Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.

Curcumin (Cur), a natural polyphenolic compound extracted from the rhizomes of plants belonging to the Zingiberaceae and Araceae families, has attracted considerable interest for its remarkable antioxidant, anti-inflammatory, antibacterial, and anticancer activities. Extensive studies have focused on its potential in treating various diseases, including cancers, neurodegenerative diseases, inflammation, and autoimmune disorders. However, its clinical application has been hampered by inherent physicochemical challenges, such as poor aqueous solubility, short half-life, and low bioavailability. To address these challenges, nanodrug delivery systems have been developed to improve the pharmacokinetic and pharmacodynamic profiles of curcumin, thereby enhancing its therapeutic efficacy. This review summarizes the pharmacological activities and underlying mechanisms of curcumin, encompassing its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial effects. Furthermore, it highlights the significant advancements achieved through the development of curcumin-based nanomedicines. By synthesizing current findings, this review aims to provide insights that may inspire innovative strategies for the future design and broader applications of curcumin nanomedicines.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.

A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

OBJECTIVE: To investigate the effects of low-dose irradiated autologous peripheral blood reinfusion (LDIAPBR) on a rat model of radiation-induced leukopenia. METHODS: The rats were randomly divided into four groups. In the LDIAPBR group, LDIAPBR was performed 1 day before modeling (10% of the total circulating blood volume was withdrawn, irradiated with 100 mGy ex vivo, and completely reinfused). Meanwhile, the normal group and model group only underwent blood withdrawal and reinfusion of the same proportion without blood irradiation. Except for the normal group, all groups were subjected to 1 Gy X-ray whole-body irradiation to establish a radiation-induced leukopenia rat model. The positive drug group received subcutaneous injection of rhG-CSF after modeling. It was monitored that the general condition of the rats, peripheral blood cell counts, immune organ indices, bone marrow nucleated cell counts and viability, and the pathological analysis of bone marrow sections was conducted. RESULTS: The LDIAPBR group exhibited significant improvements in overall condition compared to the model group. Notably, compared with the model group, peripheral blood leukocyte and lymphocyte counts were markedly higher in the LDIAPBR group. Furthermore, there was a significant increase in both the number and viability of nucleated cells in the bone marrow. Pathological examination of bone marrow sections revealed increased nucleated cell density and reduced cavity area in the LDIAPBR group. CONCLUSION LDIAPBR can effectively improve hematological parameters and bone marrow hematopoietic function in a rat model of radiation-induced leukopenia, providing a new approach for the prevention and treatment of radiation-related injuries.
Animals ; Leukopenia/prevention & control* ; Rats ; Blood Transfusion, Autologous ; Whole-Body Irradiation ; Radiation Injuries, Experimental/therapy*

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.