METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS.

The present study aimed to explore the potential roles of the methyltransferase­like 3 (METTL3)­mediated methylation of RAS related (RRAS) mRNA in the tumorigenesis and development of bladder cancer (BCa). For this purpose, the relative expression levels of METTL3 in BCa specimens and cell lines were measured using reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis. The association between the METTL3 expression level and the clinical characteristics of patients with BCa was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis databases. Cellular experiments were performed to confirm the effects of METTL3 on the proliferative, migratory and invasive capacities of BCa cells. RT­qPCR, western blot analysis, methylated RNA immunoprecipitation (MeRIP)­qPCR and dual­luciferase report assays were utilized to verify the METTL3/RRAS/YTH N6­methyladenosine (m6A) RNA binding protein 2 (YTHDF2) regulatory axis in BCa. The results revealed that METTL3 expression was markedly increased in BCa specimens and cell lines, and was associated with poor clinical characteristics of patients with BCa. In vitro and in vivo assays demonstrated that the silencing of METTL3 markedly suppressed the proliferative, migratory and invasive capacities of BCa cells. MeRIP­PCR and dual­luciferase report assays indicated that METTL3 could bind to the m6A sites of RRAS mRNA and suppress the transcriptional activity of RRAS. YTHDF2 could recognize the m6A sites of RRAS and mediate RRAS degradation. On the whole, the findings of the present study reveal the pivotal role of METTL3­catalyzed m6A modification in BCa tumorigenesis and development. The change could facilitate BCa tumor growth and metastasis by suppressing RRAS expression in an m6A YTHDF2­dependent manner. Targeting the METTL3/RRAS/YTHDF2 regulatory axis may thus prove to be a promising strategy for the diagnosis and therapy of BCa.

Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that generally induces the progression of rapidly progressive glomerulonephritis (GN). The purpose of this study was to identify key biomarkers and immune-related pathways involved in the progression of ANCA-associated GN (ANCA-GN) and their relationship with immune cell infiltration. Methods: Gene microarray data were downloaded from the Gene Expression Omnibus (GEO). Hub markers for ANCA-GN were mined based on differential expression analysis, weighted gene co-expression network analysis (WGCNA) and lasso regression, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) of the differential genes. The infiltration levels of 28 immune cells in the expression profile and their relationship to hub gene markers were analysed using single-sample GSEA (ssGSEA). In addition, the accuracy of the hub markers in diagnosing ANCA-GN was subsequently evaluated using the receiver operating characteristic curve (ROC). Results: A total of 651 differential genes were screened. Twelve co-expression modules were obtained via WGCNA; of which, one hub module (black module) had the highest correlation with ANCA-GN. A total of 66 intersecting genes were acquired by combining differential genes. Five hub genes were subsequently obtained by lasso analysis as potential biomarkers for ANCA-GN. The immune infiltration results revealed the most significant relationship among monocytes, CD4+ T cells and CD8+ T cells. ROC curve analysis demonstrated a prime diagnostic value of the five hub genes. According to the functional enrichment analysis of the differential genes, hub genes were mainly enhanced in immune- and inflammation-related pathways. Conclusion: B cells and monocytes were closely associated with the pathogenesis of ANCA-GN. Hub genes (CYP3A5, SLC12A3, BGN, TAPBP and TMEM184B) may be involved in the progression of ANCA-GN through immune-related signal pathways.

Surgical management of growth hormone-secreting pituitary adenomas: A retrospective analysis of 33 patients.

The endoscopic endonasal transsphenoidal approach (EETA) is the primary treatment for growth hormone (GH) adenoma. This study aimed to investigate the outcomes of EETA in 33 patients with GH-secreting pituitary adenoma (PA).Thirty-three patients who underwent EETA in Eighth People's Hospital of Shenzhen between January 2013 and December 2017 were included in the comprehensive analysis. Factors affecting the extent of resection and postoperative remission rates were also reviewed.The total cut rate was 63.6% (21), and the total remission rate was 66.7% (22) in all patients after surgery. The cure rate was 60.6% (20) for 33 patients. The total removal rate and remission rate were significantly different (P = .01, P = .007) for microadenomas, macroadenomas, and giant adenomas. In addition, the total removal rate and remission rate were significantly different (P = .004, P = .007) for patients with noninvasive and invasive GH-secreting PAs. Furthermore, there were significant differences (P = .003, P = .005) in the total removal rate and remission rate of patients with different preoperative GH levels. All patients with hypertension and diabetes mellitus were normalized. Three patients exhibited recurrence after surgery. Several patients suffered from postoperative complications, including transient diabetes insipidus in 3 (9.1%) patients and postoperative transient cerebrospinal fluid leakage in 2 (6.1%) patients.EETA is an effective therapeutic approach for treating patients with GH-secreting PA with high remission and low complication rates. Therefore, EETA should be considered a primary treatment for patients with GH-secreting PA.

