Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Objective To analyze the distribution of traditional Chinese medicine(TCM)syndromes in maintenance hemodialysis(MHD)patients and to evaluate the clinical efficacy of Jianpi Yishen Paidu Therapy(mainly with the actions of strengthening spleen,tonifying kidney,and removing toxins)across different syndrome types.Methods A total of 173 patients with stage 5 chronic kidney disease(CKD)undergoing MHD at Guangzhou Hospital of Integrated Traditional and Western Medicine between October 2019 and October 2024 were enrolled.Statistical analysis was performed on TCM syndrome distribution.Patients were categorized into three groups based on whether they received Jianpi Yishen Paidu Therapy for 2 weeks and their syndrome differentiation:spleen-kidney qi deficiency syndrome group(n=25),spleen-kidney yang deficiency syndrome group(n=39),and control group(n=109).Baseline data and laboratory parameters were collected to assess therapeutic efficacy of Jianpi Yishen Paidu Therapy.Results(1)Among deficiency patterns,spleen-kidney qi deficiency and spleen-kidney yang deficiency syndromes predominated;among excess syndromes,dampness-turbidity and blood stasis syndromes were most common.(2)Adjunctive Jianpi Yishen Paidu therapy enhanced treatment efficacy by decreasing serum creatinine(Scr),blood urea nitrogen(BUN),and cystatin C(Cys-C)levels while increasing hemoglobin(Hb)and serum albumin(ALB)(P＜0.05).Regarding calcium-phosphorus metabolism,the spleen-kidney qi deficiency group showed reduced serum phosphorus(P+)(P＜0.05),while both treatment groups(spleen-kidney qi/yang deficiency)exhibited elevated serum calcium(Ca2+)(P＜0.05)but with no intergroup difference in parathyroid hormone(PTH)(P＞0.05).No significant differences were observed in lipid profiles[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)]among the three groups(P＞0.05).Dialysis vintage was significantly shortened in both treatment groups versus controls(P＜0.05).Conclusion MHD patients primarily exhibit spleen-kidney qi/yang deficiency syndromes(deficiency in the origin syndrome)and dampness-turbidity/blood stasis syndromes(excess in the superficiality syndrome).Syndrome differentiation-based intervention with Jianpi Yishen Paidu Therapy effectively delays renal function decline,improves calcium-phosphorus metabolism,and elevates Hb and ALB levels in MHD patients.

Objective To investigate the therapeutic effects of Modified Baihu Decoction for sepsis-associated encephalopathy(SAE)patients with qi deficiency and toxin stagnation syndrome.Methods A randomized controlled trial was conducted in 72 SAE patients diagnosed with qi deficiency and toxin stagnation syndrome admitted to the Intensive Care Unit of Guangzhou Hospital of Intergrated Traditonal and West Medicine(affiliated to Guangzhou University of Chinese Medicine)between March 2024 and February 2025.Patients were randomly assigned to treatment group(n=36)and control group(n=36)using a random number table.The control group received conventional western therapy,while the treatment group additionally received Modified Baihu Decoction for 5 days.Changes in traditional Chinese medicine(TCM)syndrome scores,Glasgow Coma Scale(GCS)scores,and serum levels of procalcitonin(PCT),interleukin-6(IL-6),and N-terminal pro-brain natriuretic peptide(NT-proBNP)were observed.Improvement in consciousness and TCM syndrome efficacy were evaluated.Results(1)During the treatment period,6 patients from each group dropped out.A total of 60 patients were ultimately included in the statistical analysis,with 30 patients in each group.(2)After 5 days of treatment,the total effective rate for improving consciousness was 80.00％(24/30)in the treatment group and 63.33％(19/30)in the control group.Intergroup comparison(by chi-square test)showed that the consciousness improvement efficacy was significantly superior in the treatment group compared to the control group(P＜0.05).(3)After 5 days of treatment,the total effective rate for improving TCM syndrome was 60.00％(18/30)in the treatment group and 26.67％(8/30)in the control group.Intergroup comparison(by chi-square test)demonstrated significantly superior TCM syndrome improvement in the treatment group(P＜0.05).(4)After treatment,serum levels of PCT,IL-6,and NT-proBNP significantly decreased in both groups compared to baseline levels(P＜0.05 or P＜0.01).The treatment group showed significantly greater reductions in serum PCT,IL-6,and NT-proBNP levels than the control group(P＜0.05 or P＜0.01).(5)After treatment,GCS scores increased significantly from baseline levels in both groups(P＜0.05 or P＜0.01),while TCM syndrome scores significantly decreased(P＜0.05 or P＜0.01).The treatment group demonstrated significantly greater improvement in GCS score elevation and TCM syndrome score reduction than the control group(P＜0.01).Conclusion Modified Baihu Decoction effectively reduces inflammatory response and improves consciousness and TCM clinical symptoms in SAE patients with qi deficiency and toxin stagnation syndrome.

