Intersection of Aging and Particulate Matter 2.5 Exposure in Real World: Effects on Inflammation and Endocrine Axis Activities in Rats.

Exposure to particulate matter 2.5 (PM2.5) is detrimental to multiple organ systems. Given the factor that aging also alters the cellularity and response of immune system and dysfunction of hypothalamic-pituitary-adrenal, -gonad and -thyroid axes, it is imperative to investigate whether chronic exposure to PM2.5 interacts with aging in these aspects. In this study, two-months-old Sprague-Dawley rats were exposed to real world PM2.5 for 16 months. PM2.5 exposure diminished the relative numbers of CD4+ T cells and CD8+ T cells and increased the relative number of B cells in the peripheral blood of male rats. Conversely, only reduced relative number of CD4+ T cells was seen in the blood of female rats. These shifts resulted in elevated levels of proinflammatory factors interleukin-6 and tumor necrosis factor-α in the circulatory systems of both sex, with females also evidencing a rise in interleukin-1ß levels. Moreover, heightened interleukin-6 was solely discernible in the hippocampus of female subjects, while increased tumor necrosis factor-α concentrations were widespread in female brain regions but confined to the male hypothalamus. Notable hormonal decreases were observed following PM2.5 exposure in both sex. These comprised declines in biomolecules such as corticotrophin-releasing hormone and cortisol, generated by the hypothalamic-pituitary-adrenal axis, and thyroid-releasing hormone and triiodothyronine, produced by the hypothalamic-pituitary-thyroid axis. Hormonal elements such as gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone, derived from the hypothalamic-pituitary-gonad axis, were also diminished. Exclusive to male rats was a reduction in adrenocorticotropic hormone levels, whereas a fall in thyroid-stimulating hormone was unique to female rats. Decreases in sex-specific hormones, including testosterone, estradiol, and progesterone, were also noted. These findings significantly enrich our comprehension of the potential long-term health repercussions associated with PM2.5 interaction particularly among the aging populace.

Comprehensive analysis of disulfidptosis-related genes: a prognosis model construction and tumor microenvironment characterization in clear cell renal cell carcinoma.

BACKGROUND: Disulfidptosis, a form of cell death induced by abnormal intracellular accumulation of disulfides, is a newly recognized variety of cell death. Clear cell renal cell carcinoma (ccRCC) is a usual urological tumor that poses serious health risks. There are few studies of disulfidptosis-related genes (DRGs) in ccRCC so far. METHODS: The expression, transcriptional variants, and prognostic role of DRGs were assessed. Based on DRGs, consensus unsupervised clustering analysis was performed to stratify ccRCC patients into various subtypes and constructed a DRG risk scoring model. Patients were stratified into high or low-risk groups by this model. We focused on assessing the discrepancy in prognosis, TME, chemotherapeutic susceptibility, and landscape of immune between the two risk groups. Finally, we validated the expression and explored the biological function of the risk scoring gene FLRT3 through in vitro experiments. RESULTS: The different subtypes had significantly different gene expression, immune, and prognostic landscapes. In the two risk groups, the high-risk group had higher TME scores, more significant immune cell infiltration, and a higher probability of benefiting from immunotherapy, but had a worse prognosis. There were also remarkable differences in chemotherapeutic susceptibility between the two risk groups. In ccRCC cells, the expression of FLRT3 was shown to be lower and its overexpression caused a decrease in cell proliferation and metastatic capacity. CONCLUSIONS: Starting from disulfidptosis, we established a new risk scoring model which can provide new ideas for doctors to forecast patient survival and determine clinical treatment plans.

Diagnostic efficacy of a combination of the Chinese thyroid imaging reporting and data system and shear wave elastography in detecting category 4a and 4b thyroid nodules.

