Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans

OBJECTIVE: To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To study the characteristics of bronchoalveolar lavage fluid (BALF) microbial distribution at different stages of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and its relationship with immune function. METHODS: A total of 108 children with RMPP were enrolled. The relative abundance, richness, and diversity of BALF microbiota, as well as immune function, were compared between the acute phase (n=61) and recovery phase (n=47). The correlations between the richness and diversity of BALF microbiota and immune function were analyzed. RESULTS: The relative abundance of Propionibacterium, as well as the Simpson index, Shannon index, Chao1 index, and Observed species index of BALF microbiota in the acute phase were significantly lower than those in the recovery phase (P<0.05). The relative abundances of Streptococcus and Prevotella, as well as the levels of complement C3, complement C4, immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM), were significantly higher in the acute phase than in the recovery phase (P<0.05). Simpson, Shannon, Chao1, and Observed species indices were negatively correlated with levels of complement C3, complement C4, IgA, IgM, and IgG (P<0.05). CONCLUSIONS In children with RMPP, the relative abundance of Propionibacterium and the richness and diversity of BALF microbiota in the acute phase are lower than those in the recovery phase, while the relative abundances of Streptococcus and Prevotella are higher in the acute phase. Microbial richness and diversity are closely related to immune function.
Humans ; Male ; Pneumonia, Mycoplasma/microbiology* ; Female ; Bronchoalveolar Lavage Fluid/microbiology* ; Child, Preschool ; Child ; Infant ; Microbiota