CLIC1-mediated autophagy confers resistance to DDP in gastric cancer.

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular chloride channel 1 (CLIC1) expression was increased in AGS/DDP and MKN28/DDP, and as compared to the parental cells, autophagy was activated. In addition, the sensitivity of gastric cancer cells to DDP was decreased compared to the control group, and autophagy increased after overexpression of CLIC1. On the contrary, gastric cancer cells were more sensitive to cisplatin after transfection of CLIC1siRNA or treatment with autophagy inhibitors. These experiments suggest that CLIC1 could alter the sensitivity of gastric cancer cells to DDP by activating autophagy. Overall, the results of this study recommend a novel mechanism of DDP resistance in gastric cancer.

Prevalence and unfavorable outcome of frailty in older adults with gastric cancer: a systematic review and meta-analysis.

BACKGROUND AND AIM: Previous studies reported inconsistent results on the prevalence and prognostic implications of frailty among older adults with gastric cancer. This systematic review synthesized available literature pertaining on this topic to establish the prevalence and unfavorable outcomes of frailty in older adults with gastric cancer. METHODS: A comprehensive search was conducted across multiple English databases including PubMed, Cochrane Library, CINAHL, Embase, and Web of Science as well as Chinese databases, namely, CNKI, Wan Fang, and CBM, from inception to July 4, 2023, to identify potential studies. Data related to the incidence of frailty and its unfavorable outcomes in older adults with gastric cancer were extracted. RevMan5.3 and R 4.2.2 were used to evaluate pooled prevalence, hazard ratios (HR), and 95% confidence interval (CI). RESULTS: This review comprehensively selected 13 studies, comprising 9 cohort studies and 4 cross-sectional studies, on 44,117 older adults diagnosed with gastric cancer. The incidence of frailty among older adults with gastric cancer ranged from 10 to 71%. The pooled prevalence of frailty was 29% (95% CI 0.21-0.39). Frailty was found to be associated with an elevated risk of postoperative complications (HR = 1.99, 95% CI 1.45-2.73), prolonged postoperative hospital stay (HR = 2.68, 95% CI 2.38-3.02), likelihood of readmission (HR = 3.28, 95% CI 1.77-6.08), and an increased mortality risk (HR = 1.60, 95% CI 1.36-1.90). CONCLUSIONS: Frailty was associated with a poor prognosis in older adults with gastric cancer. Clinical medical staff should focus on the frailty of older adults with gastric cancer, conduct large-scale, multicenter, and prospective studies and early screening of patients, and provide guidance for the implementation of prevention and treatment strategies.

Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer.

BACKGROUND: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated. METHODS: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism. RESULTS: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS. CONCLUSIONS: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.

Fine-Tuning Tridentate Ligands for the Construction of Nanotube-Based Boron Imidazolate Frameworks with High Chemical Stability.

Two unusual nanotube-based boron imidazolate frameworks (BIF-134 and BIF-135) were synthesized by a dual-ligand synthetic strategy under solvothermal conditions. In the structure of BIF-134 ([Co(BH(2-mim)3)(BTC)1/3](HBH(2-mim)3)1/3(NMA); 2-mim = 2-methylimidazole, NMA = N-methylacetamide, and BTC = 1,3,5-benzene tricarboxylate), one part of boron imidazolate ligands participate in the structural skeleton coordination, while another part of boron imidazolate ligands act as guest molecules that are located between adjacent nanotubes, which enhance the stability of the framework by the host-guest interaction and the pore space partition effects. It was found to be highly stable in air, water, organic solvents, and a wide pH range (pH 0-12). However, in the structure of BIF-135 ([Zn(BH(2-mim)3)(CHTC)1/3]; CHTC = 1,3,5-cyclohexanetricarboxylate), all boron imidazolate ligands participate in the structural skeleton coordination; there is no boron imidazolate guest molecule in the pores. The topology of BIF-135 is similar to that of BIF-134 by replacing BTC with CHTC and replacing Co with Zn. Furthermore, the obtained BIFs exhibited third-order nonlinear optical properties and potential optical limiting applications demonstrated by reverse saturable absorption.

Magnetic resonance imaging (MRI) radiomics of papillary thyroid cancer (PTC): a comparison of predictive performance of multiple classifiers modeling to identify cervical lymph node metastases before surgery.

PURPOSE: To compare predictive efficiency of multiple classifiers modeling and establish a combined magnetic resonance imaging (MRI) radiomics model for identifying lymph node (LN) metastases of papillary thyroid cancer (PTC) preoperatively. MATERIALS AND METHODS: A retrospective analysis based on the preoperative MRI scans of 109 PTC patients including 77 patients with LN metastases and 32 patients without metastases was conducted, and we divided enroll cases into trained group and validation group. Radiomics signatures were selected from fat-suppressed T2-weighted MRI images, and the optimal characteristics were confirmed by spearman correlation test, hypothesis testing and random forest methods, and then, eight predictive models were constructed by eight classifiers. The receiver operating characteristic (ROC) curves analysis were performed to demonstrate the effectiveness of the models. RESULTS: The area under the curve (AUC) of ROC based on MRI texture diagnosed LN status by naked eye was 0.739 (sensitivity = 0.571, specificity = 0.906). Based on the 5 optimal signatures, the best AUC of MRI radiomics model by logistics regression classifier had a considerable prediction performance with AUCs 0.805 in trained group and 0.760 in validation group, respectively, and a combination of best radiomics model with visual diagnosis of MRI texture had a high AUC as 0.969 (sensitivity = 0.938, specificity = 1.000), suggesting combined model had a preferable diagnostic efficiency in evaluating LN metastases of PTC. CONCLUSION: Our combined radiomics model with visual diagnosis could be a potentially effective strategy to preoperatively predict LN metastases in PTC patients before clinical intervention.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

Exosome-mediated transfer of CLIC1 contributes to the vincristine-resistance in gastric cancer.

Our previous study shows that high Chloride intracellular channel 1 (CLIC1) expression can efficiently enhance invasion and migration of gastric cancer (GC) cells in vitro. Growing evidences have found that exosomes are involved in chemotherapy resistance in several cancers including GC. We aimed to evaluate the effect of the exosome-mediated transfer of CLIC1 in the vincristine-resistance of GC. The effect of exosome-mediated transfer of CLIC1 on the development of resistance to vincristine in GC cell line SGC-7901 and the potential underlying mechanisms were investigated by Cell Counting Kit-8 (CCK8), RT-PCR, and Western blotting. Exosomes were isolated from cell supernatants by differential ultracentrifugation. Comparing with SGC-7901, the expression level of CLIC1 is higher in vincristine­resistant cell line SGC-7901/VCR (P < 0.05). After silencing the expression of CLIC1 by RNA interference, the half inhibition concentration (IC50) to vincristine decreased significantly in SGC-7901/VCR, and the expression of CLIC1 decreased significantly in exosomes from SGC-7901/VCR. After 48 h co-culturing with exosomes from SGC-7901/VCR, the IC50 to vincristine in SGC-7901 increased significantly, and the expression of CLIC1, P-gp, and Bcl-2 were significantly up-regulated. CLIC1 was closely associated with the resistance to vincristine in GC, and exosome-mediated transfer of CLIC1 could induce the development of resistance to vincristine in vitro. The possible mechanism was related to up-regulated P-gp and Bcl-2. However, in vivo study was needed to confirm the results in future.

Issues on peritoneal metastasis of gastric cancer: an update.

BACKGROUND: Peritoneal metastasis (PM) is one of the most common forms of metastasis with a very poor prognosis in patients with gastric cancer (GC). The mechanisms, diagnosis, and management of PM remain controversial. MAIN BODY: Stephen Paget's "seed-and-soil" hypothesis gives us an illustration of the mechanisms of PM. Recently, hematogenous metastasis and exosomes from GC are identified as novel mechanisms for PM. Diagnostic accuracy of conventional imaging modalities for PM is not satisfactory, but texture analysis may be a useful adjunct for the prediction of PM. Biological markers in peritoneal washings are helpful in identifying patients at high risk of PM, but many limitations remain to be overcome. Response of PM from systemic chemotherapy alone is very limited. However, conversion therapy is confirmed to be safe and able to prolong the survival of GC patients with PM. As an important part of conversion therapy, intraperitoneal chemotherapy with taxanes has become an ideal approach with several advantages. Additionally, gastrectomy should be considered in patients who would tolerate surgery if a remarkable response to chemotherapy was observed. CONCLUSION: Texture analysis is a reliable adjunct for the prediction of PM, and conversion therapy provides a new choice for GC patients with PM. The underlying mechanisms and new biological markers for GC patients with PM should be the direction of future studies. Furthermore, significant aspects of conversion therapy, such as timing and method of the operation, and the indications remain to be clarified.

Distinguishable Prognostic Signatures of Left- and Right-Sided Colon Cancer: a Study Based on Sequencing Data.

BACKGROUND/AIMS: Left- and right-sided colon cancers are considered to be two different diseases and have altered outcomes. However, specific molecules to predict the prognosis of left- and right-sided colon cancers are currently lacking. METHODS: Expression profiling of colon cancer were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of left- and right-sided colon cancers were compared by DESeq analysis. The prognostic values of DEGs were assessed by univariate and multivariate Cox regression. Prognostic index models of two side colon cancers were conducted with prognostic values genes, respectively. Interaction of DEGs was then analyzed by the protein-protein interaction (PPI). Different biology function of two sides of colon cancer was assessed by Gene Set Enrichment Analysis (GSEA). RESULTS: A total of 167 DEGs were identified between left- and right-sided colon cancers based on TCGA data. Using univariate COX regression analysis, five genes (PHACTR3, CKMT2, CYP2W1, ERFE, HOXC4) were related to overall survival in left-sided, and eight distinguishable genes (EREG, ERFE, HOXC6, SLC22A31, TFF1, GFI1, ZG16, RASL10B) in right-sided. Further, left-sided prognostic model was established with PHACTR3 and CKMT2 (HR=2.040; 95%CI=1.004-4.145; P=0.049). Distinguishable prognostic signature for right-sided colon cancer was established based on EREG, ERFE, GFI1, and RASL10B (HR=3.530; 95%CI: 1.934-6.444; P< 0.001) in multivariate analysis. PPI analysis of 167 DEGs showed that CCL5, GNG4, GNLY, GZMH, DRD2, and FASLG genes were at the core of interaction network. In GSEA function analysis, four pathways, including antigen processing and presentation, natural killer cell mediated cytotoxicity, intestinal immune network for Iga production, and type I diabetes mellitus, were significantly enriched in the DEGs of the right-sided colon cancer. CONCLUSIONS: This study constructs a panel of potential prognostic model of left- and right-sided colon cancers, respectively. We also provide molecular biological alterations between left- and right-sided colon cancers.

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways.

BACKGROUND/AIMS: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. METHODS: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. RESULTS: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGß1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGß1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. CONCLUSIONS: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.

Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data.

The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00-0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC.

A Novel Scoring System for Diagnosing Acute Mesenteric Ischemia in the Emergency Ward.

BACKGROUND: Early diagnosis of acute mesenteric ischemia (AMI) based on clinical judgment has been proved to be too difficult. Therefore, it is important for identifying clinical parameters that can differentiate AMI from other acute abdomen upon presentation. METHODS: We analyzed a database of 106 consecutive patients admitted to the emergency ward for suspected AMI in whom diagnosis of AMI was confirmed by laparotomy, CT angiography or mesenteric angiography. The patients' demographics, previous history, clinical signs, results of laboratory investigations and ultrasonography were collected. Diagnostic cutoff value of quantitative indexes was derived from the receiver operating curve. Multivariate logistic regression was used to identify risk factors for AMI and formulated these risk factors into a scoring system. RESULTS: A total of 45 patients (42.5%) were confirmed to have AMI. Compared with other acute abdomen, AMI had significantly increased level of white blood cell (Odds ratio (OR) 16.11, 95% confidence interval (CI) 1.10-235.34), red cell distribution width (OR 27.65, 95% CI 1.53-501.02), mean platelet volume (OR 16.06, 95% CI 1.48-174.50) and D-dimer (OR 42.91, 95% CI 2.56-718.09). A diagnostic score was calculated by adding points assigned to the four parameters, and a cutoff score of four best identified patients with AMI, with sensitivity, specificity, positive and negative predictive values of 97.8, 91.8, 89.8 and 98.2%, respectively. CONCLUSION: This scoring system based on easily available parameters could be used as a useful tool for differentiating AMI from other acute abdomen in the emergency ward. Prospective studies with large sample remain needed for validating the results.

Exosomes in tumor microenvironment: novel transporters and biomarkers.

Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation. TD exosomes also may facilitate tumor growth and metastasis by inhibiting immune surveillance and by increasing chemoresistance via removal of chemotherapeutic drugs. Therefore, TD-exosomes might be potential targets for therapeutic interventions via their modification or removal. For example, exosomes can serve as specific delivery vehicles to tumors of drugs, small molecules, or agents of prevention and gene therapy. Furthermore, the biomarkers detected in exosomes of biological fluids imply a potential for exosomes in the early detection and diagnosis, prediction of therapeutic efficacy, and determining prognosis of cancer. Although exosomes may serve as cancer biomarkers and aid in the treatment of cancer, we have a long way to go before we can further enhance the anti-tumor therapy of exosomes and develop exosome-based cancer diagnostic and therapeutic strategies.

Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: The possible role of BRAF(V) (600E) mutation in the diagnosis and prognosis of papillary thyroid carcinoma (PTC) remains controversial. A systematic review to investigate the diagnostic and prognostic role of BRAF(V) (600E) mutation in patients with PTC is urgently needed. METHODS: A systematic review of relevant literatures was performed in PubMed, EMBASE and CENTRAL. The incremental accuracy (IA) of fine needle aspiration biopsy plus BRAF(V) (600E) mutation analysis over fine needle aspiration biopsy alone, and the statistical data about the association of BRAF(V) (600E) mutation and the prognosis of PTC (risk ratios (RR) for dichotomous data, standard mean differences for continuous data and hazard ratios (HRs) for disease-free survival (DFS) were pooled. Subgroup analysis was performed to explain the heterogeneities. RESULTS: A total of 67 studies were included. The pooled IA was 2% (95% confidence interval (CI): 0·5-4%). The pooled RR for gender, multifocality, lymph node metastasis, extrathyroidal invasion and pathological stage was 1·11 (95% CI: 0·98-1·25), 1·17 (95% CI: 1·09-1·24), 1·36 (95% CI: 1·20-1·53), 1·60 (95% CI: 1·41-1·82), and 1·49 (95% CI: 1·33-1·68), respectively. The pooled standard mean differences for age and tumour size were 0·14 (95% CI: 0·04-0·23) and 0·21 (95% CI: 0·1-0·32), respectively. The pooled HR for DFS was 1·96 (95% CI: 1·62-2·37). Subgroup analysis showed that these statistical results were affected by the geographical background of patients, study design and detection methods. CONCLUSIONS: BRAF(V) (600E) mutation analysis can not only be used in the diagnosis of PTC, but can also predict its prognosis.

Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis.

BACKGROUND: It has been postulated that non-steroidal anti-inflammatory drugs (NSAIDs) use leads to decreased prostate cancer (PCa) risk. In recent years, NSAIDs' role in PCa development has been extensively studied; however, there is not yet a definitive answer. Moreover, the epidemiological results for NSAIDs' effect on PCa-specific mortality have been inconsistent. Therefore, we performed a meta-analysis to examine the controversy. METHODS: We performed a literature database search and included all published studies conducted in the general population exposed to any NSAID, extracting an odds ratio (OR) or a hazard ratio (HR) with 95% confidence intervals (95% CIs) that compared the incidence of PCa or PCa-specific mortality with non-exposure. We derived a pooled OR or HR using random or fixed effects models, as appropriate. Subgroup analyses were also performed. RESULTS: Thirty-nine studies (20 case-control and 19 cohort studies) were included in this analysis. Thirty-one studies were available concerning NSAID use and PCa incidence and eight studies on PCa-specific mortality. Compared to non-use, aspirin use was statistically significantly associated with PCa incidence risk, and the association was slightly stronger for advanced PCa than for total PCa (OR = 0.92, 95% CI = 0.87 to 0.97 for total PCa; OR = 0.81, 95% CI = 0.73 to 0.89 for advanced PCa). Aspirin use seems also to be associated with a modest reduction in PCa-specific mortality (HR = 0.86, 95% CI = 0.78 to 0.96 for total PCa; OR = 0.81, 95% CI = 0.71 to 0.92 for advanced PCa). Generally, the pooled effects for any NSAIDs, NA-NSAIDs and cyclooxygenase-2 inhibitors demonstrated no adverse or beneficial effects on PCa development or PCa-specific mortality, but the results were not consistent. The effect estimates did not vary markedly when stratified by study design and study quality but varied by geographic region. Furthermore, long-term aspirin use (≥ 4 years) was also significantly associated with reduced PCa incidence (OR = 0.88, 95% CI 0.79 to 0.99). CONCLUSIONS: The present meta-analysis provides support for the hypothesis that aspirin use is inversely related to PCa incidence and PCa-specific mortality. The effect estimates, varying by geographic region, deserve further investigation.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

[The role of caveolin-1 for carbon black nanoparticles uptake in vitro].

