ObjectiveTo analyze the risk factors for long-term cardiovascular events in patients undergoing long-term peritoneal dialysis （PD）， and to construct and validate a visual nomogram prediction model based on multiple parameters. MethodsA prospective cohort study was conducted， consecutively enrolling 248 maintenance PD patients （dialysis duration ≥ 3 months）. Demographic characteristics， clinical indicators， laboratory parameters， and echocardiographic indices （including left ventricular ejection fraction ［LVEF］， ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity （E/e’）， etc.） were collected. The composite endpoint was defined as the occurrence of cardiovascular events or cardiovascular death， with non-cardiovascular death as the competing risk and loss to follow-up or the end of follow-up as censoring events. Fine-Gray competing risks model was used to screen independent predictors， based on which a nomogram model was constructed. Internal validation was performed using the Bootstrap method （1 000 resamplings）， and the concordance index （C-index） and time-dependent receiver operating characteristic （time-dependent ROC） curve were calculated to evaluate the model performance. ResultsWith a median follow-up of 29 months （interquartile range： 24–35 months）， 88 patients （35.48%） reached the composite endpoint， including 80 cases of cardiovascular events and 8 cases of cardiovascular death， and 4 patients died of non-cardiovascular causes. Multivariate Fine-Gray analysis revealed that age， diabetes mellitus， hemoglobin （HGB） level and E/e' ratio were independent influencing factors of the composite endpoint. Specifically， each 1-year increase in age was associated with a 3.0% increase in the risk of the composite endpoint （HR=1.030， P=0.006）； patients with diabetes mellitus had a 167.9% higher risk compared with non-diabetic patients （HR=2.679， P=0.007）； each 1g/L increase in HGB level contributed to a 1.5% reduction in the risk （HR=0.985， P=0.003）； and each 0.1 increase in E/e' ratio led to a 7.2% increase in the risk （HR=1.072， P=0.045）. The nomogram model had a C-index of 0.76 （95% CI： 0.698–0.820）， and the AUC of the time-dependent ROC curve reached 0.849 at 23 months of follow-up. ConclusionIncreased age， complicated with diabetes mellitus， decreased HGB， and elevated E/e' ratio are independent risk factors of long-term occurrence of cardiovascular events and cardiovascular death in patients undergoing long-term PD. The nomogram model constructed based on the above variables has good predictive value and clinical applicability， which can provide a reference for cardiovascular risk stratification and individualized intervention in long-term PD patients.

ObjectiveTo observe the prognosis effect of soluble programmed death ligand-1（sPD-L1） in treating patients with advanced lung adenocarcinoma treated with epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） and the influence of Yiqi Yangyin Jiedu prescription. MethodA prospective cohort-controlled study was conducted to enroll patients treated with EGFR-TKIs in the first line of treatment，who were admitted to the Oncology Department of Longhua Hospital and Shanghai Chest Hospital from May 1^st， 2021 to June 30^th， 2023， and they were evaluated as non-progressive and identified with deficiency of Qi and Yin after one month of treatment. The patients were divided into an exposed group （EGFR-TKIs combined with Yiqi Yangyin Jiedu prescription） and a non-exposed group （EGFR-TKIs alone）according to whether or not they were treated with Yiqi Yangyin Jiedu prescription and were treated until disease progression， or death and intolerable adverse reactions occurred. The enzyme-linked immunosorbent assay （ELISA） was applied to detect the level of sPD-L1 in patients at the time of enrollment and disease progression，and Cox risk proportionality model was used to analyze the independent prognostic factors affecting disease progression of patients treated with EGFR-TKIs. ResultA total of 90 patients （39 in the exposed group and 51 in the non-exposed group） undergoing disease progression after EGFR-TKI treatment were enrolled. At the time of enrolment and after disease progression，the levels of serum sPD-L1 in the 90 patients were 12.06 （27.54） ng·L^-1 and 41.99 （62.93） ng·L^-1，respectively. Compared with that at the time of enrollment， the serum sPD-L1 level in the 90 patients was significantly increased after disease progression （P<0.01）. The serum sPD-L1 level in patients in the exposed group was 12.27 （24.78） ng·L^-1 and 29.57 （61.12）ng·L^-1 respectively at the time of enrolment and after disease progression. In the non-exposed group， patients had serum sPD-L1 levels of 11.81 （28.46） ng·L^-1 and 49.54 （74.12） ng·L^-1 respectively at the time of enrolment and after disease progression. Compared with that at the time of enrollment， the serum sPD-L1 level in the two groups of patients was significantly increased after disease progression （P<0.01）. In addition， compared with that in the non-exposed group， the sPD-L1 level in the exposed group was greatly reduced after disease progression（P<0.01）. Cox multifactorial analysis showed that sPD-L1 level and age at the time of enrolment were associated with patients' progression-free survival（PFS），and that low levels of sPD-L1 （<12.06 ng·L^-1） prolonged the PFS and reduced the risk of disease progression in patients treated with EGFR-TKIs compared with high levels of sPD-L1. ConclusionElevated sPD-L1 level is a poor prognostic factor for the long-term efficacy of EGFR-TKIs，and treatment with Yiqi Yangiin Jiedu prescription can down-regulate sPD-L1 level of patients treated with EGFR-TKIs.

