Efficacy and Safety of Immune Checkpoint Inhibitors Combined With Chemotherapy as First-line Treatment for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Different clinical trials for recurrent or metastatic nasopharyngeal carcinoma have studied different combinations of immuno-oncology in first-line treatment, but the optimal choice has not been determined. OBJECTIVE: To systematically examine and compare the efficacy and safety of different immune checkpoint inhibitors (ICIs) combined with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. METHODS: Several electronic databases were systematically searched up to February 2023. Articles meeting the inclusion criteria were included. RESULTS: Three RCTs were eligible in the study. Compared with placebo plus gemcitabine-cisplatin (GP), toripalimab plus GP (HR = 0.59, 95% CI: 0.37-0.95) was significantly associated with a better OS. Tislelizumab plus GP generated best progression-free survival (PFS) benefit (HR = 0.50, 95% CI: 0.37-0.67), greatest improvement in 1-year PFS rate (RR = 3.00, 95% CI: 1.84-5.22), and objective response rate (ORR) (RR = 1.26, 95% CI: 1.04-1.53) over the placebo plus GP. Furthermore, tislelizumab plus GP appeared to be safer than toripalimab plus GP and camrelizumab plus GP in terms of adverse events (AEs)-grade ≥3, treatment-related AEs (TRAEs)-grade ≥3, serious AEs (SAEs), treatment-related SAEs (TRSAEs), and AEs leading to discontinuation of treatment. CONCLUSION AND RELEVANCE: In recurrent or metastatic nasopharyngeal carcinoma, programmed death 1 (PD-1) inhibitors plus GP as first-line treatment have better survival outcomes than placebo plus GP with comparable toxicity. Toripalimab plus GP shows the best OS benefit over placebo plus GP, while tislelizumab plus GP generates the best PFS, 1-year PFS rate, ORR, and safety. Tislelizumab plus GP could be the best choice among the ICIs combined with chemotherapy regimens as first-line treatment in recurrent or metastatic nasopharyngeal carcinoma.

Management and Prognosis of Acute Post-Cataract Surgery Endophthalmitis: A 10-Year Retrospective Analysis in Eastern China.

Acute post-cataract surgery endophthalmitis (APSE) is a serious vision-threatening complication of cataract surgery. Analysis of the management and prognosis in cases of APSE may provide better guidance for future treatment. Fifty-six patients (56 eyes) diagnosed with APSE between 2013 and 2022 were retrospectively reviewed. The incidence of APSE rate was 0.020% (95% CI: 0.011-0.029%). Intraocular cultures were positive in 18 (32.1%) cases, with 21 organisms isolated. Coagulase-negative staphylococci was the predominant isolate (12/21; 57.1%). The time from surgery to the onset of endophthalmitis was 7 days (interquartile range: 3-16) in patients with good best-corrected visual acuity (BCVA) (≥20/70) and 3 days (interquartile range: 1-8) in those with poor BCVA (<20/70). Multivariate linear regression analysis revealed that initial BCVA (logMAR) (p < 0.001), time from onset to initial intravitreal antibiotics (IVAs) (p < 0.001), and positive culture of highly virulent pathogens (p = 0.018) displayed significantly positive associations with the final BCVA (logMAR). Adjunctive use of intravitreal corticosteroids and systemic antibiotics were unrelated to a favorable final BCVA. In conclusion, the severity of the visual condition at baseline, as well as delayed treatment, are risk factors for poor visual outcomes in APSE.

Superb microvascular imaging for evaluation of microvascularity in breast nodules compared with conventional Doppler imaging.

