LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B.

BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.

The effects of Cu-phenanthrene co-contamination on adsorption-desorption behaviors of phenanthrene in soils.

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants in the environment, which are teratogenic, carcinogenic, and mutagenic. Co-contamination of PAHs and heavy metal commonly exists in soil. In this study, 20 types of soils with different properties in China were collected and comprehensively characterized. Phenanthrene (Phe) and Cu (II) were selected as representatives of PAHs and heavy metals, respectively. The adsorption-desorption behaviors of Phe under Phe contamination and Cu (II)-Phe co-contamination in 20 types of soils were studied. The adsorption-desorption behaviors of Phe in 20 types of soils varied greatly, and adsorption of Phe in the soils followed both linear partitioning and nonlinear surface adsorption. Soil organic matter (SOM) plays an important role in the adsorption-desorption behavior of Phe. When the concentrations of Phe were >50 µg/L, soft carbon (SC) fraction of SOM not black carbon (BC) contributed more to the adsorption of Phe. Soil dissolved organic matter (DOM), especially fulvic acid and humic acid fractions, contributes to the adsorption of Phe. Under the effect of Cu (II) (60 mg/L in solution), the adsorption capacity of soil for Phe increased, which possibly resulted from lowered pH, the existence of the cation-π bonding and the "bonding bridge" effect. The systematic investigation of adsorption-desorption behaviors of Phe in soils under heavy metal-PAHs co-contamination will provide a scientific basis for the calculation of soil environmental capacity in the future.

The Relationship between Thyrotropin Serum Concentrations and Thyroid Carcinoma.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the pituitary gland and plays a role in regulating the production and secretion of thyroid hormones by the thyroid gland. This precise feedback loop is essential for maintaining a harmonious balance of thyroid hormones in the body, which are vital for numerous physiological processes. Consequently, TSH serves as a significant marker in assessing thyroid function, and deviations from normal TSH levels may indicate the presence of a thyroid disorder. Thyroid cancer (TC) is the malignant tumor within the endocrine system. In recent years, numerous experts have dedicated their efforts to discovering efficacious biomarkers for TC. These biomarkers aim to improve the accurate identification of tumors with a poor prognosis, as well as facilitate active monitoring of tumors with a more favorable prognosis. The role of TSH in the thyroid gland underscores its potential influence on the occurrence and progression of TC, which has garnered attention in the scientific community. However, due to the limited scope of clinical research and the dearth of high-quality foundational studies, the precise impact of TSH on TC remains unclear. Consequently, we present a comprehensive review of this subject, aiming to offer a valuable reference for future research endeavors.

ISG15 is a potential therapeutic target for osteosarcoma: a comprehensive analysis based on bioinformatics and in vitro experiments.

BACKGROUND: The expression of aberrant interferon-stimulated gene 15 (ISG15) is connected with various human diseases, including cancer. ISG15 is involved in tumor formation and metastasis. However, its role in osteosarcoma is uncertain. METHODS: ISG15 expression in pan-cancer from RNA Sequencing data were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. The relationship between ISG15 expression and prognosis was assessed through TCGA clinical survival data. Immunohistochemistry (IHC) images of ISG15 were retrieved using the Human Protein Atlas to analyze the differences in selected normal and tumor tissues. Gene enrichment analysis and signaling pathway analysis were used to assess the potential role of ISG15 in sarcoma, and the correlation between ISG15 expressions and immune cell infiltration levels was estimated by immune infiltration analysis. The expression levels of ISG15 were assessed by qRT-PCR and IHC. Colony formation, wound healing assay and transwell assay were used to detect the effects of ISG15 on the biological behaviors of osteosarcoma cells. The correlation between ISG15 levels and CD8+/CD68+ cells was further examined by double-labeled immunofluorescence. The chemotactic effect of ISG15 on CD8+/CD68+ cells was demonstrated by chemotactic experiments and flow cytometry. RESULTS: ISG15 was highly expressed in most cancers, while high ISG15 expression was significantly correlated with poor overall survival. Gene enrichment analysis in sarcoma suggested that antigen processing and presentation might be involved in the oncogenic mechanism of ISG15. Further immune infiltration analysis showed that high ISG15 expression might reflect the infiltration level of certain immune cells. Additionally, our verification showed that ISG15 was significantly related to the occurrence and metastasis of osteosarcoma, and knockdown of ISG15 significantly altered cell biological behavior, resulting in decreased proliferation, migration and invasion capabilities of osteosarcoma cells. The high expression of ISG15 in osteosarcoma tissue was associated with a high level of CD68+ immune cell infiltration while a low level of CD8+ T cell infiltration. CD68+ immune cells were recruited in vitro by overexpression of ISG15, which on the contrary could weaken the chemotaxis of CD8+ T cells. CONCLUSION: High ISG15 expression is an inherent feature of osteosarcoma and triggers tumorigenesis and metastasis by regulating tumor immunogenicity. ISG15 is expected to be the target of osteosarcoma treatment.

