Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

ObjectiveTo understand the death status of major chronic diseases among the registered residents in Xuhui District， Shanghai from 2007 to 2021， and to analyze the probability and trend of premature death， so as to provide an evidence for the policy-making of disease control and prevention. MethodsBased on the data from the death registration system of the registered residents in Xuhui District， Shanghai from 2007 to 2021， the mortality rate of major chronic diseases， life expectancy without cause of death， potential years of life lost （PYLL）， average years of life lost （AYLL）， and premature death rate were calculated. Joinpoint 4.8 software was used to calculate the annual percentage change （APC） of premature death rate and its trend. ResultsIn 2021， the mortality rate and standardized mortality rate of four major chronic diseases， namely cardiovascular and cerebrovascular diseases， malignant tumors， diabetes mellitus and chronic lower respiratory diseases among the registered residents in Xuhui District， Shanghai was 767.75/100 000 and 234.69/100 000， respectively， accounting for 85.63% of the total causes of death among the residents in Xuhui District， Shanghai. The PYLL， AYLL and PYLL rate were 10 710.00 person-years， 1.49 years per person， and 11.43‰， respectively. Life expectancy increased by 14.91 years after removing the four major chronic diseases. From 2007 to 2021， the premature death rate of chronic diseases among the registered residents in Xuhui District decreased from 9.38% to 7.91% （APC=-1.09%，P<0.05）. Malignant tumors had the highest rate in premature death， and the premature death rate was higher in males than that in females， with a slower rate of decline than in females. Cardiovascular and cerebrovascular diseases， malignant tumors and chronic lower respiratory diseases showed a significant decreasing trend in premature death rate （APC=-1.30%， -1.20%， -5.42%， P<0.05）， while diabetes mellitus showed a significant increasing trend in premature death rate （APC=3.20%， P<0.05）. There was a significant increasing trend in the rate of premature death from diabetes mellitus in males （APC=5.15%， P<0.05） and a decreasing trend in the rate of premature death from diabetes mellitus in females （APC=-0.76%， P<0.05）. ConclusionCardiovascular and cerebrovascular diseases， malignant tumors， diabetes mellitus and chronic lower respiratory diseases are the main causes of death among the registered residents in Xuhui District. The probability of premature death of the residents in Xuhui District from major chronic diseases is at a low level， indicating that the prevention and control of chronic diseases in Xuhui District has achieved some success， but it is still difficult to realize the goals of the Outline of the "Healthy China 2030" Plan. Therefore， it is necessary to comprehensively carry out the control of risk factors such as tobacco use， harmful alcohol consumption， salt intake， hypertension， hyperglycemia and obesity， especially to strengthen the control of risk factors for male residents， as well as early diagnosis and treatment of malignant tumors， cardiovascular and cerebral vascular diseases and diabetes mellitus， and to implement the disease management mechanism to reduce premature death.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

Objective:To analyze the clinical and laboratory characteristics of patients with cryoglobulinemia.Methods:It is a cross-sectional study. The patients diagnosed with cryoglobulinemia in our hospital were enrolled from July 2017 to March 2023. The baseline information of patients, included age, gender, qualitative, and quantitative results of serum cryoglobulins, initial clinical manifestations, etiology, serum complement 3 and 4, and the renal pathological manifestations. The clinical and laboratory characteristics of patients with different types of cryoglobulinemia were analyzed.Results:There were 62 patients (30.7%) with type Ⅰ cryoglobulinemia, 58 patients (28.7%) with type Ⅱ cryoglobulinemia, and 82 patients (40.6%) with type Ⅲ cryoglobulinemia enrolled in this study. Among these patients, 56 of primary cryoglobulinemia, 76 of autoimmune diseases, 29 of tumor-related diseases, and 52 of infectious diseases were observed. Clinical symptoms related to skin lesions (124 cases, 61.4%) and kidney damage (87 cases, 43.1%) were the most common initial clinical manifestations and arthralgia/arthritis (50 cases, 24.8%), peripheral neuropathy (33 cases, 16.3%), fatigue (28 cases, 13.9%), fever (23 cases, 11.4%) were also observed in some patients. The clinical symptoms varied in different types of cryoglobulinemia. 29.0% patients (18/62) with type Ⅰ had fatigue, which was higher than those with type Ⅱ (10.3%, 6/58) and type Ⅲ (4.9%, 4/82) ( P<0.05); Kidney damage occurred in 56.9% (33/58) patients with type Ⅱ and 52.4% (43/82) patients with type Ⅲ, which was higher than that in type Ⅰ patients (17.7%, 11/62) ( P<0.05); Only 4 patients (4.9%, 4/82) with type Ⅲ had peripheral neuropathy, which was lower than those with type Ⅰ (17.7%, 11/62) and type Ⅱ (31.0%, 18/58) ( P<0.05). The quantity of cryoglobulins in patients with type Ⅲ cryoglobulinemia [122 (82, 177) mg/L] was significantly lower than that in patients with type Ⅰ [695(229, 3 499) mg/L] ( P<0.001) and type Ⅱ cryoglobulinemia [350 (107, 1 874) mg/L] ( P<0.001). Complement 4 decreased in 49.0% (99/202) of patients and complement 3 decreased in 42.6% (86/202) of patients. Membranoproliferative glomerulonephritis (36.0%, 9/25) and endocapillary proliferative glomerulonephritis (32.0%, 8/25) were the main renal pathological manifestations of cryoglobulin nephropathy. Conclusions:The most common clinical manifestations of cryoglobulinemia are skin and kidney damage. The clinical manifestations of patients with cryoglobulinemia vary in different types of cryoglobulins. Serum complement decreases in nearly half of cryoglobulinemia patients.

