ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

Neurological diseases have high morbidity and disability rates， posing a severe threat to human health. Cli nical manifestations include motor， sensory， cognitive and conscious disorders. Chaihu jia longgu muli decoction is derived from Treatise on Febrile Diseases ， with the effects of harmonizing Shaoyang， activating Yang and clearing heat， and tranquilizing the mind. This paper systematically reviews the research progress in clinical application and mechanism of Chaihu jia longgu muli decoction in the field of neurological diseases. It has been found that the decoction shows favorable efficacy in various neurological diseases such as insomnia， depression， epilepsy， vertigo， migraine and vascular dementia. The specific mechanisms are related to regulating neurotransmitter levels， repairing neuronal function， alleviating neuroinflammation， improving mitochondrial dysfunction and regulating intestinal flora. In the future， standardized prospective follow-up cohorts should be established， and core outcome indicators should be clearly defined to strengthen the evidence base. Furthermore， multidisciplinary research should be leveraged to expand the therapeutic value of Chaihu jia longgu muli decoction in the management of neurological diseases.

Objective To explore the feasibility and image quality of respiratory-gated total-body ¹⁸F-FDG PET/CT imaging with a 4-minute acquisition in patients with malignant tumors. Methods Sixty-two patients with pathologically confirmed malignant tumors (118 lesions measured) who underwent total-body ¹⁸F-FDG PET/CT examination were consecutively enrolled at the Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, from September 23, 2021 to November 23, 2021, and their clinical and imaging data were retrospectively collected. PET data was acquired over 12 minutes with simultaneous respiratory waveform recorded. The data were reconstructed into four image sets: gated-12 group and gated-4 group (using all counts and the first 4-minute counts, respectively) and ungated-12 group and ungated-6 group (using all counts and the first 6-minute counts, respectively) reconstructed with respiratory gating that retained counts corresponding to the half respiratory window near end-expiration. Image quality assessment and quantitative analysis of lesions were performed and compared among the four image sets, and subgroup analyses were performed according to lesion location, size, and metabolic activity. Results The effective counts of 4 sets of PET images were highest in ungated-12 group, followed by ungated-6 group and gated-12 group, and lowest in gated-4 group (P＜0.001). Regardless of the metabolic level and size of the lesions, compared with the ungated-12 group and the ungated-6 group, the lesions in the gated-12 group showed higher maximum, average, and peak standardized uptake values (SUV_max, SUV_mean, and SUV_peak), tumor liver uptake ratio, tumor blood pool uptake ratio, and smaller metabolic volume (P＜0.05); There was no statistically significant difference in the above indicators between the gate-12 group and the gate-4 group. The background noise of gate-4 group images is slightly higher than that of gate-12 group images (Liver SUV_SD: [0.17＋0.05] vs [0.14＋0.04]); Blood pool SUV_SD: (0.08 ± 0.03) vs (0.06 ± 0.03). There was a statistically significant difference in subjective scores of PET image quality among the four groups (P＜0.001). The subjective scores of image quality in the gated-12 group (4.79 ± 0.41) were not significantly different from those in the non gated-12 group (4.97 ± 0.17) and non gated-6 group (4.79 ± 0.45), but were higher than those in the gated-4 group ([4.17 ± 0.45], P＜0.001)， And the scores have good consistency (Kappa＞0.75). Conclusion In total-body PET/CT imaging for malignant tumors, 4-minute respiratory-gated acquisition can achieve comparable quantitative performance to longer respiratory gating imaging while significantly shortening acquisition time. This approach demonstrates promising potential for clinical application.

Brain imaging abnormalities are present in schizophrenia (SZ) and bipolar disorder (BD), demonstrating disease-specific changes, yet they also share similarities in certain brain regions or functional characteristics, with SZ potentially exhibiting more extensive brain damage compared to BD. Structural magnetic resonance imaging (MRI) studies demonstrated widespread gray matter reductions in SZ, particularly in the prefrontal and temporal lobes. In BD, gray matter thickening was observed in the prefrontal lobes during manic episodes, while a reduction in gray matter was noted in the amygdala and hippocampus during depressive episodes. Both SZ and BD exhibited increased ventricular volume and reduced overall brain volume. Functional MRI studies revealed reduced functional connectivity in the prefrontal and temporal lobes in SZ, with decreased global and local efficiency in brain regions such as the hippocampus and cingulate gyrus. BD showed enhanced connectivity in the anterior cingulate gyrus and the default mode network (DMN). Both SZ and BD demonstrated altered functional connectivity in areas such as the striatum, salience network, central executive network and DMN. Diffusion tensor imaging studies showed decreased fractional anisotropy (FA) in the corpus callosum of SZ, with a decrease in FA in the left fronto-occipital fasciculus in BD. Both SZ and BD exhibited reduced FA in the uncinate fasciculus and corpus callosum. Magnetic resonance spectroscopy revealed decreased concentrations of glutathione, N-acetylaspartate (NAA) and inositol in the anterior cingulate gyrus of SZ. In BD, glutathione and inositol concentrations were elevated in the anterior cingulate gyrus, while NAA levels decreased during depressive episodes and increased during remission. Both SZ and BD showed increased levels of glutamate and gamma-aminobutyric acid in the prefrontal cortex. This article provides a review of the current evidence on the differences and similarities in multimodal magnetic resonance brain imaging between SZ and BD, aiming to offer a reference for future exploration of neuroimaging biomarkers and the neurobiological mechanisms of SZ and BD.

