WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical ß-catenin pathway.

BACKGROUND: 5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection. METHODS: 5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy. RESULTS: In this study, the WNT/ß-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells. CONCLUSIONS: These data underscored the activation of the WNT/ß-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.

Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality.

Importance: Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective: To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants: This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures: PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures: All-cause mortality, cancer mortality, and cardiovascular mortality. Results: This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance: In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Investigating diagnostic potential of long non-coding RNAs in head and neck squamous cell carcinoma using TCGA database and clinical specimens.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and prognostically challenging cancer worldwide. The role of long non-coding RNAs (lncRNAs) in cancer regulation is progressively being understood. This study aims to identify lncRNAs with diagnostic potential as biomarkers for HNSCC. Statistical analysis was performed on expression data from the Cancer Genome Atlas (TCGA) database to identify potential lncRNAs associated with HNSCC. Four selected lncRNAs were validated using real-time quantitative reverse transcription polymerase chain reaction and correlated with clinical factors. Functional roles were further investigated. A total of 488 differentially expressed lncRNAs were identified in TCGA-HNSC. After rigorous evaluation based on p-values, survival analysis, and ROC analysis, 24 lncRNAs were prioritized for additional investigation. LINC00460, LINC00941, CTC-241F20.4, and RP11-357H14.17 were established as candidate diagnostic biomarkers. These lncRNAs exhibited elevated expression in HNSCC tissues and were associated with poor prognosis. Combining them showed high diagnostic accuracy. Notably, LINC00460 and CTC-241F20.4 demonstrated a significant elevation in the advanced stages of HNSCC. We constructed an lncRNA-mRNA regulatory network, and the array of significant regulatory pathways identified included focal adhesion, regulation of epithelial cell migration, and others. Additionally, these lncRNAs were found to influence immune responses by modulating immune cell infiltration in the HNSCC microenvironment. Our research indicates that LINC00460, LINC00941, RP11-357H14.17, and CTC-241F20.4 may have diagnostic and prognostic importance in HNSCC. Furthermore, we have gained insights into their potential functional roles, particularly about immune responses and interactions in the microenvironment.

Proteomics in Cardiovascular disease.

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD.

Identification of circular RNA hsa_circ_0034621 as a novel biomarker for carotid atherosclerosis and the potential function as a regulator of NLRP3 inflammasome.

BACKGROUND AND AIMS: NLRP3 inflammasome plays a key role in vascular inflammation and atherosclerosis. Circular RNAs (circRNAs) are involved in disease development by regulating gene expression, and have emerged as promising novel disease biomarkers. This study aimed to identify the NLRP3 inflammasome-associated circRNA biomarkers of carotid atherosclerosis. METHODS: Based on the differential expression profiles of circRNAs in patients with carotid artery plaque (CAP) and healthy controls, hsa_circ_0043621, hsa_circ_0051995, and hsa_circ_0123388 were screened and validated using real-time quantitative polymerase chain reaction (RT-qPCR). Potential circRNA-miRNA-mRNA interactions were explored using a luciferase assay. The biological roles of the validated circRNAs were investigated in human umbilical vein endothelial cells (HUVECs) using Western blotting, transwell, and CCK-8 assays. Clinical significance was assessed using receiver operating characteristic (ROC) curves and logistic regression analysis. RESULTS: The expression levels of all candidate circRNAs were significantly higher in patients with CAP than in controls (p<0.05), which was consistent with the results of the microarray analysis. Overexpression of hsa_circ_0043621 significantly increased the expression of NLRP3, induced migration of HUVECs, and inhibited cell proliferation. hsa_circ_0043621 demonstrated reasonable diagnostic accuracy for CAP detection and increased intima-media thickness (IMT). hsa_circ_0043621 upregulation was an independent predictor of an increased risk of CAP and increased IMT. CONCLUSIONS: hsa_circ_0043621 is a valuable circulating biomarker of carotid atherosclerosis and may contribute to its pathogenesis by regulating the NLRP3 inflammasome.

MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.

The p53 tumor suppressor protein plays an important role in physiological and pathological processes. MDM2 and its homolog MDMX are the most important negative regulators of p53. Many studies have shown that MDMX promotes the growth of cancer cells by influencing the regulation of the downstream target gene of tumor suppressor p53. Studies have found that inhibiting the MDMX-p53 interaction can effectively restore the tumor suppressor activity of p53. MDMX has growth-promoting activities without p53 or in the presence of mutant p53. Therefore, it is extremely important to study the function of MDMX in tumorigenesis, progression and prognosis. This article mainly reviews the current research progress and mechanism on MDMX function, summarizes known MDMX inhibitors and provides new ideas for the development of more specific and effective MDMX inhibitors for cancer treatment.

