Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

Can botulinum toxin injection alleviate the pain of bruxism? A Bayesian network analysis and a single-arm analysis.

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods. Materials and methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model. Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment (P < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32). Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted.

PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations.

The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify their classification. We described a broad series of colloid and papillary patterns of MAs, indicating that papillary pattern presented papillary cystic proliferation of mucinous columnar cells as salivary intraductal papillary mucinous neoplasms with recurrent AKT1 E17K mutations, whereas colloid adenocarcinomas containing large mucinous pools or lakes around the malignant epithelial nests or islands harbored BRAF V600E mutations with worse prognosis. Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors.

Head and neck carcinoma in children: A clinicopathological study of 42 cases.

Background/purpose: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma. Materials and methods: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed. Results: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%. Conclusion: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

[Determination of polybrominated diphenyl ethers in marine sediments by composite chromatography column purification-gas chromatography-negative chemical ionization-mass spectrometry].

Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants. Because they lack the ability to form chemical bonds, PBDEs can easily enter the sediment environment. The accurate qualitative and quantitative analysis of PBDEs in sediments is of great importance for the accurate assessment of PBDE pollution in this environment. Sediments contain many impurities. Therefore, PBDEs in sediment should be purified before analysis to reduce the matrix effect. A method based on gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI/MS) was developed to determine 13 PBDEs in marine sediment samples using a column packed with deactivated silica gel, acidified silica gel, Florisil, and anhydrous sodium sulfate. Sediment samples were extracted by ultrasonication with a mixed solvent of n-hexane-dichloromethane (3∶1, v/v). After two cycles of ultrasonic extraction, the extract was purified by a composite chromatographic column and eluted with n-hexane-dichloromethane (3∶1, v/v). Thirteen PBDEs were determined by GC-NCI/MS in selected-ion monitoring (SIM) mode. The effects of different fillers, eluents, and elution volumes on the purification of PBDEs in the composite column were compared and analyzed, and the GC-NCI/MS analysis conditions were optimized. Three different packing columns were used to purify the sample extract. The first column was packed with 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, 3 g of Florisil, and 6 g of anhydrous sodium sulfate; the second column was packed with 3 g of Florisil, 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, and 6 g of anhydrous sodium sulfate; and the third column was packed with 3 g of deactivated silica, 6 g of acidified silica, 3 g of deactivated silica, and 6 g of anhydrous sodium sulfate. Among these columns, that packed with 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, 3 g of Florisil, and 6 g of anhydrous sodium sulfate showed the best purification effect. The 13 PBDEs showed good linearity in the mass concentration range of 0.1-20 µg/L with correlation coefficients (r2) greater than 0.995 (decabromodiphenyl oxide (BDE-209), r2>0.99). The limits of quantification (S/N=10) was 0.002-0.126 µg/kg. The average recoveries of the 13 PBDEs at three spiked levels of 0.2, 1.0, and 4.0 µg/kg were 85.3%-101.3%, 84.8%-113.6%, and 86.3%-94.7% with relative standard deviations of 4.4%-14.0%, 0.4%-4.9%, and 1.9%-6.6%, respectively. These findings indicate that the method has high sensitivity and accuracy as well as good precision. Finally, the method was applied to the analysis and detection of PBDEs in actual marine sediment samples. The results revealed that the sediment samples contained different contents of the 13 PBDEs, and high detection rates were obtained for lower-brominated PBDE homologs. The detection rate of bis(4-bromophenyl) ether (BDE-15) was 100%, and the detected content of BDE-209 was as high as 60.49 µg/kg. These results demonstrate that the developed method is suitable for the accurate qualitative and quantitative analysis of PBDEs in marine sediment samples.

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells.

BACKGROUND: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. METHODS: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. RESULTS: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. CONCLUSIONS: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Bibliometric analysis of immunotherapy for head and neck squamous cell carcinoma.

Background/purpose: Head and neck squamous cell carcinoma (HNSCC) is a serious disease endangering the health of patients, and the application of immunotherapy in HNSCC is gradually emerging. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of immunotherapy for HNSCC. Materials and methods: Publications related to immunotherapy for HNSCC from 2002 to 2021 were searched in the Web of Science Core Collection database. The software VOSviewers, CiteSpace, and the R package 'bibliometrix' were used to perform this bibliometric analysis. Results: A total of 1297 publications were from 63 countries, led by the USA and China. The number of publications related to immunotherapy for HNSCC has increased rapidly from 2015. University of Pittsburgh and The University of Texas M.D. Anderson Cancer Center are the main research institutions. Oral Oncology is the most popular journal in this field, and the Journal of Clinical Oncology is the most highly co-cited journal. These publications were from 7569 authors, with Robert L. Ferris publishing the most papers and being the most frequently co-cited. Clinical trials related to nivolumab and pembrolizumab have attracted wide attention. 'Immune checkpoint inhibitors', 'human papillomavirus', 'programmed cell death-ligand 1', and 'programmed cell death protein 1' are the main keywords of emerging research hotspots. Conclusion: This study presents a comprehensive summary of the trends and development of immunotherapy for HNSCC, identifies the research frontier and hotspot direction, and could provide a valuable reference for researchers in this field.

Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma.

OBJECTIVES: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. MATERIALS AND METHODS: This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays. RESULTS: RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. CONCLUSIONS: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target.

Thermally Activated Microstructural Evolution of PtIrCu Alloyed Nanorings: Insights from Molecular Dynamics Simulations.

Nanoalloys have attracted extensive interest from the research and industrial community due to their unique properties. In this work, the thermally activated microstructural evolution and resultant collapse of PtIrCu nanorings were investigated using molecular dynamics simulations. Three PtIrCu nanorings with a fixed outer radius and varied inner radii were addressed to investigate the size effects on their thermal and shape stabilities. The shape factor was introduced to monitor their shape changes, and a common neighbor analysis was employed to characterize the local structures of atoms. The results reveal that both the thermal and shape stabilities of these nanorings can be remarkably improved by decreasing the inner radius. Furthermore, they all experienced the evolutionary process from ring to pie and spherelike morphologies, finally resulting in structural collapse. The stacking faults were observed in these rings during the heating process. Our work sheds light on the fundamental understanding of alloyed nanorings subjected to heating, hence offering a theoretical foundation for their syntheses and applications.

Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC), a newly designated entity of odontogenic cysts, is an intraosseous jaw cyst that is entirely or predominantly lined by orthokeratinized squamous epithelium. The aim of this study was to report a large series of OOC to substantiate its clinicopathologic profiles and to investigate PTCH1 mutations in OOCs. METHOD: The clinicopathologic features of 167 OOCs from 159 patients were analyzed and the immunohistochemical expression of markers related to cell differentiation and proliferation was evaluated. Furthermore, PTCH1 mutations were analyzed in 14 fresh samples of OOC. RESULTS: OOCs occurred mostly in the third and fourth decades (60.4%) with a male predilection (66.7%). The lesions developed more often in the mandible than maxilla, primarily in the posterior mandible and ramus. Eight patients (5.0%) showed multiple locations of either bilateral posterior mandible (n = 6) or both the maxilla and mandible. Radiographically, the majority of OOCs (91.2%) showed a well-demarcated, unilocular radiolucency with 14 multilocular cases (8.8%). A follow-up of 131 patients (123 treated by enucleation with or without marsupialization and eight by peripheral ostectomy) revealed no recurrence during an average period of 4.56 years after surgery. Immunohistochemistry indicated lower proliferative activity and a varying epithelial differentiation pattern in OOC compared with odontogenic keratocysts (OKC). No PTCH1 mutation was detected, except for three known single nucleotide polymorphisms. CONCLUSION: The clinicopathological and molecular differences between OOC and OKC justified their separation, and unlike OKCs, OOCs did not harbor PTCH1 mutations, suggesting different pathogenesis underlying these two jaw cysts.

Emerging Role of High Glucose Levels in Cancer Progression and Therapy.

Extensive research has indicated that high glucose levels play an important role in cancer. A high glycaemic index, glycaemic load diet, high sugar intake, high blood glucose and diabetes mellitus all increase the risk of cancer. Various signals are involved in high glucose-induced tumorigenesis, cancer proliferation, apoptosis, invasion and multidrug resistance. Reactive oxygen species might be important targets in cancer progression that are induced by high glucose levels. Drugs such as metformin and resveratrol may inhibit high glucose-induced cancer. As the impact of high glucose levels on cancer progression and therapy is a novel finding, further research is required.

Salivary gland papillary adenocarcinoma with intestinal-like features: Clinicopathologic, immunohistochemical, and genetic study of six cases.