Iodine nutrition and papillary thyroid cancer.

Thyroid cancer (TC) is the most frequent endocrine malignancy. The incidence of TC, especially papillary thyroid carcinoma (PTC), has continued to rise all over the world during the past few years, for reasons that are not entirely clear. Though the phenomenon of overdiagnosis is occurring, it is not the sole driver of the substantial increase in incidence. Lifestyle, environmental factors, or complications are considered to be potential risk factors. Among these factors, iodine is a micronutrient that is vital to thyroid function. The effect of iodine intake on PTC has been controversial for many years and the epidemiological or experimental studies provided diametrically opposite conclusions. Combining all these studies, we found that iodine nutrition may affect the overall prevalence, distribution of the histological types, and clinicopathological aggressiveness of TC, especially PTC. However, the available evidence is poor due to the impact of various internal and external related factors. Therefore, this article sums up available results from both epidemiological and experimental studies, future studies are also warranted to expound on the relationship between overall PTC prevalence and iodine intake.

The relationship between urinary iodine concentration and papillary thyroid cancer: A systematic review and meta-analysis.

Background: The effect of iodine on papillary thyroid cancer (PTC) has been controversial for many years. Since urinary iodine is an effective indicator of iodine intake, some recent epidemiological studies have described the relationship between urinary iodine concentration (UIC) and PTC. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for case-control studies about UIC and PTC published before September 2022. Results are presented as the overall odds ratio (OR) and 95% confidence intervals (CI). Results: According to the analysis of the included studies, excessive iodine intake (UIC≥300ug/L) was positively associated with the occurrence of PTC patients compared with healthy controls (OR4.05, 95%CI 1.64-10.02, P=0.002). Meanwhile, adequate iodine exposure (100≤UIC<200ug/L) may play a protective role in the occurrence of PTC compared with healthy individuals (OR 0.36, 95%CI 0.14-0.91, P=0.03) while the difference in the prevalence of insufficient iodine intake (UIC<100ug/L) and iodine above requirements (200≤UIC<300ug/L) among the two groups were not significant (deficiency: OR 0.38, 95%CI 0.13-1.16, P=0.09; above requirements: OR 0.92, 95%CI 0.40-2.10, P=0.84). After comparing the UIC levels of PTC patients with those of other thyroid diseases, we found that there was also no significant difference in the incidence of different levels of UIC in the two groups (excessive: OR 1.25, 95%CI 0.87-1.80, P=0.22; above requirements: OR 0.93, 95%CI 0.77-1.14, P=0.49; adequate: OR 0.96, 95%CI 0.78-1.17, P=0.67; deficiency: OR 1.02, 95%CI 0.86-1.22, P=0.80). The result of this meta-analysis also did not support the relationship between UIC and the BRAF mutation and lymph node metastasis (LNM) of PTC patients. Besides, we also found that studies on the relationship between urinary iodine and PTC may be influenced by the way UIC was measured. Conclusion: The 10 case-control included studies involved a total of 6,544 participants. The results of this meta-analysis showed excessive iodine intake, that is, UIC≥300ug/L was associated with the occurrence of PTC but not with BRAF mutation and LNM while adequate iodine intake (100≤UIC<200ug/L) may be one of the protective factors for PTC.

