X-Shaped Knot Fixation and Double Posteromedial Portals for the Treatment of Posterior Cruciate Ligament Tibial Avulsion Fractures With Retention of the Posterior Septum.

Posterior cruciate ligament (PCL) avulsion fractures at the tibial attachment site are managed using various techniques. Some surgeries involve internal fixation with an adjustable double-loop plate, anterior-to-posterior suture suspension fixation, hollow lag screw fixation, and steel wire fixation. In this case, an X-shaped knot and double posteromedial portals are used to retain the posterior septum for fixation. In this technique, we describe double posteromedial portals are used in this method. The internal joint is fixed with an X-shaped knot, and the external joint is fixed with SwiveLock, which puts the wire belt binding PCL compression bone block in a perfect tension state. This surgical technique can achieve a sound functional reduction.

A stable delivery system for curcumin: Fabrication and characterization of self-assembling acylated kidney bean protein isolate nanogels.

The construction of protein-based nano-gels as curcumin delivery system effectively enhances the stability and bioavailability of curcumin. In this study, acylation modification and self-assembly techniques were jointly employed to construct acylated kidney bean protein isolate (AKBPI)-nanogels. Optimal conditions for AKBPI-nanogels were determined to be pH 7, concentration of 2 mg/mL, and temperature at 90℃ for 30 min. The optimized AKBPI-nanogels exhibited excellent uniformity as evidenced by decreasing average particle size (137.35 nm) and polydispersity index (0.38). Acylation enhanced the intermolecular interactions within the nanogel by reducing the polarity of tyrosine microenvironment and free sulfhydryl groups. AKBPI-nanogels demonstrated remarkable characteristics in terms of pH sensitivity, salt concentration, and storage tolerance. The curcumin-loaded AKBPI-nanogels exhibited an encapsulation efficiency of 92.30 % and maintained high antioxidant activity. In simulated gastrointestinal digestion, AKBPI-nanogels facilitated the controlled release and higher bioavailability of curcumin. Therefore, AKBPI-nanogels can be a stable tool for delivering curcumin.

A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling.

MP-HJ-1b is a novel microtubule inhibitor that we designed and reported previously. Ferroptosis is a newly identified type of nonapoptotic cell death induced by ferrous catalysis and lipid peroxidation. Here, transcriptomics, proteomics, and molecular docking analyses were combined to explore the novel effects of MP-HJ-1b on tumors. Both omics analyses suggested that MP-HJ-1b affects ribosomes, and we confirmed that it inhibits the ribosomal component proteins RPL35 and MRPL28. Colchicine was used as an analog, and the results showed that MP-HJ-1b and colchicine increased reactive oxygen species and malondialdehyde levels and decreased reduced glutathione levels, suggesting that they promoted ferroptosis in HeLa cells. Specifically, MP-HJ-1b downregulated SLC7A11 and GPX4 to enhance the classical pathway of ferroptosis, while colchicine upregulated LC3A/B-II and enhanced autophagy. Clinically, the serum concentrations of ferrous ions, reduced glutathione, and Hcy were higher in cervical cancer patients than in healthy individuals. ALT, AST, Cho, HDL-C, and LDL-C levels were decreased in the serum of patients. Our study expands understanding of the way MP-HJ-1b promotes cell death and enriches research on microtubule inhibitors in the ferroptosis field.

Improvement of foaming properties of ovalbumin: Insights into the synergistic effect of preheating and high-intensity ultrasound on physicochemical properties and structure analysis.