LncRNA SNHG5: A new budding star in human cancers.

Long non-coding RNA (LncRNA) belongs to non-coding RNAs longer than 200 nucleic acids. More and more studies have revealed that lncRNA can participate in the occurrence and pathophysiology of diseases, especially in cancers. Although research on lncRNAs has doubled year by year, little is known about the specific regulatory mechanisms of lncRNAs in diseases. The main purpose of this review is to explore the molecular mechanism and clinical significance of SNHG5 in cancers. We systematically search Pubmed to obtain relevant literature on SNHG5. In this review, the functional role, molecular mechanism, and clinical significance of SNHG5 in human cancers are described in detail. Small nucleolar RNA host gene 5 (SNHG5) has been shown to be involved in the development and tumorigenesis of a variety of cancers (colorectal, bladder, gastric, endometrial, acute lymphocytic leukemia, osteosarcoma, etc.). Its disorder is closely related to metastasis, pathological staging, and prognosis. LncRNA SNHG5 might be a potential and novel diagnostic marker for cancer patients, a target for molecular targeted therapy, and a prognostic diagnostic marker.

Intracranial solitary fibrous tumor: Report of two cases.

RATIONALE: Intracranial solitary fibrous tumor (ISFT) is a rare spindle cell tumor derived from dendritic mesenchymal cells expressing CD34 antigens, which are widely distributed in human connective tissues. PATIENT CONCERNS: In two case reports, we describe a 61-year-old woman and a 42-year-old man who present with intracranial malignant SFTs. Computed tomography or magnetic resonance imaging of head revealed that the largest size is about 3.3 × 3.0 cm in left occipital part and 4.0 × 3.0 cm in right skull base. DIAGNOSIS: Postoperative pathological results demonstrated that all of two cases are SFT. Case one: Immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation (CD)34, B-cell lymphoma 2 (Bcl-2) and Vimentin (Vim). Case two: The tumor was distinctively positive for Bcl-2, but not for CD34 and Vim. INTERVENTIONS: One of the two patients recurred 6 years after the first tumor resection. After the recurrence, two gamma knife treatments were given, and another operation was performed about five years later. In one case, only tumor resection was performed. OUTCOMES: Case one: The postoperative neurological status was substantially improved and regular follow-up examinations for 6 months postsurgery have shown that the patient is currently disease-free. Case two: The patient achieved a good outcome, with no epilepsy or other neurological symptoms experienced on a regular 6-month follow-up. The patient is currently disease free. LESSONS: Imaging findings can be used to assist the diagnosis. The diagnostic method is pathology, and total surgical resection is the most effective treatment. The main treatment methods were total resection, supplemented by radiotherapy and chemotherapy if necessary.

Retrospective analysis of 52 patients with prolactinomas following endoscopic endonasal transsphenoidal surgery.

BACKGROUND: Prolactinomas affect patients' quality of life and even endanger lives. The study aimed to investigate the effect of the endoscopic endonasal transsphenoidal approach (EETA) on 52 patients with prolactinomas. METHODS: A total of 52 patients with prolactinomas who had previously undergone EETA in the People's Hospital of Xinjiang Uygur Autonomous Region between January 2013 and December 2017 were retrospectively analyzed. Factors affecting the extent of resection and postoperative remission rates were also investigated. RESULTS: All the patients were pathologically diagnosed with prolactinomas. Compared with giant adenomas, the total removal rate of microadenomas and macroadenomas was significantly increased (P < .05). In addition, the total removal rate of patients with noninvasive prolactin adenomas was significantly higher than patients with invasive prolactinadenomas (P < .05). Furthermore, there were no significant differences in postoperative remission rates among patients with prolactin adenomas from different ethnic groups (P > .05). Also preoperative administration of bromocriptine and preoperative prolactin (PRL) levels did not significantly affect therapeutic outcomes postsurgery (P > .05). Postoperative menstruation was improved or normalized in 20 (38.5%) female patients, vision was improved or normalized in 15 (28.8%) patients, and headaches were improved or normalized in 22 (42.3%) patients. Sexual function was improved in 2 male patients following surgery. A total of 6 patients exhibited a recurrence following surgery. A number of patients suffered from postoperative complications, including transient diabetes insipidus in 5 (9.6%) patients and postoperative transient cerebrospinal fluid leakage in 2 (3.8%) patients. CONCLUSION: The results of this study demonstrated that tumor size, preoperative PRL levels, and invasion of adenomas represent independent factors that can affect the success of surgery. The results suggested that EETA represents a therapeutic strategy for the treatment of patients with prolactinoma with high remission rates and low complication rates. Therefore, EETA should be considered a primary treatment for patients with prolactinomas who are not responsive to treatment with medical therapy.

