Ischemic stroke(IS) is a complex pathological process involving multiple cellular and molecular mechanisms and it is characterized by high mortality, high disability, and high recurrence. In recent years, the incidence of IS in China has been increasing year by year, and it has a trend of occurring in increasingly young individuals. Herb pairs are the smallest unit of traditional Chinese medicine(TCM) compatibility and an important part of TCM compounding, and the research on them is of great significance in guiding the clinical medication. Pharmacological studies have confirmed that certain herb pairs can exert anti-ischemic effects through various pathways such as reducing inflammation, alleviating oxidative stress, protecting the nervous system, and promoting neovascularization. By reviewing the relevant articles in the past decade, this paper probes into the combination rules, modern experimental studies, and combination ratios of the commonly used herb pairs from the etiology and pathogenesis of IS and summarizes 18 commonly used and deeply studied herb pairs, with a view to providing reference for the application, research, and development of clinical medicines.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Ischemic Stroke/metabolism* ; Medicine, Chinese Traditional

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.

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.

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Objective:To investigate the effect of embedded guidance technique assisted transconjunctival lower eyelid blepharoplasty.Methods:A retrospective study was conducted to include 88 patients who underwent transconjunctival blepharoplasty and tear trough deformity correction with orbital septum fat release and fixation (referred to as transconjunctival lower eyelid blepharoplasty) at the Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, from October 2021 to August 2022. There were 9 male patients (10.23%) and 79 female patients (88.77%), aged 22 to 51 years, with an average age of (34.42±6.17) years. The internal fixation of septum fat flap was assisted with embedded guidance technique, and the Barton grades system was used to evaluate the surgical effect, while the patient satisfaction and complications were collected.Results:The followed-up period is 6-16 months. Before operation, 35 eyes (19.89%) were classified as Barton Ⅰ, 86 eyes (48.86%) were classified as Barton Ⅱ, and 55 eyes (31.25%) were classified as Barton Ⅲ. After transconjunctival lower eyelid blepharoplasty, 151 eyes (85.80%) recovered to Barton grade 0, 22 eyes (12.50%) recovered to grade Ⅰ, 3 eyes (1.70%) recovered to grade Ⅱ, and no case was grade Barton Ⅲ. The patient satisfaction score was (9.14±1.22) points, and 78 patients (88.64%) were very satisfied. Only 6 patients (6.82%) showed mild complications, mainly including postoperative bilateral lower eyelid asymmetry (3 cases), mild bilateral orbital area ecchymosis (2 cases) and mild surface depression at internal fixation position (1 case).Conclusions:The transconjunctival lower eyelid blepharoplasty assisted by the embedded guidance technique achieves favorable results with high patient satisfaction and few complications.

Objective To investigate the expression and prognostic significance of serum protease C1 inhib-itor(SERPING1)and plasminogen activator inhibitor type 1(SERPINE1)in patients with sepsis.Methods A total of 132 patients with sepsis treated in the hospital from March 2018 to March 2020 were se-lected as the sepsis group.According to whether they died within 28 days of admission,they were divided into a death group(n=34)and a survival group(n=98).Enzyme linked immunosorbent assay was used to detect the expression of serum SERPING1 and SERPINE1.Multivariate Logistic regression model and receiver oper-ating characteristic curve were used to study the value of serum SERPING1 and serpine1 in evaluating the prognosis of patients'death.Results[Compared with the control group,serum SERPING1(331.12±51.80 ng/L vs.639.04±91.12 ng/L)was lower and serum serpine1(412.67±64.84 ng/L vs.42.33±10.32 ng/L)was higher in the sepsis group,and the differences were statistically significant(P＜0.05).[Compared to the survival group,the levels of serum SERPINE1,procalcitonin,C-reactive protein,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score in the death group were higher,while serum SERPING1 was lower,and the differences were statistically significant(all P＜0.05).Serum SERPING1 showed negative correlation with APACHE Ⅱ and SOFA scores(r=-0.779,-0.653,P＜0.05),while serum SERPINE1 showed positive correlation with APACHE Ⅱ and SO-FA scores(r=0.740,0.685,P＜0.05).APACHE Ⅱ score,SOFA score,and serum SERPINE1 were risk fac-tors affecting the prognosis of sepsis patients,while serum SERPING1 was a protective factor.The area under the curve of serum SERPING1 and SERPINE1 combined for the evaluation of the death in sepsis patients was 0.938(95％CI:0.893-0.968),which was significantly higher than 0.860(95％CI:0.812-0.899)and 0.838(95％CI:0.781-0.868)of the single detection,and the differences were statistically significant(Z=3.861,4.015,P＜0.001).Conclusion The elevated levels of serum SERPING1 and SERPINE1 in patients with sepsis are related to the severity of the patient's condition.The combination of the two has high prognos-tic value for sepsis patients.

Heart failure with preserved ejection fraction(HFpEF)is a highly heterogeneous systemic condition and represents the predominant form of heart heart failure(HF)worldwide.Current pharmacotherapies for HFpEF are limited and lack specific targeted drugs.Recent studies suggest that non-pharmacological strategies serve as adjuncts to conventional pharmacological treatment,offering improvements in symptoms,quality of life,and reducing the risk of rehospitalization for HF in patients with HFpEF.These strategies include CD34 stem cell transplantation,the greater splanchnic nerve ablation,atrial septal shunting,atrial pacing,myocardial contractility modulation,left ventricular expander,baroreceptor stimulation,and others.This review comprehensively summarizes the latest clinical evidence on non-pharmacological treatments for HFpEF,with the aim of advancing the understanding of treatment strategies for this condition.