Molecularly Imprinted Heterostructure-Assisted Laser Desorption Ionization Mass Spectrometry Analysis and Imaging of Quinolones.

Quinolone residues resulting from body metabolism and waste discharge pose a significant threat to the ecological environment and to human health. Therefore, it is essential to monitor quinolone residues in the environment. Herein, an efficient and sensitive matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS) method was devised by using a novel molecularly imprinted heterojunction (MIP-TNs@GCNs) as the matrix. Molecularly imprinted titanium dioxide nanosheets (MIP-TNs) and graphene-like carbon nitrides (GCNs) were associated at the heterojunction interface, allowing for the specific, rapid, and high-throughput ionization of quinolones. The mechanism of MIP-TNs@GCNs was clarified using their adsorption properties and laser desorption/ionization capability. The prepared oxygen-vacancy-rich MIP-TNs@GCNs heterojunction exhibited higher light absorption and ionization efficiencies than TNs and GCNs. The good linearity (in the quinolone concentration range of 0.5-50 pg/µL, R2 > 0.99), low limit of detection (0.1 pg/µL), good reproducibility (n = 8, relative standard deviation [RSD] < 15%), and high salt and protein resistance for quinolones in groundwater samples were achieved using the established MIP-TNs@GCNs-MALDI/MS method. Moreover, the spatial distributions of endogenous compounds (e.g., amino acids, organic acids, and flavonoids) and xenobiotic quinolones from Rhizoma Phragmitis and Rhizoma Nelumbinis were visualized using the MIP-TNs@GCNs film as the MALDI/MS imaging matrix. Because of its superior advantages, the MIP-TNs@GCNs-MALDI/MS method is promising for the analysis and imaging of quinolones and small molecules.

Analysis of Age-Related Changes in Lower Facial Fat Compartments and of the Course of Blood Vessels Using Computed Tomography.

BACKGROUND: According to the volume restoration theory, lower facial fat compartments tend to selectively atrophy or hypertrophy with age. The aim of this study was to demonstrate age-related changes in lower facial fat compartments using computed tomography, with strict control of the body mass index and underlying diseases. METHODS: This study included 60 adult women in three age-based categories. The thicknesses of the jowl, labiomandibular, and chin fat compartments were measured using computed tomographic images. The distribution and arrangement of facial blood vessels were further analyzed to provide evidence of the safety of rejuvenation strategies based on the facial volumetric theory. RESULTS: The inferior part of the superficial jowl fat compartment and deep jowl fat compartment thickened with age. The deep layer of the labiomandibular fat compartment thinned with age, and the superficial layer thickened with age. The deep and superficial layers of the chin compartments thickened with age. The facial vein passes through the lower mandibular border at the anterior edge of the masseter muscle and moves upward, perpendicular to the lower mandibular border. The high-risk area of the facial artery had an angle of approximately 45 degrees to the lower mandibular border. CONCLUSIONS: This study suggests that with age, selective thickening or thinning occurs in different lower facial fat compartments. The mandible and masseter muscle were used as reference markers to analyze the courses of the facial artery and facial vein, which can help clinicians to reduce vascular injury.

A single atom cobalt anchored MXene bifunctional platform for rapid, label-free and high-throughput biomarker analysis and tissue imaging.

Few of single-atom materials have been served as platform to analyze small molecules for surface assisted laser desorption/ionization mass spectrometry (SALDI-MS). Herein, a novel single Co atom-anchored MXene (Co-N-Ti3C2) is prepared to achieve enhanced SALDI-MS and mass spectrometry imaging (MSI) performance for the first time. The Co-N-Ti3C2 films were prepared by a simple in situ self-assembly strategy to generate an efficient SALDI-MS platform. Compared to typical inorganic/organic matrices, Co-N-Ti3C2 films exhibit superior performance in small molecules detection with ultra-high sensitivity (LOD at amol level), excellent repeatability (CV <4%), clean background and wide analyte coverage, enabling accurate quantitative analysis of various low-concentration metabolites from 1 µL biofluid in seconds. Its usage efficiently enhanced SALDI-MS detection of various small-molecule biomarkers such as amino acids, succinic acid, itaconic acid, arachidonic acid, citrulline, prostaglandin E2, creatinine, uric acid, glutamine, D-mannose, cholesterol and inositol in positive ion mode. The blood glucose level in humans was successfully determined from a linearity concentration range (0.25-10 mM). Notably, the Co-N-Ti3C2 assisted SALDI-MSI enables study the spatial distribution of small molecules covering the range central to metabolomics at a high resolution on a tissue section. Furthermore, Co-N-Ti3C2 platform revealed a specific peak profile that distinguishes osteoarthritis (OA) from rheumatoid arthritis (RA) tissue. Density functional theory theoretical investigation revealed that single Co atoms anchored on Ti3C2 could highly enhanced the ionization ability of metabolites, resulting in high-sensitivity and heterogeneous metabolome coverage.