RRM1 expression and the clinicopathological characteristics of patients with non-small cell lung cancer treated with gemcitabine.

BACKGROUND: The usefulness of ribonucleotide reductase catalytic subunit M1 (RRM1) for predicting the therapeutic effects of gemcitabine-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. RRM1-positive patients show unique clinicopathological features. METHODS: Here, we performed a meta-analysis to systematically evaluate the relationship between RRM1 expression and the clinicopathological characteristics of NSCLC patients treated with gemcitabine-containing regimens. A comprehensive electronic and manual search was performed to identify relevant articles. The pooled relative risk (RR) and 95% CI were used to estimate the relation between the clinicopathological characteristics of NSCLC patients and RRM1 expression. RESULTS: The study included 31 observational studies and 3,667 patients. The analysis showed no significant association between RRM1 expression and pathological type, stage, and smoking status; however, RRM1 positivity was significantly lower in women than in men (43.0% vs 51.7%, RR=0.84, 95% CI: 0.74-0.94, P=0.004). CONCLUSION: The present pooled analyses demonstrated that RRM1 positivity in women with advanced NSCLC was associated with a higher rate of response to gemcitabine-containing regimens. Immunohistochemistry may be valuable to prescreen for RRM1 expression in clinical practice, whereas PCR can be routinely used as a verification method. These findings will help design suitable molecular-targeted therapies for NSCLC.

[Characterization of cadmium uptake kinetics in cadmium pollution-safe rice material.] / æ°´ç¨»é•‰å®‰å ¨ææ–™çš„é•‰å¸æ”¶åŠ¨åŠ›å­¦ç‰¹å¾.

The characteristics of cadmium (Cd) uptake kinetics in a pollution-safe rice variety of D62B were studied in a hydroponic experiment under different Cd levels and stress time, with a common variety Luhui17 as the control. The results showed that Cd uptake in root of D62B was significantly lower than that of Luhui17 under different stress times. The differences in Cd uptake of the two rice varieties increased with the extension of absorption time. Total Cd amount of Luhui17 was 1.3 times as much as that of D62B when the absorption time was 72 h. Meanwhile, the Cd uptake kinetic of the two varieties accorded to Michaelis-Menten equation, and little difference in Michaelis constants (Km) was observed in the two varieties. However, the maximum uptake rate (Vmax) of Luhui17 was 2 times as much as that of D62B. Once the stress time was more than 48 h, the transfer coefficients of D62B was lower than that of Luhui17, and the Cd distribution ratio in root of D62B was much higher, indicating that D62B had greater accumulation ability in root compared with Luhui17. In conclusion, the Cd uptake and transfer ability of D62B were lower than those of Luhui17.

Molecular characterization of Beclin 1 in rare minnow (Gobiocypris rarus) and its expression after waterborne cadmium exposure.

Beclin 1 plays an important role in autophagy and apoptosis which are well documented in mammals. However, relevant reports are rare in fish. This study characterized Beclin 1 of the rare minnow Gobiocypris rarus (rmBeclin 1), which encodes a peptide of 447 amino acids using RT-PCR and RACE. The deduced peptide showed 96.4 and 80.8% similarity to Beclin 1 of common carp and human, respectively. Semiquantitative RT-PCR revealed that rmBeclin 1 was ubiquitously expressed in all tested tissues of male and female fish in all developmental stages, even unfertilized eggs. RT-qPCR revealed that rmBeclin 1 mRNA transcripts were significantly up-regulated in gills after a 12 h treatment with waterborne CdCl2 but were decreased thereafter. However, rmBeclin 1 expression was decreased in the brain, but it was not significantly changed in other tissues. Subchronic CdCl2 exposure significantly increased rmBeclin 1 in the brain, but it distinctly decreased rmBeclin 1 in the gill and hepatopancreas. A dose-dependent effect was not observed in mature fish treated for 96 h, but a dose-dependent effect existed in immature fish treated for 10 days. Longer treatment (10 day) caused a significantly higher expression of rmBeclin 1 in the larvae groups. These data suggest that alterations in rmBeclin 1 after CdCl2 exposure are tissue-specific and time-related and that the dose-dependent effect was restricted to a certain concentration range and exposure time.

[Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars].

OBJECTIVE: To investigate the effects of intralesional steroid, interferon alpha-2b or verapamil injection on proliferation, apoptosis and TGF-beta1 expression in keloid and hypertrophic scar in vivo. METHODS: 6 patients with keloids and 6 patients with hypertrophic scar were treated with intralesional injection of triamcinolone acetonide (40 mg/ml) or IFN alpha-2b (15 x 10(5) U/ml) or verapamil (2.5 mg/ml). Samples were collected on the 7th day after intralesional injection. Samples of untreated keloid and hypertrophic scar and normal skin were used as control. Expression of PCNA and TGF-beta1 was detected in situ by immunohistochemical staining, and apoptosis was detected in situ by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL). RESULTS: 1) Triamcinolone acetonide could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, as well as inducing apoptosis. 2) IFN alpha-2b could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, but not inducing apoptosis; 3) Verapamil could also prohibit proliferative scars through inhibiting proliferation and TGF-beta1 expression in fibroblasts, as well as inducing apoptosis. While the effect of inducing apoptosis was stronger than that of triamcinolone acetonide, the effect of inhibiting TGF-beta1 expression was weaker than those of triamcinolone acetonide and IFN alpha-2b. CONCLUSIONS: Although intraleional injection of steroid, interferon alpha-2b or verapamil were all effective in the treatment of keloid and hypertrophic scar, their mechanisms are not similar.

[The role of cell pathway in apoptosis of fibroblasts from proliferative scar induced by steroid or IFN].

OBJECTIVE: This paper is to investigate the effects of steroid or IFN alpha-2b on apoptosis and cell pathway of fibroblasts from keloids, hypertrophic scars and normal skins and different responses of different fibroblasts. METHODS: 6 samples from keloid, hypertrophic scar and normal skin were collected respectively and fibroblasts from different sources were cultured in vitro. After different fibroblasts were treated with dexamethasone (0.1 mg/ml) or IFN alpha-2b (1000 U/ml), Bax and Bcl-2 protein expressions were detected in situ by immunohistochemical staining; DNA ladders of different fibroblasts were observed by gel electrophoresis; and relative activated (phospho-) ERK1/2 and JNK pathways were detected by method of FACE ELISA. RESULTS: Dexamethasone could induce apoptosis of fibroblasts from keloids, hypertrophic scars and normal skins through activating (phospho-) ERK1/2 and JNK pathways; IFN alpha-2b could not induce apoptosis of fibroblasts from different sources. IFN alpha-2b could inhibit (phospho-) ERK1/2 pathway and could not affect (phospho-) JNK pathways of fibroblasts from keloid and hypertrophic scar. IFN alpha-2b could affect neither (phospho-) ERK1/2 pathway nor (phospho-) JNK pathways of fibroblasts from normal skin. CONCLUSIONS: The responses of different fibroblasts to steroid or IFN alpha-2b were different.

[Expression of nestin and neurogenin 3 in the human fetal pancreas].

OBJECTIVE: To examine the expression of nestin and neurogenin 3 (Ngn3), the markers of pancreatic stem cells, in the human fetal pancreas. METHODS: The human fetal pancreas tissue of 12 and 14 weeks were examined for the expression of nestin and Ngn3 using the techniques of immunofluorescence dye and RT-PCR. RESULTS: Both nestin and Ngn3 expressed widely in 12 and 14 weeks before in human fetal pancreatic tissue. In these positive cells there was no co-expressing insulin or glucagon. There were nestin and Ngn3 co-expressing cells in ducts but not in the islets. The results of RT-PCR also indicated the expression of nestin and Ngn3. CONCLUSIONS: There was no expression of the markers of mature endocrine cells in the nestin and Ngn3 positive cells, and they were the marks of no-differentiation cells in the human fetal pancreatic tissue.