Ischemic stroke is a common cerebrovascular disease， characterized by hypoxia and nutritional deficiency in local brain tissue due to insufficient blood supply. Angiogenesis， the formation of new vascular networks on the basis of existing blood vessels， is of great significance for increasing blood flow in the ischemic area of brain tissue， restoring blood and oxygen supply， and improving disease prognosis. This complex process is regulated by various factors， including cytokines， growth factors， and signaling pathways. Among these， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is considered a key regulatory pathway. It not only plays an important role in anti-apoptosis and promoting cell survival， but also regulates cell growth， differentiation， migration， and survival， while deeply participating in the regulation of angiogenesis. Chinese medicine offers unique advantages with its multi-component， multi-target， and multi-pathway approach in the treatment of stroke， showing significant potential in treating ischemic stroke. In recent years， it has been found that Chinese medicine can promote angiogenesis after ischemic stroke through the PI3K/Akt signaling pathway. This paper focuses on the PI3K/Akt signaling pathway as the research entry point， and explores in-depth the mechanisms by which Chinese medicine monomers， active components， extracts， derivatives， drug pairs， and Chinese medicine compounds promote angiogenesis after ischemic stroke. The research discusses the regulation of microRNAs （miRNA）， endothelial progenitor cells （EPCs）， apoptosis， upstream pro-angiogenic factors， and downstream target molecules. The paper also elaborates on related research progress， aiming to reveal how Chinese medicine can exert its potential utility in ischemic stroke treatment through this key signaling pathway， providing a theoretical basis for clinical treatment.

Ischemic stroke is a common cerebrovascular disease， characterized by hypoxia and nutritional deficiency in local brain tissue due to insufficient blood supply. Angiogenesis， the formation of new vascular networks on the basis of existing blood vessels， is of great significance for increasing blood flow in the ischemic area of brain tissue， restoring blood and oxygen supply， and improving disease prognosis. This complex process is regulated by various factors， including cytokines， growth factors， and signaling pathways. Among these， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is considered a key regulatory pathway. It not only plays an important role in anti-apoptosis and promoting cell survival， but also regulates cell growth， differentiation， migration， and survival， while deeply participating in the regulation of angiogenesis. Chinese medicine offers unique advantages with its multi-component， multi-target， and multi-pathway approach in the treatment of stroke， showing significant potential in treating ischemic stroke. In recent years， it has been found that Chinese medicine can promote angiogenesis after ischemic stroke through the PI3K/Akt signaling pathway. This paper focuses on the PI3K/Akt signaling pathway as the research entry point， and explores in-depth the mechanisms by which Chinese medicine monomers， active components， extracts， derivatives， drug pairs， and Chinese medicine compounds promote angiogenesis after ischemic stroke. The research discusses the regulation of microRNAs （miRNA）， endothelial progenitor cells （EPCs）， apoptosis， upstream pro-angiogenic factors， and downstream target molecules. The paper also elaborates on related research progress， aiming to reveal how Chinese medicine can exert its potential utility in ischemic stroke treatment through this key signaling pathway， providing a theoretical basis for clinical treatment.

Our research reveals the critical role of the suprachiasmatic nucleus (SCN) vasoactive intestinal peptide (VIP) neurons in mediating light-induced transient forgetting. Acute exposure to bright light selectively impairs trace fear memory by activating VIP neurons in the SCN, as demonstrated by increased c-Fos expression and Ca²⁺ recording. This effect can be replicated and reversed through optogenetic and chemogenetic manipulations of SCN VIP neurons. Furthermore, we identify the SCN → PVT (paraventricular nucleus of the thalamus) VIP neuronal circuitry as essential in this process. These findings establish a novel role for SCN VIP neurons in modulating memory accessibility in response to environmental light cues, extending their known function beyond circadian regulation and revealing a mechanism for transient forgetting.
Animals ; Vasoactive Intestinal Peptide/metabolism* ; Male ; Mice ; Neurons/metabolism* ; Suprachiasmatic Nucleus/physiology* ; Light ; Mice, Inbred C57BL ; Memory/physiology* ; Fear/physiology* ; Suprachiasmatic Nucleus Neurons/metabolism* ; Optogenetics ; Proto-Oncogene Proteins c-fos/metabolism*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.

OBJECTIVE To evaluate the cost-effectiveness of apatinib combined with adriamycin in the second-line chemotherapy of platinum-resistant recurrent ovarian cancer （OC） from the perspective of the health system in China. METHODS A three-state partitioned survival model was constructed based on the APPROVE clinical trial and related literature data， with a model simulation time frame of 10 years and a 4-week cycle， and both cost and utility values were discounted using a 5% discount rate. Cost and quality-adjusted life years （QALYs） were used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the cost-effectiveness of apatinib combined with adriamycin versus adriamycin chemotherapy in the second-line treatment of platinum-resistant recurrent OC. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS The results of base-case analysis indicated that compared with chemotherapy alone， ICER of patients receiving apatinib combined with adriamycin was 124 678.25 yuan/QALY， which was less than willingness-to-pay （WTP） threshold set in this study [3 times per capita gross domestic product （GDP） of China in 2022 （257 094 yuan）]. The results of scenario analysis showed that， with the extension of the simulation time limit， the ICER of apatinib combined with adriamycin was gradually reduced， and the decline was gradually reduced， but both were less than WTP threshold. The results of single factor sensitivity analysis showed that the factors that had the greatest impact on ICER were the utility value of progression， body surface area， discount rate，and the cost of best supportive treatment， etc. The results of probability sensitivity analysis showed that under WTP threshold set in this study， the economic probability of apatinib combined with adriamycin was about 99%. CONCLUSIONS From the perspective of China’s health system， using three times the per capita GDP in 2022 as the WTP threshold， the combination of apatinib and adriamycin is more cost-effective than adriamycin alone in second-line chemotherapy for platinum-resistant recurrent OC.

