BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

This study investigated the epidemic status of H3N2 influenza virus and the genetic evolution characteristics of hemagglutinin(HA)and neuraminidase(NA)of H3N2 subtype influenza viruses isolated in Shandong Province during 2023-2024,to understand their compatibility with vaccine strains and drug resistance status.A total of 25 H3N2 subtype influenza virus strains were randomly selected from the strains isolated by the influenza surveillance network laboratory.The HA and NA genes were sequenced with the vaccine strains recommended by the WHO as a reference.Monitoring of sensitivity to oseltamivir and zanamivir was conducted through neuraminidase inhibition experiments.The H3N2 influenza viruses in Shandong Province belonged to the 3C.2a1b.2a.2a.3a.1 clade.Nucleotide sequence analysis revealed that the HA1 and NA genes were closely related to the WHO-recommended vaccine strain A/Darwin/9/2021 for the current season,with homology rates of 97.8%-98.2%and 98.9%-99.3%,respectively.Amino acid sequence analysis indicated 22 amino acid sequence variations in the HA1 protein,and antigenic drift was detected in 8 strains.A glycosylation site was added at position 94 of the HA protein in all 25 strains.Variations occurred in the NA antigenic determinants of some strains.Neuraminidase inhibition experiments indicated that all tested influenza viruses were sensitive to oseltamivir and zanamivir.Some differences in HA and NA proteins were observed between the monitored strains and vaccine strains.Continued monitoring of the molecular evolution characteristics of influenza viruses is necessary to understand the risk of influenza outbreaks,and their effects on the effectiveness of influenza vaccines and therapeutic drugs.

Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

BACKGROUND:The cervical facet joint,as an important anatomical structure of the posterior column of the cervical spine,plays an important role in neck activity,stress transmission,and maintaining cervical stability. In recent years,anatomical and biomechanical studies have shown that asymmetry of cervical facet joints can cause degeneration of facet joints,which may be the main cause of cervical spine degeneration in young people. Existing research is mostly focused on adults,and there are also reports on preschool and school-age children in China,while there are few reports on the morphological parameters of cervical facet joints in adolescents.OBJECTIVE:Through three-dimensional reconstruction of the cervical facet joints in adolescents,measuring their relevant morphological parameters,and comparing them with those in children and adults,we explored the age-related changes in the morphological development of cervical facet joints,providing a theoretical basis for the diagnosis,treatment,and prevention of cervical spondylosis arising from cervical facet joints.METHODS:A total of 62 adolescents aged 13-18 years were selected to undergo spiral CT scan of cervical vertebrae and 3D reconstruction,requiring no bone destruction,tumor,deformity,or fracture,no changes in vertebrae morphology and structure,no previous spinal operations. The guardian's informed consent to the experimental protocol was obtained. By age group,group A was 13-14 years old;group B was 15-16 years old;group C was 17-18 years old. Thecorrelation morphometry and statistical analysis of C2-C7 facet joints were performed in adolescents of each group.RESULTS AND CONCLUSION:(1) In three groups of subjects,the facet joint surface heights and widths displayed decreasing and increasing trends in relation to the change of vertebra order. The facet joint surfaces on the inferior surface showed larger height and width compared to the corresponding indicators on the superior surface. (2) The intra-articular height of the articular process was lowest in C5 among the three groups of ages,and it showed a positive correlation with age. (3) Among the three groups,the gaps between the articular surfaces of the joints in C4-5 of group A,C3-4 of group B,and C4-5 of group C weresignificantly larger than the rest of the gaps in each group. Except for C4-5,there were no significant differences between the two groups. Except for C2-3,the remaining gaps between the vertebrae in group C were significantly larger than those in the two groups. (4) It is indicated that the morphology of the cervical facet joint surface gradually transitions from circular to elliptical as the vertebral order increases. In inter-group comparison,facet joint surface height is significantly affected by age compared to facet joint surface width. The area of the lower facet joint surface of each segment is greater than that of the upper facet joint surface,with only significant differences in the shape and area of C4-5 and C5-6. In addition,the minimum height of the facet joint is located at C5,and the significantly widened gap between the facet joint surfaces is mainly located at C3-4 and C4-5. Therefore,cervical instability often occurs at the mid-level.

Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury(COVID-19-associated KI)and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth,People's,hospital from December 2022 to February 2023.Serum levels of inflammatory factors and chemokines were measured by using enzyme-linked immunosorbent assay(ELISA).In vitro,human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein.The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR(qRT-PCR)and ELISA.Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells(HK-2)in vitro to assess cytokine secretion.Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19,8(20.50%)had creatinine levels above the reference interval,which indicated the occurrence of KI.The levels of peripheral tumor necrosis factor-α(TNF-α)in the COVID-19 patient with KI group[(18.33±8.20)pg/mL]were significantly higher than those in the non-KI group[(11.88±6.50)pg/mL](P=0.015).In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α,interleukin-1β(IL-1β)and chemokine C-X-C motif ligand 10(CXCL10)in THP-1 macrophage cells(P＜0.001).Furthermore,the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α,IL-1β and CXCL10 by HK-2 cells(P=0.005).When anti-TNF-α antibody(Infliximab)was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells,the secretion level of TNF-α by HK-2 cells decreased dramatically(P＜0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI,implying the significance of TNF-α in the occurrence of COVID-19-associated KI.In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells,leading to increased inflammatory responses in renal cells,which may contribute to the development of COVID-19-associated KI.Therefore,targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.

Objective To observe the change patterns of functional connectivity(FC)of basal forebrain subregions in Alzheimer disease(AD)patients.Methods Totally 42 AD patients(AD group)and 41 healthy controls(HC group)were retrospectively enrolled.Seed-based FC analysis was performed on basal forebrain subregions(Ch123 and Ch4)based on their resting-state functional MRI data and compared between groups.Results Compared with HC group,FC between left Ch4 and left hippocampus as well as left posterior cingulate gyrus significantly decreased,but between right Ch4 and right precentral gyrus,as well as right postcentral gyrus increased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Meanwhile,FC between left Ch123 and left superior temporal gyrus,left insula,between right Ch123 and left superior temporal gyrus,left temporal pole significantly increased,while between right Ch123 and right orbital superior frontal gyrus,right orbital inferior frontal gyrus significantly decreased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Conclusion FC changes of different basal forebrain subregions in AD patients were various.

Objective:To investigate the relationship between empathy and meaning in life among medical students,and explore the mediating role of altruistic behavior.Methods:A total of 581 medical students were recrui-ted.They were assessed with the Interpersonal Reactivity Index-C(IRI-C),Altruistic Behavior Questionnaire of College Students(ABQ-CS),and Quadripartite Existential Meaning Scale(QEMS).The bootstrap method was used to test the hypothesized mediating effect.Results:The scores of IRI-C were positively correlated with the scores of ABQ-CS and QEMS(r=0.45,0.21,Ps＜0.001).The scores of ABQ-CS were positively correlated with the QEMS scores(r=0.46,P＜0.001).Altruism was a complete mediator between empathy and meaning in life,the indirect effect was 0.20(95％CI:0.15-0.26).Conclusion:This study reveals the underlying connections a-mong altruistic behavior,empathy,and meaning in life among medical students,suggesting that interventions targe-ting empathy and altruistic behavior may enhance their meaning in life.

Rare diseases pose significant diagnostic and therapeutic challenges,carrying a high disease burden,their management critically reflects a nation's public health resilience.Currently,China faces key challenges such as scarce treatments,fragmented services,and low drug accessibility in rare disease care,which urgently require systemic solutions.Digital-intelligent technology as a key breakthrough are expected to resolve the challenges in this field.Although its application in the field of rare diseases is gradually expanding,there is a lack of systematic compilation of studies to elucidate how to precisely enhance the precision,synergy and sustainability of diagnosis and treatment.The key challenges in rare disease care concentrate in four areas:inefficiency in prenatal screening,uneven distribution of medical resources,low efficiency in social organization collaboration,and ineffective information dissemination.The"4C"strategy,based on digital-intelligent technology,can address these issues:①coordination,boost prenatal screening awareness and capacity via digital-intelligent platforms to strengthen prevention;②cooperation,deepen collaboration within specialist networks,empowering institutions to enhance diagnostic capacity;③co-creation,empower support organizations to optimize resources,efficiency;④cognition,minimize information dissipation through efficient platforms,improving patient and family quality of life.This establishes an integrated digital-intelligent rare disease model encompassing"screening-diagnosis-treatment-care".