Background: Neovascularity visualization in breast nodules is challenging due to the limitations of conventional Doppler imaging methods. This study aims to assess the performance of superb microvascular imaging (SMI) in evaluating the microvascularity of breast nodules (diameter ≤2 cm). The comparison of performances of SMI with color Doppler flow imaging (CDFI) and power Doppler imaging (PDI) was made by using a three-factor scoring system of vascularity. This study also investigated the common features of microvascularity in small malignant nodules on SMI for early differentiating from benign nodules. Methods: Ninety-one female patients (with 125 breast nodules) were enrolled in this retrospective study. All the breast nodules were examined by grayscale ultrasonography (US), CDFI, PDI, and SMI. The number, morphologic features, and distribution of blood vessels were scored to evaluate the nodular vascularity in light of the three-factor scoring system. The diagnostic value of SMI for microvascularity in breast nodules was analyzed and compared with CDFI and PDI. Results: Histological analysis showed 53 malignant and 72 benign nodules. The vascularity grades detected by SMI were significantly different from those of CDFI and PDI (P<0.05). SMI detected 47 grade-IV nodules of the total 125 nodules (37.6%), which was more than those detected by CDFI (10.4%, 13/125) and PDI (12.8%, 16/125), while more grade-I nodules were detected by CDFI (42.4%, 53/125) and PDI (36.8%, 46/125) compared with SMI (21.6%, 27/125). Differences in the vessel number, morphologic features, and distribution between benign and malignant breast nodules were significant on SMI (P<0.05). The vessel number ≥6, penetrating vessels, and a mixed distribution of vessels in peripheral and central nodular tissues were the common features of microvascularity in the grade-IV malignant nodules on SMI, whereas the blood vessels in the benign nodules were straight and branching and peripherally distributed. Conclusions: In comparison with CDFI and PDI, SMI enhances microvascularity detection, depicts the microvascular architecture in breast nodules and has potential in the differential diagnosis of malignant nodules from benign nodules.

Exogenous Hydrogen Sulfide Induces A375 Melanoma Cell Apoptosis Through Overactivation of the Unfolded Protein Response.

Purpose: Melanomas are highly malignant and rapidly develop drug resistance due to dysregulated apoptosis. Therefore, pro-apoptotic agents could be effective for the management of melanoma. Hydrogen sulfide is ubiquitous in the body, and exogenous hydrogen sulfide has been reported to show inhibitory and pro-apoptotic effects on cancer cells. However, whether high concentrations of exogenous hydrogen sulfide have pro-apoptotic effects on melanoma and its mechanisms remain unknown. Hence, this study aimed to explore the pro-apoptotic effects and mechanisms of exogenous hydrogen sulfide on the A375 melanoma cell line treated with a hydrogen sulfide donor (NaHS). Methods: The cell proliferation test, flow cytometric analysis, Hoechst 33258 staining, and Western blotting of B-cell lymphoma 2 and cleaved caspase-3 were used to explore the pro-apoptotic effects of hydrogen sulfide on A375 cells. The transcriptional profile of NaHS-treated A375 cells was further explored via high-throughput sequencing. Western blotting of phosphorylated inositol-requiring enzyme 1α (p-IRE1α), phosphorylated protein kinase R-like ER kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homologous protein, glucose-regulating protein 78, IRE1α, PERK, and eIF2α was performed to verify the changes in the transcriptional profile. Results: NaHS inhibited A375 melanoma cell proliferation and induced apoptosis. The endoplasmic reticulum stress unfolded protein response and apoptosis-associated gene expression was upregulated in NaHS-treated A375 melanoma cells. The overactivation of the unfolded protein response and increase in endoplasmic reticulum stress was verified at the protein level. Conclusion: Treatment with NaHS increased endoplasmic reticulum stress, which triggered the overactivation of the unfolded protein response and ultimately lead to melanoma cell apoptosis. The pro-apoptotic effect of NaHS suggests that it can be explored as a potential therapeutic agent in melanoma.

Efficacy and safety of loteprednol etabonate versus fluorometholone in the treatment of patients after corneal refractive surgery: a meta-analysis.

