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.

Objective: To investigate the distribution characteristics of Kidd blood group antigens, phenotypes and genotypes in Xinjiang and their influence on the risk of coronary heart disease. Methods: Samples from 7 981 patients treated at People's Hospital of Xinjiang Uygur Autonomous Region from August 1, 2023 to May 31, 2024 were collected for Jk(a-b-) phenotype screening via urea hemolysis test, followed by the third-generation sequencing (TGS). Kidd blood group Jk and Jk antigens in 1 081 patients with coronary heart disease and 1 021 healthy people were detected, and their phenotype frequency distribution was analyzed and corresponding gene frequencies were calculated. Correlation analysis and logistic regression were used to evaluate the influence of Kidd blood group antigen expression on coronary heart disease risk. Results: Two Jk(a-b-) phenotype samples were detected, both resulting from novel gene mutation combinations. Comparative analysis of two groups revealed a higher proportion of the Jk(a-b+) phenotype in the case group (22.5%, 243/1 081) than in the control group (18.5%, 189/1 021). Moreover, Kidd blood group phenotype distribution varied significantly across all ethnic groups in the case group (P<0.05). In the control group, the Hui ethnic group exhibited the highest JK JK genotype frequency 64.15% (34/53). In the case group, the highest JK allele frequency was observed in Mongol ethnic group 56.31% (125/222), and the lowest in Han patients 45.71% (341/746). The expression of Jk antigen was negatively correlated with coronary heart disease (P<0.05). Conclusion: The distribution of Kidd blood group system varied across ethnic groups in Xinjiang. The expression of Jk antigen may have protective effect on coronary heart disease, which provides a basis for future clinical blood transfusion treatment and the mechanism study of the correlation between Kidd blood group and coronary heart disease.

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

Objective To explore the difference in left ventricular reverse remodeling(LVRR)between coarctation of aorta(CoA)complicated by bicuspid aortic valve(BAV)and that by tricuspid aortic valve(TAV)after percutaneous intervention.Methods The clinical data on 47 patients undergoing percutaneous balloon dila-tion and stent implantation due to CoA in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2014 to December 2021 were retrospectively analyzed.According to the preoperative imaging data,there were 18 patients with BAVA and 29 with TAV.The results of echocardiography before and one year after the procedure were compared.Results CoA Vmax,CoA PG,LVEDd,LVEDdi,LVM and LVMI were significantly improved in CoA patients one year after percutaneous intervention,and 23.4%of the patients developed left ventricular reverse remodeling.AV Vmax,AV PG and LVEDdi in the patients with BAV were higher than those in the TAV group(P = 0.005 and P = 0.007;P = 0.03),and the rate of left ventricular reverse remodeling in BAV patients was lower than that in TAV patients,but there was no statistical significance.Multivariate analysis did not find any influence factors affecting left ventricular reverse remodeling one year after the procedure.Conclusions Part of the CoA patients develops left ventricular remodeling reversal one year after percutaneous intervention.LVRR in patients with BAV is lower than that in those with TAV,which still needs further clinical research.

Objective To evaluate the clinical outcome of kidney transplantation from donation after brain death(DBD)donors complicated with acute kidney injury(AKI).Methods Clinical data of 216 DBD donors were retrospectively analyzed,and they were divided into the AKI group(n=69)and control group(n=147)according to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines.Donors in the AKI group were further divided into the KDIGO stage 1 and stage 2-3 subgroups.One hundred and thirty-five recipients were assigned into the AKI group and 288 recipients in the control group.Postoperative recovery of renal function and clinical outcomes of the recipients were recorded.The risk factors of delayed graft function(DGF)were identified.Results The highest serum creatinine(Scr)level,Scr level before procurement,the highest blood sodium level and blood sodium level before procurement in the AKI group were higher than those in the control group.The application duration of vasopressors in the AKI group was longer than that in the control group.In the AKI group,the amount of fluid resuscitation within 48 h was higher,the HCO3-level at admission was lower,and the incidence of diabetes insipidus and hypotension was higher than those in the control group.The highest Scr level and the Scr level before procurement in KDIGO stage 2-3 donors were significantly higher than those in KDIGO stage 1 counterparts(all P＜0.05).Compared with the control group,the incidence of DGF and acute rejection was higher,the proportion of continuous renal replacement therapy was higher,the Scr level within postoperative 90 d was higher,and the urine amount within postoperative 3 d was less than those of recipients in the AKI group.Compared with KDIGO stage 1 recipients,KDIGO stage 2-3 recipients had higher Scr levels at postoperative 3,4,5 and 15 d,and less urine amount at postoperative 2 d(all P＜0.05).Univariate analysis showed that donor age,the highest Scr level,the highest blood sodium level and the amount of fluid resuscitation within 48 h were the risk factors for DGF in recipients after kidney transplantation.Multivariate analysis showed that donor age was the independent risk factor for DGF in recipients after kidney transplantation(all P＜0.05).Conclusions For the application of DBD donors complicated with AKI,active organ maintenance should be performed to alleviate AKI.It exerts no effect upon graft function and survival rate at postoperative 6 months,which may achieve equivalent efficacy as non-AKI donors and may be used as a source of extended criteria donor kidneys.

Objective:To evaluate the effect of gender factors on the potency of oxycodone inhibiting responses to laryngeal mask airway (LMA) insertion in patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-59 yr, with a body mass index of 18-28 kg/m 2, scheduled for elective surgery with general anesthesia using LMA, were divided into 2 groups according to gender: male group (group M) and female group (group F). The dose of oxycodone was determined by using modified Dixon′s up-and-down method. Oxycodone 0.1 mg/kg was intravenously infused in the first patient of each group, and propofol 3 μg/ml was simultaneously given by target-controlled infusion. When bispectral index value ≤60 after the equilibration between effect-site concentration and plasma concentration was achieved, cisatracurium 0.2 mg/kg was intravenously injected, and 3 min later the LMA was inserted. When the response to LMA insertion was positive, the dose of oxycodone was increased in the next patient, otherwise the dose was decreased, and the ratio between the two successive doses was 1.1. The process was repeated until the 7th turning point occurred. The positive response to LMA insertion was defined as an increase in the maximum heart rate or in the maximum mean arterial pressure >20% of the baseline value with 2 min after insertion. The median effective dose (ED 50) and 95% confidence interval of oxycodone inhibiting responses to LMA insertion were calculated by the probit analysis. Results:Twenty-eight cases were finally included in M group and 25 cases in F group. The ED 50 (95% confidence interval) of oxycodone was 0.105 (0.091-0.115) mg/kg in group M and 0.087 (0.082-0.094) mg/kg in group F. The ED 50 of oxycodone was significantly higher in group M than in group F ( P<0.001). Conclusions:The effect of oxycodone inhibiting responses to nociceptive stimulation induced by LMA insertion is related to gender factors, with increased potency in females.

Objective:To summarize the experience of brain death determination under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) assisted circulatory support, especially apnea test (AT) precautions, and to provide references for brain death determination in this scenario.Methods:In 78 patients who had VA-ECMO at Organ Transplant Center, Zhengzhou People's Hospital from October 2019 to December 2023, 8 organ donors had brain death determination under VA-ECMO assisted circulatory support. Baseline data, clinical data, and VA-ECMO data during AT trial were collected from these 8 patients to summarize the process of brain death determination.Results:Six of the 8 donors met the criteria of brain death; 10 EEG, 12 evoked potentials and 15 ATs were performed. Complications in ATs, including hypotension, decreased oxygenation and arrhythmia, were alleviated after timely improved VA-ECMO flow and applied cardiotonic and pressor drugs.Conclusion:AT is key for successful brain death determination in organ donors under VA-ECMO assisted circulatory support; therefore, complications should be closely monitored and managed.

Objective:To explore the standardized performance of a FISH probe before clinical detection.Methods:The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test.Results:The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001.Conclusion:For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

This review described the management of 11 recipients hospitalized with severe COVID-19 after kidney transplantation during the omicron variant epidemic in Shanghai from December 2022 to January 2023.After withdrawing oral immunosuppressants and starting immunoreplacement therapy, taking small molecule antiviral drugs and treating mixed infections, 10 recipients recovered and were discharged.One critically recipient died from a mixed bacterial and fungal infection after 80-day treatment.No overproduction of inflammatory cytokines was observed during treatment.And no rejection occurred during a cessation of oral immunosuppression.Delayed administration(>1 week of SARS-CoV-2 infection)of small molecule antiviral agents could effectively control viral replication.And there was simultaneous restoration of immune function.

Objective:To evaluate the efficacy and safety of thoracic radiotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) with different metastatic sites.Methods:A retrospective analysis was performed among 830 ES-SCLC patients who were admitted to our hospital from 2010 to 2019. They all received the first-line chemotherapy and had no progression after chemotherapy. 341 patients of them received thoracic radiotherapy after chemotherapy. The main endpoint was overall survival. The Chi-square test was used to compare the categorical data including gender and age, etc. Univariate survival analysis was estimated by Kaplan-Meier method and the log-rank test was used to compare the survival curves between two groups. A multivariate prognostic analysis was made by the Cox proportional hazard model.Results:In all the patients, the overall survival (OS) was 12.4 months. The patients with thoracic radiotherapy had significantly higher OS than the patients without thoracic radiotherapy (15.2 months vs.10.8 months, P<0.001). Thoracic radiotherapy significantly improved the OS in patients without liver metastasis (16.0 months vs.11.4 months, P<0.001) in the oligometastatic patients. But for the oligometastatic patients with liver metastasis, the OS benefit was not significant (14.2 months vs. 10.6 months, P=0.072). For polymetastatic patients without liver metastasis, thoracic radiotherapy offered significant OS benefits (14.5 months vs.10.9 months, P<0.001), but for the polymetastatic patients with liver metastasis, the OS was not improved with thoracic radiotherapy (10.2 months vs.9.2 months, P=0.715). Conclusions:In ES-SCLC patients, thoracic radiotherapy provides significant OS benefits in patients with oligometastases ES-SCLC without liver metastasis and for the liver metastatic patients may also benefit from thoracic radiotherapy based on the effectiveness of chemotherapy. In patients with multiple metastases, thoracic radiotherapy only improves the OS in patients without liver metastasis, but does not improve the prognosis in patients with liver metastasis.