Chemoproteomic Profiling of Signaling Metabolite Fructose-1,6-Bisphosphate Interacting Proteins in Living Cells.

Fructose-1,6-bisphosphate (FBP), a cellular endogenous sugar metabolite in the glycolytic pathway, has recently been reported to act as a signaling molecule to regulate various cellular events through the engagement of important proteins. Though tremendous progress has been made in identifying specific FBP-protein interactions, the comprehensive identification of FBP-interacting proteins and their regulatory mechanisms remains largely unexplored. Here, we describe a concise synthetic approach for the scalable preparation of a photoaffinity FBP probe that enables the quantitative chemoproteomic profiling of FBP-protein interactions based on photoaffinity labeling (PAL) directly in living cells. Using such a protocol, we captured known FBP targets including PKM2 and MDH2. Furthermore, among unknown FBP-interacting proteins, we identified a mitochondrial metabolic enzyme aldehyde dehydrogenase 2 (ALDH2), against which FBP showed inhibitory activity and resulted in cellular ROS upregulation accompanied by mitochondrial fragmentation. Our findings disclosed a new mode of glucose signaling mediating by the FBP-ALDH2-ROS axis.

A Hierarchical Hydrogel Impregnation Strategy Enables Brittle-Failure-Free 3D-Printed Bioceramic Scaffolds.

3D-printed bioceramic scaffolds offer great potential for bone tissue engineering (BTE) but their inherent brittleness and reduced mechanical properties at high porosities can easily result in catastrophic fractures. Herein, this study presents a hierarchical hydrogel impregnation strategy, incorporating poly(vinyl alcohol) (PVA) hydrogel into the macro- and micropores of bioceramic scaffolds and synergistically reinforcing it via freeze-casting assisted solution substitution (FASS) in a tannic acid (TA)-glycerol solution. By effectively mitigating catastrophic brittle failures, the hydrogel-impregnated scaffolds showcase three- and 100-fold enhancement in mechanical energy absorption under compression (5.05 MJ m-3) and three-point bending (3.82 MJ m-3), respectively. The reinforcement mechanisms are further investigated by experimental and simulation analyses, revealing a multi-scale synergy of fracture and fragmentation resistance through macro and micro-scale fiber bridging, and nano and molecular-scale hydrogel reinforcement. Also, the scaffolds acquire additional antibacterial and drug-loading capabilities from the hydrogel phase while maintaining favorable cell biocompatibility. Therefore, this study demonstrates a facile yet effective approach for preparing brittle-failure-free bioceramic scaffolds with enhanced biological functionalities, showcasing immense potential for BTE applications.

Prognostic impact of spread through air spaces in patients with ≤2 cm stage IA lung adenocarcinoma.

Background: In 2015, the World Health Organization (WHO) included spread through air space (STAS) as a new invasive mode of lung cancer. As a new mode of lung cancer dissemination, STAS has a significant and negative impact on patient prognosis. The surgical approach as well as lymph node dissection (LND) for STAS-positive patients is currently unclear. The aim of this study was to investigate the impact of different surgical approaches to STAS and LND on the prognosis of patients with ≤2 cm stage IA lung adenocarcinoma (LUAD). This study also investigated the possible relationship between STAS and the micropapillary histological subtype and its impact on patient prognosis. Methods: A total of 212 patients with LUAD were included in this study from January 2016 to December 2017, and the overall survival (OS) of the patients was compared. The chi-square test and t-test were applied to compare the clinicopathological data of the patients, and the Cox model was used for the multivariate survival analysis. Results: Of the 212 patients, 93 (43.9%) were STAS positive. The univariate analysis showed that the surgical approach, LND type, micropapillary pattern (MP), solid pattern, and STAS were risk factors for OS. The multivariate analysis showed that the surgical approach, MP, and STAS were risk factors for OS. The STAS-positive patients who underwent lobectomy had a better prognosis than those who underwent sublobar resection; however, there was no significant difference between the two surgical procedures in the STAS-negative group. Additionally, the STAS-positive patients who underwent systematic lymph node dissection (SLND) had a better prognosis than those who underwent limited lymph node dissection (LLND); however, there was no significant difference between the two LNDs in the STAS-negative group. Conclusions: STAS plays an important role in patient prognosis and is an independent risk factor for OS of patients with ≤2 cm stage IA LUAD. When STAS is positive, the choice of lobectomy with SLND may result in a better long-term prognosis for patients.

The impact of inhalation injury on fluid resuscitation in major burn patients: a 10-year multicenter retrospective study.

BACKGROUND: It remains unclear whether additional fluid supplementation is necessary during the acute resuscitation period for patients with combined inhalational injury (INHI) under the guidance of the Third Military Medical University (TMMU) protocol. METHODS: A 10-year multicenter, retrospective cohort study, involved patients with burns ≥ 50% total burn surface area (TBSA) was conducted. The effect of INHI, INHI severity, and tracheotomy on the fluid management in burn patients was assessed. Cumulative fluid administration, cumulative urine output, and cumulative fluid retention within 72 h were collected and systematically analyzed. RESULTS: A total of 108 patients were included in the analysis, 85 with concomitant INHI and 23 with thermal burn alone. There was no significant difference in total fluid administration during the 72-h post-burn between the INHI and non-INHI groups. Although no difference in the urine output and fluid retention was shown in the first 24 h, the INHI group had a significantly lower cumulative urine output and a higher cumulative fluid retention in the 48-h and 72-h post-burn (all p < 0.05). In addition, patients with severe INHI exhibited a significantly elevated incidence of complications (Pneumonia, 47.0% vs. 11.8%, p = 0.012), (AKI, 23.5% vs. 2.9%, p = 0.037). For patients with combined INHI, neither the severity of INHI nor the presence of a tracheotomy had any significant influence on fluid management during the acute resuscitation period. CONCLUSIONS: Additional fluid administration may be unnecessary in major burn patients with INHI under the guidance of the TMMU protocol.

TCF19 promotes cell proliferation and tumor formation in lung cancer by activating the Raf/MEK/ERK signaling pathway.

OBJECTIVE: This study aimed to investigate TCF19's role in lung cancer development, specifically its involvement in the RAF/MEK/ERK signaling pathway. METHODS: Lung cancer tissue analysis revealed significant TCF19 overexpression. In vitro experiments using A549 and Hop62 cells with TCF19 overexpression demonstrated enhanced cell growth. Transgenic mouse models confirmed TCF19's role in primary tumor development. Transcriptome sequencing identified altered gene expression profiles, linking TCF19 to RAF/MEK/ERK pathway activation. Functional assays elucidated underlying mechanisms, revealing increased phosphorylation of Raf1, MEK1/2, and ERK1/2. Inhibiting RAF1 or ERK through shRaf1 or ERK inhibitor reduced cell cycle-related proteins and inhibited TCF19-overexpressing cell growth. RESULTS: TCF19 was identified as an oncogene in lung carcinoma, specifically impacting the RAF/MEK/ERK pathway. Elevated TCF19 levels in lung cancer suggest targeting TCF19 or its associated pathways as a promising strategy for disease management. CONCLUSION: This study unveils TCF19's oncogenic role in lung cancer, emphasizing its modulation of the RAF/MEK/ERK pathway and presenting a potential therapeutic target for TCF19-overexpressing lung cancers.

Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

Comparison between different advanced cannulation techniques for difficult biliary cannulation: a systematic review with a meta-analysis.

Objective: This study aimed to systematically evaluate the efficacy and safety of the double-guidewire technique along with other methods (persistent standard cannulation techniques, transpancreatic sphincterotomy, and pancreatic stent-assisted technique) for difficult biliary cannulation. Methods: Two researchers searched for literature on the efficacy and safety of the double-guidewire technique and other techniques in difficult biliary cannulation in databases, including PubMed, Embase, Cochrane, China National Knowledge Infrastructure, and Wanfang Data, based on the inclusion and exclusion criteria. The success rate of cannulation, duration of cannulation, post-ERCP pancreatitis, and overall postoperative complications were also analyzed using RevMan 5.4 software. Results: In total, 20 randomized controlled trial (RCT) studies involving 2008 participants were identified. The success rate of cannulation in the double-guidewire technique was much higher than that in persistent standard cannulation techniques [RR = 1.37, 95%CI (1.05, 1.79), p = 0.02]. However, it was lower than the success rate observed with transpancreatic sphincterotomy [RR = 0.89, 95%CI (0.81, 0.97), p = 0.01]. There was no significance in post-ERCP pancreatitis [RR = 1.09, 95% CI (0.85, 1.40), p = 0.49], overall postoperative complications [RR = 0.90, 95% CI (0.56, 1.45), p = 0.66], and duration of cannulation [SMD = -0.14, 95%C I (-1.43, 1.15), p = 0.83] between the double-guidewire technique and other techniques. Conclusion: This study demonstrated that the success rate of cannulation ranged from transpancreatic sphincterotomy to the double-guidewire technique and then to persistent standard cannulation techniques.

Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Identification and coregulation pattern analysis of long noncoding RNAs in the mouse brain after Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified. METHODS: In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). RESULTS: The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed. CONCLUSIONS: This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.

Prognostic value of CDKN2A in head and neck squamous cell carcinoma via pathomics and machine learning.