Activity cliffs (ACs) are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target. ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures. Nonetheless, they also form a major source of prediction error in structure-activity relationship (SAR) models. To date, several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs. In this paper, we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet, tailored for ACs. Through extensive comparison with multiple baseline models on 30 benchmark datasets, the results showed that ACtriplet was significantly better than those deep learning (DL) models without pre-training. In addition, we explored the effect of pre-training on data representation. Finally, the case study demonstrated that our model's interpretability module could explain the prediction results reasonably. In the dilemma that the amount of data could not be increased rapidly, this innovative framework would better make use of the existing data, which would propel the potential of DL in the early stage of drug discovery and optimization.

Brain imaging abnormalities are present in schizophrenia (SZ) and bipolar disorder (BD), demonstrating disease-specific changes, yet they also share similarities in certain brain regions or functional characteristics, with SZ potentially exhibiting more extensive brain damage compared to BD. Structural magnetic resonance imaging (MRI) studies demonstrated widespread gray matter reductions in SZ, particularly in the prefrontal and temporal lobes. In BD, gray matter thickening was observed in the prefrontal lobes during manic episodes, while a reduction in gray matter was noted in the amygdala and hippocampus during depressive episodes. Both SZ and BD exhibited increased ventricular volume and reduced overall brain volume. Functional MRI studies revealed reduced functional connectivity in the prefrontal and temporal lobes in SZ, with decreased global and local efficiency in brain regions such as the hippocampus and cingulate gyrus. BD showed enhanced connectivity in the anterior cingulate gyrus and the default mode network (DMN). Both SZ and BD demonstrated altered functional connectivity in areas such as the striatum, salience network, central executive network and DMN. Diffusion tensor imaging studies showed decreased fractional anisotropy (FA) in the corpus callosum of SZ, with a decrease in FA in the left fronto-occipital fasciculus in BD. Both SZ and BD exhibited reduced FA in the uncinate fasciculus and corpus callosum. Magnetic resonance spectroscopy revealed decreased concentrations of glutathione, N-acetylaspartate (NAA) and inositol in the anterior cingulate gyrus of SZ. In BD, glutathione and inositol concentrations were elevated in the anterior cingulate gyrus, while NAA levels decreased during depressive episodes and increased during remission. Both SZ and BD showed increased levels of glutamate and gamma-aminobutyric acid in the prefrontal cortex. This article provides a review of the current evidence on the differences and similarities in multimodal magnetic resonance brain imaging between SZ and BD, aiming to offer a reference for future exploration of neuroimaging biomarkers and the neurobiological mechanisms of SZ and BD.

Objective Patients with acute coronary syndrome(ACS)combined with chronic kidney disease(CKD)are at high risk of major adverse cardiovascular events(MACE),and early prediction is crucial for improving prognosis.Non-invasive detection methods,due to their simplicity and safety,have become important tools for assessing risks in such patients.This study aims to evaluate the application value of non-invasive detection indicators in predicting MACE in ACS patients with CKD.Methods The study included 216 ACS patients with CKD,divided into a Non-MACE group(n=149)and a MACE group(n=67).General patient data,non-invasive detection indicators,electrocardiogram(ECG),and cardiac function indicators were collected.Univariate and multivariate logistic regression analyses were performed to explore the relationship between these indicators and MACE.A nomo-gram prediction model was constructed,and its performance was evaluated using ROC curve analysis,calibration curve,and decision curve analysis.Results Univariate analysis showed that age,BMI,SVR,SVRI,HRV,QTd,SDNN,LVEF,LVEDd,SCOPA-AUT score,and GRACE score were significantly associated with MACE.Multivariate analysis identified SVRI,QTd,SDNN,LVEF,LVEDd,SCOPA-AUT score,and GRACE score as independent risk factors for MACE.ROC curve analysis revealed that the model had an AUC value of 0.979,sensi-tivity of 0.925,specificity of 0.966,and accuracy of 0.9537,indicating high diagnostic accuracy.Calibration curve and decision curve analyses further confirmed the model's reliability.Conclusion Non-invasive detection indicators,including SVRI,QTd,SDNN,LVEF,LVEDd,SCOPA-AUT score,and GRACE score,have significant value in predicting MACE in ACS patients with CKD.The constructed prediction model provides an effective tool for clinical risk assessment.

Activity cliffs(ACs)are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target.ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures.Nonetheless,they also form a major source of prediction error in structure-activity relationship(SAR)models.To date,several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs.In this paper,we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet,tailored for ACs.Through extensive comparison with multiple baseline models on 30 benchmark datasets,the results showed that ACtriplet was significantly better than those deep learning(DL)models without pre-training.In addition,we explored the effect of pre-training on data representation.Finally,the case study demonstrated that our model's interpretability module could explain the prediction results reasonably.In the dilemma that the amount of data could not be increased rapidly,this innovative framework would better make use of the existing data,which would propel the potential of DL in the early stage of drug discovery and optimization.