Schizophrenia is a severe mental illness with a significant disease burden.The interaction between oxidative stress and pro-inflammatory factors promotes chronic neuroinflammation and immune damage,leads to dysregulation of dopaminergic and glutamatergic pathways and occurrence of psychotic symptoms and is believed to be closely related to the pathogenesis of schizophrenia.In this paper,we aim to identify biomarkers within the tryptophan kynurenine metabolic pathway,the WNT/β-Catenin pathway and the NF-κB pathway,and dopamine metabolism.These pathways have been extensively studied and are known to be involved in the interac-tion between inflammation and oxidative stress.We will also explore the potential application of related antioxidants in the diagnosis and treatment of schizophrenia,summarizing their current research progress.

Objective To investigate the clinical efficacy of gandouling tablets in patients with Wilson disease(WD)and the role of autophagy in it.Methods A total of 77WD patients admitted to the Department of Neurology of the First Affiliated Hospital of Anhui U-niversity of Chinese Medicine from February 2021 to October 2022 were retrospectively collected,and divided into treatment group(n=42)and control group(n=35).The treatment group was treated with gandouling tablets(GDLT)combined with western medicine,the control group was treated with western medicine.A total of 40healthy siblings of the patients were selected as the healthy group.The ser-um Beclin-1,p62 and LC3-Ⅱ levels of all subjects were detected by enzyme-linked immunosorbent assay(ELISA),and gene ex-pression levels were detected by extracting peripheral blood single nucleated cells and real-time quantitative polymerase chain reaction(RT-qPCR).All WD patients were scored on the unified Wilson disease rating scale(UWDRS).The correlation between the changes of UWDRS score and the levels of Beclin1,LC3-Ⅱ and p62 in WD patients was also analyzed.The effects of GDLT treatment on UW-DRS score and autophagy proteins Beclin-1,p62 and LC3-Ⅱ in WD patients were analyzed.Results The expression levels of Beclin-1,LC3-Ⅱ protein and mRNA were increased and p62 was significantly decreased in WD patients.UWDRS scores were posi-tively correlated with Beclin-1 and LC3-Ⅱ,and negatively correlated with p62.After GDLT intervention,UWDRS score improved sig-nificantly,Beclin-1 and LC3-Ⅱ levels decreased significantly,and p62 increased significantly(P＜0.05).Conclusion Beclin-1,p62,LC3-Ⅱ are closely related to the development of WD,which is of great significance for the evaluation and prognosis of WD.GDLT intervention can inhabit the overactivation of WD autophagy and reverse the progression of WD.

OBJECTIVE: Bo investigate the regulatory relationship between NKD1 and YWHAE and the mechanism of NKD1 for promoting tumor cell proliferation. METHODS: HCT116 cells transfected with pcDNA3.0-NKD1 plasmid, SW620 cells transfected with NKD1 siRNA, HCT116 cells with stable NKD1 overexpression (HCT116-NKD1 cells), SW620 cells with nkd1knockout (SW620-nkd1^-/- cells), and SW620-nkd1^-/- cells transfected with pcDNA3.0-YWHAE plasmid were examined for changes in mRNA and protein expression levels of YWHAE using qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NKD1 to the promoter region of YWHAE gene. The regulatory effect of NKD1 on YWHAE gene promoter activity was analyzed by dual-luciferase reporter gene assay, and the interaction between NKD1 and YWHAE was analyzed with immunofluorescence assay. The regulatory effect of NKD1 on glucose uptake was examined in the tumor cells. RESULTS: In HCT116 cells, overexpression of NKD1 significantly enhanced the expression of YWHAE at both the mRNA and protein levels, while NKD1 knockout decreased its expression in SW620 cells (P < 0.001). ChIP assay showed that NKD1 protein was capable of binding to the YWHAE promoter sequence; dual luciferase reporter gene assay showed that NKD1 overexpression (or knockdown) in the colon cancer cells significantly enhanced (or reduced) the transcriptional activity of YWHAE promoter (P < 0.05). Immunofluorescence assay demonstrated the binding of NKD1 and YWHAE proteins in colon cancer cells. NKD1 knockout significantly reduced glucose uptake in colon cancer cells (P < 0.01), while YWHAE overexpression restored the glucose uptake in NKD1-knockout cells (P < 0.05). CONCLUSION NKD1 protein activates the transcriptional activity of YWHAE gene to promote glucose uptake in colon cancer cells.
Humans ; Colonic Neoplasms ; HCT116 Cells ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; RNA, Messenger ; Glucose ; Calcium-Binding Proteins/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; 14-3-3 Proteins/metabolism*

Objective To investigate the diagnostic value of lean test in Benign paroxysmal positional vertigo of posterior semicircular canal （PC-BPPV）. Methods We retrospectively included the clinical data of 220 patients with unilateral PC-BPPV who were admitted to the Department of Neurology，Jiaxing Second Hospital.All patients underwent lean test first，and then Dix-Hallpike test was performed to study the clinical characteristics of patients with vertigo induced by lean test. Results 133 （60.5%） patients induced PC-BPPV typical upbeat torsional nystagmus during the lean test. During the Dix-Hallpike test，the maximum slow phase angular velocity （SPV） of the induced upbeat nystagmus was higher than the SPV value induced by the lean test，and the latency and duration of the induced nystagmus were significantly different from the lean test （P 0.001）. Conclusion The lean test has a certain reference value for the diagnosis of PC-BPPV. It is effective for the diagnosis of PC-BPPV. The lean test induces a small nystagmus and mild autonomic symptoms compare to suspension position. In view of its simplicity，the lean test can be performed before the Dix-Hallpike operation.

Objective To explore the research hotspots and development trend on vascular dizziness/vertigo based on visual analysis. Methods The Web of Science Core Collection Database was searched for papers on vascular dizziness/vertigo from January 2008 to March 2023. The CiteSpace 6.2.R2 software was used for visual analysis of the literature. Results There were a total of 1298 papers，with an increasing number of published papers from January 2008 to March 2023. A total of 424 institutions from 83 countries/regions had published relevant papers. The United States ranked first in terms of the number of published papers（331 papers） and betweenness centrality（0.25）. Johns Hopkins University was the number one institution in terms of the number of published papers （56 papers），Newman-toker and David E were the most prolific authors. The most common keyword was ischemic stroke. According to keyword clustering，research in this field focused on early diagnosis of vascular dizziness/vertigo from risk factors and bedside examinations and infarction of the anterior inferior cerebellar artery supply area. In recent years，researchers had more interests in case reports，video electronystagmograms，and pathophysiological mechanisms in this field. Conclusion There are growing international studies on vascular dizziness/vertigo. Early diagnosis of vascular dizziness/vertigo through risk factors and bedside examinations in the emergency room is a research hotspot in this field. Researchers should focus on these topics in future studies.

Speech expression is an important high-level cognitive behavior of human beings. The realization of this behavior is closely related to human brain activity. Both true speech expression and speech imagination can activate part of the same brain area. Therefore, speech imagery becomes a new paradigm of brain-computer interaction. Brain-computer interface (BCI) based on speech imagery has the advantages of spontaneous generation, no training, and friendliness to subjects, so it has attracted the attention of many scholars. However, this interactive technology is not mature in the design of experimental paradigms and the choice of imagination materials, and there are many issues that need to be discussed urgently. Therefore, in response to these problems, this article first expounds the neural mechanism of speech imagery. Then, by reviewing the previous BCI research of speech imagery, the mainstream methods and core technologies of experimental paradigm, imagination materials, data processing and so on are systematically analyzed. Finally, the key problems and main challenges that restrict the development of this type of BCI are discussed. And the future development and application perspective of the speech imaginary BCI system are prospected.
Brain ; Computers ; Humans ; Imagery, Psychotherapy ; Speech ; Technology