Heterotopic pancreas in the gallbladder: A case report.

BACKGROUND: Heterotopic pancreas (HP) refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas. HP occurs mostly in the stomach, duodenum, and colon, and rarely in the gallbladder. CASE SUMMARY: A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years. An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder. The patient underwent a laparoscopic cholecystectomy, and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder. The patient had a favorable recovery and was discharged on postoperative day 3. She did not report any symptoms or complications at the 6-mo postoperative follow-up. Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy. CONCLUSION: This case provides more information about HP in the gallbladder, a rare occurrence.

Peptide hydrogel based electrochemical biosensor for simultaneous monitoring of H2O2 and NO released from three-dimensional cultured breast cancer cells.

An antifouling peptide hydrogel-based electrochemical biosensor was developed for real-time monitoring of hydrogen peroxide (H2O2) and nitric oxide (NO) released by 3D cultured breast cancer cells upon drug stimulation. Platinum nanoparticles (Pt NPs) were electrodeposited on titanium mesh (Pt NPs/TM) to enhance sensitivity and shown to possess excellent electrocatalytic ability toward H2O2 and NO. The composite hydrogel formed by co-assembling of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) and a fluorine methoxycarbonyl group-functionalized Lys-(Fmoc)-Asp was coated on Pt NPs/TM electrode surface to provide cellular scaffolding. Their favorable biocompatibility promoted cell adhesion and growth, while good hydrophilicity endowed the sensor with greatly enhanced antifouling capability in complex cell culture environments. The biosensor successfully determined H2O2 and NO secretion from both non-metastatic and metastatic breast cancer cells in real time. Our results demonstrated robust associations between reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and cell malignancy, with the main difference in oxidative stress between the two subtypes of cells being NO release, particularly emphasizing RNS's critical leading in driving cancer metastasis and invasion progression. This sensor holds great potential for cell-release research under the in vivo-like microenvironment and could reveal RNS as an attractive therapeutic target for treating breast cancer.

SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.

Lymph node (LN) metastasis is the dominant cause of death in bladder cancer (BCa) patients, but the underlying mechanism remains largely unknown. In recent years, accumulating studies have confirmed that bidirectional mitochondria-nucleus communication is essential for sustaining multiple function of mitochondria. However, little has been studied regarding whether and how the translocation of mitochondrial proteins is involved in LN metastasis. In this study, we first identified that the SUMO E3 ligase MUL1 was significantly downregulated in LN-metastatic BCa tissues and correlated with a good prognosis. Mechanistically, MUL1 SUMOylated HSPA9 at the K612 residue, leading to HSPA9 export from mitochondria and interaction with SUZ12 and in the nucleus. Consequently, MUL1 induced the ubiquitination-mediated degradation of SUZ12 and EZH2 and induced downstream STAT3 pathway inhibition in a HSPA9-dependent manner. Importantly, mutation of HSPA9 SUMO-conjugation motifs limited the translocation of mitochondrial HSPA9 and blocked the HSPA9-SUZ12 and HSPA9-EZH2 interactions. With mutation of the HSPA9 K612 site, the suppressive role of MUL1 overexpression was lost in BCa cells. Further in vitro and in vivo assays revealed that MUL1 inhibits the metastasis and proliferation of BCa cells. Overall, our study reveals a novel function and molecular mechanism of SUMO E3 ligases in LN metastasis.

FDX1 downregulation activates mitophagy and the PI3K/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production.

BACKGROUND: Mitochondrial dysfunction and metabolic reprogramming can lead to the development and progression of hepatocellular carcinoma (HCC). Ferredoxin 1 (FDX1) is a small mitochondrial protein and recent studies have shown that FDX1 plays an important role in tumor cuproptosis, but its role in HCC is still elusive. In this study, we aim to investigate the expression and novel functions of FDX1 in HCC. METHODS: FDX1 expression was first analyzed in publicly available datasets and verified by immunohistochemistry, qRT-PCR and Western blot. In vitro and in vivo experiments were applied to explore the functions of FDX1. Non-targeted metabolomics and RNA-sequencing were used to determine molecular mechanism. mRFP-GFP-LC3 lentivirus transfection, Mito-Tracker Red and Lyso-Tracker Green staining, transmission electron microscopy, flow cytometry, JC-1 staining, etc. were used to analyze mitophagy or ROS levels. Hydrodynamic tail vein injection (HTVi) and patient-derived organoid (PDO) models were used to analyze effect of FDX1 overexpression. RESULTS: FDX1 expression is significantly downregulated in HCC tissues. FDX1 downregulation promotes HCC cell proliferation, invasion in vitro and growth, metastasis in vivo. In addition, FDX1 affects metabolism of HCC cells and is associated with autophagy. We then confirmed that FDX1 deficiency increases ROS levels, activates mitophagy and the PI3K/AKT signaling pathway in HCC cells. Interestingly, scavenging ROS attenuates the tumor-promoting role and mitophagy of FDX1 downregulation. The results of HTVi and PDO models both find that FDX1 elevation significantly inhibits HCC progression. Moreover, low FDX1 expression is associated with shorter survival and is an independent risk factor for prognosis in HCC patients. CONCLUSIONS: Our research had investigated novel functions of FDX1 in HCC. Downregulation of FDX1 contributes to metabolic reprogramming and leads to ROS-mediated activation of mitophagy and the PI3K/AKT signaling pathway. FDX1 is a potential prognostic biomarker and increasing FDX1 expression may be a potential therapeutic approach to inhibit HCC progression.