PURPOSE: To perform a systematic evaluation of the efficacy and safety of loteprednol etabonate (LE) 0.5% versus fluorometholone (FML) 0.1% for treating patients after corneal refractive surgery with the aim of providing an evidence-based rationale for clinical drug selection. METHODS: Electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, WanFang, and CNKI) were searched (from inception to December 2021) for comparative clinical studies that evaluated LE versus FML treatment for post-corneal refractive surgery patients. Meta-analysis was performed using the RevMan 5.3 software. The pooled risk ratio (RR) and weighted mean difference (WMD) with corresponding 95% confidence interval (CI) were calculated. RESULTS: Nine studies with a total sample size of 2677 eyes were included in this analysis. FML 0.1% and LE 0.5% produced a similar incidence of corneal haze within 6 months after surgery (P = 0.13 at 1 month, P = 0.66 at 3 months, and P = 0.12 at 6 months). There was no statistically significant difference between the two groups in terms of the mean logMAR postoperative uncorrected distance visual acuity (WMD: - 0.00; 95% CI: - 0.01 to 0.00; P = 0.29) and spherical equivalent (WMD: 0.01; 95% CI: - 0.01 to 0.03; P = 0.35). LE 0.5% appears to have a higher tendency to reduce the incidence of ocular hypertension compared FML 0.1%, but there was no statistical significance (RR: 0.63; 95% CI: 0.27 to 1.50; P = 0.30). CONCLUSION: This meta-analysis demonstrated that LE 0.5% and FML 0.1% had comparable efficacy in preventing corneal haze and corticosteroid-induced ocular hypertension, with no difference in visual acuity in patients after corneal refractive surgery.

COVID-19 vaccine response and safety in patients with cancer: An overview of systematic reviews.

Background: To date, the COVID-19 pandemic does not appear to be overcome with new variants continuously emerging. The vaccination against COVID-19 has been the trend, but there are multiple systematic reviews on COVID-19 vaccines in patients with cancer, resulting in redundant and sub-optimal systematic reviews. There are still some doubts about efficacy and safety of the COVID-19 vaccine in cancer patients. Purpose: To identify, summarize and synthesize the available evidence of systematic reviews on response and COVID-19 vaccine safety in patients with cancer. Methods: Multiple databases were searched from their inception to May 1, 2022 to fetch the relevant articles. Study quality was assessed by AMSTAR2. The protocol of this study was registered on PROSPERO (CRD42022327931). Results: A total of 18 articles were finally included. The seroconversion rates after first dose were ranged from 37.30-54.20% in all cancers, 49.60-62.00% in solid cancers and 33.30-56.00% in hematological malignancies. The seroconversion rates after second dose were ranged from 65.30-87.70% in all cancers, 91.60-96.00% in solid cancers and 58.00-72.60% in hematological malignancies. Cancer types and types of therapy could influence vaccine response. COVID-19 vaccines were safe and well-tolerated. Conclusions: This study suggests COVID-19 vaccine response is significantly lower in cancer patients. Number of received doses, cancer types and treatment strategies could influence response of COVID-19 vaccine in cancer patients. COVID-19 vaccines are safe and well-tolerated. Considering the emergence of several new variants of SARS-CoV-2 with potential influence on ongoing vaccination programs, there is a need for booster doses to increase the effectiveness of COVID-19 vaccines. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022327931, identifier CRD42022327931.

Systematic pan-cancer analysis showed that RAD51AP1 was associated with immune microenvironment, tumor stemness, and prognosis.

Although RAD51 associated protein 1 (RAD51AP1) is crucial in genome stability maintenance, it also promotes cancer development with an unclear mechanism. In this study, we collected intact expression data of RAD51AP1 from the public database, and verified it was significantly over-expressed in 33 cancer types and correlated with poor prognosis in 13 cancer types, including glioma, adrenocortical carcinoma, lung adenocarcinoma. We further authenticated that RAD51AP1 is up-regulated in several typical cancer cell lines and promotes cancer cell proliferation in vitro. Moreover, we also demonstrated that RAD51AP1 was significantly positively related to cancer stemness score mRNAsi in 27 cancer types and broadly correlated to tumor-infiltrating immune cells in various cancers in a diverse manner. It was also negatively associated with immunophenoscore (IPS) and Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) scores and positively correlated with mutant-allele tumor heterogeneity (MATH), tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression in multiple cancers. The tumor stemness enhancing and tumor immune microenvironment affecting functions of RAD51AP1 might compose its carcinogenesis mechanism. Further investigations beyond the bioinformatics level should confirm these findings in each specific cancer.

Clinical Retrospective Analysis of 243 Patients with Rhinofacial Ulcers.

Purpose: The clinical and pathological data of patients with rhinofacial ulcers were retrospectively reviewed and analyzed to lay the foundation for standardized clinical treatment. Patients and Methods: We retrospectively analyzed the clinical data, etiology, pathological features, treatment methods, and prognosis of 243 patients with rhinofacial ulcers treated in the Departments of Otorhinolaryngology and Dermatology at six hospitals in Shandong Province, China from July 2014 to October 2021. The clinical characteristics and treatment methods of the rhinofacial ulcers were summarized to provide a basis for standardizing patients' diagnosis and treatment. Results: The male-to-female ratio of the 243 patients was 2.04:1, and their ages ranged from 25 to 91 years. The most common sites were the cheek, nasal dorsum, and upper lip. The common primary diseases were basal-cell carcinoma, squamous-cell carcinoma, and odontogenic fistula, but rare triggers played important roles in some cases, such as infection, autoimmune diseases, and adverse drug reactions. Surgical treatment was feasible for tumor ulcers; 71 patients with basal-cell carcinoma and 50 with squamous-cell carcinoma were treated with Mohs micrographic surgery. During the follow-up period of 1-84 months, most of the rhinofacial ulcers were cured, while natural killer/T-cell lymphoma, angiosarcoma, and melanoma were important causes of death. Conclusion: Various causes may lead to rhinofacial skin ulcers, and some cases lacking specificity of clinical manifestations are easily misdiagnosed in clinical practice. Histopathological biopsy is valuable for confirming the diagnosis, after which correct etiological treatment is very important.

[Association of Next Generation Sequencing Based Genotypic Profiling with MICM Characteristics in NPM1 Mutated Acute Myeloid Leukemia].

OBJECTIVE: To explain the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) by analyzing the association between next-generation sequencing (NGS) profiles and MICM characteristics in patients with this AML subtype. METHODS: Data of 238 NPM1mut patients with available NGS information on 112 genes related to blood disease was collected, and χ2 test and nonparametric test were used to analyze the distribution association between NGS-detecting mutations and conventional MICM parameters. RESULTS: In entire NPM1mut cohort, totaling 240 NPM1 mutation events were identified, of whom 10 (10/240, 4.2%) were missense mutations, which did not involve any W288 or W290 locus and were found exclusively in NPM1mut/FLT3-ITD- group. All but one of these missense mutations (9/10, 90%) were accompanied by AML subtype-defining recurrent cytogenetic or molecular abnormalities, of which 7 cases were in the low risk and 2 in the high risk. NPM1mut occurred solely as an insertion/deletion (indel) type in the NPM1mut/FLT3-ITD+ group. The incidence of favorable plus unfavorable karyotypes in NPM1mut/FLT3-ITD- group was higher than in NPM1mut/FLT3-ITD+ group (6.4% vs. 0, P=0.031). The positive rates of CD34 and CD7 in NPM1mut/FLT3-ITD+ group were significantly higher than in NPM1mut/FLT3-ITD- group (CD34: 47.9% vs. 20.6%, P<0.001; CD7: 61.5% vs. 29.9%, P<0.001). Logistic analysis showed that FLT3-ITD independently predicted for CD34+ and CD7+ [odds ratio (OR)=5.29, 95%CI: 2.64-10.60, P<0.001; OR=3.47, 95%CI: 1.79-6.73, P<0.001; respectively]. Ras-pathway mutations independently predicted for HLA-DR+ (OR=4.05, 95%CI: 1.70-9.63, P=0.002), and KRAS mutation for MPO- (OR=0.18, 95%CI: 0.05-0.62, P=0.007). TET2/IDH1 mutations independently predicted for CD34- and CD7- (OR=0.26, 95%CI: 0.11-0.62, P=0.002; OR=0.30, 95%CI: 0.14-0.62, P=0.001; respectively), and MPO+ (OR=3.52, 95%CI: 1.48-8.38, P=0.004). DNMT3A-R882 independently predicted for CD7+ and HLA-DR+ (OR=3.59, 95%CI: 1.80-7.16, P<0.001; OR=13.41, 95%CI: 4.56-39.45, P<0.001; respectively), and DNMT3A mutation for MPO-(OR=0.35, 95%CI: 1.48-8.38, P=0.004). CONCLUSION: Co-existing FLT3-ITD in NPM1mut AML independently predicts for CD34+ and CD7+, co-existing Ras-pathway mutation for HLA-DR+ and MPO-, co-existing TET2/IDH1 mutation for CD34-, CD7-, and MPO+, and co-existing DNMT3A mutation for HLA-DR+, CD7+, and MPO-, thereby providing a new mechanism explanation for the immunophenotypic heterogeneity of these AML patients.

Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation.

Pogona vitticeps has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that nr5a1 (Nuclear Receptor Subfamily 5 Group A Member 1), a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-nr5a1 and W-nr5a1), which are both expressed and can recombine. Three transcript isoforms of Z-nr5a1 were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced 16 isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-nr5a1) is likely to produce truncated polypeptides that contain a structurally normal DNA-binding domain and could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosome affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the genetic sex determination (GSD) system of P. vitticeps is a W-borne dominant female-determining gene that may be controlled epigenetically.

Stanniocalcin-2 promotes cell EMT and glycolysis via activating ITGB2/FAK/SOX6 signaling pathway in nasopharyngeal carcinoma.

Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.

[The Mutated Gene Sequenced by NGS and the Correlation of Their Coexistent Mutual Exclusiveness in NPM1 Mutated Acute Myeloid Leukemia].

OBJECTIVE: To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) detected by next generation sequencing (NGS) and their coexistence and mutual exclusivity relationship in the AML subtype. METHODS: The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1mut were collected. The χ2 test and non-parametric test were used to analyze the distribution correlation between the genes in the mutational spectrum. RESULTS: Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1mut was 4.5 (range 2－14), among them, there were 5.0 (range 2－10) for NPM1mut/FLT3-ITD+ and 4.0 (range 2－14) for NPM1mut/FLT3-ITD- cases, but it was no significant difference between the two groups (P=0.378). A total of 240 NPM1 mutational events were detected out in entire 238 NPM1mut patients, of which 10 (4.2%) were missense mutations, and were all found in NPM1mut/FLT3-ITD- patients. Most (9/10, 90%) of these NPM1 missense mutations were accompanied by AML subtype-defining cytogenetic or molecular abnormalities, of which 7 patients were in low risk or 2 in high risk. The most common NPM1mut coexisting mutations were DNMT3A (104, 43.7%), followed were FLT3-ITD (95, 39.9%) and FAT1 (57, 23.9%), FLT3-ITD and DNMT3A showed significant coexistence (P=0.005). FLT3-ITD showed significantly reciprocal exclusivity with FLT3-nonITD (P<0.001), NRAS (P<0.001), PTPN11 (P=0.017) and IDH1 (P=0.005), and showed an exclusivity inclination with KRAS (P=0.073). In addition, FLT3-nonITD along with KRAS (P=0.035), NRAS along with KRAS (P=0.008) and PTPN11 (P=0.039) coexisted significantly. CONCLUSION: Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1mut AML provide a mechanism explaining biological diversity and clinical heterogeneity in this AML subset.

MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. METHODS: The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). RESULTS: miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3'untranslated region (3'UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What's more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. CONCLUSIONS: These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.

Prognostic and immunological significance of metastasis associated lung adenocarcinoma transcript 1 among different kinds of cancers.

LncRNAs belong to the type of noncoding RNA transcripts, which exceed 200 nucleotides in size. MALAT1 as one of the earlier identified lncRNAs in cancer is investigated by more and more scientific researchers. Expression, clinical significance and function of MALAT1 in pan-cancer exist as big difference. To detect the expression and clinical significance of MALAT1 gene precisely and comprehensively among different kinds of cancers, some classical databases such as GEPIA, TIMER, KM Plotter, and PrognoScan were fully applied. An immunological role of MALAT1 among different kinds of cancers was also determined in TIMER database. Our results showed that MALAT1 was differently expressed in different kinds of cancers using GEPIA, Oncomine, and TIMER databases to analyze. Especially, MALAT1 high RNA level was related to the early stage in lung and gastric cancer patients. MALAT1 expression was closely related to prognosis among different cancer patients. Furthermore, expression of MALAT1 was related to tumor immune cell infiltrating. Expression level of MALAT1 was also related to immune makers such as macrophage, T cell, NK cells, and so on. These findings indicate that MALAT1 could be a potential prognostic biomarker of some kinds of cancer and was significantly correlated with tumor-infiltrating immune cells in a wide variety of cancers.

