification of small molecules capable of simultaneously blocking CD47/SIRPα and PD-1/PD-L1 interactions has remained imperative. METHODS: SMC18, a small molecule with the capacity of targeting both SIRPα and PD-L1 was obtained using MST. The efficiency of SMC18 in interrupting CD47/SIRPα and PD-1/PD-L1 interactions was tested by the blocking assay. The function of SMC18 in enhancing the activity of macrophages and T cells was tested using phagocytosis assay and co-culture assay. The antitumor effects and mechanisms of SMC18 were investigated in the MC38-bearing mouse model. RESULTS: SMC18, a small molecule that dual-targets both SIRPα and PD-L1 protein, was identified. SMC18 effectively blocked CD47/SIRPα interaction, thereby restoring macrophage phagocytosis, and disrupted PD-1/PD-L1 interactions, thus activating Jurkat cells, as evidenced by increased secretion of IL-2. SMC18 demonstrated substantial inhibition of MC38 tumor growths through promoting the infiltration of CD8+ T and M1-type macrophages into tumor sites, while also priming the function of CD8+ T cells and macrophages. Moreover, SMC18 in combination with radiotherapy (RT) further improved the therapeutic efficacy. CONCLUSION: Our findings suggested that the small molecule compound SMC18, which dual-targets the CD47/SIRPα and PD-1/PD-L1 pathways, could be a candidate for promoting macrophage- and T-cell-mediated phagocytosis and immune responses in cancer immunotherapy.

Hemin blocks TIGIT/PVR interaction and induces ferroptosis to elicit synergistic effects of cancer immunotherapy.

The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8+ T cell-mediated cytotoxicity. Immune checkpoint blockade (ICB) could induce tumor ferroptosis through IFN-γ released by immune cells, indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor growth. However, the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored yet. In this study, the small molecule Hemin that could bind with TIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking assay. Hemin could effectively restore the IL-2 secretion from Jurkat-hTIGIT cells. Hemin reinvigorated the function of CD8+ T cells to secrete IFN-γ and the elevated IFN-γ could synergize with Hemin to induce ferroptosis in tumor cells. Hemin inhibited tumor growth by boosting CD8+ T cell immune response and inducing ferroptosis in CT26 tumor model. More importantly, Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor model. In summary, our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell ferroptosis, which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment.

Prediction model of radiotherapy outcome for Ocular Adnexal Lymphoma using informative features selected by chemometric algorithms.

BACKGROUND: Ocular Adnexal Lymphoma (OAL) is a non-Hodgkin's lymphoma that most often appears in the tissues near the eye, and radiotherapy is the currently preferred treatment. There has been a controversy regarding the prognostic factors for systemic failure of OAL radiotherapy, the thorough evaluation prior to receiving radiotherapy is highly recommended to better the patient's prognosis and minimize the likelihood of any adverse effects. PURPOSE: To investigate the risk factors that contribute to incomplete remission in OAL radiotherapy and to establish a hybrid model for predicting the radiotherapy outcomes in OAL patients. METHODS: A retrospective chart review was performed for 87 consecutive patients with OAL who received radiotherapy between Feb 2011 and August 2022 in our center. Seven image features, derived from MRI sequences, were integrated with 122 clinical features to form comprehensive patient feature sets. Chemometric algorithms were then employed to distill highly informative features from these sets. Based on these refined features, SVM and XGBoost classifiers were performed to classify the effect of radiotherapy. RESULTS: The clinical records of from 87 OAL patients (median age: 60 months, IQR: 52-68 months; 62.1% male) treated with radiotherapy were reviewed. Analysis of Lasso (AUC = 0.75, 95% CI: 0.72-0.77) and Random Forest (AUC = 0.67, 95% CI: 0.62-0.70) algorithms revealed four potential features, resulting in an intersection AUC of 0.80 (95% CI: 0.75-0.82). Logistic Regression (AUC = 0.75, 95% CI: 0.72-0.77) identified two features. Furthermore, the integration of chemometric methods such as CARS (AUC = 0.66, 95% CI: 0.62-0.72), UVE (AUC = 0.71, 95% CI: 0.66-0.75), and GA (AUC = 0.65, 95% CI: 0.60-0.69) highlighted six features in total, with an intersection AUC of 0.82 (95% CI: 0.78-0.83). These features included enophthalmos, diplopia, tenderness, elevated ALT count, HBsAg positivity, and CD43 positivity in immunohistochemical tests. CONCLUSION: The findings suggest the effectiveness of chemometric algorithms in pinpointing OAL risk factors, and the prediction model we proposed shows promise in helping clinicians identify OAL patients likely to achieve complete remission via radiotherapy. Notably, patients with a history of exophthalmos, diplopia, tenderness, elevated ALT levels, HBsAg positivity, and CD43 positivity are less likely to attain complete remission after radiotherapy. These insights offer more targeted management strategies for OAL patients. The developed model is accessible online at: https://lzz.testop.top/.