A Three-Dimensional Electrochemiluminescence Sensor Integrated with Peptide Hydrogel for Detection of H2O2 Released from Different Subtypes of Breast Cancer Cells.

Breast cancer is a malignant tumor, with various subtypes showing different behaviors. Endogenous H2O2 is an important marker of tumor progression, which makes it important to study the relationship between breast cancer subtypes and H2O2 for pathogenesis and treatment strategies, but this has rarely been reported so far. In this work, we constructed a three-dimensional (3D) electrochemiluminescence (ECL) sensing platform for the detection of H2O2 released from two typical subtypes of breast cancer cells (MCF-7 cells for luminal A-type and MDA-MB-231 cells for three negative breast cancers, TNBCs). To adequately replicate the tumor microenvironment, the peptide hydrogel was introduced as a scaffold for 3D cell culture. The titanium foam (TF) was used as a 3D electrode to better match the 3D culture substrate. N-(4-Aminobutyl)-N-ethylisoluminol (ABEI) was selected as the ECL emitter and assembled into the peptide hydrogel by hydrogen bonding and π-stacking, which resulted in a stable and homogeneous distribution of ABEI along the hydrogel fibers. Furthermore, basic amino acids were introduced to provide alkaline microenvironment for ABEI. Therefore, ABEI exhibited high ECL efficiency, resulting in a high sensitivity with an ultralow detection limit of 0.023 nM (S/N = 3) for H2O2 of the proposed ECL biosensor. MCF-7 and MDA-MB-231 cells were cultured in a 3D peptide hydrogel/ABEI/TF electrode, respectively, and endogenous H2O2 was successfully monitored. A notably significant difference of H2O2 released between MDA-MB-231 cells and MCF-7 cells without stimulation but similar extra release with stimulation were observed. These findings may help understand the physiological mechanisms behind the various subtypes and reactive oxygen species (ROS)-related treatment for breast cancer.

Research progress on miR-124-3p in the field of kidney disease.

MicroRNAs (miRNAs) are 18-25 nucleotides long, single-stranded, non-coding RNA molecules that regulate gene expression. They play a crucial role in maintaining normal cellular functions and homeostasis in organisms. Studies have shown that miR-124-3p is highly expressed in brain tissue and plays a significant role in nervous system development. It is also described as a tumor suppressor, regulating biological processes like cancer cell proliferation, apoptosis, migration, and invasion by controlling multiple downstream target genes. miR-124-3p has been found to be involved in the progression of various kidney diseases, including diabetic kidney disease, calcium oxalate kidney stones, acute kidney injury, lupus nephritis, and renal interstitial fibrosis. It mediates these processes through mechanisms like oxidative stress, inflammation, autophagy, and ferroptosis. To lay the foundation for future therapeutic strategies, this research group reviewed recent studies on the functional roles of miR-124-3p in renal diseases and the regulation of its downstream target genes. Additionally, the feasibility, limitations, and potential application of miR-124-3p as a diagnostic biomarker and therapeutic target were thoroughly investigated.

Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Suppression of P53 Pathway is an Important Factor Inducing Acute Graft-versus-Host Disease Through T Cell Activation Based on Bioinformatics Analysis.

Purpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question. Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort. Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis. Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.

[Determination of the derivatization reactivity between α/ß-dicarbonyl compounds and standard citrullinated peptides based on matrix-assisted laser desorption ionization-time-of-flight mass spectrometry].

