Repair of exposure and fracture of the porous high-density polyethylene framework after ear reconstruction.

OBJECTIVE: To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction. STUDY DESIGN: A prospective case study. METHODS: From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient. RESULTS: After follow-up for 3-36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived. CONCLUSION: The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury.

Introduction: Endothelial cells play important roles in neurodegenerative diseases caused by diabetes, therefore, we aimed at investigating the mechanisms through which endothelial cells are involved in diabetes development. Methods: Single cell analysis was performed to identify the major endothelial cell subtypes in cardiovascular tissues that are involved in diabetes development. A cell-cell communication approach was then used to identify ligand-receptor interaction pairs between these cell types. Differential expression analysis between the two experimental groups [standard chow diet group and diabetogenic diet with cholesterol (DDC) group] was used to identify diabetes-related differentially expressed genes (DEGs). The upregulated genes were used to identify candidate ligands or receptors, as well as the corresponding cell types. Cell trajectory inference was performed to identify the stage of cell development and changes in expression of candidate ligands or receptors during cell development. Gene set enrichment analysis (GSEA) was conducted to investigate the biological functions of genes of purpose. Finally, molecular dynamics simulations (MDSs) were used to predict potential drugs with the ability to target the proteins of purpose. Results: Seven cell types, including five endothelial cell subtypes (EC_1, EC_2, EC_3, EC_4, and EC_EndMT), were identified from endothelial cell-enriched single cell samples from the heart and aorta of mice. Cell-cell communication analysis revealed the potential ligand-receptor interactions between these cell types while five important ligand-receptor-associated genes, including Fn1, Vcam1, Fbn1, Col4a1, and Col4a2, were established by differential expression analysis. Among them, Vcam1 is mainly expressed in EC_EndMT and is involved in interactions between EC_EndMT and other cells. Cell trajectory extrapolation analysis revealed a shift from EC_2/EC_4 to EC_EndMT and a shift from EC_EndMT to EC_3/EC_1 during the progression of diabetes. GSEA analysis revealed that upregulation of VCAM1 may have inhibitory effects on cell growth and energy metabolism. Conclusion: EC_EndMT subtypes have a complex role in neurodegenerative diseases caused by diabetes. Through mechanisms involved in cell-cell communication, Vcam1 may play an important role in dysregulation of biological functions of EC_ EndMT. Molecular docking results of the quercetin-VCAM1 complex suggest that quercetin may be an effective drug for targeting this protein.

Corrigendum: Three-Dimensional Cartilage Regeneration Using Engineered Cartilage Gel With a 3D-Printed Polycaprolactone Framework.

[This corrects the article DOI: 10.3389/fbioe.2022.871508.].

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment.

Cognition may be improved by the active ingredients of the Yiqi Qingre Ziyin method in patients with atrophic rhinitis (AR). This study aimed to identify potential targets of the Yiqi Qingre Ziyin method for the treatment of patients with cognitive impairment. Nasal mucosal tissue samples from patients with AR were subjected to proteomic assays, and differentially expressed proteins were obtained. To explore the mechanism of AR leading to mild cognitive impairment (MCI), a differential analysis of AR related differential proteins in the MCI related GSE140831 dataset was performed. Most AR-related differential proteins are also differentially expressed in peripheral blood tissues of MCI, have similar biological functions and are enriched in similar pathways. These co-expressed differential factors in AR and MCI are known as common differential proteins of AR and MCI (CDPAM). Based on the analysis and validation of the random forest, support vector machine and neural network models, CDPAM acted as a diagnostic marker for MCI risk. Cytochrome C (CYCS) was significantly upregulated in the peripheral blood of patients with MCI. The active ingredients in the Yiqi Qingre Ziqin method were obtained and targeted 137 proteins. Among these targeted proteins, CYCS belong to the CDPAM set. Molecular docking and molecular dynamics analysis revealed that baicalein, an active ingredient in the Yiqi Qingre Ziyin method, stably targeted the CYCS protein. Results of the enrichment analysis revealed that the up-regulation of CYCS expression may have a defensive effect on the cells to resist foreign stimuli. Therefore, baicalein, an active ingredient in the Yiqi Qingre Ziyin method, may prevent the development and progression of MCI by targeting the CYCS protein.

