Identification of Biomarkers, Pathways, Immune Properties of Mitophagy Genes, and Prediction Models for Intervertebral Disc Degeneration.

Background: Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD. Methods: Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples. Results: We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group. Conclusion: We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD.

Clinical value of serum polyunsaturated fatty acids in patients with gastric polyps.

Polyunsaturated fatty acids (PUFAs) are vital nutrients in human physiology and are implicated in various chronic diseases. However, the relationship between PUFAs and gastric polyps remains unclear. This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess PUFA levels in the serum of 350 patients, along with analyzing the ω-6 to ω-3 ratio. The results revealed significant differences in the levels of C16:1, C18:1, C18:2, α-C18:3, γ-C18:3, C20:1, C20:4, C20:5, ω-3-C22:5, ω-6-C22:5, and C22:6, as well as ω-6 to ω-3 ratio between the control and gasteic polyp groups. Moreover, setting the threshold for ω-6: ω-3 at 10 revealed a close correlation between polyp occurrence and this ratio. These findings suggest that PUFAs and the ω-6 to ω-3 ratio hold promise as potential early screening markers for gastric polyps. However, further research is imperative to elucidate the underlying mechanisms and therapeutic potential of PUFAs in managing gastric polyps.

Bioinformatic Analysis and Clinical Case Studies Identify CD276 as a Promising Diagnostic Biomarker for Clear Cell Renal Cell Carcinoma.

OBJECTIVE: This study aimed to explore the relationship between CD276 and clear cell renal carcinoma (ccRCC) and assess the diagnostic value of CD276 in ccRCC. METHODS: Expression levels of CD276 in ccRCC and para-cancer tissues were compared and analyzed retrospectively using data obtained from TCGA and GEO databases. The clinical data was analyzed prospectively. Immunohistochemistry and RT-PCR analyses were used to analyze the expression of CD276 at the mRNA and protein levels. These analyses compared the expression between ccRCC tissues and para-cancer tissues obtained from 70 patients with ccRCC. Next, ELISA was used to analyze peripheral blood samples from 70 patients with ccRCC and 72 healthy individuals, facilitating the differentiation of ccRCC patients from normal controls. Finally, we utilized the Kaplan-Meier method to generate ROC curves for assessing the diagnostic value of CD276 for ccRCC. RESULTS: Analysis of TCGA and GEO data revealed that the mRNA expression of CD276 was higher in ccRCC tissues than in para-cancer tissues (P < .05). Clinical validation using IHC and RT-PCR confirmed that the expression of CD276 was higher in ccRCC tissues than in para-cancer tissues, both at the mRNA and protein levels (P < .05). ELISA demonstrated that the expression of CD276 was higher in ccRCC patients than in normal individuals, and patients with a higher pathological grade showed higher expression of CD276 in the peripheral blood than those with a lower pathological grade (P < .05). ROC curves drawn from the above three datasets demonstrated that CD276 had a high diagnostic value for ccRCC (AUC = .894, .795, .938, respectively). CONCLUSION: The expression of CD276 was higher in ccRCC tissues and positively associated with the pathological grade. Therefore, CD276 may serve as a molecular biomarker for ccRCC prediction.

Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain, distension, and altered bowel habits. Probiotics may alleviate IBS symptoms, but clinical trials remain conflicting. AIMS: To conduct a systematic review and meta-analysis of clinical trials to evaluate the efficacy and safety of probiotics for IBS patients. METHODS: We searched relevant trials in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar from 2000 to June 2023. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes. A risk ratio (RR) and a 95% CI were calculated for dichotomous outcomes. RESULTS: A total of 20 studies involving 3011 patients were obtained. The results demonstrated that probiotics are more effective than placebo in reducing global IBS symptoms improvement rate (RR = 1.401, 95% CI 1.182-1.662, P < 0.001) and quality of life scores (SMD = 0.286, 95% CI = 0.154-0.418, P < 0.001). Subgroup analyses showed that a shorter treatment time (less than eight weeks) could reduce distension scores (SMD = 0.197, 95% CI = 0.038-0.356, P = 0.015). High doses (daily dose of probiotics ≥ 10ˆ10) or multiple strains of probiotics exhibit beneficial effects on abdominal pain (SMD = 0.412, 95% CI = 0.112-0.711, P = 0.007; SMD = 0.590, 95% CI = 0.050-1.129, P = 0.032; respectively). However, there was no significant benefit on global symptom scores (SMD = 0.387, 95% CI 0.122 to 0.653, P = 0.004) with statistically high inter-study heterogeneity (I2 = 91.9%, P < 0.001). Furthermore, there was no significant inter-group difference in terms of adverse events frequency (RR = 0.997, 95% CI 0.845-1.177, P = 0.973). CONCLUSION: Probiotics are effective and safe for IBS patients. High doses or multiple probiotic strains seem preferable, but definite conclusions are challenging due to the high heterogeneity. Large-scale, well-designed, and rigorous trials are needed to confirm their effectiveness.

Real-Time Reconstruction of HIFU Focal Temperature Field Based on Deep Learning.

Objective and Impact Statement: High-intensity focused ultrasound (HIFU) therapy is a promising noninvasive method that induces coagulative necrosis in diseased tissues through thermal and cavitation effects, while avoiding surrounding damage to surrounding normal tissues. Introduction: Accurate and real-time acquisition of the focal region temperature field during HIFU treatment marked enhances therapeutic efficacy, holding paramount scientific and practical value in clinical cancer therapy. Methods: In this paper, we initially designed and assembled an integrated HIFU system incorporating diagnostic, therapeutic, and temperature measurement functionalities to collect ultrasound echo signals and temperature variations during HIFU therapy. Furthermore, we introduced a novel multimodal teacher-student model approach, which utilizes the shared self-expressive coefficients and the deep canonical correlation analysis layer to aggregate each modality data, then through knowledge distillation strategies, transfers the knowledge from the teacher model to the student model. Results: By investigating the relationship between the phantoms, in vitro, and in vivo ultrasound echo signals and temperatures, we successfully achieved real-time reconstruction of the HIFU focal 2D temperature field region with a maximum temperature error of less than 2.5 °C. Conclusion: Our method effectively monitored the distribution of the HIFU temperature field in real time, providing scientifically precise predictive schemes for HIFU therapy, laying a theoretical foundation for subsequent personalized treatment dose planning, and providing efficient guidance for noninvasive, nonionizing cancer treatment.

Serpin peptidase inhibitor, clade E, member 2 in physiology and pathology: recent advancements.

Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs and secreted by many cell types. The multiple functions of serpin E2 are mainly mediated through regulating urokinase-type plasminogen activator (uPA, also known as PLAU), tissue-type plasminogen activator (tPA, also known as PLAT), and matrix metalloproteinase activity, and include hemostasis, cell adhesion, and promotion of tumor metastasis. The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.

Total body water percentage and 3rd space water are novel risk factors for training-related lower extremity muscle injuries in young males.

PURPOSE: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis. METHODS: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q1, Q3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. RESULTS: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, odds ratio = 3.114) and 3rd space water > 0.95% (p = 0.045, odds ratio = 2.342) were independent risk factors for lower extremity muscle injuries. CONCLUSION: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts.

BACKGROUND: Prostate cancer (PCa) is a widespread malignancy, predominantly affecting elderly males, and current methods for diagnosis and treatment of this disease continue to fall short. The marker Ki-67 (MKI67) has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells, including those of PCa. Hence, verifying the association between MKI67 and the diagnosis and prognosis of PCa, using bioinformatics databases and clinical data analysis, carries significant clinical implications. AIM: To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa. METHODS: For cohort 1, the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. For cohort 2, the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa. RESULTS: In cohort 1, MKI67 expression was correlated with prostate-specific antigen (PSA), Gleason Score, T stage, and N stage. The receiver operating characteristic (ROC) curve showed a strong diagnostic ability, and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval (PFI). The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa. In cohort 2, MKI67 expression was significantly related to the Gleason Score, T stage, and N stage; however, it was negatively associated with the PFI. The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa. Multivariate COX regression analysis was performed to select risk factors, including PSA level, N stage, and MKI67 expression. A nomogram was established to predict the 3-year PFI. CONCLUSION: MKI67 expression was positively associated with the Gleason Score, T stage, and N stage and showed a strong diagnostic and prognostic ability in PCa.

