Objective To analyze the clinical data of patients with neurosyphilis(NS)and explore factors influencing their activity of daily living(ADL).Methods The clinical data of 90 patients with NS was retrospectively analyzed,and the ADL scores at admission were assessed by using the Barthel index(BI).The patients were divided into no-dependency,mild-dependency,and moderate-to-severe-dependency groups.The influencing factors of ADL were explored through comparative analysis and multiple linear regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of clinical indicators for poor ADL recovery(BI score≤60)at discharge in patients.Results Among the 90 NS patients,the average age was 54.17±12.45 years,with 70 males(77.78%).The most common clinical manifestation was abnormal mental behavior(44.44%),followed by limb sensory or motor disorders(25.56%)and dysarthria(16.67%).Based on the BI scores,41 patients(45.6%)were independent,31 patients(34.4%)had mild dependence,and 18 patients(20.0%)had moderate to severe dependence.The comparison results of the three groups showed that the neutrophil-to-lymphocyte ratio(NLR)was gradually increased[2.80(1.97,4.73)vs.3.80(2.28,4.89)vs.5.37(3.76,7.20)]which was higher in the moderate-to-severe-dependency group than in the independent and the mildly-dependent group(P<0.05);cerebrospinal fluid protein concentration[427(341,644)mg/L vs.553(425,830)mg/L vs.933(641,1706.5)mg/L]was gradually increased and there were significant differences in pairwise comparisons(P<0.05).Multiple linear regression analysis showed that NLR(β=-0.242,P=0.018)and cerebrospinal fluid protein concentration(β=-0.461,P<0.001)were negatively correlated with ADL at admission.The area under curve(AUC)for cerebrospinal fluid protein concentration in predicting poor ADL recovery at discharge was 0.806(95%CI:0.708-0.883,P<0.001),with an optimal cutoff value of 620 mg/L,sensitivity of 86.7%,and specificity of 69.4%.Conclusion The main clinical manifestations of NS patients are psychiatric/behavioral abnormalities.Elevated NLR and cerebrospinal fluid protein concentration may be associated with the decreased ADL.Early active intervention of inflammatory response and cerebrospinal fluid protein abnormalities may provide a new way to improve the prognosis of patients.

Objective:To characterize the brain structure of Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to analyze the correlation between the characteristics of the brain structure and the degree of brain development.Methods:A case-control study.The data of 52 children who were diagnosed with ASD according to the diagnostic criteria for ASD in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition of the United States at the Department of Psychology of Qingdao University Affiliated Women and Children′s Hospital from January 2023 to April 2024 were prospectively analyzed.Meanwhile, 48 gender- and age-matched typically developing (TD) children in Qingdao were also included.The three-dimensional T1 weighted imaging sequences of all patients were obtained using a GE 3.0T magnetic resonance imaging scanner.Automated brain segmentation techniques were used to obtain the standardized volumes of each brain structure (the ratio of the absolute volume of the brain structure to the whole brain volume).Two-independent-samples t and Mann-Whitney U tests were used to compare the standardized volumes of different brain regions between the 2 groups.Pearson and Spearman correlation analyses were used to depict the correlations between volume data of brain areas with significant differences and Gesell Developmental Scale scores. Results:Compared with those in the TD group, the volumes of the left grey matter[25.45%(0.70%) vs.25.16%(1.05%)], the right grey matter [(25.89±0.71)% vs.(25.51±0.73)%], the right lateral orbitofrontal cortex [(0.62±0.03)% vs.(0.59±0.05)%], the right medial orbitofrontal cortex[(0.48±0.04)% vs.(0.46±0.04)%], the right pars triangularis [(0.38±0.07)% vs.(0.35±0.05)%], the left hippocampus [0.22%(0.04%) vs.0.20%(0.02%)], the right hippocampus [0.23%(0.04%) vs.0.22%(0.02%)], the left parahippocampal gyrus [0.15%(0.03%) vs.0.14%(0.02%)], the right parahippocampal gyrus [(0.15±0.02)% vs.(0.14±0.02)%], the left fusiform gyrus [(0.82±0.08)% vs.(0.78±0.08)%], the right superior temporal gyrus [(0.96±0.10)% vs.(0.90±0.09)%], the left insular lobe [(0.54±0.03)% vs.(0.53±0.04)%], the right insular lobe [(0.55±0.03)% vs.(0.53±0.04)%], the right inferior parietal cortex [(1.40±0.16)% vs.(1.33±0.12)%], the right precuneus cortex [(0.99±0.09)% vs.(0.94±0.09)%], the right putamen [(0.37±0.04)% vs.(0.35±0.03)%], the left pallidum [(0.14±0.01)% vs.(0.13±0.01)%], the right pallidum [0.14%(0.02%) vs.0.13%(0.01%)], and the right thalamus [(0.51±0.04)% vs.(0.49±0.03)%] were significantly increased in the ASD group (all P<0.05).Nonetheless, the volumes of the left pericalcarine cortex [(0.19±0.04)% vs.(0.20±0.04)%] and the corpus callosum posterior region [0.05%(0.01%) vs.0.06%(0.01%)] in the ASD group were considerably smaller than those in the TD group (all P<0.05).Correlation analysis showed that the right thalamus volume was negatively correlated with the Gesell-adaptation development quotient in children with ASD ( r=-0.276, P=0.048).The volumes of the left fusiform gyrus and left pericalcarine cortex were negatively correlated with the Gesell-fine motor development quotient in children with ASD ( r=-0.290, P=0.037; r=-0.368, P=0.007). The right precuneus cortex volume was negatively correlated with the Gesell-personal and social competence development quotient in children with ASD ( r=-0.396, P=0.007). Conclusions:Children with ASD show abnormalities in the volumes of multiple brain regions, and some brain regions are related to the degree of brain development.Automatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in both ASD and TD children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

