CD90's role in vascularization and healing of rib fractures: insights from Dll4/notch regulation.

BACKGROUND: Vascularization after rib fracture is a crucial physiological process that is essential for the repair and healing of the rib. Studies have shown that CD90 plays a critical role in regulating rib fracture healing, but the underlying mechanism of its role has not been fully elucidated. METHODS: CD90 adenovirus knockout mice were used to construct a rib injury model. The bone healing was observed by micro-CT. CD31/EMCN immunofluorescence staining was performed on bone tissue to observe the density of H-shaped and L-shaped blood vessels at the site of bone injury. CD31 and EMCN dual-stained single cells from the rib fracture sites were detected by flow cytometry. The periosteal stem cells transfected with CD90 or Notch1 overexpression and silencing vector were co-cultured with osteoblast MC3T3-E1 in osteogenic induction medium. Moreover, bone microvascular endothelial cells were extracted from the rib injury and co-cultured with the periosteal stem cells transfected with CD90. CCK-8 was used to detect cell viability, RT-qPCR and Western blot were used to detect Notch1, Notch2, Notch3, Notch4, CD31, HIF-1α, CD90, RUNX2, OCN and OPN expression. Alkaline phosphatase (ALP) staining and alizarin red staining were used to observe mineralized nodules. Immunofluorescence staining was used to detect the expression of Dll4, Notch, and CD90 in each group of cells. The angiogenesis experiment was conducted to observe cellular vascular formation. RESULTS: Compared with the Adsh-NC group, the bone healing in the Adsh-CD90 group was significantly impaired, with a marked reduction in the number and volume of blood vessels at the rib fracture site, as evidenced by CD31/EMCN immunofluorescence staining, which showed a reduction in the number of H type vessels at the site of bone injury. It was found that CD90 depletion can inhibit the signaling of Dll4/Notch in the rib fracture site. Furthermore, we found that overexpression of Notch1 reverses the impairment of tubule formation in bone microvascular endothelial cells caused by CD90 suppression.r.Dll4 protein reverses the inhibitory effect of CD90 deletion on periosteal stem cells and MC3T3-E1 cell viability and osteogenesis. In the end, we found that overexpression of Notch1 and CD90 can promote angiogenesis of bone microvascular endothelial cells and Notch pathway activation. CONCLUSION: CD90 can affect vascular formation in mouse rib fractures, and CD90 may be regulated by Dll4/Notch.

Raman spectroscopy for esophageal tumor diagnosis and delineation using machine learning and the portable Raman spectrometer.

Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.

Incidence, impact and predictors of residual device patency after left atrial appendage closure with the LACbes device.

BACKGROUND: The residual device patency (RDP) after left atrial appendage closure (LAAC) with the LACbes device has not been specifically explored in atrial fibrillation (AF) patients. This study aims to explore the incidence, impact and predictors of RDP detected by cardiac computed tomography angiography (CCTA) post LAAC. METHODS: AF patients implanted with the LACbes device were prospectively enrolled. CCTA device surveillance was performed at 3 months post-procedure. Major adverse events (MAEs), including stroke/transient ischemic attack, major bleeding and all-cause death, were evaluated. RESULTS: Among 141 patients with CCTA surveillance, 56 (39.7%) showed no visible leak and 85 (60.3%) showed RDP. During the median follow-up of 443 [232, 706] days, the presence of RDP was not associated with an increased risk of MAEs (adjusted hazard ratio [HR]: 4.07, 95% confidence interval [CI]: 0.49-34.24, p = 0.196), while peri-device leak (PDL) at the lobe was associated with heightened risks of MAEs (adjusted HR: 6.85, 95% CI: 1.62-28.89, p = 0.009). In patients with PDL at the lobe, antiplatelet after 6 months (HR: 0.20, 95% CI: 0.05-0.91, p = 0.038) was independent protective predictor of MAEs. Besides, current smoking (odds ratio [OR]: 7.52, 95% CI: 2.68-21.08, p < 0.001) and maximum diameter of LAA orifice (OR: 1.16, 95% CI: 1.00-1.34, p = 0.048) were independent predictors of PDL at the lobe. CONCLUSIONS: Presence of PDL at the device lobe detected by CCTA at 3-month post LAAC with LACbes is associated with unfavorable prognosis in AF patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03788941.

