Correlation of TBX21 gene polymorphisms with ankylosing spondylitis in a Chinese population.

Genome-wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case-control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single-nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)-B27+ AS in allelic (C vs. T: odds ratio [OR] = 1.52, 95%CI = 1.09-2.11, corrected p [pc] = .028), heterozygous (CT vs. TT: OR = 1.63, 95%CI = 1.13-2.34, pc = .016) and dominant (CT + CC vs. TT: OR = 1.60, 95%CI = 1.12-2.28, pc = .018) models. Furthermore, the haplotype rs4794067/C-rs11657479/C of TBX21 was found to increase the risk of HLA-B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA-B27+ AS patients within the Chinese population.

Genetic variations of IL10 and IL6R genes in acute anterior uveitis in Han Chinese.

BACKGROUND: Several autoimmune disorders have been linked to polymorphisms in IL10 and IL6R genes. This research aimed to study whether single nucleotide polymorphisms (SNPs) in the genes of IL10 and IL6R were associated with acute anterior uveitis (AAU) in Han Chinese. METHODS: Genotyping was carried out by the iPLEX Gold Genotyping Assay. Our study comprised 420 patients with AAU and 918 healthy subjects from Han Chinese. Using the chi-square (χ2) test, alleles and genotypes were analyzed between AAU subjects and healthy controls. RESULTS: All ten SNPs were successfully genotyped and four SNPs (IL10/rs1800871, IL10/rs3021094, IL10/rs2222202, IL6R/rs4845618) exhibited weak associations with AAU, as indicated by their Puncorr values. However, upon applying the Bonferroni correction, there was no significant association between AAU and the control subjects. Additionally, the haplotype analysis of the ten SNPs revealed no association with AAU. CONCLUSION: Our findings suggested that polymorphisms of the tested ten SNPs on the IL10 and IL6R genes did not show any association with the risk of developing AAU among the Han Chinese population.

HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target?

BACKGROUND: Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target. METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma. RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy. CONCLUSION: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.

Insights into Predicting Tooth Extraction from Panoramic Dental Images: Artificial Intelligence vs. Dentists.

OBJECTIVES: Tooth extraction is one of the most frequently performed medical procedures. The indication is based on the combination of clinical and radiological examination and individual patient parameters and should be made with great care. However, determining whether a tooth should be extracted is not always a straightforward decision. Moreover, visual and cognitive pitfalls in the analysis of radiographs may lead to incorrect decisions. Artificial intelligence (AI) could be used as a decision support tool to provide a score of tooth extractability. MATERIAL AND METHODS: Using 26,956 single teeth images from 1,184 panoramic radiographs (PANs), we trained a ResNet50 network to classify teeth as either extraction-worthy or preservable. For this purpose, teeth were cropped with different margins from PANs and annotated. The usefulness of the AI-based classification as well that of dentists was evaluated on a test dataset. In addition, the explainability of the best AI model was visualized via a class activation mapping using CAMERAS. RESULTS: The ROC-AUC for the best AI model to discriminate teeth worthy of preservation was 0.901 with 2% margin on dental images. In contrast, the average ROC-AUC for dentists was only 0.797. With a 19.1% tooth extractions prevalence, the AI model's PR-AUC was 0.749, while the dentist evaluation only reached 0.589. CONCLUSION: AI models outperform dentists/specialists in predicting tooth extraction based solely on X-ray images, while the AI performance improves with increasing contextual information. CLINICAL RELEVANCE: AI could help monitor at-risk teeth and reduce errors in indications for extractions.

The correlation of endoplasmic reticulum aminopeptidase 1 polymorphisms with Behçet's disease: a meta-analysis.

OBJECTIVES: Substantial evidence has highlighted the mediation of endoplasmic reticulum aminopeptidase 1 (ERAP1) in the onset of Behçet's disease (BD), which can be differentially converted by ERAP1 variants. To comprehensively elaborate this issue, we undertook the meta-analysis to estimate the liaison of ERAP1 polymorphisms with BD risk. METHODS: Literatures were retrieved in a standardised fashion and data underwent multi-perspective analyses utilizing STATA Statistical Software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) of manifold comparisons between BD sufferers and healthy masses were exploited to evaluate the extent of relevance. RESULTS: Overall analyses suggested that the meanings of ERAP1 polymorphisms in BD susceptibility varied among plentiful variations, where rs10050860, rs17482078, rs2287987, rs1065407 and rs72773968 presented pathogenic influence and rs26618 acted out beneficial function, while rs27044, rs26653, rs27895 and rs3734016 had no pronounced biological significance. Additionally, the effect of rs30187 is not yet determined. Moreover, race appeared a crucial ingredient as Mongolian were more susceptible to suffering from BD than Caucasian, while the diagnostic criteria of BD exerted a relative inconspicuous role, where the International Study Group criteria slightly attenuated the pathogenicity of ERAP1 polymorphisms compared with the International Criteria for Behçet's Disease. Finally, an exceeding importance was attached to the proceeding analysis based on disparities in BD symptoms, ERAP1 haplotypes and HLA-B*51 in computing the hazard zonation of ERAP1 polymorphisms on BD tendency. CONCLUSIONS: The present meta-analysis prompted the heterogeneous influences of ERAP1 polymorphisms on BD development, which were malleable under the discrepancies in genetic grounds and disease diagnoses.

Relationship between Uveitis and the Differential Reactivity of Retinal Microglia.

Uveitis, a complicated group of ocular inflammatory diseases, can be affected by massive pathogenic contributors such as infection, autoimmunity, and genetics. Although it is well known that many pathological changes, including disorders of the immune system and disruption of the blood-retinal barrier, count much in the onset and progression of uveitis, there is a paucity of safe and effective treatments, which has exceedingly hindered the appropriate treatment of uveitis. As innate immune cells in the retina, microglia occupy a salient position in retinal homeostasis. Many studies have reported the activation of microglia in uveitis and the mitigation of uveitis by interfering with microglial reactivity, which strongly implicates microglia as a therapeutic target. However, it has been increasingly recognized that microglia are a nonhomogeneous population under different physiological and pathological conditions, which makes it essential to thoroughly have knowledge of their specific characteristics. The paper outlines the various properties of activated microglia in uveitis, summarizes the connections between their polarization patterns and the manifestations of uveitis, and ultimately is intended to enhance the understanding of microglial versatility and expedite the exploration of promising strategies for visual protection.

One-Stage Repair of Alveolar Cleft and Nasal Deformities Using Grafts From Nasal Septum: Application of Vomer, Ethmoid, and Septal Cartilage.

BACKGROUND: Patients with alveolar cleft unrepaired suffer from nasal deformities of different magnitude. Bone and cartilage grafts are harvested through several incisions. In this study, we present a method to simultaneously correct nasal deformities and repair alveolar cleft using grafts from the nasal septum. PATIENTS AND METHODS: All 6 patients with unilateral cleft lip and palate have alveolar cleft unrepaired combined with nasal deformity. Computed tomography scans and 3-dimensional-printed models of vomer and ethmoid bone were used for the purpose of preoperative design and for assessing the magnitude of deformity. Grafts of bone and cartilage from deviated septum were harvested by septoplasty through which dorsum deviation was corrected. Bone grafts from vomer and ethmoid were then fixed to the prepared alveolar cleft to repair the defect and elevate the alar base. Septal cartilage was adjusted into different shapes of grafts and deformities of nasal tip, nostrils, and columella were then corrected by rhinoplasty to restore the symmetry of the nose. RESULTS: Symmetry of nostrils was improved. The height of alar base on the cleft side was elevated to the level close to the noncleft side. Deviation of the septum, nasal dorsum, and columella was corrected. Projection of the nasal tip was adjusted to facial midline. Midface aesthetics was generally improved. CONCLUSION: Application of septal grafts reduce the number of incisions. One-stage repair of alveolar cleft and nasal deformities, with the aid of digital design, improves the postoperative experience and the general outcome of the surgery.

Inhibition Effect of Phosphorus Poisoning on the Dynamics and Redox of Cu Active Sites in a Cu-SSZ-13 NH3-SCR Catalyst for NOx Reduction.

