Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To investigate the effects of advanced maternal age(AMA)on synaptic pruning of the hippocampus of offspring rats.Methods Offspring of 3-month-old SD female rats and 3-month-old SD male rats were designated as the appropriate age group(Ctl group),while offspring of 12-month-old SD female rats and 3-month-old SD male rats were assigned to AMA group.Hippocampal tissues from both groups(n=3 per group at each time point)were subjected to Golgi staining on postnatal days(P)7,28,and 60.Dendritic complexity,spine density(DS),and morphology of immature brain neurons at different age stages were compared between the two groups.Results Compared with Ctl group,the dendritic length of AMA group on P7,P28,and P60 was significantly shortened,and the average number of intersections between dendrites and concentric circles on P28 and P60 was also significantly decreased(P<0.05).Compared with Ctl group,the dendritic spine density of AMA group was significantly decreased on P7,P28,and P60.Notably,the density of thin-shaped dendritic spines in AMA group was increased on P7,whereas the densities of stubby-shaped and mushroom-shaped dendritic spines were decreased(P<0.05).On P28 in AMA group,the densities of thin-shaped and mushroom-shaped dendritic spines were significantly increased compared with Ctl group,while the density of stubby-shaped dendritic spines was significantly decreased(P<0.05).The densities of stubby-shaped and mushroom-shaped dendritic spine were markedly lower in AMA group on P60 than those in Ctl group(P<0.05).Conclusions During postnatal brain development periods,there were abnormalities in synaptic pruning in the hippocampal region of the offspring of the AMA,which manifested as reduced dendritic complexity,decreased dendritic spine density,and disorganized dendritic spine morphology.It could be one of the key mechanisms underlying brain dysfunction in the offspring of AMA.

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective To investigate the effect of Tan Ⅰ on SA-AKI in rats by mediating Wnt/β-catenin signaling pathway.Methods Sprague-Dawley rats were randomly divided into the following groups(n=8 per group,including 2 reserve animals per group):Sham,SA-AKI,SA-AKI+5 mg/kg Tan I,SA-AKI+10 mg/kg Tan I,SA-AKI+15 mg/kg Tan I(SA-AKI+Tan I),SA-AKI+salinomycin sodium(SS,Wnt signal inhibitor,SA-AKI+SS),SA-AKI+SS+Tan I,SA-AKI+laduviglusib(LG,Wnt signal activator,SA-AKI+LG),and SA-AKI+LG+Tan I.Rat SA-AKI model was induced by cecal ligation and puncture(CLP),with Tan I,SS,and LG administered via intraperitoneal injection.Hematoxylin-eosin and TUNEL staining were used to observe renal tissue pathological damage.Enzyme-linked immunosorbent assay was used to detect serum concentrations of neutrophil gelatinase-associated lipocalin(NGAL),IL-1β,IL-8,IL-6,and TNF-α.Creatinine(Cre)and blood urea nitrogen(BUN)kit were used to detect serum Cre and BUN concentrations.Western blot and immunofluorescence staining were used to detect the expression and fluorescence intensity of Wnt1,GSK3β,and β-catenin.Results Administration of Tan I at doses of 10 mg/kg and 15 mg/kg significantly attenuated renal injury in rats with SA-AKI(P<0.05),suppressed the levels of SA-AKI biomarkers NGAL,Cre,and BUN and pro-inflammatory cytokines(P<0.05),reduced apoptosis,and downregulated Wnt1 and GSK3β while upregulating β-catenin expression(P<0.05).Although Tan I at 5 mg/kg exhibited a modest protective effect against SA-AKI in rats,no statistically significant difference was observed compared to the sham group(P>0.05).SS weakened CLP-induced kidney injury and the production of inflammatory cytokines in rats(P<0.05),and LG further aggravated CLP-induced kidney injury in rats(P<0.05).Tan Ⅰ reversed the promoting effect of LG on kidney injury in SA-AKI rats(P<0.05).Conclusion Tan Ⅰ provides a protective effect on CLP-induced SA-AKI rat by inhibiting Wnt/β-catenin signaling pathway.

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

Objective:To construct an explainable artificial intelligence(AI) model of risk characteristics of papillary thyroid carcinoma(PTC), and to explore its value of it combined with clinical features in predicting cervical lymph node metastasis(CLNM) in PTC patients.Methods:From January 2021 to September 2022, 422 patients(422 nodules) with pathologically confirmed PTC underwent thyroidectomy and neck lymph node dissection in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively collected, the patients were randomly divided into training set and test set according to the ratio of 7∶3. Ultrasonographic features highly correlated with PTC risk characteristics were extracted by traditional machine learning method, and an intelligent prediction model with optimal probability of risk characteristics was established. Then, a risk model for predicting CLNM of PTC patients was constructed in combination with clinical features. The diagnostic effectiveness of the model was evaluated by drawing a ROC curve and calculating the area under curve (AUC).Results:In the AI explaineable model of PTC risk characteristics in the test set, the intelligent diagnosis model of calcification based on logistic regression classification showed the highest diagnostic efficiency, with an AUC of 0.87 ( P<0.05). Compared with the probability model of risk characteristic of PTC alone, the comprehensive model combined with clinical characteristics showed higher diagnostic efficiency in predicting CLNM of PTC patients, with AUC of 0.97, diagnostic critical value of 0.15, corresponding accuracy, sensitivity and specificity of 92.65%, 92.76% and 92.54%, respectively (all P<0.05). Conclusions:The explaineble risk characteristics of PTC AI model combined with clinical features can effectively predict the cervical lymph node metastasis of PTC, and then provide effective information for clinical decision-making of PTC patients.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.