Ovalbumin (OVA), characterized by its high concentration in eggs, possesses remarkable foaming properties. Nevertheless, OVA is highly sensitive to thermal changes and acid-base conditions, substantially hampering its application potential for foaming purposes within the food industry. This experiment aimed to examine the effects of preheating and high-intensity ultrasound (HIU) treatment at different powers on OVA foaming properties and explore the underlying mechanisms. The results revealed that OVA exhibited the highest foaming capacity (31.5 %) and foaming stability (96.7 %) under the treatment condition of 200w + 60°C. Additionally, significant improvements were observed in the content of free sulfhydryl groups (37.27 µmg/g), solution viscosity (142.33 mPa·s), and surface hydrophobicity (37.27 µg BPB) under this condition. The absolute value of the zeta potential (-10.28 mV) was significantly increased in the 200w + 60°C treatment group. Moreover, the polymer dispersity index of OVA (0.6045) was significantly reduced, resulting in improved dispersion than the control group. The structural analysis revealed significant changes in the α-helix and ß-sheet content of OVA after treatment at 200w + 60 °C. The X-ray diffraction pattern exhibited sharper peaks, indicating a crystal structure, and the fluorescence peak displayed a slight blue shift along with increased hydrophobicity. Moreover, the preheating and HIU treatment induced a continuous uneven and irregular pore structure in OVA, which ultimately enhanced its foaming properties. In conclusion, the preheating and HIU treatment offers a novel approach to enhance the foaming properties of OVA.

Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes.

Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn-infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro. Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-ß1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-ß1/Smads axis to promote metastasis.

CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy-dependent ferroptosis.

Cisplatin is the first-line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy-dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR-508-3p/Bcl-2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.

Osteoarthritis related epigenetic variations in miRNA expression and DNA methylation.

Osteoarthritis (OA) is chronic arthritis characterized by articular cartilage degradation. However, a comprehensive regulatory network for OA-related microRNAs and DNA methylation modifications has yet to be established. Thus, we aimed to identify epigenetic changes in microRNAs and DNA methylation and establish the regulatory network between miRNAs and DNA methylation. The mRNA, miRNA, and DNA methylation expression profiles of healthy or osteoarthritis articular cartilage samples were downloaded from Gene Expression Omnibus (GEO) database, including GSE169077, GSE175961, and GSE162484. The differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially methylated genes (DMGs) were analyzed by the online tool GEO2R. DAVID and STRING databases were applied for functional enrichment analysis and protein-protein interaction (PPI) network. Potential therapeutic compounds for the treatment of OA were identified by Connectivity map (CMap) analysis. A total of 1424 up-regulated DEGs, 1558 down-regulated DEGs, 5 DEMs with high expression, 6 DEMs with low expression, 1436 hypermethylated genes, and 455 hypomethylated genes were selected. A total of 136 up-regulated and 65 downregulated genes were identified by overlapping DEGs and DEMs predicted target genes which were enriched in apoptosis and circadian rhythm. A total of 39 hypomethylated and 117 hypermethylated genes were obtained by overlapping DEGs and DMGs, which were associated with ECM receptor interactions and cellular metabolic processes, cell connectivity, and transcription. Moreover, The PPI network showed COL5A1, COL6A1, LAMA4, T3GAL6A, and TP53 were the most connective proteins. After overlapping of DEGs, DMGs and DEMs predicted targeted genes, 4 up-regulated genes and 11 down-regulated genes were enriched in the Axon guidance pathway. The top ten genes ranked by PPI network connectivity degree in the up-regulated and downregulated overlapping genes of DEGs and DMGs were further analyzed by the CMap database, and nine chemicals were predicted as potential drugs for the treatment of OA. In conclusion, TP53, COL5A1, COL6A1, LAMA4, and ST3GAL6 may play important roles in OA genesis and development.

Ultrasonic diagnosis of delayed hematoma during emergency removal of traumatic intracranial hematoma: A case report and literature review.

RATIONALE: It is emergency and vital during neurosurgical procedure in traumatic intracranial when an acute intraoperative brain bulge (AIBB) is occurred. It is important to get a diagnosis quickly. PATIENT CONCERNS: A 44-year-old man was undergone a neurosurgical procedure for the left side of traumatic intracranial hematoma. An AIBB was occurred during the surgery. Computed tomography (CT) is always used in diagnosis when an AIBB is occurred, but more time is needed when CT is conducted. DIAGNOSES: We diagnosed the AIBB through bedside real-time ultrasound, and a delayed hematoma which caused the AIBB was found. INTERVENTIONS: A further neurosurgical procedure of right intracranial hematoma was performed for the patient. OUTCOMES: The surgical effect and the patient's prognosis were significantly improved. LESSONS: Through this patient, we should pay more attention to the application of perioperative of real-time ultrasonic monitoring, to provide more convenience for surgical patients, and improve the prognosis of them.

Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis.

Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.

Salivary Fusobacterium nucleatum serves as a potential diagnostic biomarker for gastric cancer.

BACKGROUND: As one of the most common tumors, gastric cancer (GC) has a high mortality rate, since current examination approaches cannot achieve early diagnosis. Fusobacterium nucleatum (Fn) primarily colonized in the oral cavity, has been reported to be involved in the development of gastrointestinal tumor. Until now, little is known about the relationship between salivary Fn and GC. AIM: To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells. METHODS: The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients, 31 atrophic gastritis (AG) patients, 35 non-AG (NAG) patients, 26 gastric polyp (GP) patients, and 20 normal controls (NC) from Qilu Hospital of Shandong University from January 2019 to December 2020. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4. Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells. The expression of epithelial-mesenchymal transition (EMT) markers was detected using western blot assay. RESULTS: We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG, NAG, and GP patients and NC (P < 0.001). ROC curve analysis showed a favorable capability of Fn (73.33% sensitivity; 82.14% specificity; area under the curve: 0.813) in GC diagnosis, which was superior to that of CEA, CA19-9, CA72-4, ferritin, and sialic acid. The Fn level in saliva of GC patients was increased as the TNM stage increased. GC patients with lymph node metastasis had higher Fn levels than those without metastasis. Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells. Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin, vimentin, and snail. CONCLUSION: Fn abundance in saliva could be used as a promising biomarker to diagnose GC, and Fn infection could promote GC metastasis by accelerating the EMT process.

A panel of necroptosis-related genes predicts the prognosis of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) has become one of the deadliest malignancies in the world. Since necroptosis plays a crucial role in regulating the immune system, it is necessary to develop novel prognostic biomarkers associated with necroptosis and explore its potential role in PAAD. The transcriptome RNA-seq data of PAAD were downloaded from the TCGA and GTEx databases. A prognostic signature was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression, and its prognostic value was evaluated by nomogram and validated in an independent GEO cohort. We identified a total of 24 differentially expressed NRGs in PAAD, and constructed a prognostic signature with 5 NRGs, which showed good performance in predicting the prognosis of PAAD patients. The ROC curves for 1-, 3-, and 5-year survival rate were 0.652, 0.778, and 0.817, respectively. This prognostic signature showed consistent prognosis prediction in an independent patient cohort. Furthermore, the correlations between 5-NRGs signature and TMB, MSI, histopathological classification, immune infiltration, immune types, and immunomodulators were all significant. Notably, the expression profiles of the five NRGs in exosomes of serum were consistent with their expression in tumor tissues. These data suggested that the 5-NRGs signature is a promising biomarker for predicting the prognosis of PAAD.

The Application Value of Syndecan-2 Gene Methylation for Colorectal Cancer Diagnosis: A Clinical Study and Meta-Analyses.

Objective: Syndecan-2 (SDC2) methylation has been previously reported as a sensitive biomarker for the early detection of colorectal cancer (CRC). Droplet digital PCR (ddPCR) is the latest development of PCR technology. It can accurately detect and quantify the target sequence of nucleic acid. ddPCR is widely used in research and clinical diagnosis. In the present study, we aimed to develop a ddPCR method to detect SDC2 gene methylation and evaluate the diagnostic value of SDC2 gene methylation. Methods: First, a ddPCR method was developed to measure SDC2 methylation in stool samples collected from 51 cases of normal, 23 cases of adenoma, and 86 cases of CRC. Subsequently, a meta-analysis of existing studies was conducted to judge the diagnostic value of SDC2 gene methylation in CRC. PUBMED, EMBASE, Web of Science, and Scopus databases were searched for relative studies. Meta-analysis was performed using Meta Disc 1.4 and STATA 15.0 software. Results: The ddPCR showed that the linearity, sensitivity, and specificity for the detection of SDC2 gene methylation could be down to 0.1% methylation level and 5 ng of methylated DNA input. In 109 cases of CRC, 107 cases could be detected, and the sensitivity was 98.17%. The median value of the percentage of methylated reference (PMR) in colorectal adenoma and CRC patients was significantly higher compared with the normal individuals (p < 0.001). In addition, we found that the PMR value was associated with the clinical staging of CRC. The difference of PMR in stage II and stage IIIA was statistically significant (p < 0.05). Moreover, the meta-analysis showed that 11 out of 87 studies were identified to report the feasibility of SDC2 gene methylation as a method to diagnose early CRC. The pooled sensitivity and specificity of SDC2 gene methylation test for CRC were 0.80 [95% CI (0.68-0.88)] and 0.93 [95% CI (0.91-0.94)], respectively. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) were 52.46 [95% CI (30.43-90.45)] and 0.94 [95% CI (0.92, 0.96)], respectively. Conclusions: The ddPCR method was more sensitive and convenient to detect SDC2 gene methylation, and the pooled analysis showed that methylated SDC2 was a valuable biomarker for the non-invasive detection of CRC.

Salivary Fusobacterium nucleatum serves as a potential biomarker for colorectal cancer.

Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.

Clinical value of lncRNA CCAT1 in serum extracellular vesicles as a potential biomarker for gastric cancer.

Long non-coding RNAs (lncRNAs) in extracellular vesicles (EVs) are considered to be novel non-invasive biomarkers for gastric cancer (GC). lncRNA colon cancer-associated transcript 1 (CCAT1) is aberrantly expressed in certain types of cancer. However, the role of EV lncRNA CCAT1 in patients with GC remains unclear. The current study aimed to assess the expression levels of lncRNA CCAT1 in the serum EVs of patients with GC and evaluate its potential clinical value. EVs were isolated from serum using a commercial kit and ultracentrifugation, and were identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Serum EV lncRNA CCAT1 levels in patients with GC, chronic gastritis or atypical hyperplasia and healthy control subjects were detected by reverse transcription-quantitative PCR. Additionally, lncRNA CCAT1 was detected in GC and adjacent non-cancerous tissue samples. Serum EVs were successfully isolated and identified in all patients. The results revealed that serum EV lncRNA CCAT1 levels in patients with GC were significantly higher compared with those in healthy controls, patients with chronic gastritis or atypical hyperplasia (all P<0.05). Additionally, EV lncRNA CCAT1 expression levels were significantly different among various groups based on the depth of invasion, distant metastasis and the Tumor-Node-Metastasis stage. The area under the curve (AUC) value of EV lncRNA CCAT1 was 0.890 [95% confidence interval (CI), 0.826-0.937] with 79.6% sensitivity and 92.6% specificity. The combination of EV lncRNA CCAT1 and carcinoembryonic antibody produced an AUC value of 0.910 (95% CI, 0.849-0.951) with the sensitivity and specificity of 80.5 and 92.6%, respectively. In addition, lncRNA CCAT1 was determined to be stable in serum EVs. The expression levels of lncRNA CCAT1 in GC tissue were positively correlated with those in serum EVs, and high levels of lncRNA CCAT1 were associated with a low disease-free survival rate in patients with GC. The results of the present study demonstrated that serum EV lncRNA CCAT1 levels were upregulated in patients with GC compared with those healthy subjects and patients with other illnesses, and may therefore be used as a novel biomarker for this type of cancer.