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Bone Neoplasms/immunology* ; Computational Biology/methods* ; Gene Expression Profiling/methods* ; Humans ; Osteosarcoma/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Tumor-Associated Macrophages/immunology*

Objective:To investigate the mechanism of Wnt5a in lentoid body (LB) induction from human embryonic stem cells (hESCs).Methods:A "three-stage" protocol was used for LB differentiation from hESCs in vitro, and Wnt5a level was modified by adding exogenous 500 ng/ml Wnt5a on day 18 as Wnt5a treatment group.Cells of control group and Wnt5a treatment group were collected on day 35.Cells were photographed by using the Zeiss Axio Observer Z1 microscope.Transcriptome sequencing was applied by Illumina.Genes with P value≤0.05 and fold change≥1.5 were identified as differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to determine the biological functions of DEGs. Results:Compared with the control group, larger lentoid bodies were obtained in the Wnt5a treatment group.Transcriptome sequencing result showed that 478 genes were down-regulated and 201 genes were up-regulated in the Wnt5a treatment group compared with the control group, and Wnt5a up-regulated both lens cell differentiation and lens specific gene expression.Bioinformatics analysis result showed that most DEGs were involved in extracellular matrix remodeling, suggesting that Wnt5a regulated extracellular matrix remodeling during lens cell differentiation.The enrichment analysis result also showed that epithelial-to-mesenchymal transformation related processes were inhibited after Wnt5a treatment, suggesting that Wnt5a inhibited the abnormal differentiation of lens cells (especially lens epithelial cells) during lens cell differentiation.Wnt5a influenced the processes related to cytoskeleton remodeling.Conclusions:Wnt5a may act in lens cells through MAPK/ERK signaling pathways to affect ECM and cell cytoskeletal organization, which provides a new direction for studying lens development.

To explore the effect of application of soft tissue loosening and acetabular reconstruction in hip replacement for patients with severe femoral head necrosis on joint function.
 Methods: From June 2012 to August 2016, 68 patients with severe femoral head necrosis (Ficat III, IV) underwent total hip replacement with soft tissue release and acetabular reconstruction at the Second Xiangya Hospital of Central South University. Total hip replacement is performed by the posterolateral approach. The acetabulum was rebuilt and the length of the affected limb was prolonged after clearing the scar tissue, proliferating the epiphysis, releasing the abductor muscle group and the adductor muscle group, dissecting the soft tissue around the acetabulum. One year after surgery, Harris score, X-ray positive lateral radiograph for the affected side and full-length X-ray examination for both lower extremities were performed to evaluate the curative effect.
 Results: The postoperative follow-up time ranged from 1.0 to 5.5 years. All patients' femoral heads returned to normal anatomical position and the affected limb length was restored to 1.5-3.5 cm; all patients did not damage the sciatic nerve. The Harris scores for 68 patients increased from 38.6±7.5 to 78.2±5.7 (P=0.029) in the first year after surgery.
 Conclusion: During hip replacement surgery for severe femoral head necrosis, soft tissue dissection and acetabular reconstruction can be used to ensure anatomical reconstruction for the acetabular fossa and to improve abductor function.
Acetabulum ; Arthroplasty, Replacement, Hip ; Femur Head ; Femur Head Necrosis ; surgery ; Follow-Up Studies ; Humans ; Radiography ; Treatment Outcome

Objective:To explore the diagnostic value of 64‐slice spiral CT for in‐stent restenosis (ISR) after percuta‐neous coronary intervention (PCI) in patients with coronary heart disease (CHD) .Methods :A total of 120 CHD patients after PCI received 64‐slice spiral CT angiography and routine coronary angiography (CAG ) respectively . Then coronary ISR was assessed .Results:With CAG as the gold standard ,sensitivity ,specificity ,positive predictive value and negative predictive value were 87.5% ,95.3% ,80.0% and 97.3% respectively for 64‐slice spiral CT cor‐onary angiography in diagnosis of ISR .Conclusion :The 64‐slice spiral CT coronary angiography possesses high sensitivity and accuracy diagnosing coronary in‐stent restenosis ,which can be used as one of noninvasive measures for postoperative follow‐up after percutaneous coronary intervention .