Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective:To development a deep learning（DL） model based on conventional MRI for automatic segmentation and differential diagnosis of nasopharyngeal carcinoma（NPC） and nasopharyngeal lymphoma（NPL）. Methods:The retrospective study included 142 patients with NPL and 292 patients with NPC who underwent conventional MRI at Renmin Hospital of Wuhan University from June 2012 to February 2023. MRI from 80 patients were manually segmented to train the segmentation model. The automatically segmented regions of interest（ROIs） formed four datasets: T1 weighted images（T1WI）, T2 weighted images（T2WI）, T1 weighted contrast-enhanced images（T1CE）, and a combination of T1WI and T2WI. The ImageNet-pretrained ResNet101 model was fine-tuned for the classification task. Statistical analysis was conducted using SPSS 22.0. The Dice coefficient loss was used to evaluate performance of segmentation task. Diagnostic performance was assessed using receiver operating characteristic（ROC） curves. Gradient-weighted class activation mapping（Grad-CAM） was imported to visualize the model's function. Results:The DICE score of the segmentation model reached 0.876 in the testing set. The AUC values of classification models in testing set were as follows: T1WI: 0.78（95%CI 0.67-0.81）, T2WI: 0.75（95%CI 0.72-0.86）, T1CE: 0.84（95%CI 0.76-0.87）, and T1WI+T2WI: 0.93（95%CI 0.85-0.94）. The AUC values for the two clinicians were 0.77（95%CI 0.72-0.82） for the junior, and 0.84（95%CI 0.80-0.89） for the senior. Grad-CAM analysis revealed that the central region of the tumor was highly correlated with the model's classification decisions, while the correlation was lower in the peripheral regions. Conclusion:The deep learning model performed well in differentiating NPC from NPL based on conventional MRI. The T1WI+T2WI combination model exhibited the best performance. The model can assist in the early diagnosis of NPC and NPL, facilitating timely and standardized treatment, which may improve patient prognosis.
Humans ; Nasopharyngeal Carcinoma/diagnostic imaging* ; Deep Learning ; Magnetic Resonance Imaging ; Retrospective Studies ; Nasopharyngeal Neoplasms/diagnostic imaging* ; Lymphoma/diagnostic imaging* ; Diagnosis, Differential ; ROC Curve ; Male ; Female ; Middle Aged ; Adult

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.

Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.

Objective:To assess the consistency of ultrasound and dual-energy computed tomography (DECT) in the diagnosis of gouty arthritis(GA), reasons of the differences were further analyzed.Methods:The ultrasound and DECT images of 150 knee joints from 147 patients diagnosed with gout at the Gout Specialty Clinic of Qingdao University Affiliated Hospital from February 2022 to October 2023 were retrospectively analyzed. According to anatomy, the knee joint was anatomically segmented into five regions: intra-articular, anterior, posterior, medial, and lateral.Location of monosodium urate (MSU) deposition was meticulously recorded. The Kappa consistency test was employed to assess the consistency of the two examination results in different regions of the knee joint. The McNemar chi-square test was utilized to conduct a differential analysis between DECT and ultrasound results.Results:Double contour sign(DCS) (81.2%, 92/112) was the most common intra-articular ultrasound sign in knee joints with GA. In the extra-articular region, MSU was commonly deposited in and around the popliteal tendon (ultrasound: 51.6%, 66/128; DECT: 54.7%, 70/128). Corresponding MSU deposits on DECT were found in 9 of 92 joints with DCS and in 9 of 49 joints with aggregates detected on ultrasound.In the assessment of MSU deposits, ultrasound showed an overall higher positive rate than DECT (87.3% vs. 72.3%, P=0.001), with poor consistency between the two examinations (Kappa=0.153). In distinct anatomical regions, ultrasound and DECT showed high consistency in the medial (Kappa=0.697) and lateral (Kappa=0.718) sides and the difference was not statistically significant ( P>0.05). Intra-articular (Kappa=0.289) and anterior (Kappa=0.303) regions exhibited only fair consistency, with statistically significant diagnostic differences ( P<0.05). When exclusively assessing cases with tophus, ultrasound and DECT demonstrated high consistency in the medial and lateral aspects(Kappa=0.685, 0.748) without statistical difference ( P>0.05). In the anterior region, the consistency between the two examinations was moderate (Kappa=0.256), while in the intra-articular region, the consistency of the two methods was lower (Kappa=0.147), and the differences was statistically significant ( P<0.001). Conclusions:Both ultrasound and DECT exhibit good diagnostic capabilities for gouty knee arthritis.However, the consistency between the two techniques varies in different anatomical locations. Clinical assessment should be tailored based on the specific anatomical position. DECT has an advantage in evaluating intra-articular MSU deposits, while ultrasound is more sensitive to detect early and scattered MSU deposits.

Objective:To assess the discriminatory value of the Thyroid Follicular Tumor Ultrasound Risk Stratification System (F-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and to compare its performance with other risk stratification systems(RSS).Methods:A retrospective analysis was conducted on 325 patients (327 thyroid nodules) diagnosed postoperatively as FTC or FTA at Affiliated Hospital of Qingdao University from January 2016 to December 2023. The cases were divided into FTC group (81 nodules) and FTA group (246 nodules). The nodules were classified based on F-TIRADS, the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS), the 2015 American Thyroid Association guidelines (ATA guidelines), and the 2017 European Thyroid Association Thyroid Imaging Reporting and Data System (EU-TIRADS) by two ultrasound physicians. Multivariate Logistic regression analysis was used to identify independent predictors associated with FTC. Diagnostic performance of the 4 RSS was compared using postoperative pathological results as the gold standard.Results:Multivariate Logistic regression analysis showed maximum diameter, solid composition, hypoechogenicity, unclear or angular margins, marginal or ring calcifications, trabecular structure, and central blood flow were independent predictors of FTC( OR=1.914, 3.427, 9.926, 9.163, 45.918, 3.191, 8.936, respectively; all P<0.05). Within each RSS, the actual malignancy rate increased with higher risk categories, aligning closely with the recommended malignancy rates (except for ATA guidelines). The optimal cut-off values for distinguishing FTC from FTA were FTC risk 50%-90% in F-TIRADS, C-TIRADS 4B, moderately suspicious nodules in ATA guidelines, and EU-TIRADS 4, with areas under the curve of 0.916, 0.808, 0.827, and 0.836, respectively. F-TIRADS demonstrated the best overall performance (sensitivity: 82.72%, specificity: 82.93%), with significant differences compared with C-TIRADS, ATA guidelines, and EU-TIRADS (all P<0.05). Conclusions:F-TIRADS is highly effective in distinguishing FTA from FTC, outperforming C-TIRADS, ATA Guidelines, and EU-TIRADS. Clinicians should pay close attention to solid hypoechoic nodules with unclear or angular margins, marginal or ring calcifications, central blood flow, or a trabecular structure.

Objective To investigate the feasibility and clinical experience of kidney transplantation from donors with Marfan syndrome (MFS). Methods Clinical data of 2 recipients undergoing kidney transplantation from the same MFS patient were retrospectively analyzed and literature review of 2 cases was conducted. Characteristics and clinical diagnosis and treatment of kidney transplantation from MFS patients were summarized. Results The Remuzzi scores of the left and right donor kidneys of the MFS patient during time-zero biopsy were 1 and 2. No significant difference was observed in the renal arteriole wall compared with other donors of brain death and cardiac death. Two recipients who received kidney transplantation from the MFS patient suffered from postoperative delayed graft function. After short-term hemodialysis, the graft function of the recipients received the left and right kidney began to gradually recover at postoperative 10 d and 20 d. After discharge, serum creatinine level of the recipient received the left kidney was ranged from 80 to 90 μmol/L, whereas that of the recipient received the right kidney kept declining, and the lowest serum creatinine level was 232 μmol/L before the submission date (at postoperative 43 d). Through literature review, two cases successfully undergoing kidney transplantation from the same MFS donor were reported. Both two recipients experienced delayed graft function, and then renal function was restored to normal. Until the publication date, 1 recipient has survived for 6 years, and the other recipient died of de novo cerebrovascular disease at postoperative 2 years. Conclusions MFS patients may serve as an acceptable source of kidney donors. However, the willingness and general conditions of the recipients should be carefully evaluated before kidney transplantation. Intraoperatively, potential risk of tear of renal arterial media should be properly treated. Extensive attention should be paid to the incidence of postoperative complications.