Objectives: Differential diagnosis of benign and malignant thyroid imaging reporting and data system (TIRADS) category 4a and 4b nodules can be difficult using conventional ultrasonography (US). The objective of this study was to evaluate the diagnostic efficacy of a combination of the Chinese-TIRADS (C-TIRADS) and shear wave elastography (SWE) in detecting malignant nodules among category 4a and 4b thyroid nodules. Methods: Among 409 thyroid nodules in 332 patients that we included in this study, 106 thyroid nodules were diagnosed as category 4a and 4b using C-TIRADS. We used SWE to measure the maximum Young's modulus (Emax) values of category 4a and 4b thyroid nodules. We calculated the diagnostic efficacy of only the C-TIRADS, only SWE, and a combination of C-TIRADS with SWE, and compared these, while taking the pathology results as the gold standard. Results: The area under the ROC curve (AUC), sensitivity, and accuracy values of the combination of C-TIRADS and SWE (0.870, 83.3%, and 84.0%, respectively) were all higher when compared with the values of only the C-TIRADS (0.785, 68.5%, and 78.3%, respectively) or only SWE (0.775, 68.5%, and 77.4%, respectively) in the diagnosis of category 4a and 4b thyroid nodules. Conclusion: In this study, we found that the combination of C-TIRADS and SWE significantly improved the diagnostic efficacy in detecting malignant nodules among category 4a and 4b thyroid nodules, and this could provide a reference for further use of this combination by clinicians for diagnosis and treatment.

Mid-term follow-up surgical results in 284 cases of clival chordomas: the risk factors for outcome and tumor recurrence.

OBJECTIVE: Skull base chordoma (SBC) is rare and one of the most challenging diseases to treat. We aimed to assess the optimal timing of adjuvant radiation therapy (RT) and to evaluate the factors that influence resection and long-term outcomes. METHODS: In total, 284 patients with 382 surgeries were enrolled in this retrospective study. Postsurgically, 64 patients underwent RT before recurrence (pre-recurrence RT), and 47 patients underwent RT after recurrence. During the first attempt to achieve gross-total resection (GTR), when the entire tumor was resected, 268 patients were treated with an endoscopic midline approach, and 16 patients were treated with microscopic lateral approaches. Factors associated with the success of GTR were identified using χ2 and logistic regression analyses. Risk factors associated with chordoma-specific survival (CSS) and progression-free survival (PFS) were evaluated with the Cox proportional hazards model. RESULTS: In total, 74.6% of tumors were marginally resected [GTR (40.1%), near-total resection (34.5%)]. History of surgery, large tumor volumes, and tumor locations in the lower clivus were associated with a lower GTR rate. The mean follow-up period was 43.9 months. At the last follow-up, 181 (63.7%) patients were alive. RT history, histologic subtype (dedifferentiated and sarcomatoid), non-GTR, no postsurgical RT, and the presence of metastasis were associated with poorer CSS. Patients with pre-recurrence RT had the longest PFS and CSS, while patients without postsurgical RT had the worst outcome. CONCLUSION: GTR is the goal of initial surgical treatment. Pre-recurrence RT would improve outcome regardless of GTR.

Influence of lesion size on shear wave elastography in the diagnosis of benign and malignant thyroid nodules.

In shear wave elastography (SWE) studies, the optimal cutoff value of Young's modulus for the diagnosis of benign and malignant thyroid nodules varies greatly, which affects the clinical application of the method. The objective of this study was to evaluate the influence of thyroid nodule size on the clinical diagnostic efficacy of SWE. A total of 356 thyroid nodules of 280 patients were divided into three groups according to size (Group A: ≤ 1 cm; Group B: 1-2 cm; Group C: ≥ 2 cm). SWE was used to measure the maximum Young's modulus (Emax) values of all thyroid nodules. Receiver operating characteristic (ROC) curves were drawn with pathological results as the gold standard. For all nodules, the optimal cutoff value of Emax in SWE for diagnosing malignant thyroid nodules was 36.2 kPa. The sensitivity and specificity were 76.5% and 78.4%, respectively. Groups A, B, and C had different optimal Emax cutoff values of 33.7 kPa, 37.7 kPa, and 55.1 kPa, respectively. The area under the ROC curve (AUC) values of Groups A, B, and C (0.844, 0.886, and 0.935, respectively) were all greater than the values for all lesions (0.830). The specificity values of Groups A, B, and C (86.4%, 82.6%, and 88.2%, respectively) were all increased, and the sensitivity values of Groups B and C (89.7% and 96.4%, respectively) were also increased compared with the values for all lesions. Thyroid nodule size affects the optimal Emax cutoff value of SWE. We suggest that different cutoff values be used to diagnose benign and malignant thyroid nodules according to lesion size.

Chinesization of the quality of life assessment, venous device-port, and its reliability and validity tests for patients with breast cancer.

OBJECTIVE: To translate the assessment item sets of the Canadian version of the quality of life assessment, venous device-port for breast cancer patients with chest and arm ports (i.e. different implanting sites) into Chinese version, and to conduct a test of reliability and validity for it. METHODS: According to the Brislin translation model, quality of life assessment, venous device-port underwent literal and back translations, and the Chinese version of quality of life assessment, venous device-port was preliminarily revised by consulting an expert and a preliminary test. A total of 270 cancer patients undergoing chemotherapy were assessed during the use of ports, and the reliability and the validity of the Chinese version of quality of life assessment, venous device-port scale were then tested. RESULTS: The scale consisted of 23 yes/no items and seven numerical rating scales. The total Cronbach's α coefficient of the scale was 0.829, and each item ranged from 0.812 to 0.845. The item-level content validity index was 0.67-1.00, and the scale-level content validity index/average and the scale-level content validity index/universal agreement were 0.98 and 0.90, respectively. The correlation coefficient of the repeated measurement results of the scale was 0.554 (p < 0.01). Exploratory factor analysis showed that the cumulative explained variance of five common factors was 64.197%. CONCLUSION: The Chinese version of quality of life assessment, venous device-port scale is an effective assessment tool for quality of life with good reliability and validity in breast cancer patients with different implantation sites for totally implanted venous access devices in northern China.

Identification of a prognostic 28-gene expression signature for gastric cancer with lymphatic metastasis.

Gastric cancer (GC) patients have high mortality due to late-stage diagnosis, which is closely associated with lymph node metastasis. Exploring the molecular mechanisms of lymphatic metastasis may inform the research into early diagnostics of GC. In the present study, we obtained RNA-Seq data from The Cancer Genome Altas and used Limma package to identify differentially expressed genes (DEGs) between lymphatic metastases and non-lymphatic metastases in GC tissues. Then, we used an elastic net-regularized COX proportional hazard model for gene selection from the DEGs and constructed a regression model composed of 28-gene signatures. Furthermore, we assessed the prognostic performance of the 28-gene signature by analyzing the receive operating characteristic curves. In addition, we selected the gene PELI2 amongst 28 genes and assessed the roles of this gene in GC cells. The good prognostic performance of the 28-gene signature was confirmed in the testing set, which was also validated by GSE66229 dataset. In addition, the biological experiments showed that PELI2 could promote the growth and metastasis of GC cells by regulating vascular endothelial growth factor C. Our study indicates that the identified 28-gene signature could be considered as a sensitive predictive tool for lymphatic metastasis in GC.

Incidence and severity of sexual dysfunction among women with breast cancer: a meta-analysis based on female sexual function index.

PURPOSE: Previous meta-analyses have examined the prevalence of sexual dysfunction among women with cancer, but there is no breast cancer (BC)-specific study. We therefore conducted a meta-analysis to examine the prevalence and severity of female sexual dysfunction (FSD) in women with BC. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, WanFang Data, and VIP for relevant studies published between April 2000 and January 2017. Data were extracted from studies which assessed FSD prevalence and sexual function in women with BC using the female sexual function index (FSFI). Meta-analyses were performed by pooling the prevalence rates of FSD and total FSFI scores. Meta regression was performed to explore the sources of heterogeneity. RESULTS: We selected 19 published studies involving a total of 2684 women with BC. In this study population, overall FSD prevalence was 73.4% (95% confidence interval (CI) 64.0%, 82.8%), and the total FSFI score was 19.28 (95% CI 17.39, 21.16). Among Asian, American, and European women with BC, there were significant differences in FSD prevalence (P < 0.001), and there was marginally significant difference (P = 0.07) in sexual function between these groups. There was also a marginally significant difference between individuals from mainland China and from other countries in FSD prevalence (P = 0.06) and FSFI score (P = 0.07). CONCLUSIONS: Overall, women with BC have high FSD prevalence and low sexual function. American women with BC have a higher average FSD prevalence and lower average sexual function than Asian women with BC. The FSD prevalence in women with BC in mainland China was slightly higher than in other countries.

Fabrication of ternary MoS2-polypyrrole-Pd nanotubes as peroxidase mimics with a synergistic effect and their sensitive colorimetric detection of l-cysteine.

