Antibody-platinum (IV) prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma.

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.

Combining Liposuction and Thread-Lifting for Middle-Lower Facial Rejuvenation.

BACKGROUND: Thread-lifting (TL) is a minimally-invasive technique for facial rejuvenation, whereas liposuction is commonly used for facial contouring. This retrospective cohort study aims to introduce and evaluate a novel technique that combines liposuction and thread-lifting for mid-lower facial rejuvenation. METHODS: Consecutive patients who underwent TL for mid-lower facial rejuvenation from May 2016 to May 2021 were divided into thread-lifting group (TL group) or thread-lifting plus liposuction group (TLL group) according to whether liposuction was performed adjunctively. The co-primary outcomes were the changes between the preoperative and 6-month postoperative Wrinkle Severity Rating Scale (WSRS) and Facial Aging Evaluation Scale (FAES). RESULTS: A total of 185 patients (184 females) with an average age of 34.5±5.5 years were included. There were no significant differences in patients' age, number of threads, and preoperative WSRS and FAES between the two groups. The TLL group (n = 128) had significantly lower postoperative WSRS (1.5±0.6 vs. 1.8±0.8, p<0.001) and FAES (2.5±1.4 vs. 3.8±2.1, p<0.001) than the TL group (n = 57). The decrease in WSRS (0.8±0.6 vs. 0.2±0.7, p<0.001) and FAES (2.7±1.3 vs. 1.6±1.6, p<0.001) were greater in the TLL group. Only 3.8% patients experienced slight side effects and totally recovered. CONCLUSIONS: The combination of TL and liposuction is an effective and safe technique for simultaneous contour improvement and facial rejuvenation in middle-aged East Asian females. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Risk factors for sternal wound infection after open-heart operations: A systematic review and meta-analysis.

We aimed to quantitatively and systematically elucidate the rationality of the examined variables as independent risk factors for sternal wound infection. We searched databases to screen studies, ascertained the variables to be analysed, extracted the data and applied meta-analysis to each qualified variable. Odds ratios and mean differences were considered to be the effect sizes for binary and continuous variables, respectively. A random-effects model was used for these procedures. The source of heterogeneity was evaluated using a meta-regression. Publication bias was tested by funnel plot and Egger's test, the significant results of which were then calculated using trim and fill analysis. We used a sensitivity analysis and bubble chart to describe their robustness. After screening all variables in the eligible literature, we excluded 55 because only one or no research found them significant after multivariate analysis, leaving 33 variables for synthesis. Two binary variables (age over 65 years, NYHA class >2) and a continuous variable (preoperative stay) were not significant after the meta-analysis. The most robust independent risk factors in our study were diabetes mellitus, obesity, use of bilateral internal thoracic arteries, chronic obstructive pulmonary disease, prolonged surgery time, prolonged ventilation and critical preoperative state, followed by congestive heart failure, atrial fibrillation, renal insufficiency, stroke, peripheral vascular disease and use of an intra-aortic balloon pump. Relatively low-risk factors were emergent/urgent surgery, smoking, myocardial infarction, combined surgery and coronary artery bypass grafting. Sternal wound infection after open-heart surgery is a multifactorial disease. The detected risk factors significantly affected the wound healing process, but some were different in strength. Anything that affects wound healing and antibacterial ability, such as lack of oxygen, local haemodynamic disorders, malnutrition condition and compromised immune system will increase the risk, and this reminds us of comprehensive treatment during the perioperative period.

AIEgens for synergistic anticancer therapy.

Cancer is a mortal disease that can invade other parts of the body and cause severe complications. Despite their continuous progress, conventional cancer therapies including surgery, chemotherapy, and radiation therapy have their inherent limitations. To improve the precision of cancer treatment, maximize the therapeutic effect and minimize mortality, synergistic therapies combining imaging guiding technologies, phototherapy, and other therapies have emerged due to the mutually strengthening therapeutic efficacy. However, traditional organic phototherapeutic agents are limited since their aggregation in aqueous media usually affects both their luminescence behavior and therapeutic effect. In contrast, aggregate-induced emission luminogens (AIEgens) provide an ideal solution to develop phototherapy with bright fluorescence and a significant treatment effect in the aggregate state. Combining AIE-based phototherapy and conventional therapies benefits from synergistic effects and extends the potential of developing accurate cancer therapy. AIE-based synergistic therapy has been popularly discussed with such unexplored potential in recent years. This review will introduce the most recent progress of AIE-based synergistic cancer therapy.