Phosphorus (P) stemming from biodiesel and/or lubricant oil additives is unavoidable in real diesel exhausts and deactivates gradually the Cu-SSZ-13 zeolite catalyst for ammonia-assisted selective catalytic NOx reduction (NH3-SCR). Here, the deactivation mechanism of Cu-SSZ-13 by P-poisoning was investigated by ex situ examination of the structural changes and by in situ probing the dynamics and redox of Cu active sites via a combination of impedance spectroscopy, diffuse reflection infrared Fourier transform spectroscopy, and ultraviolet-visible spectroscopy. We unveiled that strong interactions between Cu and P led to not only a loss of Cu active sites for catalytic turnovers but also a restricted dynamic motion of Cu species during low-temperature NH3-SCR catalysis. Furthermore, the CuII ↔ CuI redox cycling of Cu sites, especially the CuI → CuII reoxidation half-cycle, was significantly inhibited, which can be attributed to the restricted Cu motion by P-poisoning disabling the formation of key dimeric Cu intermediates. As a result, the NH3-SCR activity at low temperatures (200 °C and below) decreased slightly for the mildly poisoned Cu-SSZ-13 and considerably for the severely poisoned Cu-SSZ-13.

Evaluation of a novel artificial intelligence-based screening system for diabetic retinopathy in community of China: a real-world study.

PURPOSE: To evaluate the performance of an AI-based diabetic retinopathy (DR) grading model in real-world community clinical setting. METHODS: Participants with diabetes on record in the chosen community were recruited by health care staffs in a primary clinic of Zhengzhou city, China. Retinal images were prospectively collected during December 2018 and April 2019 based on intent-to-screen principle. A pre-validated AI system based on deep learning algorithm was deployed to screen DR graded according to the International Clinical Diabetic Retinopathy scale. Kappa value of DR severity, the sensitivity, specificity of detecting referable DR (RDR) and any DR were generated based on the standard of the majority manual grading decision of a retina specialist panel. RESULTS: Of the 193 eligible participants, 173 (89.6%) were readable with at least one eye image. Mean [SD] age was 69.3 (9.0) years old. Total of 321 eyes (83.2%) were graded both by AI and the specialist panel. The κ value in eye image grading was 0.715. The sensitivity, specificity and area under curve for detection of RDR were 84.6% (95% CI: 54.6- 98.1%), 98.0% (95% CI: 94.3-99.6%) and 0.913 (95% CI: 0.797-1.000), respectively. For detection of any DR, the upper indicators were 90.0% (95% CI: 68.3-98.8), 96.6% (95% CI: 92.1-98.9) and 0.933 (95% CI: 0.933-1.000), respectively. CONCLUSION: The AI system showed relatively good consistency with ophthalmologist diagnosis in DR grading, high specificity and acceptable sensitivity for identifying RDR and any DR. TRANSLATIONAL RELEVANCE: It is feasible to apply AI-based DR screening in community. PRECIS: Deployed in community real-world clinic setting, AI-based DR screening system showed high specificity and acceptable sensitivity in identifying RDR and any DR. Good DR diagnostic consistency was found between AI and manual grading. These prospective evidences were essential for regulatory approval.

Ferulic acid (FA) protects human retinal pigment epithelial cells from H2 O2 -induced oxidative injuries.

The aim of present study is to investigate whether Ferulic acid (FA), a natural polyphenol antioxidant, was able to protect ARPE-19 cells from hydrogen peroxide (H2 O2 )-induced damage, and elucidate the underlying mechanisms. Our results revealed that FA pre-treatment for 24 hours can reverse cell loss of H2 O2 -induced ARPE-19 cells via the promotion of cell proliferation and prevention of apoptosis, as evidenced by 5-ethynyl-2'-deoxyuridine (EdU) incorporation and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay, respectively. Moreover, the addition of FA (5 mM) can decrease Bax and cleaved caspase-3 protein expression, but increase Bcl-2 protein expression in ARPE-19 cells. Furthermore, H2 O2 -induced oxidative stress in ARPE-19 cells was significantly alleviated by FA, illustrated by reduced levels of ROS and MDA. In addition, the attenuated antioxidant enzymes activities of (SOD, CAT and GPX) and GSH level were reversed almost to the normal base level by the pre-addition of FA for 24 hours. In all assays, FA itself did not exert any effect on the change of the above parameters. These novel findings indicated that FA effectively protected human ARPE-19 cells from H2 O2 -induced oxidative damage through its pro-proliferation, anti-apoptosis and antioxidant activity, suggesting that FA has a therapeutic potential in the prevention and treatment of AMD.

