Quercetin Inhibits Neuronal Pyroptosis and Ferroptosis by Modulating Microglial M1/M2 Polarization in Atherosclerosis.

Atherosclerosis (AS) with iron and lipid overload and systemic inflammation is a risk factor for Alzheimer's disease. M1 macrophage/microglia participate in neuronal pyroptosis and recently have been reported to be the ferroptosis-resistant phenotype. Quercetin plays a prominent role in preventing and treating neuroinflammation, but the protective mechanism against neurodegeneration caused by iron deposition is poorly understood. ApoE-/- mice were fed a high-fat diet with or without quercetin treatment. The Morris water maze and novel object recognition tests were conducted to assess spatial learning and memory, and nonspatial recognition memory, respectively. Prussian blue and immunofluorescence staining were performed to assess the iron levels in the whole brain and in microglia, microglia polarization, and the degree of microglia/neuron ferroptosis. In vitro, we further explored the molecular biological alterations associated with microglial polarization, neuronal pyroptosis, and ferroptosis via Western blot, flow cytometry, CCK8, LDH, propidium iodide, and coculture system. We found that quercetin improved brain lesions and spatial learning and memory in AS mice. Iron deposition in the whole brain or microglia was reversed by the quercetin treatment. In the AS group, the colocalization of iNOS with Iba1 was increased, which was reversed by quercetin. However, the colocalization of iNOS with PTGS2/TfR was not increased in the AS group, suggesting a character resisting ferroptosis. Quercetin induced the expression of Arg-1 and decreased the colocalizations of Arg-1 with PTGS2/TfR. In vitro, ox-LDL combined with ferric ammonium citrate treatment (OF) significantly shifted the microglial M1/M2 phenotype balance and increased the levels of free iron, ROS, and lipid peroxides, which was reversed by quercetin. M1 phenotype induced by OF caused neuronal pyroptosis and was promoted to ferroptosis by L-NIL treatment, which contributed to neuronal ferroptosis as well. However, quercetin induced the M1 to M2 phenotype and inhibited M2 macrophages/microglia and neuron pyroptosis or ferroptosis. In summary, quercetin alleviated neuroinflammation by inducing the M1 to M2 phenotype to inhibit neuronal pyroptosis and protected neurons from ferroptosis, which may provide a new idea for neuroinflammation prevention and treatment.

Ethanol-Induced Hepatic Ferroptosis Is Mediated by PERK-Dependent MAMs Formation: Preventive Role of Quercetin.

SCOPE: Iron deposition is frequently observed in alcoholic liver disease (ALD), which indicates a potential role of ferroptosis in its development. This study aims to explore the effects of quercetin on ferroptosis in ALD and elucidates the underlying mechanism involving the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) mediated by protein kinase RNA-like endoplasmic reticulum kinase (PERK). METHODS AND RESULTS: C57BL/6J mice are fed either a regular or an ethanol-containing liquid diet (with 28% energy form ethanol) with or without quercetin supplementation (100 mg kg-1 BW) for 12 weeks. Ethanol feeding or treatment induced ferroptosis in mice and AML12 cells, which is associated with increased MAMs formation and PERK expression within MAMs. Quercetin attenuates these changes and protects against ethanol-induced liver injury. The antiferroptotic effect of quercetin is abolished by ferroptosis inducers, but mimicked by ferroptosis inhibitors and PERK knockdown. The study demonstrates that PERK structure, rather than its kinase activity (transfected with the K618A site mutation that inhibits kinase activity-ΔK plasmid or protein C terminal knockout-ΔC plasmid of PERK), mediates the enhanced MAMs formation and ferroptosis during the ethanol exposure. CONCLUSION: Quercetin ameliorates ethanol-induced liver injury by inhibiting ferroptosis via modulating PERK-dependent MAMs formation.

The Risk Factors and Clinical Outcomes in Hepatitis B Seropositive and Seronegative Renal Transplant Patients.