Mayo adhesive probability score is associated with perioperative outcomes in retroperitoneal laparoscopic adrenalectomy.

BACKGROUNDS: This study aimed to determine whether the Mayo adhesive probability score (MAP), which evaluated adherent perinephric fat (APF), is useful in evaluating the difficulty of retroperitoneal laparoscopic adrenalectomy (RLA), and to analyse the correlation between MAP and perioperative parameters. METHODS: Clinical data of 104 patients with adrenal adenoma who underwent RLA were collected for retrospective analysis. According to the CT images obtained before surgery, patients were divided into two groups: High MAP group (2-5 points) and Low MAP group (0-1 points). Comparison of the general clinical characteristics and the perioperative data between the two groups was made. RESULTS: There were more male patients (73.7% versus 34.3%), more patients with a smoking history (24.3% versus 7.5%), higher BMI (25.7 versus 23.2, kg/m2 ), and bigger (23.8 versus 18.5, mm) neoplasm in the high MAP group (P < 0.05). Significant difference was observed in operative time (128.8 versus 102.3, min), estimated blood loss (47.2 versus 25.2, ml) and drainage tube removal time (4.0 versus 3.2, d) between the two groups (P < 0.05). A high MAP score (P < 0.001) and the size of tumour (P = 0.024) were independent risk factors for extended operative time. A higher BMI (OR = 1.525, P < 0.001) and larger tumour size (OR = 2.862, P = 0.004) were independent risk factors for a high MAP score. CONCLUSIONS: MAP score was associated with the perioperative outcomes of RLA. BMI and tumour size were better indicators of MAP score, which can influence the difficulty of RLA.

Adenosine and L-proline can possibly hinder Chinese Sacbrood virus infection in honey bees via immune modulation.

Sacbrood virus (SBV) infects larvae of honey bees, resulting in infected larvae becoming fluid-filled sacs. Our previous studies showed that the extract of herbal medicine, Radix Isatidis, could inhibit Chinese SBV (CSBV) infection in Asian honey bees (Apis cerana). Here, two compounds, adenosine and L-proline, which were previously reported to be associated with immune modulation, were identified in R. Isatidis extract and then selected for an evaluation of their antiviral effect on CSBV infection in A. cerana. Our results revealed that both adenosine and L-proline could significantly mitigate the impact of CSBV on the growth and development of infected larvae and modulate hosts' immune responses by downregulating the expression of immune genes in infected larvae. The results gained from this study suggest that adenosine and L-proline could possibly interfere CSBV infection via immune modulation to avoid exacerbations and nonspecific damage to infected larvae's own tissues.

Hybrid peptide NTP-217 triggers ROS-mediated rapid necrosis in liver cancer cells by induction of mitochondrial leakage.

Liver cancer is the third leading cause of cancer-associated mortality globally, and >830,000 patients with liver cancer undergoing treatment succumbed to the disease in 2020, which indicates the urgent need to develop a more effective anti-liver cancer drug. In our previous study, nucleus-targeting hybrid peptides obtained from the fusion of LTX-315 and the rhodamine B group possessed potent anti-adherent cancer cell activity. Hybrid peptides accumulated in the cell nucleus and damaged the nuclear membrane, resulting in the transfer of reactive oxygen species (ROS) from the cytoplasm to the nucleus and the induction of apoptosis. However, the source of the high concentration of ROS within the cytoplasm is unclear. Moreover, although our previous study demonstrated that hybrid peptides possessed potent anticancer activity against adherent cancer cells, their efficacy on liver cancer remained unexplored. The current study found that the hybrid peptide NTP-217 killed liver cancer cells after 4-h treatment with a half-maximal inhibitory concentration of 14.6-45.7 µM. NTP-217 could stably accumulate in the liver tumor tissue and markedly inhibited liver tumor growth in mice. Furthermore, NTP-217 destroyed mitochondria and induced the leakage of mitochondrial contents, resulting in the generation of a substantial quantity of ROS. Unlike the apoptosis induced by 24 h of treatment by NTP-217, 4 h of treatment caused ROS-mediated necrotic cell death. These findings suggested that short-time treatment with hybrid peptides could trigger ROS-mediated rapid necrosis in liver cancer cells, and provided a basis for the future development of hybrid peptides as anti-liver cancer agents.

