Objective:To unveil the pathological changes associated with demyelination in schizophre-nia(SZ)and its consequential impact on interstitial fluid(ISF)drainage,and to investigate the thera-peutic efficacy of ursolic acid(UA)in treating demyelination and the ensuing abnormalities in ISF drainage in SZ.Methods:Female C57BL/6J mice,aged 6-8 weeks and weighing(20±2)g,were randomly divided into three groups:control,SZ model,and UA treatment.The control group received intraperitoneal injection(ip)of physiological saline and intragastric administration(ig)of 1％carboxy-methylcellulose sodium(CMC-Na).The SZ model group was subjected to ip injection of 2 mg/kg dizo-cilpine maleate(MK-801)and ig administration of 1％CMC-Na.The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801.The treatment group received UA pretreatment via ig administration for one week,followed by a two-week drug intervention for all the three groups.Behavioral assessments,including the open field test and prepulse inhibition experiment,were conducted post-modeling.Subsequently,changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions.Immunofluorescence analysis was employed to examine alterations in aquaporin 4(AQP4)polarity distribution in the brain and changes in protein expres-sion.Myelin reflex imaging using Laser Scanning Confocal Microscopy(LSCM)was utilized to study modifications in myelin within the mouse brain.Quantitative data underwent one-way ANOVA,followed by TukeyHSD for post hoc pairwise comparisons between the groups.Results:The open field test re-vealed a significantly longer total distance[(7 949.39±1 140.55)cm vs.(2 831.01±1 212.72)cm,P＜0.001]and increased central area duration[(88.43±22.06)s vs.(56.85±18.58)s,P=0.011]for the SZ model group compared with the controls.The UA treatment group exhibited signifi-cantly reduced total distance[(2 415.80±646.95)cm vs.(7 949.39±1 140.55)cm,P＜0.001]and increased central area duration[(54.78±11.66)s vs.(88.43±22.06)s,P=0.007]compared with the model group.Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the star-tle reflex in the model group relative to the controls(P＜0.001 for both),with the treatment group dis-playing significant improvement(P＜0.001 for both).Myelin sheath analysis indicated significant demy-elination in the model group,while UA treatment reversed this effect.Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thala-mus in the model group relative to the controls[(13.93±3.35)mm2 vs.(2.79±0.94)mm2,P＜0.001 for diffusion area;(2.48±0.38)mm2 vs.(0.05±0.12)mm2,P＜0.001 for reflux area],with sig-nificant impairment of drainage in brain regions.The treatment group demonstrated significantly reduced tracer diffusion and reflux areas[(7.93±2.48)mm2 vs.(13.93±3.35)mm2,P＜0.001 for diffusion area;(0.50±0.30)mm2 vs.(2.48±0.38)mm2,P＜0.001 for reflux area].Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls[(3 663.88±733.77)μm2 vs.(13 354.92±4 054.05)μm2,P＜0.001].The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression[(11 104.68±3 200.04)μm2 vs.(3 663.88±733.77)μm2,P＜0.001].Conclusion:UA intervention ameliorates behavioral performance in SZ mice,Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function.The underlying mechanism may involve the improve-ment of demyelination and ISF drainage dysregulation in SZ mice.

Objective To analyze the hot spots,rules and distribution on safety research of inhalation preparations at home and abroad in the past 20 years,and to summarize the current status of safety and risk control research on inhalation preparations.Methods This reaserch is based on the literature related to the safety and risk control of inhalation preparations in the core collection database of the Web of Science.With the help of Excel 2021 and CiteSpace6.1.R3,visualized processing and analysis were carried out on the annual number of publications,countries,institutions,authors,co-occurrence of keywords,clustering and prominence.Results A total of 365 articles were included,the annual publication number in the field of the safety and risk control of inhalation preparations was less than 30 per year from 2002 to 2018.But since 2019,the number of articles published this year has exceeded 30.Through the analysis of the cooperation network of countries and institutions,the top four countries in terms of publication volume are the United States,the United Kingdom,Germany,and China,and the top three institutions are AstraZeneca,GlaxoSmithKline and Pfizer.Through the analysis of the author cooperation network,the cooperation network between European and American authors was formed earlier,and a certain research group has appeared in 2002.In contrast,a more concentrated cooperation network has been formed in China in 2020.Conclusions In the past 20 years,the research on inhalation preparations has mainly focused on their safety and efficacy,while there are few studies on their risk control.There is a disconnect between safety assessment and risk assessment,and the future focus maybe focused on the adverse reaction assessment and risk management research of inhalation preparations.

