Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]

Objective To deeply understand the anatomical basis of temporomandibular joint disorders,and explore and master the pathological characteristics of anterior displacement of temporomandibular joint disc through cadaveric dissection and 3D printing technology.Methods By dissecting the temporomandibular joints of 40 head and neck specimens,the bilateral structures of the temporomandibular joints were measured to obtain condyle and articular disc data.3D modeling was carried out using 3ds Max software and printed out a model of temporomandibular joint.The pathological model of the anterior disc displacement with reduction(ADDwR)was simulated by adjusting the opening degree,the position of the articular disk,and the position of the condyle of the model.Results The precise data of the right and left temporomandibular joint discs and condyle were successfully obtained by dissection and measurement.The thickness of the anterior band of left temporomandibular joint discs was(2.02±0.57)mm,the thickness of the middle band was(1.46±0.33)mm,the thickness of the posterior band was(3.00±0.46)mm,the anterior-posterior diameter was(9.60±0.72)mm,and the internal-external diameter was(17.73±0.84)mm.While the thickness of the anterior band of right temporomandibular joint discs was(1.84±0.35)mm,and the thickness of the middle band was(1.43±0.28)mm,the thickness of posterior band was(3.08±0.49)mm,the anterior-posterior diameter was(9.30±0.88)mm,and the internal-external diameter was(17.38±1.10)mm.The internal-external diameter of the left temporomandibular joint condyle was(18.97±0.41)mm,and the anterior-posterior diameter was(8.56±0.43)mm;the internal-external diameter of the right temporomandibular joint condyle was(18.86±0.75)mm,and the anterior-posterior diameter was(8.40±0.30)mm.The standard temporomandibular joint model was printed out by the measured data.The model was utilized to simulate the physiological state of temporomandibular joint under normal conditions,as well as the three pathological states of closed mouth,closed mouth to open mouth,and open mouth in the case of ADDwR.Conclusion The temporomandibular joint model can more intuitively present the changes of anatomical structure in reversible temporoman-dibular joint disorders,which is helpful for understanding and mastering the different classification of this disease.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Objective To deeply understand the anatomical basis of temporomandibular joint disorders,and explore and master the pathological characteristics of anterior displacement of temporomandibular joint disc through cadaveric dissection and 3D printing technology.Methods By dissecting the temporomandibular joints of 40 head and neck specimens,the bilateral structures of the temporomandibular joints were measured to obtain condyle and articular disc data.3D modeling was carried out using 3ds Max software and printed out a model of temporomandibular joint.The pathological model of the anterior disc displacement with reduction(ADDwR)was simulated by adjusting the opening degree,the position of the articular disk,and the position of the condyle of the model.Results The precise data of the right and left temporomandibular joint discs and condyle were successfully obtained by dissection and measurement.The thickness of the anterior band of left temporomandibular joint discs was(2.02±0.57)mm,the thickness of the middle band was(1.46±0.33)mm,the thickness of the posterior band was(3.00±0.46)mm,the anterior-posterior diameter was(9.60±0.72)mm,and the internal-external diameter was(17.73±0.84)mm.While the thickness of the anterior band of right temporomandibular joint discs was(1.84±0.35)mm,and the thickness of the middle band was(1.43±0.28)mm,the thickness of posterior band was(3.08±0.49)mm,the anterior-posterior diameter was(9.30±0.88)mm,and the internal-external diameter was(17.38±1.10)mm.The internal-external diameter of the left temporomandibular joint condyle was(18.97±0.41)mm,and the anterior-posterior diameter was(8.56±0.43)mm;the internal-external diameter of the right temporomandibular joint condyle was(18.86±0.75)mm,and the anterior-posterior diameter was(8.40±0.30)mm.The standard temporomandibular joint model was printed out by the measured data.The model was utilized to simulate the physiological state of temporomandibular joint under normal conditions,as well as the three pathological states of closed mouth,closed mouth to open mouth,and open mouth in the case of ADDwR.Conclusion The temporomandibular joint model can more intuitively present the changes of anatomical structure in reversible temporoman-dibular joint disorders,which is helpful for understanding and mastering the different classification of this disease.

Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*