Safety and Activity of Programmed Cell Death 1 Versus Programmed Cell Death Ligand 1 Inhibitors for Platinum-Resistant Urothelial Cancer: A Meta-Analysis of Published Clinical Trials.

BACKGROUND: Programmed death 1/ligand 1 (PD-1/L1) inhibitors have acceptable antitumor activity in patients with platinum-resistant urothelial cancer (UC). However, the reliability and comparability of the antitumor activity, safety profiles and survival outcomes of different immune checkpoint inhibitors are unknown. Our objective was to compare the clinical efficacy and safety of anti-PD-1/PD-L1 therapies in platinum-resistant UC patients. METHODS: We reviewed the published trials from the PubMed, Embase and Cochrane Library databases up to August 2020. A well-designed mirror principle strategy to screen and pair trial characteristics was used to justify indirect comparisons. The primary end point was the objective response rate (ORR). The safety profile and survival outcomes were also evaluated. The restricted mean survival time (RMST) up to 12 months was calculated. RESULTS: Eight studies including 1,666 advanced or metastatic UC patients (1,021 patients with anti-PD-L1 treatment and 645 patients with anti-PD-1 treatment) met the study criteria. The ORRs of anti-PD-1 and PD-L1 therapy were 22% (95% CI, 18%-25%) and 15% (95% CI, 13%-17%) with all studies combined. The proportions of the treated population with a confirmed objective response (I2 = 0; P = 0.966; HR, 1.60; 95% CI, 1.23-2.07; P < 0.001) and disease control (I2 = 30.6%; P = 0.229; HR, 1.35; 95% CI, 1.10-1.66; P = 0.004) were higher with anti-PD-1 therapy than with anti-PD-L1 therapy. The treatment-related adverse events (AEs) (I2 = 78.3%; P = 0.003; OR, 1.09; 95% CI, 0.65-1.84; P = 0.741) and grade 3-5 treatment-related AEs (I2 = 68.5%; P = 0.023; OR, 1.69; 95% CI, 0.95-3.01; P = 0.074) of anti-PD-1 therapy were comparable to those of anti-PD-L1 therapy. The RMST values at the 12-month follow-up were 9.4 months (95% CI,: 8.8-10.0) for anti-PD-1 therapy and 9.3 months (95% CI, 8.8-9.7) for anti-PD-L1 therapy (z = 0.26, P = 0.794). There was no significant difference between patients in the anti-PD-1 and anti-PD-L1 groups (12-month overall survival (OS): 43% versus 42%, P = 0.765. I2 = 0; P = 0.999; HR, 0.95; 95% CI, 0.83-1.09; P = 0.474). CONCLUSIONS: The results of our systematic comparison suggest that anti-PD-1 therapy exhibits better antitumor activity than anti-PD-L1 therapy, with comparable safety profiles and survival outcomes. These findings may contribute to enhanced treatment awareness in patients with platinum-resistant UC.

Investigation of Mg-xLi-Zn alloys for potential application of biodegradable bone implant materials.