Protein citrullination is an irreversible post-translational modification process regulated by peptidylarginine deiminases (PADs) in the presence of Ca2+. This process is closely related to the occurrence and development of autoimmune diseases, cancers, neurological disorders, cardiovascular and cerebrovascular diseases, and other major diseases. The analysis of protein citrullination by biomass spectrometry confronts great challenges owing to its low abundance, lack of affinity tags, small mass-to-charge ratio change, and susceptibility to isotopic and deamidation interferences. The methods commonly used to study the protein citrullination mainly involve the chemical derivatization of the urea group of the guanine side chain of the peptide to increase the mass-to-charge ratio difference of the citrullinated peptide. Affinity-enriched labels are then introduced to effectively improve the sensitivity and accuracy of protein citrullination by mass spectrometry. 2,3-Butanedione or phenylglyoxal compounds are often used as derivatization reagents to increase the mass-to-charge ratio difference of the citrullinated peptide, and the resulting derivatives have been observed to contain α-dicarbonyl structures. To date, however, no relevant studies on the reactivity of dicarbonyl compounds with citrullinated peptides have been reported. In this study, we determined whether six α-dicarbonyl and two ß-dicarbonyl compounds undergo derivatization reactions with standard citrullinated peptides using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Among the α-dicarbonyl compounds, 2,3-butanedione and glyoxal reacted efficiently with several standard citrullinated peptides, but yielded a series of by-products. Phenylglyoxal, methylglyoxal, 1,2-cyclohexanedione, and 1,10-phenanthroline-5,6-dione also derivated efficiently with standard citrullinated peptides, generating a single derivative. Thus, a new derivatization method that could yield a single derivative was identified. Among the ß-dicarbonyl compounds, 1,3-cyclohexanedione and 2,4-pentanedione successfully reacted with the standard citrullinated peptides, and generated a single derivative. However, their reaction efficiency was very low, indicating that the ß-dicarbonyl compounds are unsuitable for the chemical derivatization of citrullinated peptides. The above results indicate that the α-dicarbonyl structure is necessary for realizing the efficient and specific chemical derivatization of citrullinated peptides. Moreover, the side chains of the α-dicarbonyl structure determine the structure of the derivatives, derivatization efficiency, and generation (or otherwise) of by-products. Therefore, the specific enrichment and precise identification of citrullinated peptides can be achieved by synthesizing α-dicarbonyl structured compounds containing affinity tags. The proposed method enables the identification of citrullinated proteins and their modified sites by MS, thereby providing a better understanding of the distribution of citrullinated proteins in different tissues. The findings will be beneficial for studies on the mechanism of action of citrullinated proteins in a variety of diseases.

Managing intraoperative rupture of internal carotid pseudoaneurysms during endoscopic transnasal optic canal decompression: a case report.

Background: Endoscopic transnasal optic canal decompression is widely used in the treatment of traumatic optic neuropathy (TON) following head and craniofacial trauma. Intraoperative hemorrhage is a catastrophic surgical complication during optic canal decompression. Case description: We present two cases of patients with TON who suffered unexpected intra-operative massive bleeding during endoscopic transnasal optic canal decompression. After intraoperative hemostasis was achieved, emergent cerebral angiograms demonstrated the formation of internal carotid pseudoaneurysms, which were immediately embolized with coils combined with or without Onyx with balloon assistance. One of these cases was also complicated by a postoperative cerebrospinal fluid leak, which failed to be treated with lumbar drainage but was successfully repaired with endoscopic transnasal surgery. Conclusion: The intra-operative rupture of ICA pseudoaneurysm is a rare but catastrophic complication in TON patients. Intraoperative massive bleeding indicates rupture of ICA pseudoaneurysm. Postoperative emergency angiography and endovascular therapy should be arranged to evaluate and repair the cerebral vascular injury. Endoscopic trans-nasal surgery repairing CSF leaks resistant to lumbar drainage could be efficient and safe following pseudoaneurysm embolization.

Stabilization of TGF-ß Receptor 1 by a Receptor-Associated Adaptor Dictates Feedback Activation of the TGF-ß Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance.

Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug-resistant CSCs. Through a genome-wide CRISPR activation screen utilizing stem-like drug-resistant properties as a readout, the TGF-ß receptor-associated binding protein 1 (TGFBRAP1) is identified as a TGF-ß-inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF-ß receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF-ß signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly-ubiquitination and proteasomal degradation. Moreover, hyperactive TGF-ß signaling in turn up-regulates TGFBRAP1 expression in drug-resistant CSC-like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF-ß signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF-ß signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1-mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF-ß signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels. METHODS: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated. RESULTS: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively. CONCLUSION: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 .

