Objective To investigate the characteristics of imprinted differentially methylated regions (iDMRs) in placentas and their correlation with preeclampsia (PE). Methods A total of 43 healthy pregnant women (control group) and 33 pregnant women with PE (PE group) at Shanghai Putuo Maternity and Infant Hospital and International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University School of Medicine from September 2021 to September 2023 were selected. A total of 3 362 CpG sites in 62 iDMRs were analyzed in 76 placenta and 5 maternal blood samples using BisCap targeted bisulfite resequencing (BisCap-seq) assays. The CpG sites in the CpG islands of the iDMRs were assessed for their methylation levels and methylation linkage disequilibrium (MLD). Imprinted methylation haplotype blocks (iMHBs) were constructed based on MLD. The methylation levels and variablility of CpG sites and iMHBs were compared among the healthy placenta, PE placenta and blood samples. Results The CpG sites in the CpG islands of the iDMRs exhibited intermediate methylation, with adjacent sites displaying high MLD (methylation levels: 0.35-0.65, D’ ＞ 0.8). A total of 185 iMHBs were constructed using these coupled CpG sites, 60 placenta-specific iMHBs and 38 somatic iMHBs were found to be differentially methylated in the placenta compared with maternal blood (P_adj＜0.05). Twenty-seven iMHBs were identified with differentially variable methylation patterns in the placenta. The iMHBs methylation was unchanged in the PE placentas compared to the healthy placentas. Twenty-seven differentially methylated cytosines (DMCs) were identified outside the iMHBs structure, among which the methylation levels of 19 CpG sites showed statistically significant differences between the PE group and the control group (P_adj＜0.05). The quantitative results of placental compositions of maternal plasma cell-free DNA (cfDNA) using placenta-specific haplotype (PSH) were highly correlated with those estimated by a deconvolution methodology (r＝0.973, P＜0.01). Conclusions The genomic imprinting features in the PE placentas were obvious, and PSH could be a potential marker of the placenta to quantify the placental compositions of maternal plasma cfDNA.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

Objective:To investigate the clinical efficacy of three-connections and four-screwings technique in the treatment of high double column acetabular fractures through a single ilioinguinal approach.Methods:A retrospective study was conducted to analyze the data of 42 patients who had been treated for high double column acetabular fractures from June 2017 to June 2020 at Trauma Ward 2, Department of Orthopedics and Traumatology, The First Hospital of Traditional Chinese Medicine of Changde. There were 19 males and 23 females with an age of (42.7±25.6) years. 29 injuries were due to a traffic accident, 12 ones to fall from a height, and one to fall. The time from injury to operation was (4.5±2.1) days. All the patients were treated by the three-connections and four-screwings technique through a single ilioinguinal approach. Briefly, the anterior column was connected and secured to the main bone using 3 routes, and the posterior column was attached and fixated to the anterior column reset using 2 or 3 of the 4 screwings. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, hip function at the last follow-up and complications during the follow-up were recorded.Results:For this cohort, the operation time was (150.0±30.5) min, and intraoperative blood loss (300.0±50.0) mL. According to the Matta scale for postoperative acetabular fracture reduction, 34 cases were excellent, 6 cases good, and 2 cases acceptable, with an excellent and good rate of 95.2% (40/42). After operation one patient had fat liquefaction and wound exudation which responded to drainage and dressing change. The 42 patients were followed up for (15.0±3.4) months. All fractures healed after (11.0±2.0) months. By the modified Merle d'Aubigné & Postel scoring system, the hip function was evaluated at the last follow-up as excellent in 33 cases, as good in 6 cases, and as fair in 3 cases, yielding an excellent and good rate of 92.9% (39/42).Conclusions:In the treatment of high double column acetabular fractures, the three-connections and four-screwings technique through a single ilioinguinal approach can lead to fine reduction and rigid fixation by lag screw compression and neutralization plate protection. Consequently, early functional exercises can be performed to secure good therapeutic outcomes for the patients.

Objective:To investigate the relationship between the expression level of thymocyte selection-associated high mobility group box protein ( TOX) gene and the radiosensitivity of lower-grade glioma (LGG) patients. Methods:Using bioinformatics research methods, 474 LGG patients from The Cancer Genome Atlas (TCGA) database were selected as the test set (TCGA-474 set), and two different genetic data sets ( n=412 and n=171) from the Chinese Glioma Genome Atlas (CGGA) database were selected as the validation set (CGGA-412 set and CGGA-171 set). Patients were stratified based on whether received radiotherapy, and divided into the high and low TOX expression group according to the expression level of TOX gene in LGG. Survival curves of all patients were plotted. The overall survival (OS) and progression-free survival (PFS) of patients in the high and low TOX expression groups were compared and analyzed using log-rank test. Results:Multivariate analysis of OS in the TCGA-474 set showed that high expression of TOX was a protective factor for OS ( HR=0.061, 95% CI: 0.005-0.791, P=0.044). After stratification analysis based on radiotherapy and adjustment for confounding factors, the HR (95% CI) of patients with high TOX expression in the TCGA-474, CGGA-412, and CGGA-171 sets were 0.405 (0.261-0.629), 0.581 (0.418-0.806), and 0.464 (0.269-0.800), respectively, with P values of <0.001, 0.001, and 0.008, respectively. Among patients receiving radiotherapy in the TCGA-474 set, the OS and PFS of patients with high TOX expression were significantly longer than those in the low TOX expression group, and the differences were statistically significant (both P<0.001). The OS benefit of patients with high expression of TOX was significantly prolonged in both the CGGA-412 and CGGA-171 sets compared to those with low TOX expression, and the differences were statistically significant (both P<0.001). Conclusion:The high expression of TOX may be related to the radiosensitivity of LGG, which may be a gene marker of the radiosensitivity of LGG.

Objective:To investigate the clinical features and multimodal imaging features of eyes with perifoveal exudative vascular anomalous complex (PEVAC).Methods:A retrospective case study. From February 2014 to November 2020, 7 eyes of 7 patients with PEVAC diagnosed by ophthalmology examination in Department of Ophthalmologyof Peking University People's Hospital were included in this study. There were 6 males and 1 female. The age was 60.1±9.1 years. All were monocular. The chief complaints of visual deformation and vision loss were 3 and 1 cases, respectively. All patients underwent best corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT), fundus fluorescein angiography (FFA). BCVA examination was performed using the standard logarithmic visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. OCT angiography (OCTA) and indocyanine green angiography (ICGA) were performed in 4 and 2 eyes, respectively. Three eyes were treated with intravitreal injection of anti-vascular endothelial growth factor (VEGF) combined with local laser photocoagulation. Two eyes were treated with laser photocoagulation alone. The follow-up time was 16.7±19.1 months. During follow-up, relevant examinations were performed with the same equipment and methods as at the initial diagnosis. The multimodal imaging characteristics and treatment response of the affected eyes were observed.Results:The baseline logMAR BCVA was 0.33±0.19 (0.20-0.80). All eyes showed isolated hemangiomatous lesions in the macular fovea with rigid retinal exudation, and 2 adjacent isolated hemangiomatous lesions were observed in 1 eye. FFA and ICGA examination showed that all eyes with macular hemangiomatous lesions showed clear boundary and strong fluorescence in the early stage. No other retinal or choroidal vascular abnormalities were observed. On OCT examination, circular lumen-like structures with strong reflective wall near the fovea were observed in the macular region of all eyes, accompanied by intraretinal cystic lumen. The macular central retinal thickness (CMT) was 326±125 (207-479) μm. In the four eyes examined by OCTA, blood flow signals were observed in the circular lumenoid structures with strong reflective walls adjacent to the fovea. Blood flow signals were observed in the superficial capillary layer (SCP) and deep capillary layer (DCP) of the retina in 3 eyes. SCP showed blood flow signal in 1 eye. In 4 eyes treated with intravitreal injection of anti-VEGF drugs, there was no significant improvement in the intraretinal capsule space after treatment. Subretinal fluid absorption, retinal cystoid edema persisted, and rigid exudation decreased in 1 eye. CMT decreased and BCVA increased in 5 eyes treated with laser photocoagulation or laser photocoagulation alone. At last follow-up, logMAR BCVA was 0.16±0.06 (0.10-0.20) and CMT was 212±34 (154-252) μm. Compared with baseline, the difference of BCVA was statistically significant ( t=2.661, P=0.037). Conclusions:The fundus of PEVAC patients is characterized by solitary or multiple solitary hemangiomatous lesions in the macular fovea. Round lumenoid structures with strong reflective walls, with or without intraretinal cystic lumen, rigid exudate, and subretinal fluid, in which blood flow signals can be seen in OCT.