Pre-epithelialized cryopreserved tracheal allograft for neo-trachea flap engineering.

Background: Tracheal reconstruction presents a challenge because of the difficulty in maintaining the rigidity of the trachea to ensure an open lumen and in achieving an intact luminal lining that secretes mucus to protect against infection. Methods: On the basis of the finding that tracheal cartilage has immune privilege, researchers recently started subjecting tracheal allografts to "partial decellularization" (in which only the epithelium and its antigenicity are removed), rather than complete decellularization, to maintain the tracheal cartilage as an ideal scaffold for tracheal tissue engineering and reconstruction. In the present study, we combined a bioengineering approach and a cryopreservation technique to fabricate a neo-trachea using pre-epithelialized cryopreserved tracheal allograft (ReCTA). Results: Our findings in rat heterotopic and orthotopic implantation models confirmed that tracheal cartilage has sufficient mechanical properties to bear neck movement and compression; indicated that pre-epithelialization with respiratory epithelial cells can prevent fibrosis obliteration and maintain lumen/airway patency; and showed that a pedicled adipose tissue flap can be easily integrated with a tracheal construct to achieve neovascularization. Conclusion: ReCTA can be pre-epithelialized and pre-vascularized using a 2-stage bioengineering approach and thus provides a promising strategy for tracheal tissue engineering.

One stage reconstruction of mid-face fistulous defects after maxillary sinus carcinoma resection with chimeric perforator free flaps.

BACKGROUND: The reconstruction of large fistulous defects following the radical ablation of maxillary sinus carcinoma remains challenging. The procedure requires not only the coverage of both intra-nasal lining and cheek skin but also sufficient obliteration of dead space between the two surfaces. In this report, we present our experience on the reconstruction of through-and-through defects in the mid-face with poly-foliated chimeric perforator flaps. METHODS: Nine patients (five males and four females) who received a two-skin paddled and one muscle segment chimeric perforator flap reconstruction after maxillary sinus carcinoma ablation between March 2015 and December 2019 were retrospectively reviewed in authors' hospital. The mean age of the patients was 59.11. Six patients were diagnosed as squamous cell carcinoma, two as adenoid cystic carcinoma, and one as adenocarcinoma. Brown class IIIa defects were found in eight patients, and one patient had a Brown class IVa defect. The mean size of intra-nasal defect was 5.67 × 4.06 cm2 , and the mean size of facial skin defect was 8.94 × 6.56 cm2 . ALT flaps were used in five patients, LD flaps in four patients. The minor skin paddle was firstly inset to the mucosal defect site as the lining. Then, the muscle segment was inset to eliminate the dead cavity. Finally, the major skin paddle was inset to recover the cutaneous defect. RESULTS: In ALT group, the mean size of the minor skin paddle was 5.7 × 4.7 cm2 , and the mean size of the major skin paddle was 8.7 × 6.6 cm2 . In LD group, the mean size of the minor skin paddle was 6.88 × 4.38 cm2 , and the mean size of the major skin paddle was 11 × 7.75 cm2 .All donor sites were closed primarily. All flaps survived and no partial flap loss was encountered. The mean follow-up time was 14.67 months, and there were no major postoperative complications. CONCLUSION: The use of poly-foliated chimeric perforator free flaps can provide functional and aesthetic coverage for extensive through-and-through mid-face defects without significant donor-site morbidities.

Strategies to Improve AFT Volume Retention After Fat Grafting.