Radiomics analysis based on single phase and different phase combinations of radiomics features from tri-phasic CT to distinguish renal oncocytoma from chromophobe renal cell carcinoma.

OBJECTIVES: To investigate different radiomics models based on single phase and the different phase combinations of radiomics features from 3D tri-phasic CT to distinguish RO from chRCC. METHODS: A total of 96 patients (30 RO and 66 chRCC) were enrolled in this study. Radiomics features were extracted from unenhanced phase (UP), corticomedullary phase (CMP), and nephrographic phase (NP) CT images. Feature selection was based on the least absolute shrinkage and selection operator regression (LASSO) method. The selected features were used to develop different radiomics models using logistic regression (LR) analysis, including model 1 (UP), model 2(CMP), model 3(NP), model 4(UP+CMP), model 5(UP+NP), model 6(CMP+NP), and model 7(UP+CMP+NP). The radiomics model demonstrating the highest discrimination performance was utilized to construct the combined model (model 8) with clinical factors. A nomogram based on the model 8 was established. To evaluate the diagnostic performance of the different models, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used. Delong's test was utilized to assess the statistical significance of the AUC improvement across the models. RESULTS: Among the seven radiomics models, model 7 exhibited the highest AUC of 0.84 (95% CI 0.69, 0.99), and model 7 demonstrated a significantly superior AUC compared to the other radiomics models (all P < 0.05). The AUC values of radiomics models based on two phases (model4, mode5, mode6) were greater than the models based on single phase (model1, mode2, mode3) (all P < 0.05). Model 3 illustrated the best performance of the three radiomics models based on single phase with an AUC of 0.76 (95% CI 0.57, 099). Model 6 illustrated the best performance of the three radiomics models based on two-phases combination with an AUC of 0.83 (0.66, 0.99). Model 8 achieved an AUC of 0.93 (95% CI 0.83, 1.00) which is higher than those all radiomics models. CONCLUSION: Radiomics models based on combination of radiomics features from UP, CMP, and NP can be a useful and promising technique to differentiate RO from chRCC. Moreover, the model combining clinical factors and radiomics features showed better classification performance to distinguish them.

Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort: The Shanghai Aging Study.

INTRODUCTION: Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community-based cohort was limited only in high-income countries. METHODS: This study included 1857 dementia-free community residents recruited in 2009-2011 and followed up in waves 2014-2016 and 2019-2023 in the Shanghai Aging Study. We intended to explore the relationships of baseline plasma ALZpath phosphorylated tau 217 (p-tau217), p-tau181, neurofilament light chain (NfL) with follow-up incident dementia, Alzheimer's disease (AD), and amyloidosis. RESULTS: Higher concentrations of plasma p-tau217, p-tau181, and NfL were correlated to higher decline speed of Mini-Mental State Examination score, and higher risk of incident dementia and AD. The p-tau217 demonstrated a significant correlation with longitudinal neocortical amyloid-beta (Aß) deposition (r = 0.57 [0.30, 0.76]) and a high accuracy differentiating Aß+ from Aß- at follow-ups (area under the receiver operating characteristic curve = 0.821 [0.703, 0.940]). DISCUSSION: Plasma p-tau217 may be an early predictive marker of AD and Aß pathology in older community-dwelling individuals.Highlights: Plasma p-tau217, p-tau181, and NfL were positively associated with long-term cognitive decline and risk of incident dementia.Plasma p-tau217 showed a better performance distinguishing Aß+ individuals from Aß- individuals at follow-ups.Plasma NfL may be a suitable predictor of general cognitive decline in older community-dwelling individuals.

Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Optimizing vestibular neuritis management with modular strategies.

Objective: This study proposes a "modular management" approach for vestibular neuritis (VN) to reduce chronicization and improve patient prognosis. The approach involves multi-factor grading and hierarchical intervention and was found to be more effective than traditional treatment strategies. Methods: This retrospective analysis compared two groups of VN patients from two medical institutions. The intervention group of 52 patients received "modular management," while the control group of 51 patients did not receive this kind of management. Analyzed the early treatment strategies, 6-month prognosis, and other indicators of the two groups of patients, compared and analyzed their overall prognosis, and identified the risk factors affecting the chronicization. Results: The modular management group had lower dizziness severity, better balance, lower anxiety, and higher video head impulse testing (v-HIT) gain after 6 months of onset. Analysis of factors related to persistent postural-perceptual dizziness (PPPD) in patients with VN showed positive correlations between the time from onset to diagnosis and PPPD, and Vertigo Symptom Scale (VSS), Dizziness Handicap Inventory (DHI), anxiety, and depression. Normalized vestibular rehabilitation was negatively correlated with PPPD, while gender, age, and early steroid use had no significant correlation. The multi-factor logistic regression model correctly classified 93.20% of the study subjects with a sensitivity of 87.50% and specificity of 94.90%. Conclusion: The proposed "modular management" scheme for VN is a comprehensive and dynamic approach that includes health education, assessment, rehabilitation, therapy, evaluation, and prevention. It can significantly improve patient prognosis and reduce chronicization by shifting from simple acute treatment to continuous management.

Efficacy of Poria cocos and Alismatis rhizoma against diet-induced hyperlipidemia in rats based on transcriptome sequencing analysis.

Hyperlipidemia, a common metabolic disease, is a risk factor for cardiovascular diseases, Poria cocos (PC) and Alismatis rhizoma (AR) serve as a potential treatment. A systematic approach based on transcriptome sequencing analysis and bioinformatics methods was developed to explore the synergistic effects of PC-AR and identify major compounds and potential targets. The phenotypic characteristics results indicated that the high dose (4.54 g/kg) of PC-AR reduced total cholesterol (TC), elevated high-density lipoprotein cholesterol (HDL-C) levels, and improved hepatocyte morphology, as assessed via hematoxylin and eosin (H&E) staining. Transcriptomic profiling processing results combined with GO enrichment analysis to identify the overlapping genes were associated with inflammatory responses. The cytokine-cytokine receptor interaction pathway was found as a potential key pathway using geneset enrichment analysis. Core enrichment targets were selected according to the PC-AR's fold change versus the model. Real-time quantitative PCR analysis validated that PC-AR significantly downregulated the expression of Cxcl10, Ccl2, Ccl4, Cd40 and Il-1ß mRNA (P < 0.05). Molecular docking analysis revealed the significant compounds of PC-AR and the potential binding patterns of the critical compounds and targets. This study provides further evidence that the therapeutic effects of PC-AR on hyperlipidemia in rats through the regulation of inflammation-related targets.

Family function and adolescent altruistic behavior: the multiple mediating effects of self-affirmation and psychological resilience.

Introduction: The current study aimed to explore the relationship between family function and adolescent altruistic behavior, as well as the mediating effects of self-affirmation and psychological resilience in this relationship. Methods: A survey was conducted on 972 high school students in Guangdong Province using the Family APGAR, GHQSense of Adequacy, Chinese version of Connor-Davidson Resilience Scale, and Altruistic Behavior Scale. Results: Results found that the score of psychological resilience of males was significantly higher than that of females, but the score of altruistic behavior was significantly lower than that of females. Family function had a positive predictive effect on altruistic behavior. Psychological resilience played a mediating role between family function and altruistic behavior. Self-affirmation and psychological resilience played chain mediating roles between family function and altruistic behavior. Discussion: This study indicated that family care is crucial for the development of adolescent altruistic behavior, and that it can promote the development of altruistic behavior through the enhancement of self-affirmation and psychological resilience.