Aryldiazonium-Salt-Triggered Carboxylative Azotization of Pyrroles or Indoles with Polyhalomethanes via Halogen-Atom Transfer (XAT).

A halogen-atom-transfer (XAT)-based method for carbonylazotization of pyrroles or indoles with aryldiazonium salts and polyhalomethanes via dual C(sp2)-H bond functionalization is described. Using aryldiazonium salts realizes carbonylation/azotization of pyrroles or indoles via polyhalomethyl-radical-mediated and electrophilic substitution, thus providing a green, efficient, and step-economy approach for synthesis of multifunctional pyrroles or indoles from the easily available substrates. Notably, this strategy relies on the use of aryldiazonium salts to extend the well-established iodine atom transfer to bromine or chlorine atom transfer.

Photocurable injectable Janus hydrogel with minimally invasive delivery for all-in-one treatment of gastric perforations and postoperative adhesions.

Background: Surgical sutures for sealing gastric perforations (GP) are associated with severe inflammation and postoperative adhesions. Hydrogel bioadhesives offer a potential alternative for sutureless repair of GP; however, their application in minimally invasive surgery is limited due to their prefabricated patch-form, lacking in situ gelation capability. In this study, we emphasized an all-in-one minimally invasive strategy for sutureless repair of acute GP. Methods: an injectable photocurable Janus hydrogel was synthesized, and their ability to seal GP was performed. A rat GP model was used to verify the wound healing and antiadhesion efficiency of hydrogels, and a rabbit GP model was used to verify their laparoscopic feasibility. A fresh human corpse GP model was further employed to verify the user-friendliness of a minimally invasive deliverable (MID) device. A minipig GP model was utilized to evaluate the all-in-one minimally invasive strategy for the treatment of acute GP. Results: Such injectable Janus hydrogel exhibited asymmetric adhesiveness, where the inner-facing side of the hydrogel displays strong sealing and wound healing abilities for GP, while the outward-facing side prevents postoperative adhesion formation. We further developed a minimally invasive deliverable (MID) device integrating hydrogel-delivery parts and photocrosslinking-gelation parts in a laparoscope system. The precise delivery and rapid fluid-tight sealing process of the injectable Janus hydrogel using the MID device for in situ GP repair were demonstrated in a simulated clinical scenario. The in vivo effectiveness of GP sutureless repair was successfully validated in porcine models, with further exploration of the underlying mechanism. Conclusions: Our findings reveal that the injectable Janus hydrogel offers an all-in-one strategy for sutureless GP repair and concurrent prevention of postoperative adhesion formation by incorporating the MID device in minimally invasive surgery, presenting the significant potential to reduce patient surgical complications.

The role of lactate in cardiovascular diseases.

Cardiovascular diseases pose a major threat worldwide. Common cardiovascular diseases include acute myocardial infarction (AMI), heart failure, atrial fibrillation (AF) and atherosclerosis. Glycolysis process often has changed during these cardiovascular diseases. Lactate, the end-product of glycolysis, has been overlooked in the past but has gradually been identified to play major biological functions in recent years. Similarly, the role of lactate in cardiovascular disease is gradually being recognized. Targeting lactate production, regulating lactate transport, and modulating circulating lactate levels may serve as potential strategies for the treatment of cardiovascular diseases in the future. The purpose of this review is to integrate relevant clinical and basic research on the role of lactate in the pathophysiological process of cardiovascular disease in recent years to clarify the important role of lactate in cardiovascular disease and to guide further studies exploring the role of lactate in cardiovascular and other diseases. Video Abstract.

