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OBJECTIVE: To investigate the mechanisms behind acquired resistance to erlotinib in head and neck squamous cell carcinoma (HNSCC) with a focus on the role of cancer-associated fibroblasts (CAFs) and the PI3K/AKT signaling pathway. MATERIALS AND METHODS: This study analyzed gene expression profiles of erlotinib-sensitive and -resistant HNSCC cell lines using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. It included microarray and RNA-sequencing data, differentially expressed genes (DEGs) analysis, and pathway enrichment. In vitro experiments assessed the functional role of CAFs and the impact of the extracellular matrix component COL5A2 on erlotinib resistance. RESULTS: We identified 124 DEGs associated with erlotinib resistance, with key genes like COL5A2 significantly upregulated. CAFs were found to highly express COL5A2, enhancing erlotinib resistance by activating the PI3K/AKT pathway. Higher erlotinib resistance scores correlated with increased infiltration of CAFs. CONCLUSIONS: Erlotinib resistance in HNSCC is significantly influenced by the tumor microenvironment (TME), particularly through CAFs and the PI3K/AKT pathway. Targeting these mechanisms may offer new therapeutic strategies to overcome resistance in HNSCC patients.

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INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.

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BACKGROUND: Continuous advancements and breakthroughs in flexible gastrointestinal endoscopy have led to alternatives to colonic anastomosis. OBJECTIVE: This study aimed to evaluate the feasibility and safety of end-to-end colonic anastomosis using a single flexible endoscope with the novel through-the-scope "bow-tie" (TTS-BT) device and conventional metal clips in a porcine model. DESIGN: Animal study. SETTINGS: Animal laboratory at China Medical University. PATIENTS: Eight healthy pigs were included. INTERVENTIONS: Eight animals underwent total colonic severance and anastomoses with through-the-scope "bow-tie" devices and metal clips. MAIN OUTCOME MEASURES: The primary outcomes were the success rate of the anastomosis and survival rate during 3-month follow-up. Furthermore, the secondary outcomes were anastomotic site healing, reintervention rate, and rate of anastomotic complications such as bleeding, leakage, stenosis, and obstruction. Six pigs were euthanized, and necropsies were performed 3 months postoperatively, while two pigs were fed for long-term observation. The anastomotic stoma was histologically analyzed using Hematoxylin-eosin and Masson's trichrome staining. RESULTS: End-to-end colonic anastomoses were successfully performed using through-the-scope "bow-tie" devices, and satisfactory healing was achieved in all pigs. The success rate of anastomosis was 100% (8/8). All animals survived postoperatively without anastomotic complications, including bleeding, leakage, or obstruction; however, two cases of stenosis occurred (25%), and one case (12.5%) required reintervention. LIMITATIONS: Large-scale studies should be conducted to verify the feasibility and safety of the through-the-scope "bow-tie" device in other parts of the intestine. CONCLUSIONS: Flexible endoscopy with the through-the-scope "bow-tie" device is feasible and safe for intraluminal colonic anastomosis. This study may expand the indications for full-thickness endoscopic resection in the future. See Video abstract.

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Cortisol is a well-known stress biomarker; this study focuses on using electrochemical immuno-sensing to measure the concentration of cortisol selectively and sensitively in artificial samples. Anti-cortisol antibodies have been immobilised on polycrystalline Au electrodes via strong covalent thiol bonds, fabricating an electrochemical bio-immunosensor for cortisol detection. IrOx was then anodically electrodeposited as a reference electrode on a commercial screen-printed electrode and electrochemical impedance spectrometry (EIS) studies were used to correlate the electrochemical response to cortisol concentration and the induced changes in charge transfer resistance (Rct). A linear relationship between the Rct and the logarithm of cortisol concentration was found in concentrations ranging from 1 ng/mL to 1 mg/mL with limit of detection at 11.85 pg/mL (32.69 pM). The modification of the reference electrode with iridium oxide has greatly improved the reproducibility of the screen-printed electrode. The sensing system can provide a reliable and sensitive detection approach for cortisol measurements.