LINC01123 enhances osteosarcoma cell growth by activating the Hedgehog pathway via the miR-516b-5p/Gli1 axis.

The lncRNA LINC01123 has been reported to act as an oncogene in many human cancers. Nevertheless, the function and underlying mechanism of LINC01123 in osteosarcoma (OS) remain unclear. This study aimed to explore the roles and mechanisms of LINC01123 in OS progression. In this study, the expression of LINC01123 was significantly upregulated in OS cell lines than in a human osteoblast cell line. Furthermore, in vitro and in vivo experiments confirmed that knockdown of LINC01123 suppressed cell progression. Mechanistically, LINC01123 acted as a competing endogenous RNA by sponging miR-516b-5p, thus, increasing Gli1 expression by directly targeting its 3'UTR. Taken together, LINC01123 enhances OS proliferation and metastasis via the miR-516b-5p/Gli1 axis. Therefore, LINC01123 may be a potential therapeutic target for OS treatment.

Myeloid/lymphoid neoplasm with CEP110-FGFR1 fusion: An analysis of 16 cases show common features and poor prognosis.

Objectives: The 8p11 myeloproliferative syndrome (EMS) is an extremely rare, generally aggressive haematologic malignancies. This study provided the clinical outcomes and therapeutic strategies for EMS patients confirmed with CEP110-FGFR1 fusion. Methods: We report here a case of translocation (8;9) (p12;q33)/CEP110-FGFR1 who received allo-HSCT and achieved molecular remission. We searched the PubMed database for relevant medical literatures published between 1992 and 2018. We generalized the laboratory results, clinical features, therapeutic outcomes for EMS with confirmed CEP110-FGFR1 fusion. Results: We identified 16 EMS cases with CEP110-FGFR1 fusions including our patient. The observed common syndrome features were characterized as follows: a male predominance, fatigue (35.7%), tonsil hypertrophy (41.7%), lymphadenopathy (53.8%), hepatosplenomegaly (54.5%). leukocytosis (greater than 20.0 × 109/L, 71.4%), coexisting of eosinophilia and monocytosis (93.3%), and frequent progression to acute leukaemia. High incidence of tonsil hypertrophy and monocytosis may be a feature of EMS with CEP110/FGFR1 fusions. The CR rate for EMS was 23.1%. One patient treated with highly selective FGFR kinase inhibitor, INCB054828, achieved complete molecular remission rapidly. Allo-HSCT was performed in 8 patients. The median survival time for those patients was 9.0 (95%CI 5.599-12.601) months, with a range between 5 and 27 months. Allogeneic HSCT could improve survival in selected patients. Conclusion: FGFR1 and RUNX1 may be potential therapeutic targets for clinical trials. More accumulation of cases is also needed to determine whether allo-HSCT could be an optimal approach.

Dietary cadmium exposure causes elevation of blood ApoE with triglyceride level in mice.

Cadmium (Cd) is a widespread toxic occupational and environmental pollutant, and its effect on lipid metabolism dysregulation has been observed. In this study, we utilized two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) technologies to explore changes in the blood plasma proteins of mice exposed to Cd. From the 2-DE, 8 protein spots were screened in response to Cd exposure, and the identities of these proteins were revealed by MALDI-TOF MS. Western blotting was applied to analyze the expression of the apolipoproteins in both plasma and liver, which were consistent with Cd-induced dyslipidemia of their composed lipid. Moreover, the Cd-induced apolipoprotein ApoE upregulation was due to inhibition of autopahgic flux in the Cd exposed mice. It was further observed from the mouse liver that Cd reduced the expression of the lipid uptake receptor low-density lipoprotein receptor (LDLR), which might be responsible for the coordinated elevation in blood triglycerides and abnormal apolipoproteins. This study may provide a new insight into the mechanism of Cd-induced dyslipidemia and the risk of cardiovascular diseases.

