ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

Objective To investigate the influence and threshold effect of preoperative intraocular pressure(IOP)on secondary glaucoma(SG)after pars plana vitrectomy(PPV).Methods A retrospective analysis was conducted on 88 patients with retinal detachment who developed SG after PPV(SG group)treatment at Hebei Eye Hospital from January 2020 to January 2024.Meanwhile,88 patients with retinal detachment who underwent PPV at the same hospital during the same period but did not develop SG postoperatively were selected as non-SG group in a 1:1 ratio.Univariate analysis was used to compare the differences in clinical data between the two groups.A stratified regression model was applied to analyze the correlation between postoperative characteristics and preoperative IOP.Multivariate logistic regression analysis was used to identify the factors affecting the occurrence of SG after PPV,with multicollinearity diagnosis and sensitivity analysis performed for the parameters.Additionally,the threshold effect of preoperative IOP on the risk of postoperative SG was analyzed.A predictive model was constructed based on the results of multivariate logistic regression.The receiver operating characteristic(ROC)curve was employed to evaluate the efficacy and accuracy of the predictive model,while the calibration curve and clinical decision curve were utilized to assess the consistency between the predictive model and actual conditions as well as the clinical practicality of the model.Results Compared with non-SG group,SG group had a higher proportion of patients with a history of diabetes,family history of glaucoma,a higher preoperative IOP,higher proportion of postoperative closed anterior chamber angle status,longer silicone oil tamponade duration(≥6 months),higher incidence of silicone oil emulsification(P<0.05).Postoperative anterior chamber angle status(closed)was significantly positively correlated with preoperative IOP levels(P<0.05).Multivariate logistic regression analysis showed that history of diabetes,family history of glaucoma,silicone oil emulsification,postoperative anterior chamber angle closure,silicone oil tamponade duration≥6 months,and preoperative IOP≥21 mmHg were independent risk factors for SG after PPV(P<0.05).Multicollinearity diagnosis indicated no significant collinearity among the above variables.Sensitivity analysis showed that the association tended to be null when E=5.014.With the increase of preoperative IOP,the probability of SG after PPV in patients showed an upward trend.The threshold effect analysis revealed that when preoperative IOP≥19 mmHg,the probability of SG after PPV increased significantly with the elevation of preoperative IOP(OR=2.942,95%CI 1.794-4.826,P<0.001).After adjusting for covariates,preoperative IOP remained an independent influencing factor for different degrees of SG after PPV(OR=7.392,95%CI 1.379-12.510,P=0.001).Before and after validation,the area under the ROC curves(AUCs)of the model for predicting SG after PPV were 0.987(95%CI 0.974-1.000,P<0.001)and 0.989(95%CI 0.969-1.000,P<0.001),with sensitivities of 0.9332 and 0.9545,and specificities of 0.9981 and 0.9773,respectively.Both the calibration curve and decision curve analysis demonstrated that the predictive model had good discrimination and accuracy.Conclusion Preoperative IOP is an influencing factor and a sensitive indicator for the development of SG after PPV in patients with retinal detachment.

Objective To evaluate the efficacy,safety,and cost-effectiveness of berberine-based quadruple therapy vs.the clarithromycin-based quadruple therapy for Helicobacter pylori(H.pylori)eradication in treatment-na?ve patients.Methods This was a single-center,prospective,open-label randomized controlled trial.A total of 404 treatment-naive patients with H.pylori infection who visited the Outpatient Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital from September 2021 to May 2024 were enrolled.The patients were randomly assigned in a 1:1 ratio to two groups:berberine quadruple therapy group(berberine+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202)and clarithromycin quadruple therapy group(clarithromycin+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202).Both groups received a 14-day treatment course.The H.pylori eradication rate,incidence of adverse reactions,medication compliance,and treatment costs were compared between the two groups.Results By intention-to-treat(ITT)analysis,eradication rate did not differ significantly between the two groups[89.1%(180/202)in berberine quadruple therapy group vs.89.6%(181/202)in clarithromycin quadruple therapy group,P=0.872].The per-protocol(PP)analysis also showed no significant difference in the eradication rate between the two groups[90.4%(179/198)vs.91.3%(178/195),P=0.763].The incidence of adverse reactions in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group[18.2%(36/198)vs.38.5%(75/195),P<0.001].Specifically,the incidence of taste disturbance in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group(3.0%vs.15.4%,P<0.001).There was no statistically significant difference in medication compliance between the two groups[98.5%(195/198)in berberine quadruple therapy group vs.97.9%(191/195)in clarithromycin quadruple therapy group,P=0.688].The fixed direct medical cost per patient was significantly lower in berberine quadruple therapy group than that in clarithromycin quadruple therapy group(402.08 yuan vs.693.94 yuan).Conclusions The berberine-based quadruple therapy is as effective as traditional clarithromycin-based quadruple therapy for eradicating H.pylori,with the advantages of a lower incidence of adverse reactions and lower cost.It represents a safe,effective,and economical treatment option worthy of further promotion and application.