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Fluorescent 4D printing materials, as innovative materials that combine fluorescent characteristics with 4D printing technology, have attracted widespread interest and research. In this study, green lignin-derived carbon quantum dots (CQDs) were used as the fluorescent module, and renewable poly(propylene carbonate) polyurethane (PPCU) was used for toughening. A new low-cost fluorescent polylactic acid (PLA) composite filament for 4D printing was developed using a simple melt extrusion method. The strength of the prepared composite was maintained at 32 MPa, while the elongation at break increased 8-fold (34 % increase), demonstrating excellent shape fixed ratio (∼99 %), recovery ratio (∼92 %), and rapid shape memory recovery speed. The presence of PPCU prevented fluorescence quenching of the CQDs in the PLA matrix, allowing the composite to emit bright green fluorescence under 365 nm ultraviolet light. The composite exhibited shear thinning behavior and had an ideal melt viscosity for 3D printing. The results obtained demonstrated the versatility of these easy-to-manufacture and low-cost filaments, opening up a novel and convenient method for the preparation of strong, tough, and multifunctional PLA materials, increasing their potential application value.

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Cytosine modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), play crucial roles in numerous biological processes. Current analytical methods are often constrained to the separate detection of either 5mC or 5hmC, or the combination of both modifications. The ability to simultaneously detect C, 5mC, and 5hmC at the same genomic locations with precise stoichiometry is highly desirable. Herein, we introduce a method termed engineered deaminase-assisted sequencing (EDA-seq) for the simultaneous quantification of C, 5mC, and 5hmC at the same genomic sites. EDA-seq utilizes a specially engineered protein, derived from human APOBEC3A (A3A), known as eA3A-M5. eA3A-M5 exhibits distinct deamination capabilities for C, 5mC, and 5hmC. In EDA-seq, C undergoes complete deamination and is sequenced as T. 5mC is partially deaminated resulting in a mixed readout of T and C, and 5hmC remains undeaminated and is read as C. Consequently, the proportion of T readouts (P T) reflects the collective occurrences of C and 5mC, regulated by the deamination rate of 5mC (R 5mC). By determining R 5mC and P T values, we can deduce the precise levels of C, 5mC, and 5hmC at particular genomic locations. We successfully used EDA-seq to simultaneously measure C, 5mC, and 5hmC at specific loci within human lung cancer tissue and their normal counterpart. The results from EDA-seq demonstrated a strong concordance with those obtained from the combined application of BS-seq and ACE-seq methods. EDA-seq eliminates the need for bisulfite treatment, DNA oxidation or glycosylation and uniquely enables simultaneous quantification of C, 5mC and 5hmC at the same genomic locations.

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BACKGROUND: MASH is a common clinical disease that can lead to advanced liver conditions, but no approved pharmacotherapies are available due to an incomplete understanding of its pathogenesis. Damaged DNA binding protein 1 (DDB1) participates in lipid metabolism. Nevertheless, the function of DDB1 in MASH is unclear. METHODS: Clinical liver samples were obtained from patients with MASH and control individuals by liver biopsy. Hepatocyte-specific Ddb1-knockout mice and liver Hmgb1 knockdown mice were fed with a methionine-and choline-deficient diet to induce MASH. RESULTS: We found that the expression of DDB1 in the liver was significantly decreased in MASH models. Hepatocyte-specific ablation of DDB1 markedly alleviated methionine-and choline-deficient diet-induced liver steatosis but unexpectedly exacerbated inflammation and fibrosis. Mechanistically, DDB1 deficiency attenuated hepatic steatosis by downregulating the expression of lipid synthesis and uptake genes. We identified high-mobility group box 1 as a key candidate target for DDB1-mediated liver injury. DDB1 deficiency upregulated the expression and extracellular release of high-mobility group box 1, which further increased macrophage infiltration and activated HSCs, ultimately leading to the exacerbation of liver inflammation and fibrosis. CONCLUSIONS: These data demonstrate the independent regulation of hepatic steatosis and injury in MASH. These findings have considerable clinical implications for the development of therapeutic strategies for MASH.

