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

A public hospital Party branch,in the establishment of the"Four Orientations"project(Leading groups work effectively,Party branches work with promising methods,Party building achieves a fame with brand,and each unit has its own model)and"Four Strengths"(strong political role,strong Party branch team,strong team of Party members,and strong per-formance)has combined its work with bold exploration at the intersection of party building and discipline development.The branch has refined a distinctive"Bridge Culture"concept,symbolizing its identity,and has implemented four key projects:"Building bridges""Consolidating bridges""Expanding bridges"and"Preserving bridges".Collectively,these initiatives have led to the development of a"Bridge Culture"brand.The branch's role,as a vanguard in discipline advancement and public health services,has been fully leveraged,aiming to drive high-quality development of discipline through the vehicle of ideological and political work.

Objective:To construct a fall risk prediction model for patients with hematologic malignancies and to provide a reference for the risk assessment and accurate management of falls.Methods:The prospective study design was adopted to facilitate the selection of 510 patients with hematologic malignant in Qilu Hospital of Shandong University for investigation, and relevant data such as patient demographic characteristics, disease treatment and drugs were collected. The LASSO-Logistic regression was used to screen the risk factors of falls in patients with hematologic malignancies, to construct a nomogram risk prediction model. The receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the predictive performance of the model. Bootstrap resampling were used to validate internal validation of the model.Results:Among 510 patients with hematological malignancies, there were 273 males and 237 females, aged 53.0 (41.0, 63.0) years old. A total of 6 risk factors were included in the fall risk prediction model for patients with hematological malignancies, which were disease type ( OR = 0.185, 95% CI 0.061 - 0.562), body temperature ≥38 ℃ ( OR = 2.239, 95% CI 1.128 - 4.445), pain ( OR = 15.581, 95% CI 6.592 - 36.829), anemia ( OR = 4.097, 95% CI 1.536 - 10.927), days of bone marrow suppression ( OR = 3.341, 95% CI 1.619 - 6.893), and assessment of daily self-care ability ( OR = 3.160, 95% CI 1.051 - 9.506)(all P<0.05). The ROC curve of the fall risk prediction model was 0.884 (95% CI 0.841-0.927). The optimal threshold, sensitivity, and specificity of the risk prediction model were 0.248, 87.4% and 75.6%. The internal validation C statistic was 0.873. The Calibration curve was almost coincides with the ideal curve, and the model Brier score was 0.080. Conclusions:The constructed fall risk prediction model has good predictive performance, which can efficiently and objectively quantify the risk of falls, and provide a reference for the early assessment and effective prevention of falls in patients with hematological malignancies.

Objective:To investigate the predictive value of preoperative γ-glutamyl transferase/lymphocyte count ratio (GLR) levels for postoperative tumor recurrence in liver transplant recipients with liver cancer.Methods:The clinical data of 158 recipients who were diagnosed with hepatocellular carcinoma (hereinafter referred to as liver cancer) and received liver transplantation at the No. 900 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to October 2022 were retrospectively analyzed. X-tile software, the Kaplan-Meier method, univariate and multivariate Cox regression, and other statistical methods were performed. The predictive value of preoperative GLR levels for postoperative tumor recurrence in liver transplant recipients with liver cancer and the risk factors for tumor recurrence in liver cancer patients post-liver transplantation were analyzed.Results:The X-tile software analysis confirmed that 96.8 was the optimal cutoff value for the preoperative GLR level to predict recurrence. The grouping threshold for survival analysis using the GLR cutoff value was 96.8. The tumor recurrence rates at 1, 3, and 5 years after surgery in the low-level GLR group (90 cases) and the high-level GLR group were 19.3% vs. 44.2%, 31.8% vs. 60.0%, and 34.1% vs. 62.9% (68 cases), respectively, and the differences were statistically significant between the two groups ( P<0.05). The Kaplan-Meier survival curve analysis results showed that the overall postoperative survival rate and recurrence-free survival rate were significantly lower in the high-level GLR group than the low-level GLR group ( P<0.05). The univariate Cox analysis result showed that there were statistically significant differences in preoperative aspartate aminotransferase, alpha fetoprotein, surgery time, maximum diameter of a solitary tumor, presence or absence of microvascular invasion, presence or absence of portal vein tumor thrombus, and preoperative GLR levels between the two groups ( P<0.05). Multivariate Cox analysis results showed that preoperative alpha-fetoprotein ≥400 ng/ml, GLR≥96.8, and the maximum diameter of a solitary tumor ≥5.0 cm were independent risk factors for postoperative tumor recurrence in liver transplant recipients with liver cancer ( P<0.05). Conclusion:GLR levels have a certain predictive value for postoperative tumor recurrence in liver transplant recipients with liver cancer. Furthermore, the postoperative tumor recurrence rate is relatively high when the preoperative GLR level in liver transplant recipients with liver cancer is ≥96.8.

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.

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.