A Modified Cosmetic Genioplasty Can Affect Airway Space Positively in Skeletal Class II Patients: Studying Alterations of Hyoid Bone Position and Posterior Airway Space.

BACKGROUND: Improving the posterior airway space is one of the most important functions of genioplasty. Studies have shown that the posterior airway space (PAS) can play an important role in the evaluation of obstructive sleep apnea syndrome (OSAS). The purpose of this study is to evaluate the airway safety of our modified technology by observing the impact on PAS in skeletal Class II patients without OSAS. METHODS: We have modified a cosmetic genioplasty, which can guarantee the continuity of the lower edge of the bilateral mandible by rotating the chin segment clockwise. Fourteen patients submitted to our modified cosmetic genioplasty alone were included in the study. The facial convexity angle and the ratio of the face were measured by analyzing photographs. The position of the hyoid bone and the width of the PAS were measured by analyzing lateral cephalograms. The volume and the cross-sectional area (CSA) of the PAS were measured using 3D reconstruction. The Wilcoxon signed-rank test and paired samples t test were used to assess the significance of differences of the data (p < 0.05). RESULTS: Soft tissue measurements were statistically different (p = 0.001) and achieved satisfactory results. The position of the hyoid bone moved up (LX: p = 0.004; LML: p = 0.056) and forward (LY: p = 0.001; LCV3: p = 0.016). The increase in the CSA had statistical significance (p < 0.005). There were significant statistical differences in the total airway volume and hypopharynx (p = 0.001), except in the oropharynx (p = 0.096). CONCLUSIONS: Our modified genioplasty not only achieved better cosmetic results by ensuring the continuity of the lower edge of the bilateral mandible but also exerted a significant positive impact on the posterior airway space for patients with skeletal class II, thus helping reduce the prevalence of OSAS. We hence suggest performing this modified cosmetic genioplasty on the skeletal class II patients with/without OSAS if necessary. 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 .

Inhibitory effect of luteolin on the proliferation of human breast cancer cell lines induced by epidermal growth factor.

The aim of the present study was to investigate the mechanism of the inhibitory effect of luteolin on the proliferation of breast cancer cells induced by epidermal growth factor (EGF) in vitro. MTT assay was used to detect the inhibitory effect of luteolin on the proliferation of MCF-7 and MDA-MB-231 cells as well as the effect on the proliferation of MCF-7 cells induced by EGF. Western blotting was used to detect the effects of luteolin on the expression of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (Erk) 1/2 and signal transducers and activators of transcription-3 (STAT3) in MCF-7 cells induced by EGF. The results showed that luteolin could significantly inhibit the proliferation of MCF-7 and MDA-MB-231 cells, and the inhibitory effect on MCF-7 cells was more prominent. Moreover, luteolin could inhibit the proliferation of MCF-7 cells induced by EGF. Western blotting results showed that luteolin and AG1478 (an inhibitor of EGFR signaling) could inhibit the expression of p-EGFR and p-STAT3 in MCF-7 cells induced by EGF. Luteolin, LY294002 (an inhibitor of Akt signaling) and PD98059 (an inhibitor of Erk1/2 signaling) could inhibit the expression of p-Akt and p-Erk1/2 respectively in MCF-7 cells induced by EGF. Our data suggest that luteolin may inhibit EGF-induced activities of EGFR signaling pathway in human breast cancer cell lines, and PI3K/Akt, MAPK/Erk1/2, STAT3 signal pathways may be the major pathways that mediate the inhibitory effect of luteolin on EGFR signaling. Overall, our results may provide a theoretical foundation for the development of luteolin as anti-tumor drug.

[Inhibition of methicillin-resistant Staphylococcus aureus biofilm by honokiol].

