Medical cross-modal retrieval aims to achieve semantic similarity search between different modalities of medical cases, such as quickly locating relevant ultrasound images through ultrasound reports, or using ultrasound images to retrieve matching reports. However, existing medical cross-modal hash retrieval methods face significant challenges, including semantic and visual differences between modalities and the scalability issues of hash algorithms in handling large-scale data. To address these challenges, this paper proposes a Medical image Semantic Alignment Cross-modal Hashing based on Transformer (MSACH). The algorithm employed a segmented training strategy, combining modality feature extraction and hash function learning, effectively extracting low-dimensional features containing important semantic information. A Transformer encoder was used for cross-modal semantic learning. By introducing manifold similarity constraints, balance constraints, and a linear classification network constraint, the algorithm enhanced the discriminability of the hash codes. Experimental results demonstrated that the MSACH algorithm improved the mean average precision (MAP) by 11.8% and 12.8% on two datasets compared to traditional methods. The algorithm exhibits outstanding performance in enhancing retrieval accuracy and handling large-scale medical data, showing promising potential for practical applications.
Algorithms ; Semantics ; Humans ; Ultrasonography ; Information Storage and Retrieval/methods* ; Image Processing, Computer-Assisted/methods*

Online hashing methods are receiving increasing attention in cross modal medical image retrieval research. However, existing online methods often lack the learning ability to maintain semantic correlation between new and existing data. To this end, we proposed online semantic similarity cross-modal hashing (OSCMH) learning framework to incrementally learn compact binary hash codes of medical stream data. Within it, a sparse representation of existing data based on online anchor datasets was designed to avoid semantic forgetting of the data and adaptively update hash codes, which effectively maintained semantic correlation between existing and arriving data and reduced information loss as well as improved training efficiency. Besides, an online discrete optimization method was proposed to solve the binary optimization problem of hash code by incrementally updating hash function and optimizing hash code on medical stream data. Compared with existing online or offline hashing methods, the proposed algorithm achieved average retrieval accuracy improvements of 12.5% and 14.3% on two datasets, respectively, effectively enhancing the retrieval efficiency in the field of medical images.
Semantics ; Humans ; Algorithms ; Information Storage and Retrieval/methods* ; Diagnostic Imaging ; Image Processing, Computer-Assisted/methods*

Swine enteric coronaviruses(SeCoV),such as porcine epidemic diarrhea virus(PEDV),transmissible gastroenteritis virus(TGEV),and porcine delta coronavirus(PDCoV),cause severe diarrhea in piglets,resulting in substantial losses in pig farming.In this study we establish a triple fluorescence reverse transcription-quantitative PCR(RT-qPCR)method for the simultaneous de-tection of PEDV,TGEV,and PDCoV.The specific primers and probes for each target virus were designed based on conserved sequences from the PEDV M gene,the TGEV ORF 1b gene,and the PDCoV ORF 1b gene respectively.Following the optimization of parameters and conditions,a triple RT-qPCR method was successfully established to simultaneously detect PEDV,TGEV,and PD-CoV.The developed assay exhibits strong specificity for these three pathogens without any cross-reaction with other common porcine viruses like CSFV,PCV2,PoRVA,PRV,and PRRSV.The de-tection limit of linear templates for pTOPO-PEDV 128,pTOPO-TGEV 116,and pTOPO-PDCoV 125 recombinant plasmids were 16.835,17.610 and 17.020 copies/μL,respectively.The intra group and inter group coefficients of variation were less than 5％,with no significant differences observed(P＞0.05).Moreover,the detection consistency rate of the developed RT-qPCR was compared with standard method and showed 100％agreement.Out of 35 small intestine tissue samples,17 tested positive for PEDV,resulting in a positive rate of 48.57％(17/35).The tests for TGEV and PDCoV yielded negative results,and no mixed infections were detected.Based on the above results,the tri-ple RT-qPCR method established is specific,sensitive,stable,and rapid,and can be used for clinical detection and differential diagnosis of PEDV,TGEV,and PDCoV simultaneously,providing a method for the detection and epidemiological investigation of porcine diarrhea coronaviruses.

OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.