BACKGROUND: Salivary gland tumors with papillary architecture and intestinal-like mucinous cytologic features are rare. Their clinicopathologic and genetic features are not fully understood, and whether they represent one separate entity remains unclear. METHODS: Six salivary adenocarcinomas with papillary architecture and intestinal-like mucinous cytologic features were reported. Immunostaining was done for CK7, CK20, CDX2, SOX10, S100, MUC1, MUC2, and MUC5AC. Tumor DNA samples were extracted for Sanger sequencing. Previously reported morphology-analogous cases were reviewed. RESULTS: Six cases involved the palate (2), retromolar region (1), submandibular region (1), tongue (1), and mandible (1). Five cases were followed up, with one case of recurrence 1 year after surgery, one death from cerebral infarction 7 days after surgery, and three cases without signs of recurrence or metastasis over 5 years. All cases had abundant mucinous production and presented a typical immunophenotype common to salivary primaries, CK7 & MUC1 positive, CK20 & CDX2 negative. Sanger sequencing demonstrated recurrent AKT1 E17K mutations in four cases (4/6, 66.7%). A review of reported salivary intestinal-like tumors revealed 3 out of 13 cases presented with papillary morphology and CDX2 negative. Some salivary papillary neoplasms with mucinous cytologic features termed as intraductal papillary neoplasms or mucinous adenocarcinomas were also reported with AKT1 E17K mutations. CONCLUSION: We describe 6 cases of salivary gland papillary adenocarcinoma with intestinal-like mucinous cytologic features, which are different from conventional intestinal-type adenocarcinoma, presenting a consistent immunophenotype of CK7 & MUC1 positive, CK20 & CDX2 negative and exhibiting recurrent AKT1 E17K mutations.

Association between rs20456 and rs6930913 of Kinesin-Like Family 6 and Hypertension in a Chinese Cohort.

This study aimed to investigate the relationship between kinesin-like family 6 (KIF6) polymorphisms and hypertension in a northeast Chinese cohort. In this study, two single nucleotide polymorphisms of KIF6 (rs20456 and rs6930913) and their haplotype were analyzed in 382 hypertension patients and 378 controls with SHEsis analysis platform, and the gene-environmental interactions were evaluated with logistic regression analysis. After adjusting for confounding factors, significantly lower risk of hypertension was observed in participants with genotype TC (0.416 (CI 0.299-0.578), p < 0.001) and CC (0.577 (0.389-0.857), p=0.007) of rs20456 compared with TT. For rs6930913, allele T (0.522 (0.386-0.704), p < 0.001), genotype TT (0.325 (0.205-0.515), p < 0.001), and genotype CT (0.513 (0.379-0.693), p < 0.001) were significantly associated with lower risk of hypertension than allele C and CC genotype, respectively. Gene-environment analyses confirmed the significant influence on hypertension by the interactions between genotypes distribution in rs20456 (CT: p=0.036, TT: p=0.022) and smoking status. No interactions were found between smoking and rs6930913, except those with dominant or recessive genetic models (both P s =0.006). There were no interactions between KIF6 and overweight (all P s > 0.05). Haplotype analyses showed that CC (p=0.005) and TC (p=0.001) of rs20456 and rs6930913 were significantly associated with a statistically increased risk of hypertension. The false-positive report probability (FPRP) analysis was used to verify significant findings. In conclusions, KIF6 might affect the susceptibility of hypertension. The allele C (rs20456) and allele T (rs690913) were inclined to protect individuals from hypertension both in genotype and haplotype analyses.

An unexpected discovery toward novel membrane active sulfonyl thiazoles as potential MRSA DNA intercalators.

Aim: With the increasing emergence of drug-resistant bacteria, the need for new antimicrobial agents has become extremely urgent. This work was to develop sulfonyl thiazoles as potential antibacterial agents. Results & methodology: Novel hybrids of sulfonyl thiazoles were developed from commercial acetanilide and acetylthiazole. Hybrids 6e and 6f displayed excellent inhibitory efficacy against clinical methicillin-resistant Staphylococcus aureus (MRSA) (minimum inhibitory concentration = 1 µg/ml) without obvious toxicity toward normal mammalian cells (RAW 264.7). The combination uses were found to improve the antimicrobial ability. Further preliminary antibacterial mechanism experiments showed that the active molecule 6f could effectively interfere with MRSA membrane and insert into MRSA DNA. Conclusion: Compounds 6e and 6f could serve as potential DNA-targeting templates toward the development of promising antimicrobial agents.

Observation on the clinical effect of thunder-fire moxibustion combined with acupressure on ocular muscle spasm: A clinical randomized controlled trial.

