Objective To observe the efficacy of nomogram model based on enhanced MRI radiomics,deep learning(DL)and clinical features for differentiating spinal tuberculosis and pyogenic spondylitis.Methods Totally 59 cases of spinal tuberculosis and 66 of pyogenic spondylitis were retrospectively enrolled.Radiomics,DL and clinical features relevant to differentiating spinal tuberculosis and pyogenic spondylitis were selected.Then a predictive model was constructed using logistic regression based on the selected optimal features,and a comprehensive nomogram model was developed through combination of the above features.The effectiveness of these models for distinguishing spinal tuberculosis from pyogenic spondylitis were visualized based on receiver operating characteristic curves,calidration curves and decision curves.Results The nomogram model demonstrated the highest area under the curve(AUC)in both training set and test set,with AUC of 0.997 and 0.920,respectively.In test set,DeLong test indicated that the difference of AUC between the nomogram model and clinical model was significant(P=0.002),while no significant difference was observed between the nomogram model and the other models(all P＞0.05).The nomogram model provided the highest overall net benefit and exhibited good calibration for distinguishing spinal tuberculosis from pyogenic spondylitis.Conclusion Nomogram model based on enhanced MRI radiomics,DL and clinical features demonstrated high efficacy for differentiating spinal tuberculosis from pyogenic spondylitis.

Objective:To investigate whether continuous cardiac output (CO) parameters obtained by LiDCO in hemodynamic monitoring of severe patients are consistent with pulse index continuous cardiac output (PiCCO).Methods:From May 18, 2024 to January 10, 2025, 12 critically ill patients who were monitored by PiCCO in the Intensive Care Unit Department of China-Japan Friendship Hospital were prospectively collected. The PiCCO and LiDCO systems were simultaneously connected to the same critically ill patient, injected with ice saline for external calibration, and the average of paired continuous CO measurements were collected. Bland-Altman was used to analyze whether the two were consistent, and Spearman was used to analyze the correlation between norepinephrine dosage and bias.Results:In the data series of 70 pairs, the CO measured by PiCCO was 5.55±1.74, and the CO measured by LiDCO was 4.40(2.90, 6.50), with a bias of 0.52(95% CI: 0.07-0.96) and an upper limit of agreement of 4.2(95% CI: 3.4-4.9), the lower limit of the conformance limit was -3.1(95% CI: -3.9 to -2.4), and the percentage error was 66%, exceeding the clinically acceptable 45%. In the data series where norepinephrine was continuously pumped at the time of data collection, there was a moderate positive correlation between norepinephrine dosage and absolute bias ( r=0.47, P<0.05). There were statistically significant differences in absolute values of bias between groups defined as 0.5 μg/(kg·min) and 1 μg/(kg·min) ( P<0.05). Conclusions:There is no clinically acceptable consistency between LiDCO and PiCCO for continuous CO monitoring in severe patients, and the size of bias may be related to the dosage of norepinephrine.

The drugs used to improve brain metabolism mainly include ergotamine derivatives,GABA derivatives,vitamin B6 derivatives,neuropeptides,morpholines,hormones and other.However,these drugs may have adverse reactions during clinical application.This article focuses on the adverse effects of commonly used drugs for brain metabolism,and reviews the studies on the new state of pharmaceutical substances,such as drug combination,chiral resolution of isomers,crystal form of dominant drugs,co-crystal drugs and nanodrugs,with the aim of reducing adverse reactions.By summarizing the research on modifying the solid state of drugs to mitigate adverse reactions,this article provides new research insights for obtaining new drug with less adverse reaction and greater clinical value.

Bovine neosporosis,a significant disease affecting the livestock industry,is caused by the protozoan parasite Neospora caninum(N.caninum).The current absence of efficacious vaccines and therapeutics necessitates the exploration of novel interventions.Cordycepin,a bioactive nucleo-side derived from Cordyceps militaris,has garnered attention for its diverse pharmacological properties.This study endeavors to elucidate the inhibitory effects of cordycepin on N.caninum in-fection.The cytotoxicity of cordycepin to bovine macrophages was assessed using the CCK-8 assay to ascertain a non-toxic concentration range.The impact of cordycepin on the N.caninum burden within bovine macrophages was evaluated using qPCR analysis and immunofluorescence assays.Additionally,the modulation of cytokine,interferon,and defensin expression induced by N.cani-num in the presence of cordycepin was examined through qRT-PCR analysis.The results showed that cordycepin exhibited negligible cytotoxicity to bovine macrophages at concentrations ranging from 2.812 5 to 180.000 0 μmol/L,compared to the control group.At concentrations of 5.625 0,11.250 0,and 22.500 0 μmol/L,cordycepin significantly reduced the intracellular N.caninum loads and diminished the intensity of intracellular parasite fluorescence.While N.caninum infection downregulated the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,and IL-6,cordycepin treatment robustly induced their expression.Furthermore,although cordycepin treatment reduced the expression levels of IFN-α,IFN-β,and IFN-γ that were upregulated by N.caninum infection,it maintained substantial expression levels.In conclusion,cordycepin demon-strates a promising resistance against N.caninum infection,suggesting its potential as a therapeu-tic agent for the treatment of bovine neosporosis.