OBJECTIVE: To investigate the protein expression of caveolin-1 in type II alveolar epithelial cells (A549) exposed to carbon black nanoparticles (CB NPs) and the role of caveolin in the endocytosis of CB NPs. METHODS: A549 cells were exposed to 0, 25, 50, 100, 200, and 400 µg/ml CB NPs for 24 h; then, trypan blue assay was applied to determine the cell viability. A549 cells were also exposed to 0, 25, 50, and 100 µg/ml CB NPs for 24 h, then, transmission electron microscopy (TEM) and flow cytometry were applied to observe the morphological change of cells and cellular side scatter (SSC), and Western blot was used to analyze the effect of CB NPs on the protein expression of caveolin-1. A549 cells were co-exposed to1 µg/ml filipin and 100 µg/ml CB NPs for 24 h, then, the cellular SSC was observed. RESULTS: Compared with controls, the A549 cells exposed to 200 and 400 µg/ml CB NPs had the cell viability decreased by 38.2% and 46.6%, respectively (P < 0.05), while those exposed to 25, 50, and 100 µg/ml CB NPs showed no significant decrease in cell vitality (P > 0.05). The protein expression of caveolin-1 was significantly higher in the cells exposed to 50 and 100 µg/ml CB NPs than in controls (P < 0.05). The TEM showed that plasmalemmal vesicles containing black particles were found in the cytoplasm of the cells exposed to 50 and 100 µg/ml CB NPs. The flow cytometry showed that the cellular SSC ratio increased from 1.007 to 1.331 as the dose of CB NPs rose within 0 ∼ 100 µg/ml and fell to 1.25 after the cells were co-exposed to1 µg/ml filipin and 100 µg/ml CB NPs. CONCLUSION: Carbon black nanoparticles can be transferred into A549 cells by endocytosis, but caveolin-mediated endocytic pathway plays a minor role in this process.

[Effect of N,N-dimethylformamide on calcium homeostasis and the calpain gene expression in human hepatocytes].

OBJECTIVE: To investigate the effect of N,N-dimethylformamide (DMF) on calcium homeostasis and calpain I and II gene expression in human hepatocytes (HL-7702). METHODS: HL-7702 cells were exposed to different concentrations of DMF (10, 25, 50, 100, or 200 mmol/L); other HL-7702 cells, which were used as a control group, were exposed to the equal volume of DMEM; the intracellular Ca(2+) concentration was monitored using the calcium fluorescent probe (fluo-3/AM). After 24-h exposure to DMF (10, 25, 50, 100, 150, or 200 mmol/L), the morphology of hepatocytes was observed under an inverted phase contrast microscope, and the cell viability was measured by MTT assay. After 24-h exposure to DMF (10, 25, 50, 100, or 150 mmol/L), the mRNA expression levels of calpain I and II in hepatocytes were measured by real-time quantitative PCR. RESULTS: There were significant differences in cell viability among different exposure groups (P < 0.01); the 50, 100, 150, and 200 mmol/L DMF exposure groups had a significantly lower cell viability than the control group (P < 0.05). Under the inverted phase contrast microscope, HL-7702 cells gradually lost the original shape, with swelling and shrinking, as the dose of DMF increased, and those treated with 150 mmol/L DMF even became round and floated. The fluorescence density of fluo-3 in hepatocytes increased as the dose of DMF rose, demonstrating a dose-response relationship, and there were significant differences among these exposure groups (P < 0.05). There were significant differences in mRNA expression levels of calpain I and II among these exposure groups (P < 0.01), and the expression increased as the dose of DMF rose; but DMF did not promote the mRNA expression of calpain I at a concentration of 150 mmol/L. CONCLUSION: DMF can cause damage to hepatocytes, which is related to intracellular calcium increase and calpain mRNA increase.

Sarcopenia prevalence in patients with cancer and association with adverse prognosis: A nationwide survey on common cancers.

OBJECTIVE: Although previous studies have implicated the negative outcomes of sarcopenia, evidence is limited to one or a few types of cancer. The aim of this study was to evaluate the distribution and influencing factors of sarcopenia, and explore the relationship between sarcopenia and cancer prognosis in a large oncological population. METHODS: This observational cohort study included patients diagnosed with malignant cancer between May 2011 and January 2019. Hematologic and anthropometric parameters were collected prospectively. Low skeletal muscle mass and radiodensity were diagnosed using clinical indicators, according to the two prediction models. The importance of potential risk factors for sarcopenia was estimated by subtracting the predicted degrees of freedom from the partial χ2 statistic. Hazard rates of death were calculated using the hazard function and Cox regression analyses. RESULTS: We included 13 761 patients with cancer; the prevalence of sarcopenia was 33%. The median age was 58 y and 7135 patients (52%) were men. Patients with sarcopenia had a worse nutritional status and quality of life than those without sarcopenia. Age was the most important risk factor for sarcopenia compared with body mass index or TNM stage. Additionally, patients with sarcopenia had a significantly higher and earlier peak risk for mortality. After adjusting for baseline characteristics, sarcopenia was independently associated with mortality in the research population (hazard ratio, 1.429; P < 0.001) and most cancer types. CONCLUSION: Age is the most important risk factor for sarcopenia even in patients with cancer. Sarcopenia is strongly associated with a poor quality of life and reduced overall survival.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.