Three-Dimensional Cartilage Regeneration Using Engineered Cartilage Gel With a 3D-Printed Polycaprolactone Framework.

The feasibility of the three-dimensional (3D) cartilage regeneration technology based on the "steel (framework)-reinforced concrete (engineered cartilage gel, ECG)" concept has been verified in large animals using a decalcified bone matrix (DBM) as the framework. However, the instability of the source, large sample variation, and lack of control over the 3D shape of DBM have greatly hindered clinical translation of this technology. To optimize cartilage regeneration using the ECG-framework model, the current study explores the feasibility of replacing the DBM framework with a 3D-printed polycaprolactone (PCL) framework. The PCL framework showed good biocompatibility with ECG and achieved a high ECG loading efficiency, similar to that of the DBM framework. Furthermore, PCL-ECG constructs caused a milder inflammatory response in vivo than that induced by DBM-ECG constructs, which was further supported by an in vitro macrophage activation experiment. Notably, the PCL-ECG constructs successfully regenerated mature cartilage and essentially maintained their original shape throughout 8 weeks of subcutaneous implantation. Quantitative analysis revealed that the GAG and total collagen contents of the regenerated cartilage in the PCL-ECG group were significantly higher than those in the DBM-ECG group. The results indicated that the 3D-printed PCL framework-a clinically approved biomaterial with multiple advantages including customizable shape design, mechanical strength control, and standardized production-can serve as an excellent framework for supporting the 3D cartilage regeneration of ECG. This provides a feasible novel strategy for the clinical translation of ECG-based 3D cartilage regeneration.

Exploring the Mechanism of Yiqi Qingre Ziyin Method in Regulating Neuropeptide Expression for the Treatment of Atrophic Rhinitis.

Atrophic rhinitis (AR) is a chronic disease that causes severe structural changes to the nasal mucosa leading to squamous epithelial metaplasia. However, treatment regarding AR remains a major challenge. We used network pharmacology and molecular docking methods to explore the potential mechanisms of the Yiqi Qingre Ziyin method to modulate neuropeptides in the treatment of AR. The active ingredients of the Yiqi Qingre Ziyin method and their targets of action were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database Analysis Platform (TCMSP). Disease targets for AR were obtained from four databases: GeneCards, PharmGKB, DrugBank, and Online Mendelian Inheritance in Man (OMIM). A total of 59 active ingredients, 39 potential targets, and 76 relevant neuropeptides were obtained after deduplication. We constructed target interaction networks with the STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the 14 potential target proteins. We used Cytoscape software to construct the "drug-active ingredient-potential target" and "ingredient-target-pathway" networks of the Yiqi Qingre Ziyin method for treating AR. Molecular docking results suggest that dipeptidyl peptidase 4 (DPP4), opioid receptor gene d1 (OPRD1), and opioid receptor m1 (OPRM1) are key targets for the Yiqi Qingre Ziyin method. Therefore, this study proposed a potential mechanism for the treatment of AR by affecting the expression of neuropeptide-related genes (including DPP4, OPRD1, and OPRM1), which may potentially improve the immune microenvironment of the nasal mucosa.

An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes.

The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics.

A prediction modeling based on SNOT-22 score for endoscopic nasal septoplasty: a retrospective study.

BACKGROUND: To create a nomogram prediction model for the efficacy of endoscopic nasal septoplasty, and the likelihood of patient benefiting from the operation. METHODS: A retrospective analysis of 155 patients with nasal septum deviation (NSD) was performed to develop a predictive model for the efficacy of endoscopic nasal septoplasty. Quality of life (QoL) data was collected before and after surgery using Sinonasal Outcome Test-22 (SNOT-22) scores to evaluate the surgical outcome. An effective surgical outcome was defined as a SNOT-22 score change ≥ 9 points after surgery. Multivariate logistic regression analysis was then used to establish a predictive model for the NSD treatment. The predictive quality and clinical utility of the predictive model were assessed by C-index, calibration plots, and decision curve analysis. RESULTS: The identified risk factors for inclusion in the predictive model were included. The model had a good predictive power, with a AUC of 0.920 in the training group and a C index of 0.911 in the overall sample. Decision curve analysis revealed that the prediction model had a good clinical applicability. CONCLUSIONS: Our prediction model is efficient in predicting the efficacy of endoscopic surgery for NSD through evaluation of factors including: history of nasal surgery, preoperative SNOT-22 score, sinusitis, middle turbinate plasty, BMI, smoking, follow-up time, seasonal allergies, and advanced age. Therefore, it can be cost-effective for individualized preoperative assessment.