Implant therapy after osteosarcoma surgery is a major clinical challenge currently, especially the requirements for mechanical properties, degradability of the implants, and their inhibition of residual tumor cells. Biodegradable magnesium (Mg) alloy as medical bone implant material has full advantages and huge potential development space. Wherein, Mg-lithium (Li) based alloy, as an ultra-light alloy, has good properties for implants under certain conditions, and both Mg and Li have inhibitory effects on tumor cells. Therefore, Mg-Li alloy is expected to be applied in bone implant materials for mechanical supporting and inhibiting tumor cells simultaneously. In this contribution, the Mg-xLi-Zinc (Zn) series alloys (x = 3 wt%, 6 wt%, 9 wt%) were prepared to study the influence of different elements and contents on the structure and properties of the alloy, and the biosafety of the alloy was also evaluated. Our data showed that the yield strength, tensile strength, and elongation of as-cast Mg-xLi-Zn alloy were higher than those of as-cast Mg-Zn alloy; Mg-xLi-Zn alloy can kill osteosarcoma cells (MG-63) in a concentration-dependent manner, wherein Mg-3Li-Zn alloy (x = 3 wt%) and Mg-6Li-Zn alloy (x = 6 wt%) promoted the proliferation of osteoblasts (MC3T3) at a certain concentration of Li. In summary, our study demonstrated that the Mg-6Li-Zn alloy could be potentially applied as a material of orthopedic implant for its excellent multi-functions.

Can American Joint Committee on Cancer prognostic groups be individualized in patients undergoing surgery for Stage IV invasive upper tract Urothelial Carcinoma?

Purpose: We explored whether the modified American Joint Committee on Cancer tumor-node-metastasis prognostic stage group IV can be individualized in a large population-based cohort of surgically treated invasive upper tract urothelial carcinoma (UTUC) patients. Methods: Invasive UTUC patients from the Surveillance, Epidemiology and End Results database (2004-2015) were screened for inclusion. A total of 10,482 eligible cases were identified. Cancer-specific survival (CSS) after surgery was analyzed using Kaplan-Meier plots. Results: According to the most recent pathological prognostic group classification, the 5-year mortality rates of T4NxM0 (n=493), TxN1M0 (n=597), TxN2M0 (n=424) and pTxNxM1 (n=677) patients were 41.1% (95% CI 35.2% to 47.0%), 38.6% (95% CI 33.1% to 44.1%), 40.4% (95% CI 33.0% to 47.8%) and 14.2% (95% CI 9.9% to 18.5%), respectively (T4N0M0 vs. TxNxM1, P<0.001; TxN1M0 vs. TxNxM1, P<0.001; TxN2M0 vs. TxNxM1, P<0.001). Stage IV tumors were subdivided on the basis of the mortality data (Modification 1): stage IVa tumors were considered nonmetastatic (T4NxM0, TxN1-2M0; 5-year CSS 39.9%), and stage IVb tumors were considered metastatic (pTxNxM1; 5-year CSS 14.2%). Stage IV tumors were also subdivided according to the grade classification (Modification 2): stage IVa tumors were considered low grade (T4NxM0, TxN1-2M0, TxNxM1; G1-2; n=141), and stage IVb tumors were considered metastatic (T4NxM0, TxN1-2M0, TxNxM1; G3-4; n=2050). The 5-year CSS rates for stage IVa and IVb patients were 76.3% (95% CI 68.7% to 83.9%) and 31.4% (95% CI 28.5% to 34.3%), respectively (P<0.001). Conclusions: Stage IV patients were stratified into two prognostically different risk groups depending on metastasis or grade. The subclassification of stage IV can increase the level of prognostic detail and individualize the prediction of survival in invasive UTUC patients.

Effects of different levels of TGF-ß expression and tumor cell necrosis rates in osteosarcoma on the chemotherapy resistance of osteosarcoma.