Clinical features of idiopathic epiretinal membrane in children and the factors influencing postoperative visual acuity.

PURPOSE: To describe the characteristics and surgical outcomes of idiopathic epiretinal membrane (iERM) in children and to determine the factors associated with postoperative visual acuity (VA). METHODS: We retrospectively reviewed the medical records of 17 patients with iERM (age, < 18 years) who had undergone ERM surgery from 2009 to 2021. Spectral-domain optical coherence tomography features were documented. The eyes with iERMs involving the fovea were assigned to the localized and diffused groups depending on the morphological description of the membrane. Multiple linear regression analysis was used to explore the factors associated with the final VA. RESULTS: The mean age was 9.2 ± 3.8 years. The mean follow-up period was 38.9 ± 45.4 months. After surgery, the central foveal thickness and the best-corrected VA (BCVA) improved significantly (all, P < 0.05). Fourteen eyes with iERMs showed involvement of the foveal area (localized group, six eyes; diffused group, eight eyes). There were no significant differences in the preoperative BCVA between the two groups (P = 0.064). However, the final BCVA was better in the diffused group than in the localized group (P = 0.043). Multiple regression analysis indicated that the localized membrane (P = 0.042) and lower preoperative BCVA (P = 0.043) were factors associated with a worse final VA in pediatric iERMs. CONCLUSIONS: Surgical removal of ERM showed a high anatomical and functional success rate in children. In pediatric patients with iERMs involving the fovea, a good VA was more common when the membrane was diffused than when it was localized.

Predictive effect of TCED-HFV grading and imaging biomarkers on anti-VEGF therapy in diabetic macular edema.

BACKGROUND: To evaluate the predictive effect of TCED-HFV grading and imaging biomarkers on anti-vascular endothelial growth factor (anti-VEGF) treatment in diabetic macular edema (DME). METHODS: 81 eyes of 81 DME patients who were treated with anti-VEGF were included in this retrospective cohort study. All patients underwent a comprehensive ophthalmic examination at baseline and follow-up, including best-corrected visual acuity (BCVA), fundus photography, and spectral domain-optical coherence tomography (SD-OCT). Baseline imaging biomarkers were qualitatively and quantitatively graded according to the TCED-HFV classification protocol, and DME was divided into early stage, advanced stage, severe stage, and atrophy stage. RESULTS: Six months post treatment, central subfield thickness (CST) in 49 eyes (60.5%) had decreased by 10% from baseline, 30 eyes (37.0%) had achieved CST < 300 µm, and 45 eyes (55.6%) had BCVA improved by more than five letters. Multivariate regression analysis revealed that eyes with baseline CST ≥ 390 µm had a higher probability of ≥ 10% reduction in CST from baseline, and eyes with abundant hyperreflective dots (HRD) had a lower probability of 10% reduction in CST (all P < 0.05). Eyes with vitreomacular traction (VMT) or epiretinal membrane (ERM) at baseline were less likely to reach the end point of CST < 300 µm (P < 0.05). BCVA increases of more than five letters were less likely in eyes with baseline BCVA ≥ 69 letters, complete or partial destruction of ellipsoid zone (EZ) at baseline (all P < 0.05). TCED-HFV staging was negatively correlated with BCVA at both baseline and 6 months (Kendall's tau-b=-0.39 and - 0.55, all P < 0.01). TCED-HFV staging was positively correlated with CST at 6 months (Kendall's tau-b = 0.19, P = 0.049) and negatively correlated with the reduction of CST (Kendall's tau-b=-0.32, P < 0.01). CONCLUSION: The TCED-HFV grading protocol facilitates a comprehensive assessment of DME severity, standardizes the grading of multiple imaging biomarkers, and predicts the anatomical and functional outcomes of anti-VEGF treatment.

Potential Molecular Mechanism of Upregulated Aryl Hydrocarbon Receptor Nuclear Translocator 2 in Nasopharyngeal Carcinoma.

