Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Objective:To investigate the effect of Lulongzaisheng decoction on ferroptosis in aplastic anemia (AA) model mice and its potential mechanism of action on AA.Methods:Using female BALB/c mice as controls (control group), a mouse model of AA was established by intraperitoneal injection of interferon-γ (IFN-γ) combined with oral gavage of busulfan. The AA group was treated with continuous oral gavage of Lulongzaisheng decoction for 10 days. The effects on the Jak2/Stat3/Acsl4 signaling pathway were assessed. Bone marrow biopsy and histopathological examination were performed to observe the degree of AA in each group of mice. Flow cytometry was used to detect the production of lipid reactive oxygen species (ROS) in the bone marrow cells. Immunohistochemical staining was performed to observe the expression of 4-HNE in the sternum. Western blot analysis was conducted to determine the protein expression levels of Jak2, p-Jak2, Stat3, p-Stat3, and Acsl4. ELISA was used to measure the levels of interleukin-6 (IL-6) in the peripheral blood plasma.Results:Compared with the control group, mice in the AA group exhibited a reduction in hematopoietic tissues within the bone marrow cavity and significant fatty infiltration. In contrast, mice in the AA+Lulongzaisheng decoction group showed partial recovery of the bone marrow and a decrease in fatty infiltration. The lipid ROS proportions in the control, AA, and AA+Lulongzaisheng decoction groups were (47.01±3.07) %, (53.81±1.99) %, and (49.50±3.98) %, respectively ( P<0.05), indicating that the AA + Lulongzaisheng decoction group had a slightly lower accumulation of lipid ROS than the AA group. The expression areas of 4-HNE in the bone marrow cavity for the control, AA, and AA+Lulongzaisheng decoction groups were (6.34±1.07) %, (35.26±3.68) %, and (16.97±1.30) %, respectively ( P<0.05), demonstrating a significant reduction in 4-HNE accumulation in the bone marrow in the AA + Lulongzaisheng decoction group compared with that in the AA group. Compared with the control group, the AA group exhibited upregulated expression of the ferroptosis-related protein Acsl4, along with increased expression of p-Stat3 and p-Jak2. In the AA+ Lulongzaisheng decoction group, the expression of Acsl4 was downregulated, whereas those of p-Stat3 and p-Jak2 were inhibited ( P<0.05). The levels of IL-6 in the peripheral blood plasma were (65.60±6.01), (166.50±3.32), and (119.37±4.29) pg/ml in the control, AA, and AA+Lulongzaisheng decoction groups, respectively ( P<0.05). Compared with the AA group, the AA + Lulongzaisheng decoction group exhibited a significant decrease in IL-6 levels. Conclusion:This study shows that Lulongzaisheng decoction has a significant therapeutic effect on AA model mice by regulating the Jak2/Stat3/Acsl4 pathway. The mechanism of action of this traditional Chinese medicine involves inhibiting the Jak2/Stat3 signaling pathway and regulating the expression of Acsl4, thereby improving hematopoietic function in AA model mice. These findings provide new drug targets and treatment strategies for the treatment of AA.

Closed-loop neuromodulation, especially using the phase of the electroencephalography (EEG) rhythm to assess the real-time brain state and optimize the brain stimulation process, is becoming a hot research topic. Because the EEG signal is non-stationary, the commonly used EEG phase-based prediction methods have large variances, which may reduce the accuracy of the phase prediction. In this study, we proposed a machine learning-based EEG phase prediction network, which we call EEG phase prediction network (EPN), to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data. We verified the performance of EPN on pre-recorded data, simulated EEG data, and a real-time experiment. Compared with widely used state-of-the-art models (optimized multi-layer filter architecture, auto-regress, and educated temporal prediction), EPN achieved the lowest variance and the greatest accuracy. Thus, the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Machine Learning ; Signal Processing, Computer-Assisted ; Male ; Adult ; Neural Networks, Computer ; Brain Waves/physiology*

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To establish a method for the rapid detection of varicella-zoster virus (VZV) by recombinase-aid amplification (RAA) combined with Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system.Methods:Clinical samples of suspected herpes zoster in Shandong province and Shanghai from 2023 to 2024 were collected, nucleic acids of positive samples were extracted, RAA-specific primers and crRNA (CRISPR RNA, crRNA) were designed for the conserved region of VZV, and the fluorescence intensity generated by Cas12a non-specific cleavage of single-stranded fluorescent probes was used to screen highly sensitive crRNAs and optimize the concentrations of crRNA, Cas12a and ssDNA probes. The sensitivity and reproducibility of the RAA-CRISPR/Cas12a detection method were evaluated by using synthesized plasmids and clinical samples, and the specificity of the method was evaluated by using other viral nucleic acids. The method was used to detect clinical samples by using the method and quantitative real-time PCR (qPCR) method, and the detection rate and consistency of the two method were compared.Results:The highly sensitive crRNA-4 was screened from the four crRNAs designed, and a VZV detection method for RAA-CRISPR/CAS12a based on fluorescence intensity measurement was established, which could be detected at 37℃ in 45 min, and the sensitivity of the detection could reach 10 copies/μL, a minimum clinical sample with a Ct value of 38.980 can be detected. It has high specificity and no cross-reactivity with Adenovirus 7, Herpes simplex virus type I, Herpes simplex virus type II, Coxsackieviruses A16, Cytomegalovirus, Epstein-Barr virus, Measles virus, Mumps virus, Enterovirus 71, Japanese encephalitis virus genotype 5. It has good stability, and can be successfully detected in low, medium and high concentrations of viral positive plasmids with good consistency. The detection rate of the clinically positive samples was 100%, which was completely consistent with the qPCR test result.Conclusions:RAA isothermal amplification technology combined with CRISPR-CAS12a technology was used to establish an accurate method for the detection of VZV virus, which was highly sensitive, specific, and had low requirements for experimental conditions, and could be completed within 45 min, which could provide strong technical support for the early detection of VZV.

Objective To investigate the value of patient data-based real-time quality control(PBRTQC)in internal quality control(IQC)for blood cells analysis based on the data from patients.Methods The data of patients'blood cells,including white blood cell count(WBC),hemoglobin(Hb),red blood cell count(RBC),hematocrit(HCT),mean corpuscular volume(MCV),mean cor-puscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC),and platelet(PLT)were collected from August 1,2023 to February 26,2024,and the extracted patient data were analyzed on the AI-based real-time quality control intelligent moni-toring platform.The corresponding IQC data for this period were reviewed,and the results of PBRTQC and IQC were compared and an-alyzed.The causes of the emerging warning or alarm prompts were checked and analyzed to explore the application value of PBRTQC in the IQC process of blood cell analysis.Results It is found that when the quality control product was unstable due to overlong opening time of the reagent or improper storage conditions,and the performance changes of the operating system during the detection process,the PBRTQC intelligent monitoring platform was able to issue risk warning or alarm prompt in advance.PBRTQC may have certain limi-tations,such as the error of red blood cell count,which need to be identified.Conclusion PBRTQC is superior to IQC in blood cell analysis and may play a complementary role in IQC.Meanwhile,it is necessary to exclude the possibility that PBRTQC is significantly influenced by the patient population in medical laboratories.

Objective To investigate the value of patient data-based real-time quality control(PBRTQC)in internal quality control(IQC)for blood cells analysis based on the data from patients.Methods The data of patients'blood cells,including white blood cell count(WBC),hemoglobin(Hb),red blood cell count(RBC),hematocrit(HCT),mean corpuscular volume(MCV),mean cor-puscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC),and platelet(PLT)were collected from August 1,2023 to February 26,2024,and the extracted patient data were analyzed on the AI-based real-time quality control intelligent moni-toring platform.The corresponding IQC data for this period were reviewed,and the results of PBRTQC and IQC were compared and an-alyzed.The causes of the emerging warning or alarm prompts were checked and analyzed to explore the application value of PBRTQC in the IQC process of blood cell analysis.Results It is found that when the quality control product was unstable due to overlong opening time of the reagent or improper storage conditions,and the performance changes of the operating system during the detection process,the PBRTQC intelligent monitoring platform was able to issue risk warning or alarm prompt in advance.PBRTQC may have certain limi-tations,such as the error of red blood cell count,which need to be identified.Conclusion PBRTQC is superior to IQC in blood cell analysis and may play a complementary role in IQC.Meanwhile,it is necessary to exclude the possibility that PBRTQC is significantly influenced by the patient population in medical laboratories.

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Objective:To investigate the effect of Lulongzaisheng decoction on ferroptosis in aplastic anemia (AA) model mice and its potential mechanism of action on AA.Methods:Using female BALB/c mice as controls (control group), a mouse model of AA was established by intraperitoneal injection of interferon-γ (IFN-γ) combined with oral gavage of busulfan. The AA group was treated with continuous oral gavage of Lulongzaisheng decoction for 10 days. The effects on the Jak2/Stat3/Acsl4 signaling pathway were assessed. Bone marrow biopsy and histopathological examination were performed to observe the degree of AA in each group of mice. Flow cytometry was used to detect the production of lipid reactive oxygen species (ROS) in the bone marrow cells. Immunohistochemical staining was performed to observe the expression of 4-HNE in the sternum. Western blot analysis was conducted to determine the protein expression levels of Jak2, p-Jak2, Stat3, p-Stat3, and Acsl4. ELISA was used to measure the levels of interleukin-6 (IL-6) in the peripheral blood plasma.Results:Compared with the control group, mice in the AA group exhibited a reduction in hematopoietic tissues within the bone marrow cavity and significant fatty infiltration. In contrast, mice in the AA+Lulongzaisheng decoction group showed partial recovery of the bone marrow and a decrease in fatty infiltration. The lipid ROS proportions in the control, AA, and AA+Lulongzaisheng decoction groups were (47.01±3.07) %, (53.81±1.99) %, and (49.50±3.98) %, respectively ( P<0.05), indicating that the AA + Lulongzaisheng decoction group had a slightly lower accumulation of lipid ROS than the AA group. The expression areas of 4-HNE in the bone marrow cavity for the control, AA, and AA+Lulongzaisheng decoction groups were (6.34±1.07) %, (35.26±3.68) %, and (16.97±1.30) %, respectively ( P<0.05), demonstrating a significant reduction in 4-HNE accumulation in the bone marrow in the AA + Lulongzaisheng decoction group compared with that in the AA group. Compared with the control group, the AA group exhibited upregulated expression of the ferroptosis-related protein Acsl4, along with increased expression of p-Stat3 and p-Jak2. In the AA+ Lulongzaisheng decoction group, the expression of Acsl4 was downregulated, whereas those of p-Stat3 and p-Jak2 were inhibited ( P<0.05). The levels of IL-6 in the peripheral blood plasma were (65.60±6.01), (166.50±3.32), and (119.37±4.29) pg/ml in the control, AA, and AA+Lulongzaisheng decoction groups, respectively ( P<0.05). Compared with the AA group, the AA + Lulongzaisheng decoction group exhibited a significant decrease in IL-6 levels. Conclusion:This study shows that Lulongzaisheng decoction has a significant therapeutic effect on AA model mice by regulating the Jak2/Stat3/Acsl4 pathway. The mechanism of action of this traditional Chinese medicine involves inhibiting the Jak2/Stat3 signaling pathway and regulating the expression of Acsl4, thereby improving hematopoietic function in AA model mice. These findings provide new drug targets and treatment strategies for the treatment of AA.