INTRODUCTION: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients. METHODS: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. RESULTS: We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31-27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01-9.74; p = 0.047). CONCLUSION: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.

Excess iron accumulation mediated senescence in diabetic kidney injury.

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high-fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, ß-galactosidase staining, 5-ethynyl-2-deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG-treated cells caused increased LDH release from normal cells. Iron metabolism-related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 µM) upregulated gamma-H2A.X variant histone and increased the senescence markers in HG-treated cells. The treatment of deferoxamine (0.5 µM) had the opposite effect. Compared to the non-DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co-localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.

Bibliometric analysis of myelin imaging studies of patients with multiple sclerosis (2000-2022).

Background: Multiple sclerosis (MS) is a condition that can impact the central nervous system (CNS) and cause damage to the myelin, which is responsible for facilitating the normal transmission of electrical impulses along the nerves. We performed a bibliometric analysis of the scientific publications on myelin imaging in MS to reveal the development trends in this field and to evaluate research trends in myelin imaging in MS. Methods: The Web of Science Core Collection was searched for articles related to myelin imaging in MS published between January 2000 and December 2022. CiteSpace, VOSviewer, and R language were used to evaluate and visualize contributions by and co-occurrence relationships among countries and institutions, authors, journals, citations, keywords, and so on. Results: A total of 1,639 articles addressed the topic of myelin imaging in MS. The United States had the largest number of annual publications. The University of London was the institution with the highest number of publications (n=118) and citations (n=9,885). The top 3 productive authors were all from the University of British Columbia in Canada. An article published by Mackay et al. in 1994 had the most citations (n=272). Neuroimage [impact factor (IF) =7.40, Journal Citation Reports quartile 1 (Q1)] was the most productive journal in terms of the number of articles relating to myelin imaging in MS (n=149). In recent years, myelin water imaging, synthetic magnetic resonance imaging (SyMRI), inhomogeneous magnetization, positron emission tomography (PET) imaging, and aquaporin-4 (AQP4) have been researched hotspots of myelin imaging in MS. Conclusions: With advancements in the pathophysiological research on myelin changes in MS, myelin imaging is playing an important role in the diagnosis and treatment of MS. In addition, the use of new sequences of myelin imaging to distinguish MS from other inflammatory demyelinating diseases is a future development trend in this field.

Lung adenocarcinoma with brain metastasis detected dual fusion of LOC399815-ALK and ALK-EML4 in combined treatment of Alectinib and CyberKnife: A case report.

INTRODUCTION: The anaplastic lymphoma kinase (ALK) gene fusion occurs in approximately 3% to 7% of nonsmall cell lung cancer (NSCLC), in which occurs approximately 23% to 31% of brain metastasis patients in poor prognosis. ALK tyrosine kinase inhibitors have shown efficacy in treating ALK-positive (ALK+) NSCLC. More than 90 distinct subtypes of ALK fusions have been identified through sequencing technique and would lead to significant differences in clinical efficacy, it is necessary to guide clinical treatment effectively by gene detection. PATIENT CONCERNS: A 56-year-old nonsmoking female admitted to hospital due to cough, expectoration, and chest pain. Chest computed tomography revealed a space-occupying lesion in the upper left lobe (5.0 cm × 2.4 cm × 2.9 cm), multiple enlarged lymph nodes in mediastinum 3A and 5 (largest size 1.5 cm × 1.4 cm), and evidence of thoracic vertebral metastasis, brain magnetic resonance imaging also showed brain metastasis. DIAGNOSES: Lung adenocarcinoma with brain metastasis. INTERVENTIONS: The patient initially received conventional first-line chemotherapy, which led to a deteriorated condition. Blood-base liquid biopsy by next-generation sequencing resulted in double ALK fusions, in which with a neo-partner of lncRNA (LOC399815-ALK). Following subsequent treatment with Alectinib and stereotactic radiotherapy (CyberKnife) was subsequently employed to manage the brain metastatic lesions, resulting in a substantial decreased in both the number and size of tumor lesions. OUTCOMES: The patient's response to therapy efficacy resulted in a substantial decreased in both the number and size of tumor lesions that assessed comprehensively evaluated through computed tomography imaging and ctDNA sequencing. Patient's condition has been under control for over 29 months. CONCLUSION: Liquid biopsy may reveal the rare fusion forms of ALK, precisely guiding personalized treatment, and providing a reference method for longitudinal monitoring and efficacy evaluation of ALK-tyrosine kinase inhibitors in NSCLC patients.

