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*

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

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OBJECTIVE: To examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

Objective To systematically evaluate the qualitative research on the experience and feeling of elderly patients with hip fracture during rehabilitation.Methods We searched databases including the PubMed,Embase,Web of Science,Cochrane Library,CNAIHL,CNKI,Wanfang,VIP,SinoMed.The literature of qualitative research on the exercise rehabilitation experience of stroke patients from the establishment of the database to August 17,2023 was retrieved.Results A total of 59 clear research topics were extracted,and 14 new categories were formed after induction and integration,which were finally merged into 5 integrated results.Integration results 1:Perceived benefits of exercise rehabilitation.Integration results 2:Multiple driving forces of exercise rehabilitation.Integration results 3:Gradual loss of patience in long-term rehabilitation.Integrated results 4:Generating new rehabilitation needs and actively coping with them.Integrated results 5:There are many difficulties in carrying out self-rehabilitation.Conclusion During the process of exercise rehabilitation for stroke patients,medical personnel should pay attention to the patients'actual feelings,inner needs,and the practical challenges they face in participating in exercise rehabilitation.Personalized exercise rehabilitation facilitation strategies should be developed for stroke patients,aiming for the scientific and precise advancement of exercise rehabilitation,and ultimately improving long-term rehabilitation outcomes for patients.

Objective:To explore the genotypes and clinical phenotypes of three families with Liddle Syndrome(LS).Methods:In this study, three young patients with hypertension and hypokalemia were confirmed LS through second-generation sequencing genetic testing. Members of the three families were screened for genes, and genotypes and clinical phenotypes were analyzed.Results:This study identified three patients in Family 1 carrying a possible pathogenic heterozygous variant c. 1859A>G(p.Y620C) in the SCNN1B gene(sodium channel epithelia 1β subunit). Five patients in family 2 and family 3 carried the pathogenic heterozygous variant c. 1789dup(p.R597Pfs*11) in the SCNN1B gene. Following three months of treatment with salt restriction and triamterene, blood pressure and potassium levels returned to normal in all eight patients.Conclusion:LS patients typically present clinically with early-onset hypertension accompanied by hypokalemia, but there is clinical heterogeneity. It is recommended to conduct genetic testing on suspected patients as early as possible to confirm the diagnosis and initiate timely treatment with effective medications so as to reduce the complications of target organs.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To conduct an overview of systematic reviews on the safety and effectiveness of early mobilization in stroke patients.Methods:Systematic reviews of early mobilization in stroke were electronically searched on China National Knowledge Infrastructure, WanFang Data, VIP, Chinese Biology Medicine, Cochrane Library, PubMed, Web of Science, CINAHL, Embase, and the Joanna Briggs Institute Evidence-Based Health Care Center Database. The search period was from database establishment to May 2023. Two researchers independently conducted literature screening, data extraction, and methodological quality evaluation of the included literature, as well as evidence summary and grading.Results:A total of 10 systematic reviews were included. The methodological quality evaluation showed that one article was of medium quality, two articles were of low quality, and seven articles were of extremely low quality. The evidence quality evaluation indicated that there were three pieces of high-quality evidence, 17 pieces of medium-quality evidence, 21 pieces of low-quality evidence, and 17 pieces of extremely low-quality evidence.Conclusions:Early mobilization is beneficial for improving the daily living ability and limb motor function of stroke patients, reducing the incidence of complications, shortening hospital stay, and enhancing their walking ability in the short term. However, the quality of evidence in the systematic review is relatively low, and further improvement is needed in the research design of early mobilization intervention measures to provide strong support for clinical practice.

The epidemiological and spatiotemporal distribution characteristics of human leptospirosis in Zhejiang Province from 2018 to 2022 were analyzed,to provide a scientific basis for formulating leptospirosis prevention and control strategies.Data on leptospirosis were collected from the China Information System for Disease Control and Prevention,and analyzed with descriptive epidemiological methods.ArcMap 10.8 software was used for spatial autocorrelation analysis and visual display of the results.SaTScan 10.1.2 software was used for spatiotemporal scanning,to analyze and describe the spatiotemporal aggrega-tion characteristics of leptospirosis.A total of 255 human cases of leptospirosis were reported in Zhejiang Province from 2018 to 2022,including one death;the average annual incidence was 0.084 3/100 000,and the average annual mortality was 0.000 3/100 000.The highest incidence of leptospirosis in Zhejiang occurred from August to October.Most cases were in middle-aged and older people 45-86 years of age(221 cases,86.67％).The number of cases was highest among people 65-69 years of age(57 cases).The male to female ratio was 4.67∶1.The main occupation was farming(190 cases,74.51％).The cumulative number of cases in Wenzhou and Lishui in 3 years(201 cases)accounted for 78.82％of the total cases.The global spatial auto-correlation analysis from 2018 to 2022 showed that the incidence of leptospirosis in the province presented a positive spatial au-tocorrelation.Local spatial autocorrelation analysis indicated that the"high-high"gathering areas were concentrated primarily in Wenzhou,Lishui,and Taizhou in the mountainous and hilly areas of southern Zhejiang Province.Spatiotemporal scanning anal-ysis revealed three clusters with high incidence in southern Zhejiang Province.The incidence of leptospirosis in Zhejiang Prov-ince showed clear regional clustering and seasonality,and the high incidence area was mainly in the mountainous and hilly areas of southern Zhejiang Province.The cases occurred mainly in middle-aged and older male farmers.Health education among rural resi-dents should be strengthened to prevent potential epidemic risks.

Malaria is a global disease affecting a large portion of the world’s population. Although vaccines have recently become available, their efficacies are suboptimal. We generated virus-like particles (VLPs) that expressed either apical membrane antigen 1 (AMA1) or microneme-associated antigen (MIC) of Plasmodium berghei and compared their efficacy in BALB/c mice. We found that immune sera acquired from AMA1 VLP- or MIC VLP-immunized mice specifically interacted with the antigen of choice and the whole P. berghei lysate antigen, indicating that the antibodies were highly parasite-specific. Both VLP vaccines significantly enhanced germinal center B cell frequencies in the inguinal lymph nodes of mice compared with the control, but only the mice that received MIC VLPs showed significantly enhanced CD4+ T cell responses in the blood following P. berghei challenge infection. AMA1 and MIC VLPs significantly suppressed TNF-α and interleukin-10 production but had a negligible effect on interferon-γ. Both VLPs prevented excessive parasitemia buildup in immunized mice, although parasite burden reduction induced by MIC VLPs was slightly more effective than that induced by AMA1. Both VLPs were equally effective at preventing body weight loss. Our findings demonstrated that the MIC VLP was an effective inducer of protection against murine experimental malaria and should be the focus of further development.