This study aims to enhance the prognosis prediction of Head and Neck Squamous Cell Carcinoma (HNSCC) by employing artificial intelligence (AI) to analyse CDKN2A gene expression from pathology images, directly correlating with patient outcomes. Our approach introduces a novel AI-driven pathomics framework, delineating a more precise relationship between CDKN2A expression and survival rates compared to previous studies. Utilizing 475 HNSCC cases from the TCGA database, we stratified patients into high-risk and low-risk groups based on CDKN2A expression thresholds. Through pathomics analysis of 271 cases with available slides, we extracted 465 distinctive features to construct a Gradient Boosting Machine (GBM) model. This model was then employed to compute Pathomics scores (PS), predicting CDKN2A expression levels with validation for accuracy and pathway association analysis. Our study demonstrates a significant correlation between higher CDKN2A expression and improved median overall survival (66.73 months for high expression vs. 42.97 months for low expression, p = 0.013), establishing CDKN2A's prognostic value. The pathomic model exhibited exceptional predictive accuracy (training AUC: 0.806; validation AUC: 0.710) and identified a strong link between higher Pathomics scores and cell cycle activation pathways. Validation through tissue microarray corroborated the predictive capacity of our model. Confirming CDKN2A as a crucial prognostic marker in HNSCC, this study advances the existing literature by implementing an AI-driven pathomics analysis for gene expression evaluation. This innovative methodology offers a cost-efficient and non-invasive alternative to traditional diagnostic procedures, potentially revolutionizing personalized medicine in oncology.

Investigative biological therapies for primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by dryness of the eyes and mouth. The histological feature is mononuclear cell infiltration in exocrine glands, primarily salivary and lachrymal glands. As the disease progresses, some other tissues and organs may be involved and extraglandular manifestations ensue. The major current treatments are palliative and empirical, and in most cases the outcomes are not satisfactory. Emerging data indicate a critical role of lymphocytes in its development and progression. While pioneering work targeting B cells has demonstrated some encouraging results, more trials are warranted to validate the safety and efficacy. In addition, modulation of T cell function with abatacept ameliorates the severity of pSS. Furthermore, clinical trials to inhibit important cytokines involved in its formation have been carried out. In this article, we summarize and compare current biological therapies in order to find new and effective treatments for pSS.

Association between preoperative anxiety states and postoperative complications in patients with esophageal cancer and COPD: a retrospective cohort study.

BACKGROUND: Esophageal cancer brings emotional changes, especially anxiety to patients. Co-existing anxiety makes the surgery difficult and may cause complications. This study aims to evaluate effects of anxiety in postoperative complications of esophageal cancer patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with esophageal cancer and co-existing COPD underwent tumor excision. Anxiety was measured using Hospital Anxiety and Depression Scale (HAD) before surgery. Clavien-Dindo criteria were used to grade surgical complications. A multiple regression model was used to analyze the relationship between anxiety and postoperative complications. The chi-square test was used to compare the differences in various types of complications between the anxiety group and the non-anxiety group. A multinomial logistic regression model was used to analyze the influencing factors of mild and severe complications. RESULTS: This study included a total of 270 eligible patients, of which 20.7% had anxiety symptoms and 56.6% experienced postoperative complications. After evaluation by univariate analysis and multivariate logistic regression models, the risk of developing complications in anxious patients was 4.1 times than non-anxious patients. Anxious patients were more likely to develop pneumonia, pyloric obstruction, and arrhythmia. The presence of anxiety, surgical method, higher body mass index (BMI), and lower preoperative oxygen pressure may increase the incidence of minor complications. The use of surgical methods, higher COPD assessment test (CAT) scores, and higher BMI may increase the incidence of major complications, while anxiety does not affect the occurrence of major complications (P = 0.054). CONCLUSION: Preoperative anxiety is associated with postoperative complications in esophageal cancer patients with co-existing COPD. Anxiety may increase the incidence of postoperative complications, especially minor complications in patient with COPD and esophageal cancer.

Prenatal diagnosis of interrupted aortic arch using high-definition flow render mode and spatiotemporal image correlation.

OBJECTIVES: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. METHODS: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. RESULTS: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD-flow combined with STIC than that in the 2D combined with HD-flow. CONCLUSION: HD-flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value.

Incremental high average-utility itemset mining: survey and challenges.

The High Average Utility Itemset Mining (HAUIM) technique, a variation of High Utility Itemset Mining (HUIM), uses the average utility of the itemsets. Historically, most HAUIM algorithms were designed for static databases. However, practical applications like market basket analysis and business decision-making necessitate regular updates of the database with new transactions. As a result, researchers have developed incremental HAUIM (iHAUIM) algorithms to identify HAUIs in a dynamically updated database. Contrary to conventional methods that begin from scratch, the iHAUIM algorithm facilitates incremental changes and outputs, thereby reducing the cost of discovery. This paper provides a comprehensive review of the state-of-the-art iHAUIM algorithms, analyzing their unique characteristics and advantages. First, we explain the concept of iHAUIM, providing formulas and real-world examples for a more in-depth understanding. Subsequently, we categorize and discuss the key technologies used by varying types of iHAUIM algorithms, encompassing Apriori-based, Tree-based, and Utility-list-based techniques. Moreover, we conduct a critical analysis of each mining method's advantages and disadvantages. In conclusion, we explore potential future directions, research opportunities, and various extensions of the iHAUIM algorithm.

Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.

Imbibition Characteristics and Influencing Factors of the Fracturing Fluid in a Tight Sandstone Reservoir.

The strong reservoir heterogeneity and complex microscopic pore structure in the Linxing area make it prone to water block damage during imbibition development. In order to explore the influence of reservoir microscopic characteristics on imbibition efficiency, taking the tight sandstone gas reservoir in the Linxing area of Ordos Basin as an example, the heterogeneity of the tight sandstone reservoir in the study area is characterized in terms of physical and chemical characteristics as well as the microscopic pore structure. Using nuclear magnetic resonance, high-pressure mercury pressure, and other testing methods, spontaneous seepage experiments in real sandstone were carried out to study the distribution law of different pore structures and seepage characteristics at different times and to systematically evaluate the microscopic pore characteristics of dense sandstone reservoirs and the factors affecting seepage and suction. The results show that due to the strong microscopic heterogeneity of tight sandstone, the macroscopic properties cannot directly reflect the microscopic characteristics, and the response to imbibition efficiency is stronger. The pore size is the main controlling factor affecting imbibition, and the contribution rate of the micropore and mesopore mainstream pore size spaces is higher than that of the macropore. Micropores provide imbibition power, and mesopores provide an imbibition interval. High-porosity and high permeability reservoirs are more conducive to imbibition replacement. The intercrystalline pores have a great influence on the imbibition efficiency, and the influence of intergranular pores and dissolution pores on the imbibition cannot be underestimated. The smaller the relative sorting coefficient, interfacial tension, and contact angle, the better the imbibition effect of fracturing fluid. Research results have theoretical guiding significance for spontaneous imbibition to improve oil recovery.

"Severe blepharoptosis correction with the fixation of levator complex and conjoint fascial sheath: 12 Years of Experience in a Single Center."

BACKGROUND: The correction of severe blepharoptosis is one of the most challenging surgeries in plastic surgery. This study introduces a novel self-reinforced fixation technique combining the levator complex with conjoint fascial sheath for the correction of severe blepharoptosis and reviews the postoperative results over the preceding 12 years. METHODS: This retrospective review included all patients who underwent self-reinforced fixation with or without conjoint fascial sheath at the authors' center between 2010 and 2022. The clinical data of the two groups were collected and evaluated. RESULTS: All patients were followed up for 6 months to 8 years postoperatively. The mean postoperative MRD1 and LF increased significantly in both groups. Sufficient correction of ptosis was achieved in 32 (65.31%) and 84 (81.56%) eyelids in Groups I and II, respectively. The mean eyelid lagophthalmos was 1.27± 0.91 mm and 0.85 ± 0.89 mm in Groups I and II, respectively. The most common complication was undercorrection of ptosis, which was observed in 14 eyelids (28.57%) and 15 eyelids (14.56%) in Groups I and II, respectively. CONCLUSIONS: The self-reinforced fixation technique was effective in correcting severe congenital ptosis in Chinese patients. The clinical effect was consistent in the long-term follow-up cases, and the recurrence rate was low. Thus, this technique can enhance the strength of the levator muscle and maintain appropriate elasticity of eye closure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway.

We evaluated the expression profiles of differentially expressed miRNAs (DEmiRNAs) involved in human fetal skin development via high-throughput sequencing to explore the expression difference and the regulatory role of miRNA in different stages of fetal skin development. Analysis of expression profiles of miRNAs involved collecting embryo samples via high-throughput sequencing, then bioinformatics analyses were performed to validate DEmiRNAs. A total of 363 miRNAs were differentially expressed during the early and mid-pregnancy of development, and upregulated DEmiRNAs were mainly concentrated in the let-7 family. The transfection of let-7b-5p slowed down HaCaT cell proliferation and promoted apoptosis, as evidenced by the cell counting kit-8 assay, quantitative real-time polymerase chain reaction, and flow cytometry. The double luciferin reporter assay also confirmed let-7b-5p and ΔNp63 downregulation through the combination with the 3'-untranslated region of ΔNp63. Moreover, treatment with a let-7b-5p inhibitor upregulated ΔNp63 and activated the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. The let-7b-5p caused a converse effect on HaCaT cells because of Np63 upregulation. Let-7b-5p regulates skin development by targeting ΔNp63 via PI3K-AKT signaling, contributing to future studies on skin development and clinical scar-free healing.