Nomogram for Predicting Survival in Locally Advanced Cervical Cancer with Concurrent Chemoradiotherapy plus or Not Adjuvant Chemotherapy: A Retrospective Analysis Based on 2018 FIGO Staging.

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

Surgical Removal of Foramen Ovale Osteophyte Completely Relieved Atypical Trigeminal Neuralgia: A Case Report and Literature Review.

Atypical trigeminal neuralgia (TN), usually caused by nonvascular compression, lacks a clearly localized trigger and complete remission periods. Although variations of foramen ovale may compress the mandibular nerve branch of the trigeminal nerve, resulting in atypical TN, only a few case reports are reported in the literature. The authors describe a case of a 50-year-old female diagnosed with atypical TN for two months. A high-resolution computed tomography imaging revealed an osteophyte of the left foramen ovale that may compress the mandibular nerve branch of the trigeminal nerve. The patient underwent osteophyte resection, and the pain disappeared completely and immediately after surgery without recurrence in the follow-up to six months. The numbness was also relieved slightly. This case provides a new perspective on the clinical diagnosis and treatment of patients with atypical TN.

Associated factors of periodontitis and predicted study among young man in China: a population-based cross-sectional study.

BACKGROUND: Periodontitis represents the foremost oral condition in young men, strongly correlated with socioeconomic elements and oral health behaviors. This research aimed to assess the prevalence of periodontitis and associated associations with socio-demographics and oral health practices for subsequent Hazard Ratio (HR) estimation. METHODS: A total of 46,476 young men were recruited to the study between August 2022 and October 2023. A questionnaire on socio-demographic factors and oral health-related behaviors related to periodontitis was completed. The standard procedure was used for oral examination. Logistic regression and hazard ratios were used to estimate the influencing factors, whereas the nomogram was used to predict the risk of periodontitis in young men. RESULTS: A total of 46,476 young men were surveyed and completed the questionnaire. The overall prevalence of periodontitis among young men was 1.74%. Out of these, 1.7% had mild periodontitis and 0.6% had moderate periodontitis. Age and dental calculus were important factors in the periodontal health of young men. This nomogram, which includes 7 easily obtainable clinical characteristics routinely collected during periodontitis risk assessment, provides clinicians with a user-friendly tool to assess the risk of periodontal disease in young men. CONCLUSIONS: Regular dental prophylaxis is crucial for young men to maintain their gingival health and prevent the onset of periodontitis. Dental calculus plays a prominent role in this matter, as it serves as a significant contributing factor.

Do bubbles matter amid PBC for trigeminal neuralgia?

BACKGROUND: As a simple and safe alternative intervention, percutaneous balloon compression (PBC) has been gradually adopted by a growing number of neurosurgeons to treat trigeminal neuralgia. A pear-shaped opacity observed fluoroscopically, which indicates full suffusion of Meckel's cave conducting sufficient pressure against Gasserian ganglion, is believed to be the key to its success. Sometimes, a bitten pear may appear due to bubbles in the balloon but is usually ignored. OBJECTIVE: This study aims to investigate the effects of the bubbles on postoperative outcomes. METHODS: Patient data were obtained from the consecutive cases undergoing PBCs in our department between 2019 and 2021. Among them, pain and numbness were used to assess the efficacy of PBC based on Barrow Neurology Institute (BNI) scoring system. It was defined as an effective outcome if the postoperative pain intensity grade was lower than II. And those with numbness grade > II were regarded as numb incidence. RESULTS: We eventually recruited 59 cases, including 42 in full pear and 17 in bitten pear groups with follow-up time up to 44 months. The early effective rates were 95.2% and 82.4%, respectively (p > 0.05), which turned to 88.1% and 52.9% during the last follow-up period (p < 0.01). This result indicated that the bitten pear gave rise to a significantly higher recurrence. In terms of numbness, there was no significant difference. CONCLUSION: Gas does not yield enough pressure as liquid, and cannot exert enough pressure to the semilunar ganglion. Therefore, air evacuation should not be ignored before injection.

Periodontal disease and risk of Alzheimer's disease: A two-sample Mendelian randomization.

BACKGROUND: Evidence from observational studies and clinical trials suggests an association between periodontal disease and Alzheimer's disease (AD). However, the causal relationship between periodontal disease and AD remains to be determined. METHODS: We obtained periodontal disease data from the FinnGen database and two sets of AD data from the IEU consortium and PGC databases. Subsequently, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between periodontal disease and AD. RESULTS: The results of the random-effects IVW analysis revealed no evidence of a genetic causal relationship between periodontal disease and AD, regardless of whether the AD data from the IEU consortium or the AD data from the PGC database were utilized. No heterogeneity, multiple effects of levels, or outliers were observed in this study. CONCLUSIONS: Our findings indicate that there is no causal relationship between periodontal disease and AD at the genetic level.

[Inhibition of connexin 43-mediated hemichannel activity promotes odontoblast differentiation of human dental pulp cells induced by lipopolysaccharide].

PURPOSE: To investigate the role and mechanism of connexin 43（Cx43）in odontoblast differentiation of human dental pulp cells (hDPCs) induced by lipopolysaccharide (LPS). METHODS: The maxillary first molar injury model of SD rats was established. The expression pattern of Cx43 in dental pulp repair after injury was detected by immunofluorescence(IF) staining. hDPCs was respectively stimulated with 0, 1, 10, 100 and 1 000 ng/mL LPS for 6 h to screen the optimal concentration, and then the expression of Cx43 was inhibited and overexpressed in hDPCs. Quantitative real-time PCR(qRT-PCR) and Western blot(WB) were used to detect the expression of Cx43 and dentin sialophosphoprotein (DSPP), dental matrix protein-1 (DMP-1), osterix (Osx) and extracellular signal-regulated kinase (ERK) activity. Furthermore, hDPCs were treated with specific Cx43 channel inhibitors to investigate the effect of Cx43-mediated channel activity in odontoblast differentiation of hDPCs, and to explore the role and mechanism of Cx43 in regulating odontoblast differentiation of hDPCs induced by LPS. Statistical analysis was performed with SPSS 26.0 software package. RESULTS: IF results showed that Cx43 was mainly expressed in the odontoblast layer in healthy dental pulp tissues. At 3-24 h after tooth injury, the expression of Cx43 decreased and then gradually increased to the normal level; from 3 days to 2 weeks after injury, the expression of Cx43 tended to be down-regulated which was in the odontoblast layer and pulp proper. The expression of DSPP mRNA was significantly up-regulated in the hDPCs stimulated with 10 ng/mL LPS for 6 h(P＜0.01). Inhibition of Cx43 significantly up-regulated the expression of DSPP, DMP-1 and Osx mRNA induced by LPS in hDPCs(P＜0.05), while overexpression of Cx43 obviously inhibited the expression of factors related to LPS-induced odontoblast differentiation(P＜0.01) and the fluorescence intensity of DSPP. 10 ng/mL LPS activated ERK signal in hDPCs, and overexpression of Cx43 significantly attenuated the activity of ERK signal induced by LPS(P＜0.01). Inhibition of Cx43-mediated hemichannel (HC) promoted mRNA expression of factors related to odontoblast differentiation in hDPCs and the activity of ERK signal induced by LPS(P＜0.05), while blocking Cx43-mediated gap junction channel (GJC) inhibited odontoblast differentiation. CONCLUSIONS: Cx43 participates in the regulation of dental pulp repair after injury, and its expression shows a downward trend as a whole. Inhibition of Cx43 or blocking of HC promotes LPS-induced ERK signal activity and odontoblast differentiation of hDPCs.

Riveting technique in percutaneous balloon compression for trigeminal neuralgia remedy.

BACKGROUND: The percutaneous balloon compression (PBC) is a safe and simple treatment for trigeminal neuralgia. It works by compressing the Gasserian ganglion to block pain signals from the trigeminal nerve. To ensure effectiveness, it is important to focus the compression on the lower part of the balloon. OBJECTIVE: To validate the efficacy of a riveting technique, specifically pulling an inflated balloon, in order to apply enhanced compression on the ganglion. METHODS: To compare this novel technique with the conventional approach, a retrospective investigation was conducted on consecutive PBCs performed in our department between 2019 and 2022. For postoperative outcome assessment, efficacy was defined as achieving a VAS score of 0 or an improvement exceeding 5 points. Postoperative numbness was graded as none, mild, or severe based on its impact on daily life and tolerance level. RESULTS: Excluding cases with missed follow-up, a total of 179 participants were included in the study, and their follow-up period ranged up to 40 months. Postoperatively, symptomatic remission was achieved by 98.1% (52/53) of patients in the riveting technique group compared to 87.3% (110/126) in the conventional group (P<0.05). At the last follow-up period, with recurrence observed over time, the long-term efficacy of riveting and conventional groups were 94.3% and 74.6%, respectively (P<0.05). The majority of cases in both groups experienced ipsilateral facial numbness immediately following PBC, which appeared to diminish after 3 months in both groups without significant difference between them (P>0.05).

Revisiting the Efficacy of Redo Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND: Microvascular decompression (MVD) is an effective nondestructive neurosurgical procedure for trigeminal neuralgia (TN). However, some patients may undergo surgery failure or experience pain recurrence, sparking debates on the need for reoperation. METHODS: We conducted a retrospective analysis of 103 cases of patients with primary TN who underwent redo MVD at our center between January 2020 and December 2022. Comparative prognostic assessments were performed by comparing these cases against a cohort of 348 patients who underwent primary MVD during the same study period. RESULTS: During the redo MVD cases, arachnoid membranes adhesions (80.6%) and Teflon adhesions with/without granuloma (86.4%) as well as remaining vascular compression (36.9%) were observed. After the reoperation, an immediate relief rate of 94.2% was observed. During a mean follow-up period of 17.4 ± 4.4 months, a long-term relief rate of 89.3% was achieved. Postoperative complications included 3 cases of persistent paresthesia, 1 case each of hearing loss, cerebrospinal fluid leak, and facial palsy. Ten cases without evident compression received nerve combing and all experienced immediate complete relief, with only 1 patient experiencing recurrence 9 months after surgery. Compared to the primary MVD group, the reoperation group had a higher average age, longer disease duration, and operating time (P < 0.05). However, there were no significant differences in immediate relief rate, long-term relief rate, or complications between the 2 groups. The main cause of persistent symptom was inadequate decompression, such as missing the offending vessel; while the recurrent was primarily due to Teflon adhesion or granuloma formation. CONCLUSIONS: The redo MVD for TN is equally efficacious and safe compared to the primary procedure, with an emphasis on meticulous dissection and thorough decompression. Additionally, nerve combing proves to be an effective supplementary option for patients without obvious compression.

Hypoxic Bone Mesenchymal Stem Cell-Derived Exosomes Direct Schwann Cells Proliferation, Migration, and Paracrine to Accelerate Facial Nerve Regeneration via circRNA_Nkd2/miR-214-3p/MED19 Axis.

Background: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism. Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments. Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p. Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI.

Downscaling of environmental indicators: A review.

Environmental indicators at different scales are important for environmental management, daily life, and scientific research. Because of the lack of statistics below a national scale for many environmental indicators, scholars have developed various downscaling methods to obtain finer-scale and diverse forms of data for different environmental indicators. However, the existing downscaling methods for environmental indicators are diverse and fragmented. Here, we reviewed the downscaling methods by reclassifying the environmental indicators from a life cycle perspective into five categories: natural resources use and related attributes; material and energy consumption; environmental discharge; climate change; and environmental footprints. We first provide a general introduction to downscaling theory in the environmental field, including definitions, techniques, and evolution. We then elaborate on downscaling methods and make an inventory of the five categories of environmental indicators. We summarize the downscaling methods commonly applied to specific indicators, scale transformation, the strengths and limitations of corresponding methods, and provide specific examples. Next, we discuss ways to select or construct downscaling methods based on four principles: objective orientation, data accessibility, model feasibility, and model adjustment. Finally, we explore the future direction of downscaling and provide insights for improving downscaling for environmental indicators. In this review, we generalize and clarify the downscaling techniques for environmental indicators, which will help facilitate the appropriate selection of downscaling methods by researchers.

Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion.

Tumor cells and surrounding immune cells undergo metabolic reprogramming, leading to an acidic tumor microenvironment. However, it is unclear how tumor cells adapt to this acidic stress during tumor progression. Here we show that carnosine, a mobile buffering metabolite that accumulates under hypoxia in tumor cells, regulates intracellular pH homeostasis and drives lysosome-dependent tumor immune evasion. A previously unrecognized isoform of carnosine synthase, CARNS2, promotes carnosine synthesis under hypoxia. Carnosine maintains intracellular pH (pHi) homeostasis by functioning as a mobile proton carrier to accelerate cytosolic H+ mobility and release, which in turn controls lysosomal subcellular distribution, acidification and activity. Furthermore, by maintaining lysosomal activity, carnosine facilitates nuclear transcription factor X-box binding 1 (NFX1) degradation, triggering galectin-9 and T-cell-mediated immune escape and tumorigenesis. These findings indicate an unconventional mechanism for pHi regulation in cancer cells and demonstrate how lysosome contributes to immune evasion, thus providing a basis for development of combined therapeutic strategies against hepatocellular carcinoma that exploit disrupted pHi homeostasis with immune checkpoint blockade.

