OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

BACKGROUND:How to repair bone defect has been a clinical problem for a long time.The effective ingredients of traditional Chinese medicine have good biological activity and therapeutic effect,and the combination of effective ingredients of traditional Chinese medicine and tissue engineering materials has a broad prospect in the field of bone repair.The combination of different effective ingredients of traditional Chinese medicine and scaffolds has similarities in their functional relationships. OBJECTIVE:To collect the cases of the combinations of effective ingredients of traditional Chinese medicine and scaffolds,then analogize tissue engineering scaffolds and effective ingredients of traditional Chinese medicine into two types of traditional Chinese medicine that generate compatibility relationships based on the inspiration of the compatibility of seven emotions and summarize the relationship between the two based on their functional relationships. METHODS:Relevant articles from January 1998 to January 2024 were searched in PubMed and China National Knowledge Infrastructure(CNKI),using English search terms"traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold"and Chinese search terms"traditional Chinese medicine,effective ingredients of traditional Chinese medicine,traditional Chinese medicine monomers,bone tissue engineering,bone tissue engineering scaffold,scaffold,tissue engineering,bone defect,bone repair."A total of 88 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Both tissue engineering scaffold materials and active ingredients of traditional Chinese medicine have been widely used in the field of bone repair.Although they have obvious advantages in osteogenesis,there are still many shortcomings.Many studies are dedicated to preparing composite materials from the two,hoping to exert a detoxification and synergism through the interaction between the two.(2)Some drugs and materials can promote each other in osteogenesis,antibacterial,and promoting angiogenesis,enhancing their original effects.Inspired by the traditional concept of prescription compatibility,this article summarized it as a"Mutual promotion"relationship and provided examples to support it.(3)Some drugs can enhance the strength of materials,while some materials can achieve sustained release and controlled release effects,increase drug loading and stability,or achieve targeted delivery of drugs loaded on them.The article summarized this unilateral enhancement effect as a"Mutual assistance"relationship.(4)The combination of some traditional Chinese medicine and materials can reduce the toxic side effects of the other party.The article summarizes this detoxification relationship as"Mutual restraint and detoxification."(5)The article provided a new perspective on traditional Chinese medicine composite scaffolds,inspired by the seven emotions compatibility relationship and based on the classification of action relationships.It introduced traditional Chinese medicine concepts into the field of tissue engineering,providing new research ideas for subsequent researchers of composite scaffolds,and providing certain convenience in material selection and matching.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.