PURPOSE: The clinical significance of transforming growth factor ß (TGF-ß) and tumor cell necrosis rate (TCNR) in the expression of osteosarcoma and its effects of chemotherapy resistance on osteosarcoma were explored. PATIENTS AND METHODS: 94 cases of neoadjuvant chemotherapy osteosarcoma patients at the Third Affiliated Hospital of Kunming Medical University between January 2014 and January 2019 were collected. Samples tested for TGF-ß were collected before chemotherapy, the tumor cell necrosis rate of pathological samples before and after chemotherapy was determined. Others analyzed covariates included 12 prognostic factors that may be associated with chemotherapy resistance in previous studies: age, BMI, initial diagnosis time (The time from symptom onset to first medical attention), KPS score, initial tumor size, lymphocytes/leukocytes rate (LWR), neutrophils/lymphocytes rate (NLR), albumin, aspartate transaminase (AST), low density lipoprotein (LDL), blood urea nitrogen (BUN), alkaline phosphatase (ALP), the endpoints included progression-free survival (PFS) and overall survival (OS), response evaluation criteria in solid tumours by RECIST guideline (version 1.1). RESULT: 1. A total of 94 cases were examined for expression of TGF-ß in pathological specimens, 45 cases were TGF-ß high expression (47.9%) and 49 cases were TGF-ß low expression (52.1%); 2. The BMI, LDL, ALP, NLR in TGF-ß high expression group was significantly increased compared to TGF-ß low expression group; the Initial diagnosis time, KPS in TGF-ß high expression group was significantly decreased compared to TGF-ß low expression group, all P < 0.05; 3. Effect of chemotherapy was positively with positive cell rate (P < 0.01 r = 0.337) and TGF-ß total score (P < 0.0001 r = 0.635), while effect of chemotherapy was no correlation with degree of dyeing score (P > 0.05); there was significant difference in change from baseline after chemotherapy between TGF-ß high expression group and TGF-ß low expression group (P = 0.045); 4. Median OS 61.4 months in the TGF-ß high expression group, median OS 68.1 months in the TGF-ß low expression group, one-year survival rate, there was statistically significant difference in two groups (P = 0.045); median PFS 44.8 months in the TGF-ß high expression group, median PFS 56.2 months in the TGF-ß low expression group, There was no statistically significant difference in two groups (P > 0.05); 5. A total of 92 cases were examined for TCNR after chemotherapy, 62 were TCNR ≤ 90% (67.4%), 30 were TCNR > 90% (32.6%); 6. the Initial diagnosis time, KPS, in TCNR > 90% group was significantly increased compared to TCNR ≤ 90% group; the initial tumor size, BUN, ALP in TCNR > 90% group was significantly decreased compared to TCNR ≤ 90% group, all P < 0.05; 7. TCNR was negatively correlated with the change from baseline after chemotherapy (P < 0.001 r = -0.411); there was no statistically significant difference between TCNR > 90% group and TCNR ≤ 90% group in change from baseline after chemotherapy (P > 0.05); 8. Median OS 67.8 months in the TCNR > 90% group, median OS 61.7 months in the TCNR ≤ 90% group, there was statistically significant difference between two groups (P = 0.040); median PFS 57.4 months in the TCNR > 90% group, median PFS 40.5 months in the TCNR ≤ 90% group, there was statistically significant difference between two groups (P = 0.036); 9. TGF-ß total score was negatively correlated with TCNR (P < 0.001 r = -0.571). CONCLUSION: The results of this study suggested that the higher expression of TGF-ß, the lower expression of TCNR, which more likely to induce chemotherapy resistance among patients with osteosarcoma and lead to poor prognosis.

Investigation of Mg-Zn-Y-Nd alloy for potential application of biodegradable esophageal stent material.

In recent years, due to unhealthy dietary habits and other reasons, advanced esophageal cancer patients are on the rise, threatening human health and life safety at all times. Stents implantation as an important complementary or alternative method for chemotherapy has been widely applied in clinics. However, the adhesion and proliferation of pathological cells, such as tumor cells, fibroblasts and epithelial cells, may interfere the efficacy of stents. Further multiple implantation due to restenosis may also bring pain to patients. In this contribution, we preferred a biodegradable material Mg-Zn-Y-Nd alloy for potential application of esophageal stent. The hardness testing showed that Mg-Zn-Y-Nd alloy owned less mechanical properties compared with the commercial esophageal stents material, 317L stainless steel (317L SS), while Mg-Zn-Y-Nd displayed significantly better biodegradation than 317L SS. Cell apoptosis assay indicated Mg-Zn-Y-Nd inhibited adhesion and proliferation of tumor cells, fibroblasts and epithelial cells. Our research suggested potential application of Mg-Zn-Y-Nd alloy as a novel material for biodegradable esophageal stent.