Exophytic benign prostatic hyperplasia presenting as a polycystic pelvic mass.

We report a case of an exophytic benign prostatic hyperplasia presenting as a polycystic pelvic mass. A 69-year-old man presented with an incidental finding of a pelvic mass of over 18 years. Digital rectal examination revealed a mass on the right anterior rectal wall 8 cm from the anal opening. His current prostate-specific antigen was 3.187 ng/mL. Enhanced computed tomography and magnetic resonance imaging demonstrated an occupancy in the right pelvis. A laparoscopic resection of the pelvic tumor was performed and pathologists identified it as an exophytic benign prostatic hyperplasia nodule. No significant recurrence was found at the 6-month follow-up.

Regulation of the integrin αVß3- actin filaments axis in early osteogenic differentiation of human mesenchymal stem cells under cyclic tensile stress.

BACKGROUND: Integrins are closely related to mechanical conduction and play a crucial role in the osteogenesis of human mesenchymal stem cells. Here we wondered whether tensile stress could influence cell differentiation through integrin αVß3. METHODS: We inhibited the function of integrin αVß3 of human mesenchymal stem cells by treating with c(RGDyk). Using cytochalasin D and verteporfin to inhibit polymerization of microfilament and function of nuclear Yes-associated protein (YAP), respectively. For each application, mesenchymal stem cells were loaded by cyclic tensile stress of 10% at 0.5 Hz for 2 h daily. Mesenchymal stem cells were harvested on day 7 post-treatment. Western blotting and quantitative RT-PCR were used to detect the expression of alkaline phosphatase (ALP), RUNX2, ß-actin, integrin αVß3, talin-1, vinculin, FAK, and nuclear YAP. Immunofluorescence staining detected vinculin, actin filaments, and YAP nuclear localization. RESULTS: Cyclic tensile stress could increase the expression of ALP and RUNX2. Inhibition of integrin αVß3 activation led to rearrangement of actin filaments and downregulated the expression of ALP, RUNX2 and promoted YAP nuclear localization. When microfilament polymerization was inhibited, ALP, RUNX2, and nuclear YAP nuclear localization decreased. Inhibition of YAP nuclear localization could reduce the expression of ALP and RUNX2. CONCLUSIONS: Cyclic tensile stress promotes early osteogenesis of human mesenchymal stem cells via the integrin αVß3-actin filaments axis. YAP nuclear localization participates in this process of human mesenchymal stem cells. Video Abstract.

Comparing perioperative and oncological outcomes of transanal and laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of randomized controlled trials and prospective studies.

INTRODUCTION: Meta-analysis of the results of transanal total mesorectal excision (taTME) and laparoscopic TME (laTME) regarding perioperative and oncological outcomes have been conducted. Due to the lack of high-quality randomized controlled trials (RCTs) and prospective studies in the included literature, the conclusions are unreliable. This study included RCTs and prospective studies for analysis to obtain more reliable conclusions. MATERIALS AND METHODS: Systematic searches of the PubMed, Embase, and Cochrane Library databases were conducted up to June 2023. To assess the quality, the Cochrane quality assessment tool and the Newcastle-Ottawa Scale were employed. The perioperative and oncological outcomes were then analyzed. The I2 statistic was used to evaluate statistical heterogeneity and sensitivity analyses was conducted. RESULTS: A total of 22 studies, comprising 5056 patients, were included in the analysis, of which 6 were RCTs and 16 were prospective studies. The conversion rate in the taTME group was significantly lower than that in the laTME group (OR 0.14, 95% CI 0.09 to 0.22, P < 0.01), and the circumferential resection margin (CRM) was longer (MD 0.99 mm, 95% CI 0.66 to 1.32 mm, P < 0.01), with a lower rate of positive CRM involvement (OR 0.68, 95% CI 0.47 to 0.97, P = 0.03). No statistically significant differences were found in terms of the operation time, intraoperative blood loss, complications, anastomotic leakage, uroschesis, obstruction, secondary operation, hospital stay, urethral injury, readmission, mortality rate within 30 days, mesorectal resection quality, number of harvested lymph nodes, distal resection margin (DRM), positive DRM, local recurrence, and distance recurrence (P > 0.05). CONCLUSION: According to the findings of this meta-analysis, which is based on RCTs and prospective studies, taTME appears to have an advantage over laTME in terms of conversion rate and CRM involvement.