Associations of Combined Lifestyle Factors with MAFLD and the Specific Subtypes in Middle-Aged and Elderly Adults: The Dongfeng-Tongji Cohort Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the crucial pathogenesis for intra-hepatic and extra-hepatic diseases, especially in elderly adults. Lifestyle management may be a modifiable cost-effective measure for MAFLD prevention, but the evidence is limited. A total of 23,408 middle-aged and elderly individuals were included in a longitudinal study from 2008 to 2018. Combined lifestyle scores (range 0-6) were evaluated by BMI, smoking, drinking, diet, physical activity, and sleep. Logistic regression models were used to calculate ORs for the risks of MAFLD and specific subtypes. The mean age of participants was 61.7 years, and 44.5% were men. Compared with poor lifestyle (scores 0-2), ORs (95% CIs) of the ideal lifestyle (scores 5-6) were 0.62 (0.57-0.68) for MAFLD, 0.31 (0.28-0.34) for MAFLD with excess weight and obesity, 0.97 (0.75-1.26) for MAFLD with diabetes, and 0.56 (0.51-0.62) for MAFLD with metabolic dysregulation. Additionally, lifestyle improvement was associated with lower risks of MAFLD (OR, 0.76; 95% CI, 0.68-0.86), MAFLD with excess weight and obesity (OR, 0.72; 95% CI, 0.63-0.81), MAFLD with diabetes (OR, 0.74; 95% CI, 0.54-1.02) and MAFLD with metabolic dysregulation (OR, 0.49; 95% CI, 0.43-0.55), respectively. Our findings suggest that adherence to a combined healthy lifestyle was associated with lower risks of MAFLD, particularly in excess weight/obese individuals or those with metabolic dysregulation.

Therapeutic Effects of Perilla Phenols in Oral Squamous Cell Carcinoma.

The herbal medicine perilla leaf extract (PLE) exhibits various pharmacological properties. We showed that PLE inhibits the viability of oral squamous cell carcinoma (OSCC) cells. HPLC analysis revealed that caffeic acid (CA) and rosmarinic acid (RA) are the two main phenols in PLE, and reduced OSCC cell viability in a dose-dependent manner. The optimal CA/RA combination ratio was 1:2 at concentrations of 300-500 µM but had no synergistic inhibitory effect on the viability of OSCC cells. CA, RA, or their combination effectively suppressed interleukin (IL)-1ß secretion by OSCC OC3 cells. Long-term treatment with CA and CA/RA mixtures, respectively, induced EGFR activation, which might cause OC3 cells to become EGFR-dependent and consequently increased the sensitivity of OC3 cells to a low dose (5 µM) of the EGFR tyrosine kinase inhibitor gefitinib. Chronic treatment with CA, RA, or their combination exhibited an inhibitory effect more potent than that of low-dose (1 µM) cisplatin on the colony formation ability of OSCC cells; this may be attributed to the induction of apoptosis by these treatments. These findings suggest that perilla phenols, particularly CA and RA, can be used as adjuvant therapies to improve the efficacy of chemotherapy and EGFR-targeted therapy in OSCC.

A novel near-infrared EGFR targeting probe for metastatic lymph node imaging in preclinical mouse models.