NLRC5, a valuable marker for the diagnosis and prognostic assessment of hepatocellular carcinoma.

BACKGROUND: NLR family CARD domain containing 5 (NLRC5) is involved the initiation and progression of several cancers. However, its role in hepatocellular carcinoma (HCC) is still unclear. This study aimed to explore the expression, clinical significance, and regulated gene sets of NLRC5 in HCC. METHODS: Data related to NLRC5 was extracted from The Cancer Genome Atlas (TCGA) database and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to verify the NLRC5 mRNA expression in HCC. Immunohistochemistry (IHC) and western blot were performed to detect the NLRC5 protein level in HCC. The clinical significance of NLRC5 was investigated after separating patients into NLRC5-positive and NLRC5-negative groups based on the IHC results. Gene set enrichment analysis (GSEA) was performed to detect gene sets regulated by NLRC5 in HCC. RESULTS: Increased NLRC5 mRNA and protein expression were found in HCC tissues compared to paracancerous tissues. Moreover, enhanced NLRC5 protein expression was associated with a higher presence rate of cirrhosis, a higher TNM stage, and a shorter 3-year overall survival (OS) of HCC participants. Finally, gene sets related to cancer metastasis were up-regulated in the NLRC5 high phenotype. CONCLUSIONS: NLRC5 is a potential marker for the diagnosis and prognostic assessment of HCC.

Downregulation of GATS gene inhibits proliferation, clonogenicity and migration in triple negative breast cancer cells MDA-MB-231 by cell autophagy.

The triple negative breast cancer (TNBC) accounts for 15% to 20% of the total number of breast cancer diagnosed. A number of clinical studies have shown that TNBC has a high risk of early recurrence and distant metastasis, and a low rate of disease free survival and total survival. The premise of TNBC deterioration was abnormal proliferation and migration of tumor cells, and this study firstly showed that GATS gene could promote proliferation of MDA-MB-231 breast cancer cells. Through lentiviral expression system, the GATS gene was konckdown by shGATS lentivirus infection in the MDA-MB-231 cells, and the result indicated it could remarkably decrease the ability of cell proliferation and migration. Real-time PCR, western blot and immunofluorescence experiments showed the expressions of protein LC3, and p-Akt in shGATS cell group were lower than the shCtrl group. Therefore, we suggest the GATS could promote the MDA-MB-231 cell proliferation, migration and clonogenicity through cell autophagy by the PI3K/Akt pathway, which paved the way for further study the function of GATS in TNBC, and GATS may potentially be a target for gene therapy against triple negative breast cancer.

Continuously Tuning Electronic Properties of Few-Layer Molybdenum Ditelluride with in Situ Aluminum Modification toward Ultrahigh Gain Complementary Inverters.

Semiconducting molybdenum ditelluride (2H-MoTe2), a two-dimensional (2D) transition metal dichalcogenide, has attracted extensive research attention due to its favorable physical properties for future electronic devices, such as appropriate bandgap, ambipolar transport characteristic, and good chemical stability. The rational tuning of its electronic properties is a key point to achieve MoTe2-based complementary electronic and optoelectronic devices. Herein, we demonstrate the dynamic and effective control of the electronic properties of few-layer MoTe2, through the in situ surface modification with aluminum (Al) adatoms, with a view toward high-performance complementary inverter devices. MoTe2 is found to be significantly electron doped by Al, exhibiting a continuous transport transition from p-dominated ambipolar to n-type unipolar with enhanced electron mobility. Using a spatially controlled Al doping technique, both p- and n-channels are established on a single MoTe2 nanosheet, which gives complementary inverters with a record-high gain of ∼195, which stands out in the 2D family of materials due to the balanced p- and n-transport in Al-modified MoTe2. Our studies coupled with the tunable nature of in situ modification enable MoTe2 to be a promising candidate for high-performance complementary electronics.