ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.