OBJECTIVE: To investigate the effect of dexmedetomidine combined with pulmonary protective ventilation against lung injury in patients undergoing surgeries for esophageal cancer with one-lung ventilation (OLV). METHODS: Forty patients with undergoing surgery for esophageal cancer with OLV were randomly divided into pulmonary protective ventilation strategy group (F group) and dexmedetomidine combined with protective ventilation strategy group (DF group; =20). In F group, lung protective ventilation strategy during anesthesia was adopte, and in DF group, the patients received intravenous infusion of dexmedetomidine hydrochloride (0.3 μg · kg ·h) during the surgery starting at 10 min before anesthesia induction in addition to protective ventilation strategy. Brachial artery blood was sampled before ventilation (T), at 30 and 90 min after the start of OLV (T and T, respectively) and at the end of the surgery (T) for analysis of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), arterial oxygenation pressure (PaO), oxygenation index (OI) and lung compliance (CL). RESULTS: At the time points of T, T and T, SOD level was significantly higher and IL-6 level was significantly lower in the DF group than in F group ( < 0.05). The patients in DF group showed significantly higher PaO, OI and CL index than those in F group at all the 3 time points. CONCLUSIONS Dexmedetomidine combined with pulmonary protective ventilation strategy can reduce perioperative lung injury in patients undergoing surgery for esophageal cancer with OLV by suppressing inflammation and oxidative stress to improve lung function and reduce adverse effects of the surgery.
Analgesics, Non-Narcotic ; pharmacology ; therapeutic use ; Dexmedetomidine ; pharmacology ; therapeutic use ; Esophageal Neoplasms ; drug therapy ; surgery ; Humans ; Lung ; drug effects ; surgery ; One-Lung Ventilation ; Oxidative Stress ; drug effects ; Treatment Outcome

OBJECTIVE: To investigate the effect of dexmedetomidine combined with pulmonary protective ventilation against lung injury in patients undergoing surgeries for esophageal cancer with one-lung ventilation (OLV). METHODS: Forty patients with undergoing surgery for esophageal cancer with OLV were randomly divided into pulmonary protective ventilation strategy group (F group) and dexmedetomidine combined with protective ventilation strategy group (DF group; =20). In F group, lung protective ventilation strategy during anesthesia was adopte, and in DF group, the patients received intravenous infusion of dexmedetomidine hydrochloride (0.3 μg · kg ·h) during the surgery starting at 10 min before anesthesia induction in addition to protective ventilation strategy. Brachial artery blood was sampled before ventilation (T), at 30 and 90 min after the start of OLV (T and T, respectively) and at the end of the surgery (T) for analysis of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), arterial oxygenation pressure (PaO), oxygenation index (OI) and lung compliance (CL). RESULTS: At the time points of T, T and T, SOD level was significantly higher and IL-6 level was significantly lower in the DF group than in F group ( < 0.05). The patients in DF group showed significantly higher PaO, OI and CL index than those in F group at all the 3 time points. CONCLUSIONS Dexmedetomidine combined with pulmonary protective ventilation strategy can reduce perioperative lung injury in patients undergoing surgery for esophageal cancer with OLV by suppressing inflammation and oxidative stress to improve lung function and reduce adverse effects of the surgery.
Dexmedetomidine ; Esophageal Neoplasms ; therapy ; Humans ; Lung ; Malondialdehyde ; One-Lung Ventilation

Objective:To analyze the influence of CD19 isoforms to the efficacy of CD19/CD3 Bispecific T-cell Engager (BiTE) antibody, and explore the resistance mechanism of BiTE immunotherapy.Methods:Semi-quantitative RT-PCR (qRT-PCR) was used to detect the expression of CD19 mRNA isoforms before and after BiTE treatment in a patient with CD19 + B cell acute lymphoblastic leukemia (ALL) . CD19 isoforms were analyzed by Sanger sequencing. Flow cytometry and transcriptome sequencing were performed to analyze the expression of cell lineage specific molecules before and after BiTE treatment. Results:The expression of CD19 isoform with exon 2 deletion was identified at diagnosis. After relapsed and treatment of BiTE antibody, the patient did not achieve remission and CD19 antigen on leukemic cells turned negative detected by flow cytometry after BiTE treatment. However the expression ratio of CD19 isoform with exon 2 deletion was not increased. Flow cytometry phenotype and transcriptome sequencing confirmed that no linage switching developed, which suggested the expression of CD19 isoform caused by exon alternative splicing and lineage switching was not related to CD19 epitope loss in this patient. This patient achieved complete remission by sequential administration of self-developed CD22 CAR-T and CD19 CAR-T after disease progression.Conclusion:Targeting or combining an alternative antigen specific CAR-T may be a promising treatment option after losing CD19 expression in relapsed ALL.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.