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.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

ObjectiveTo establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. MethodsBackground data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. ResultsBoth male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). ConclusionThis study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in adolescents, with potential causes etiologies associated with mesenchymal stem cells, genetic factors, histological features, and biomechanical aspects. Biomechanically, the pelvis, serving as the central and majort load-bearing structure, exhibits morphological and alignment abnormalities highly correlated with the development of AIS. Recent studies have extensively explored three-dimensional pelvic parameters and kinematics, demonstrating that abnormal pelvic characteristics may contribute to AIS onset and progression and are increasingly incorporated into clinical interventions. This review summarizes sagittal and coronal features of the spine-pelvis, as well as the influence of three-dimensional kinematic features on the pathogenesis of AIS, providing insights for advancing the study of spine-pelvis features related to AIS.
Humans ; Scoliosis/pathology* ; Adolescent ; Spine/pathology* ; Pelvis/pathology* ; Biomechanical Phenomena

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Objective : To investigate the effects and underlying mechanisms of high mobility group nucleosome-binding domain protein 2(HMGN2) on lung adenocarcinoma cells. Methods : This work first analyzed the association between HMGN2 and lung adenocarcinoma tissues using The Cancer Genome Atlas(TCGA) database. Lung adenocarcinoma tissues and adjacent normal tissues were collected to compare the differential expression levels of HMGN2. The expression of HMGN2 mRNA in lung adenocarcinoma cell lines A549 and NC-H1299 were detected by qRT-PCR and Western blot. HMGN2 expression was knocked down using si-RNA technology, with the control group transfected with an equivalent amount of NC-siRNA, and the si-RNA group transfected with si-HMGN2. Stable transfected cell lines were established based on si-RNA knockdown efficiency. The effects of HMGN2 knockdown on the growth, movement, and spread of lung adenocarcinoma cells were assessed using CCK-8, Transwell assays, scratch assays, colony formation assays, and EdU assays. Transcriptome sequencing analysis revealed pathways related to tumorigenesis associated with HMGN2. The relative expression levels of MAPK pathway proteins after HMGN2 knockdown were detected by Western blot. Results : HMGN2 mRNA expression was significantly elevated in lung cancer tissues and lung adenocarcinoma cell lines(P<0.05). After HMGN2 knockdown, cell proliferation, migration, and invasion were significantly reduced(P<0.05), and the phosphorylation levels of the MAPK signaling pathway markedly decreased(P<0.05). Conclusion HMGN2 enhances the proliferation, migration, and invasion of lung adenocarcinoma cells, and its mechanism may be closely related to the activation of the MAPK signaling pathwayviaphosphorylation.