Objective: To study the inhibition of methicillin-resistant Staphylococcus aureas (MRSA) biofilm by honokiol. Methods: We used triphenyl tetrazolium chloride method to evaluate the inhibition of biofilm formation and mature by honokiol. We used congo red agar and spectrophotometer to detect the influence of honokiol on polysaccharide intercellular adhesion formation and extracellular DNA release. RT-PCR analysis was used to determine the effect of honokiol on expression of icaA, cidA and agrA. Results: Honokiol showed strong antimicrobial activity both on biofilm formation and mature biofilm of MRSA 41573. Minimum inhibitory concentration was 10 µg/mL for biofilm formation and 50 µg/mL for mature biofilm. Minimum bactericidal concentration was 20 µg/mL for biofilm formation and 100 µg/mL for mature biofilm. Honokiol showed synergy effect with vancomycin and it significantly increased the sensitivity of mature biofilm to vancomycin. Polysaccharide intercellular adhesion formation and extracellular DNA release were effectively inhibited by honokiol. Extracellular DNA release decreased by 28.3% when honokiol at 1/8 MIC. After incubated with 1/2 MIC of honokiol for 16 h, the relative expression of icaA, cidA and agrA of MRSA41573 was reduced by 59.1%, 56% and 72.3%, respectively. Conclusion: Honokiol can significantly inhibit biofilm formation of MRSA41573 and its mechanism is mainly the inhibited expression of icaA and cidA to influence the synthesis of polysaccharide intercellular adhesion and extracellular DNA. Moreover, it also affect biofilm formation by QS system.

[Progress in gene regulation mechanisms of Staphylococcus biofilm development--A review].

Bacterial resistance is a threat to public health. Bacterial biofilm formation is one of the main reasons for persistent infection caused by bacteria. Biofilm development is a complex process that involves many factors and genes which play various roles in all stages of the biofilm formation. This review focuses on the gene regulatory mechanisms relate to the biofilm formation of Staphylococcus, the most common pathogen that causes nosocomial infection, as well as the latest developments of pharmacological anti-biofilm therapies. We also address new strategy to treat bacterial infection and the development of drugs and vaccines against biofilm resistance.

Spinel Mn-Co oxide in N-doped carbon nanotubes as a bifunctional electrocatalyst synthesized by oxidative cutting.

The notorious instability of non-precious-metal catalysts for oxygen reduction and evolution is by far the single unresolved impediment for their practical applications. We have designed highly stable and active bifunctional catalysts for reversible oxygen electrodes by oxidative thermal scission, where we concurrently rupture nitrogen-doped carbon nanotubes and oxidize Co and Mn nanoparticles buried inside them to form spinel Mn-Co oxide nanoparticles partially embedded in the nanotubes. Impressively high dual activity for oxygen reduction and evolution is achieved using these catalysts, surpassing those of Pt/C, RuO2, and IrO2 and thus raising the prospect of functional low-cost, non-precious-metal bifunctional catalysts in metal-air batteries and reversible fuel cells, among others, for a sustainable and green energy future.

Hollow and yolk-shell iron oxide nanostructures on few-layer graphene in Li-ion batteries.

We report a simple and template-free strategy for the synthesis of hollow and yolk-shell iron oxide (FeOx) nanostructures sandwiched between few-layer graphene (FLG) sheets. The morphology and microstructure of this material are characterized in detail by X-ray diffraction, X-ray absorption near-edge structure, X-ray photoelectron spectroscopy, Raman spectroscopy, scanning and transmission electron microscopy. Its properties are evaluated as negative electrode material for Li-ion batteries and compared with those of solid FeOx/FLG and two commercial iron oxides. In all cases, the content of carbon in the electrode has a great influence on the performance. The use of pristine FLG improves the capacity retention and further enhancement is achieved with the hollow structure. For a low carbon loading of 18 wt. %, the presence of metallic iron in the hollow and yolk-shell FeOx/FLG composite significantly enhances the capacity retention, albeit with a relatively lower initial reversible capacity, retaining above 97% after 120 cycles at 1000 mA g(-1) in the voltage range of 0.1-3.0 V.

[Inhibitory effects of biochanin A on the efflux pump of methicillin-resistant Staphylococcus aureus (MRSA)].