BACKGROUND: Autologous fat grafting has gained increasing popularity used in plastic surgery as a strategy to improve functional and aesthetic outcome. However, variable augmentation results have concerned surgeons in that volume loss of grafted fat reported fluctuates unsteadily. AIM: An optimal technique that clinically maximizes the long-term survival rate of transplantation is in urgent need to be identified. METHOD: The PubMed/MEDLINE database was queried to search for animal and human studies published through March of 2022 with search terms related to adipose grafting encompassing liposuction, adipose graft viability, processing technique, adipose-derived stem cell, SVF and others. RESULTS: 45 in vivo studies met inclusion criteria. The principal of ideal processing technique is effective purification of fat and protection of tissue viability, such as gauze rolling and washing-filtration devices. Cell-assisted lipotransfer including SVF, SVF-gel and ADSCs significantly promotes graft retention via differentiation potential and paracrine manner. ADSCs induce polarization of macrophages to regulate inflammatory response, mediate extracellular matrix remodeling and promote endothelial cell migration and sprouting, and differentiate into adipocytes to replace necrotic cells, providing powerful evidence for the benefits and efficacy of cell-assisted lipotransfer. CONCLUSION: Based on the current evidence, the best strategy can not be decided. Cell-assisted lipotransfer has great potential for use in regenerative medicine. But so far mechanically prepared SVF-gel is conducive to clinical promotion. PRP as endogenous growth factor sustained-release material shows great feasibility. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Harnessing the synergy of perfusable muscle flap matrix and adipose-derived stem cells for prevascularization and macrophage polarization to reconstruct volumetric muscle loss.

Muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful engraftment. We developed porcine stomach musculofascial flap matrix (PDSF) comprising extracellular matrix (ECM) and intact vasculature. PDSF had a dominant vascular pedicle, microcirculatory vessels, a nerve network, well-retained 3-dimensional (3D) nanofibrous ECM structures, and no allo- or xenoantigenicity. In-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins (e.g., collagens, glycoproteins, proteoglycans, and ECM regulators) that, as shown by Gene Ontology term enrichment analysis, are functionally related to musculofascial biological processes. Moreover, PDSF-human adipose-derived stem cell (hASC) synergy not only induced monocytes towards IL-10-producing M2 macrophage polarization through the enhancement of hASCs' paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts (HSMMs) and human umbilical vein endothelial cells (HUVECs) in static triculture conditions. Furthermore, PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs, which integrated with PDSF and induced the maturation of vascular networks in vitro. In a xenotransplantation model, PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T cells. In a volumetric muscle loss (VML) model, prevascularized PDSF augmented neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue formation. These results indicate that hASCs' integration with PDSF enhances the cells' dual function in immunomodulation and angiogenesis. Owing in part to this PDSF-hASC synergy, our platform shows promise for vascularized muscle flap engineering for VML reconstruction.

Upregulation LncRNA MEG3 expression suppresses proliferation and metastasis in melanoma via miR-208/SOX4.

Long non-coding RNAs (lncRNAs) regulate gene expression and play a significant role in cancer progression. Previously, downregulation of lncRNA MEG3 was shown to associate with poor clinical outcomes in melanoma patients. The basis for this association has not been described and the aims of this study were to identify a role for lncRNA MEG3 in melanoma and to describe its regulatory mechanism of action. RT-qPCR was used to detect lncRNA MEG3 expression in melanoma cells and tissues. Luciferase reporter assays were used to identify lncRNA MEG3 downstream targets. Melanoma cells were transfected with various expression vectors and these transfected cells were assessed for; migration, colony formation, proliferation, in vivo tumorigenesis, and metastatic potential. Melanoma cell lines were found to be sensitive to lncRNA MEG3 expression levels and overexpression was found to inhibit melanoma cell proliferation and invasion, both in vitro and in vivo. Luciferase reporter assays identified miR-208 and SOX4 as downstream targets of lncRNA MEG3. Overexpression of miR-208 and silencing of SOX4 rescued invasion and proliferation by cells that overexpressed lncRNA MEG3. Moreover, lncRNA MEG3 inhibited cancer stem cell differentiation and suppressed melanoma progression and metastasis through inhibition of miR-208 by SOX4.

Treatment of Anaphylaxis After Injection of Stem Cell Exosomes With 5-Fluorouracil and Triamcinolone Acetonide.