Over the past few years, nanomaterials-based enzymatic mimics have attracted tremendous attention due to their excellent catalytic activity and environmental stability. In this work, ternary MoS2-polypyrrole (PPy)-Pd nanotubes have been prepared through a hydrothermal reaction and in situ redox polymerization process between pyrrole monomer and Na2PdCl4. The prepared MoS2-PPy-Pd nanotubes exhibited a higher peroxidase-like catalytic activity than individual MoS2, MoS2-PPy, PPy-Pd and MoS2-Pd nanocomposites due to the synergistic catalytic effect between the three components. The catalytic kinetic of MoS2-PPy-Pd nanotubes follows Michaelis-Menten behaviors, exhibiting a good affinity to both 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 substrates. On the basis of high peroxidase-like catalytic efficiency of the MoS2-PPy-Pd nanotubes, a simple and convenient colorimetric strategy for the rapid and sensitive detection of l-cysteine with a detection limit of 0.08 µM has been developed. In addition, a high selectivity towards the detection of l-cysteine is achieved. This work present an opportunity of the prepared ternary MoS2-PPy-Pd nanotubes for promising potential applications in biosensing, environmental monitoring, and medical diagnostics.

Development of a Quality of Sexual Life Questionnaire for Breast Cancer Survivors in Mainland China.

BACKGROUND There is a great need for a quality of sexual life questionnaire (QVS) in breast cancer survivors (BCSs) based on the Chinese social culture since the imported tools lack localization verification. To develop a QVS in BCSs and determine its validity and reliability. MATERIAL AND METHODS In the qualitative study, a total of 21 BCSs were interviewed by purposive sampling and snowball sampling; and in the quantitative study, a total of 249 BCSs, who were admitted and received outpatient follow-up, were investigated. Regarding construct validity, factor analysis was performed. The female sexual function index (FSFI), self-rating depression scale (SDS), and Locke-Wallace marital adjustment test (LWMAT) were used to evaluate criterion validity. Cronbach's alpha coefficient was used as an index of internal consistency. To evaluate test-retest reliability, 50 patients were re-evaluated after 1 week. RESULTS We put 28 items in the factor analysis model: (1) 5 factors were extracted by exploratory factor analysis (EFA), with a cumulative contribution of 60.37%; (2) the confirmatory factor analysis (CFA) showed that the path coefficients among the factors were all above 0.5, and the standardized load coefficients of the most items were above 0.5; (3) the Cronbach's alpha coefficient was 0.929 for the overall questionnaire, and ranged from 0.571 to 0.869 for the 5 factors; (4) the correlation coefficients between the overall questionnaire and the FSFI, SDS, and LWMAT were 0.582, -0.456 and 0.515, respectively (P<0.01); and (5) the test-retest correlation coefficient was 0.816, and the split-half-reliability coefficient was 0.899. CONCLUSIONS The QVS in BCSs has good reliability and validity, and can be used to assess the quality of sexual life among BCSs in Mainland China.

One-step in situ growth of ZnS nanoparticles on reduced graphene oxides and their improved lithium storage performance using sodium carboxymethyl cellulose binder.

ZnS nanoparticles are in situ grown on reduced graphene oxides (rGO) via a simplified one-step hydrothermal method. Sodium carboxymethyl cellulose (CMC) is firstly applied as the binder for ZnS based anodes and shows a more advantageous binding effect than PVDF. To simplify the synthesis procedure, l-cysteine is added as the sulfur source for ZnS and simultaneously as the reducing agent for rGO. The average diameter of ZnS nanoparticles is measured to be 13.4 nm, and they uniformly disperse on the rGO sheets without any obvious aggregation. As anode materials, the CMC bound ZnS-rGO nanocomposites can maintain a high discharge capacity of 705 mA h g-1 at a current density of 500 mA g-1 for 150 cycles. The significantly improved electrochemical performance mainly derives from the combined effects of the small and uniformly dispersed ZnS nanoparticles, the high conductivity and structural flexibility of rGO and the strong binding ability of CMC.

Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury.

OBJECTIVE: This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R) injury via glycogen synthase kinase 3ß (GSK-3ß) and the mitochondrial permeability transition pore (mPTP) through inhibition of endoplasmic reticulum stress (ERS). METHODS AND RESULTS: H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3ß phosphorylation and GRP94 expression. NECA increased GSK-3ß phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3ß and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3ß phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3ß and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. CONCLUSION: These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3ß via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3ß inactivation by NECA.

Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo.

IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy.