Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals ; OX40 Ligand/physiology* ; Purpura, Thrombocytopenic, Idiopathic/immunology* ; Cell Differentiation ; Mice ; T-Lymphocytes, Helper-Inducer/cytology* ; T Follicular Helper Cells/cytology* ; Signal Transduction ; Receptors, OX40 ; Mice, Inbred C57BL ; Humans ; Female

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Ionizing radiation occurs not only during nuclear and radiological terrorist attacks or nuclear accidents but also in medical applications and daily life. In recent years, the potential toxic effects of low-dose ionizing radiation on the male reproductive system have raised public health concerns. Most specifically, for the testis, a highly sensitive target organ to ionizing radiation, there is an urgent need to determine the mechanisms underlying the association between radiation-induced spermatogenic failure and male infertility. Focusing on the potential injurious effects of low-dose ionizing radiation on spermatogenesis, this review presents a summary and analysis of various underlying mechanisms including oxidative stress, apoptosis, and DNA damage repair and reviews recent domestic and international strategies for protecting against radiation-induced reproductive system damage in order to offer references for future research on the injurious effects of low-dose radiation on spermatogenesis and relevant protection.

Objective To compare the changes in biological indicators of human corneal epithe-lial(HCET)cells and rabbit corneas after exposure to different doses of ultraviolet B(UVB)radia-tion,so as to evaluate the impact of UVB radiation on corneal injury effects.Methods In cell exper-iment,HCET cells were divided into groups with radiation doses of 0,6,12,18,and 24 mJ/cm2.The effect of UVB radiation on HCET cell viability was detected using the CCK-8 assay,and the level of intracellular DNA damage was assessed by immunofluorescence.In the animal experiment,15 healthy New Zealand white rabbits(30 eyes)were randomly divided into groups with radiation doses of 0,1.35,2.16,4.32,and 6.48 J/cm2.The UVB exposure time for the radiation groups was 30 minutes per day for 3 consecutive days.Corneal injury was evaluated using methods such as slit-lamp microscopy,sodium fluorescein staining,central corneal thickness measurement,optical coherence tomography(OCT)imaging,and hematoxylin and eosin(HE)staining.Results Compared with the control group,cell viability in the radiation groups gradually decreased,and the level of DNA damage gradually increased with increasing radiation dose.As the radiation dose increased in the radiation groups,the degree of corneal opacity in rabbits gradually worsened,the central corneal area gradu-ally thickened,and OCT revealed high-intensity scattered light signals with the formation of shadow areas.Results from HE staining,immunohistochemistry,Western blot(WB),and sodium fluores-cein staining showed that the 1.35 J/cm2 group caused mild corneal injury,with damage reaching the corneal epithelial layer.In the 2.16 J/cm2 group,the corneal injury presented as dense punctate distribution,with damage extending from the epithelial layer to the superficial stroma.The number of ephrin type-A receptor 2(EphA2)protein-stained cells was relatively small,and the staining was light,showing a weak positive result.In the 4.32 J/cm2 and 6.48 J/cm2 groups,the corneal injury was irreversible,with damage gradually progressing from the corneal epithelial layer and superficial stroma to the endothelial layer.The number of EphA2 protein-stained cells was relatively large,and the staining was dark,showing a strong positive result.Conclusion This study comprehensively e-valuates the dose-dependent injury effects of UVB on HCET cells and New Zealand white rabbit cor-neas through cell and animal experiments.It elucidates that UVB radiation could induce corneal cell DNA damage,promote inflammatory responses,and trigger apoptosis by upregulating γ-phosphoryla-ted histone H2AX(γH2AX)and EphA2.The self-repair ability and process of corneal injury are preliminarily explored,providing a basis for further research on mechanisms of corneal injury caused by ultraviolet radiation and the development of protective drugs.

High intensity ultraviolet radiation exists in special military operation environments such as oceans,plateaus,polar regions and deserts,which is a leading contributor to eye damage and can lead to luminous keratitis,dry eyes,pterygium,cataract and macular degeneration.Ultraviolet radiation can cause acute and chronic injury to eyes by inducing DNA damage,oxidative stress and inflammatory reaction.The commonly used clinical drugs have played a role in relieving symptoms and promoting the repair of ocular tissues,but there are still limitations.The research on targeted therapeutic drugs,proteins and their derived peptides,vitamins and their coenzymes,as well as natural active ingredients of animals and plants has provided new ideas for the development of more effective drugs that can protect eyes from ultraviolet and for medical support to China's army in special environments.Based on the literature currently available,this paper reviews the eye injury caused by ultraviolet radiation and therapeutic drugs in terms of types of eye diseases,injury mechanisms,treatment strategies and drug development.

Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.

BACKGROUND:Both calorie restriction and time-restricted feeding,as two common dietary patterns,have been shown to improve health by regulating metabolism.However,the difference between these dietary patterns,metabolic indices,as well as the gut microbiota still requires further attention.OBJECTIVE:To explore the differences of calorie restriction and time-restricted feeding on the metabolic indices and gut microbiota of mice.METHODS:The C57BL/6J mice were randomly divided into three groups of ad libitum,calorie restriction,and time-restricted feeding(n=6 per group)for 28 weeks of dietary intervention.Various parameters such as body weight,food intake,glucose tolerance,serum fasting insulin,Homeostasis Model Assessment of Insulin Resistance,and leptin were measured.The impact of different interventions on the gut microbiota structure in mice was explored using 16S rRNA sequence analysis.Key operational taxonomic units responsive to dietary interventions were identified through LEfSe analysis.RESULTS AND CONCLUSION:(1)Compared with the ad libitum group,the body weight,food intake,area under the glucose tolerance curve of the calorie restriction and time-restricted feeding groups were decreased(P＜0.01),and the serum leptin was decreased(P＜0.05).The fasting insulin level and serum leptin level of the calorie restriction group were decreased(P＜0.05)and were significantly lower than those of the time-restricted feeding group(P＜0.05);homeostasis model assessment of insulin resistance decreased in the calorie restriction group(P＜0.01).(2)Compared with the ad libitum group,the αdiversity of gut microbiota in the calorie restriction group and the time-restricted feeding group was decreased(P＜0.05),but the diversity of the time-restricted feeding group was slightly lower than that in the calorie restriction group.(3)There were 15 key operational taxonomic units related to calorie restriction and the time-restricted feeding intervention,of which 8 were positively correlated with metabolic phenotypes and their abundance decreased,and 3 were negatively correlated with metabolic phenotypes and their abundance increased(P＜0.05).OTU819 Lachnospiraceae_UCG-006 was positively correlated with body weight,area under the glucose tolerance curve,homeostasis model assessment of insulin resistance,and fasting insulin,while OTU1397 Muribaculaceae was negatively correlated with these indicators.The results show that both calorie restriction and the time-restricted feeding intervention can improve the weight and glucose metabolism of mice,and both intervention modes caused the remodeling of the gut microbiota,which helped to improve the metabolic disorders.

Objective:To construct a hierarchical training course system for neonatal nurses based on core competencies, to provide a reference for meeting the training needs of neonatal nurses under the new situation.Methods:Through literature review, questionnaire survey on training needs, and focus group interviews, a preliminary hierarchical training curriculum system for neonatal nurses was developed. Two rounds of Delphi correspondence were conducted with 19 domestic experts to finalize the system.Results:The effective questionnaire recovery rates of the two rounds of expert consultation were 95.00% and 100.00%, and the expert authority coefficient was 0.916, the Kendall harmony coefficient of the first round of expert opinions was 0.351 ( P<0.001), and the Kendall harmony coefficient of the second round of expert opinions was 0.463 ( P<0.001). The hierarchical training course structure and course training content are formed, including N0: 3 first-level items, 9 second-level items, 80 third-level items, N1: 3 first-level items, 9 second-level items, 91 third-level items, N2: 3 first-level items, 9 second-level items, 86 third-level items, N3: 3 first-level items, 10 second-level items, 81 third-level items, N4: 3 first-level items, 10 second-level items, 76 third-level items. Conclusions:The hierarchical training course system for neonatal nurses based on the core competence of nurses is scientific and practical, which can provide a reference for the hierarchical training of neonatal nurses.

Objective To investigate the correlation of vascular senescence indicators,brachial-ankle pulse wave velocity(baPWV),cardio-ankle vascular index(CAVI),ankle-brachial index(ABI)with total burden of MRI in patients with cerebral small vessel disease(CSVD).Methods A total of 200 CSVD patients admitted to our hospital from November 2023 to October 2024 were retrospectively recruited,and based on their total MRI burden,they were divided into a low-burden group(score:0-1,103 cases)and a high-burden group(score:2-4,97 cases).A athero-sclerosis monitoring device(VS-1500A)was used to detect baPWV,CAVI,and ABI values.The relationships of the three indicators with total MRI burden score and their predictive values for the burden score were analyzed.Results The high-burden group had significantly higher BMI,el-evated homocysteine and uric acid levels,and increased baPWV and CAVI,but lower ABI than the low-burden group(P＜0.01).Multivariate logistic analysis showed that baPWV,CAVI and ABI were independent influencing factors for high MRI burden of CSVD patients.Spearman correlation analysis showed that baPWV and CAVI values were positively correlated(r=0.589,P=0.000;r=0.458,P=0.000),and ABI was negatively correlated with the total MRI burden score of CSVD patients(r=-0.352,P=0.000).ROC curve analysis showed that baPWV(AUC=0.816,P=0.000),CAVI(AUC=0.725,P=0.000)and ABI(AUC=0.676,P=0.000)were all predic-tors for high MRI burden score in CSVD patients.Conclusion baPWV and CAVI are positively,and ABI is negatively correlated with the total MRI burden score of CSVD patients.baPWV,CAVI and ABI show higher predictive value for the high burden score,with baPWV most significant.