Non-coding RNA in infantile hemangioma.

Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, but its pathogenesis has not been fully discovered. From the cellular perspective, CD133+ stem cells orchestrate the proliferation and development of IH. Regarding molecular mechanisms, hypoxia inducible factor-1α, renin-angiotensin system, and vascular endothelial growth factor are current study hotspots, while non-coding RNAs (ncRNAs) might be essential factors participating in this network. Therefore, this article reviewed published studies concerning the roles of ncRNAs in IH and listed noted miRNAs, lncRNAs, and circRNAs. Other ncRNAs, such as snRNAs, snoRNAs, and tsRNAs, though have not been examined in IH, are mentioned as well to discuss their potential functions. Due to the continuous development of sequencing technologies and computational pipelines for ncRNAs annotation, relevant studies will provide evidence to gradually enhance acknowledgments of ncRNAs' role in IH. The pathogenesis of IH might be revealed and the treatment protocol would be optimized in the future. IMPACT: Non-coding RNAs (ncRNAs) play critical roles in infantile hemangioma. This article thoroughly reviewed all ncRNAs (miRNAs, lncRNAs, and circRNAs) mentioned in previous studies regarding the pathogenesis of infantile hemangioma. Other ncRNAs are promising subjects for further investigation. This review introduced the emerging ncRNAs that need to be explored in IH.

"Evolution" of intravascular leiomyomatosis.

BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare and specific type of smooth muscle tumor that is histologically benign but has a malignant biological behavior. It is commonly associated with a history of uterine leiomyomas. CASE PRESENTATION: A 36-year-old woman, G1P1, presented to the hospital with left lower abdominal pain for 2 months and she has accepted hysteroscopic myomectomy about 1 year ago. Ultrasound venography, echocardiography and computed tomography venography (CTV) of inferior vena cava were performed, which revealed IVL located in left intramural myometrium walls growing along the left ovarian vein reaching the level of the lumbar 5-sacral 1 disc. Laparoscopic bilateral salpingo-oophorectomy and hysterectomyis were scheduled. The IVL in the left ovarian vein and parauterine venous plexus were detected and excised completely during surgery. IVL was diagnosed by postoperative pathology and immunohistochemistry. The patient recovered well after surgery. No surgical-related or anesthesia-related complications occurred.The 3-month follow-up CTV of inferior vena cava and echocardiography examination revealed normal. CONCLUSIONS: The cause of IVL is unknown, this observation demonstrates that hysteroscopic myomectomy might lead to the occurrence of IVL.

Comparison of Different Laparoscopic Sacropexy Procedures for Advanced Uterine Prolapse: A Retrospective Analysis.

STUDY OBJECTIVE: To compare the long-term outcomes and complications of 3 different variants of laparoscopic sacropexy. DESIGN: Single-center retrospective cohort study. SETTING: A tertiary university hospital. PATIENTS: A total of 483 patients with advanced uterine prolapse who underwent laparoscopic sacrohysteropexy (LSH), laparoscopic supracervical hysterectomy with concomitant laparoscopic sacrocervicopexy (LSCH + LSC), or total laparoscopic hysterectomy with concomitant laparoscopic sacrocolpopexy (TLH + LSC). INTERVENTIONS: Demographic data, Pelvic Organ Prolapse Quantification scores, questionnaire results, surgical conditions, postoperative outcomes, and complications were all extracted from medical and follow-up records. MEASUREMENTS AND MAIN RESULTS: Between April 2012 and December 2020, 277 women underwent LSH, 95 women underwent LSCH + LSC, and 111 women underwent TLH + LSC. LSH procedures were associated with statistically significantly least blood loss and least postoperative hospital days and catheterization days (all p <.001). During the median follow-up of 32 months (13-117 months), analysis of the data revealed notable anatomic correction in all groups regarding Pelvic Organ Prolapse Quantification measurements (p <.001), and the anatomic cure rate showed no significant difference among these 3 groups (p = .273). No statistically significant differences were detected for prolapse recurrence (p = .171) and functional improvements among these groups. Neither intraoperative injuries (p = .098) nor total postoperative complications (p = .218) differed considerably, whereas the rate of severe postoperative complications (p <.001) including mesh exposure (p = .004) was significantly higher in the TLH + LSC group than that in the other groups. CONCLUSIONS: LSH is the appropriate choice for women with uterine prolapse without contraindications for uterine preservation. For patients with benign uterine lesions and a normal cervix, LSCH + LSC is a safer approach that provides similar anatomic results and improved quality of life scores that are similar to those of TLH + LSC. For patients with lesions in the uterus and cervix, TLH + LSC should be selected.

A prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant from benign pulmonary nodules.

BACKGROUND: Lung cancer remains the leading cause of cancer deaths across the world. Early detection of lung cancer by low-dose computed tomography (LDCT) can reduce the mortality rate. However, making a definitive preoperative diagnosis of malignant pulmonary nodules (PNs) found by LDCT is a clinical challenge. This study aimed to develop a prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant pulmonary nodules from benign PNs. METHODS: We assessed three DNA methylation biomarkers (PTGER4, RASSF1A, and SHOX2) and clinically-relevant variables in a training cohort of 110 individuals with PNs. Four machine-learning-based prediction models were established and compared, including the K-nearest neighbors (KNN), random forest (RF), support vector machine (SVM), and logistic regression (LR) algorithms. Variables of the best-performing algorithm (LR) were selected through stepwise use of Akaike's information criterion (AIC). The constructed prediction model was compared with the methylation biomarkers and the Mayo Clinic model using the non-parametric approach of DeLong et al. with the area under a receiver operator characteristic curve (AUC) analysis. RESULTS: A prediction model was finally constructed based on three DNA methylation biomarkers and one radiological characteristic for identifying malignant from benign PNs. The developed prediction model achieved an AUC value of 0.951 in malignant PNs diagnosis, significantly higher than the three DNA methylation biomarkers (0.912, 95% CI:0.843-0.958, p = 0.013) or Mayo Clinic model (0.823, 95% CI:0.739-0.890, p = 0.001). Validation of the prediction model in the testing cohort of 100 subjects with PNs confirmed the diagnostic value. CONCLUSION: We have shown that integrating DNA methylation biomarkers and radiological characteristics could more accurately identify lung cancer in subjects with CT-found PNs. The prediction model developed in our study may provide clinical utility in combination with LDCT to improve the over-all diagnosis of lung cancer.

Management of uterine cystic adenomyosis by laparoscopic surgery: case report.

BACKGROUND: Endometriosis of the uterine body can be manifested as diffuse solid lesions or cystic lesions. The former is common, while the latter is rare, especially for cystic adenomyosis larger than 5 cm. CASE PRESENTATION: A 30-year-old woman was admitted for severe and worsening dysmenorrhea. Ultrasound examination revealed a rare well-circumscribed cystic lesion about 5.5 × 4 × 5.0 cm. CA-125 level was slightly elevated. She accepted laparoscopic surgery and the adenomyotic tissues were excised. The histopathology of the specimen demonstrated the endometrial glands in the walls of cysts and an area of extensive hemorrhage can be seen in the inner wall of cyst. The patient made a good recovery after surgery and her symptoms complete resoluted. CONCLUSIONS: This is a rare case of a cystic adenomyotic lesion that was treated by laparoscopic surgery.

Laparoscopic salpingostomy for two types of hydrosalpinx: a step-by-step video tutorial.

OBJECTIVE: This study aims to illustrate our laparoscopic salpingostomy approach for two types of hydrosalpinx, emphasizing various reproductive surgical techniques. DESIGN: A step-by-step demonstration of the technique is provided alongside narrated video footage. SETTING: University hospital. PATIENT(S): Infertile patients with hydrosalpinx seeking natural conception. INTERVENTION(S): Laparoscopic salpingostomy for clubbed hydrosalpinx is demonstrated with video and includes the following steps: creating an opening into the tube at the terminal end for hydrosalpingeal fluid drainage; dissecting and removing peritubal and periovarian adhesions; excising redundant fimbrial tissues to restore fimbrial mobility; evert the mucosa using an intussusception method until endothelial folds are visible; confirming tubal patency with a dye test; heating the serosal surface of the tube to evert the edges; suturing the edges using 5-0 vicryl to the proximal serosa of the tube circumferentially with an inverting suture technique; thoroughly irrigating with Ringer's solution to remove blood clots and debris; and applying auto-crosslinked hyaluronan gel to the exposed raw surface. Salpingostomy for the cystic type differs, notably in carefully shaving the adhesive tubal end from the ovary until the tubo-ovarian ligament is completely exposed. MAIN OUTCOME MEASURE(S): The primary aim of salpingostomy is to reduce the likelihood of distal tube re-obstruction. If hydrosalpinx recurs after salpingostomy, there remains a possibility of requiring additional surgery, such as salpingectomy, before in vitro fertilization. RESULT(S): Extensive adhesions were meticulously dissected and removed from the peritoneal cavity. Fimbrial mobility was restored to establish a patent fallopian tube capable of ovum pickup. Electrocoagulation and suturing techniques were employed to evert the tube edges, effectively reducing the risk of re-obstruction. The utilization of an inverting suture technique aided in inwardly turning the cut edges, minimizing the risk of adhesion formation. CONCLUSION(S): Laparoscopic salpingostomy, when performed by surgeons proficient in reproductive surgical techniques, provides a significant option for patients with hydrosalpinx seeking natural conception. The decision to preform salpingostomy or salpingectomy is usually made intraoperatively on the basis of the severity of tubal disease. Clinical history is also an important factor in decision to perform salpingostomy.

The roles of genetic mutation and cytokines/chemokines in immune response and their association with uveal melanoma patient outcome.

The impact of tumor mutations and the interplay of cytokines and chemokines on the immune response and clinical outcomes in uveal melanoma (UM) warrants further exploration. In our study, we delved into the correlation between genetic alterations and survival rates in a cohort of 188 UM patients, utilizing data from cBioPortal. We assessed the composition of immune cell populations within 80 UM tumors by examining RNA sequence-based gene expression data from The Cancer Genome Atlas (TCGA). Furthermore, we scrutinized the relationship between genetic mutations and the expression of cytokines and chemokines, as well as their influence on various immune cell subsets. Our investigation revealed a significant association between the presence of mutated GNAQ or SF3B1 genes and improved progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) when compared to patients with non-mutated counterparts. In contrast, the presence of immune response gene mutations was associated with a detrimental effect on PFS, DSS, and OS. We also observed that the expression levels of cytokines and chemokines were positively linked to the infiltration of immune killer cells and inversely related to the populations of B cells and dendritic cells. Elevated expression levels of PDCD1, TNF, IL6, CXCL9, and CXCL10 were found to be correlated with reduced OS. Intriguingly, an increase in CD8+ T cell populations was associated with a poorer OS, a finding that warrants further investigation. These findings underscore the potential utility of cytokines/chemokines expression levels, immune cell subsets, and mutation status as critical biomarkers for the selection of patients who are most likely to benefit from immunotherapeutic interventions. Our research provides valuable insights that could guide the development of more targeted and effective treatment strategies for UM patients.

Single­cell RNA sequencing reveals heterogeneity in ovarian cancer and constructs a prognostic signature for prognostic prediction and immunotherapy.

BACKGROUND: Ovarian cancer (OC) is one of the cancers with a high incidence at present, which poses a severe threat to women's health. This study focused on identifying the heterogeneity among malignant epithelial cell OC and constructing an effective prognostic signature to predict prognosis and immunotherapy according to a multidisciplinary study. METHODS: The InterCNV algorithm was used to identify the heterogeneity of OC based on the scRNA-seq and bulk RNA-seq data. Six algorithms selected EMTscore. An effective prognostic signature was conducted using the COX and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The texting datasets were used to assess the accuracy of the prognostic signature. We evaluated different immune characteristics and immunotherapy response differences among other risk groups. RESULTS: A prognostic signature including 14 genes was established. The patients in the high-risk group have poor survival outcomes. We also found that the patients in the low-risk group have higher immune cell infiltration, enrichment of immune checkpoints, and immunotherapy response, suggesting that the patients in the low-risk group may be more sensitive to immunotherapy. Finally, the laboratory test results showed that KREMEN2 was identified as a novel biomarker and therapeutic target for OC patients. CONCLUSIONS: Our study established a GRG signature consisting of 16 genes based on the scRNA-seq and bulk RNA-seq data, which provides a new perspective on the prediction of prognosis and treatment strategy for OC.

FoxO1-modulated macrophage polarization regulates osteogenesis via PPAR-γ signaling.

Periodontitis, a common chronic inflammatory disease, epitomizes a significant impairment in the host immune system and an imbalance of bone metabolism. Macrophage polarization, a dynamic process dictated by the microenvironment, intricately contributes to the interplay between the immune system and bone remodeling, namely the osteoimmune system. Forkhead box protein O1 (FoxO1) has been shown to play a dramatic role in mediating oxidative stress, bone mass, as well as cellular metabolism. Nevertheless, the function and underlying mechanisms of FoxO1 in regulating macrophage polarization-mediated osteogenesis in periodontitis remain to be further elucidated. Here, we found that FoxO1 expression was closely linked to periodontitis, accompanied by aggravated inflammation. Notably, FoxO1 knockdown skewed macrophage polarization from M1 to the antiinflammatory M2 phenotype under inflammatory conditions, which rescued the impaired osteogenic potential. Mechanistically, we revealed that the enhancement of the transcription of peroxisome proliferator-activated receptor (PPAR) signaling in FoxO1-knockdown macrophages. In agreement with this contention, GW9662, a specific inhibitor of PPAR-γ signaling, greatly aggravated macrophage polarization from M2 to the M1 phenotype and attenuated osteogenic potential under inflammatory conditions. Additionally, PPAR-γ signaling agonist rosiglitazone (RSG) was applied to address ligature-induced periodontitis with attenuated inflammation. Our data lend conceptual credence to the function of FoxO1 in mediating macrophage polarization-regulated osteogenesis which serves as a novel therapeutic target for periodontitis.

Methylation related genes are associated with prognosis of patients with head and neck squamous cell carcinoma via altering tumor immune microenvironment.

Background/purpose: Analysis of methylomes may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to identify methylation-related differentially expressed genes (mrDEGs), and to assess their efficacy in predicting patients' survival, tumor immune microenvironment alterations and immune checkpoints in patients with HNSCC. Materials and methods: The methylome and transcriptome data of 528 HNSCC and 50 normal samples from TCGA database were used as training cohort. We identified mrDEGs and constituted a risk score model using Kaplan-Meier analysis and multivariate Cox regression. The prognostic efficacy of the risk score was validated in GSE65858 and GSE41613. We determined the enrichment of previously defined biological processes of mrDEGs. We separated the HNSCC patients into low-risk and high-risk groups and compared their immune cell infiltration and immune checkpoints' expressions. Results: The risk score model was constituted by nine prognostic mrDEGs, including LIMD2, SYCP2, EPHX3, UCLH1, STC2, PRAME, SLC7A4, PLOD2, and ACADL. The risk score was a significant prognostic factor both in training (P < 0.001) and validation dataset (GSE65858: P = 0.008; GSE41613 = 0.015). The prognostic mrDEGs were enriched in multiple immune-associated pathways. Effector immune cells were increased in low-risk patients, including CD8+ T cells, activated CD4+ T cells, and plasma cells, whereas tumor associated M2 macrophages were recruited in the high-risk group. Expressions of immune checkpoints were generally higher in low-risk patients, including CTLA-4, PD-1 and LAG3. Conclusion: The mrDEGs can stratify HNSCC patients' prognosis, which correlates with alterations in tumor immune infiltrations and immune checkpoints.

Curcumin and analogues against head and neck cancer: From drug delivery to molecular mechanisms.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most life-threatening diseases which also causes economic burden worldwide. To overcome the limitations of traditional therapies, investigation into alternative adjuvant treatments is crucial. PURPOSE: Curcumin, a turmeric-derived compound, demonstrates significant therapeutic potential in diverse diseases, including cancer. Furthermore, research focuses on curcumin analogues and novel drug delivery systems, offering approaches for improved efficacy. This review aims to provide a comprehensive overview of curcumin's current findings, emphasizing its mechanisms of anti-HNSCC effects and potential for clinical application. METHOD: An electronic search of Web of Science, MEDLINE, and Embase was conducted to identify literature about the application of curcumin or analogues in HNSCC. Titles and abstracts were screened to identify potentially eligible studies. Full-text articles will be obtained and independently evaluated by two authors to make the decision of inclusion in the review. RESULTS: Curcumin's clinical application is hindered by poor bioavailability, prompting the exploration of methods to enhance it, such as curcumin analogues and novel drug delivery systems. Curcumin could exhibit anti-cancer effects by targeting cancer cells and modulating the tumor microenvironment in HNSCC. Mechanisms of action include cell cycle arrest, apoptosis promotion, reactive oxygen species induction, endoplasmic reticulum stress, inhibition of epithelial-mesenchymal transition, attenuation of extracellular matrix degradation, and modulation of tumor metabolism in HNSCC cells. Curcumin also targets various components of the tumor microenvironment, including cancer-associated fibroblasts, innate and adaptive immunity, and lymphovascular niches. Furthermore, curcumin enhances the anti-cancer effects of other drugs as adjunctive therapy. Two clinical trials report its potential clinical applications in treating HNSCC. CONCLUSION: Curcumin has demonstrated therapeutic potential in HNSCC through in vitro and in vivo studies. Its effectiveness is attributed to its ability to modulate cancer cells and interact with the intricate tumor microenvironment. The development of curcumin analogues and novel drug delivery systems has shown promise in improving its bioavailability, thereby expanding its clinical applications. Further research and exploration in this area hold great potential for harnessing the full therapeutic benefits of curcumin in HNSCC treatment.