Tumor-derived Endothelial Cell: Important Etiological Factors in Endometriosis.

BACKGROUND AND AIM: Endometriosis (EMS) is a very complex disease with high heterogeneity. Recently, single-cell RNA sequencing (scRNA-seq) has been applied to comprehensively characterize cellular heterogeneity. Here, we built a new transcriptomic profile of EMS cellular signatures. METHODS: Three women diagnosed with endometriosis were recruited. Their fresh eutopic endometrium (EM) and ectopic endometrium (EC) tissues were sampled during surgery. ScRNA-seq was performed on 10x Genomics Chromium. RESULTS: Thirty cell clusters were identified as more than ten different cell types using cell type-specific marker genes. Re-clustering analysis revealed five subtypes of endothelial cells (ECs). Compared to EM, the proportion of tumor-derived ECs (IGFBP3+) was significantly increased in EC (43.8 vs. 16.0%). 63 differentially expressed genes (DEGs) between tumor-derived ECs and normal ECs were enriched in "angiogenesis", such as EFNB2, DLL4, and THSD7A. Subsequently, 114 retrospective EMS cases were included in clinical validation studies of EFNB2. It was co-expressed with PECAM1 and IGFBP3 and significantly increased in EC. Meanwhile, the recurrence rate of women with EFNB2++ expression was significantly higher than that of EFNB2+ cases (p <0.05). CONCLUSIONS: The significant increase in tumor-derived ECs characterized by neovascularization may be an important pathological feature of EMS. In addition, EFNB2 plays an important role and is closely related to the recurrence of EMS.

Analysis and prediction of postoperative recurrence of unilateral upper ureteral calculi in 243 cases (nomogram).

Objective: This study aimed to identify the risk factors for postoperative recurrence of unilateral upper ureteral calculi and develop a predictive nomogram. Patients and Methods: A retrospective analysis was conducted on 243 patients diagnosed with unilateral upper ureteral calculi who were treated at our hospital between January 1, 2016 and December 31, 2018. Patients were divided into two groups: recurrence or non-recurrence cohort. Differences in age, gender, smoking and/or drinking habit, laterality, stone diameter, ureteral stricture, stone incarceration, urinary tract infection, surgical intervention, operation time, body mass index, and metabolic syndrome were analyzed. Discrete risk factors were screened, and a nomogram was developed to predict the probability of stone recurrence. Results: The study found that the recurrence of ureteral calculi was associated with factors including stone diameter, ureteral stricture, stone incarceration, surgical intervention, operation time, metabolic syndrome, body mass index, triglycerides, diabetes, and high blood pressure (p < 0.05). Ureteral stricture, surgical intervention, metabolic syndrome, and triglycerides were found to be discrete risk factors for stone recurrence (p < 0.05). In addition, the study revealed that the stone recurrence rate of metabolic syndrome patients was significantly elevated (p < 0.05), as demonstrated by the survival curve. Lastly, using the nomogram, with an area under the curve value of 0.929, the recurrence rate of ureteral calculi was predicted. Conclusions: The study identified that preoperative ureteral stricture, laparoscopic ureterolithotomy, metabolic syndrome, and triglycerides are closely related to postoperative recurrence of ureteral calculi. The nomogram developed in this study can be used as a predictive tool for the recurrence rate of ureteral calculi.

Aryldiazonium Salt-Triggered [2 + 2 + 1] Heteroannulation of Indoles by an Arylhydrazone Radical-Relayed 1,5-Hydrogen Atom Transfer.

An unprecedented three-component [2 + 2 + 1] annulation cascade of indoles with aryldiazonium salts and polyhalomethanes or acetone is presented by dual hydrogen atom transfer (HAT) and C-H functionalization. By employing readily accessible aryldiazonium salts as the radical initiators and electrophiles and polyhalomethanes and acetone as the C1 units, this method unprecedentedly constructs a pyrazole ring on an indole ring skeleton through the formation of two C-N bonds and a C-C bond in a single reaction.

SIX1 induced HULC modulates neuropathic pain and Schwann cell oxidative stress after sciatic nerve injury.

Neuropathic pain is a severe and debilitating condition caused by damage to the peripheral nerve or central nervous system. Although several mechanisms have been identified, the underlying pathophysiology of neuropathic pain is still not fully understood. Unfortunately, few effective therapies are available for this condition. Therefore, there is an urgent need to investigate the underlying mechanisms of neuropathic pain to develop more effective treatments. Long non-coding RNAs (lncRNAs) have recently gained attention due to their potential to modulate protein expression through various mechanisms. LncRNAs have been implicated in many diseases, including neuropathic pain. This study aimed to identify a novel lncRNA involved in neuropathic pain progression. The lncRNA microarray analysis showed that lncRNA Upregulated in Liver Cancer (HULC) was significantly upregulated in spinal cord tissue of sciatic nerve injury (SNI) rats. Further experiments confirmed that HULC promoted neuropathic pain progression and aggravated H2O2-induced Schwann cell injury. Mechanistically, Sine Oculis Homeobox 1 (SIX1) regulated the transcriptional expression of HULC, and both SIX1 and HULC were involved in neuropathic pain and Schwann cell injury. The results of our research indicate the existence of a previously unknown SIX1/HULC axis that plays a significant role in the development and progression of neuropathic pain, shedding light on the complex mechanisms that underlie this debilitating condition. These findings offer novel insights into the molecular pathways involved in neuropathic pain. This study underscores the potential of targeting lncRNAs as a viable approach to alleviate the suffering of patients with neuropathic pain.

Polyetheretherketone (PEEK) as a Potential Material for the Repair of Maxillofacial Defect Compared with E-poly(tetrafluoroethylene) (e-PTFE) and Silicone.

Silicone and e-poly(tetrafluoroethylene) (e-PTFE) are the most commonly used artificial materials for repairing maxillofacial bone defects caused by facial trauma and tumors. However, their use is limited by poor histocompatibility, unsatisfactory support, and high infection rates. Polyetheretherketone (PEEK) has excellent mechanical strength and biocompatibility, but its application to the repair of maxillofacial bone defects lacks a theoretical basis. The microstructure and mechanical properties of e-PTFE, silicone, and PEEK were evaluated by electron microscopy, BOSE machine, and Fourier transformed infrared spectroscopy. Mouse fibroblast L929 cells were incubated on the surface of the three materials to assess cytotoxicity and adhesion. The three materials were implanted onto the left femoral surface of 90 male mice, and samples of the implants and surrounding soft tissues were evaluated histologically at 1, 2, 4, 8, and 12 weeks post-surgery. PEEK had a much higher Young's modulus than either e-PTFE or silicone (p < 0.05 each), and maintained high stiffness without degradation long after implantation. Both PEEK and e-PTFE facilitated L929 cell adhesion, with PEEK having lower cytotoxicity than e-PTFE and silicone (p < 0.05 each). All three materials similarly hindered the motor function of mice 12 weeks after implantation (p > 0.05 each). Connective tissue ingrowth was observed in PEEK and e-PTFE, whereas a fibrotic peri-prosthetic capsule was observed on the surface of silicone. The postoperative infection rate was significantly lower for both PEEK and silicone than for e-PTFE (p < 0.05 each). PEEK shows excellent biocompatibility and mechanical stability, suggesting that it can be effective as a novel implant to repair maxillofacial bone defects.