For the treatment of patients with oral squamous cell carcinoma (OSCC), the imaging of cervical lymph nodes and the evaluation of metastastic progression are of great significance. In recent years, the development of new non-radioactive lymph node tracers has been an area of intense research. Here, we report the synthesis, good biocompatibility, and in vivo evaluation of a new small molecule near-infrared (NIR) fluorescence probe by the conjugation of Lapatinib to S0456 (LP-S). We show that like Lapatinib, LP-S binds to the epidermal growth factor receptor (EGFR) resulting in high quality fluorescence imaging of metastatic lymph nodes in OSCC mouse models. After local injection of LP-S into the tumor, the lymphatic drainage pathway and lymph nodes can be clearly identified by NIR fluorescence imaging. Further, the LP-S probe shows higher contrast and longer retention in metastatic lymph nodes, allowing them to be differentiated from normal lymph nodes, and affording a new choice for fluorescence-guided surgery. Scheme. Chemical synthesis and application of EGFR targeting probe LP-S for imaging of metastatic lymph nodes (mLNs) in OSCC.

Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease.

Purpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.

Four indices on Gd-EOB-DTPA-enhanced MRI can estimate liver functional reserve compared to ICG-R15: A systematic review and meta-analysis.

AIMS: To evaluate the value of four indices of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance as a potential imaging marker of liver functional reserve. METHODS: PubMed/Medline, Embase, Cochrane Library, and Web of Science were searched for studies concerning the relationship between Gd-EOB-DTPA-enhanced MRI and liver functional reserve estimated by ICG-R15, Pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated, Meanwhile, Sensitivity and subgroup analyses were performed along with Egger's test for the estimation of publication bias and potential heterogeneity. RESULTS: 14 publications with 1285 patients were included. The pooled r between relative liver enhancement (RLE), reduction rate of T1 relaxation time of the liver (rrT1), liver-to-spleen ratio (LSR), liver-to-muscle ratio (LMR), and ICG-R15 were -0.49 (95% CI, -0.56 to -0.41, p < 0.05), -0.47 (95% CI, -0.57 to -0.36, p < 0.05), -0.45 (95% CI, -0.55 to -0.34, p < 0.05), -0.50 (95% CI, -0.61 to -0.38, p < 0.05). moderate heterogeneity was observed between studies on rrT1, LSR, LMR, and ICG-R15 (p ≤ 0.05), but no significant heterogeneity was observed between RLE and ICG-R15. Further analysis shows that there was a notable heterogeneity between subgroup analysis of LSR and ICG-R15 stratified by years of publication, as well as rrT1 and LMR stratified by total patients and study design, the distribution funnel plots and the results of Egger's test showed no evidence of publication bias. CONCLUSIONS: RLE, LSR, LMR, and rrT1 all correlated significantly with ICG-R15-estimated hepatic functional reserve. The four indices represent a promising imaging biomarker in the prediction of liver functional reserve.

Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome.

Background: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) share various similarities in clinical symptoms, pathogenesis, and treatment. UC concurrent IBS tends toward more severe symptoms and worse prognosis, and promising feasible therapies for the overlapping symptoms remains a challenge. Rhubarb peony decoction (RPD) is a well-known traditional Chinese medicine that has been widely applied in treating UC. RPD may exert extensive therapeutic effects on both IBS and UC. However, the common mechanism of its treatment remains unclear. We aimed to assess the potential pharmacological mechanism of RPD in the treatment of overlapping IBS and UC. Methods: The active components and targets of RPD were retrieved from ETCM, TCMSP, BATMAN-TCM, and TCM databases. The disease targets were screened by searching the DrugBank, OMIM, TTD, and PharmGKB databases. PPI network analysis was performed and visualized via the STRING platform and Cytoscape software. GO and KEGG enrichment analyses of the hub genes of RPD were predicted to elucidate the potential molecular mechanism. Subsequently, molecular docking was carried out to verify the combination of active compounds with core targets. Results: By integrating all targets of RPD and disease, a total of 31 bioactive ingredients were identified including quercetin, kaempferol, aloe-emodin, beta-sitosterol, and (+)-catechin, etc. JUN, TP53, MAPK1, RELA, MYC, and ESR1 were explored as potential therapeutic targets among 126 common drug-disease-related targets. They were enriched in the AGE-RAGE signaling pathway in diabetic complications, as well as the NF-kappa B signaling pathway and MAPK signaling pathway. Additionally, some active ingredients were identified as candidates for binding to the hub targets via molecular docking, further suggesting their anti-inflammatory and antioxidative properties. Conclusion: RPD may exert the overall treatment effect for UC and IBS overlap syndrome via the biological mechanism of "multi-ingredients, multi-targets, and multi-pathways" on inflammation, oxidative stress, immune, oncogenicity, and gut microbiota dysbiosis.