Objective To explore the value of artificial intelligence federated learning system based on chest X-ray films for pathogen diagnosis of community-acquired pneumonia(CAP)in children.Methods Totally 900 cases of CAP children from 2 hospitals were retrospectively enrolled,including bacterial,viral and mycoplasma CAP(each n=300),and chest posteroanterior X-ray films were collected.Meanwhile,chest posteroanterior X-ray films of 5856 children from the publicly available dataset GWCMCx were collected,including 4273 CAP images and 1583 healthy chest images.All above 6756 images were divided into training set(n=5359)and validation set(n=1397)at the ratio of 8∶2.Then a pathogen diagnosis model of children CAP was established based on attention mechanism.Binary and ternary diagnostic algorithms were designed,and federated deployment training was performed.The efficacy of this system for pathogen diagnosis of children CAP was analyzed and compared with DenseNet model.Results Based on all data,the accuracy of the obtained artificial intelligence federated learning system model for diagnosing children CAP was 97.00%,with the area under the curve(AUC)of 0.990.Based on hospital data,the AUC of this system using single imaging data and clinical-imaging data for pathogen diagnosis of children CAP was 0.858 and 0.836,respectively,both better than that of DenseNet model(0.740,both P＜0.05).Conclusion The artificial intelligence federated learning system based on chest X-ray films could be used for pathogen diagnosis of children CAP.

Objective To observe the alterations in functional complexity of brain regions in autism spectrum disorder(ASD)patients and correlations with the predicted brain age.Methods Open brain resting-state functional MRI(rs-MRI)data of 93 ASD patients and 96 typically developing adolescents(healthy subjects)were downloaded.The functional complexity in brain regions were extracted with self-developed virtual digital brain software,and the alterations in functional complexity of brain regions in ASD patients and correlations with their ages were analyzed.Two networks were prospectively trained with data of 65 ASD patients and 67 healthy subjects as the training set to predict brain age,and the results were evaluated,and the predicting errors were compared using test set,i.e.the other 28 ASD patients and 29 healthy subjects.Results Compared to healthy subjects,on the basis of anatomical automatic labeling(AAL)atlas,ASD patients exhibited significantly reduced functional complexity based on Shannon entropy in the left precuneus,left cuneus and right parahippocampal gyrus.Conversely,functional complexity of ASD patients based on permutation entropy significantly increased in the left cuneus and right cerebellar Crus Ⅱ region.The left hippocampus showed reduced functional complexity based on Pearson correlation coefficient,while the left middle temporal gyrus showed increased functional complexity based on Pearson correlation coefficient.The functional complexity in brain regions of ASD patients were not closely correlated with ages(all|r|＜0.4).According to the trained fully connected network,the predicted brain ages of ASD patients and healthy subjects in test set were all lower than their physiological ages,but no significant difference was found between the prediction errors of ASD patients and healthy subjects(P=0.283).Conclusion Functional complexity changed in some brain region functions in ASD patients.The predicted brain ages of ASD patients based on the obtained fully connected network were on the low side,but not obviously affected by the alterations of functional complexity in brain regions.

Objective　To establish a dual droplet digital PCR (ddPCR) assay for herpes simplex virus type I (HSV-1) and varicella-zoster virus (VZV). Methods The specific primers and probes were derived based on the conserved regions of HSV-1 and VZV genome. The primer-probe combinations were screened, and the annealing temperatures and primer-probe concentration ratios of the dual-droplet digital PCR reaction were optimized to establish a dual-droplet digital PCR reaction system for HSV-1 and VZV, which was tested for other viruses and validated for clinical samples. The sensitivity, specificity, and reproducibility of the established dual microtiter digital PCR method were analyzed. Results The optimal concentrations of primers and probes for the dual ddPCR detection method of HSV-I and VZV were determined to be 800 nmol/L and 250 nmol/L, respectively, with an optimal annealing temperature of 56 ℃. The correlation coefficient (R2) of the standard curve of the dual ddPCR assay was 0.99, showing a clear linear relationship. The method showed high sensitivity, with the lowest detection limit of herpes simplex virus type I being 2.97 copies/μL, and for VZV being 2.73 copies/μL. The repeatability was high with a small coefficient of variation and stable detection results; the specificity was excellent, and no cross-reaction was found with herpes simplex virus type Ⅱ, Epstein-Barr virus, Adenovirus, Coxsackievirus (CA6/CA10/CA16), Cytomegalovirus, Human Cytomegalovirus, Human enterovirus 71, Japanese Encephalitis virus, West Nile virus, Measles virus, Mumps virus, and human nucleic acids. Conclusions The dual droplet digital PCR assay for herpes simplex virus type I and varicella-zoster virus established in this experiment has strong sensitivity, specificity, and high repeatability, and can provide a solution for rapid quantitative detection of the two viruses in different scenarios.

Connectome/methods* ; Magnetic Resonance Imaging/methods* ; Brain/diagnostic imaging* ; Head ; Brain Mapping/methods* ; Nerve Net