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BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is unavoidable even despite the development of more effective surgical approaches. During hepatic IRI, activated HSC (aHSC) are involved in liver injury and recovery. APPROACH AND RESULT: A proportion of aHSC increased significantly both in the mouse liver tissues with IRI and in the primary mouse HSCs and LX-2 cells during hypoxia-reoxygenation. "Loss-of-function" experiments revealed that depleting aHSC with gliotoxin exacerbated liver damage in IRI mice. Subsequently, we found that the transcription of mRNA and the expression of B and T lymphocyte attenuator (BTLA) protein were lower in aHSC compared with quiescent HSCs. Interestingly, overexpression or knockdown of BTLA resulted in opposite changes in the activation of specific markers for HSCs such as collagen type I alpha 1, α-smooth muscle actin, and Vimentin. Moreover, the upregulation of these markers was also observed in the liver tissues of global BLTA-deficient (BTLA-/-) mice and was higher after hepatic IRI. Compared with wild-type mice, aHSC were higher, and liver injury was lower in BTLA-/- mice following IRI. However, the depletion of aHSC reversed these effects. In addition, the depletion of aHSC significantly exacerbated liver damage in BTLA-/- mice with hepatic IRI. Furthermore, the TGF-ß1 signaling pathway was identified as a potential mechanism for BTLA to negatively regulate the activation of HSCs in vivo and in vitro. CONCLUSIONS: These novel findings revealed a critical role of BTLA. Particularly, the receptor inhibits HSC-activated signaling in acute IRI, implying that it is a potential immunotherapeutic target for decreasing the IRI risk.

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BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis. PURPOSE: The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated. PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive. MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT). COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy). ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ2 or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance. RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ＜ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients. CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.

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BACKGROUND: Epidemiological evidence has indicated the occurrence of idiopathic pulmonary fibrosis (IPF) with coexisting lung cancer is not a coincidence. The pathogenic mechanisms shared between IPF and non-small cell lung cancer (NSCLC) at the transcriptional level remain elusive and need to be further elucidated. METHODS: IPF and NSCLC datasets of expression profiles were obtained from the GEO database. Firstly, to detect the shared dysregulated genes positively correlated with both IPF and NSCLC, differentially expressed analysis and WGCNA analysis were carried out. Functional enrichment and the construction of protein-protein network were employed to reveal pathogenic mechanisms related to two diseases mediated by the shared dysregulated genes. Then, the LASSO regression was adopted for screening critical candidate biomarkers for two disorders. Moreover, ROC curves were applied to evaluate the diagnostic value of the candidate biomarkers in both IPF and NSCLC. RESULTS: The 20 shared dysregulated genes positively correlated with both IPF and NSCLC were identified after intersecting differentially expressed analysis and WGCNA analysis. Functional enrichment revealed the 20 shared genes mostly enriched in extracellular region, which is critical in the organization of extracellular matrix. The protein-protein networks unrevealed the interaction of the 11 shared genes involving in collagen deposition and the connection between PYCR1 with PSAT1. PSAT1, PYCR1, COL10A1 and KIAA1683 were screened by the LASSO regression. ROC curves comprising area under the curve (AUC) verified the potential diagnostic value of PSAT1 and COL10A1 in both IPF and NSCLC. CONCLUSIONS: We revealed dysregulated extracellular matrix through aberrant expression of the relevant genes, which provided further understanding for the common molecular mechanisms predisposing the occurrence of both IPF and NSCLC.

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Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

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Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

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Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Results: Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

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BACKGROUND: Remimazolam is a new benzodiazepine used for procedural sedation and general anesthesia. Several studies have used remimazolam for bendable bronchoscopy. AIM: To assess the safety and efficacy of remimazolam for sedation in patients undergoing bendable bronchoscopy by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: We searched the EMBASE, PubMed, Cochrane Library, and Web of Science databases for RCTs on bendable bronchoscopic procedural sedation with remimazolam vs conventional sedatives (CS). RESULTS: Five studies with 1080 cases were included. Remimazolam had the same sedation success rate compared with CS [relative risk (RR): 1.35, 95%CI: 0.60-3.05, P = 0.474, I2 = 99.6%]. However, remimazolam was associated with a lower incidence of hypotension (RR: 0.61; 95%CI: 0.40-0.95, P = 0.027; I2 = 65.1%) and a lower incidence of respiratory depression (RR: 0.50, 95%CI: 0.33-0.77, P = 0.002, I2 = 42.3%). A subgroup analysis showed a higher success rate of sedation with remimazolam than midazolam (RR: 2.45, 95%CI: 1.76-3.42, P < 0.001). Compared with propofol, the incidence of hypotension (RR: 0.45, 95%CI: 0.32-0.64, P < 0.001, I2 = 0.0%), respiratory depression (RR: 0.48, 95%CI: 0.30-0.76, P = 0.002, I2 = 78.4%), hypoxemia (RR: 0.36, 95%CI: 0.15-0.87, P = 0.023), and injection pain (RR: 0.04, 95%CI: 0.01-0.28, P = 0.001) were lower. CONCLUSION: Remimazolam is safe and effective during bronchoscopy. The sedation success rate was similar to that in the CS group. However, remimazolam has a higher safety profile, with fewer inhibitory effects on respiration and circulation.