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer.

Gastric cancer (GC) is the fifth most common cause of cancer-associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 (SLC2A2) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC50 were estimated using quantification of the tumor immune contexture from human RNA-seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription-quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2-related differentially expressed genes were enriched predominantly in 'chylomicron assembly', 'plasma lipoprotein particle assembly', 'high-density lipoprotein particle', 'chylomicron', 'triglyceride-rich plasma lipoprotein particle', 'very-low-density lipoprotein particle'. 'intermembrane lipid transfer activity', 'lipoprotein particle receptor binding', 'cholesterol transporter activity' and 'intermembrane cholesterol transfer activity'. In addition, 'cholesterol metabolism', and 'fat digestion and absorption' were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease-specific survival and progression-free interval. Multivariate regression analysis demonstrated that SLC2A2 could independently prognosticate GC and the nomogram model showed favorable performance for survival prediction. SLC2A2 may be a prospective prognostic marker for GC. The prediction model may improve the prognosis of patients with GC in clinical practice, and SLC2A2 may serve as a novel therapeutic target to provide immunotherapy plans for GC.

Fully endoscopic microvascular decompression for trigeminal neuralgia: technical note and early outcomes.

Microscopic microvascular decompression (MVD) has been considered a curative and reliable method for treating classical trigeminal neuralgia (TN) for decades. Endoscopy can provide bright illumination and a panoramic view, which enhances the visualization of the posterior fossa. In view of the above advantages of endoscopy, it gradually became an option for MVD for treating TN. This study was performed to evaluate the advantages of fully endoscopic MVD for treating TN and is presented with a description of our operative technique. From January 2020 to January 2022, 95 classical TN patients underwent fully endoscopic MVD performed by the same surgeon and assistant in our department. The assistant held the endoscope, and the surgeon operated. Brain stem auditory evoked potentials (BEMPs) were routinely monitored. For every patient, the neurovascular conflict was identified, and complete decompression was achieved. The Barrow Neurological Institute (BNI) pain intensity score was used to evaluate the degree of facial pain. The intraoperative findings, postoperative outcomes, and complications were analyzed. Immediately after the operation, 93 patients (97.9%) achieved complete pain relief (BNI score of I). Two patients (2.1%) still had some pain, but it could be adequately controlled with medicine (BNI score of III). During the 12-36 months of follow-up, recurrence was found in 3 patients (3.2%), including one patient (1.1%) with a BNI score of II and 2 patients (2.1%) with a BNI score of III. Complications were found in 5 patients (5.3%), including facial numbness in 3 patients (3.2%), vertigo in one patient (1.1%), and headache in one patient (1.1%). There were no cases of mortality, stroke, hearing impairment, facial paralysis, or other complications. Fully endoscopic MVD is a safe and effective method for treating TN. It provides bright illumination and a panoramic view for surgeons to better observe neurovascular conflicts in deep areas of the cerebellopontine angle (CPA).

Research Progress on Mechanism and Management of Adverse Drug Reactions of Anlotinib.

Anti-angiogenesis therapy plays a vital role in the treatment of tumors, with anlotinib as its representative targeted drug. Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) with inhibitory effects on tumor growth tumor angiogenesis. In Phase III clinical trials, anlotinib demonstrated better overall survival and progression-free survival than placebo in patients with advanced non-small cell lung cancer (NSCLC), and was approved for the first time as a third-line treatment for refractory advanced NSCLC. Going far beyond that, anlotinib has shown encouraging results in a variety of malignancies, including medullary thyroid carcinoma, renal cell carcinoma, gastric cancer and esophageal squamous cell carcinoma. Nevertheless, anlotinib has been subject to some controversy in terms of adverse events due to its widespread use. In this review, the mechanism of action, pharmacokinetic characteristics, adverse reactions in clinical use and management of anlotinib were summarized.

Lumbar Endoscopic Unilateral Laminotomy With Bilateral Decompression Surgery in Severe Lumbar Stenosis Under Electrophysiological Monitoring-Focused on Full-Visualized Trephine/Osteotome.

