International Journal of Medical Sciences最新文献

The pursuit of extreme longevity is a popular topic. Advanced technologies such as metabolomics and proteomics have played a crucial role in unraveling complex molecular interactions and identifying novel longevity-related biomarkers in long-lived individuals. This review summarizes key longevity-related biomarkers identified through metabolomics, including high levels of omega-3 polyunsaturated fatty acids (PUFAs), short-chain fatty acids (SCFAs) and sphingolipids, as well as low levels of tryptophan. Proteomics analyses have highlighted longevity-related proteins such as apolipoprotein E (APOE) and pleiotrophin (PTN), along with lower S-nitrosylated and higher glycosylated proteins found from post-translational modification proteomics as potential biomarkers. We discuss the molecular mechanisms that could support the above biomarkers' potential for healthy longevity, including metabolic regulation, immune homeostasis maintenance, and resistance to cellular oxidative stress. Moreover, multi-omics studies of various long-lived cohorts are encompassed, focusing on how the integration of various omics technologies has contributed to the understanding of longevity. This comprehensive review aims to provide new biological insights and pave the way for promoting health span.

Background: Climate change, with increasing temperatures, poses a health threat to patients on maintenance hemodialysis (MHD). Seasonal variations in body composition have been documented in this population. We hypothesized that climate warming could further exacerbate these effects. In this study we investigated the impact of climate warming on the body composition of MHD patients residing in subtropical Taiwan. Methods: This longitudinal observational study enrolled MHD patients in subtropical northern Taiwan. We assessed monthly blood pressure (BP), laboratory data, and body composition via bioimpedance spectroscopy over a three-year period. Generalized estimating equation (GEE) was employed to analyze the seasonal and annual variations in these parameters. Additionally, we explored associations between climatic variables and body composition parameters. Results: Forty patients completed the study. BP, laboratory values, and body composition exhibited significant seasonal variations. Compared with those in winter, participants had greater relative overhydration (OH) in spring, summer, and fall. Warmer months were associated with a higher lean tissue index (LTI) and a lower fat tissue index (FTI). Notably, summers across the study years showed a further increase in relative OH and FTI, accompanied by a decrease in LTI. While BP and most laboratory parameters remained stable throughout the study period, sodium and potassium levels displayed annual variations. GEE analysis revealed positive associations between rising ambient temperature and increased fluid overload, fat mass, and decreased muscle mass. Conclusions: Our findings demonstrate that climate warming is associated with variations in the body composition of MHD patients residing in a subtropical climate. These changes can have implications in MHD patients due to their heightened vulnerability to environmental changes. Further research is needed across diverse geographic regions to develop optimal care strategies in a warming world.

Background: This study aimed to develop a combined ultrasound (US)-pathology model to predict the axillary status more accurately after NST in breast cancer. Methods: This retrospective study included breast cancer patients who received NST at the First Affiliated Hospital of Nanjing Medical University from 2015 to 2022. Clinical, US, and pathological data were collected. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of axillary pathological complete response (pCR). The model was developed using the predictors and validated. Results: A total of 657 patients were enrolled in this study. Two multivariate logistic analyses were performed before and after the operation. The results showed that the clinical lymph nodes, ER status, HER2 status, chemotherapy response of primary tumor, hilum structure of axillary lymph nodes (ALNs) after NST, blood flow of ALNs after NST, vascular invasion, pathological size, and Miller-Payne grade (all p < 0.05) were independent predictors of axillary pCR. The US-based and combined US-pathology models were developed based on preoperative and postoperative information. The two models had an area under the receiver operating characteristic curve (AUC) of 0.821 and 0.883, respectively, which was significantly higher than that of the fine-needle aspiration model (AUC: 0.735). Conclusion: In this study, based on the US-based model, a combined model incorporating the characteristics of ALNs under US and breast pathology was developed and validated to predict axillary pCR.

Background: Intrahepatic cholangiocarcinoma (ICC), one type of highly malignant tumor, has a poor prognosis. However, the specific role of the polycystic kidney and hepatic disease 1 (PKHD1) gene in ICC has not yet been evaluated. This study aimed to investigate the potential function and mechanism of the PKHD1 gene in ICC. Methods: Quantitative real-time PCR was applied to detect the expression of PKHD1 mRNA in human ICC and adjacent normal tissues. CRISPR/Cas9 technique was used to construct PKHD1 partially knockout (PKHD1-/+) ICC cell lines. In the vitro study, the effects of PKHD1 on the malignant biological behavior of ICC cells were examined by Edu, RTCA, migration, and invasion assays. The expression levels of proteins were detected using western blotting, immunohistochemistry, and flow cytometry. Furthermore, DAPT, an antagonist of the Notch1 signaling pathway, was used in the rescue experiment in vitro. Results: Compared with normal tissues, PKHD1 mRNA expression was significantly down-regulated in human cholangiocarcinoma tissues (P<0.001). At the same time, the expressions of Notch pathway-related proteins were dramatically increased in PKHD1(-/+) ICC cells (P<0.001). Moreover, tumor proliferation, migration, and invasion were promoted in loss-of-function experiments in vitro and in vivo, which was partially reversed by DAPT. Conclusions: PKHD1 inhibits the proliferation, migration, and invasion of ICC, and the Notch pathway may be the downstream mechanism of the negative regulatory effect of PKHD1 during the progression of ICC.

Objectives: Epidemiological evidence has shown that genetics and environment are associated with the risk of hypertension. However, the specific SNP effects of a cluster of crucial genes in the RAAS system on the risk of hypertension are unclear. Methods: A case-control study was performed on the baseline participants of Environment and Chronic Disease in Rural Areas of Heilongjiang China (ECDRAHC) study. According to the inclusion and exclusion criteria, 757 subjects (428 hypertensive patients) were enrolled. A total of 32 SNP sites and related haplotypes, involved in AGT (angiotensinogen), ACE (angiotensin-converting enzyme), AGTR1, CYP11B2 (aldosterone-synthase), LDLR (low-density lipoprotein receptor), LRP5 (low-density lipoprotein receptor associated protein 5), LRP6 (low-density lipoprotein receptor associated protein 6), PPARG (peroxisome proliferator-activated receptor gamma) and ACE2 (angiotensin-converting enzyme 2) genes which exert important roles in renin-angiotensin-aldosterone system (RAAS) system were analyzed. Furthermore, a polygenic scoring model was established to assess individual risk of developing hypertension based on the comprehensive SNPs effects in genes related the RAAS system. Results: After controlling the impact of confounding factors, multivariate logistic regression analysis revealed that the distribution of AGT/rs5046, LRP6/rs12823243 and ACE2/rs2285666 was associated with susceptibility to essential hypertension. In genetic score model, the score > -0.225 had a higher risk, the OR (95%CI) was 1.229 (1.110, 1.362). Conclusions: To the best of our knowledge, this is the first time a hypertension risk scoring model on RAAS associated gene cluster has been constructed, which will provide a novel approach for prevention and control of essential hypertension.

Background and objective: The aim of this research is to investigate whether the GRIm score serves as a novel prognostic tool for predicting the survival rates among early breast cancer patients undergoing surgical treatment. Methods: This retrospective study included 313 cases of breast cancer patients hospitalized in our hospital from January 2015 to November 2015. All enrolled patients received surgery and had no metastasis. The GRIm score was based on five objective markers: (1) albumin level (<3.5 g/L = 1 point), (2) LDH level (≥245 U/L = 1 point); (3) AST-to-ALT ratio (≥1.44 = 1 point); (4) total bilirubin level (≥21 μmol/ml = 1 point); (5) NLR (≥1.51 = 1 point). The best critical value was 1.51 for NLR by ROC. Patients were categorized into two groups based on GRIm scores: low-score group (0 point) and high-score group (1 to 5 points). Kaplan-Meier method and log rank test were utilized to estimate disease free survival (DFS) and overall survival (OS). Both univariate analysis and multivariate Cox analysis were used to analyze the relationship among the enrolled parameters. Nomograms were formulated reliant on the outcomes of multivariate Cox analysis. Results: Based on the GRIm score, the cohort was divided into two groups: a low-score group with 81 cases and a high-score group with 232 cases. The mean DFS and OS were significantly prolonged in low-score group compared to high-score group (DFS: 74.39 vs. 66.20 months, χ²=8.729, P=0.0031; OS: 83.71 vs. 76.40 months, χ²=8.729, P=0.0031). According to multivariable analysis, GRIm score was notably correlated with DFS (HR: 2.789, 95% CI: 1.304-5.965, P= 0.004) and OS (HR: 3.015, 95% CI: 1.409-10.087, P=0.004). Nomograms exhibited excellent predictive performance for DFS (C-index: 0.823) and OS (C-index: 0.807). Conclusions: GRIm score serves as a predictive tool for assessing the prognosis of early breast cancer patients. Nomograms based on GRIm score show good prediction ability.

Currently, there is no consensus on the treatment protocol for ossicular chain trauma. This study aims to investigate the classification and treatment strategies for traumatic ossicular chain dislocation. We retrospectively analyzed 15 patients. Traumatic ossicular chain dislocations were categorized based on the location of trauma identified during surgery: Type I-ossicular trauma without stapediovestibular dislocation; Type II-stapediovestibular dislocation (with or without associated incus dislocation). Of the 10 patients with Type I trauma, 9 experienced head trauma, and 1 had a penetrating injury to the external auditory canal. Among these, 2 cases involved incudomalleolar dislocation, 2 cases incus dislocation, 5 cases incudostapedial dislocation, and 1 case a fracture of the anterior and posterior arches of the stapes. Seven patients exhibited conductive hearing loss, while 3 presented with mixed hearing loss. Ossiculoplasty was performed using partial ossicular replacement prostheses (PORP) in 8 patients and total ossicular replacement prostheses (TORP) in 2 patients. Postoperative air conduction thresholds significantly improved in all 10 patients. In Type II trauma, all 5 patients had a penetrating injury to the external auditory canal, resulting in varying degrees of hearing loss. Postoperatively, 3 patients experienced improvement in hearing, while 2 showed no significant change. All patients developed vertigo and tinnitus following the trauma, with vertigo resolving after surgery. Pneumolabyrinth was detected in 2 patients. We propose a novel classification system for traumatic ossicular chain dislocation. Treatment strategies should be tailored according to the specific trauma type.

Background: Breast cancer (BC) is the most common cancer among women globally and poses the leading health threat to women worldwide, with persistently high incidence rates. Mitophagy is a selective autophagy process that specifically targets mitochondria within the cell, maintaining cellular energy balance and metabolic health by identifying and degrading damaged mitochondria. Although there is an understanding of the relationship between mitophagy and cancer, the specific mechanisms remain unclear due to the complexity and diversity of mitophagy, suggesting that it could be an effective and more targeted therapeutic approach for BC. Methods: In this study, we meticulously examined the BC expression and clinical pathology data from The Cancer Genome Atlas (TCGA) to assess the expression profiles, copy number variations (CNV), and to investigate the correlation, function, and prognostic impact of 34 mitophagy-related genes (MRGs). Differentially expressed genes (DEGs) were identified based on group classification. Lasso and Cox regression were used to determine prognostic genes for constructing a nomogram. Single-cell analysis mapped the distribution of these genes in BC cells. Additionally, the association between gene-derived risk scores and factors such as immune infiltration, tumor mutational burden (TMB), cancer stem cell (CSC) index, and drug responses was studied. In vitro experiments were conducted to confirm the analyses. Results: We included 34 MRGs and subsequently generated a risk score for 7 genes, including RPLP2, PCDHGA2, PRKAA2, CLIC6, FLT3, CHI3L1, and IYD. It was found that the low-risk group had better overall survival (OS) in BC, higher immune scores, but lower tumor mutational burden (TMB) and cancer stem cell (CSC) index, as well as lower IC50 values for commonly used drugs. To enhance clinical applicability, age and staging were incorporated into the risk score, and a more comprehensive nomogram was constructed to predict OS. This nomogram was validated and showed good predictive performance, with area under the curve (AUC) values for 1-year, 3-year, and 5-year OS of 0.895, 0.765, and 0.728, respectively. Conclusion: Our findings underscore the profound impact of prognostic genes on the immune response and prognostic outcomes in BC, indicating that they can provide new avenues for personalized BC treatment and potentially improve clinical outcomes.

Background: Alterations in circulating CCL4 levels have been implicated in coronary artery disease (CAD), but the causal relationship and underlying mechanisms remain unclear. Objective: This study aims to analyse the role of CCL4 and its receptor (CCR5) in CAD using Mendelian randomisation (MR) analysis, bulk RNA and single cell RNA sequencing (scRNA-seq). Methods: The MR analysis was used to determine the causal relationship between 91 circulating inflammatory proteins and CAD. Bulk RNA sequencing data was used to demonstrate the expression profile of CCL4/CCR5. The localisation of CCL4/CCR5 was determined using scRNA-seq data. Functional enrichment analyses were used to infer the potential role of CCL4 in CAD. Additional clinical samples were utilized to validate the results of MR. Results: We identified six circulating inflammatory proteins associated with CAD. Of these, CCL4 was identified as a key inflammatory cytokine associated with CAD risk for MR analysis.The bulk RNA sequencing data from the Gene Expression Omnibus (GEO) datasets showed that CCR4 receptor(CCR5) expression was significantly higher in human atherosclerotic plaques compared to controls. Notably, scRNA-seq analysis revealed CCL4 was highly expressed in T cells, monocytes and macrophages. Clinical specimens confirmed high levels of serum CCL4 expression in CAD patients by ELISA.Functional enrichment analysis revealed that CCL4 was primarily enriched in the cytokines and cytokine receptors, viral proteins with cytokines and cytokine receptors, and chemokine signaling pathways. Conclusion: Our study presented a genetic insight into the pathogenetic role of CCL4-CCR5 in CAD, which may provide new insights for further mechanistic and clinical investigations of inflammatory cytokine-mediated CAD.

Purpose: This study aimed to assess subperiosteal implants concerning bone stress and screw displacement, utilizing finite element analysis to determine the optimal screw diameter for enhanced bone support. Methods: Computed tomography data were translated into STL format, generating two skull models. Subperiosteal implants were constructed on these models and placed accordingly. Employing the finite element analysis method, screws with 1.5 mm and 2 mm diameter were inserted into one of the models to evaluate their impact under a 250 N chewing force. Results: The 2 mm screw demonstrated superior performance compared to the 1.5 mm variant, showcasing reduced residual stress on the bone and implant. However, the 1.5 mm screw exhibited less implant movement. Conclusion: The finite element analysis suggests the 2 mm screw diameter as more advantageous over the 1.5 mm variant for subperiosteal implants. Nevertheless, this investigation marks the initial stages in exploring this treatment option's potential.