Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To investigate the effect of progression of disease within 24 months(POD24)on overall survival(OS)in patients with mantle cell lymphoma(MCL),and compare the clinical characteristics between POD24 and non-POD24 patients.Methods:A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020.According to the occurrence of POD24,the patients were grouped for prognostic evaluation and clinical characteristics comparison.Results:Univariate Cox regression analysis showed that POD24,PLT,albumin,MIPI score,ECOG PS score,LDH were the factors influencing OS in newly diagnosed MCL patients(all P＜0.05).The results of multivariate Cox regression analysis showed that POD24[HR=16.797(95％CI:3.671-76.861),P＜0.001],albumin＜40 g/L[HR=3.238(95％CI:1.095-9.572),P=0.034]and ECOG PS score≥2[HR=4.005(95％CI:1.033-15.521),P=0.045]were independent risk factors influencing OS in MCL patients.The incidence of PLT＜100 × 109/L(33.3％vs 5.9％,P=0.033)and ECOG PS score≥2(45.5％vs 5.9％,P=0.040)were significantly higher in POD24 patients than those in non-POD24 patients.Conclusion:POD24 is an independent poor prognostic factor affecting the OS of MCL patients,and the patients with PLT＜100 × 109/L and ECOG PS score ≥2 at diagnosis have a higher probability of POD24.

Objective:To investigate the effect of endothelial activation and stress index(EASIX)on the prognosis of patients with angioimmunoblastic T-cell lymphoma(AITL)and peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS),and to compare the clinical characteristics of patients in the low EASIX and high EASIX groups.Methods:The clinical data of 59 newly diagnosed AITL and PTCL-NOS patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to September 2021 were retrospectively analyzed.The optimal cut-off value of EASIX was determined by receiver operating characteristic(ROC)curve;The chi-square test was used to analyze the correlation between EASIX and clinical features of patients with AITL and PTCL-NOS;The Kaplan-Meier survival curve was used to analyze the overall survival(OS)and progression-free survival(PFS)of the patients;Univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:The optimal cut-off value of EASIX was 0.95,based on which the patients were divided into a low EASIX(＜0.95)group and a high EASIX(≥ 0.95)group.Compared with the low EASIX group,the high EASIX group had a higher proportion of patients with advanced Ann Arbor stage,higher risk according to IPI,elevated LDH,hypoproteinemia,anemia,B symptoms,extranodal involvement,and bone marrow involvement.Survival analysis showed that the OS and PFS of patients in the high EASIX group were significantly shorter than those in the lower EASIX group(P＜0.001).The multivariate analysis showed that EASIX was an independent risk factor for OS[HR=7.217(95％CI:1.959-26.587),P=0.003]and PFS[HR=2.718(95％CI:1.032-7.161),P=0.043]of PTCL patients.Conclusion:High EASIX in newly diagnosed patients with AITL and PTCL-NOS suggests a poor prognosis,and high EASIX is a risk factor affecting prognosis of the patients.

This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.

Objectives:To explore the risk factors of major adverse cardiovascular events (MACEs) in immune checkpoint inhibitor (ICI) related myocarditis and establish a predictive model.Methods:This was a retrospective case-control study. Tumor patients diagnosed with ICI related myocarditis in the First Affiliated Hospital of Guangzhou Medical University from May 2019 to August 2023 were selected and divided into non-MACE group and MACE group based on whether MACE occurred. Clinical and imaging data of the two groups were collected. Univariate and multivariate logistic regression models were used to analyze the risk factors for MACE in patients with ICI related myocarditis. According to the results of multivariate logistic regression analysis, R 4.1.0 software was used to construct the MACE risk prediction model for these patients and draw a nomogram. The receiver operating characteristic curve was used to evaluate the prediction ability of the prediction model.Results:A total of 35 patients with ICI related myocarditis, aged (63.9±8.2) years, were included, including 28 males (80%). There were 18 patients in the non-MACE group and 17 patients in the MACE group. Multivariate logistic regression analysis showed that elevated neutrophil to lymphocyte ratio ( OR=1.115, 95% CI 1.007-1.235, P=0.036) and ST-T segment changes ( OR=24.942, 95% CI 1.239-502.194, P=0.036) were risk factors for MACE in patients with ICI related myocarditis. The receiver operating characteristic curve indicated that the area under the curve of the prediction model was 0.967 (95% CI 0.916-1.000, P<0.001), with a sensitivity of 88.2% and specificity of 100%, demonstrating good predictive ability. Conclusion:Elevated neutrophil to lymphocyte ratio and ST-T segment change are independent risk factors for MACE in patients with ICI related myocarditis. Risk prediction model based on the above two indicators can assist in the early identification and individualized intervention of ICI related myocarditis patients.