Lower serum creatinine to cystatin C ratio associated with increased incidence of frailty in community-dwelling elderly men but not in elderly women.

BACKGROUND: Sarcopenia has been reported to play an important role in frailty syndrome. The serum creatinine/serum cystatin C ratio (Scr/Cys C ratio) has recently been recognized as a valuable indicator for assessing sarcopenia. However, few studies have examined the association between serum creatinine/serum cystatin C ratio and frailty. The objective of this study is to investigate the relationship between the serum creatinine/serum cystatin C ratio and frailty among older adults residing in the community. METHODS AND MATERIALS: A Total of 1926 community-dwelling older adults aged ≥ 60 years in the 2011 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The participants' frailty status was determined using a 39 item frailty index (FI), which classified individuals as "robust" (FI ≤ 0.1), "pre-frailty" (0.1 < FI < 0.25), or "frailty" (FI ≥ 0.25). The Scr/Cys C ratio was determined by dividing the serum creatinine level (mg/dL) by the cystatin C level (mg/L). The one-way analysis of variance(ANOVA) and Chi-squared test (χ2)were applied to compare the differences between the 3 groups. Both linear regression and logistic regression models were used to further investigate the relationship between Scr/Cys C ratio and frailty. RESULTS: After adjusting for potential confounding factors, the study revealed that participants in the Q1 quartile of Scr/Cys C ratio had increased odds of frailty (Q1vs.Q4: OR = 1.880, 95% CI 1.126-3.139, p = 0.016) compared with those in the Q4 quartile group. In fully adjusted logistic regression models, male participants in the Q2 quartile of Scr/Cys C ratio were significantly correlated with higher odds of pre-frailty (Q2 vs.Q4: OR = 1.693, 95%CI 1.040-2.758, p = 0.034). However, this correlation was not observed in females (OR = 0.984, 95% CI 0.589-1.642, p = 0.950,). Additionally, the study observed an increase in both the frailty index and the incidence of frailty as age increased in both males and females. CONCLUSION: Among community-dwelling older adults, lower Serum creatinine to cystatin C ratio were found to be associated with increased odds of frailty prevalence in males.

Methodological Validation of Sedimentation Velocity Analytical Ultracentrifugation Method for Adeno-Associated Virus and Collaborative Calibration of System Suitability Substance.

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and high sedimentation coefficient substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF (high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the relative standard deviation (RSD) could be within 5%. Even for empty or partially less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4 × 1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235 nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Because of the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control) laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.

Development and validation of an interpretable radiomic signature for preoperative estimation of tumor mutational burden in lung adenocarcinoma.

Background: Tumor mutational burden (TMB) is a promising biomarker for immunotherapy. The challenge of spatial and temporal heterogeneity and high costs weaken its power in clinical routine. The aim of this study is to estimate TMB preoperatively using a volumetric CT-based radiomic signature (rMB). Methods: Seventy-one patients with resectable lung adenocarcinoma (LUAD) who underwent whole-exome sequencing (WXS) from 2011 to 2014 were enrolled from the institutional biobank of Tianjin Medical University Cancer Institute and Hospital (TMUCIH). Forty-nine LUAD patients with WXS from the Cancer Genome Atlas Program (TCGA) served as the external validation cohort. Computed tomography (CT) volumes were resampled to 1-mm isotropic, semi-automatically segmented, and manually adjusted by two radiologists. A total of 3,108 radiomic features were extracted via PyRadiomics and then harmonized across cohorts by ComBat. Features with inter-segmentation intra-class correlation coefficient (ICC) > 0.8, low collinearity, and significant univariate power were passed to the least absolute shrinkage and selection operator (LASSO)-logistic classifier to discriminate TMB-high/TMB-low at a threshold of 10 mut/Mb. The receiver operating characteristic (ROC) curve analysis and calibration curve were used to determine its efficiency. Shapley values (SHAP) attributed individual predictions to feature contributions. Clinical variables and circulating biomarkers were collected to find potential associations with TMB and rMB. Results: The top frequently mutated genes significantly differed between the Chinese and TCGA cohorts, with a median TMB of 2.20 and 3.46 mut/Mb and 15 (21.12%) and 9 (18.37%) cases of TMB-high, respectively. After dimensionality reduction, rMB comprised 21 features, which reached an AUC of 0.895 (sensitivity = 0.867, specificity = 0.875, and accuracy = 0.873) in the discovery cohort and 0.878 (sensitivity = 1.0, specificity = 0.825, and accuracy = 0.857 in a consist cutoff) in the validation cohort. rMB of TMB-high patients was significantly higher than rMB of TMB-low patients in both cohorts (p < 0.01). rMB was well-calibrated in the discovery cohort and validation cohort (p = 0.27 and 0.74, respectively). The square-filtered gray-level concurrence matrix (GLCM) correlation was of significant importance in prediction. The proportion of circulating monocytes and the monocyte-to-lymphocyte ratio were associated with TMB, whereas the circulating neutrophils and lymphocyte percentage, original and derived neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were associated with rMB. Conclusion: rMB, an intra-tumor radiomic signature, could predict lung adenocarcinoma patients with higher TMB. Insights from the Shapley values may enhance persuasiveness of the purposed signature for further clinical application. rMB could become a promising tool to triage patients who might benefit from a next-generation sequencing test.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Survival outcome and prognostic factors for early-onset and late-onset metastatic colorectal cancer: a population based study from SEER database.

Colorectal cancer is the third most common cancer worldwide and there has been a concerning increase in the incidence rate of colorectal cancer among individuals under the age of 50. This study compared the survival outcome between early-onset and late-onset metastatic colorectal cancer to find the differences and identify their prognostic factors. We obtained patient data from SEER database. Survival outcome was estimated using Kaplan-Meier survival curves and compared using the log-rank test. Univariate and multivariate analyses were conducted utilizing COX models to identify their independent prognostic factors. A total of 10,036 early-onset metastatic colorectal (EOCRC) cancer patients and 56,225 late-onset metastatic colorectal cancer (LOCRC) patients between 2010 and 2019 were included in this study. EOCRC has more survival benefits than LOCRC. Tumor primary location (p < 0.001), the location of metastasis (p < 0.001) and treatment modalities (p < 0.001) affect the survival outcomes between these two groups of patients. Female patients had better survival outcomes in EOCRC group (p < 0.001), but no difference was found in LOCRC group (p = 0.57). In conclusion, our study demonstrated that EOCRC patients have longer survival time than LOCRC patients. The sex differences in survival of metastatic colorectal cancer patients are associated with patients' age. These findings contribute to a better understanding of the differences between metastatic EOCRC and LOCRC, and can help inform the development of more precise treatment guidelines to improve prognosis.

Survival benefits of palliative gastrectomy for gastric cancer patients with liver metastasis: a population-based propensity score-matched cohort analysis.

Background and aims: Palliative primary tumor resection (pPTR) can benefit colorectal cancer patients with liver metastasis. Whether pPTR benefiting gastric cancer (GC) patients with liver metastasis is still controversial. Methods: Data on patients with metastatic GC diagnosed between 2010 to 2019 was extracted from SEER database. Propensity score analysis with 1:1 matching was performed. The univariable and multivariable Cox proportional hazards regression models were used to explore prognostic factors. Kaplan-Meier method was used to analyze survival outcomes. Results: Of 5691 GC patients with liver metastasis, 468 were included in the matched cohorts. The results showed that the median survival time was 6 months in the non-surgery groups and 14.5 months in the surgery groups (p < 0.001). Multivariable analysis showed that surgery was a protective prognostic factor for overall survival [hazard ratio (HR) = 0.416] as well as cancer-specific survival (HR = 0.417). Also, pPTR was only recommended for GC patients with isolated liver metastasis. Moreover, pPTR combined with chemotherapy brought the greatest therapeutic effect. Conclusion: pPTR benefits GC patients with isolated liver metastasis, and GC patients with liver metastasis receiving pPTR combined with chemotherapy had the best survival outcomes than any other therapeutic model.

Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus.

IMPORTANCE: Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs and vaccines against alphaviruses are few available, but several host antiviral factors have been reported. Here, we used GETV as a model of alphaviruses to screen for additional host factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified to inhibit GETV replication by inducing ubiquitination of the glycoprotein E2, causing its degradation by recruiting the E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using GETV as a model virus, focusing on the relationship between viral structural proteins and host factors to screen antiviral host factors provides new insights for antiviral studies on alphaviruses.

Clinicopathological and genetic characteristics of gastric neuroendocrine tumour (NET) G3 and comparisons with neuroendocrine carcinoma and NET G2.

AIMS: To characterise the clinicopathological and genetic characteristics of gastric neuroendocrine tumour G3 (gNET G3) and to compare them with those of gastric neuroendocrine carcinoma (gNEC) and gNET G2. METHODS AND RESULTS: A total of 115 gastric neuroendocrine neoplasms (NENs) were included, of which gNET G3 was different from gNET G1/G2 in terms of tumour location (P = 0.029), number (P = 0.003), size (P = 0.010), the Ki67 index (P < 0.001), lymph node metastasis (P < 0.001) and TNM stage (P = 0.011), and different from gNEC/gastric mixed neuroendocrine-non-neuroendocrine neoplasm (gMiNEN) in terms of tumour size (P = 0.010) and the Ki67 index (P = 0.001). High-resolution copy number (CN) profiling and validation experiments showed CN gains and high expression of DLL3 in gNET G3. Hierarchical clustering analysis based on CN characteristics showed that gNET G3 was separated from gNEC but mixed with gNET G2. In gene set enrichment analysis, eight pathways were significantly enriched in gNEC when comparing gNET G3 and gNEC (P < 0.05), while no pathways were enriched when comparing gNET G3 and gNET G2. Whole-exome sequencing and validation experiments showed nonsense mutation of TP53 in one gNET G3, with wild-type staining for p53. In gNEC, TP53 mutations were detected in four of eight cases, and abnormal expression of p53 was detected in all cases. CONCLUSION: Gastric NET G3 is a distinct entity with unique genetic characteristics, which are different from those of gNEC than gNET G2. Our results provide insight into some molecular alterations that may contribute to the development and progression of gNET G3 and serve as potential therapeutic targets.

Meta-analysis of the correlation between CT-based features and invasive properties of pure ground-glass nodules.

Several studies have revealed that computed tomography (CT) features can make a distinction in the invasive properties of pure ground-glass nodules (pGGNs). However, imaging parameters related to the invasive properties of pGGNs are unclear. This meta-analysis was designed to decipher the correlation between the invasiveness of pGGNs and CT-based features, and ultimately to be conducive to making rational clinical decisions. We searched a series of databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, wanfang, CNKI, VIP, as well as CBM databases, until September 20, 2022, for the eligible publications only in Chinese or English. This meta-analysis was implemented with the Stata 16.0 software. Ultimately, 17 studies published between 2017 and 2022 were included. According to the meta-analysis, we observed a larger maximum size of lesions in invasive adenocarcinoma (IAC) versus that in preinvasive lesions (PIL) [SMD = 1.37, 95% CI (1.07-1.68), P < 0.05]. Meanwhile, there were also increased mean CT values of IAC [SMD = 0.71, 95% CI (0.35, 1.07), P < 0.05], the incidence of pleural traction sign [OR = 1.94, 95% CI (1.24, 3.03), P < 0.05], the incidence of IAC spiculation [OR = 1.55, 95% CI (1.05, 2.29), P < 0.05] in comparison to those of PIL. Nevertheless, IAC and PIL exhibited no significant differences in vacuole sign, air bronchogram, regular shape, lobulation and vascular convergence sign (all P > 0.05). Therefore, IAC and PIL manifested different CT features of pGGNs. The maximum diameter of lesions, mean CT value, pleural traction sign and spiculation are important indicators to distinguish IAC and PIL. Reasonable use of these features can be helpful to the treatment of pGGNs.

Generative pretraining from large-scale transcriptomes for single-cell deciphering.

Exponential accumulation of single-cell transcriptomes poses great challenge for efficient assimilation. Here, we present an approach entitled generative pretraining from transcriptomes (tGPT) for learning feature representation of transcriptomes. tGPT is conceptually simple in that it autoregressive models the ranking of a gene in the context of its preceding neighbors. We developed tGPT with 22.3 million single-cell transcriptomes and used four single-cell datasets to evalutate its performance on single-cell analysis tasks. In addition, we examine its applications on bulk tissues. The single-cell clusters and cell lineage trajectories derived from tGPT are highly aligned with known cell labels and states. The feature patterns of tumor bulk tissues learned by tGPT are associated with a wide range of genomic alteration events, prognosis, and treatment outcome of immunotherapy. tGPT represents a new analytical paradigm for integrating and deciphering massive amounts of transcriptome data and it will facilitate the interpretation and clinical translation of single-cell transcriptomes.

LINC00886 Negatively Regulates Malignancy in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. This study aimed to identify specific long noncoding RNAs (lncRNAs) associated with ATC, and further investigated their biological functions and molecular mechanism underlying regulation of malignancy in ATC. We searched for lncRNAs associated with dedifferentiation and screened out specific lncRNAs significantly deregulated in ATC by using transcriptome data of dedifferentiation cancers from Fudan University Shanghai Cancer Center (FUSCC) and the Gene Expression Omnibus (GEO) database. The above lncRNAs were analyzed to identify a potential biomarker in thyroid cancer patients from the FUSCC, GEO, and The Cancer Genome Atlas, which was then investigated for its functional roles and molecular mechanism in ATC in vitro. The clinicopathological association analyses revealed that LINC00886 expression was significantly correlated with dedifferentiation and suppressed in ATC. In vitro, LINC00886 was confirmed to negatively regulate cell proliferation, and cell migration and invasion of ATC. LINC00886 physically interacted with protein kinase R (PKR) and affected its stability through the ubiquitin/proteasome-dependent degradation pathway in the ATC cell. Decreased PKR caused by downregulation of LINC00886 enhanced the activity of eukaryotic initiation factor 2α (eIF2α) via reducing phosphorylation of eIF2α and thus promoted protein synthesis to maintain ATC malignancy. Our findings identify LINC00886 as a novel biomarker of thyroid cancer and suggest that LINC00886/PKR/eIF2α signaling is a potential therapeutic target in ATC.

Targeting Tumor Hypoxia Inhibits Aggressive Phenotype of Dedifferentiated Thyroid Cancer.

CONTEXT: Hypoxia is commonly observed in multiple aggressive cancers. Its role remains unclear in the biology and therapy of dedifferentiated thyroid cancer (DDTC). OBJECTIVE: We aimed to elucidate hypoxia's roles in DDTC tumor biology. METHODS: We discovered and confirmed hypoxia's correlation with dedifferentiation status, poor prognoses, and immune checkpoints in thyroid cancer using transcriptome data from our center and Gene Expression Omnibus (GEO) database. Then, the effect of targeting hypoxia was investigated via treating anaplastic thyroid cancer (ATC) cells with acriflavine (ACF) in vitro and in vivo, and hypoxia was analyzed for its association with response to immunotherapy in patients. RESULTS: Hypoxia score was positively associated with dedifferentiation status, and high hypoxia score significantly correlated with reduced overall survival, TP53 mutation, and elevated expression of immunosuppression-related markers in DDTC. ACF and siRNA targeting HIF-1α significantly suppressed growth and proliferation of thyroid cancer cells in vitro and in vivo, and reduced c-MYC and PDL1 expression in ATC. HIF-1α showed a positive correlation with PDL1 expression in DDTC. Integrated analyses of phosphoproteome and RNA sequencing data revealed that ACF's target was connected with differentiation genes and immune checkpoints via tumor-related kinases in ATC. Furthermore, hypoxia score was associated with immunotherapeutic response in some cancer types. CONCLUSION: Hypoxia score serves as a significant indicator for dedifferentiation status, prognoses, and immunotherapeutic response predicted by Tumor Immune Dysfunction and Exclusion in DDTC patients. Targeting hypoxia by ACF is useful to alleviate aggressive phenotype of ATC in a preclinical model of DDTC.

Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Objectives: To identify a prognosis-related subtype of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) and comprehend its contributions to molecular characteristics, immune characteristics, and their potential benefits in immunotherapy and chemotherapy for HNSCC. Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis of CAFs from the samples of HNSCC patients derived from Gene Expression Omnibus (GEO), to identify the prognosis-related subtype of CAFs. CAFs were clustered into five subtypes, and a prognosis-related subtype was identified. Univariate and multivariate cox regression analyses were performed on the cohort selected from The Cancer Genome Atlas (TCGA) to determine signature construction, which was validated in GSE65858 and GSE42743. A prognostic signature based on 4 genes was constructed, which were derived from prognosis-related CAFs. The molecular characteristics, immune characteristics as well as the predicted chemosensitivity and immunotherapeutic response in the signature-defined subgroups were analyzed subsequently. Results: The patients with higher CAF scores correlated with poor survival outcomes. Additionally, a high CAF score correlated with lower infiltration levels of many immune cells including M1 macrophages, CD8+ T cells, follicular T helper cells, monocytes, and naïve B cells. High CAF score also demonstrated different enrichment pathways, mutation genes and copy number variated genes. Furthermore, patients with high CAF scores showed lower sensitivity for chemotherapy and immunotherapy than those with low CAF scores. Conclusion: The results of our study indicate the potential of the CAF signature as a biomarker for the prognosis of HNSCC patients. Furthermore, the signature could be a prospective therapeutic target in HNSCC.

A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma.

Acral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and has a higher incidence in East Asians. We perform single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor heterogeneity and immune environment. We define 5 orthogonal functional cell clusters that are involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of enriched TGF-beta, Type I interferon, and cholesterol efflux signaling are significantly associated with good prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples have significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 have higher expression in the exhaustive CD8+ T cells of acral melanoma. Key findings are verified in two independent validation sets. This study contributes to our better understanding of acral melanoma.

Integrated analysis of novel macrophage related signature in anaplastic thyroid cancer.

PURPOSE: Patients with anaplastic thyroid cancer (ATC) have a very poor prognosis. Immunotherapy is a potential treatment, while the current outcome is limited which may be due to the complicated tumor microenvironment (TME). Tumor associated macrophages (TAMs) is the most abundant cell in the TME of ATC. We aimed to clarify the novel indicators based on TAM in ATC. METHODS: Transcriptome files were downloaded from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis, cox regression, support vector machine, and random forest were utilized to identify TAM-related prognostic genes. Consensus clustering and principal component analysis were performed for integrated analysis. Moreover, external validation (Fudan University Shanghai Cancer Center cohort) was conducted in 23 ATC samples via immunohistochemistry. RESULTS: ATC patients with an abundance of TAMs had a poorer prognosis. Four TAM related genes (FZD6, RBBP8, PREX1, HSD3B7) were identified and a TAM-related prognostic index (TAMRPI) was constructed with high area under the curve (AUC). Next, high TAMRPI was related to the higher level of TAM infiltration and upregulation of several pathways, such as E2F targets, IL6-JAK-STAT3, and G2M checkpoint. Immune checkpoint TIM-3 and CSF1R were positively associated with TAMRPI, and dysfunction of T cells was increased in high TAMRPI subset. Moreover, in the external validation of protein level, strong expression of TAM related genes was related to poorer prognosis, which was further supported by time-dependent AUC analysis. CONCLUSION: TAM is negatively correlated to the prognosis of ATC. FZD6, RBBP8, PREX1, and HSD3B7 are potential biomarkers of ATC.

Prevalence of sarcopenia was higher in women than in men: a cross-sectional study from a rural area in eastern China.

Background: There were limited studies specifically evaluating whether the difference of the prevalence of sarcopenia exists in men and women in older adults from rural areas in China. The aim of this study was to compare the prevalence of sarcopenia between men and women in a rural area in eastern China and to explore the underlying causes. Methods: This study included 1,105 participants aged 60-89 years. Muscle mass was measured by bio-electrical impedance analysis. Hand grip strength was measured by Jamar Hydraulic Hand Dynamometer. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia-2019 Consensus. Data were analyzed using log-binomial and linear regression. Results: The prevalence of sarcopenia was 21.7% in women and 12.9% in men among the study cohort. After adjusting for age, education level, number of diseases, income level, smoking, drinking, and eating habits, proportion of people with sarcopenia was 1.49-fold greater in women than in men (PR = 1.49, 95% CI [1.01-2.26], P = 0.055). Conclusions: The prevalence of sarcopenia in elderly women in this rural area of eastern China is higher than in men, suggesting that women in rural areas in China seem to be more vulnerable for sarcopenia, thus early screening and prevention need to be provided for them to address such gender disparity in health.

MTA1-TJP1 interaction and its involvement in non-small cell lung cancer metastasis.

Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC. Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1. In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.

The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma.

N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.

Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma.

Background: Patients with advanced thyroid carcinoma (TC), such as anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), and locally advanced papillary thyroid carcinoma (PTC), have poor prognoses and require novel treatments. Immune checkpoint (ICP) inhibitors have demonstrated encouraging and good results; nevertheless, their effect in advanced TCs remains largely unclear. Thus, we demonstrated ICP profiles and investigated their potential clinical significance. Methods: A total of 234 TC patients were involved, with 22 ATCs, 44 PDTCs, and 168 PTCs, including 58 advanced PTCs. Immunohistochemistry was performed to evaluate nine ICPs [programmed cell death ligand 1 (PDL1), Programmed cell death 1 (PD1), cytotoxic T lymphocyte-associated protein 4 (CTLA4), B and T lymphocyte attenuator (BTLA), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), lymphocyte activation gene 3 (LAG3), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B7 homolog 3 (B7-H3), and T-cell immunoglobulin and mucin domain- 3 protein (TIM3)] expression via tissue microarrays (TMAs), and clinical correlations were analyzed simultaneously. Results: ATC had the highest positive rate of ICPs among the three pathological types, as well as relatively high ICP co-expression. ATC with high expression of PDL1 positivity had a poor prognosis. Shorter survival was associated with VISTA, B7H3, TIM3, and TIGIT expression in PDTC. The greater the co-expression of these four ICPs, the poorer the prognosis in PDTC patients. VISTA and B7H3 were the two most commonly expressed ICPs in advanced PTC, both of which were linked to a poor prognosis. Conclusions: PDL1 is linked to the overall survival (OS) of ATC. A subset of PDTC is likely immunogenic with poor prognosis and co-expression of VISTA, B7H3, TIM3, and TIGIT. Furthermore, VISTA and B7H3 are prognostic biomarkers in advanced PTC. Single or combined blockade targeting these ICPs might be effective for advanced TCs in the future.