Prognostic significance of common preoperative laboratory variables in penile squamous cell carcinoma.

OBJECTIVE: To investigate the predictive value of common preoperative laboratory variables in patients undergoing bilateral inguinal lymph node dissection surgery for penile squamous cell carcinoma. METHODS: We retrospectively analyzed the records of 228 patients who had bilateral inguinal lymph node dissection for penile squamous cell carcinoma to assess the following clinical factors: preoperative laboratory measurements, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, serum calcium, total protein, globulin, pathological factors and survival rates after surgery. RESULTS: The percentage of positive lymph nodes was 52.6%. Univariate analysis showed that the tumor stage and grade, the presence of metastasis, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and globulin were significantly associated with the disease-specific survival (all P < 0.05). At multivariate analysis, only the neutrophil-to-lymphocyte ratio had an independent effect (hazard ratio 2.131; P = 0.035). The predictive accuracy of the neutrophil-to-lymphocyte ratio was the best among the laboratory variables. The predictive accuracy of the basic pathological factors was significantly increased by incorporating the neutrophil-to-lymphocyte ratio prognosticator. CONCLUSION: The neutrophil-to-lymphocyte ratio before inguinal lymph node dissection might be useful for predicting the prognosis of patients with penile squamous cell carcinoma.

MiR-204-3p Inhibited the Proliferation of Bladder Cancer Cells via Modulating Lactate Dehydrogenase-Mediated Glycolysis.

MicroRNAs (miRNAs) are endogenous non-coding RNAs that negatively regulate the expression of downstream targeted mRNAs. Increasing evidence has suggested that miRNAs act as tumor suppressors or oncogenes to interfere the progression of cancers. Here, we showed that miR-204-3p was decreased in bladder cancer tissues and cell lines. Down-regulation of miR-204-3p was significantly associated with a poor prognosis in bladder cancer patients. Overexpression of miR-204-3p inhibited proliferation and induced apoptosis in bladder cancer cells. Furthermore, miR-204-3p was found to bind to the 3'-untranslated region (UTR) of the lactate dehydrogenase (LDHA), which consequently reduced the expression of both mRNA and protein of LDHA. Interestingly, overexpression of miR-204-3p decreased glucose consumption and lactate production of bladder cancer cells. Overexpression of LDHA relieved the growth inhibition and cell apoptosis enhancement by miR-204-3p in bladder cancer cells. These results demonstrated that miR-204-3p negatively modulated the proliferation of bladder cancer cells via targeting LDHA-mediated glycolysis. MiR-204-3p might be a promising candidate for designing anticancer medication.

Correlation analyses of thyroid-stimulating hormone and thyroid autoantibodies with differentiated thyroid cancer.

PURPOSE: To investigate the feasibilities and clinical values of thyroid-stimulating hormone (TSH) and thyroid autoantibodies in predicting differentiated thyroid cancer (DTC). METHODS: 500 patients with thyroid nodules who underwent surgery for the first time in our hospital from January 2014 to December 2016 were selected, including 250 patients definitely diagnosed pathologically with DTC and 250 patients definitely diagnosed with benign thyroid nodules after operation. Serum thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and TSH levels before operation were evaluated in both groups. According to the reference ranges of TgAb and TPOAb, they were divided into negative and positive groups. According to the TSH reference range, they were divided into decreased, normal and increased groups. Statistical analyses were conducted, respectively. RESULTS: The serum TgAb level in the DTC group was significantly increased compared with that in benign thyroid nodule group (p=0.01). The positive rate of TgAb in DTC group was also significantly higher than that in benign thyroid nodule group (p<0.01). The level of serum TPOAb in the DTC group was not significantly different from that in the benign thyroid nodule group (p=0.25). The level of serum TSH in the DTC group was significantly increased compared with that in the benign thyroid nodule group (p<0.01). There was a statistically significant difference in the comparison of the distribution of TSH between the DTC group and benign thyroid nodule group (p<0.01). Univariate analysis showed that TgAb and TSH were correlated with DTC. Multivariate logistic regression analysis results showed that serum positive TgAb and increased TSH wre significantly correlated with DTC. TSH level in DTC with cervical lymph node metastasis group was significantly increased compared with DTC without such metastasis group (p<0.01). CONCLUSIONS: Increased levels of serum TgAb and TSH may be risk factors for DTC. Whether the two indicators can be used as predictors of DTC screening needs to be confirmed in large-sample prospective trials. Increased serum TSH level is closely related to DTC with cervical lymph node metastasis.