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DNA cytosine methylation (5-methylcytosine, 5mC) is a predominant epigenetic modification that plays a critical role in a variety of biological and pathological processes in mammals. In active DNA demethylation, the 10-11 translocation (TET) dioxygenases can sequentially oxidize 5mC to generate three modified forms of cytosine, 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Beyond being a demethylation intermediate, recent studies have shown that 5fC has regulatory functions in gene expression and chromatin organization. While some methods have been developed to detect 5fC, genome-wide mapping of 5fC at base resolution is still highly desirable. Herein, we propose a chemical labeling enrichment and deamination sequencing (CLED-seq) method for detecting 5fC in genomic DNA at single-base resolution. The CLED-seq method utilizes selective labeling and enrichment of 5fC-containing DNA fragments, followed by deamination mediated by apolipoprotein B mRNA-editing catalytic polypeptide-like 3A (APOBEC3A or A3A) and sequencing. In the CLED-seq process, while all C, 5mC, and 5hmC are interpreted as T during sequencing, 5fC is still read as C, enabling the precise detection of 5fC in DNA. Using the proposed CLED-seq method, we accomplished genome-wide mapping of 5fC in mouse embryonic stem cells. The mapping study revealed that promoter regions enriched with 5fC overlapped with H3K4me1, H3K4me3, and H3K27ac marks. These findings suggest a correlation between 5fC marks and active gene expression in mESCs. In conclusion, CLED-seq is a straightforward, bisulfite-free method that offers a valuable tool for detecting 5fC in genomes at a single-base resolution.

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BACKGROUND: Head and neck soft tissue sarcoma (HNSTS), rare and heterogeneous malignancies, are treated primarily treated with surgery. However, prognostic indicators that might guide HNSTS management are poorly defined. PURPOSE: Main purpose of this study is to find variables linked to HNSTS patients' prognosis. Assessment of the Tumor, Node, Metastatis (TNM) system is the secondary purpose. STUDY DESIGN, SETTING, SAMPLE: This study is a retrospective cohort performed on HNSTS patients who received surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University from January 1, 2006, to December 31, 2014. Strict inclusion criteria were applied. PREDICTOR VARIABLE: The predictor variable was a set of heterogenous risk factors and were grouped into the following categories: demographic (age and gender), clinical (primary tumor, tumor region, tumor size, and TNM stage), and treatment (surgical margin, treatment therapy). MAIN OUTCOME VARIABLE(S): The primary outcome variables were time to 5-year disease-free survival (DFS) and 5-year overall survival (OS). The secondary outcome variables were time to 5-year tumor local recurrence and metastasis. COVARIATES: Not applicable. ANALYSES: Descriptive statistical analysis was carried out. Pearson χ2 test was employed in univariate analysis. Cox regression was modified for multiple variable analysis with components that had significant P values in univariate analysis or variables with potential prognostic value. Log-rank test was applied to compare survival situations under various variables. P value less than .05 was statistically significant. RESULTS: The sample was composed of 100 subjects with a mean age of 43.47 (standard deviation: 16.15) years old and 56 (56%) were male. The 5-year DSF and OS were 59 and 60%, respectively. Variables associated with poor DFS and OS were age > 60 years (P = .003, hazard ratio [HR]: 4.95, 95% confidence interval [CI]: 1.71,14.1; P = .005, HR: 4.48, 95% CI: 1.57,12.8) and non-primary tumors (P＜.001, HR: 8.41, 95% CI: 2.85,24.8; P = .002, HR: 6.90, 95% CI: 2.46,19.4), respectively. Maxilla and skull base cancers had local recurrence (12/18, 66.7%) more common. T2 (TNM) tumor displayed higher tendency in DFS(P = .009, HR: 4.20, 95% CI: 1.42,12.4) and metastasis(P = .09, HR: 3.51, 95% CI: 0.82,15.0) than T1 (TNM) tumors. CONCLUSION AND RELEVANCE: Poor prognosis is associated with maxilla and skull base tumors as well as patients over 60 years. TNM stage appeared to have limited prognostic significance.