Radiofrequency Ablation of Unifocal Papillary Thyroid Microcarcinoma With BRAF V600E Mutation.

CONTEXT: To date there is no study on the feasibility of radiofrequency ablation (RFA) for papillary thyroid microcarcinomas (PTMCs) with BRAF V600E mutation. OBJECTIVE: This study was designed to evaluate the efficiency, safety, and prognosis of ultrasound (US)-guided percutaneous RFA for unifocal PTMCs with BRAF V600E mutation. MATERIALS AND METHODS: Sixty patients with 60 unifocal BRAF V600E mutation-positive PTMCs who received US-guided RFA between January 2020 and December 2021 were retrospectively analyzed. The mean maximum PTMC tumor diameter was 5.8 ± 1.7 mm (range, 2.5-10.0 mm). All PTMCs were pathologically confirmed by fine needle aspiration or core needle biopsy, and BRAF V600E mutation was confirmed to be positive by real-time fluorescent quantitative polymerase chain reaction. Contrast-enhanced ultrasound (CEUS) was performed immediately after RFA to evaluate whether PTMCs were extendedly ablated. Ultrasound was performed 1, 3, 6, and 12 months after RFA and every 6 months thereafter to evaluate the changes in the ablation zone, local recurrence, and cervical lymph node metastasis (LNM). The complications were recorded and evaluated. RESULTS: Extended ablation was achieved in all enrolled patients. The ablation zone sizes increased immediately after RFA compared with those of tumors before treatment. One month later, the ablation zone sizes were smaller than immediately after RFA. At the last follow-up assessment, 42 nodules (70.0%) completely disappeared and the ablation zones of 18 nodules (30.0%) showed fissure-like changes. No local recurrence or cervical LNM was detected. Voice change (1.7%) was the only major complication. CONCLUSION: RFA is effective and safe in treating unifocal PTMCs with BRAF V600E mutation, especially when surgery is not feasible or refused by patients who are unwilling to continue active surveillance.

Application of Auricular Cartilage Scaffold Combined With L-Shaped Prosthesis in Asian Rhinoplasty.

Rhinoplasty is a common surgical procedure in medical cosmetology. From patients with saddle nose deformity to beauty seekers with low and short noses, this surgery is mainly sought to improve the nose's appearance. To investigate the effect of modified auricular cartilage scaffold combined with L-shaped prosthesis in rhinoplasty. This retrospective study included 54 patients who underwent auricular cartilage augmentation rhinoplasty with L-shaped implants in our hospital from July 2018 to July 2021. The function of nasal ventilation and olfaction was inspected. As a result, the degree of nasal tip protrusion and the changes in the superior lip angle of columella were improved. The patients' satisfaction was measured a year after the surgery. Patients who underwent auricular cartilage augmentation rhinoplasty with L-shaped prosthesis were satisfied with the surgery outcomes. Using a protective auricular cartilage scaffold combined with an L-shaped implant for augmentation rhinoplasty reduced the shortage of the application and reinforced the stability of the auricular cartilage augmentation rhinoplasty. At >12 months follow-up, there were no serious adverse effects on nasal ventilation and olfactory function in any of the patients. The presented method made full use of auricular cartilage so that it reduced the harvest of the cartilage. Besides, it achieved the remarkable lift of the nose tip, thus simulating the appearance of costal cartilage rhinoplasty. Furthermore, the risk of implant exposure was efficiently reduced, making it worthy of clinical application.