Objective To investigate the correlation between glycemic variability metrics and the risk of diabetic foot(DF)in patients with type 2 diabetes mellitus(T2DM)utilizing flash glucose monitoring(FGM)tech-nology.Methods A retrospective analysis was conducted on 233 hospitalized patients with T2DM,with or without DF,who were treated in the Department of Endocrinology at Lianyungang First People's Hospital from January 2021 to May 2022 and monitored using FGM.Patients were categorized into a non-DF group(n=147)and a DF group(n=86)based on the presence of DF.The study compared general clinical characteristics,biochemical parameters,and glycemic variability metrics between the two groups and performed subgroup analyses.Binary logistic regression was employed to identify factors associated with the risk of DF,while receiver operating characteristic(ROC)curves were utilized to assess the predictive value of glycemic variability metrics for DF.Results Compared with the non-DF group,patients in the DF group exhibited significantly longer disease duration,higher body mass index(BMI),glycated hemoglobin(HbA1c),urinary albumin-to-creatinine ratio(UACR),alanine aminotransferase(ALT),serum uric acid(SUA),mean amplitude of glycemic excursions(MAGE),coefficient of variation(CV),mean of daily differences(MODD),and mean blood glucose(MBG),but lower fasting C-peptide(FCP),fasting insulin(FINS),high-density lipoprotein cholesterol(HDL-C),and time in range(TIR),with statistically signifi-cant differences(P<0.05).Subgroup analysis revealed that TIR was associated with the incidence of DF and diabetic retinopathy(DR).Binary logistic regression analysis identified HbA1c,MAGE,MODD,and MBG as risk factors for DF,while TIR was a protective factor(P<0.05).ROC curve analysis demonstrated that the area under the curve(AUC)for predicting DF using HbA1c,TIR,MAGE,MODD,MBG,and their combination were 0.646,0.850,0.868,0.764,0.619,and 0.967,respectively,indicating superior performance of the combined prediction model.Conclusions HbA1c,TIR,MAGE,MODD,and MBG are critical factors associated with the development of DF in patients with T2DM.Targeted early interventions aimed at optimizing these glycemic variability indicators may effectively reduce the incidence of DF.

OBJECTIVE: To evaluate the functional and aesthetic evaluation of external fixator lengthening through plantar approach for fourth brachymetatarsia. METHODS: A retrospective analysis was conducted on 20 patients (23 feet) with fourth brachymetatarsia who met the selection criteria between January 2016 and January 2024, including 3 males and 17 females, with 8 left, 9 right, and 3 bilateral cases. The mean age was 24.7 years (range, 14-51 years). The preoperative metatarsal shortening length was (13.8±3.2) mm. The preoperative American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was 79.5±3.9, the visual analogue scale (VAS) score of appearance satisfaction was 1.7±0.8, and the appearance index (AI) score was 13.6±0.9. All patients underwent external fixator lengthening through plantar approach. The lengthening length of metatarsal bone, lengthening ratio, healing time, and healing index were recorded. Functional outcomes were assessed using the AOFAS forefoot score, VAS score of appearance satisfaction, and quality-of-life impact with AI questionnaire. RESULTS: All 20 patients were followed up 14-55 months with an average of 36.3 months. During the follow-up, complications occurred in 4 cases (17.4%), including 2 cases of metatarsophalangeal joint stiffness, which had no significant effect on the function and appearance. Delayed union of osteotomy occurred in 1 case (healed at 12 weeks after operation). Pin loosening occurred in 1 case and recovered after outpatient reinforcement. No complications related to plantar scar occurred. At last follow-up, the lengthening length of metatarsal bone was (13.9±3.1) mm, and the lengthening ratio was 25.8%±5.6%. All cases achieved bony union, with a mean healing time of (64.3±12.5) days and a healing index of (46.9±4.8) d/cm. At last follow-up, AOFAS score was 98.9±2.1, the VAS score of appearance satisfaction was 9.3±0.7, and the AI score was 0.6±0.8, which significantly improved when compared with those before operation ( t=27.398, P<0.001; t=32.994, P<0.001; t=56.135, P<0.001). CONCLUSION External fixator lengthening through plantar approach is a safe and effective technique for fourth brachymetatarsia, achieving satisfactory functional and aesthetic outcomes.
Humans ; Male ; Female ; Adult ; External Fixators ; Retrospective Studies ; Bone Lengthening/instrumentation* ; Middle Aged ; Metatarsal Bones/abnormalities* ; Adolescent ; Young Adult ; Treatment Outcome ; Patient Satisfaction ; Esthetics ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery*