Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Mice ; Animals ; Humans ; Glioblastoma/pathology* ; Endothelial Cells/pathology* ; DNA Copy Number Variations ; Brain/metabolism* ; Brain Neoplasms/pathology*

Objective To measure the change of facial volume maintenance rate after autologous fat grafted for repaired progressive facial hemiatrophy by using three-dimensional digital technology.Methods 3D scanner was used to acquire facial data in 10 patients with progressive facial hemiatrophy before operation;Mimics 17.0 software was used to reconstruce patients' facial 3D model and to calculate the volume of facial tissue defect;autologous fat was grafted to repair facial deformity.The facial volume maintenance rate was calculated in all the patients 3 months and 6 months after operation.Results We had performed facial 3D data acquisition and facial repaired with autologus fat grafted in 10 patients;patients' facial morphology was improved.The mean facial volume maintenance rate was (35.80±3.44)％ in 3 months and (27.82±3.80)％ 6 months after surgery.Conclusions The mean facial volume maintenance rate in postoperative 3 months is inferior to that in 6 months in single autologous fat grafted for repairing progressive facial hemiatrophy.

Blood Coagulation Disorders ; physiopathology ; Blood Pressure ; physiology ; Hemodynamics ; physiology ; Humans ; Orthostatic Intolerance ; physiopathology ; Platelet Count ; Posture ; physiology

Objective:To investigate the effect of continuous use of aspirin on gallbladder function and thromboembolism risk in the patients undergoing laparoscopic cholecystectomy. Methods:Totally 100 patients undergoing laparoscopic cholecystectomy from October 2010 to October 2014 were selected as the subjects. All the patients were given aspirin for a long time and randomly divided into two groups. The patients in the observation group were treated with aspirin continuously, and the control group suspended aspirin 7 days before the surgery and administrated aspirin continuously after the surgery. The perioperative thromboembolism,changes in gallbladder function and coagulation function, and intraoperative and postoperative differences in the indicators were compared between the groups. Results:The gallbladder volume in the observation group decreased, and the gallbladder contraction rate and emptying index were higher than those on the 7th day before the surgery(P < 0.05). The above indices were significantly better than those in the control group (P < 0.05). There was no significant change in the coagulation function after the treatment in both groups(P >0.05). There were no significant differences in the operative time,intraoperative blood loss, postoperative drainage and postoperative hospital stay between the groups (P > 0.05). The total incidence of perioperative thromboembolism in the observation group was 2.0%,which was significantly lower than that in the control group(P< 0.05).Conclusion:Continuous use of aspirin during laparoscopic cholecystectomy is beneficial to reducing the volume of gallbladder, promoting gallbladder emptying and reducing the risk of perioperative thromboembolism. The reasonable use has no obvious effect on the postoperative coagulation function.

Objective To explore the changes in the endogenous sulfur dioxide (SO2) pathway in the myocardial hypertrophy induced by the angiotensin Ⅱ (Ang Ⅱ) in mice.Methods Fourteen healthy C57BL mice,9 weeks old,were randomly divided into control group(n =7) and Ang Ⅱ group(n =7),and capsule osmotic pump with pre loaded 9 g/L saline and Ang Ⅱ was implanted into the back of each mouse subcutaneously.Mter 2 weeks,the mice were executed.The heart weight/body weight (HW/BW) and the left heart weight/full heart weight (LVW/HW) of the mice were measured.The microstructure of the cardiac myocyte was observed by hematoxylin-eosin (HE) staining under the microscope.The expression of myocardial alpha myosin heavy chain (α-MHC) was detected by immunohistochemistry and Western blot methods.SO2 enzymes aspartate aminotransferase 1 (AAT1) and AAT2 protein expression were detected by Western blot method.Myocardial SO2 content and AAT activity were measured by high performance liquid chromatography with fluorimetric detection and colometric method.Results Compared with control group,the HW/BW and LVW/HW in mice of Ang Ⅱ group were significantly increased (all P ＜ 0.O1),the cardiac myocytes were hypertrophy,and α-MHC positive staining in the cytoplasm of myocardium was weakened.Moreover,Western blot data showed that α-MHC protein expression in heart tissue of Ang Ⅱ-treated mice was decreased significantly (allP ＜ 0.05).Simultaneously,the data showed that AAT2 protein expression,SO2 content and AAT activity in heart tissue of Ang Ⅱ-treated mice were also decreased markedly[(1.093 ±0.131) μ mol/g protein vs.(0.737 ±0.233) μmol/g protein,P ＜ 0.05;(7.979 ± 1.317) U/rmg protein vs.(6.470 ± O.516) U/mg protein,P ＜ 0.01].Furthermore,there was a negative correlation between LVW/HW and cardiac SO2 content in heart tissue (r =-0.56,P ＜ 0.05).Conclusions Myocardial endogenous SO2/AAT2 pathway is down-regulated in the development of myocardial hypertrophy induced by Ang Ⅱ in mice.

Postural tachycardia syndrome (POTS) is one type of orthostatic intolerance.The treatment for POTS including non-drug treatment and medications,such as α-receptor agonists,β-recepter blockers and oral rehydration salts.The prognostic meaning of biomarkers and hemodynamic parameters in the POTS children treated with midodrine hydrochloride are discussed in this paper.

Hypertension in children and adolescents is defined as systolic blood pressure(SBP)and/ or dias-tolic blood pressure(DBP)≥95th percentile for age,gender and height,on at least 3 occasions. Primary hypertension is more common among children of older age or adolescents,while secondary hypertension accounts for more cases for younger children. Among causes of secondary hypertension,renovascular diseases,renal parenchymal diseases,cardio-vascular diseases,and endocrine diseases are common. An initial evaluation can be reached after history taking and physical examination,to decide whether it should be primary or secondary hypertension. Laboratory tests and procedures can further confirm the classification and etiology. There is an increase in prevalence of hypertension in children and adolescents,and an in - time diagnosis and evaluation of hypertension is important to help patients receive a better management of their conditions.