Background: Currently, the benefits of nasopharyngeal carcinoma (NPC) therapy are limited, and it is necessary to further explore possible therapeutic targets. Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) has been extensively studied in other cancer species, but little has been explored in NPC. The aim of this study was to verify the expression level of ARNT2 and its underlying mechanism in NPC. Methods: Datasets containing ARNT2 mRNA expression levels were retrieved and collected from various databases to explore the expression status of ARNT2 in NPC. ARNT2-related coexpressed genes, differential expressed genes, and target genes were obtained for functional enrichment analysis. The potential target gene of ARNT2 and their regulatory relationship were studied through ChIP-seq data. CIBERSORTx was used to assess the immune infiltration of NPC, and the association with ARNT2 expression was calculated through correlation analysis. Results: ARNT2 was upregulated and possessed an excellent discriminatory capability in NPC samples. ARNT2 positively correlated target genes were clustered in pathways in cancer, while negatively correlated target genes were enriched in immune-related pathway. The ChIP-seq information of ARNT2 and histone showed that prostaglandin-endoperoxide synthase 2 (PTGS2) was a potential target gene of ARNT2. CIBERSORTx revealed the immunity status in NPC, and ARNT2 expression was correlated with infiltration of five immune cells. Conclusions: ARNT2 is overexpressed in NPC and may regulate PTGS2 to participate in the cancer process. ARNT2 serves as a key oncogenic target in NPC patients.

Case report: Intrapericardial thrombus aspiration in early stage of pericardial thrombosis for cardiac tamponade complicating percutaneous left atrial appendage closure.

Introduction: Pericardial thrombosis that complicates pericardial bleeding is a life-threatening emergency in interventional cardiology, and surgery remains the only definitive treatment option. We report the first case of successful intrapericardial thrombus aspiration using a dedicated thrombus aspiration catheter in the early stage of pericardial thrombosis. Case report: A 76-year-old woman with non-valve atrial fibrillation underwent percutaneous left atrial appendage (LAA) closure for secondary prevention of stroke. A 24-mm Watchman device was deployed under fluoroscopic guidance. Post-deployment angiography revealed LAA perforation, which led to the rapid onset of cardiac tamponade. Emergency pericardiocentesis was performed and the deep-seated device was redeployed at a more proximal position to seal the distal perforation. Pericardial bleeding was controlled after the drainage of 400 ml of blood. However, the patient re-developed cardiac tamponade following a period of stability. The patient was diagnosed with early-stage pericardial thrombosis based on echocardiographic findings of a hypoechoic effusion in the pericardial space. Thrombus aspiration using a pigtail catheter and long sheath failed; however, we performed successful intrapericardial thrombus aspiration using a dedicated thrombus aspiration catheter. We drained 120 ml of sludge-like blood, and the patient underwent successful conservative management without surgical intervention. Conclusion: This case report highlights the potential usefulness of a percutaneous intrapericardial thrombus aspiration technique using a dedicated thrombus aspiration catheter in selected patients with early-stage pericardial thrombosis, as a less invasive alternative to cardiac surgery.

EFFECTS OF ECTOPIC INNER FOVEAL LAYERS ON FOVEAL CONFIGURATION AND VISUAL FUNCTION AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the effects of ectopic inner foveal layers (EIFLs) on foveal configuration recovery and visual acuity after idiopathic epiretinal membrane removal and analyze the relationship of foveal configuration recovery between 1-month and long-term postoperatively. METHODS: This retrospective study included 216 consecutive eyes with idiopathic epiretinal membrane that underwent vitrectomy surgery. A comprehensive ophthalmic examination was performed for all patients before and 1, 4, 10, and 24 months after surgery. We observed the postoperative anatomical and functional recovery of eyes with and without EIFLs and analyzed the association between short-term and long-term anatomical recovery. RESULTS: The presence of EIFL was associated with severe preoperative visual damage ( P < 0.001) and was considered as a negative factor for postoperative foveal depression recovery ( P < 0.001). No significant difference was found in postoperative best-corrected visual acuity between the eyes with and without EIFLs ( P = 0.442). For eyes with Stage II epiretinal membranes, 17.6% developed EIFLs postoperatively, which did not affect the final best-corrected visual acuity. Overall, 24.5% of epiretinal membranes restored the foveal configurations at 1 month postoperatively, and 14.7% continued recovering during the follow-up. Foveal structure recovery in eyes with EIFLs was associated with earlier stage, fewer microcystic macular edema, complete interdigitation zone layer, and a thinner central foveal thickness (all P < 0.05) at 1 month postoperatively. CONCLUSION: The EIFL is associated with severe preoperative visual damage and is a negative factor for postoperative anatomical recovery, but it is a minor factor for postoperative visual acuity. We also found an association of foveal configuration recovery between 1 month and long-term after surgery.

Identification of NLE1/CDK1 axis as key regulator in the development and progression of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, which is a severer threaten to human health because of its extremely high morbidity and mortality. In this study, the role of Notchless homolog 1 (NLE1) in the development of NSCLC was investigated and the underlying mechanism was explored. The outcomes showed that NLE1 expression is significantly higher in tumor tissues than normal tissues, and is correlated with the pathological stage. The regulation of NSCLC development by NLE1 was also visualized by the in vitro and in vivo loss-of-function studies, which indicated the inhibition of cell growth and migration, as well as enhancement of cell apoptosis on condition of NLE1 knockdown. As for the mechanism, it was demonstrated that NLE1 may execute its tumor-regulating function through activating E2F1-mediated transcription of CDK1, and PI3K/Akt signaling pathway was also supposed as a downstream of NLE1 in the regulation of NSCLC. Both CDK1 overexpression and treatment of Akt pathway activator could reverse the NLE1 knockdown induced NSCLC inhibition to some extent. In conclusion, this study identified NLE1 as a novel tumor promotor in the development and progression of NSCLC, which may be a potential therapeutic target in the treatment of NSCLC.

Laryngeal Squamous Cell Carcinoma: Clinical Significance and Potential Mechanism of Cell Division Cycle 45.

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45, CDC6, KIF2C, and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45. Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

Suprachoroidal hemorrhage associated with pars plana vitrectomy.

PURPOSE: To analyze the characteristics, related risk factors, and prognosis of suprachoroidal hemorrhage (SCH) associated with pars plana vitrectomy (PPV). METHODS: Cases of SCH associated with PPV excluding trauma were retrospectively analyzed in Beijing Tongren Hospital between January 2010 and June 2020. The data collected included general data, myopia status, axial length, state of the crystalline lens, SCH onset time, range, treatment method, visual prognosis, and methods of operation and anesthesia. Patients were divided into those with SCH related to the first PPV (Group 1), and SCH related to second intraocular surgery in the vitrectomized eye (Group 2). Patients were also classified by the SCH onset time into either the expulsive suprachoroidal hemorrhage group (ESCH) and the delayed suprachoroidal hemorrhage group (DSCH). The general data, related risk factors, and the visual prognosis of SCH in the different groups were analyzed. RESULTS: SCH associated with PPV was studied in 28 cases with an incidence of 0.06 %; 16 males and 12 females. The mean age of the patients was (53.51 ± 10.21) years old, the mean follow-up time was (24.94 ± 14.60) days, and the mean axial length was (28.21 ± 3.14) mm. Of these cases, 21 were classified as high myopia, 25 as aphakia/ pseudophakic, and 7 as focal hemorrhage. Silicone oil removal occurred in 12 cases (43 %). Patients in Group 2 were younger than Group 1 (P = 0.005). In terms of treatment and prognosis, 5 eyes were simply closely observed, 4 were given single suprachoroidal drainage, 15 were given suprachoroidal drainage combined with silicone tamponade, 2 underwent anterior chamber puncture, and 2 gave up treatment. A follow-up vision: NLP ~ 20/30; among them, 2 eyes with NLP (7.14 %), 6 of ≥ 20/200 (21.43 %). The final outcomes presented a significantly positive correlation with baseline vision but no significant correlation with age or axial length. CONCLUSIONS: SCH has a higher incidence rate after a second intraocular surgery in a vitrectomized eye which is associated with the lack of vitreous support and easier fluctuation of intraocular pressure. SCH associated with PPV is more localized and has a relatively good prognosis; high myopia and aphakic/ pseudophakic eyes are risk factors. Active treatment can effectively improve visual prognosis. TRIAL REGISTRATION: Retrospective case series study, not applicable.

A Comprehensive Evaluation of miR-144-3p Expression and Its Targets in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive type of head and neck squamous cell carcinoma (HNSCC) with a relatively high rate of morbidity and mortality. An altered miR-144-3p level in LSCC with a small number of patients has been previously reported. However, the clinical implication of miR-144-3p and its involved mechanism underlying this disease is not clearly elucidated. In this work, we aimed to confirm the expression of miR-144-3p with larger samples and also to identify target genes for the investigation of the underlying mechanism of miR-144-3p in LSCC. The levels of miR-144-3p were downregulated in 155 samples of LSCC tissues as compared to 26 non-LSCC samples (SMD: -0.78; 95% confidence interval (CI): -1.23, -0.32). The AUC of 0.90 in the summarized ROC curve also indicated a potential ability to differentiate LSCC from non-LSCC tissues, with a sensitivity of 0.78 and a specificity of 0.88. With respect to the molecular mechanism, we predicted the potential targets from online-based prediction, peer-reviewed publications, and RNA-seq and microarray data. In particular, the genes influenced by transfection with miR-144-3p in the LSCC FaDu cell line were collected from the microarray GSE56243. Lastly, 12 novel targets for miR-144-3p in LSCC were obtained by different algorithms. In conclusion, our study confirmed the loss or downregulation of miR-144-3p in LSCC, which might contribute to the LSCC tumorigenesis and progression via regulation of the 12 novel targets, such as IL24, ITGA6, and CEP55. In the future, further investigations are required to validate the present results.

Surgical strategies for glottic carcinoma with a giant thyroid tumor A case report and literature review.

Description of strategies for preventing surgical complications in the treatment of laryngeal carcinomas associated with giant thyroid cancer. For this study, the clinical data of an elderly patient with laryngeal carcinoma associated with a large thyroid tumor, diabetes and hypertension were used. The patient's tumor was removed with simultaneous surgery performed by the thyroid surgery department and the laryngeal surgery department; the patient was followed for more than 3 years and the scars of tracheal granulation and laryngeal adhesions were removed with repeated laser interventions. The literature review was carried out on the Wanfang database, on the China How Net database and on the MEDLINE database via Computer. The final research keywords used for the study were "squamous cell carcinoma" and "glottis" or "larynx" / "larynx", "surgery", "thyroid cancer" and "simultaneous surgery". RESULTS: After completion of the intervention, the nasogastric tube and tracheal cannula were successfully removed, the glottis was successfully reconstituted and oral respiration, phonation and oral feeding were normally resumed. CONCLUSION: The multidisciplinary approach for the simultaneous removal of a laryngeal carcinoma associated with a bulky thyroid tumor in elderly subjects with multi-system and multi-organ damage has been successfully implemented. There are only a few such cases presented in the literature to illustrate risk prevention strategies for postoperative complications, including postoperative infection, extubation difficulties and loss of speech, which deserve to be known. KEY WORDS: Glottic carcinoma, Thyroid tumor, Laser surgery multidisciplinary, Tracheal cannula, Vocal cords.

The underlying molecular mechanism and identification of transcription factor markers for laryngeal squamous cell carcinoma.

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein-protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs - BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 - were screened via Kaplan-Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13-0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.

Laryngeal Squamous Cell Carcinoma: Potential Molecular Mechanism and Prognostic Signature Based on Immune-Related Genes.

BACKGROUND Immune-related genes (IRGs) are closely related to the incidence and progression of tumors, potentially indicating that IRGs play an important role in laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS An RNA sequencing dataset containing 123 samples was collected from The Cancer Genome Atlas. Based on immune-related differentially expressed genes (IRDEGs), a potential molecular mechanism of LSCC was explored through analysis of information in the Gene Ontology (GO) resource and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPIs). A regulatory network of transcriptional regulators and IRDEGs was constructed to explore the underlying molecular mechanism of LSCC at the upstream level. Candidates from IRDEGs for signature were screened via univariate Cox analysis and using the least absolute shrinkage and selection operator (LASSO) technique. The IRDEG signature of LSCC was constructed by using a multivariate Cox proportional hazards model. RESULTS GO and KEGG analysis showed that IRDEGs may participate in the progression of LSCC through immune-related reactions. PPI analysis demonstrated that, among the IRDEGs in LSCC, the Kininogen 1; C-X-X motif chemokine ligand 10; elastase, neutrophil expressed; and LYZ genes are hub genes in the development of LSCC. At the upstream level, SPI1, SP140, signal transducer and activator of transcription 4, zinc finger E-box binding homeobox, and Ikaros family zinc finger 2 are the hub transcriptional regulators of IRDEGs. The risk score based on the IRDEG signature was able to distinguish prognosis in patients with LSCC and represents an independent prognostic risk factor for LSCC. CONCLUSIONS From the perspective of IRGs, we first constructed an IRDEG signature related to the prognosis of LSCC, which can be used as a novel marker to predict prognosis in patients with LSCC.