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BACKGROUND: Remimazolam is characterized by rapid action and inactive metabolites. It is used as the general anesthetic for many clinical surgeries. In this study, we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients. AIM: To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults. METHODS: The PubMed, Web of Science, the Cochrane Library databases were queried for the relevant key words "remimazolam," "and propofol," "and gastrointestinal endoscopy or gastroscopy." The search scope was "Title and Abstract," and the search was limited to human studies and publications in English. Seven studies wherein remimazolam and propofol were compared were included for the meta-analysis. RESULTS: We selected seven randomized controlled trials involving 1445 cases for the analysis. Remimazolam reduced the hypotension (relative risk, RR = 0.44, 95%CI: 0.29-0.66, P = 0.000), respiratory depression (RR = 0.46, 95%CI: 0.30-0.70, P = 0.000), injection pain (RR = 0.12, 95%CI: 0.05-0.25, P = 0.000), bradycardia (RR = 0.37, 95%CI: 0.24-0.58, P = 0.000), and time to discharge [weighted mean difference (WMD) = -0.58, 95%CI: -0.97 to -0.18, P = 0.005], compared to those after propofol administration. No obvious differences were observed for postoperative nausea and vomiting (RR = 1.09, 95%CI: 0.97-1.24, P = 0.151), dizziness (RR = 0.77, 95%CI: 0.43-1.36, P = 0.361), successful sedation rate (RR = 0.96, 95%CI: 0.93-1.00, P = 0.083), or the time to become fully alert (WMD = 0.00, 95%CI: -1.08-1.08, P = 0.998). CONCLUSION: Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults. However, further studies are required to confirm these findings.

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Temperature-responsive separation membranes can significantly change their permeability and separation properties in response to changes in their surrounding temperature, improving efficiency and reducing membrane costs. This study focuses on the modification of polyvinylidene fluoride (PVDF) membranes with amphiphilic temperature-responsive copolymer and inorganic nanoparticles. We prepared an amphiphilic temperature-responsive copolymer in which the hydrophilic poly(N-isopropyl acrylamide) (PNIPAAm) was side-linked to a hydrophobic polyvinylidene fluoride (PVDF) skeleton. Subsequently, PVDF-g-PNIPAAm polymer and graphene oxide (GO) were blended with PVDF to prepare temperature-responsive separation membranes. The results showed that temperature-responsive polymers with different NIPAAm grafting ratios were successfully prepared by adjusting the material ratio of NIPAAm to PVDF. PVDF-g-PNIPAAm was blended with PVDF with different grafting ratios to obtain separate membranes with different temperature responses. GO and PVDF-g-PNIPAAm formed a relatively stable hydrogen bond network, which improved the internal structure and antifouling performance of the membrane without affecting the temperature response, thus extending the service life of the membrane.

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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. METHODS: Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. RESULTS: Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. CONCLUSION: This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

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OBJECTIVE: To investigate the potential risk factors for mortality in fungal infection in anti-melanoma differentiation-associated gene 5 antibody-positive associated interstitial lung disease (MDA5-ILD). METHODS: Patients diagnosed with MDA5-ILD from April 2017 to November 2022 were included. The demographic data, laboratory examinations, therapeutic and follow-up information were recorded. Fungal infection diagnosis was established based on a combinations of host factors, clinical features and mycologic evidences. High-dose corticosteroid therapy was defined as the initial corticosteroid doses > 240mg/d. The primary endpoint was mortality. Potential factors for fungal infection occurrence and prognostic factors were analyzed using logistic regression analysis and Cox proportional hazards regression. RESULTS: In total, 121 patients with MDA5-ILD were included. During follow-up, 41 (33.9%) patients had suffered fungal infection and 39.0% (16/41) of whom had ever received high-dose corticosteroid therapy. The median interval from corticosteroid use to the occurrence of fungal infection was 29 (10-48) days. The mean survival time of patients with fungal infection was 234.32 ± 464.76 days. The mortality in MDA5-ILD with fungal infection was 85.4% (35/41), which was significantly higher than those without (85.4% VS 56.3%, P < 0.001). High-dose corticosteroid therapy (P = 0.049) was independent risk factor for fungal infection occurrence. Decreased serum albumin level (P = 0.024) and high-dose corticosteroid therapy (P = 0.008) were both associated with increased mortality in MDA5-ILD patients with fungal infection. CONCLUSION: Fungal infection is associated with an increased mortality in MDA5-ILD. The serum albumin level and corticosteroid dose should be taken into consideration when treating MDA5-ILD. Key Points • This study showed fungal infection is associated with an increased mortality in MDA5-ILD. In MDA5-ILD patients with fungal infection, the presence of decreased serum albumin level and high-dose corticosteroid therapy were identified as predictors for mortality.

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