OBJECTIVE: To study the inhibitory effect of biochanin A on efflux system of Methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Inhibitory effects of biochanin A on efflux system of Strain MRSA41577 were evaluated using double dilution method, two plate method and fluorescence spectrophotometry. Real time PCR and SDS-PAGE were applied to detect the expression of MRSA41577 norA and to analyze the changes of MRSA41577 efflux protein before and after dosing biochanin A in association with liquid chromatography mass spectrometry to determinate protein variation. RESULTS: Biochanin A alone had no inhibitory effect on MRSA41577, but it showed synergy effect with ciprofloxacin in inhibition MRSA41577 in which 40pg/mL biochanin A decreased the minimum inhibitory concentration (MIC) value of ciprofloxacin from 64 microg/mL to 8 microgg/mL. Biochanin A significantly increased the accumulation of ciprofloxacin in MRSA41577 in a time-dependent manner. At 15 min, biochanin A increased ciprofloxacin in MRSA41577 by 83%, which is similar to that of reserpine (positive control). Further mechanism studies indicated that biochanin A could reduce the expression of nor A in ciprofloxacin-treated MRSA41577. After incubated with biochanin A and ciprofloxacin for 16 h, the relative expression of nor A of MRSA41577 was reduced by 65%. SDS-PAGE analysis showed that the total protein profiles of MRSA41577 were significantly changed after treatment with biochanin A for 16h, in which both norA protein and efflux system ABC transporter ATP-binding protein were significantly decreased. CONCLUSION: Biochanin A could inhibit Methicillin-resistant Staphylococcus aureus efflux system through reducing pathogen' s expression of nor A and norA protein.

Full-thickness skin graft versus split-thickness skin graft for radial forearm free flap donor site closure: protocol for a systematic review and meta-analysis.

BACKGROUND: The radial forearm free flap (RFFF) serves as a workhorse for a variety of reconstructions. Although there are a variety of surgical techniques for donor site closure after RFFF raising, the most common techniques are closure using a split-thickness skin graft (STSG) or a full-thickness skin graft (FTSG). The closure can result in wound complications and function and aesthetic compromise of the forearm and hand. The aim of the planned systematic review and meta-analysis is to compare the wound-related, function-related and aesthetics-related outcome associated with full-thickness skin grafts (FTSG) and split-thickness skin grafts (STSG) in radial forearm free flap (RFFF) donor site closure. METHODS: A systematic review and meta-analysis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed. Electronic databases and platforms (PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI)) and clinical trial registries (ClinicalTrials.gov, the German Clinical Trials Register, the ISRCTN registry, the International Clinical Trials Registry Platform) will be searched using predefined search terms until 15 January 2024. A rerun of the search will be carried out within 12 months before publication of the review. Eligible studies should report on the occurrence of donor site complications after raising an RFFF and closure of the defect. Included closure techniques are techniques that use full-thickness skin grafts and split-thickness skin grafts. Excluded techniques for closure are primary wound closure without the use of skin graft. Outcomes are considered wound-, functional-, and aesthetics-related. Studies that will be included are randomized controlled trials (RCTs) and prospective and retrospective comparative cohort studies. Case-control studies, studies without a control group, animal studies and cadaveric studies will be excluded. Screening will be performed in a blinded fashion by two reviewers per study. A third reviewer resolves discrepancies. The risk of bias in the original studies will be assessed using the ROBINS-I and RoB 2 tools. Data synthesis will be done using Review Manager (RevMan) 5.4.1. If appropriate, a meta-analysis will be conducted. Between-study variability will be assessed using the I2 index. If necessary, R will be used. The quality of evidence for outcomes will eventually be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: This study's findings may help us understand both closure techniques' complication rates and may have important implications for developing future guidelines for RFFF donor site management. If available data is limited and several questions remain unanswered, additional comparative studies will be needed. SYSTEMATIC REVIEW REGISTRATION: The protocol was developed in line with the PRISMA-P extension for protocols and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 17 September 2023 (registration number CRD42023351903).

Hederagenin reduces Aß-induced oxidative damage, decreases Aß deposition and promotes cell survival by the P13†K/Akt signaling pathway.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. ß-amyloid (Aß) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aß activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aß injury. Therefore, Aß-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aß injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aß-induced oxidative damage, and reduced apoptosis via the PI3 K/Akt signaling pathway. HG inhibited Aß deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aß; therefore, more natural active products are expected to be applied in AD therapy.

Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease.

Introduction: Disulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn's disease (CD) has not been thoroughly explored. Methods: Firstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD. Results: In this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis. Discussion: In this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.