Objective To analyze and identify the volatile constituents in different parts(flowers,stems and leaves)of Huai chrysanthemumin,and to lay a theoretical foundation for the comprehensive utilization for it.Methods The volatile oil in different parts of Huai chrysanthemumin were extracted by hydrodistillation,respectively.Their constituents were analyzed by gas chromatography-mass spectrometry(GC-MS).The compounds were identified by library search and literature screening.The relative percentage of each compound was obtained by the area normalization method.The differences in their chemical compositions were analyzed by Venn diagram,principal component analysis(PCA)and cluster heat map analysis.Results A total of 62 volatile chemical components were identified from different parts of Huai chrysanthemumin,including monoterpenes,sesquiterpenes,and their derivatives,as well as a small amount of aliphatic compounds.32,42 and 40 volatile components were detected from the flowers,stems and flowers,respectively.Furthermore 17 volatile components were shared by three parts,whereas 5,6 and 16 volatile components were unique to the flowers,stems and leaves,respectively.The results of stoichiometric analysis showed that both PCA and cluster heat map analysis could separate the flowers,stems and leaves,and their volatile components were different.Conclusion The types and contents of the volatile oil in the stems,leaves and flowers of Huai chrysanthemumin have certain variability,which provide a scientific basis for the further medicinal or industrial exploitation of different parts of Huai chrysanthemumin.

BackgroundChronic insomnia is characterized by a prolonged and recurrent course. The efficacy of repeated transcranial magnetic stimulation （rTMS） as a physical therapy method to improve sleep quality remains inadequately supported by evidence， particularly regarding its relationship with personality traits. ObjectiveTo explore the efficacy and influencing factors of rTMS in the treatment of chronic insomnia， and to provide insights into its therapeutic potential. MethodA total of 46 patients who met the diagnostic criteria for chronic insomnia according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and were treated at the Third Hospital of Mianyang from September 2022 to September 2023 were selected. Prior to treatment， participants underwent assessments using the Eysenck Personality Questionnaire （EPQ）， Hamilton Depression Scale-17 item （HAMD-17） and Hamilton Anxiety Scale （HAMA）. The Pittsburgh Sleep Quality Index （PSQI） was used to assess sleep quality before treatment， at the end of the second week of treatment and one week post-treatment. ResultsAt the end of the second week of treatment， patients exhibited significantly improved total PSQI score and subscale scores related to subjective sleep quality， sleep latency， sleep duration， sleep efficiency， sleep disturbance and daytime dysfunction （t=4.755~13.361， P<0.01）， with 24 cases （54.35%） showing effective treatment outcomes. Multiple linear regression analysis showed that introverted and extroverted personality traits contributed significantly to the regression equation （B=0.317， P<0.01）， explaining 29.90% of the total variation （R²=0.299）. ConclusionrTMS treatment may effectively improve the sleep quality of patients with chronic insomnia， with its therapeutic effect appearing to associated with introverted and extroverted personality traits. ［Funded by National Natural Science Project of China （number， 82372080）］

Objective To investigate the relationship between the expression of keratin 15(KRT15)and keratin 18(KRT18)proteins in colorectal cancer tissue and their clinicopathological features and prognosis.Methods A total of 97 patients with colorectal cancer who underwent surgical treatment in a hospital from June 2018 to June 2019 were selected as the study objects.Immunohistochemistry was used to detect the ex-pression of KRT15 and KRT18 protein in colorectal cancer tissues and adjacent tissues,and the differences of KRT15 and KRT18 protein expression in colorectal cancer patients with different clinicopathological features were compared.The patients with colorectal cancer were followed up for 3 years after discharge,and their o-verall survival(OS)during the follow-up period was analyzed.Kaplan-Meier survival curve and Log-rank test were used to analyze the difference in OS rate among colorectal cancer patients with different KRT15 and KRT18 protein expression.Univariate and multivariate COX proportional regression analysis was performed to analyze the factors affecting the prognosis of patients with colorectal cancer.Results The positive expres-sion rates of KRT15 and KRT18 protein in colorectal cancer tissues were higher than those in adjacent tis-sues,and the difference was statistically significant(P＜0.05).The positive expression rates of KRT15 and KRT18 protein in colorectal cancer tissues of patients with low differentiation,TNM Ⅲ stage,perineural inva-sion and preoperative carcinoembryonic antigen(CEA)level ≥5 ng/mL were higher than those of patients with medium-high differentiation,TNM Ⅰ-Ⅱ stage,without perineural invasion and preoperative CEA level＜5 ng/mL,the difference was statistically significant(P＜0.05).The 3-year OS rates of colorectal cancer patients with positive expression of KRT15 and KRT18 protein were 64.29％and 60.00％respectively,which were lower than those of patients with negative expression of KRT15 and KRT18 protein(83.64％and 85.96％respec-tively),and the difference was statistically significant(x2=6.497,7.987,P＜0.05).Multivariate COX pro-portional regression analysis showed that TNM stage Ⅲ,positive expression of KRT15 protein and positive expression of KRT18 protein were risk factors affecting the survival of patients with colorectal cancer(P＜0.05).Conclusion The expression of KRT15 and KRT18 protein in colorectal cancer tissues can provide ref-erence for prognosis assessment of patients with colorectal cancer.