Knockdown of Galectin-9 alleviates rheumatoid arthritis through suppressing TNF-α-induced activation of fibroblast-like synoviocytes.

The role of Galectin-9 (Gal-9) in the pathogenesis of rheumatoid arthritis (RA) remains unclear. This study aimed to investigate the mechanism of action and therapeutic potential of Gal-9 in RA. We detected Gal-9 expression in clinical samples, explored the mechanism of function of Gal-9 by knockdown and overexpression in fibroblast-like synoviocytes (FLSs), and further verified it in collagen-induced arthritis (CIA) model. We found that the levels of Gal-9 were considerably elevated in RA synovium than in osteoarthritis (OA) patients. A substantial decrease of Gal-9 was demonstrated after tumor necrosis factor (TNF-α) inhibitor treatment in the plasma of patients with RA. Additionally, transcriptome sequencing revealed that Gal-9 was involved in the regulation of the TNF-α pathway. Gal-9 was considerably upregulated after TNF-α stimulation in FLSs, and knockdown of Gal-9 substantially inhibited TNF-α activated proliferation, migration and inflammatory response. According to cell transcriptome sequencing results, we further confirmed that Gal-9 could achieve these effects by interacting with MAFB and affecting PI3K/AKT/mTOR pathway. Finally, we knocked down Gal-9 on the CIA model and found that it could alleviate the progression of arthritis. In conclusion, our study revealed that the knockdown of Gal-9 could inhibited TNF-α induced activation in RA through MAFB, PI3K/AKT/mTOR.

The Effectiveness of Using CO2 Fractional Laser and Mebo Burn Ointment Together in Treating Scars on the Face after Surgery.

Background: This study aimed to investigate the efficacy and safety of CO2 fractional laser combined with Mebo burn ointment in treating facial postoperative scars. Methods: Sixty patients with facial postoperative scars in the department of plastic surgery of Sun Yat-sen Memorial Hospital from January 2020 to June 2022 were divided into a control group (30 cases) and a study group (30 cases). Both groups received CO2 fractional laser treatment, but the study group also received Mebo burn ointment application. Results: The study found that both methods resulted in a significant decrease in Sawada score and a significant increase in Investigator Global Assessment score after treatment (P < 0.05), with the study group showing a more significant improvement and higher patient satisfaction (P < 0.05). All patients experienced varying degrees of bleeding, swelling, and erythema immediately after treatment, with two cases of pigmentation and two cases of persistent erythema in the control group, and one case of pigmentation and one case of persistent erythema in the study group. Adverse reactions were minimal, with the study group showing better tolerance. Conclusions: The study suggests that CO2 fractional laser combined with Mebo burn ointment is an effective and safe treatment for facial postoperative scars.

Quantitative MRI Analysis of Brachial Plexus and Limb-Girdle Muscles in Upper Extremity Onset Amyotrophic Lateral Sclerosis.

BACKGROUND: Recent evidence highlights the potential of axonal degeneration as a biomarker for amyotrophic lateral sclerosis (ALS) detection. However, the diagnostic potential of peripheral nerve axon changes in ALS remains unclear. PURPOSE: To evaluate the diagnostic performance of quantitative MRI of the brachial plexus and limb-girdle muscles (LGMs) in patients with upper extremity onset of ALS. STUDY TYPE: Retrospective. POPULATION: 47 patients with upper extremity onset of ALS and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions with short-tau inversion recovery sequences, T2-weighted turbo spin-echo Dixon sequence. ASSESSMENT: The cross-sectional area (CSA) and nerve-muscle T2 signal intensity ratio (nT2) of the bilateral brachial plexus as well as the CSA and fat fraction (FF) of the bilateral LGMs were assessed by two radiologists. Disease severity and clinical stage of ALS patients were assessed by two neurologists. STATISTICAL TESTS: Student's t-test, Wilcoxon rank-sum test, binary logistic regression, interclass correlation coefficient, receiver operating characteristic analysis, and correlation analysis were performed for MRI quantitative metrics and clinical variables. Significance level: P < 0.05. RESULTS: In the affected limbs of patients with ALS, the CSA of the brachial plexus roots, trunks, and cords and the nT2 values of the brachial plexus trunks were significantly smaller than in the healthy controls. In the LGMs, the affected limbs of ALS showed significantly smaller CSA and higher FF than controls. The model containing parameters such as brachial plexus trunk CSA, subscapularis CSA, infraspinatus CSA, and subscapularis FF had excellent diagnostic efficacy for ALS. Additionally, increased subscapularis FF and supraspinatus FF were correlated with disease severity, and subscapularis CSA was negatively correlated with the clinical stage. DATA CONCLUSION: Brachial plexus thinning, LGM atrophy, and fatty infiltration might serve as MRI-derived biomarkers for ALS with upper extremity onset. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Revealing mechanism of Methazolamide for treatment of ankylosing spondylitis based on network pharmacology and GSEA.

Methazolamide is a carbonic anhydrase (CA) inhibitor with satisfactory safety. Our previous studies have demonstrated the elevation of CA1 expression and the therapeutic effect of Methazolamide in Ankylosing spondylitis (AS). In this study, we explored the pathogenic role of CA1 and the pharmacological mechanism of Methazolamide in AS through Gene Set Enrichment Analysis (GSEA) and network pharmacology. Seven out of twelve CA1 related gene sets were enriched in AS group. CA1 was core enriched in above seven gene sets involving zinc ion binding, arylesterase activity and one carbon metabolic process. Functional analysis of the candidate target genes obtained from the intersection of AS associated genes and Methazolamide target genes indicated that Methazolamide exerts therapeutic effects on AS mainly through inflammatory pathways which regulate the production of tumor necrosis factor, IL-6 and nitric oxide. PTGS2, ESR1, GSK3ß, JAK2, NOS2 and CA1 were selected as therapeutic targets of Methazolamide in AS. Molecular docking and molecular dynamics simulations were performed successfully. In addition, we innovatively obtained the intersection of Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and GSEA results, and found that 18 GO terms and 5 KEGG terms were indicated in the pharmacological mechanism of Methazolamide in AS, involving bone mineralization, angiogenesis, inflammation, and chemokine signaling pathways. Nevertheless, validation for these mechanisms is needed in vivo/vitro experiments.

Impact of Two Urethral Stent Types on the Complications After One-Stage Hypospadias Repair Using the Duckett Procedure: A retrospective cohort study.

PURPOSE: The purpose of this study was to evaluate whether the new nickel-titanium alloy stents are superior to traditional silicone stents in hypospadias repair surgery to prevent complications such as urinary fistula. METHODS: This retrospective cohort study included 576 patients with hypospadias who underwent the placement either with nickel-titanium alloy stents or traditional silicone stents after hypospadias surgery between March 2002 and August 2019. The patients were assigned into the nickel-titanium alloy stent group (group NTAS) and the silicone stent group (group SS). The primary outcome was assessed with the rate of urinary fistula occurrence at four weeks (stent removal time), and the secondary outcomes were decided on the rate of other complications such as urethral stricture, and urethral diverticulum, infection, etc. The occurrence of complications in both groups was compared and the important contributing factors of urinary fistula and urethral stricture were determined. RESULTS: Among 576 patients, 398 were assigned into group NTAS while 178 were into group SS. 35 patients in the group NTAS and 30 in the group SS developed urinary fistula with a ratio of 8.8% and 16.9%, respectively (p = 0.005). Subgroup analysis showed that the differences were mainly in preschool patients (≤ 6 years) (p = 0.004) and those with the penile type of hypospadias (p = 0.008). In addition, urethral stricture complicated five patients in the NTAS group and two in the SS group with a ratio of 1.3% and 1.1%, respectively (p = 1.000). Logistic regression showed that hypospadias type (p = 0.001) and stent type (p = 0.001) are the important risk factors for urethral fistula. CONCLUSIONS: Nickel-titanium alloy stents reduced the occurrence of urinary fistula complications after hypospadias repair in preschool patients, and can be optioned as a better choice for hypospadias surgery.