[Survival and immune response of rural HIV/AIDS patients after free antiretroviral therapy].

OBJECTIVE: To assess the adherence, immunologic and survival responses in HIV-infected patients receiving free antiretroviral therapy (ART). METHODS: All adult HIV-infected patients in Wenxi county who started antiretroviral treatment (ART) between 01 July 2001 and 31 December 2006 and aged above 18 years were included in this study. Epidemiological survey and laboratory tests were performed before, 0.5 months after, 1 months after, 2 months after and every 3 months after initiation of ART to recognize the adherence, efficacy (CD(4)(+) T cell counts) and survival to the regimens. RESULTS: The median follow-up time period was 16.5 months (Interquartile: 15.5 - 20.8 months). At baseline, the median of CD(4)(+) T cell counts were 154 cells/microl (Interquartile: 81 - 212 cells/microl). Treatment was effective in most of the patients, the CD(4)(+) T cell count of patients increased after the initiation of ART. The maximum increase was recorded at month 3, from the median of 154 cells/microl to 220 cells/microl (P < 0.001), and thereafter the count remained stable. When comparing with patients with baseline CD(4)(+) T cell count > or = 100 cells/microl, those with baseline CD(4)(+) T cell count < 100 cells/microl showed a higher mean increase in the first three months of treatment. The cumulative probability rates of remaining alive were 0.94, 0.88 and 0.87 at 3, 12, 24 months, respectively. In multivariate Cox's proportional hazard models, after adjustment for the type ofinitial regimens (NVP vs. EFV/IDV), CD(+)(4) T cell count of less than 50 cells/microl (vs. 50 cells/microl or more) was strongly associated with death hazard ratio 0.21 (95%CI: 0.06 - 0.68). CONCLUSION: Our data showed that ART was effective for improving immunologic response of adult patients with HIV/AIDS. CD(4)(+) T cell count at initiation was associated with survival time in patients starting ART, suggesting that monitoring of CD(4)(+) T count should be strengthened to early initiate antiretroviral therapy for HIV-infected patients.

[Survival analysis of 530 HIV infected former unsafe commercial blood and plasma donors].

OBJECTIVE: To investigate HIV survival time and it's influencing factors among former commercial blood and plasma donors engaged in unsafe blood donation practices in China. METHODS: HIV/AIDS cases from 8 counties (districts) in 4 provinces confirmed prior to January 24, 2006 related with former commercial blood and plasma donors were selected and data regarding infection, AIDS progression, death, and influencing factors were retrospectively collected. RESULTS: In 530 cases of HIV infection, 334 (63.0%) cases had developed AIDS, 168 (50.3%) had received antiretroviral therapy (ART), and 152 (29.0%) had died. For the 530 cases, there was an average (10.1 +/- 1.8) years of observation from time of infection. Among 166 AIDS patients not receiving ART, average survival was 9.1 years (95% CI: 9.1 - 9.4), with an 8 year survival rate of 52.0%. Among 168 AIDS patients receiving ART, average survival was 12.1 years (95% CI: 11.9 - 12.3), with a 12-year survival rate of 80.0%. In 3 years of ART, average survival was longer in the treatment group as compared to the no treatment group with a hazard ratio for death of 12.2. Univariate analysis showed a significant difference (P < 0.05) in AIDS patient average survival based on gender, age, location, ART status, and baseline CD(4)(+) T cells count. Results from multivariate COX-regression showed that highly active ant iretroriral therapy (HAART) was the strongest protective factor for prolonging AIDS patients' survival (HR = 13.3, P = 0.00). CONCLUSION: Although there are many factors influencing AIDS patients survival, intervention with HAART is the principle measure to prolong survival and decrease the risk of death.