Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Non-functioning pituitary adenomas(NFPAs)are relatively common.Apart from hyperprolactinemia caused by pituitary compression,they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects.Previously considered a uniform entity,NFPAs are actually a highly heterogeneous group of tumors,including aggressive subtypes like silent corticotroph adenomas(SCA)and null cell adenomas.The 2022 WHO new classification of pituitary tumors employs transcription factors[e.g.,pituitary-specific transcription factor 1(PIT-1),T-box transcription factor 19(TBX19,also known as TPIT),steroidogenic factor 1(SF-1)]for detailed categorization,allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages,including silent gonadotroph adenomas,SCA,and plurihormonal PIT-1-positive adenomas.This helps identify highly invasive subtypes with high recurrence risk,guiding clinical diagnosis and treatment,prognostic assessment,and individualized management.The new classification also provides a theoretical basis for targeted therapies of NFPAs(e.g.,somatostatin analogs and temozolomide).This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications,aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis,treatment,and prognostic assessment.

BACKGROUND:Ankle fracture complicated with deltoid ligament injury is clinically common,and one stage repair of deltoid ligament with internal fracture fixation has gradually become a main therapeutic method,which can significantly reduce the long-term complications of ankle joint.In recent years,new progress has been made in anatomical structure characteristics and dynamic biomechanical research of deltoid ligament,thus greatly improving repairing techniques for injury in the deep layer of deltoid ligament,but there are still some controversies.OBJECTIVE:To explore the clinical efficacy of suture anchor and medial malleolus repair in the treatment of ankle joint fractures with the deep layer of deltoid ligament.METHODS:A total of 56 patients with ankle joint fractures and complete fracture of the deep and superficial layer of deltoid ligament treated in Affiliated Haikou Hospital,Xiangya School of Medicine,Central South University from January 2017 to January 2022 were selected,and they were divided into two groups according to different treatment methods in repairing the deep layer of deltoid ligament with suture anchor:suture anchor repair group(n=32)and medial malleolus repair group(n=24).The medial clear space of ankle joint and American Orthopedic Foot and Ankle Society Score of patients in the two groups were evaluated before and after operative treatment.RESULTS AND CONCLUSION:(1)All the 56 patients finished the surgery smoothly and were followed up for more than 12 months after operation.Their ankle fracture healed,and the time for fracture healing was 8-12 weeks,with a mean of 10.5 weeks.(2)The medial clear space of ankle joint in the two groups 12 months after operation was remarkably narrower than that before operation,and the difference was statistically significant(P＜0.001).The medial clear space of ankle joint in the two groups maintained a normal range 12 months after operation,and there was no statistically significant difference between the two groups(P＞0.05).(3)The AOFAS scale of patients in the two groups 6 and 12 months after operation was obviously bigger than that before operation(P＜0.001),but there was no statistically significant difference in the American Orthopedic Foot and Ankle Society Score of patients between the two groups at corresponding time points(P＞0.05).(4)It is concluded that both suture anchor and medial malleolus repair in the treatment of injury in the deep layer of deltoid ligament can recover the medial clear space of ankle joint,effectively keep the stability of ankle,and thus achieve good clinical efficacy.

Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis,synovial cell proliferation,neo-vascularization,and bone and cartilage destruction.Its pathogenesis is complex and has not yet been fully elucidated.A variety of cells,cytokines and signaling pathways are involved in the pathogenesis of RA.Hypoxia-inducing factor(HIF)and oxygen-sensing signaling pathway(PHD-HIF-VHL)are closely related to the occurrence and development of RA,and play an important role in syno-vial cell proliferation,inflammatory response and cartilage destruction.In this study,the research progress of oxygen sensing signaling pathway in RA was described from the aspects of the mechanism of oxygen sensing signaling pathway and its involvement in the patho-genesis of RA,in order to provide ideas and theoretical basis for the research of anti-RA drugs by targeting important molecules of oxy-gen sensing signaling pathway.

Purpose To explore the clinical and pathological features,differential diagnosis,treatment methods and prognosis of urachal adenocarcinoma.Methods Nineteen cases of urachal adenocarcinoma were collected and an-alyzed by combining clinical symptoms,auxiliary examinations,histology,immunohistochemical,and genetic testing and 11 cases of bladder adenocarcinomas.Results Among the 19 patients(15 males,4 females;age range:33-75 years,mean:55 years),tumors were located at the dome or anterior wall of the bladder.Histological subtypes includ-ed mucinous adenocarcinoma(6 cases),adenocarcinoma not otherwise specified(4 cases),enteric-type adenocarci-noma(6 cases),adenocarcinoma with focal mucinous differentiation(1 case),adenocarcinoma with signet-ring cell carcinoma(1 case),and metastatic urachal adenocarcinoma(1 case).Immunophenotypic analysis revealed membra-nous positivity for β-catenin,diffuse positivity for CK34βE 12,MUC-2,and CK20,focal CK7 positivity in some cases,and rare GATA-3 positivity.Mutations in p53 were observed,while KRAS,NRAS,BRAF,and PIK3CA mutations were absent.In colorectal adenocarcinomas,CK34βE12 positivity was 40％,nuclear β-catenin positivity was 48％,and MUC-2 expression was approximately 50％.In bladder adenocarcinomas,GATA-3 and MUC-2 positivity rates were 45％and 63.6％,respectively.Conclusion Distinguishing urachal adenocarcinoma from colorectal and primary bladder adenocarcinomas remains challenging.Urachal adenocarcinoma should be suspected in patients with anterior bladder wall or dome lesions,gross hematuria,or mucinuria.No definitive diagnostic markers currently exist for ura-chal adenocarcinoma.Immunophenotypic features such as membranous β-catenin,MUC-2,and CK7 positivity may fa-vor urachal adenocarcinoma over colorectal adenocarcinoma.Additional markers(e.g.,GATA-3,CK20,CK34βE12)aid in differential diagnosis,though individual markers lack specificity.Comprehensive evaluation integrating clinical presentation,imaging,and clinicopathological features is essential for accurate diagnosis.

Objective To retrospectively analyze the clinical risk factors and prognosis of perioperative myocardial injury(MINS)in non-cardiac surgery patients admitted to the intensive care unit(ICU).Methods A total of 478 postoperative patients admitted to the Department of Intensive Medicine,Minhang Hospital,Fudan University from Jan 2020 to Dec 2023 were selected.They were divided into MINS group(n=302)and normal group(n=176)based on whether myocardial injury occurred within 7 days after surgery.The differences in clinical characteristics between the two groups were compared,and risk factors for perioperative myocardial injury were identified.Risk factors for mortality in the MINS group were analyzed with 30-day mortality as the clinical endpoint.Results The prevalence of acute physiology and chronic health evaluation Ⅱ(Apache Ⅱ)score,coronary artery disease,and chronic kidney disease were all higher in the MINS group than those in the normal group,with statistically significant differences(P<0.05).The proportion of emergency surgeries,co-infection,and perioperative hypotension were significantly different between the MINS group and the normal group(P<0.05).Multivariate logistic regression analysis revealed that chronic kidney disease,emergency surgery,co-infection,and intraoperative and postoperative hypotension were risk factors for MINS occurrence.Prognostic analysis indicated that perioperative hypotension was a risk factor for 30-day mortality in MINS patients.Conclusion MINS is closely associated with patients'underlying conditions,timing of surgery,and perioperative hypotension status,and especially perioperative hypotension affects the final outcomes.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.