ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.

Objective:To investigate the post-traumatic stress response in women with unintended pregnancy termination and analyze its related factors.Methods:Totally 388 women with unintended pregnancy termination from two public hospitals in Fujian were selected as the research subjects.They were assessed with the Impact of E-vent Scale-Revised(IES-R),Hospital Anxiety and Depression Scale(HADS),Connor-Davidson Resilience Scale(CD-RISC)and Perinatal Grief Scale(PGS).The total score of IES-R ≥35 was positive for post-traumatic stress disorder screening.Results:The total score of IES-R was(20.6±12.4),and the positive rate of post-traumatic stress disorder screening was 16.5％.Multiple linear regression analysis showed that the IES-R total scores were higher in those who thought pregnancy timing was appropriate than those who thought pregnancy timing was wrong(β=0.13),and lower in women with moderate pain during termination than in those with severe pain(β=-0.09).The IES-R total scores were positively correlated with gestational weeks,depression scores of the HADS and grief scores of the PGS(β=0.18,0.27,0.16),and negatively correlated with optimism scores of the CD-RISC(β=-0.12).Conclusion:The post-traumatic stress response of unintended termination of pregnancy is at a moder-ate level.Post-traumatic stress symptoms are more likely to occur in women who thought pregnancy timing is ap-propriate,and those with severe pain during pregnancy termination,large gestational weeks,high level of depression during pregnancy,and high level of grief after pregnancy termination.

The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents （HSGs） are paramount in guaranteeing the quality， reliability， and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems （AGREE-HS）， we demonstratively assessed both global coronavirus disease-2019 （COVID-19） emergency HSGs and World Health Organization （WHO） standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS， methods in the 34 emergency HSGs evaluated ranked third， trailing behind topic and recommendations. Notably， criterion 2 （the best available and most contextually relevant evidence is considered） received the highest score， whereas criterion 5 （evidence of cost and cost-effectiveness of the potential options is described） scored the lowest. Compared with the WHO standard HSGs， the COVID-19 emergency HSGs exhibited low scores in methods （P<0.05）， which was reflected in nine criteria （P<0.05）， especially in criteria 1 （systematic and transparent methods are used to identify and review the evidence） and 9 （systematic and transparent methods are used to agree upon the final recommendations）. Among the COVID-19 emergency HSGs， that developed by the WHO achieved higher scores in eight out of all nine criteria， excluding criterion 8 （P<0.05）. The clinically relevant emergency HSGs had higher scores in the criteria 3 （the evidence base is current） and 8 （the rationale behind the recommendations is clear） than other types of emergency HSGs. Collectively， the methodology for developing emergency HSGs， represented by the COVID-19 emergency HSG， underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies， streamlined evidence review protocols， and contextual relevance， all of which are influenced by external， internal， and implementation-specific factors.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

DNA origami is a powerful technique for generating nanostructures with dynamic properties and intelligent controllability. The precise geometric shapes, high programmability, and excellent biocompatibility make DNA origami nanostructures an emerging drug delivery vehicle. The shape, size of the carrier material, as well as the loading and release of drugs are important factors affecting the bioavailability of drugs. This paper focuses on the controllable design of DNA origami nanostructures, efficient drug loading, and intelligent drug release. It summarizes the cutting-edge applications of DNA origami technology in biomedicine, and discusses areas where researchers can contribute to further advancing the clinical application of DNA origami carriers.

italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the α-shape analysis to determine the habitat of L. rotata. We then carried out the climate-niche factor analysis (CNFA) to assess the vulnerability of L. rotata to climate change based on five climate variables (i.e., mean diurnal range, temperature seasonality, mean temperature of warmest quarter, precipitation of driest month and precipitation of warmest quarter) in the context of two shared socioeconomic pathways (i.e., SSP126 and SSP585) and three global climate models (CMCC-ESM2: Centro Euro-Mediterraneo sui Cambiamenti Climatici-Earth System Model version 2; HadGEM3-GC31-LL: Hadley Global Environment Model version 3-Global Coupled configuration 3.1; IPSL-CM6A-LR: Institut Pierre Simon Laplace-Climate Model version 6) during two different periods (2041-2060 and 2081-2100). The vulnerability of L. rotata to climate change was calculated by integrating the sensitivity and exposure indices of L. rotata to five climate variables. The results showed that L. rotata had the highest vulnerability to the precipitation of warmest quarter. Its vulnerability within its habitat range generally showed a spatial pattern of high value in the southern region and low in the northern region, high in the western region and low in the eastern region. In general, the vulnerability of L. rotata under the SSP585 scenario was higher than that under the SSP126 scenario. The climate data of different global climate models have some influence on the results, while the resulted uncertainty can be reduced by data integration methods. As a result of climate change, the pressure on the survival of L. rotata in the future will be intensified in the low-altitude areas such as the Yarlung Zangbo River, Yigongzangbu River, Zayu River, and Jiaomuzu River, etc., while the highly weathered scree flats or stony alpine meadows in the high-altitude zones, such as the eastern Tanggula Mountain Range, the northern part of Hengduan Mountain Range, and the western part of the Qinling Mountains, may become its refuge. It is necessary to focus on and strengthen the protection and management of L. rotata resources in these vulnerble and critical areas.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

Objective:With the in-depth study of complement dysregulation,glomerulonephritis with dominant C3 has received increasing attention,with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types.This study analyzes the clinical,pathological,and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3,aiming to avoid misdiagnosis and missed diagnoses. Methods:The clinical,pathological,and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed.According to the clinical feature and results of pathology,15 patients with post-infectious glomerulonephritis(PIGN)and 37 patients with of non-infectious glomerulonephritis(N-PIGN)were classified.N-PIGN subgroup analysis was performed,and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group,or 27 in a C3 glomerulopathy(C3G)group and 10 in a non-C3 nephropathy(N-C3G)group. Results:The PIGN group had lower creatinine values(84.60 μmol/L vs 179.62 μmol/L,P= 0.001),lower complement C3 values(0.36 g/L vs 0.74 g/L,P<0.001)at biopsy,and less severe pathological chronic lesions compared with the N-PIGN group.In the N-PIGN subgroup analysis,the C3-dominant-deposition group had higher creatinine values(235.30 μmol/L vs 106.70 μmol/L,P=0.004)and higher 24-hour urine protein values(4 025.62 mg vs 1 981.11 mg,P=0.037)than the C3-alone-deposition group.The prognosis of kidney in the PIGN group(P=0.049),the C3-alone-deposition group(P=0.017),and the C3G group(P=0.018)was better than that in the N-PIGN group,the C3-dominant-deposition group,and the N-C3G group,respectively. Conclusion:Glomerulonephritis with dominant C3 covers a variety of pathological types,and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G;in addition,the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis,and relevant diagnosis,treatment,and follow-up should be strengthened.

Objective To analyze the influencing factors and management of benign anastomotic stenosis in patients with colorectal cancer after concurrent prophylactic ileostomy.Methods The clinical data of 74 colorectal cancer patients undergoing preventive ileostomy admitted to Quanzhou First Hospital Affiliated to Fujian Medical University from April 2018 to June 2022 were selected,according to the presence or absence of anastomotic stenosis after surgery,patients were divided into anastomotic stenosis group and anastomotic normal group.The influencing factors of stenosis were analyzed using statistical methods,and the management methods for anastomotic stenosis were summarized.Results 15 cases of anastomotic stenosis occurred after surgery,with an incidence rate of 20.3%.Compared with anastomotic normal group,patients in anastomotic stenosis group had a higher proportion of preoperative radiation therapy,preoperative neoadjuvant chemotherapy,and a higher incidence of postoperative anastomotic leakage/pelvic infection,with statistical significance(P<0.05);Multivariate analysis suggests that preoperative radiotherapy,anastomotic leakage/pelvic infection are independent risk factors for anastomotic stenosis.Conclusion Patients with colorectal cancer who undergo preoperative radiotherapy,neoadjuvant chemotherapy,and postoperative anastomotic leakage/pelvic infection should pay attention to the occurrence of anastomotic stenosis after undergoing ileostomy;Postoperative anastomotic stenosis should be treated according to the characteristics of the stenosis.