Prognostic role of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in prostate cancer: A meta-analysis of results from multivariate analysis.

BACKGROUND: The prognostic role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with prostate cancer (PCa) remains inconsistent. Here we quantify the prognostic impact of these biomarkers and assess their consistency in PCa. MATERIALS AND METHODS: We systematically searched PubMed, Web of Science, and Embase for eligible studies embracing multivariate results. The Newcastle-Ottawa Scale were used to assess the study quality. Pooled hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 7228 patients from 18 studies were included in the meta-analysis. Overall, elevated pretreatment NLR was associated with poor overall survival (OS, HR 1.58, 95% CI 1.41-1.78, P < 0.001), progression-free survival (PFS, HR 1.95, 95% CI 1.53-2.49, P < 0.001) and biochemical recurrence-free survival (BRFS, HR 1.37, 95% CI 1.07-1.75, P = 0.011). And high pretreatment PLR was correlated with more inferior PFS (HR 1.62, 95% CI 1.20-2.19, P = 0.002), OS (HR 1.70, 95% CI 1.34-2.15, P < 0.001) and cancer-specific survival (CSS, HR 2.02, 95% CI 1.24-3.29, P = 0.005). Moreover, the subgroup analyses did not alter the direction of results for OS and PFS. CONCLUSION: Based on these findings, elevated NLR and PLR was associated with poor oncologic outcomes, and they can serve as prognostic factors in PCa patients.

microRNA­145 modulates migration and invasion of bladder cancer cells by targeting N­cadherin.

MicroRNA (miRNA)­145 has been demonstrated to serve a role in several types of tumors, however, the potential molecular mechanism of action of miRNA­145 in bladder cancer metastasis remains to be elucidated. This study aimed to investigate the potential modulation of miRNA­145 in bladder carcinoma and elucidate the underlying molecular mechanism. The expression of miRNA­145 in bladder adenocarcinoma tissues and bladder cancer cells was measured by reverse transcription­quantitative polymerase chain reaction. miRNA­145 mimics and inhibitor were transfected into bladder cancer (BC) cells to determine the role of miRNA­145 on cell motility and invasion measured by wound healing and transwell assays. Luciferase assay was performed to confirm whether N­cadherin was the direct target of miRNA­145. Subsequently, expression of N­cadherin and matrix metalloproteinase­9 (MMP9) in BC cells were detected by western blot analysis. miRNA­145 was significantly downregulated cells and tissues from patients with BC, compared with healthy controls. miRNA­145 markedly inhibited the ability of BC cells to migrate and invade. Furthermore, N­cadherin was identified as a target of miRNA­145 in BC cells. MMP9, acting downstream of N­cadherin, was downregulated in BC cells by miRNA­145. In the present study, miRNA­145 suppressed the migration and invasion of BC cells by regulating N­cadherin. The results of the present study indicated that miRNA­145 may function as a tumor suppressor and may have a potential to be a diagnostic and predictive biomarker, and a therapeutic target for treatment of BC.

HMGB1-mediated autophagy confers resistance to gemcitabine in hormone-independent prostate cancer cells.

As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine-induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.