OBJECTIVE: To study the difference in age estimation based on quantitative analysis of DNA methylation by MassARRAY and pyrosequencing techniques. METHODS: The methylation levels of 9 CpG sites from two independent whole blood sample sets (containing 65 and 62 samples) were detected using MassARRAY and pyrosequencing techniques. Z-score transformation was used to remove the batch effects of different techniques, and a linear regression model was used for age prediction. RESULTS: For age prediction using the MassARRAY system, the 65 samples showed a mean absolute difference (MAD) of 2.49 years before Z-score transformation of the data and 2.44 years after the transformation, similar to the results in the 62 samples (MAD of 3.36 years before and 3.42 years after Z-score transformation). For data typed from pyrosequencing, the 65 samples showed a MAD of 4.20 years before and 2.76 years after data Z-score transformation, also similar to the results in the 62 samples (MAD of 3.92 years before and 3.63 years after data transformation). CONCLUSIONS Z-score transformation can effectively reduce the system batch effect between MassARRAY and pyrosequencing. Data from the MassARRAY system allows direct age estimation without further data processing, while the pyrosequencing data may increase the error in age estimation, which can be corrected by Z-score transformation of the data.
CpG Islands/genetics* ; DNA Methylation ; High-Throughput Nucleotide Sequencing ; Linear Models ; Sequence Analysis, DNA

Objective:To explore the therapeutic effects of biofeedback therapy of perineal surface on stress urinary incontinence(SUI) in elderly women.Methods:A total of 87 elderly women with SUI treated at the outpatient clinics of Beijing Hospital and Yunnan First People's Hospital between January 2018 and December 2019 were recruited in this prospective cohort study.All participants were therapeutically divided into the perineal BF group(n=53)and the intravaginal BF group(n=34), based on the voluntary selection.In the intravaginal BF group, 3/34 cases dropped out of the study, and finally in 31 cases the treatment was completed.All patients were treated with biofeedback for 8 weeks with twice treatment per week.The quality of life was assessed by the incontinence impact questionnaire scores.Patients underwent the 1-hour pad-weighing test, pelvic floor muscle assessment and quality of life assessment by incontinence impact questionnaire(ⅡQ-7)scores before and after treatment.The effective rate of treatment, adverse reactions and treatment satisfaction scores were compared between the two groups.Results:The urine leakage and scores of ⅡQ-7 questionnaire were significantly improved after versus before 8 weeks of treatment in the perineal BF group[(4.65±2.33) g vs.(11.02±4.85) g, (7.96±5.11) scores vs.(4.34±2.66) scores, t=8.62 and 4.58, P<0.001], and in the intravaginal BF group[(3.85±1.89) g vs.(12.43±3.96) g, (3.81±1.23) scores vs.(8.29±5.01) scores, t=10.89 and 4.84, P<0.001]. Compared with before treatment, the grading of pelvic floor muscle strength was improved after treatment, but had no significant difference in the perineal BF group(3.93±2.77 vs.2.98±2.10, t=1.99, P=0.056)and in the intravaginal BF group(4.51±3.38 vs.3.07±2.02, t=2.04, P=0.051). There was no significant difference in the urine leakage, grading of pelvic floor muscle strength and scores of ⅡQ-7 questionnaire between two groups( P>0.05). The effective rate of treatment had no significant difference between the perineal and intravaginal BF groups(81.13% or 43/53 vs.83.87% or 26/31, χ2=0.10, P=0.750). The incidences of adverse effects were higher(20.59% or 7/34 vs.1.89% or 1/53, χ2=8.68, P=0.003)and the comfort levels during treatment assessed by visual analog scale(VAS)scores were lower in the intravaginal BF group than in the perineal BF group[(8.11±2.93) scores vs.(9.88±3.84) scores, t=2.95, P=0.004]. The main adverse effects included pain or discomfort, vaginal bleeding and increased vaginal discharge in the intrasvaginal BF treatment group. Conclusions:The perineal BF method is as effective as intravaginal BF in female stress urinary incontinencetreatmentin elderly women, and has fewer adverse effects.

COVID-19 had caused the epidemic in Wuhan of China in December 2019. The asymptomatic infection of COVID-19 was found with the further research. This paper summarizes the discovery of the asymptomatic infection cases, analyzes their outcomes and transmission risks, and put forward the targeted suggestions for the prevention and control of asymptomatic infection of COVID-19 according to the existing problems in epidemic response.

An important and unresolved question is how human brain regions process information and interact with each other in intertemporal choice related to gains and losses. Using psychophysiological interaction and dynamic causal modeling analyses, we investigated the functional interactions between regions involved in the decision-making process while participants performed temporal discounting tasks in both the gains and losses domains. We found two distinct intrinsic valuation systems underlying temporal discounting in the gains and losses domains: gains were specifically evaluated in the medial regions, including the medial prefrontal and orbitofrontal cortices, and losses were evaluated in the lateral dorsolateral prefrontal cortex. In addition, immediate reward or punishment was found to modulate the functional interactions between the dorsolateral prefrontal cortex and distinct regions in both the gains and losses domains: in the gains domain, the mesolimbic regions; in the losses domain, the medial prefrontal cortex, anterior cingulate cortex, and insula. These findings suggest that intertemporal choice of gains and losses might involve distinct valuation systems, and more importantly, separate neural interactions may implement the intertemporal choices of gains and losses. These findings may provide a new biological perspective for understanding the neural mechanisms underlying intertemporal choice of gains and losses.
Adult ; Brain ; diagnostic imaging ; physiology ; Brain Mapping ; Delay Discounting ; physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Pathways ; diagnostic imaging ; physiology ; Neuropsychological Tests ; Psychophysics ; Reward ; Young Adult