Bisphenol S, bisphenol F, bisphenol a exposure and body composition in US adults.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS， and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the ß (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (ß [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (ß[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (ß [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (ß [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (ß [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (ß [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (ß [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.

EEG-based major depressive disorder recognition by neural oscillation and asymmetry.

Background: Major Depressive Disorder (MDD) is a pervasive mental health issue with significant diagnostic challenges. Electroencephalography (EEG) offers a non-invasive window into the neural dynamics associated with MDD, yet the diagnostic efficacy is contingent upon the appropriate selection of EEG features and brain regions. Methods: In this study, resting-state EEG signals from both eyes-closed and eyes-open conditions were analyzed. We examined band power across various brain regions, assessed the asymmetry of band power between the hemispheres, and integrated these features with clinical characteristics of MDD into a diagnostic regression model. Results: Regression analysis found significant predictors of MDD to be beta2 (16-24 Hz) power in the Prefrontal Cortex (PFC) with eyes open (B = 20.092, p = 0.011), beta3 (24-40 Hz) power in the Medial Occipital Cortex (MOC) (B = -12.050, p < 0.001), and beta2 power in the Right Medial Frontal Cortex (RMFC) with eyes closed (B = 24.227, p < 0.001). Asymmetries in beta1 (12-16 Hz) power with eyes open (B = 28.047, p = 0.018), and in alpha (8-12 Hz, B = 9.004, p = 0.013) and theta (4-8 Hz, B = -13.582, p = 0.008) with eyes closed were also significant predictors. Conclusion: The study confirms the potential of multi-region EEG analysis in improving the diagnostic precision for MDD. By including both neurophysiological and clinical data, we present a more robust approach to understanding and identifying this complex disorder. Limitations: The research is limited by the sample size and the inherent variability in EEG signal interpretation. Future studies with larger cohorts and advanced analytical techniques are warranted to validate and refine these findings.

The role of m6A modification in type 2 diabetes: A systematic review and integrative analysis.

This study focuses on the latest developments in the studies of m6A modification and provides an up-to-date summary of the association between m6A modification and type 2 diabetes (T2D). The possible mechanisms of m6A related to T2D were summarized by literature review. The differentially expressed genes (DEGs) of m6A methylase in T2D were analyzed from 12 datasets in Gene Expression Omnibus (GEO). The associations between m6A level and T2D were explored in four electronic databases, including PubMed, EmBase, Web of Science and CNKI. Standard mean difference (SMD) and 95 % confidence interval (95 %CI) was calculated to assess the total effect in integrative analysis. Differential expression genes detected in at least three of six tissues were ZC3H13, YTHDC1/2, and IGF2BP2. LRPPRC were differentially expressed in five tissues except in arterial tissue. A total of 6 studies were included for integrative analysis. The mean m6A levels were significantly lower in T2D than those in normal controls (SMD = -1.35, 95 %CI: -2.58 to -0.11). This systematic review and integrative analysis summarize the previous studies on the association between m6A modification and T2D and the possible role of m6A modification in the progression of T2D, such as abnormal blood glucose, abnormal pancreatic ß-cell function, insulin resistance, and abnormal lipid metabolism. The integrative analysis showed that decreased level of m6A was associated with T2D. These findings provide new targets for early detection and treatment for T2D.

Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Association of household solid fuel use and long-term exposure to ambient air pollution with estimated 10-year high cardiovascular disease risk among postmenopausal women.

This study aimed to explore the separate and joint effects of long-term ambient air pollution and household air pollution exposure on 10-year high cardiovascular disease (CVD) risk among postmenopausal women. A total of 4679 postmenopausal women from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. Information of fuel type was collected by standard questionnaires and use of solid fuel was considered as a proxy for household air pollution. Data of ambient air pollutants (PM1, PM2.5, PM10, SO2, NO2, CO, O3) were obtained from the ChinaHighAirPollutants (CHAP) datasets. Logistic regression models were performed to assess the separate and joint effects of long-term exposure to ambient air pollution and use of solid fuel on 10-year high CVD risk. We found use of solid fuel and its duration and ambient air pollutants (PM1, PM2.5, PM10, SO2, NO2) were all positively associated with 10-year high CVD risk among postmenopausal women (P < 0.05). Compared to those used clean fuel and exposed to low ambient air pollution levels, odds ratios (ORs) and 95% confidence intervals (CIs) for participants using solid fuels and exposed to high ambient air pollution levels (PM1, PM2.5, PM10, SO2, NO2, CO, O3) were 1.66 (1.35, 2.05), 1.66 (1.35, 2.04), 1.49 (1.22, 1.83), 1.28 (1.05, 1.57), 1.67 (1.34, 2.07), 1.28 (1.04, 1.57), 1.46 (1.18, 1.80), respectively. Moreover, significant additive interactions of solid fuel use with PM1 and PM2.5 on 10-year high CVD risk were observed, with approximately 18% and 23% of 10-year high risk of CVD attributable to the interaction. Overall, indoor and outdoor air pollution had separate and joint effects on 10-year high CVD risk among postmenopausal women. Therefore, simultaneously improving indoor and outdoor air quality are of great importance and could have a joint impact on prevention of CVD and improved health among postmenopausal women.

Single-cell RNA sequencing to explore cancer-associated fibroblasts heterogeneity: "Single" vision for "heterogeneous" environment.

Cancer-associated fibroblasts (CAFs), a phenotypically and functionally heterogeneous stromal cell, are one of the most important components of the tumour microenvironment. Previous studies have consolidated it as a promising target against cancer. However, variable therapeutic efficacy-both protumor and antitumor effects have been observed not least owing to the strong heterogeneity of CAFs. Over the past 10 years, advances in single-cell RNA sequencing (scRNA-seq) technologies had a dramatic effect on biomedical research, enabling the analysis of single cell transcriptomes with unprecedented resolution and throughput. Specifically, scRNA-seq facilitates our understanding of the complexity and heterogeneity of diverse CAF subtypes. In this review, we discuss the up-to-date knowledge about CAF heterogeneity with a focus on scRNA-seq perspective to investigate the emerging strategies for integrating multimodal single-cell platforms. Furthermore, we summarized the clinical application of scRNA-seq on CAF research. We believe that the comprehensive understanding of the heterogeneity of CAFs form different visions will generate innovative solutions to cancer therapy and achieve clinical applications.

Association of phenotypic frailty and frailty index with type 2 diabetes and dyslipidemia in middle-aged and elderly Chinese: A longitudinal cohort study.

PURPOSE: Frailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI). MATERIALS AND METHODS: Multivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia. RESULTS: 10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05). CONCLUSION: Frailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator.

Development and validation of a short-form suboptimal health status questionnaire.

Background: Suboptimal health status (SHS) is a reversible, borderline state between optimal health and disease. Although this condition's definition is widely understood, related questionnaires must be developed to identify individuals with SHS in various populations relative to predictive, preventive, and personalized medicine (PPPM/3PM). This study presents a short-form suboptimal health status questionnaire (SHSQ-SF) that appears to possess sufficient reliability and validity to assess SHS in large-scale populations. Methods: A total of 6183 participants enrolled from Southern China constituted a training set, while 4113 participants from Northern China constituted an external validation set. The SHSQ-SF includes nine key items from the Suboptimal Health Status Questionnaire-25 (SHSQ-25), an instrument that has been applied to Africans, Asians, and Caucasians. Item analysis and reliability and validity tests were carried out to validate the SHSQ-SF. The receiver operating characteristic (ROC) curve was used to identify an optimal cutoff value for SHS diagnosis, by which the area under the curve (AUC) and 95% confidence interval (CI) were determined. Results: Cronbach's α coefficient for the training dataset was 0.902; the split-half reliability was 0.863. The Kaiser-Meyer-Olkin (KMO) value was 0.880, and Bartlett's test of sphericity was significant (χ2 = 32,929.680, p < 0.05). Both Kaiser's criteria (eigenvalues > 1) and the scree plot revealed one factor explaining 57.008% of the total variance. Standardized factor loadings for the confirmatory factor analysis (CFA) indices ranged between 0.58 and 0.74, with χ2/dƒ = 4.972, GFI = 0.996, CFI = 0.996, RFI = 0.989, and RMSEA = 0.031. The AUC was equal to 0.985 (95% CI: 0.983-0.988) for the training dataset. A cutoff value (≥ 11) was then identified for SHS diagnosis. The SHSQ-SF showed good discriminatory power for the external validation dataset (AUC = 0.975, 95% CI: 0.971-0.979) with a sensitivity of 96.2% and a specificity of 87.4%. Conclusions: We developed a short form of the SHS questionnaire that demonstrated sound reliability and validity when assessing SHS in Chinese residents. From a PPPM/3PM perspective, the SHSQ-SF is recommended for the rapid screening of individuals with SHS in large-scale populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00339-z.

Validity and reliability of the Persian version of the Suboptimal Health Status Questionnaire among university staff in Iran.

Background: Suboptimal Health Status Questionnaire-25 (SHSQ-25) is an established tool for measuring a precision health state between health and illness. The present study aims to assess the validity and reliability of a Persian version of SHSQ-25 (P-SHSQ-25) in a university staff Iranian population. Methods: A sample of 316 academic and supporting staff (163 males, age range from 23 to 64 years old) from Hamadan University of Medical Sciences, Hamadan, Iran was recruited in this population-based cross-sectional study with a questionnaire validation from Apri1 to October 2022. Forward-backward translation method was performed for the SHSQ-25 translation from English to Persian. Internal reliability, content, convergence, discriminative and construct validity of the P-SHSQ-25 were examined. The factorial structure of the P-SHSQ-25 across groups was examined using measurement invariant test. Results: In the translation process, the conceptual equivalence of the P-SHSQ-25 with the English version was confirmed. The item-content validity index and content validity ratio of all P-SHSQ-25 items were higher than the cut-off values of 0.70 and 0.62, respectively. Cronbach's α was higher than 0.70 for all P-SHSQ-25 domains. The confirmatory factor analysis (CFA) showed the fitness of five factors on the data set (comparative fit index = 0.88, and root mean square error of approximation = 0.07). The CFA model fit did not change substantially across sex, age, occupation, economic status, and body mass index (Δ comparative fit index (CFI)<0.01). Conclusions: The P-SHSQ-25 can be used as a reliable and valid tool to measure health status for screening pre-chronic disease conditions in a primary care setting among Iranian population.

Association of acute kidney injury with the risk of cognitive impairment or dementia: a systematic review and meta-analysis.

PURPOSE: Since previous studies have shown a paradoxical relationship between acute kidney injury (AKI) and risk of cognitive impairment, there is an urgent need for a meta-analysis to assess the relationship between AKI and risk of cognitive impairment or dementia. MATERIALS AND METHODS: From database inception to October 2023, we searched PubMed, OVID (Medline), Embase, Web of Science, and Cochrane Library. This study examined AKI and cognitive impairment or dementia observational studies. Two authors independently assessed cohort and cross-sectional study quality using the Newcastle-Ottawa Scale and AHRQ Scale. They also used ROBINS-I to assess bias. The meta-analysis used fixed effects. Sensitivity analysis verified results stability. The funnel plot, Egger test, and Begg test determined publication bias in the results. RESULTS: Seven studies with 423,876 patients were included in the meta-analysis. Patients with AKI were at higher risk of cognitive impairment or dementia compared to those who had not experienced AKI (OR = 1.87, 95% confidence interval [CI]: 1.77-1.98, I2=46.0%, p = 0.08). All subgroups showed a substantial connection between AKI and cognitive impairment. Compared to domestic research, the connection was stronger in overseas studies (OR = 2.18, 95% CI: 1.66-2.87). Both cognitive impairment and dementia outcomes showed a substantial connection between AKI and cognitive impairment, with OR values of 2.00 (95% CI: 1.44-2.76) and 2.04 (95% CI: 1.66-2.51). CONCLUSIONS: We found that AKI significantly increases cognitive impairment or dementia risk. Thus, early interventions to delay cognitive impairment and prevent adverse outcomes in AKI patients are needed.

Engineered Plant-Derived Nanovesicles Facilitate Tumor Therapy: Natural Bioactivity Plus Drug Controlled Release Platform.

Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.

Association between hypertriglyceridemic-waist phenotype and circadian syndrome risk: a longitudinal cohort study.

Recently, circadian syndrome (CircS) has been proposed as a new predictor of cardiometabolic risk. We aimed to investigate the relationship between the hypertriglyceridemic-waist phenotype and its dynamic status with CircS in China. We conducted a two-stage study based on the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. Multivariate logistic regression models in cross-sectional analysis and Cox proportional hazards regression models in longitudinal analysis were used to estimate the associations of hypertriglyceridemic-waist phenotypes with CircS and its components. We then applied multiple logistic regression analysis to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) for CircS risk by transformation into the hypertriglyceridemic-waist phenotype. A total of 9863 participants were included in the cross-sectional analysis and 3884 participants in the longitudinal analysis. Compared with normal waist circumference (WC) and normal triglyceride (TG) level (NWNT), CircS risk was increased with enlarged WC and high TG level (EWHT) (hazard ratio (HR) 3.87 [95% CI: 2.38, 5.39]). Similar results were observed in subgroup analyses by sex, age, smoking status, and drinking status. During follow-up, CircS risk was increased in group K (stable EWNT during follow-up) (OR 9.97 [95% CI: 6.41, 15.49]) compared with group A (stable NWNT during follow-up), while group L (baseline enlarged WC and normal TG level transformed to follow-up EWHT) had the highest risk of CircS (OR 116.07 [95% CI: 72.77, 185.14]). In conclusion, the hypertriglyceridemic-waist phenotype and its dynamic status were associated with the risk of developing CircS in Chinese adults.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort.

BACKGROUND: To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. METHODS: Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. RESULTS: During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1-2, 3, 4-5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. CONCLUSIONS: High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.