BACKGROUND:Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.Ferroptosis,a novel form of programmed cell death,is closely associated with the onset and progression of intervertebral disc degeneration;however,its precise mechanisms remain unclear.OBJECTIVE:To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells,thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration.METHODS:Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide(0,25,50,100,and 200 μmol/L),and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay.Interventions with 100 μmol/L tert-butyl hydroperoxide,10 μmol/L RSL3,or dimethylsulfoxide were applied to nucleus pulposus cells,and cell proliferation was evaluated using the EdU assay.The expression levels of ferroptosis-related proteins(glutathione peroxidase 4,ferritin heavy chain 1,PTGS2,and ACSL4)and intervertebral disc degeneration marker proteins(matrix metalloproteinase 13 and Col2A)were analyzed via western blot and immunofluorescence.Additionally,reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe.Mitochondrial morphological changes were observed under transmission electron microscopy.RESULTS AND CONCLUSION:(1)tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells.(2)tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells.(3)tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1,while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2.(4)tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells.(5)Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide,including contraction,reduced cristae,and increased membrane density.(6)tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells.In conclusion,tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells,contributing to the development of intervertebral disc degeneration.This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies.

Swine enteric coronaviruses(SeCoV),such as porcine epidemic diarrhea virus(PEDV),transmissible gastroenteritis virus(TGEV),and porcine delta coronavirus(PDCoV),cause severe diarrhea in piglets,resulting in substantial losses in pig farming.In this study we establish a triple fluorescence reverse transcription-quantitative PCR(RT-qPCR)method for the simultaneous de-tection of PEDV,TGEV,and PDCoV.The specific primers and probes for each target virus were designed based on conserved sequences from the PEDV M gene,the TGEV ORF 1b gene,and the PDCoV ORF 1b gene respectively.Following the optimization of parameters and conditions,a triple RT-qPCR method was successfully established to simultaneously detect PEDV,TGEV,and PD-CoV.The developed assay exhibits strong specificity for these three pathogens without any cross-reaction with other common porcine viruses like CSFV,PCV2,PoRVA,PRV,and PRRSV.The de-tection limit of linear templates for pTOPO-PEDV 128,pTOPO-TGEV 116,and pTOPO-PDCoV 125 recombinant plasmids were 16.835,17.610 and 17.020 copies/μL,respectively.The intra group and inter group coefficients of variation were less than 5％,with no significant differences observed(P＞0.05).Moreover,the detection consistency rate of the developed RT-qPCR was compared with standard method and showed 100％agreement.Out of 35 small intestine tissue samples,17 tested positive for PEDV,resulting in a positive rate of 48.57％(17/35).The tests for TGEV and PDCoV yielded negative results,and no mixed infections were detected.Based on the above results,the tri-ple RT-qPCR method established is specific,sensitive,stable,and rapid,and can be used for clinical detection and differential diagnosis of PEDV,TGEV,and PDCoV simultaneously,providing a method for the detection and epidemiological investigation of porcine diarrhea coronaviruses.

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.

BACKGROUND:Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.Ferroptosis,a novel form of programmed cell death,is closely associated with the onset and progression of intervertebral disc degeneration;however,its precise mechanisms remain unclear.OBJECTIVE:To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells,thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration.METHODS:Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide(0,25,50,100,and 200 μmol/L),and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay.Interventions with 100 μmol/L tert-butyl hydroperoxide,10 μmol/L RSL3,or dimethylsulfoxide were applied to nucleus pulposus cells,and cell proliferation was evaluated using the EdU assay.The expression levels of ferroptosis-related proteins(glutathione peroxidase 4,ferritin heavy chain 1,PTGS2,and ACSL4)and intervertebral disc degeneration marker proteins(matrix metalloproteinase 13 and Col2A)were analyzed via western blot and immunofluorescence.Additionally,reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe.Mitochondrial morphological changes were observed under transmission electron microscopy.RESULTS AND CONCLUSION:(1)tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells.(2)tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells.(3)tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1,while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2.(4)tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells.(5)Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide,including contraction,reduced cristae,and increased membrane density.(6)tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells.In conclusion,tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells,contributing to the development of intervertebral disc degeneration.This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.