Retinal thickness and microvascular alterations observed by optical coherence tomography in antineutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional study.

Background: As an autoimmune disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often affects multiple organs, including the ocular system. This study aims to investigate differences in retinal thickness (RT) and retinal superficial vascular density (SVD) between patients with AAV and healthy controls (HCs) using optical coherence tomography angiography (OCTA). Currently, these differences are not clear. Methods: A total of 16 AAV individuals (32 eyes) and 16 HCs (32 eyes) were recruited to this cross-sectional study conducted in the First Affiliated Hospital of Nanchang University from June 2023 to September 2023. The study protocol conformed with the tenets of the Declaration of Helsinki (as revised in 2013). Each image observed by OCTA was divided into 9 regions using the Early Treatment Diabetic Retinopathy Study (ETDRS) subzones as a guide. Results: In the full layer, the RT of AAV patients was found to be significantly reduced in the inner superior (IS, P<0.001), outer superior (OS, P=0.003), inner temporal (IT, P=0.003), and outer temporal (OT, P<0.001) regions; inner RT was significantly lower in the IS (P=0.006), OS (P<0.001), inner nasal (IN, P=0.005), outer nasal (ON, P<0.001), and center (C, P=0.01) regions than that in HCs. Outer RT of AAV patients showed a reduction in the IS (P<0.001), as well as IT (P=0.008), and OT (P<0.001) regions. No statistically significant differences were seen in the different subregions in other different layers (P>0.05). Only the inner inferior (II) and outer inferior (OI) regions of SVD in AAV patients did not differ significantly from controls. All other regions showed a reduction in SVD. The details are as follows: IS (P<0.001), OS (P<0.001), IT (P=0.005), OT (P<0.001), IN (P<0.001), ON (P<0.001), and C (P=0.003). According to receiver operating characteristic (ROC) curve analysis, the full IS region [area under the curve (AUC): 0.8892, 95% confidence interval (CI): 0.8041-0.9742, P<0.001] had the highest diagnostic value for AAV-induced reduction in RT. The IS (AUC: 0.9121, 95% CI: 0.8322-0.9920, P<0.001) region was also the most sensitive to changes in SVD of AAV individuals. In addition, we found that SVD in the IN region (r=-0.4224, 95% CI: -0.6779 to -0.0757, P=0.02) as well as mean visual acuity (r=-0.3922, 95% CI: -0.6579 to -0.0397, P=0.03) of AAV patients were negatively correlated with disease duration. However, we did not find an association between SVD and RT in this study. Conclusions: The findings from OCTA indicated a reduction in RT and SVD among patients with AAV. OCTA allows for the evaluation of AAV-related ocular lesions and holds promise for monitoring of disease progression through regular evaluations.

Global research trends on the links between prostate cancer and erectile dysfunction between 2003 and 2023: A bibliometrics and visualized study.

Background: The incidence of prostate cancer (PC) has increased in recent years. Erectile dysfunction (ED) after prostate cancer treatment has aroused extensive attention. Bibliometric analysis was designed to investigate a systematic understanding of developments between PC and ED during the past 20 years. Methods: Literatures on PC and ED were retrieved from the Web of Science Core Collection database (WoSCC). By using the VOS viewer and CiteSpace software to analysis the metrics of bibliometric literature, such as number of articles, journals, countries, institutions, authors, keywords and associated information. The number of publications per year was statistically analysed and plotted thorough Microsoft Office. In addition, Pajek software was used to adjust the visual map. Results: A total of 2332 screened articles were included in the analysis. The Journal of Sexual Medicine, ranking first among the analysed journals, published 235 articles. The United States and Canada were leaders in PC and ED research. There is a need to strengthen inter-agency cooperation in this area of research on a global scale. Mulhall JP, as the most prolific author in this area of research, published 80 articles. And Rosen RC was the author with the most co-citated (693 co-citated). The main research focus on the prevention, treatment and management of ED after PC treatment in this field through the keyword analysis. Conclusions: Research on PC and ED is expected to expand further worldwide. We found ED, as new sustainable treatment modalities, scientific postoperative management and psychological interventions for patients, may become the research hotspots and should be closely concerned in this study.

Development of a Routine Serological Test Index Panel for the Surveillance of Gastric Cancer Risk in a High-Risk Population.

OBJECTIVE: This study aims to develop a predictive model for the detection of gastric cancer risk utilizing non-invasive parameters and to assess the model's effectiveness in risk stratification for gastric cancer (GC). METHODS: A case-control study was conducted among inpatients with various gastric diseases. These individuals were categorized into two groups: the gastric cancer group (138 cases) and the chronic non-atrophic gastritis (CNAG) group (319 cases). We employed a comprehensive panel of hematological, biochemical, and coagulation parameters derived from routine blood tests. Random Forest and Logistic regression analysis was used for feature selection and model building. Statistical analyses were performed using R version 4.2.3. RESULTS: Logistic regression analysis was employed to establish risk prediction models for GC, incorporating variables such as D-dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and hemoglobin (HGB). A visual nomogram was generated as the final prediction model. The area under the receiver operating characteristic curve (AUC) for the training and test sets were 0.8093 [95% confidence interval (CI), 0.7541-0.8644], and 0.8076 [95% CI 0.7237-0.8915], respectively. Furthermore, we have developed an HTML file, featuring the Logistic equation, which enables real-time assessment of GC risk scores. CONCLUSION: The performance of this predictive model demonstrates its adequacy, making it a valuable and cost-effective noninvasive tool for identifying early gastric cancer (EGC) in patients. Consequently, this model may facilitate the implementation of targeted preventive and intervention strategies in clinical practice.

Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation.

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.

Genetic polymorphism of IL-18 influences susceptibility to lung cancer in population of eastern China.

The association of Interleukin-18 (IL-18) genetic polymorphism with lung cancer risk has yielded inconsistent findings in previous studies. The current research aims to clarify the relationship of IL-18 gene polymorphism with lung cancer susceptibility through experimental investigation and meta-analysis, providing insights for lung cancer prevention and treatment. We conducted a thorough search of major databases from their inception until March 2024. OR and 95%CI were calculated to know the results of meta-analysis. The IL-18 gene polymorphism was detected using the PCR-RFLP method. Significant associations were detected across all genetic models in allele contrast (A vs. C: Odds Ratio [OR] = 1.29, 95% Confidence Interval [CI] = 1.07-1.55, p = 0.006), homozygote comparison (AA vs. CC: OR = 1.87, 95%CI = 1.34-2.62, p < 0.001), recessive genetic model (AA vs. CT/CC: OR = 1.54, 95%CI = 1.08-2.20, p = 0.018), and dominant genetic model (AA/AC vs. CC: OR = 1.41, 95%CI = 1.12-1.78, p = 0.003). Three genotypes (AA, AC, and CC) were identified for the IL-18 -607 C/A polymorphism, with significant associations noted for the AA genotype and A allele (p = 0.018 and 0.005, respectively). This is the first study which investigates this polymorphism with lung cancer in population of eastern China. The IL-18 -607 C/A polymorphism appears to significantly increase the risk of lung cancer in the population of Eastern China. Further research is imperative to validate these findings.

Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease.

In this editorial, we comment on the article by Chen et al. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.

Multiparametric MRI-based radiomics nomogram for the preoperative prediction of lymph node metastasis in rectal cancer: A two-center study.

PURPOSE: To develop a radiomic nomogram based on multiparametric magnetic resonance imaging for the preoperative prediction of lymph node metastasis (LNM) in rectal cancer. METHODS: This retrospective study included 318 patients with pathologically proven rectal adenocarcinoma from two hospitals. Radiomic features were extracted from T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging scans of the training cohort, and the radsore model was then constructed. The combined model was obtained by integrating the Radscore and clinical models. The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic effectiveness of each model, and the best-performing model was used to develop the nomogram. RESULTS: The Radscore and clinical models exhibited similar diagnostic efficacy (DeLong's test, P > 0.05). The AUC of the combined model was significantly higher than those of the clinical and Radscore models in the training cohort (AUC: 0.837 vs. 0.763 and 0.787, P: 0.02120 and 0.02309) and the external validation cohort (AUC: 0.880 vs. 0.797 and 0.779, P: 0.02310 and 0.02471). However, the diagnostic performance of the three models was comparable in the internal validation cohort (P > 0.05). Thus, among the three models, the combined model exhibited the highest diagnostic efficiency. The calibration curve exhibited satisfactory consistency between the nomogram predictions and the actual results. DCA confirmed the considerable clinical usefulness of the nomogram. CONCLUSION: The radiomics nomogram can accurately and noninvasively predict LNM in rectal cancer before surgery, serving as a convenient visualization tool for informing treatment decisions, including the choice of surgical approach and the need for neoadjuvant therapy.

Meta-analysis of the accuracy for RASSF1A methylation in bronchial aspirates for the diagnosis of lung cancer.

OBJECTIVE: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis. METHODS: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias. RESULTS: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance. CONCLUSIONS: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer.