ObjectiveTo explore the mechanism by which Qiangjing tablets （QJT） alleviate the spermatogenic function damage caused by varicocele （VC） based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway-mediated oxidative stress. MethodsTen Sprague-Dawley （SD） rats were randomly assigned into a control group and a model group. Pathological examination confirmed the stability of the model. Thirty-six SD rats were randomized into control， model， low-dose （0.23 g·kg^-1） QJT， medium-dose （0.46 g·kg^-1） QJT， high-dose （0.92 g·kg^-1） QJT， and mazhilin （61.7 mg·kg^-1） groups， with 6 rats in each group. A rat model of experimental left varicocele （ELV） was established by partially ligating the left renal vein to simulate the human nutcracker syndrome. The rats were administrated with corresponding agents once a day for 28 consecutive days. The in vitro testicular culture model of rats was established through the Transwell chamber method and intervened with QJT-containing sera （2.3， 4.6， and 9.2 g·kg^-1）. Microscopic observation was carried out for the morphology of the left kidney. A micrometer was used to measure the diameter of the left spermatic vein （LSV）. The body weights of rats were recorded weekly， and the epididymis and testis weights were measured. The pathological changes of the testicular tissue was observed via hematoxylin-eosin （HE） staining. The levels of testosterone （T） in the cell culture supernatant and reactive oxygen species （ROS） in the rat testicular tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Flow cytometry was employed to determine the ROS content. Immunohistochemical staining was conducted to analyze Keap1， Nrf2， 3β-hydroxysteroid dehydrogenase （3β-Hsd）， GATA-binding protein-4 （Gata-4）， and proto-oncogene receptor tyrosine kinase （C-kit）. The ultrastructure of the tissue was observed by transmission electron microscopy （TEM）. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining. The expression of Keap1， Nrf2， glutathione S-transferase α2 （Gsta2）， glutathione S-transferase μ1 （Gstm1）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （Nqo1）， and thioredoxin reductase 1 （Txnrd1） was quantified by Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. ResultsCompared with the control group， the ROS content and the percentage of apoptotic cells in the model group were significantly increased （P<0.01）， the T concentration was significantly decreased （P<0.01）， the mRNA and protein expressions of Keap1 were significantly increased （P<0.01）， and the mRNA and protein expressions of Nrf2， Gsta2， Gstm1， HO-1， Nqo1 and Txnrd1 were significantly decreased （P<0.05）. Compared with the model group， the ROS content and the percentage of apoptotic cells in each dose group of the Qiangjing Tablets were significantly reduced （P<0.05）， and the mRNA and protein expressions of Keap1 were significantly decreased （P<0.05）， while the mRNA and protein expressions of Nrf2， Gsta2， Gstm1， HO-1， Nqo1 and Txnrd1 were significantly increased （P<0.05）. ConclusionQJT improves sperm motility in the rat model of VC by modulating the Keap1/Nrf2 signaling pathway and reducing oxidative stress injury.

ObjectiveTo explore the effect of cluster scalp acupuncture combined with Taijiquan training on depressive symptom, motor function, activities of daily living, serum markers, as well as brain functional connectivity (FC) and network topological properties in patients with post-stroke depression (PSD). MethodsA total of 40 PSD patients in the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from September, 2022 to September, 2023 were enrolled and randomly divided into control group (n = 20) and experimental group (n = 20). The control group received cluster scalp acupuncture alone, while the experimental group underwent Taijiquan training in addition, for four weeks. They were assessed with Hamilton Depression Scale-17 (HAMD-17), Fugl-Meyer Assessment (FMA) and Barthel Index (BI) before and after treatment, while the serum levels of dopamine (DA), 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected with enzyme-linked immunosorbent assay. Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to assess brain FC, as well as the global efficiency (Eg) and small-world property (σ) of brain networks. ResultsThe scores of HAMD-17, FMA and BI improved in both groups (t > 2.922, P < 0.01) after treatment, and improved more in the experimental group than in the control group (t > 2.517, P < 0.05). The serum levels of DA and 5-HT increased in both groups (t > 2.637, P < 0.05), and increased more in the experimental group (t > 2.192, P < 0.05). The serum levels of IL-6 and TNF-α decreased in the experimental group after treatment (t > 4.059, P < 0.001), and they were less than those in the control group (t > 2.154, P < 0.05). FC between left middle frontal gyrus and right anterior cingulate gyrus, as well as between left hippocampus and right precuneus were higher in the experimental group than in the control group after treatment (t > 3.867, P < 0.001), while Eg and σ increased in both groups (t > 2.828, P < 0.05), and they were higher in the experimental group (t > 2.675, P < 0.05). ConclusionCombination of Taijiquan training is more effective on depressive symptoms, motor function and activities of daily living in PSD patients, which may be related to up-regulation of serum DA and 5-HT, reduction of inflammatory factors, enhancement of prefrontal-limbic system functional connectivity and optimization of brain network topological properties.

With the rapid development of large language models and related technologies, various forms of patient modeling have emerged, including virtual patients, synthetic patients, artificial intelligence patients, and digital twin patients. Although these forms all share the core objective of patient simulation, they exhibit significant differences in theoretical ontology, data sources, modeling logic, and application orientation. Based on the abstraction levels of simulation objects and system mapping logic, this study systematically compares five paradigms—standardized patients, virtual patients, synthetic patients, AI patients, and digital twin patients—to clarify their conceptual boundaries and technical positioning. The findings indicate that these paradigms represent distinct modeling pathways: behavioral reproduction, scenario simulation, data generation, cognitive interaction, and individual system mapping, respectively. By constructing a multidimensional comparative framework, this study provides a theoretical foundation for the conceptual standardization of patient modeling and the strategic deployment of intelligent healthcare systems.

Objective To evaluate the consistency of multi-slice spiral CT (MSCT), Digital Radiography (DR) and fat-suppression MRI in detecting occult knee joint injury. Method Clinical data from 150 patients with suspected occult knee injuries who presented to the Department of imaging at the General Hospital of Ordnance Industry between August 2022 and August 2023 were retrospectively reviewed. All patients underwent MSCT, DR, and fat-suppression MRI for diagnostic evaluation. Arthroscopic or surgical findings served as the gold standard. We analyzed and compared the detection rates of specific types of occult knee injuries (ligament, meniscus, occult fracture, etc.) across the three modalities, as well as their ability to assess the degree of collapse and horizontal displacement in patients with knee fractures, and their overall diagnostic performance. Result According to the gold standard, among the 150 patients with suspected occult knee injury, 103 tested positive and 47 negative. Statistically significant differences were observed among MSCT, DR, and fat-suppression MRI in detecting occult fractures(P<0.05). The detection rates ranked in descending order asfollows: fat-suppression MRI>MSCT>DR. However, no significant difference were found in the detection rates of joint effusion and patellar cartilage injuries among the three techniques (P>0.05). Statistically differences were also note among the three techniques in detecting the degree of collapse and horizontal displacement in patients with knee fractures (P<0.05). Specifically fat-suppression MRI identified a higher proportion of grade 1 and 2 lesions than both MSCT and DR. Statistically significant differences were observed among the three techniques in diagnostic sensitivity and accuracy for occult knee injuries (P<0.05). Fat-suppression MRI demonstrated superior sensitivity (99.03%) and accuracy (96.67%) compared with MSCT (75.73%, 79.33%) and DR (61.17%, 68.00%). However, no significant difference was found in diagnostic specificity among the three techniques (P>0.05). Conclusion Compared with MSCT and DR, fat-suppression MRI offers higher diagnostic sensitivity and accuracy for occult knee injuries, particularly in identifying ligament injuries, meniscus injuries, and occult fractures.

Objective To evaluate the consistency of multi-slice spiral CT (MSCT), Digital Radiography (DR) and fat-suppression MRI in detecting occult knee joint injury. Method Clinical data from 150 patients with suspected occult knee injuries who presented to the Department of imaging at the General Hospital of Ordnance Industry between August 2022 and August 2023 were retrospectively reviewed. All patients underwent MSCT, DR, and fat-suppression MRI for diagnostic evaluation. Arthroscopic or surgical findings served as the gold standard. We analyzed and compared the detection rates of specific types of occult knee injuries (ligament, meniscus, occult fracture, etc.) across the three modalities, as well as their ability to assess the degree of collapse and horizontal displacement in patients with knee fractures, and their overall diagnostic performance. Result According to the gold standard, among the 150 patients with suspected occult knee injury, 103 tested positive and 47 negative. Statistically significant differences were observed among MSCT, DR, and fat-suppression MRI in detecting occult fractures(P<0.05). The detection rates ranked in descending order asfollows: fat-suppression MRI>MSCT>DR. However, no significant difference were found in the detection rates of joint effusion and patellar cartilage injuries among the three techniques (P>0.05). Statistically differences were also note among the three techniques in detecting the degree of collapse and horizontal displacement in patients with knee fractures (P<0.05). Specifically fat-suppression MRI identified a higher proportion of grade 1 and 2 lesions than both MSCT and DR. Statistically significant differences were observed among the three techniques in diagnostic sensitivity and accuracy for occult knee injuries (P<0.05). Fat-suppression MRI demonstrated superior sensitivity (99.03%) and accuracy (96.67%) compared with MSCT (75.73%, 79.33%) and DR (61.17%, 68.00%). However, no significant difference was found in diagnostic specificity among the three techniques (P>0.05). Conclusion Compared with MSCT and DR, fat-suppression MRI offers higher diagnostic sensitivity and accuracy for occult knee injuries, particularly in identifying ligament injuries, meniscus injuries, and occult fractures.

Objective To evaluate the consistency of multi-slice spiral CT (MSCT), Digital Radiography (DR) and fat-suppression MRI in detecting occult knee joint injury. Method Clinical data from 150 patients with suspected occult knee injuries who presented to the Department of imaging at the General Hospital of Ordnance Industry between August 2022 and August 2023 were retrospectively reviewed. All patients underwent MSCT, DR, and fat-suppression MRI for diagnostic evaluation. Arthroscopic or surgical findings served as the gold standard. We analyzed and compared the detection rates of specific types of occult knee injuries (ligament, meniscus, occult fracture, etc.) across the three modalities, as well as their ability to assess the degree of collapse and horizontal displacement in patients with knee fractures, and their overall diagnostic performance. Result According to the gold standard, among the 150 patients with suspected occult knee injury, 103 tested positive and 47 negative. Statistically significant differences were observed among MSCT, DR, and fat-suppression MRI in detecting occult fractures(P<0.05). The detection rates ranked in descending order asfollows: fat-suppression MRI>MSCT>DR. However, no significant difference were found in the detection rates of joint effusion and patellar cartilage injuries among the three techniques (P>0.05). Statistically differences were also note among the three techniques in detecting the degree of collapse and horizontal displacement in patients with knee fractures (P<0.05). Specifically fat-suppression MRI identified a higher proportion of grade 1 and 2 lesions than both MSCT and DR. Statistically significant differences were observed among the three techniques in diagnostic sensitivity and accuracy for occult knee injuries (P<0.05). Fat-suppression MRI demonstrated superior sensitivity (99.03%) and accuracy (96.67%) compared with MSCT (75.73%, 79.33%) and DR (61.17%, 68.00%). However, no significant difference was found in diagnostic specificity among the three techniques (P>0.05). Conclusion Compared with MSCT and DR, fat-suppression MRI offers higher diagnostic sensitivity and accuracy for occult knee injuries, particularly in identifying ligament injuries, meniscus injuries, and occult fractures.

Objective:To develop and evaluate a deep learning-based automatic measurement model for panoramic ultrasound biomicroscopy (UBM) images.Methods:A diagnostic test study was conducted.Preoperative UBM examination results of 372 patients who underwent implantable collamer lens (ICL) implantation were collected at the Eye Center of Renmin Hospital of Wuhan University between February 2021 and March 2023.A total of 1 368 panoramic UBM images were obtained to establish an image database.The dataset was divided into a training set (760 images), a validation set (86 images) and an internal test set (522 images).An expert panel consisting of three ophthalmologists annotated the images.The UNet+ + network was used to automatically segment anterior segment tissues, such as the cornea, lens and iris.In addition, image processing techniques and geometric localization algorithms were developed to automatically identify the anatomical landmarks of pupil diameter (PD), anterior chamber depth (ACD), angle-to-angle distance (ATA) and sulcus-to-sulcus distance (STS) to complete the measurement of these parameters.Additionally, 480 panoramic UBM images of 135 patients (240 eyes) from Aier Eye Hospital of Wuhan University were used as an external test set to further evaluate the performance of the model in different centers.The consistency between the measurements from the model and expert panel, the Pentacam system was assessed.Finally, 150 images were randomly selected from the external test set for a human-machine comparison to further evaluate the model's performance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109) and Aier eye Hospital of Wuhan University (No.2023IRBKY120903).Written informed consent was obtained from each subject.Results:In the internal test dataset and external test dataset, with manual labeling as the reference standard, the model achieved a mean Dice coefficient of not less than 0.882.At least 95.65% of the anatomical landmark localization results had Euclidean distance differences within 250 μm.The intraclass correlation coefficients (ICCs) for the measurements of PD, ACD, angle-to-angle ATA, and STS were at least 0.958, with mean relative errors not exceeding 2.407%.With the Pentacam measurements as the reference standard, the ICCs for PD in the internal and external test sets were 0.540 and 0.466, respectively, while the ICCs for ACD were 0.946 and 0.908, respectively.In the human-machine comparison, the ICCs between the model's measurements and those of senior experts were all not lower than 0.969.Conclusions:The deep learning-based model can automatically measure anterior segment parameters from preoperative panoramic UBM images of patients undergoing ICL surgery.The model demonstrates a consistency comparable to that of senior experts, while providing higher efficiency.In terms of ACD measurement, the model shows good agreement between the measurements obtained from the model and Pentacam system.

Objective:To systematically review the progress in the method development and application of distributed learning in the estimation of epidemiological effect and provide methodological reference for multi-center studies.Methods:We conducted a literature retrieval for English papers published up to December 31, 2023 by using keywords of "health/medical big data" and "distributed/federated learning". After consulting experts, we set criteria of paper inclusion and exclusion and created a framework for data extraction. We collected information about basic study details, including method, application, and evaluation. Two researchers independently screened the papers and extracted information. We used EndNote 20 for the management of literatures and EpiData for the management of data.Results:A total of 3 444 papers were collected, and 29 papers were included in the final analysis. Most of the papers (25, 86.2%) were published in or after 2019, and the papers were mainly from the United States (21/29, 72.4%). For the estimation of epidemiological effects, 22 distributed learning methods had been developed, including methods for logistic regression (8), Cox regression (8), Poisson regression (2), and generalized linear mixed model (GLMM) (4), as well as three platforms for distributed analysis (VLP, Vantage6, AusCAT). The 29 papers described 45 applications, with 20 (44.4%) focusing on the establishment of prediction model and 25 (55.6%) on association analysis. Importantly, except for GLMM, current distributed learning methods can estimate effects with little bias in 1-3 rounds of communication. These methods show less bias compared with meta-analysis, especially in the address of data heterogeneity and rare outcomes. However, less studies examined how differences in data structure and sparse data affect results, an area that requires further research.Conclusion:While distributed learning shows promise in epidemiological effect estimation, it is still in early development, requiring further research on data heterogeneity handling and communication efficiency improvement.

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.