Objective To investigate the effects of remimazolam(REM)on cerebral ischemia-reperfusion injury(CIRI)rats and the AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods One hundred rats were selected to construct the CIRI rat model(Mod)and stochastically separated into a Mod group,low,medium,and high dose remifentanil groups(REM-L,REM-M,REM-H),and high dose remifentanil+pathway inhibitor Compound C group(REM-H+Compound C),with 20 rats in each group.Another 20 healthy rats were included as the control(Ctrl)group.All rats were subjected to neurobehavioral scoring.The water content,infarct area,and oxidative stress indicators of brain tissue were detected.The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining.Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway.Results Compared with the Mod group,with the increase of REM dose,the movement disorders in rats were alleviated,the overall structure of brain tissue gradually recovered,pathological damage was reduced,the area of cerebral infarction,brain water content,and apoptosis rate of brain tissue cells decreased,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,and NLRP3 and Caspase-1 protein expression levels decreased,superoxide dismutase the(SOD)content and AMPK protein expression level increased(P＜0.05).Compared with the REM-H group,the REM-H+Compound C group showed aggravated motor disorders,and more severe pathological damage to brain tissue,the area of cerebral infarction,cerebral water content and apoptosis rate of brain tissue cells increased,the ROS level,MDA content and the protein expression of NLRP3 and Caspase-1 increased,while the content of SOD and the protein expression decreased(P＜0.05).Conclusion Remimazolam can enhance the antioxidant function of the body,reduce brain cell apoptosis,alleviate brain tissue injury,and thus have a certain protective effect on ischemia-reperfusion brain injury in rats,the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective To investigate the expression of ferritinophagy-related gene ELAV-like RNA binding protein 1(ELAVL1)in multiple myeloma(MM)and elucidate its diagnostic and prognostic value for MM.Methods First,we analyzed ELAVL1 expression level in healthy controls and MM patients using data from the GEO and TCGA databases.Subsequently,bone marrow specimens were collected from 28 newly diagnosed MM patients and 20 healthy controls,and qRT-PCR was employed to validate ELAVL1 expression.The diagnostic and prognostic potential of ELAVL1 was assessed using ROC curve analysis and Kaplan-Meier survival curves.Additionally,univariate and multivariate COX regression analyses were performed to identify independent risk factors for MM prognosis.Finally,KEGG and GO enrichment analyses were performed using the DAVID online platform.Results The level of ELAVL1 expression was significantly higher in newly diagnosed MM patients and refractory/relapsed MM patients than in the healthy controls(P＜0.001).Moreover,ELAVL1 expression was positively correlated with the International Staging System(ISS)stage of MM(P＜0.01).Furthermore,qRT-PCR validation confirmed that ELAVL1 expression was elevated in the 28 newly diagnosed MM patients compared to the 20 healthy controls(P＜0.001).ROC curve analysis demonstrated that ELAVL1 could effectively differentiate between newly diagnosed MM patients,healthy controls,and MGUS patients(P＜0.001 and P=0.000 2,respectively).Survival analysis revealed that high ELAVL1 expression was associated with shorter progression-free survival(P=0.0141)and overall survival(P=0.008 0).Univariate and multivariate COX regression analyses identified high ELAVL1 expression as an independent risk factor for poor MM prognosis(P=0.005 0).KEGG analysis suggested that ELAVL1 might be involved in the Hippo and MAPK signaling pathways.Conclusion High ELAVL1 expression in MM may serve as a biomarker for diagnosis and poor prognosis.ELAVL1 may promote MM initiation and progression via the Hippo and MAPK signaling pathways.

Objective:To systematically analyze the impact of various physician payment methods on medical service delivery behavior and outcomes.Methods:Based on the scoping review method,2 255 documents related to"physician","compensation","payment method",and"physician behavior"were retrieved from Web of Science,CNKI,VIP,and WanFang databases,and finally 70 studies were included based on scientific screening standards and process.Results:Fee-for-service encourages physicians to deliver an adequate volume of services but is susceptible to overtreatment;salary and capitation assist in controlling costs but can lead to insufficient service provision;the advantages of DRG/DIP in the quantity and quality of medical services weaken as the patient's condition worsens.Mixed payment methods can effectively balance the quantity and cost of medical services,while pay-for-performance is generally outstanding in improving quality.Conclusions:It is difficult for a single payment method to achieve the optimization of medical service delivery behavior and outcomes.A mixed payment system that integrates multiple payment methods with quality incentives must be established urgently.At the same time,it is recommended to deepen the reform of the mechanism for converting medical insurance balance into physician compensation,fully implement the allocation autonomy of public hospitals,and accelerate the establishment of a mixed physician payment method that is coordinated with medical insurance payment and performance appraisal.

Objective To investigate the relationship between serum cystatin C(CysC)level and the risk of Parkinson's disease(PD)in middle-aged and elderly people in China.Methods Based on the baseline survey data from the China Health and Retirement Longitudinal Study(CHARLS)in 2011,participants who were not diagnosed with PD at the time of the baseline survey were recruited.The onset of PD was tracked and followed up until 2020,and the participants were divided into PD group and non-PD group according to whether they were newly diagnosed with PD in 2020.Multivariable Logistic regression analysis was performed to assess the association between serum CysC level and the risk of PD.Subgroup and interaction analyses were performed to assess effect modifications by age,gender and depression.Additionally,restricted cubic spline(RCS)was used to explore the linear or non-linear relationship between serum CysC level and the risk of PD in different subgroups.Results We included a total of 3 339 subjects in this study,who consisted of 1 495 males(44.77％)and 1 844 females(55.23％).While baseline participants were followed until 2020,32 subjects had a new PD,and the incidence of PD was 0.96％.The median age of PD group was 63.00 years.Multivariable Logistic regression analysis found that CysC was an independent risk factor for the risk of PD,and CysC was positive significantly associated with the risk of PD(OR=2.34,95％ CI:1.14-4.82,P=0.021).Subgroup analysis showed that CysC was positively associated with PD in females(OR=2.70,95％ CI:1.30-5.58,P=0.007)and subjects aged 60 years or older(OR=5.29,95％ CI:1.69-16.53,P=0.004).RCS model indicated a linear relationship between serum CysC level and the risk of PD in females(Ptotal=0.018,Pnon-linear=0.062)and subjects aged 60 years or older(Ptotal=0.024,Pnon-linear=0.379).Conclusion High level of CysC may increase the risk of PD in middle-aged and elderly people,especially in females and those aged 60 years or older.