Novel use of an adjustable single 8-0 polypropylene suture of scleral fixation without conjunctival dissection.

BACKGROUND: This report serves to describe the use of a novel adjustable single 8-0 polypropylene suture for scleral fixation without conjunctival dissection, and to describe related clinical outcomes associated with this approach. METHODS: In this study, we retrospectively reviewed 28 eyes from 27 patients that underwent scleral fixation of the intraocular lens (IOL) without conjunctival dissection using an adjustable single 8-0 polypropylene suture at the Beijing Tongren Eye Center between April 2018 and April 2019. For this surgical approach, a 23-gauge infusion cannula was set, after which two Hoffmann scleral pockets were created. Next, 8-0 polypropylene sutures were inserted into the eye guided by 10-0 polypropylene sutures of a long straight needle. The 8-0 suture was then used to fix the haptic IOs. Finally, these 8-0 polypropylene sutures were removed from the scleral pockets, and knots were tightened with the adjustable single suture. Primary outcomes included visual acuity and postoperative complication incidence. RESULTS: For this study, outcomes for 28 eyes from 27 patients (9 female, 18 male) were assessed. Patients had a mean age of 54 ± 15.11 years-old and were followed for an average of 10.18 ± 2.76 months postoperatively. Uncorrected visual acuity in these patients improved significantly from a preoperative value of 1.269 ± 0.464 logMAR to a 3-month postoperative value of 0.409 ± 0.413 logMAR (p = 0.000). The majority of postoperative complications in these patients were temporary and self-limiting, including corneal edema (35.71%), hypotony (14.29%), elevated intraocular pressure (28.58%), and mild hyphema (7.14%). No evidence of exposure or erosion of the trimmed suture end was detected in any patients. An ultrasound biomicroscope was able to readily detect the IOL and all sutures, and IOLs were found to be well-centered without any dislocation, tilting, or subluxation upon follow-up. CONCLUSIONS: An adjustable single 8-0 polypropylene suture can reliably and effectively be used for scleral fixation without conjunctival dissection for the treatment of patients with aphakia or inadequate posterior capsule support. The novel procedure described herein may therefore be an effective means of minimizing the risk of suture-related complications in patients undergoing scleral-fixated IOL implantation. TRIAL REGISTRATION: Retrospective case series study, not applicable. NCT04476264 .

MiR-429 Involves in the Pathogenesis of Colorectal Cancer via Directly Targeting LATS2.

Colorectal cancer (CRC) is a leading cause of cancer-related death around the world whose recurrence and metastasis rate is high. Due to the underlying unclear pathogenesis, it is hard so far to predict the tumorigenesis and prevent its recurrence. YAP/TAZ has been reported to be activated and functioned as a potential oncogene in multiple cancer types and proved to be essential for the carcinogenesis of most solid tumors. In the present study, we found that YAP/TAZ was markedly upregulated in CRC tissues comparing with the adjacent noncancerous tissues due to the downregulation of LATS2, the main upstream regulator. We further identified miR-429 as a direct regulator of LATS2-YAP/TAZ activation, suggesting that the miR-429-LATS2-YAP/TAZ might be novel effective diagnostic axis and therapeutic targets for CRC.

Spillover and quantile linkage between oil price shocks and stock returns: new evidence from G7 countries.

The link between crude oil price and stock returns of the Group of Seven (G7) countries (Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States) was analyzed in this study using monthly data from January 1999 to March 2020. We adopt a similar approach to Kilian (Am Econ Rev 99(3):1053-1069, 2009) and construct a structural vector autoregression framework to decompose crude oil price shocks into oil supply shock, oil aggregate demand shock, and oil-specific demand shock. We then explore the distinct effects of different kinds of oil price shocks from various sources. Based on the decomposed oil price shocks, we apply the connectedness approach and QQ regression to find time-varying co-movements and tail dependence between oil price shocks and G7 stock returns. There is no general correlation between the decomposed oil prices and stock returns in these countries. The effects of oil price shocks on stock returns across different stock market conditions appear to be heterogeneous. Oil supply shock appears to be a net transmitter of spillover effects for all G7 countries within the sample period.

[Acupoint catgut embedding improves dysmenorrhea by suppressing activation of NLRP3 inflammasomes in uterine tissues in primary dysmenorrhea rats].

OBJECTIVE: To observe the effect of acupoint catgut embedding on the expression of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin (IL)-1ß and IL-18 in the uterine tissue of primary dysmenorrhea (PD) rats, so as to explore its underlying mechanisms in improving PD. METHODS: Forty female SD rats were randomly divided into control, model, acupoint catgut embedding and medication groups (n＝10 in each group). The PD model was established by subcutaneous injection of Estradiol Benzoate (0.5 mg/rat on the 1st and 10thday, and 0.2 mg/rat from 2nd to 9thday) and Oxytocin (2 U/rat, i．p.). The catgut embedding was applied to bilateral "Sanyinjiao" (SP6) and "Guanyuan" (CV4) on the 1st and 5th day after modeling. Rats of the medication group were treated by intragastric perfusion of Fenbid (0.8 mL/rat, 125 mg/100 mL) once daily for 10 days. The body writhing times in 30 min were recorded. The histopathological changes of the uterine were observed by H．E. staining. Western blot was used to detect the expression of NLRP 3, caspase-1, IL-1ß and IL-18 in uterine tissues. RESULTS: The body writhing times were notably more in the model group than in the control group (P<0.01), and obviously fewer in both medication and catgut embedding groups than in the model group (P<0.05, P<0.01). After modeling, the rats' endometrium was extensively exfoliated and got swelling, the histopathological score and the expression levels of NLRP3, caspase-1, IL-1ß and IL-18 proteins in the uterus tissue were evidently increased in the model group relevant to the control group (P<0.01). Following the treatment, the degree of endometrial exfoliation and edema of the uterus tissue was lightened, the pathological score was significantly reduced (P<0.01), and the expression levels of caspase-1, IL-1ß and IL-18 protein in uterus tissue were markedly decreased in both acupoint catgut embedding and medication groups (P<0.01, P<0.05). The NLRP3 protein expression was significantly decreased in the acupoint catgut embedding group compared with that in the model group (P<0.01). The therapeutic effect of acupoint catgut embedding was significantly superior to that of medication in reducing writhing times and down-regulating expression of NLPR3 protein (P<0.01). No significant differences were found between catgut embedding and medication in histopathological score, and expression levels of caspase-1, IL-1ß and IL-18 proteins (P>0.05). CONCLUSION: The acupoint catgut embedding can significantly alleviate the symptoms and pathological damage in PD rats, which may be related to its effect in inhibiting the activation of NLRP3 inflammasome in the uterine tissue.

Methylation of C/EBPα by PRMT1 Inhibits Its Tumor-Suppressive Function in Breast Cancer.

C/EBPα is an essential transcription factor involved in regulating the expression or function of certain cell-cycle regulators, including in breast cancer cells. Although protein arginine methyltransferases have been shown to play oncogenic roles in a variety of cancers, little is known about the role of arginine methylation in regulating the antiproliferation activity of C/EBPα. Here, we report that the protein arginine methyltransferase 1 (PRMT1) is overexpressed in human breast cancer and that elevated PRMT1 correlates with cancer malignancy. RNA-sequencing analysis revealed that knockdown of PRMT1 in breast cancer cells is accompanied by a decrease in the expression of pro-proliferative genes, including cyclin D1. Furthermore, tandem affinity purification followed by mass spectrometry identified PRMT1 as a component of the C/EBPα complex. C/EBPα associated with and was methylated by PRMT1 at three arginine residues (R35, R156, and R165). PRMT1-dependent methylation of C/EBPα promoted the expression of cyclin D1 by blocking the interaction between C/EBPα and its corepressor HDAC3, which resulted in rapid growth of tumor cells during the pathogenesis of breast cancer. Inhibition of PRMT1 significantly impeded the growth of cancer cells from patients with triple-negative breast cancer. This evidence that PRMT1 mediates C/EBPα methylation sheds light on a novel pathway and potential therapeutic target in breast cancer. SIGNIFICANCE: This study provides novel mechanistic insight of the role of the arginine methyltransferase PRMT1 in breast cancer pathogenesis.