Objective:To investigate how gut microbiota changes during prostate cancer radiotherapy and decipher the relationship of gut microbiota with disease progression and chronic radiation enteritis.Methods:Thirty-one patients with prostate cancer were included in this study,admitted to The First Affiliated Hospital of Xinjiang Medical University from September 2022 to December 2023.The clinical data and stool samples of the patients were collected,and patients were followed up.The collected stool specimens were subjected to 16S rRNA se-quencing to detect gut microbiota and bioinformatics analysis.Results:The relative abundance of phyla such as Firmicutes and Actinobac-teria increased,and that of Bacteroidetes decreased(P<0.05)with an increasing radiotherapeutic dose,while beta diversity was significantly higher(P=0.001).The relative abundance of the phylum Actinobacteria was significantly higher in the prostate cancer progression group than in the non-progression group(P<0.05),the relative abundances of genera such as Sutterella and Haemophilus were significantly higher in the progression group(P<0.05).That of Verrucomicrobia and its offshoots in Akkermansia was higher in the chronic radiation enteritis than in the non-enteritis group(P<0.05),while the relative abundances of Coprococcus_1 and Catabacter in the non-enteritis group were higher than those in the enteritis group(P<0.05).Conclusions:Radiotherapy dose accumulation significantly remodeled the floral structure.Sutterella and Haemophilus of the phylum Proteobacteria might be key flora in prostate cancer recurring early after treatment.An augmen-ted abundance of Akkermansia might increase the risk of chronic radiation enteritis,whereas the flora under the Lachnospiraceae branch might exert aprotective effect against chronic radiation enteritis.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Aim To investigate the mechanism of in-testinal mucosal barrier protective effect of Qingjie Huagong decoction(QJHGD)on rats with severe acute pancreatitis(SAP).Methods The SAP rat model was constructed,and the sham-operation group,the model group,the group administered with different dosages of QJHGD,and the positive control group were set up respectively.HE staining was used to observe the histopathological changes.ELISA was employed to detect the serum levels of diamine oxidase(DAO)and D-lactic acid(D-LA)in rats.Transmission electron microscopy was utilized to observe the mitochondria of ileal tissues.qRT-PCR and Western blot were applied to detect the mRNA and protein expression of PGAM5,Drp1,PINK1,Parkin,LC3B in ileal tissues of rats.Results Compared with the sham-operated group,the pancreas and ileum tissues of rats in the model group showed obvious pathological changes,with abnormal mitochondrial structure and reduced number of autoph-agic vesicles in the ileum tissues.The levels of DAO and D-LA in serum increased(P＜0.01),and the mRNA and protein expression of PGAM 5,Drp 1,PINK1,Parkin,and LC3B in the ileum tissues de-creased significantly.Compared with the model group,pancreatic and ileal pathology were improved,mito-chondrial damage in the ileum was reduced,and the number of autophagic vesicles increased in the QJHGD group.The serum levels of DAO and D-LA were re-duced,and the expression of PGAM5,Drp1,PINK1,Parkin,and LC3B mRNA and protein in the ileal tis-sues increased significantly.Conclusions QJHGD may exert a protective effect on the SAP intestinal mu-cosal barrier by regulating the PGAM5/Drp1/PINK1/Parkin axis in order to elevate the level of mitochondri-al autophagy in the intestinal epithelial cells,thereby improving the level of repair of the intestinal epithelial cells.

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 investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny