Ischemic stroke （IS） represents a major global health challenge with complex pathological mechanisms. Although modern therapies such as intravenous thrombolysis and endovascular thrombectomy have advanced， their application remains constrained by narrow therapeutic time windows， hemorrhagic risks， and uneven distribution of medical resources. Traditional Chinese medicine （TCM） demonstrates unique value in the prevention and treatment of IS， owing to its multi-component， multi-target， and holistic regulatory characteristics. This review summarized the molecular mechanisms by which active ingredients and compound formulations of TCM exert therapeutic effects against IS through the regulation of inflammatory responses， oxidative stress， excitatory toxicity， apoptosis， and autophagy. Studies have indicated that components such as curcumin， baicalin， and astragaloside Ⅳ inhibit microglial activation and the nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome to attenuate neuroinflammation， activate the nuclear factor erythroid 2-related factor 2（Nrf2）/heme oxygenase-1 （HO-1） pathway to alleviate oxidative stress， modulate glutamate receptor function to counteract excitatory toxicity， and regulate the B-cell lymphoma 2（Bcl-2）/Bcl-2-associated X protein （Bax）， cysteine aspartate-specific protease （Caspase）， and phosphatidylinositol 3 kinases （PI3K）/protein kinase B （Akt） signaling pathways to suppress neuronal apoptosis. Recent research has further revealed that TCM can modulate ferroptosis by targeting key proteins glutathione peroxidase 4 （GPX4） and acyl-coenzyme A synthetase long-chain family member 4 （ACSL4） to maintain iron homeostasis， intervene in the "microbiota-gut-brain axis" to ameliorate dysbiosis and reduce neuroinflammation， utilize exosomes for brain-targeted drug delivery， and influence neural repair processes through epigenetic regulation. Furthermore， the review discussed the integrated mechanisms of compound formulations， such as Buyang Huanwu Decoction， in improving cerebral microcirculation and promoting neurovascular remodeling via multi-component synergy. It also analyzed the strategy and advantages of integrating TCM with Western medicine for IS treatment， providing a novel theoretical foundation and research directions for future investigations and clinical translation of TCM in IS management.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To analyze the changes in coagulation during the treatment of acute promyelocytic leukemia (APL) and explore the influencing factors of coagulation in patients with APL. METHODS: Data of 166 APL patients admitted to our hospital from November 2018 to May 2023 were retrospectively analyzed, and the changes of various clinical indicators before and during treatment were compared. 166 APL patients were divided into abnormal coagulation group (n =115) and normal coagulation group (n =51) according to whether they experienced coagulation dysfunction. The basic information, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was used to screen risk factors for coagulation dysfunction and established logistic regression model. Then we developed a neural network model and ranked the importance of the influencing factors, and used receiver operating characteristic (ROC) curves to evaluate the predictive performance of the two models. RESULTS: The comparative results of various clinical indicators in 166 APL patients before and during treatment showed that systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR), platelet (PLT) and fibrinogen (FIB) were significantly increased during the treatment (P < 0.05), while glycosylated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), serum creatinine (SCr), high-sensitivity C reactive protein (hs-CRP), IL-6, TNF-α, TGF-β, white blood cells (WBC), absolute neutrophil count (ANC), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), fibrinogen degradation products (FDP) and lactate dehydrogenase (LDH) were significantly decreased during the treatment (P < 0.05). The proportion of patients with hemorrhage and high-risk APL in the abnormal coagulation group was significantly higher than that in the normal coagulation group (P < 0.05). The levels of IL-6, TNF-α, WBC, ANC, D-D, FDP and LDH in the abnormal coagulation group were significantly higher than those in the normal coagulation group (P < 0.05). The influencing factors selected by univariate analysis were incorporated into logistic regression analysis and neural network model to predict the risk of coagulation dysfunction in APL patients. ROC curves showed that the AUC of the two models were 096 and 0.908, the sensitivity were 0.824 and 0.892, the specificity were 0.940 and 0.904, the Youden index were 064 and 0.796, and the accuracy were 0.882 and 0.898, respectively. CONCLUSION High risk stratification, hemorrhage, elevated WBC, LDH, ANC and FDP levels are independent risk factors for coagulation dysfunction in APL patients. The logistic regression model and neural network model based on these risk factors demonstrate good predictive performance for coagulation dysfunction in APL patients.
Humans ; Leukemia, Promyelocytic, Acute/therapy* ; Blood Coagulation ; Retrospective Studies ; Male ; Female ; Risk Factors ; Logistic Models ; Middle Aged ; Adult ; ROC Curve

Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.

Objective To analyze the trend of influenza epidemic intensity in Urumqi City, Xinjiang, in early 2023, and to provide a reference basis for influenza surveillance, prevention and control. Methods Based on the daily number of influenza cases in Urumqi from January 1, 2023 to March 26, 2023, a generalized linear model was established to correlate the cumulative number of cases with the number of days of illness, and the corresponding doubling time was calculated. Results A total of 9 243 influenza cases were included in this study, including 7733 confirmed cases and 1510 suspected cases. The peak incidence of influenza occurred in March, and 6039 positive cases were detected, with a positivity rate of 78.09%. The age group of 3-6 years old had the highest proportion of influenza positive cases, accounting for 32.20%. The longest doubling time among confirmed cases was 13.49 (95% CI:11.95-15.47) in stage 2 (January 22 to February 13), and the shortest was in stage 3 (February 14 to March 26), which was 9.41 (95% CI:8.24-10.91). Conclusion The shorter the doubling time, the faster the speed of influenza transmission, and it is necessary to strengthen the prevention and control of influenza in winter and spring.

Objective To analyze the epidemiological characteristics and spatiotemporal clustering of varicella in Lu'an City from 2005 to 2023, and to provide a scientific basis for optimizing varicella prevention and control strategies. Methods Data on varicella cases were collected through the Chinese Center for Disease Control and Prevention Information System. Descriptive epidemiology, temporal trend analysis, seasonal analysis, spatiotemporal clustering analysis, and spatial autocorrelation analysis were conducted using QGIS, JoinPoint, SaTScan and GeoDa software. Results The average annual reported incidence rate of varicella in Lu'an City from 2005 to 2023 was 34.55/100,000, showing a trend of initial increase followed by a decrease. The peak incidence occurred from October to January of the following year (RR=1.97, LLR=1743.95, P=0.001). Students aged 0 to 19 was the primary affected group. Spatiotemporal scan analysis revealed four types of spatiotemporal clusters, with the cluster in Jin'an District from October 2017 to December 2023 being particularly prominent (RR=2.87，LLR=1734.15，P<0.001). Spatial autocorrelation analysis indicated significant clustering of varicella cases in the main urban area (Moran's I=0.216，Z=4.786，P=0.003). Conclusion The incidence of varicella in Lu'an City exhibits distinct seasonal and spatial clustering, and schools and kindergartens in the main urban area are the key to varicella prevention and control. It is necessary to enhance the monitoring of disease outbreaks during peak periods and in key areas, and to increase the two-dose vaccination rate for varicella in areas with case aggregation and among key populations.

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*