SULFORAPHANE ADMINISTRATION AFTER HEMORRHAGIC SHOCK/RESUSCITATION IN MICE REDUCES THE SECRETION OF INFLAMMATORY CYTOKINES AND INCREASES THE IMMUNOCOMPETENCE OF SPLENIC MACROPHAGES.

ABSTRACT: Objective : The purpose of this study was to investigate the immunomodulatory effects of sulforaphane (SFN), a nuclear factor erythroid 2-related factor (Nrf2) pathway activator, on splenic macrophages' immunocompetence after hemorrhagic shock/resuscitation (HS/R). Methods : Male C57/BL6 wild-type mice (n = 6 per group) were subjected to either pressure-controlled HS (MAP, 35-45 mm Hg) or a sham procedure surgery (without HS). After 90 minutes of HS, fluid resuscitation with withdrawn blood and 0.9% NaCl was performed. Sulforaphane (50 mg/kg of body weight) was applied intraperitoneally immediately after the resuscitation phase as well as 24 and 48 h thereafter, depending on group allocation. The mice were killed at 6, 24, and 72 h after resuscitation. After killing, spleens were harvested to perform Nrf2 immunofluorescence histology. Splenic macrophages were isolated and cultured to measure cytokine secretion in the cell culture supernatant. Furthermore, macrophages isolated after 24-hour resuscitation were treated with 100 ng/mL of bacterial LPS to measure immunocompetence. Matrix-assisted laser desorption/ionization mass spectrometry imaging was performed to verify the distribution of SFN in the spleen after intraperitoneal injection. Results : We showed that administered SFN reached the spleen within the first hour after administration. Furthermore, we identified that SFN increased splenic Nrf2 activation and decreased cytokine expression in splenic macrophages after HS/R. In addition, we showed that SFN exhibited splenic anti-inflammatory properties of macrophages in vitro (IL-6/IL-10-ratio of the HS/R group: 51.79 ± 9.99 [at 6 h] and 15.70 ± 3.35 [at 24 h] vs. HS/R + SFN group: 20.54 ± 5.35 [at 6 h] and 8.60 ± 2.37 [at 24 h], P < 0.05). Furthermore, SFN improved in vitro splenic macrophage immunocompetence after HS/R, as evidenced by the increased secretion of inflammatory cytokines in response to LPS stimulation in vitro . Conclusions : Our study shows that SFN can reduce inflammatory cytokines secreted by splenic macrophages after HS/R and increase their immunocompetence toward a more anti-inflammatory profile.

Quantitative analysis of both lacrimal glands in unilateral primary acquired nasolacrimal duct obstruction, based on three-dimensional fast spin echo-Cube-Flex.

OBJECTIVE: To investigate whether unilateral primary acquired nasolacrimal duct obstruction (PANDO) changes the volume and water fraction of both lacrimal glands, using three-dimensional fast spin echo (3D-FSE)-Cube-Flex images, and to identify whether the lacrimal gland is a target organ in this disease. METHODS: 3D-FSE-Cube-Flex images of both lacrimal glands in 25 healthy volunteers and 31 patients with unilateral PANDO were retrospectively reviewed. The differences in volume and water content in the lacrimal glands between the controls, non-PANDO side, and PANDO side groups were examined. Moreover, the associations between magnetic resonance imaging (MRI) parameters and disease duration were assessed with correlation analysis. RESULTS: The lacrimal gland volumes were not significantly different between the PANDO and non-PANDO side groups, compared to the control group (P = 0.484). However, the gland volumes tended to be increased bilaterally in patients with PANDO. In contrast, the gland water fractions in the PANDO and non-PANDO side groups were significantly higher than those in the control group (P = 0.009 and P = 0.014, respectively), and similar between the non-PANDO and PANDO side groups (P = 0.897). No correlation was found between the disease duration and the gland MRI parameters (volume and water fraction). CONCLUSIONS: Both lacrimal glands are affected by unilateral PANDO. A change in the water fraction of these glands appears to precede the change in volume and may be a sensitive early indicator.

Experience with flap repair after vulvar carcinoma resection: a retrospective observational study of 26 cases.

Background: A defect caused by the radical resection of vulvar cancer requires repair with flap transplantation or vulvoplasty. However, in clinical practice, the surgeons encounter difficulties while using a flap to repair the wound. Therefore, this study aimed to present a review of our practice of post-surgical defect reconstruction in cases using different skin flaps. Methods: An observational study was performed involving 26 patients with vulvar cancer who were admitted to Sun Yat-Sen Memorial Hospital between February 2015 and February 2020 for surgical and reconstructive procedures. The clinical data of these 26 patients were analyzed. All patients underwent radical resection of vulvar cancer, followed by post-surgical defect repair using random flap or axial flap transplantation (even for very complex defects). The clinical variables collected and the assessment of efficacy included survival of the flap, history of dysfunction of the recipient area, such as scar contracture, and satisfaction of the patient with the shape after external vaginal surgery. Results: Among the 26 cases in this study, all patients underwent 38 soft tissue reconstruction procedures for vulvar perineal defects during the study period. Squamous cell carcinoma was the most commonly diagnosed cancer (80.8%). The average size of the defect was 9.3×7 cm2. Rhomboid flaps were the most commonly used flaps for performing reconstruction in both the primary and recurrent groups. Poor wound healing was the most commonly discovered complication, which occurred in three of the 38 flaps (7.9%) used. Previous surgery or radiotherapy did not increase the rate of complications following successful reconstruction. Conclusions: Different skin flaps are effective premium options for post-surgical defect reconstruction, and the selective use of skin flaps for treating vulvar defects preserves the vulvar morphology and allows for relatively better functionality.

Time in range assessed by capillary blood glucose in relation to insulin sensitivity and ß-cell function in patients with type 2 diabetes mellitus: A cross-sectional study in China.

AIMS: This study investigated the association of capillary blood glucose (CBG)-assessed time in range (TIR) (3.9-10.0 mmol/L) with insulin sensitivity and islet ß-cell function. MATERIALS AND METHODS: We recruited 455 patients with type 2 diabetes mellitus. Seven-point glucose-profile data (pre- and 120 min post-main meals, bedtime) were collected over three consecutive days. Plasma glucose and serum insulin concentrations were measured at 0, 60, and 120 min after a 100 g standard steamed bread meal test. The homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index were computed to evaluate insulin resistance. The HOMA of ß-cell function (HOMA-ß) and the area under the curve between insulin and blood glucose (IAUC0-120 /GAUC0-120 ) were used to estimate ß-cell function. RESULTS: TIR was positively correlated with the 60 and 120 min insulin values, IAUC0-120 , the Matsuda index, HOMA-ß, and IAUC0-120 /GAUC0-120 (rs : 0.154, 0.129, 0.137, 0.194, 0.341, and 0.334, respectively; P < 0.05) but inversely correlated with HOMA-IR (rs : -0.239, P < 0.001). After adjusting for confounders, multinomial multiple logistic regression analysis revealed that the odds ratios (ORs) of achieving the target time in range (>70%) increased by 12% (95% confidence interval [CI]: 3-21%), 7% (95% CI: 1-14%), 10% (95% CI: 5-16%), and 45% (95% CI: 25-68%) for each 10 mIU/L increase in the 60 and 120 min insulin values, 10 unit increase in HOMA-ß, and unit increase in IAUC0-120 /GAUC0-120 , respectively (P < 0.05). Nevertheless, the OR decreased by 10% (95% CI: 1-18%) for each unit increase in HOMA-IR (P < 0.05). CONCLUSIONS: Insulin resistance and islet ß-cell function are related to capillary blood glucose-assessed TIR.

Clinical use of magnetic resonance imaging in buttock augmentation with silicone implants: a retrospective analysis.

Background: The objective of the current study was to retrospectively examine the morphological magnetic resonance imaging (MRI) characteristics of the gluteus maximus of buttock augmentation at levels of predetermined anatomic points. Methods: The present study was a retrospective cross-sectional study. Adult women who underwent high-quality MRI scanning at Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to January 2021 were included in this work. The transverse MRI data measured at the inferior point of the sacroiliac joint, just above the femoral head, and at the ischial tuberosity were collected and statistically analyzed. Results: Fifty-two cases (104 sides of female gluteus maximus) were included in the final analysis. The A point (surgery starting point) were 54.4±6.34 mm, 54.91±5.57 mm, and 73.91±5.57 mm away from the posterior midline at the level of inferior point of the sacroiliac joint, just above the femoral head, and at the ischial tuberosity, respectively. Accordingly, the thickness of the muscle at these locations was 16.0±4.17 mm, 23.4±4.40 mm, and 24.6±7.58 mm, respectively. The diameter of the implant did not exceed 14.18±1.22 cm. In addition, the gluteus maximus at the lowest point of the sacroiliac joint and above the femoral head exhibited an arc structure, which needs to be tilted to the deep plane during separation. Conclusions: Dissimilar from previous experience of blind dissection, the gluteus maximus muscle can be more scientifically and reasonably dissected using the indexes for gluteus augmentation supplied in this study.

Sulforaphane Exerts Beneficial Immunomodulatory Effects on Liver Tissue via a Nrf2 Pathway-Related Mechanism in a Murine Model of Hemorrhagic Shock and Resuscitation.

Our research explores the immunomodulatory effects of sulforaphane (SFN), a well-known nuclear factor erythroid 2-related factor 2 (Nrf2) pathway agonist, on the sterile inflammation of and ischemia-reperfusion injuries to the liver after hemorrhagic shock (HS) followed by resuscitation (R). Male C57/BL6 wild-type and transgenic ARE-luc mice were exposed to mean arterial pressure-controlled HS. Fluid resuscitation was performed after 90 min of HS, and SFN was administrated intraperitoneally after that. The animals were sacrificed at 6 h, 24 h, and 72 h after resuscitation, and their livers were extracted to perform H&E staining and myeloperoxidase (MPO) activity analysis. The Kupffer cells were isolated for cytokines profile measurements and Nrf2 immunofluorescence staining. Further, the ARE-luc mice were used to assess hepatic Nrf2 activity in vivo. We identified that SFN-activated Kupffer cells' Nrf2 pathway and modulated its cytokines expression, including TNF-α, MCP-1, KC/CXCL1, IL-6, and IL-10. Furthermore, SFN mitigated liver ischemia-reperfusion injury, as evidenced by the downregulation of the Suzuki score and the enhanced hepatic Nrf2 activity. The in vivo SFN treatment decreased neutrophils infiltration, as shown by the decreased MPO levels. Our study shows that SFN can decrease HS/R-induced hepatic ischemia-reperfusion injury and modulate the activity of Kupffer cells via an Nrf2-dependent pathway.

Sulforaphane-Dependent Up-Regulation of NRF2 Activity Alleviates Both Systemic Inflammatory Response and Lung Injury After Hemorrhagic Shock/Resuscitation in Mice.

ABSTRACT: Hemorrhagic shock/resuscitation (HS/R) is closely associated with overwhelming oxidative stress and systemic inflammation. As an effective activator of the nuclear factor-erythroid factor 2 related factor 2 (Nrf2) pathway, sulforaphane (SFN) exerts antioxidant and anti-inflammatory effects. We explored SFN's effects on alveolar macrophages (AMs), systemic inflammation, and pulmonary damage in an isolated murine HS/R model. Male C57/BL6 wild type and transgenic antioxidant response element (ARE)-luciferase (luc) mice (both n = 6 per group) were exposed to either pressure-controlled HS/R (mean arterial pressure 35-45 mm Hg for 90 min) or sham procedure (surgery without HS/R) or were sacrificed without intervention (control group). Fluid resuscitation was performed via the reinfusion of withdrawn blood and 0.9% saline. Sulforaphane or 0.9% saline (vehicle) was administrated intraperitoneally. Mice were sacrificed 6, 24, or 72 h after resuscitation. Bioluminescence imaging of ARE-luc mice was conducted to measure pulmonary Nrf2 activity. Plasma was collected to determine systemic cytokine levels. Alveolar macrophages were isolated before measuring cytokines in the supernatant and performing immunofluorescence staining, as well as Western blot for intracellular Nrf2. Histological damage was assessed via the acute lung injury score and wet/dry ratio.Hemorrhagic shock/resuscitation was associated with pulmonary Nrf2 activation. Sulforaphane enhanced pulmonary Nrf2 activity and the Nrf2 activation of AM, while it decreased lung damage. Sulforaphane exerted down-regulatory effects on AM-generated and systemic pro-inflammatory mediators, while it did not have such effects on IL-10.In conclusion, SFN beneficially enhances pulmonary Nrf2 activity and promotes Nrf2 accumulation in AMs' nuclei. This may exert not only local protective effects but also systemic effects via the down-regulation of pro-inflammatory cytokines. The administration of Nrf2 activator post-HS/R may represent an innovative treatment strategy.

Ear Reconstruction with the Combination of Expanded Skin Flap and Medpor Framework: 20 Years of Experience in a Single Center.

BACKGROUND: In ear reconstruction, the difficulty lies in reestablishing the ear's bionic form with adequate skin coverage and an appropriate framework. Skin expansion and a porous polyethylene (i.e., Medpor) framework are often used for ear reconstruction. However, a long-term review of the combined application of the expanded skin and Medpor framework has not been reported. This article reviews ear reconstruction combining these two factors over the past 20 years in the authors' center to summarize the surgical technique and analyze the postoperative results and complications. METHODS: A retrospective review was performed that included all patients who underwent ear reconstruction with expanded skin and Medpor framework in the authors' center between 1998 and 2018. RESULTS: A total of 68 patients with microtia who were admitted to the authors' center for surgical ear reconstruction were included, and 70 ears were reconstructed. Fifty-seven of the patients (83.82 percent) felt satisfied with their reconstructed ear, five patients (7.35 percent) were not satisfied with the reconstructed ear, and six patients (8.82 percent) had the frameworks removed. Fifteen patients (22.06 percent) developed complications, including framework exposure (13.24 percent), infection (4.41 percent), scar hypertrophy (4.41 percent), and hematoma (2.94 percent). CONCLUSIONS: Framework exposure limits the combined application of expanded skin flap and Medpor framework when reconstructing the ear without additional fascial interposition. Using a temporoparietal fascia or postauricular fascia flap during the operation is effective to decrease the exposure rate; however, this complication cannot be completely avoided. Using postauricular fascia and skin graft may lead to scar hypertrophy; thus, these techniques should be used with caution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Biomimetic Nanotheranostics Camouflaged with Cancer Cell Membranes Integrating Persistent Oxygen Supply and Homotypic Targeting for Hypoxic Tumor Elimination.

Treatment resistance of the tumors to photodynamic therapy (PDT) owing to O2 deficiency largely compromised the therapeutic efficacy, which could be addressed via modulating oxygen levels by using O2 self-enriched nanosystems. Here, we report on augmenting the O2-evolving strategy based on a biomimetic, catalytic nanovehicle (named as N/P@MCC), constructed by the catalase-immobilized hollow mesoporous nanospheres by enveloping a cancer cell membrane (CCM), which acts as an efficient nanocontainer to accommodate nitrogen-doped graphene quantum dots (N-GQDs) and protoporphyrin IX (PpIX). Inheriting the virtues of biomimetic CCM cloaking, the CCM-derived shell conferred N/P@MCC nanovehicles with highly specific self-recognition and homotypic targeting toward cancerous cells, ensuring tumor-specific accumulation and superior circulation durations. N-GQDs, for the first time, have been evidenced as a new dual-functional nanoagents with PTT and PDT capacities, enabling the generation of 1O2 for PDT and inducing local low-temperature hyperthermia for thermally ablating cancer cells and infrared thermal imaging (IRT). Leveraging the intrinsic catalytic features of catalase, such N/P@MCC nanovehicles effectively scavenged the excessive H2O2 to sustainably evolve oxygen for a synchronous O2 self-supply and hypoxia alleviation, with an additional benefit because the resulting O2 bubbles could function as an echo amplifier, leading to the sufficient echogenic reflectivity for ultrasound imaging. Concurrently, the elevated O2 reacted with N-GQDs and PpIX to elicit a maximally increased 1O2 output for augmented PDT. Significantly, the ultrasound imaging coupled with fluorescence imaging, IRT, performs a tumor-modulated trimodal bioimaging effect. Overall, this offers a paradigm to rationally explore O2 self-supply strategies focused on versatile nanotheranostics for hypoxic tumor elimination.

Incidence of microcarcinoma and non-microcarcinoma in ultrasound-found thyroid nodules.

BACKGROUNDS: The incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort. METHODS: We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations. RESULTS: Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1 % vs. 39.9 %, x2 = 355.69, p = 0.000), smaller size (17.5 ± 9.9 mm vs. 28.0 ± 12.5 mm, t = 23.876 p = 0.000), and higher TI-RADS score (5.5 ± 2.9 vs. 3.4 ± 3.3, t = 18.084, p = 0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2 %) nodules found by ultrasound vs. 68 (3.9 %) by palpation, x2 = 59.737, p = 0.000], and 88 (64.7 %) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3 % (48/136) vs. 16.2 % (11/68), x2 = 8.183, p = 0.004]. CONCLUSIONS: In view of the results observed in our research, malignant nodules were more common in nodules screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We suggest the recommendation against screening thyroid nodules by ultrasound needs to be re-evaluated.

EIF3H knockdown inhibits malignant melanoma through regulating cell proliferation, apoptosis and cell cycle.

Malignant melanoma (MM) causes 80% of skin cancer-related deaths and becomes the most lethal type of skin cancer. The molecular mechanism of MM is still not clear. This study aimed to reveal the relationship between MM and EIF3H. Clinical specimens were collected to preliminarily explore the role of EIF3H in MM. MM cell lines with EIF3H knockdown were constructed for investigating the effects of EIF3H on cell proliferation, apoptosis, cell cycle and cell motility. Mice xenograft model was constructed for verification in vivo. We found that EIF3H was obviously upregulated in MM tissues compared with normal skin tissues, which was correlated with tumor stage and risk of lymphatic metastasis. The in vitro results indicated that silencing EIF3H in MM cells could significantly suppress cell proliferation, promote cell apoptosis and induce cell cycle arrest. Moreover, EIF3H knockdown significantly restrained cell motility through regulating EMT-related proteins. The effects of EIF3H knockdown were also verified in mice xenograft model, which were represented by slower growth rate, smaller volume and lighter weight of tumors. Therefore, EIF3H was identified as a critical factor in the development and progression of MM which may be used as a novel therapeutic target in the treatment of MM.

Effect of interferon-α-2b and interleukin-2 combined with chemotherapy in metastatic melanoma.

BACKGROUND: To explore the efficacy and safety of interferon-α-2b and interleukin-2 combined with chemotherapy in treating patients with metastatic melanoma. METHODS: The patients with metastatic melanoma in control group (n=52) were treated with conventional DDAVC chemotherapy regimen, while those in combination group (n=52) received biotherapy with interferon-α-2b and interleukin-2 in addition to the chemotherapy in control group. At the end of the treatments, the serum immune function indicators, short-term efficacy and incidence of adverse reactions were compared between the two groups of patients, and patient's survival was followed up and recorded. RESULTS: At 1 week after treatment, it was found that the overall response rate in combination group was substantially higher than that in control group (P=0.027). Besides, according to the serologic test results at 1 week after the chemotherapy, T lymphocyte subset activity was enhanced in patients in combination group compared with that before chemotherapy, with no statistically significant difference (P>0.05), but it was notably weakened in control group in comparison with that before chemotherapy (P<0.05). Finally, it was discovered through the log-rank test that the overall survival (OS) rate in combination group was remarkably superior to that in control group (P=0.029), but there was no statistically significant difference in the progression-free survival (PFS) rate between the two groups (P=0.076). CONCLUSIONS: Compared with chemotherapy alone, interferon-α-2b and interleukin-2 combined with chemotherapy can raise the clinical short-term efficacy and long-term OS rate in the patients with metastatic melanoma and alleviate their toxic side reactions, with higher safety.