Kartogenin potentially protects temporomandibular joints from collagenase-induced osteoarthritis via core binding factor ß and runt-related transcription factor 1 binding - A rat model study.

Background/purpose: Temporomandibular joint (TMJ) osteoarthritis (TMJOA) is a chronic disease with progressive destruction of articular cartilage. This study aimed to explore the therapeutic effects of kartogenin on TMJOA via promoting the binding of core binding factor ß (CBFß) and runt-related transcription factor 1 (RUNX1). Materials and methods: Type II collagenase was injected into 35 8-week-old male Sprague Dawley rat TMJs to establish the TMJOA model. Kartogenin, or the CBFß-RUNX1 complex inhibitor (Ro5-3335), was also delivered via intra-articular injection. Subchondral bone was analyzed by MicroCT. The hematoxylin-eosin, Safranin O, and toluidine blue O staining were used to observe histopathology. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA), caspase-3 (CASP3), interleukin-1ß (IL-1ß), and collagen II (COL2) was performed. Results: TMJOA was established in rats by intra-articular injection of type II collagenase. The condylar cartilage and subchondral bone were damaged, with decreased PCNA and COL2 and increased CASP3 and IL-1 (P < .001). Compared with the OA group, kartogenin alleviated the destruction of cartilage and subchondral bone, rescued the expression of PCNA and COL2, and decreased the expression of CASP3 and IL-1ß (P < .01). Ro5-3335 did not aggravate the pathology of TMJOA but neutralized the therapeutic effects of kartogenin on TMJOA. Conclusion: Kartogenin has a potential therapeutic effect on TMJOA via promoting the CBFß-RUNX1 binding.

Therapeutic effects of kartogenin on temporomandibular joint injury by activating the TGF-ß/SMAD pathway in rats.

Patients with temporomandibular dysfunction (TMD) usually suffer from pathology or malpositioning of the temporomandibular joint (TMJ) disk, leading to the degenerative lesion of condyles. Kartogenin can promote the repair of damaged cartilage. This study aimed to explore whether intra-articular injection of kartogenin could alleviate the TMJ injury induced by type II collagenase. We measured the head withdrawal threshold and found that kartogenin alleviated the pain around TMD induced by type II collagenase. We observed the morphology of the condylar surface and found that kartogenin protected the integration of the condylar surface. We analyzed the density of the subchondral bone and found that kartogenin minimized the damage of TMJ injury to the subchondral bone. We next explored the histological changes and found that kartogenin increased the thickness of the proliferative layer and more collagen formation in the superficial layer. Then, to further ensure whether kartogenin promotes cell proliferation in the condyle, we performed immunohistochemistry of proliferating cell nuclear antigen (PCNA). The ratio of PCNA-positive cells was significantly increased in the kartogenin group. Next, immunofluorescence of TGF-ß1 and SMAD3 was performed to reveal that kartogenin activated the TGF-ß/SMAD pathway in the proliferative layer. In conclusion, kartogenin may have a therapeutic effect on TMJ injury by promoting cell proliferation in cartilage and subchondral bone. Kartogenin may be promising as an intra-articular injection agent to treat TMD.

Long working hours and all-cause mortality in China: A 26-year follow-up study.

OBJECTIVES: The relationship between long working hours and the risk of mortality has been debated in various countries. This study aimed to investigate the association between long working hours and all-cause mortality in a large population-based cohort in China. METHODS: This retrospective cohort study (N=10 269) used a large, nationally representative data set [the China Health and Nutrition Surveys (CHNS)] from 1989 to 2015. Long working hours (≥55 hours per week) were compared to standard working hours (35-40 hours per week). The outcome measure was all-cause mortality. Hazard ratio (HR) for all-cause mortality was calculated from Cox proportional hazards regression models, with stratified analyses to assess differences in mortality risk among subgroups. RESULTS: Among the participants, 411 deaths (3.52 per 1000 person-years) occurred during a median follow-up of 11.0 (range 4.0-18.0) years. After adjusting for covariates, long working hours were associated with a significantly increased risk of all-cause mortality [HR 1.49, 95% confidence intervals (CI) 1.02-2.18]. Stratified analyses revealed that this association was present only among men (HR 1.78, 95% CI 1.15-2.75) and smoking participants (HR 1.57, 95% CI 1.05-2.57). CONCLUSION: This study provides evidence of an association between long working hours and all-cause mortality, which is specifically observed among men and smokers. Targeted interventions should be implemented to reduce excessive working hours and identify individuals at elevated risk, with support from labor organizations, policymakers, and employers.