Using stem cell exosomes to treat alopecia is a new treatment in plastic surgery. However, there are few reports on the complications of this treatment. This study describes a method of using 5-fluorouracil combined with triamcinolone acetonide to treat allergic reactions caused by stem cell exosomes injection. The ultrasound results before treatment showed that the thickness of subcutaneous soft tissue in the forehead was 0.35 cm,the length and short diameter of left retroauricular lymph nodes were 1.11 and 0.46 cm, and the length and short diameter of right retroauricular lymph nodes were 1.10 and 0.45 cm. After treatment, the thickness of subcutaneous soft tissue in the forehead was 0.20 cm, the length and short diameter of the lymph nodes behind the left ear were 1.06 and 0.40 cm, respectively, and the length and short diameter of the lymph nodes behind the right ear were 1.06 and 0.36 cm, respectively. The results of treatment proved that this treatment had a therapeutic effect on the allergy of patients.

Complications Following Facial Injection of Growth Factor Solution.

OBJECTIVE: Topical injection of growth factor (GF) for facial rejuvenation is unauthorized, but it is commonly performed in China, leading to emerging and challenging complications. The purpose of this study is to investigate the clinical, imaging, and histopathologic characteristics of complications caused by facial GF injection, as well as their treatments and outcomes. METHODS: We performed a retrospective single-centered case series study on consecutive patients who were treated for complications following facial injection of GF. The primary outcome was the recurrence over follow-up period. The secondary outcomes were the subjective evaluations of the facial aesthetic, symptomatic, and psychological improvements using the Global Aesthetic Improvement Scale (GAIS) and a patient-reported outcome measurement (PROM). Kaplan-Meier analysis and log-rank test were performed to investigate the recurrence. RESULTS: A total of 32 females with an average age of 42.6 ± 9.4 years were included. Most patients received GF injections in non-medical institutes such as beauty spas and presented with uncontrollable soft tissue hyperplasia, diffuse subcutaneous swelling, and skin redness. Ultrasonography showed heterogeneous hypoechoic or echogenic areas in a thickened and disorganized subcutaneous tissue hierarchy. MRI showed flaky isointensive or hypointensive signals on T1WI and hyperintensive signals on T2WI. 37.5% patient underwent triamcinolone acetonide injection, whereas 62.5% patients underwent surgical interventions. Lipoma-like hyperplastic tissue was found during surgery. HE staining confirmed intramuscular lipoma and fibrolipomatous tissue hyperplasia. Recurrence was found in 37.5% patients over a median follow-up of 6 months. KM curves and log-rank test demonstrated no significant difference in the recurrence between patients who underwent nonsurgical or surgical interventions (p = 0.77). GAIS and PROM scores indicated substantial aesthetic, symptomatic, and psychological improvements in 70%, 91.7%, and 75% patients, respectively. CONCLUSIONS: Both surgical and nonsurgical interventions are feasible and effective treatment options for GF-induced complications. Although recurrence rate was relatively high, aesthetic, symptomatic, and psychological improvements were achieved in most patients. We developed a workflow that might help diagnose and treat complications following unknown dermal filler injections. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor-designed ZnFe2O4-based nanosystem.

The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4-based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS-DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4-PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4-PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.

Identification of fatty acid metabolism-related molecular subtype biomarkers and their correlation with immune checkpoints in cutaneous melanoma.

Purpose: Fatty acid metabolism (FAM) affects the immune phenotype in a metabolically dynamic tumor microenvironment (TME), but the use of FAM-related genes (FAMGs) to predict the prognosis and immunotherapy response of cutaneous melanoma (CM) patients has not been investigated. In this study, we aimed to construct FAM molecular subtypes and identify key prognostic biomarkers in CM. Methods: We used a CM dataset in The Cancer Genome Atlas (TCGA) to construct FAM molecular subtypes. We performed Kaplan-Meier (K-M) analysis, gene set enrichment analysis (GSEA), and TME analysis to assess differences in the prognosis and immune phenotype between subtypes. We used weighted gene co-expression network analysis (WGCNA) to identify key biomarkers that regulate tumor metabolism and immunity between the subtypes. We compared overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) between CM patients with high or low biomarker expression. We applied univariable and multivariable Cox analyses to verify the independent prognostic value of the FAM biomarkers. We used GSEA and TME analysis to investigate the immune-related regulation mechanism of the FAM subtype biomarker. We evaluated the immune checkpoint inhibition (ICI) response and chemotherapy sensitivity between CM patients with high or low biomarker expression. We performed real-time fluorescent quantitative PCR (qRT-PCR) and semi-quantitative analysis of the immunohistochemical (IHC) data from the Human Protein Atlas to evaluate the mRNA and protein expression levels of the FAM biomarkers in CM. Results: We identified 2 FAM molecular subtypes (cluster 1 and cluster 2). K-M analysis showed that cluster 2 had better OS and PFS than cluster 1 did. GSEA showed that, compared with cluster 1, cluster 2 had significantly upregulated immune response pathways. The TME analysis indicated that immune cell subpopulations and immune functions were highly enriched in cluster 2 as compared with cluster 1. WGCNA identified 6 hub genes (ACSL5, ALOX5AP, CD1D, CD74, IL4I1, and TBXAS1) as FAM biomarkers. CM patients with high expression levels of the six biomarkers had better OS, PFS, and DSS than those with low expression levels of the biomarkers. The Cox regression analyses verified that the 6 FAM biomarkers can be independent prognostic factors for CM patients. The single-gene GSEA showed that the high expression levels of the 6 genes were mainly enriched in T-cell antigen presentation, the PD-1 signaling pathway, and tumor escape. The TME analysis confirmed that the FAM subtype biomarkers were not only related to immune infiltration but also highly correlated with immune checkpoints such as PD-1, PD-L1, and CTLA-4. TIDE scores confirmed that patients with high expression levels of the 6 biomarkers had worse immunotherapy responses. The 6 genes conveyed significant sensitivity to some chemotherapy drugs. qRT-PCR and IHC analyses verified the expression levels of the 6 biomarkers in CM cells. Conclusion: Our FAM subtypes verify that different FAM reprogramming affects the function and phenotype of infiltrating immune cells in the CM TME. The FAM molecular subtype biomarkers can be independent predictors of prognosis and immunotherapy response in CM patients.

Tension-reduced closure of large abdominal wall defect caused by shotgun wound: A case report.

BACKGROUND: Large abdominal wall defect (LAWD) caused by shotgun wound is rarely reported. CASE SUMMARY: Herein, we describe a case of LAWD caused by a gunshot wound in which the abdominal wall was reconstructed in stages, including debridement, tension-reduced closure (TRC), and reconstruction with mesh and a free musculocutaneous flap. During a 3-year follow-up, the patient recovered well without hernia or other problems. CONCLUSION: TRC is a practical approach for the temporary closure of LAWD, particularly in cases when one-stage abdominal wall restoration is unfeasible due to significant comorbidities.

Lipid nanoparticle-encapsulated VEGFa siRNA facilitates cartilage formation by suppressing angiogenesis.

Cartilage is an important tissue that is widely found in joints, ears, nose and other organs. The limited capacity to regenerate makes cartilage reconstruction an urgent clinical demand. Due to the avascular nature of cartilage, we hypothesized that inhibition of vascularization contributes to cartilage formation. Here, we used VEGFa siRNA to inhibit the infiltration of the local vascular system. Optimized lipid nanoparticles were prepared by microfluidics for the delivery of siRNA. Then, we constructed a tissue engineering scaffold. Both seed cells and VEGFa siRNA-LNPs were loaded in a GELMA hydrogel. Subcutaneous implantation experiments in nude mice indicate that this is a promising strategy for cartilage reconstruction. The regenerated cartilage was superior, with significant upregulation of SOX9, COL-II and ACAN. This is attributed to an environment deficient in oxygen and nutrients, which facilitates cartilage formation by upregulating HIF-1α and FOXO transcription factors. In conclusion, a GelMA/Cells+VEGFa siRNA-LNPs scaffold was constructed to achieve superior cartilage regeneration.

Ferroptosis-related lncRNA signature predicts prognosis and immunotherapy efficacy in cutaneous melanoma.