OBJECTIVE: Although endoscopic drill has the advantages in manipulation and hemostasis, whose low efficiency and blurred vision reduce the efficacy of lumbar endoscopic unilateral laminotomy with bilateral decompression (LE-ULBD). The present study was designed to evaluate the safety and efficacy of full-visualized trephine/osteotome in the LE-ULBD surgery for severe lumbar stenosis. METHODS: Fifty-seven severe lumbar stenosis patients who underwent LE-ULBD between January 2020 to January 2023 were enrolled, who were divided into drill and visualized trephine groups. The medical records including demographics, operative duration, intraoperative electrophysiological findings, postoperative hospital stay or hospital stay, postoperative outcomes and complications were retrospectively reviewed and analyzed. RESULTS: A total of 57 patients included 15 in drill and 42 in trephine group were enrolled in the study. There was significant difference in the pre- and postoperative visual analogue scale and Oswestry Disability Index scores in both groups (p < 0.05). The mean operative duration in the trephine group (101.05 ± 12.18 minutes) was shorter than that in the drill group (134.67 ± 9.68 minutes) (p < 0.05). There was no statistical difference between the 2 groups in electrophysiological monitoring, posthospital stays, postoperative outcomes and complications. Abnormal free-electromyography (EMG) were recorded in 2 (13.3%) and 5 patients (11.9%) in the drill and trephine group. Intraoperative somatosensory evoked potential changes occurred in 3 (20%) and 3 patients (7.1%) in the drill and trephine group and all patients recovered immediately when surgery ended. No serious complications and recurrence occurred in all the patients. CONCLUSION: Full-visualized trephine/osteotome has been approved to be convenient, safe and efficient in our study, which combined with translaminar inside-out technique and EMG monitoring especially free-EMG may offer a new choice in LE-ULBD surgery for lumbar stenosis patients.

Connexin43 reduces LPS-induced inflammation in hDPCs through TLR4-NF-κB pathway via hemichannels.

OBJECTIVES: Connexin43 (Cx43) is involved in the inflammation of many tissue types. Dental caries is infectious disease resulting from mineralized tissue dissolution by a specific bacterial population, causing pulp inflammation. However, Cx43's role in dental pulp remains unclear. Here, we investigated the function of Cx43 during pulp inflammation. MATERIALS AND METHODS: We constructed a dentin injury model in Sprague-Dawley rats to investigate changes in Cx43 expression during pulp inflammation. Cx43 was inhibited in human dental pulp cells (hDPCs) that had been stimulated with lipopolysaccharide (LPS) to investigate the effect of Cx43 on inflammatory response. Promotion of TLR4-NF-κB pathway activity and special Cx43 channel inhibitors were used to clarify the function of Cx43 in hDPCs. RESULTS: Dentin injury led to low-level inflammation in dental pulp. Following dentin injury, Cx43 expression initially decreased before gradually recovering to normal levels. Cx43 inhibition reduced LPS-induced expression of inflammatory cytokines and NF-κB pathway activity. Promotion of NF-κB pathway activity counteracted the effect of Cx43 in hDPCs. Furthermore, inhibition of Cx43 hemichannels reduced LPS-induced inflammatory cytokine expression. CONCLUSIONS: Cx43 is involved in inflammation of dental pulp, while its inhibition reduced LPS-induced inflammation in hDPCs through NF-κB pathway via blockage of hemichannels.

Whole-genome CpG-resolution DNA Methylation Profiling of HNSCC Reveals Distinct Mechanisms of Carcinogenesis for Fine-scale HPV+ Cancer Subtypes.

DNA methylation is a vital early step in carcinogenesis. Most findings of aberrant DNA methylation in head and neck squamous cell carcinomas (HNSCC) are array based with limited coverage and resolution, and mainly explored by human papillomavirus (HPV) status, ignoring the high heterogeneity of this disease. In this study, we performed whole-genome bisulfite sequencing on a well-studied HNSCC cohort (n = 36) and investigated the methylation changes between fine-scaled HNSCC subtypes in relation to genomic instability, repetitive elements, gene expression, and key carcinogenic pathways. The previously observed hypermethylation phenotype in HPV-positive (HPV+) tumors compared with HPV-negative tumors was robustly present in the immune-strong (IMU) HPV+ subtype but absent in the highly keratinized (KRT) HPV+ subtype. Methylation levels of IMU tumors were significantly higher in repetitive elements, and methylation showed a significant correlation with genomic stability, consistent with the IMU subtype having more genomic stability and better prognosis. Expression quantitative trait methylation (cis-eQTM) analysis revealed extensive functionally-relevant differences, and differential methylation pathway analysis recapitulated gene expression pathway differences between subtypes. Consistent with their characteristics, KRT and HPV-negative tumors had high regulatory potential for multiple regulators of keratinocyte differentiation, which positively correlated with an expression-based keratinization score. Together, our findings revealed distinct mechanisms of carcinogenesis between subtypes in HPV+ HNSCC and uncovered previously ignored epigenomic differences and clinical implications, illustrating the importance of fine-scale subtype analysis in cancer. Significance: This study revealed that the previously observed hypermethylation of HPV(+) HNSCC is due solely to the IMU subtype, illustrating the importance of fine-scale subtype analysis in such a heterogeneous disease. Particularly, IMU has significantly higher methylation of transposable elements, which can be tested as a prognosis biomarker in future translational studies.

Aqueous Cationic Fluorinated Polyurethane for Application in Novel UV-Curable Cathodic Electrodeposition Coatings.

Aqueous polyurethane is an environmentally friendly, low-cost, high-performance resin with good abrasion resistance and strong adhesion. Cationic aqueous polyurethane is limited in cathodic electrophoretic coatings due to its complicated preparation process and its poor stability and single performance after emulsification and dispersion. The introduction of perfluoropolyether alcohol (PFPE-OH) and light curing technology can effectively improve the stability of aqueous polyurethane emulsions, and thus enhance the functionality of coating films. In this paper, a new UV-curable fluorinated polyurethane-based cathodic electrophoretic coating was prepared using cationic polyurethane as a precursor, introducing PFPE-OH capping, and grafting hydroxyethyl methacrylate (HEMA). The results showed that the presence of perfluoropolyether alcohol in the structure affected the variation of the moisture content of the paint film after flash evaporation. Based on the emulsion particle size and morphology tests, it can be assumed that the fluorinated cationic polyurethane emulsion is a core-shell structure with hydrophobic ends encapsulated in the polymer and hydrophilic ends on the outer surface. After abrasion testing and baking, the fluorine atoms of the coating were found to increase from 8.89% to 27.34%. The static contact angle of the coating to water was 104.6 ± 3°, and the water droplets rolled off without traces, indicating that the coating is hydrophobic. The coating has excellent thermal stability and tensile properties. The coating also passed the tests of impact resistance, flexibility, adhesion, and resistance to chemical corrosion in extreme environments. This study provides a new idea for the construction of a new and efficient cathodic electrophoretic coating system, and also provides more areas for the promotion of cationic polyurethane to practical applications.

PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation.

Tumor metabolic reprogramming and epigenetic modification work together to promote tumorigenesis and development. Protein lysine acetylation, which affects a variety of biological functions of proteins, plays an important role under physiological and pathological conditions. Here, through immunoprecipitation and mass spectrum data, we show that phosphoglycerate mutase 5 (PGAM5) deacetylation enhances malic enzyme 1 (ME1) metabolic enzyme activity to promote lipid synthesis and proliferation of liver cancer cells. Mechanistically, we demonstrate that the deacetylase SIRT2 mediates PGAM5 deacetylation to activate ME1 activity, leading to ME1 dephosphorylation, subsequent lipid accumulation and the proliferation of liver cancer cells. Taken together, our study establishes an important role for the SIRT2-PGAM5-ME1 axis in the proliferation of liver cancer cells, suggesting a potential innovative cancer therapy.

miR-21-5p Inhibits the Proliferation, Migration, and Invasion of Glioma by Targeting S100A10.

S100A10, a member of the S100 protein family, is upregulated in multiple human malignancies and plays a key role in regulating tumor progression. This study aimed to reveal the underlying mechanism by which S100A10 in regulates the proliferation, migration, and invasion of glioma. The expression and clinical information data of S100A10 were downloaded from public databases (TCGA, CGGA, and GEPIA2). S100A10 expression levels in glioma tumor tissues and adjacent nontumor tissues were compared by immunohistochemistry (IHC). The functional roles of S100A10 in glioma were assessed by cell counting kit-8 (CCK-8) cell proliferation assay, wound healing assay, transwell assay, and flow cytometry. miRDB and double luciferase assay were used to predict and identify potential S100A10 mRNA-complementary miRNAs, and the roles of miR-21-5p in glioma cell were examined by targeted knockdown or overexpression miR-21-5p in glioma cell lines. We found that S100A10 was overexpressed in glioma tissues and predicted a worse prognosis. S100A10 knockdown significantly inhibited glioma cell proliferation, invasion, and migration. Furthermore, we demonstrated that miR-21-5p inhibits glioma proliferation, migration, and invasion by targeting S100A10. This study showed S100A10 was a new prognostic predictor among glioma patients and provided new insights into the pathogenesis of gliomas, suggesting that miR-21-5p /S100A10 axis may serve as a valuable therapeutic target for glioma.