Application of Dual "Kite" Myomucosal Flaps for the Repair of Medium Lip Defects.

OBJECTIVE: To investigate the application of dual "kite" myomucosal flaps (subcutaneous pedicle advancement flap) for the repair of medium lip defects (one-third to one-half lip width). METHODS: Dual kite myomucosal flaps were designed in the adjacent area of the defect in 17 patients with medium lip defect with the principle of using homogenous tissue as far as possible without affecting local anatomical units. RESULTS: The follow-up time was 3 to 24 months; 16 patients showed primary wound healing, and 1 patient showed prolonged healing. The blood supply of the myomucosal flaps were reliable. The myomucosal flaps were smooth, with no proliferation of scars, and the local appearance was good. CONCLUSION: The dual kite myomucosal flaps provide a reliable method for repairing medium lip defects, decreasing the need for additional excision of normal skin tissue, and reducing skin scar.

Application of External Nasal Skin Stretching in Asian Rhinoplasty.

ABSTRACT: Asian nasal characteristics include a low dorsum, short nose, and thick skin envelope, usually requiring lengthening and elevating the nose during rhinoplasty ( Facial Plast Surg Clin North Am 2007;15(3):293-307, v). The increase in rhinoplasty popularity has resulted in a greater prevalence of complications. In a severely short and contracted nose, an extensively scarred or contracted soft tissue envelope results in weak laxity and extensibility of the nasal skin. For these patients, the essential component of rhinoplasty is to improve skin texture and obtain a sufficient nasal skin soft tissue envelope. Tissue expanders have previously been utilized to expand nasal skin and soft tissue ( Plast Reconstr Surg 2006;118(6):1447-1452; Facial Plast Surg 2019;35(1):68-72). However, nasal anatomical characteristics have limited the clinical application of tissue expanders. This article introduces a simple, noninvasive, and easily adopted method of external nasal skin stretching, which was first proposed by the senior author. This approach has been accepted by rhinoplasty surgeons in China and widely used in clinic. The approach can improve skin laxity, yield extra nasal soft tissue, and create adequate soft tissue coverage of the reconstructed nasal framework to reduce the difficulty of surgery with a reliable clinical effect.

Epidemiological Investigation of Facial Soft Tissue Injury in Chinese Preschool Children.

OBJECTIVE: The aim of this study was to analyze the epidemiological characteristics of pediatric facial soft tissue injuries of Chinese preschool-aged children in Hangzhou Plastic Surgery Hospital. METHODS: Medical records of preschool-aged children's facial injuries, 6 years and younger, from January 2017 to December 2019 were collected. Sex; age; time of injury; length of stay; causes of injury; location, type, length, and depth of wound; anesthesia methods; and treatment and evaluation of postoperative scars were analyzed. RESULTS: There were 10,862 cases (male, 6780 cases; female, 4082 cases) in the group. The ratio of male to female was 1.66:1. Mean age was 3.4 (±1.6) years; the youngest was 1 month old. The time of injury occurred frequently between 9:00 and 13:00 and 16:00 to 21:00, with the most common incident time being between 19:00 and 20:00. Collision injury was the main cause of injury (9822 [90.43%]). The most frequently injured area was the forehead (4874 [44.87%]). The main form of injury was laceration wound (9721 [89.45%]). The depth of injuries was mainly middle layer (adipose or muscular layer) (6299 [57.99%]). The length of injuries was 1.7 (±0.9) cm, ranging from 0.2 to 10.5 cm. Furthermore, 9110 cases were repaired by plastic surgeries and 1 or more antiscar measures. After 6-month to 2-year follow-up, 9 cases of animal scratch or bite, lip penetrating wound, or bumping teeth were infected and 26 cases had scar hyperplasia. The others achieved satisfactory results, and the scars were not obvious. CONCLUSION: Preschool-aged children's facial injuries have predictable patterns of occurrence, and targeted preventive measures can reduce the incidence rates. After facial injury, children should present for timely plastic surgery treatment and accept combined antiscarring measures to minimize postoperative scarring.

Iron-frataxin involved in the protective effect of quercetin against alcohol-induced liver mitochondrial dysfunction.

Emerging evidence supports the beneficial effect of quercetin on liver mitochondrial disorders. However, the molecular mechanism by which quercetin protects mitochondria is limited, especially in alcoholic liver disease. In this study, C57BL/6N mice were fed with Lieber De Carli liquid diet (28% ethanol-derived calories) for 12 weeks plus a single binge ethanol and intervened with quercetin (100 mg/kg.bw). Moreover, HepG2CYP2E1+/+ were stimulated with ethanol (100 mM) and quercetin (50 µM) to investigate the effects of mitochondrial protein frataxin. The results indicated that quercetin alleviated alcohol-induced histopathological changes and mitochondrial functional disorders in mice livers. Consistent with increased PINK1, Parkin, Bnip3 and LC3II as well as decreased p62, TOM20 and VDAC1 expression, the inhibition of mitophagy by ethanol was blocked by quercetin. Additionally, quercetin improved the imbalance of iron metabolism-related proteins expression in alcohol-fed mice livers. Compared with ethanol-treated Lv-empty HepG2CYP2E1+/+ cells, frataxin deficiency further exacerbated the inhibition of mitochondrial function. Conversely, restoration of frataxin expression ameliorated the effect of ethanol. Furthermore, frataxin deficiency reduced the protective effects of quercetin on mitochondria disordered by ethanol. Attentively, ferric ammonium citrate (FAC) and deferiprone decreased or increased frataxin expression in HepG2CYP2E1+/+, respectively. Notably, we further found FAC reversed the increasing effect of quercetin on frataxin expression. Ultimately, silencing NCOA4 attenuated the inhibition of quercetin on LDH release and mitochondrial membrane potential increase, and similar results were observed by adding FAC. Collectively, these findings demonstrated quercetin increased frataxin expression through regulating iron level, thereby mitigating ethanol-induced mitochondrial dysfunction.

Cancer-associated fibroblast-targeted nanodrugs reshape colorectal tumor microenvironments to suppress tumor proliferation, metastasis and improve drug penetration.

Cancer-associated fibroblasts (CAFs) produce a critical tumor-promoting effect by cellular crosstalk with cancer cells and remodel the extracellular matrix (ECM) to form a protective physical barrier. The simple elimination of CAFs is not sufficient to govern the CAF-shaped aggressive tumor microenvironment (TME) because of the complexity of tumors. Herein, a CAF-targeted poly (lactic-co-glycolic acid) (PLGA) nanoemulsion is tailored to simultaneously deliver doxorubicin (DOX) and small interfering RNA (siRNA) targeting hepatocyte growth factor (HGF) for the combination of chemotherapy and gene therapy. The nanoemulsion (apt-Si/DNPs) shows a high specificity towards CAFs due to the aptamer modification and efficiently induces the apoptosis of CAFs, thus decreasing ECM deposition in the TME. Importantly, the delivered siRNA reduces the expression of the HGF in the remaining CAFs, which overcomes chemotherapy-induced upregulation of HGF mRNA and prevents the reproduction of CAFs through the autocrine HGF closed-loop. Owing to these synergetic effects, tumor proliferation, migration and invasion are prominently inhibited and tumor permeability is improved significantly. Overall, these results emphasize the potential of CAF-targeted combination treatments to inhibit tumor progression and metastasis, as well as overcome therapeutic resistance.

FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study.

No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0-14), intermediate risk (IR 15-17), and high risk (HR 18-28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.