Purpose: Ferroptosis-related lncRNAs are promising biomarkers for predicting the prognosis of many cancers. However, a ferroptosis-related signature to predict the prognosis of cutaneous melanoma (CM) has not been identified. The purpose of this study was to construct a ferroptosis-related lncRNA signature to predict prognosis and immunotherapy efficacy in CM. Methods: Ferroptosis-related differentially expressed genes (FDEGs) and lncRNAs (FDELs) were identified using TCGA, GTEx, and FerrDb datasets. We performed Cox and LASSO regressions to identify key FDELs, and constructed a risk score to stratify patients into high- and low-risk groups. The lncRNA signature was evaluated using the areas under the receiver operating characteristic curves (AUCs) and Kaplan-Meier analyses in the training, testing, and entire cohorts. Multivariate Cox regression analyses including the lncRNA signature and common clinicopathological characteristics were performed to identify independent predictors of overall survival (OS). A nomogram was developed for clinical use. We performed gene set enrichment analyses (GSEA) to identify significantly enriched pathways. Differences in the tumor microenvironment (TME) between the 2 groups were assessed using 7 algorithms. To predict the efficacy of immune checkpoint inhibitors (ICI), we analyzed the association between PD1 and CTLA4 expression and the risk score. Finally, differences in Tumor Mutational Burden (TMB) and molecular drugs Sensitivity between the 2 groups were performed. Results: We identified 5 lncRNAs (AATBC, AC145423.2, LINC01871, AC125807.2, and AC245041.1) to construct the risk score. The AUC of the lncRNA signature was 0.743 in the training cohort and was validated in the testing and entire cohorts. Kaplan-Meier analyses revealed that the high-risk group had poorer prognosis. Multivariate Cox regression showed that the lncRNA signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The 1-, 3-, and 5-year survival probabilities for CM patients were 92.7%, 57.2%, and 40.2% with an AUC of 0.804, indicating a good accuracy and reliability of the nomogram. GSEA showed that the high-risk group had lower ferroptosis and immune response. TME analyses confirmed that the high-risk group had lower immune cell infiltration (e.g., CD8+ T cells, CD4+ memory-activated T cells, and M1 macrophages) and lower immune functions (e.g., immune checkpoint activation). Low-risk patients whose disease expressed PD1 or CTLA4 were likely to respond better to ICIs. The analysis demonstrated that the TMB had significantly difference between low- and high- risk groups. Chemotherapy drugs, such as sorafenib, Imatinib, ABT.888 (Veliparib), Docetaxel, and Paclitaxel showed Significant differences in the estimated IC50 between the two risk groups. Conclusion: Our novel ferroptosis-related lncRNA signature was able to accurately predict the prognosis and ICI outcomes of CM patients. These ferroptosis-related lncRNAs might be potential biomarkers and therapeutic targets for CM.

A novel inflammatory response-related signature predicts the prognosis of cutaneous melanoma and the effect of antitumor drugs.

Cutaneous melanoma (CM) is a skin cancer that is highly metastatic and aggressive, with a dismal prognosis. This is the first study to use inflammatory response-related genes to build a model and evaluate their predictive significance in CM. This study used public databases to download CM patients' mRNA expression profiles and clinical data to create multigene prognostic markers in the UCSC cohort. We compared overall survival (OS) between high- and low-risk groups using the Kaplan-Meier curve and determined independent predictors using Cox analysis. We also used enrichment analysis to assess immune cell infiltration fraction and immune pathway-related activity using KEGG enrichment analysis. Furthermore, we detected prognostic genes' mRNA and protein expression in CM and normal skin tissues using qRT-PCR and immunohistochemistry. Finally, we developed a 5-gene predictive model that showed that patients in the high-risk group had a considerably shorter OS than those in the low-risk group. The analysis of the receiver operating characteristic (ROC) curve proved the model's predictive ability. We also conducted a drug sensitivity analysis and discovered that the expression levels of prognostic genes were substantially linked with cancer cell sensitivity to antitumor medicines. The findings show that the model we developed, which consists of five inflammatory response-related genes, can be used to forecast the prognosis and immunological state of CM, giving personalized and precision medicine a new goal and direction.

Evaluation of oral implant survival rate in postmenopausal women with osteopenia/osteoporosis. A retrospective pilot study.

BACKGROUND: Implant placement is a common part of dental rehabilitation in older individuals. The role of diminished bone mineral density on the healing of dental implants remains to be elucidated. OBJECTIVE: The aim of this study was to assess the implant survival rate in postmenopausal women with osteopenia/osteoporosis. METHODS: A retrospective cohort study was conducted of postmenopausal women treated with dental implants and stratified into two groups: those receiving antiresorptive therapy (W ≥ 50 years S) or those not receiving treatment (W ≥ 50 years U). The predictor variable was osteopenia/osteoporosis treatment. The outcome variable was implant failure rate at stage two uncovering. Other study variables included: age, implant location, and bone graft placement. T-test, chi-square test, and univariate and multivariate logistic regression were computed. A p-value<0.05 was considered statistically significant. RESULTS: The sample was composed of 93 W ≥ 50 years U (197 implants) and 114 W ≥ 50 years S (189 implants). W ≥ 50 years U showed a statistically higher implant failure rate with chi-square testing compared to W ≥ 50 years S (p=0.022). However, univariate, and multivariate logistic regression between age, location, bone grafting, and implant failure did not demonstrate significant associations. CONCLUSION: Both groups integrated dental implants successfully, with a low failure rate. Implant location, bone grafting, and osteopenia/osteoporosis treatment did not significantly affect osseointegration at uncovering.

A Novel Pyroptotic and Inflammatory Gene Signature Predicts the Prognosis of Cutaneous Melanoma and the Effect of Anticancer Therapies.

Purpose: The purpose of this study was to construct a gene signature comprising genes related to both inflammation and pyroptosis (GRIPs) to predict the prognosis of patients with cutaneous melanoma patients and the efficacy of immunotherapy, chemotherapy, and targeted therapy in these patients. Methods: Gene expression profiles were collected from The Cancer Genome Atlas. Weighted gene co-expression network analysis was performed to identify GRIPs. Univariable Cox regression and Lasso regression further selected key prognostic genes. Multivariable Cox regression was used to construct a risk score, which stratified patients into high- and low-risk groups. Areas under the ROC curves (AUCs) were calculated, and Kaplan-Meier analyses were performed for the two groups, following validation in an external cohort from Gene Expression Omnibus (GEO). A nomogram including the GRIP signature and clinicopathological characteristics was developed for clinical use. Gene set enrichment analysis illustrated differentially enriched pathways. Differences in the tumor microenvironment (TME) between the two groups were assessed. The efficacies of immune checkpoint inhibitors (ICIs), chemotherapeutic agents, and targeted agents were predicted for both groups. Immunohistochemical analyses of the GRIPs between the normal and CM tissues were performed using the Human Protein Atlas data. The qRT-PCR experiments validated the expression of genes in CM cell lines, Hacat, and PIG1 cell lines. Results: A total of 185 GRIPs were identified. A novel gene signature comprising eight GRIPs (TLR1, CCL8, EMP3, IFNGR2, CCL25, IL15, RTP4, and NLRP6) was constructed. The signature had AUCs of 0.714 and 0.659 for predicting 3-year overall survival (OS) in the TCGA entire and GEO validation cohorts, respectively. Kaplan-Meier analyses revealed that the high-risk group had a poorer prognosis. Multivariable Cox regression showed that the GRIP signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The nomogram showed good accuracy and reliability in predicting 3-year OS (AUC = 0.810). GSEA and TME analyses showed that the high-risk group had lower levels of pyroptosis, inflammation, and immune response, such as lower levels of CD8+ T-cell infiltration, CD4+ memory-activated T-cell infiltration, and ICI. In addition, low-risk patients whose disease expressed PD-1 or CTLA-4 were likely to respond better to ICIs, and several chemotherapeutic and targeted agents. Immunohistochemical analysis confirmed the distinct expression of five out of the eight GRIPs between normal and CM tissues. Conclusion: Our novel 8-GRIP signature can accurately predict the prognosis of patients with CM and the efficacies of multiple anticancer therapies. These GRIPs might be potential prognostic biomarkers and therapeutic targets for CM.