ObjectiveTo investigate the effect of bone morphogenetic protein 3 （BMP3） on the expression of inflammatory factors and joint damage in adjuvant arthritis （AA） induced by Freund′s complete adjuvant （FCA） in rats. MethodsThe AIA model was established in SD rats by intradermal injection of FCA into the toes of the left hind limb， and BMP3 overexpressing adenovirus （Ad-BMP3） or control adenovirus （Ad-NC） was injected in situ into the knee joint cavity on day 8 after modeling. Subsequently， HE staining was used to observe the histopathological changes in the synovium， immunohistochemistry was used to detect the expression of BMP3 in the synovium， and ELISA was used to analyze the expression levels of IL-6， IL-1β and TNF-α in the serum. Primary fibroblast-like synoviocytes （FLS） were isolated from AIA rats， the expression of BMP3 in FLS was knocked down or overexpressed， and Western blot and qRT-PCR were used to detect the expression levels of BMP3 and inflammatory factors in FLS. ResultsHE staining confirmed the successful establishment of the AIA model. Compared with normal rats， AIA rats showed decreased BMP3 expression in synovial tissue. Knockdown of BMP3 promoted the protein expression of inflammatory factors （IL-6， IL-1β， IL-17A， TNF-α） and the mRNA expression of chemokines ［C-C motif chemokine ligand 2 （CCL2）， C-C motif chemokine ligand 3 （CCL3）， Vascular Cell Adhesion Molecule-1 （VCAM-1）］ in FLS. In contrast， overexpression of BMP3 suppressed the expression of these inflammatory factors and chemokines. Intra-articular injection of BMP3-overexpressing adenovirus in AIA rats upregulated BMP3 expression in synovial tissue and inhibited synovial inflammation and bone erosion. ConclusionBMP3 suppresses the production of inflammatory factors and chemokines in FLS， thereby alleviating synovial hyperplasia and bone erosion in arthritis.

By aggregating the essence of theories related with depressive syndrome from historical medical practitioners and based on the extensive clinical experience,traditional Chinese medicine(TCM)master Lin Yi proposed the theory of six-stagnation-based breast disease prevention and treatment.She pointed out that the occurrence of breast diseases is related to six stagnations(qi stagnancy,blood stagnancy,phlegm stagnancy,dampness stagnancy,food stagnancy,and fire stagnancy),and the treatment for breast diseases should start from the six stagnations.The development and progression of breast cancer is closely associated with the imbalance of internal environment and the formation of six stagnations,and breast cancer is one of the major diseases suitable for the TCM syndrome differentiation and treatment.For the treatment of early breast cancer,Professor Lin Yi proposed to divide early breast cancer into four stages,namely perioperative period,peri-chemotherapy period,peri-radiotherapy period,and consolidation period.Guided by the theory of six-stagnation-based breast disease prevention and treatment,therapies of soothing the liver,resolving phlegm,removing stasis,clearing heat,eliminating dampness,promoting digestion,fortifying the spleen,and tonifying the kidney are employed to harmonize the internal environment and alleviate symptoms.The theory of six-stagnation-based breast disease prevention and treatment enriches the TCM theory for the prevention and treatment of breast cancer,refines the principles and methods for the staging and syndrome differentiation of early breast cancer,and holds significant implications for enhancing the efficacy of integrated TCM and western medicine in managing early breast cancer.

Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Vaccine immunization is the most effective and cost-efficient method for infectious disease prevention and control.Since the outbreak of novel coronavirus pneumonia(caused by the novel coronavirus,COVID-19)at the end of 2019,third generation mRNA nucleic acid vaccines has been applied to stop viral spread.mRNA vaccines,rather than relying on the immune activation mode of traditional vaccines,are an innovative breakthrough using the body's own cells to produce antigens,thereby activating double specific immunity,forming immune memory,and providing more lasting specific immunity.Com-pared with the traditional first-generation(inactivated)and second-generation(genetically engineered)vaccines,mRNA vac-cines,because of the advantages provided by this platform,play important roles in the prevention and control of major sudden infectious diseases.Consequently,mRNA vaccines were the world's first COVID-19 vaccines to be applied clinically,thus ser-ving as a barometer in the field of vaccine research and development.Herein,the molecular design and presentation of mRNA vaccines,and the molecular mechanisms of their activation of the immune response are reviewed,to provide a theoretical basis for future application of novel mRNA vaccines in the prevention and control of animal infectious diseases.

Objective To explore the clinical value of three-dimensional(3D)fracture mapping in improving the consistency of Arbeitsgemeinschaft für Osteosynthesefragen(AO)/the Orthopaedic Trauma Association(OTA)classification and optimizing preoperative surgical planning for Pilon fractures.Methods This single-center retrospective cohort study included 60 Pilon fracture patients admitted to the Trauma Emergency Center of the Third Hospital of Hebei Medical University between January 2022 and December 2024.All patients underwent preoperative computed tomography(CT)scans.Image standardization and expert manual segmentation/annotation of fracture lines and fragments were performed with 3D Slicer software.3D fracture lines extracted from gold-standard models were registered to a unified standard tibial model.A 3D probability heatmap was constructed by counting spatial fracture frequency,with high-incidence zones analyzed via spatial clustering algorithms.Three orthopedic surgeons independently completed AO/OTA classification and preoperative planning with the assistance of conventional CT only and CT with 3D fracture mapping.Accuracy,time consumption,inter-observer consistency(Cohen's κ),planning time,plan modification frequency,and subjective scores were evaluated.Results The 3D fracture heatmap revealed that fracture lines predominantly concentrated in the anterolateral and posteromedial regions of the distal tibia,with an average of(4.2±1.1)hotspots,a coverage rate of(78.3±5.6)%,and(3.5±1.0)clustering areas.With 3D fracture mapping assistance,classification accuracy was improved to(88.0±5.0)%compared to(75.0±8.0)%with conventional CT(P=0.001);classification time reduced to(10.4±2.5)min from(15.2±3.1)min(P<0.001);and Cohen's κ increased from 0.68±0.05 to 0.82±0.03(P=0.002).For preoperative planning,the average planning time was(15.8±3.2)min in the 3D mapping-assisted group,which was significantly shorter than that of conventional CT group(22.5±4.3)min(P<0.001);the number of plan modifications was(1.5±0.7)times,lower than that of conventional CT group(3.2±1.1)times(P<0.001),and the subjective score was 8.9±0.9,higher than that of conventional CT group(6.8±1.2)(P<0.001).Conclusion The 3D fracture mapping accurately characterizes spatial distribution patterns of Pilon fractures,significantly improves classification accuracy,inter-observer consistency,and preoperative planning efficiency,and thus holds substantial clinical value.

[Objective]To construct a prediction model for brucellosis by using a deep neural network algorithm to improve the early detection.[Methods]We collected the clinical data of 202 brucellosis patients and 319 non-brucellosis patients admitted to Hohhot Occupational Disease Prevention and Treatment Hospital in 2023,and analyzed data such as gender,age,blood routine indices and clinical diagnosis.A prediction model for brucellosis was constructed by using a deep neural network algorithm and optimized through 10-fold cross-validation.Performance metrics included sensitivity,false negative rate,specificity,false positive rate,accuracy,positive predictive value,negative predictive value,F1 score,and area under the receiver operating characteristic curve(AUC).The optimal model was interpreted by using SHapley Additive exPlanations(SHAP)to clarify decision-making logic and feature influencing mechanisms.[Results]Data visualization analysis revealed no significant difference between brucellosis and non-brucellosis groups.The optimal model demonstrated good performance:sensitivity(85.3%),specificity(92.1%),accuracy(89.5%),AUC(96.6%),95%CI(0.937,0.977).SHAP analysis identified age,platelet count,mean platelet volume,basophil ratio,red blood cell distribution width,and absolute basophil count as significant predictors of brucellosis.[Conclusions]The deep neural network prediction model constructed in this study has good performance and can provide reliable support for the early diagnosis,prevention and control of brucellosis.Identification of key brucellosis-related influencing features will help further understand the pathogenesis of the disease,and this model holds promise for broad clinical application in the future.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:The objective of this study was to understand the incidence, spatial and temporal distribution characteristics and trends of bacillary dysentery in China from 2005 to 2024 in order to identify the high-risk groups and reveal the potential risk factors and to provide a scientific basis for optimizing the allocation of preventive and control resources, formulating targeted intervention strategies and assessing the effectiveness of the measures.Methods:The nationally reported incidence data of bacillary dysentery was collected from 2005 to 2024 in the Chinese Center for Disease Control and Prevention National Notifiable Diseases Reporting Information System. Descriptive epidemiological methods were used to analyze the population characteristics of bacillary dysentery cases. A Joinpoint regression model was constructed to examine long-term trends in reported incidence rates and spatial dynamic window scanning statistics were applied to detect spatial clusters of bacillary dysentery cases.Results:Between 2005 and 2024, 3 520 247 cases of bacillary dysentery were reported across China, with an average incidence rate of 12.88 per 100 000 people, after which the rate of decline decreased. The incidence rate showed a general downward trend, featuring a significant inflection point in 2016. It exhibited marked seasonality, peaking from May to October (summer-autumn), which weakened over time. From 2005 to 2024, the most likely clusters were in Beijing and Tianjin. Males, infants, the elderly, farmers, and children not in daycare showed many cases.Conclusions:The results revealed that the peak incidence of bacillary dysentery in China from 2005 to 2024 was featured in the summer-autumn months. High-incidence areas were mainly Beijing and Tianjin. The key groups, including males, infants, the elderly, farmers and children not in daycare, were identified. Enhancing surveillance, targeted health education, and preventive measures, especially in these key populations and in regions where the disease shows a high incidence should be strengthened.

Objective To explore the clinical value of three-dimensional(3D)fracture mapping in improving the consistency of Arbeitsgemeinschaft für Osteosynthesefragen(AO)/the Orthopaedic Trauma Association(OTA)classification and optimizing preoperative surgical planning for Pilon fractures.Methods This single-center retrospective cohort study included 60 Pilon fracture patients admitted to the Trauma Emergency Center of the Third Hospital of Hebei Medical University between January 2022 and December 2024.All patients underwent preoperative computed tomography(CT)scans.Image standardization and expert manual segmentation/annotation of fracture lines and fragments were performed with 3D Slicer software.3D fracture lines extracted from gold-standard models were registered to a unified standard tibial model.A 3D probability heatmap was constructed by counting spatial fracture frequency,with high-incidence zones analyzed via spatial clustering algorithms.Three orthopedic surgeons independently completed AO/OTA classification and preoperative planning with the assistance of conventional CT only and CT with 3D fracture mapping.Accuracy,time consumption,inter-observer consistency(Cohen's κ),planning time,plan modification frequency,and subjective scores were evaluated.Results The 3D fracture heatmap revealed that fracture lines predominantly concentrated in the anterolateral and posteromedial regions of the distal tibia,with an average of(4.2±1.1)hotspots,a coverage rate of(78.3±5.6)%,and(3.5±1.0)clustering areas.With 3D fracture mapping assistance,classification accuracy was improved to(88.0±5.0)%compared to(75.0±8.0)%with conventional CT(P=0.001);classification time reduced to(10.4±2.5)min from(15.2±3.1)min(P<0.001);and Cohen's κ increased from 0.68±0.05 to 0.82±0.03(P=0.002).For preoperative planning,the average planning time was(15.8±3.2)min in the 3D mapping-assisted group,which was significantly shorter than that of conventional CT group(22.5±4.3)min(P<0.001);the number of plan modifications was(1.5±0.7)times,lower than that of conventional CT group(3.2±1.1)times(P<0.001),and the subjective score was 8.9±0.9,higher than that of conventional CT group(6.8±1.2)(P<0.001).Conclusion The 3D fracture mapping accurately characterizes spatial distribution patterns of Pilon fractures,significantly improves classification accuracy,inter-observer consistency,and preoperative planning efficiency,and thus holds substantial clinical value.