In this study,a sensitive lateral flow immunoassay(LFIA)platform based on carbon dots-mesoporous silica nanocomposite(CD-MSNs)fluorescent probes was constructed for high-performance detection of inflammatory marker interleukin-6(IL-6).Green fluorescent carbon dots(CDs)were prepared by hydrothermal method with 3,9-perylenic acid and 3-aminopropyltriethoxysilane(APTES)as raw materials,and highly fluorescent CD-MSNs composites were then constructed by encapsulating the prepared CDs in mesoporous silica nanoparticles(MSNs).Fluorescent probes were prepared by covalent coupling of CD-MSNs with IL-6 antibody.Fluorescent immunochromatographic test strips were constructed by spraying IL-6 capture antibody and goat anti-mouse IgG on nitrocellulose membrane as detection line(T-line)and quality control line(C-line),respectively.The fluorescence immunoassay analyzer was used to quantitatively detect the fluorescence intensity of T-line,and the experimental results showed that the LFIA platform based on this probe had a good linear relationship in IL-6 concentration range of 102-106 pg/mL,and the detection limit was 64 pg/mL,which was two orders of magnitude more sensitive than that of the traditional colloidal gold test strips.This method effectively solved the issue of insufficient sensitivity of traditional LFIA technique,and provided a rapid and highly sensitive detection method for early diagnosis of inflammatory diseases.

Objective To investigate the epidemiological characteristics of knee osteoarthritis(KOA)among military personnel in plateau regions and to explore its risk factors.Methods From July 2023 to July 2024,a multi-stage stratified cluster random sampling method was employed to survey the prevalence of KOA and related risk factors among military personnel in the northwest plateau regions of China,covering different altitudes(1500-4500 m)and geographical areas(Gansu,Qinghai,Tibet,and Xinjiang).All study subjects were divided into KOA and non-KOA groups based on the presence or absence of KOA.Variables including age,gender,body mass index(BMI),education level,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury were selected for univariate analyses between groups.Variables with P<0.05 in the univariate analyses were included in the binary multifactor logistic regression to identify risk factors for KOA.Results A total of 3000 questionnaires were distributed,and 2854 valid questionnaires were collected,with a response rate of 95.13%.The sample included 2584 males and 270 females,with 510 cases of KOA,resulting in a prevalence rate of 17.9%.Univariate analysis showed that there were statistically significant differences between KOA and non-KOA groups in terms of age,BMI,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury(P<0.05).However,no significant differences were found in gender and education level(P>0.05).Binary multivariate logistic regression analysis revealed that older age(OR=1.382,P=0.017),higher BMI(P<0.01),smoking(OR=1.929,P<0.01),higher military rank(OR=1.485,P=0.007),being a member of the Armed Police(P<0.01),longer service duration(P<0.01),higher regional altitude(OR=1.459,P<0.01),lower annual average temperature(OR=1.188,P=0.001),longer training duration(P<0.01),higher perceived training intensity(OR=2.450,P<0.01),and history of knee injury(OR=2.768,P=0.002)were independent risk factors for KOA.Conclusions Older age,overweight/obesity,smoking,higher military rank,being a member of the Armed Police,longer service duration,higher altitude,cold climate,longer training duration,higher training intensity,and history of knee injury are independent risk factors for KOA among military personnel in the northwest plateau regions of China.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Humans ; Encephalomyelitis, Acute Disseminated/complications* ; COVID-19/complications* ; SARS-CoV-2 ; Brain

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.
Animals ; Rats ; PC12 Cells ; Ferroptosis/genetics* ; Reactive Oxygen Species ; Transcription Factors ; Glutathione

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Female ; Humans ; Cervix Uteri/surgery* ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/surgery* ; Carcinoma, Neuroendocrine/surgery* ; Recurrence

Cancer cachexia is a complex metabolic syndrome which is characterized by muscle wasting,fat decomposition,unplanned weight loss,anorexia and immune dysfunction.Cachexia can significantly reduce the efficacy of antitumor therapies and increase treatment-related toxicity in cancer patients.It increases the symptom burden of patients,affects the quality of their life,ultimately shortens their survival time.This article reviews the research progress of diagnosis and treatment of cancer cachexia.

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).