Objective:To evaluate the effect of superficial temporal artery to middle cerebral artery (STA-MCA) bypass on cognitive function, cerebral perfusion, and integrity of white matter tracts by comparing cognitive function scores, fractional anisotropy (FA), time to maximum (T max), and cerebral blood flow (CBF) at different time points before and after STA-MCA bypass, and analyze the relations of cognitive function with cerebral perfusion and white matter tract integrity so as to provide evidences for treatment of moyamoya disease (MMD) patients with mild cognitive impairment. Methods:A retrospective analysis was performed; 30 MMD patients with mild cognitive impairment received STA-MCA bypass at Department of Neurosurgery, Lianyungang Hospital Affiliated to Xuzhou Medical University (Lianyungang First People's Hospital) from January 2023 to August 2024 were enrolled. Before and 1, 3, and 6 months after STA-MCA bypass, all patients accepted Montreal cognitive assessment (MoCA), CT perfusion imaging, and diffusion tensor imaging (DTI). Differences in MoCA score, CBF, T max, and FA at different time points before and after surgery were compared. Spearman rank correlation was used to analyze the correlation of MoCA score with cerebral perfusion parameters and FA. Results:(1) In these MMD patients with mild cognitive impairment, CBF 3 and 6 months after STA-MCA bypass was significantly increased compared with that before STA-MCA bypass, and CBF 6 months after STA-MCA bypass was significantly higher than that 1 and 3 months after STA-MCA bypass ( P<0.05); T max 1, 3 and 6 months after STA-MCA bypass was significantly shortened compared with that before STA-MCA bypass, and T max 6 months after STA-MCA bypass was significantly shortened than that 1 and 3 months after STA-MCA bypass ( P<0.05); FA 6 months after STA-MCA bypass was significantly increased compared with that before, and 1 and 3 months after STA-MCA bypass ( P<0.05); MoCA score 6 months after STA-MCA bypass was significantly increased compared with that before and 1 month after STA-MCA bypass ( P<0.05). (2) In MMD patients with mild cognitive impairment, the preoperative MoCA score was positively correlated with preoperative CBF and FA ( r s=0.428, P=0.018; r s=0.438, P=0.015) and negatively correlated with preoperative T max ( r s=-0.380, P=0.039); 6 months after STA-MCA bypass, the MoCA score was positively correlated with CBF and FA ( r s=0.365, P=0.047; r s=0.400, P=0.028) and negatively correlated with T max ( r s=-0.371, P=0.043). Conclusion:STA-MCA bypass can improve cerebral perfusion, white matter fiber tract repair and cognitive function in MMD patients with mild cognitive impairment, and improvement of cognitive function is related to cerebral perfusion and white matter fiber tract repair.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

This experiment was conducted to study the effects of replacing feed protein by Herme-tia illucens larvae meal on immune function,intestinal morphology and microflora of Sichuan white geese.A total of 64 healthy 1-day-old Sichuan white geese were randomly allocated into 4 groups with 4 replicates in each group and 4 geese in each replicate,namely the control group,the 2％HILM,4％HILM and 8％HILM groups fed diets contained 0％,2％,4％and 8％of HILM,re-spectively.The experimental period was 40 days.The results showed that compared with the con-trol group,8％HILM increased the levels of serum IgG1,IgG2a and complement C3,and the difference was statistically significant(P＜0.01).4％HILM significantly increased the expression level of CD4(P＜0.05),and 8％HILM significantly increased the expression level of IL-10(P＜0.05).The ratio of villus length to crypt depth(VH/CD)in the jejunum and ileum in 4％HILM group was significantly increased(P＜0.05).The SIgA level of jejunum was significantly increased in all HILM replacement groups(P＞0.05).The abundance of Bacteroides in 4％HILM group were extremely significantly increased(P＜0.01),and the abundance of Bilophila and Bilophila wadsworthia were significantly decreased in all HILM replacement groups(P＜0.05).In conclu-sion,HILM can enhance the immune function of Sichuan white geese,improve the intestinal mor-phology of jejunum and ileum,enhance the local mucosal immunity of jejunum,increase the abun-dance of beneficial bacteria in cecum and decrease the abundance of harmful bacteria in cecum,and protect intestinal health.

Bovine neosporosis,a significant disease affecting the livestock industry,is caused by the protozoan parasite Neospora caninum(N.caninum).The current absence of efficacious vaccines and therapeutics necessitates the exploration of novel interventions.Cordycepin,a bioactive nucleo-side derived from Cordyceps militaris,has garnered attention for its diverse pharmacological properties.This study endeavors to elucidate the inhibitory effects of cordycepin on N.caninum in-fection.The cytotoxicity of cordycepin to bovine macrophages was assessed using the CCK-8 assay to ascertain a non-toxic concentration range.The impact of cordycepin on the N.caninum burden within bovine macrophages was evaluated using qPCR analysis and immunofluorescence assays.Additionally,the modulation of cytokine,interferon,and defensin expression induced by N.cani-num in the presence of cordycepin was examined through qRT-PCR analysis.The results showed that cordycepin exhibited negligible cytotoxicity to bovine macrophages at concentrations ranging from 2.812 5 to 180.000 0 μmol/L,compared to the control group.At concentrations of 5.625 0,11.250 0,and 22.500 0 μmol/L,cordycepin significantly reduced the intracellular N.caninum loads and diminished the intensity of intracellular parasite fluorescence.While N.caninum infection downregulated the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,and IL-6,cordycepin treatment robustly induced their expression.Furthermore,although cordycepin treatment reduced the expression levels of IFN-α,IFN-β,and IFN-γ that were upregulated by N.caninum infection,it maintained substantial expression levels.In conclusion,cordycepin demon-strates a promising resistance against N.caninum infection,suggesting its potential as a therapeu-tic agent for the treatment of bovine neosporosis.

The drugs used to improve brain metabolism mainly include ergotamine derivatives,GABA derivatives,vitamin B6 derivatives,neuropeptides,morpholines,hormones and other.However,these drugs may have adverse reactions during clinical application.This article focuses on the adverse effects of commonly used drugs for brain metabolism,and reviews the studies on the new state of pharmaceutical substances,such as drug combination,chiral resolution of isomers,crystal form of dominant drugs,co-crystal drugs and nanodrugs,with the aim of reducing adverse reactions.By summarizing the research on modifying the solid state of drugs to mitigate adverse reactions,this article provides new research insights for obtaining new drug with less adverse reaction and greater clinical value.

Objective:To investigate whether continuous cardiac output (CO) parameters obtained by LiDCO in hemodynamic monitoring of severe patients are consistent with pulse index continuous cardiac output (PiCCO).Methods:From May 18, 2024 to January 10, 2025, 12 critically ill patients who were monitored by PiCCO in the Intensive Care Unit Department of China-Japan Friendship Hospital were prospectively collected. The PiCCO and LiDCO systems were simultaneously connected to the same critically ill patient, injected with ice saline for external calibration, and the average of paired continuous CO measurements were collected. Bland-Altman was used to analyze whether the two were consistent, and Spearman was used to analyze the correlation between norepinephrine dosage and bias.Results:In the data series of 70 pairs, the CO measured by PiCCO was 5.55±1.74, and the CO measured by LiDCO was 4.40(2.90, 6.50), with a bias of 0.52(95% CI: 0.07-0.96) and an upper limit of agreement of 4.2(95% CI: 3.4-4.9), the lower limit of the conformance limit was -3.1(95% CI: -3.9 to -2.4), and the percentage error was 66%, exceeding the clinically acceptable 45%. In the data series where norepinephrine was continuously pumped at the time of data collection, there was a moderate positive correlation between norepinephrine dosage and absolute bias ( r=0.47, P<0.05). There were statistically significant differences in absolute values of bias between groups defined as 0.5 μg/(kg·min) and 1 μg/(kg·min) ( P<0.05). Conclusions:There is no clinically acceptable consistency between LiDCO and PiCCO for continuous CO monitoring in severe patients, and the size of bias may be related to the dosage of norepinephrine.