Tissue RNA Sequencing Reveals Novel Biomarkers Associated with Postoperative Keloid Recurrence.

Keloids can be resected through surgery, but they may still recur. The purpose of this study was to explore the biomarkers to predict the postoperative recurrence of keloids. Patients who underwent surgical treatment and postoperative superficial X-ray radiation between January 2019 and December 2020 were recruited with clinical data and keloid samples for RNA-seq. By screening differentially expressed genes (DEGs) between postoperative recurrent and non-recurrent sample groups and constructing a co-expression network via the weighted gene co-expression network analysis (WGCNA), an immunity-related module was chosen for subsequent analysis. By constructing a DEG co-expression network and using the Molecular Complex Detection (MCODE) algorithm, five hub genes were identified in the key module. Receiver Operating Characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the five combined hub genes was 0.776. The result of qRT-PCR showed that CHI3L1, IL1RN, MMP7, TNFAIP3, and TNFAIP6 were upregulated in the recurrent group with statistical significance (p < 0.05). Immune infiltration analysis showed that mast cells, macrophages, and T cells were the major components of the keloid immune microenvironment. This study provides potential biomarkers for predicting keloid recurrence and offers insights into genetic targets for recurrence prevention.

[Progress in neural network mechanism of tinnitus using functional magnetic resonance imaging].

Tinnitus refers to the perception of abnormal sound in the absence of external sound stimulation. It can have an impact on a person's mood, memory, attention, and mental state, although the mechanism of tinnitus is still unclear. In recent years, the research on the central neural mechanism of tinnitus has attracted the attention of scholars.Functional magnetic resonance imaging （fMRI）,as an effective imaging technology, has been actively employed in this field. This paper provides a systematic summary of studies on the central neural mechanism of tinnitus by fMRI in recent years,revealed the changes of functional connections among tinnitus-related neural networks,such as auditory network,limbic system,default mode network and salience network. The central neural mechanism of tinnitus involves multiple networks that interact with each other. By understanding this mechanism, we hope to develop more targeted prevention and treatment strategies to help patients alleviate long-term tinnitus.

Fractional microneedle radiofrequency treatment for enlarged facial pores: A real-world retrospective observational study on 75 patients.

OBJECTIVE: This study aimed to analyze the clinical results and influencing factors of the fractional microneedle radiofrequency (FMR) treatment for enlarged facial pores on different facial sites. METHODS: The clinical data of patients with enlarged facial pores who underwent FMR treatment from January 2019 to December 2020 were collected. The efficacy and complications of FMR for enlarged pores in different facial areas were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to explore the clinical factors related to the efficacy of FMR after the first treatment session. RESULTS: Totally, 75 patients with enlarged facial pores were included (full-face FMR for 45, nasal FMR for 58, frontal FMR for 45, and cheek FMR for 72 patients). All patients received more than one treatment session, two patients received five treatment sessions, and the mean number of FMR session was 1.7. The moderate to excellent improvement rates in patients with nasal, frontal and cheek enlarged pores after the first session were 13.8%, 8.9%, and 11.1%, respectively. The improvement rate rose with the increasing number of treatment sessions. Multivariate logistic regression analysis revealed that long pulse-width (300 ms) was positively associated with clinical efficacy after the first session (OR = 22.4, 95% CI [2.0-250.4], p = 0.012), compared with the short pulse-width group (100-200 ms). The main adverse effects after FMR were transient pain, erythema, and edema. A minority of patients developed acneiform eruption. CONCLUSION: This study confirms that FMR is safe and effective in improving enlarged facial pores. The pulse width is associated with the improvement of nasal enlarged pores.

Detection of an EML4-ALK fusion mutation secondary to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer: a case report.

BACKGROUND: For epidermal growth factor receptor-mutant (EGFR-mutant) advanced non-small cell lung cancer (NSCLC) patients, EGFR-tyrosine inhibitors such as gefitinib, erlotinib, and osimertinib, are recommended as the preferred first-line treatment. Unfortunately, relevant drug resistance is often inevitable and for first and second generation EGFR-tyrosine kinase inhibitors (TKIs), drug resistance most commonly (50-60% of cases) occurs at the secondary point mutation T790M. Second-line treatments may include administering the third generation of EGFR-TKIs, such as osimertinib and almonertinib. In a few relevant studies, rearrangement of the anaplastic lymphoma kinase (ALK) gene was detected in patients with T790M mutation after drug resistance to osimertinib re-occurred following administration as a second-line treatment. The studies concluded that ALK rearrangement is a rare but critical drug resistance mechanism for osimertinib. However, to date, it remains unclear whether almonertinib also triggers the same ALK rearrangement. The current case study is the first one detailing the detection of an ALK rearrangement after almonertinib resistance in advanced EGFR-mutant NSCLC, which contributes to the limited body of literature examining ALK rearrangement as a mechanism of resistance to EGFR-TKIs in advanced EGFR-mutant NSCLC. CASE DESCRIPTION: Herein, we present a 35-year-old female patient with EGFR-mutant advanced NSCLC in the last trimester of pregnancy. The patient was administered multiple treatments, including first-line icotinib and second-line almonertinib. According to the next-generation sequencing (NGS) assay after almonertinib resistance, the development of an EML4-ALK fusion mutation was considered to be a potential mechanism of almonertinib resistance. Subsequently, the patient received a combination of almonertinib and crizotinib, and at the last follow-up, the treatment showed a curative effect and then maintained a one-month stable disease. CONCLUSIONS: This case report suggests that ALK rearrangement may be a potential mechanism of almonertinib resistance. The combination of ALK TKI therapy and EGFR TKI may be a viable strategy for almonertinib-resistant NSCLC patients induced by ALK rearrangement.

Keloid Biomarkers and Their Correlation With Immune Infiltration.

Objective: This work aimed to verify the candidate biomarkers for keloid disorder (KD), and analyze the role of immune cell infiltration (ICI) in the pathology of keloid disorder. Methods: The keloid-related datasets (GSE44270 and GSE145725) were retrieved from the Gene Expression Omnibus (GEO). Then, differential expressed genes (DEGs) were identified by using the "limma" R package. Support vector machine-recursive feature elimination (SVM-RFE) and LASSO logistic regression were utilized for screening candidate biomarkers of KD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of candidate biomarkers. The candidate biomarkers were further verified through qRT-PCR of keloid lesions and the matched healthy skin tissue collected from eight cases. In addition, ICI in keloid lesions was estimated through single-sample gene-set enrichment analysis (ssGSEA). Finally, the potential drugs to the treatment of KD were predicted in the Connectivity Map Database (CMAP). Results: A total of 406 DEGs were identified between keloid lesion and healthy skin samples. Among them, STC2 (AUC = 0.919), SDC4 (AUC = 0.970), DAAM1 (AUC = 0.966), and NOX4 (AUC = 0.949) were identified as potential biomarkers through the SVM-RFE, LASSO analysis and ROC analysis. The differential expressions of SDC4, DAAM1, and NOX4 were further verified in collected eight samples by qRT-PCR experiment. ICI analysis result showed a positive correlation of DAAM1 expression with monocytes and mast cells, SDC4 with effector memory CD4+ T cells, STC2 with T follicular helper cells, and NOX4 with central memory CD8+ T cells. Finally, a total of 13 candidate small molecule drugs were predicted for keloids treatment in CMAP drug database. Conclusion: We identified four genes that may serve as potential biomarkers for KD development and revealed that ICI might play a critical role in the pathogenesis of KD.

Efficacy and adverse reactions of fractional CO2 laser for atrophic acne scars and related clinical factors: A retrospective study on 121 patients.

OBJECTIVE: This study was performed to analyze the efficacy, adverse reactions of fractional CO2  laser for atrophic acne scars, and related clinical factors. METHODS: The clinical data of 121 patients with atrophic acne scars treated with ultra-pulsed fractional CO2  laser in the Cosmetic Dermatology from August 2014 to March 2020 were retrospectively analyzed. The efficacy and adverse reactions of atrophic acne scar after fractional CO2  laser therapy were statistically analyzed. The clinical factors related to efficacy and adverse reactions after the first therapy session were analyzed by multivariate logistic regression. RESULTS: A total of 121 patients received 206 sessions of fractional CO2  laser therapy, with an average of 1.7 sessions. Moderate to excellent improvement rate reached 50.4% after the first session. Multivariate logistic regression analysis indicated that rolling scars responded better to fractional CO2  laser treatment than icepick scars (OR = 7.3, 95% CI [1.2, 43.4], p = 0.029), and scar improvement was more significant in the high-energy laser group than in the low-energy laser group (OR = 10.9, 95% CI [1.1, 106.8], p = 0.041). The main adverse reactions after fractional laser surgery were pigmentation, skin sensitivity, persistent erythema, and acneiform eruption. Multivariate logistic analysis revealed that the longer the scar duration, the higher incidence of postoperative adverse reactions (OR = 1.3, 95% CI [1.1, 1.5], p = 0.008). Compared with icepick scars, rolling scars (OR = 10.4, 95% CI [2.3, 47.7], p = 0.003) and boxcar scars (OR = 12.0, 95% CI [3.3, 44.0], p < 0.001) had higher risk of developing adverse reactions. The incidence of postoperative adverse reactions was also higher in the combined mode group (DeepFX mode + ActiveFX mode) than in the single-mode group (OR = 7.8, 95% CI [2.4, 25.5], p < 0.001). CONCLUSION: Fractional CO2 laser was effective in the treatment of atrophic acne scars, without serious adverse reactions. Scar type and laser energy were independent clinical factors affecting its efficacy. Scar course, scar type, and fractional laser mode were independent clinical factors affecting its adverse reactions.

Effects of surgery on survival of patients aged 75 years or older with Merkel cell carcinoma.

OBJECTIVE: To investigate whether surgery improves prognosis in elderly patients with Merkel cell carcinoma (MCC). MATERIALS/METHODS: Data of all patients with MCC diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Differences in baseline characteristics were analyzed among the age groups (75-80, 80-85, and ≥85 years). Multivariate Cox proportional hazards analysis was used to assess the effects of each variable on patient outcomes. The Kaplan-Meier curves were employed to evaluate MCC overall survival (OS) and MCC-specific survival (MSS). RESULTS: A total of 1156 of patients with MCC met the inclusion and exclusion criteria. The surgery rate decreased with age (75-80, 80-85, and ≥85 years were 93.3%, 91.1%, and 88.7%, respectively; p = 0.082). Multivariate Cox proportional hazards analysis showed that the OS of patients in the 80-85 years group (hazard ratio [HR] = 1.39; 95% confidence interval [CI] = 1.14-1.70; p = 0.001) and the ≥85 years group (HR = 2.18; 95% CI = 1.80-2.63; p < 0.0001) was worse than that in the 75-80 years group. Compared with the non-surgery groups, the HR for the surgery group was 0.75 for OS (95% CI = 0.56-1.00; p = 0.048) and 0.73 for MSS (95% CI = 0.48-1.10; p = 0.130). Subgroup analyses showed that patients aged ≥85 years undergoing surgery had better OS (HR = 0.65; 95% CI = 0.45-0.95; p = 0.024). CONCLUSIONS: MCC patients aged 75 years and older would benefit from surgical resection. However, surgical resection should be performed cautiously, and larger prospective clinical trials are needed to further verify these findings.