INTRODUCTION: With the rapid development of social economy, peoples dependence on computers and mobile phones is increasing day by day. This causes people to often overuse. Therefore, the incidence of Ocular muscle spasm has been increasing year by year in recent years. The disease usually starts and hides, which seriously affects the patients social image, daily life, and work. METHODS/DESIGN: We will compare the clinical efficacy of thunder-fire moxibustion combined with acupressure with pure thunder-fire moxibustion on Ocular muscle spasm using random control method. DISCUSSION: We aim to find a simple, safe, simple and effective Chinese medicine nursing technology that relieves Ocular muscle spasm. TRIAL REGISTRATION: ClinicalTrials.gov,ChiCTR2000034187, Registered on 27 June 2020.

Recombinant Human Brain Natriuretic Peptide Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting CD4+ T Cell Proliferation via PI3K/AKT/mTOR Pathway Activation.

Inflammation plays a major role in the development of myocardial ischemia-reperfusion (IR) injury. Recombinant human brain natriuretic peptide (rhBNP), a man-made version of a peptide that is elevated in heart failure, exhibits anti-inflammatory effects in various tissues. However, its role in myocardial IR injury remains unclear. In this study, we demonstrate that treatment with rhBNP provided protection for mice against myocardial IR injury as manifested by reduced infarct size and well-preserved myocardial, attenuated inflammatory infiltration and CD4+ T cell proliferation function, and inhibited expression of proinflammatory related genes. Furthermore, mechanistic studies revealed that rhBNP inhibited Jurkat T proliferation by promoting PI3K/AKT/mTOR phosphorylation. Collectively, our data suggest that the administration of rhBNP during IR injury could expand our understanding of the cardioprotective effects of rhBNP.

Notch activation leads to loss of myoepithelial differentiation and poor outcome in solid adenoid cystic carcinoma.

OBJECTIVE: We aimed to investigate Notch pathway dysregulation in solid adenoid cystic carcinoma (AdCC) and to define the association of Notch activation with cell differentiation and prognosis in AdCCs. MATERIALS AND METHODS: Notch1 mutations were detected from 125 AdCCs (62 cribriform-tubular; 63 solid). RNA-seq was performed in 16 AdCCs (6 Notch-mutant; 10 wild type). Notch activation indicator NICD and myoepithelial marker p63 were detected using immunohistochemistry and double-labelling immunofluorescence. The effect of exogenous NICD overexpression on p63 expression and cell proliferation was investigated using Western blotting and live-cell imaging. RESULTS: We identified 33 Notch1 activating mutations in 27 AdCCs including 26 solid and 1 cribriform-tubular subtypes. Six tumours harboured more than one Notch1 mutation, and 18 Notch1 mutations were novel. Most (47/63, 74.6%) solid AdCCs showed NICD overexpression, whereas 61 of 62 (98.4%) cribriform-tubular tumours were negative. NICD and p63 exhibited mutually exclusive expression, and exogenous NICD overexpression promoted cell proliferation and decreased p63 expression. NICD overexpression and Notch mutations were poor indicators for overall survival and metastasis, especially bone metastasis. CONCLUSIONS: Dysregulated Notch signalling plays a critical role in AdCC severity. Notch activation may contribute to loss of myoepithelial differentiation as well as high proliferation and metastasis rates in solid AdCC.

Clinical observation of Dan-Hong Hua-Yu oral solution in treating retinal vein occlusion.

INTRODUCTION: Retinal vein occlusion refers to diseases with decreased vision, dilated tortuous retinal veins visible on the fundus, and retinal hemorrhage, edema, and osmosis distributed along the vein. There is still no ideal intervention to treat central retinal vein occlusion. This study plan to observe the efficacy of Dan-Hong Hua-Yu oral solution in treating non-ischemic retinal vein occlusion, in order to provide new treatment ideas. METHODS/DESIGN: We plan to use random number table method, 64 cases of non-ischemic central retinal vein occlusion that meet the inclusion criteria will be randomly divided into a treatment group and a control group. The intervention group will be treated with Dan-Hong Hua-Yu oral solution according to the syndrome differentiation of Traditional Chinese medicine and the patient's fundus condition. Each group will take 4 weeks as a course of treatment and three consecutive courses of treatment without any interval during the course of treatment. Changes of visual acuity, fundus performance, and total clinical symptoms of patients before and after treatment will be observed. DISCUSSION: This study will observe the efficacy of Dan-Hong Hua-Yu oral solution in the treatment of non-ischemic central retinal vein occlusion, with a view to providing new treatment ideas. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000030625, Registered on March 08, 2020.