Objective To investigate the factors influencing the severity of cerebral white matter hyperintensity in hypertensive patients with acute cerebral infarction,and focus on the independ-ent roles of treatment adherence,advanced age,and multidimensional risk factors.Methods A single-center cross-sectional study was conducted on 262 hypertensive patients with acute cerebral infarction admitted to our department from January 2020 to June 2023.According to their score of Morisky Medication Adherence Scale(MMAS-8),they were divided into an adherence group(116 cases)and a non-adherence group(146 cases).Their demographic data,medical history,and blood pressure data were collected through electronic medical records.Fazekas score was assessed blind-ly to quantify the severity of white matter hyperintensity.MMAS-8 and Montreal Cognitive Assessment Scale(MoCA)were used to assess the behavioral indicators,and modified Rankin Scale(mRS)was employed to evaluate the neurological function.Univariate and multivariate logistic regression analyses were performed to screen the risk factors.Results There were statis-tical differences in marital status,mRS score and Fazekas score between the adherence group and the non-adherence group(P＜0.05,P＜0.01).The non-adherence group had significantly higher diastolic blood pressure than the adherence group[(87.29±7.51)mm Hg(1 mm Hg=0.133 kPa)vs(83.98±8.11)mm Hg,P=0.001].Univariate logistic regression analysis showed age of≥80 years,duration of hypertension≥5 years,systolic blood pressure,and MoCA score＜10 were no-tably correlated with severity of white matter hyperintensity(P＜0.01).Multivariate logistic re-gression analysis indicted that age of≥80 years(OR=3.305,95％CI:1.560-7.001,P=0.002),systolic blood pressure(OR=1.026,95％CI:1.008-1.044,P=0.003),MoCA score＜10(OR=5.210,95％CI:2.060-13.176,P=0.000),and treatment non-adherence(OR=2.380,95％CI:1.346-4.209,P=0.003)were independent risk factors for white matter hyperintensity severity,and duration of hypertension showed no significance in the multivariate model(P＞0.05).Conclusion Poor treatment adherence and advanced age are core factors for white matter hyper-intensity progression in hypertensive patients with acute cerebral infarction.

Background and purpose:As one of the first-line treatment methods for differentiated thyroid cancer(DTC),131I treatment is an important therapeutic approach for most patients with medium-high recurrence risk DTC after total or near-total thyroidectomy.Risk stratification and real-time dynamic assessment before 131I treatment after surgery are important steps in deciding on 131I treatment,enabling individualized treatment.This retrospective study aimed to explore the role of diagnostic whole body scan(DxWBS)in the decision-making of treatment for DTC after surgery and before 131I therapy.Methods:DTC patients who underwent pre-ablation evaluation were included.Patients were divided into low,medium and high sTg groups based on their pre-131I treatment stimulated thyroglobulin(sTg)levels(＜1 ng/mL,1 ng/mL≤sTg＜10 ng/mL,sTg≥10 ng/mL).The concordance rates of DxWBS and post treatment whole body scan(RxWBS)in each patient of the whole cohort were compared.The lesion detection rate between DxWBS and RxWBS in different sTg level groups was also explored.The"thyroid stunning effect"by DxWBS was evaluated by RxWBS.Through these analyses,the role of DxWBS in 131I treatment decision-making and its predicting treatment objectives were assessed.This study was approved by the Ethics Committee of Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences(ethics number:JS-2151).Results:A total of 91 patients were included.The low,medium and high sTg groups accounted for 15.4%(14/91),34.1%(31/91)and 50.5%(46/91)of the patients,respectively.Comparison of DxWBS and RxWBS results in the same patients in each sTg group showed no evidence of a stunning effect on 131I treatment.The overall concordance rate between DxWBS and RxWBS was 89.0%(81/91);In different sTg level groups was 100.0%(14/14),90.3%(28/31),84.8%(39/46)respectively.Taking sTg levels into consideration,DxWBS accurately predicted the need for total thyroidectomy,with a 100%(20/20)agreement with RxWBS.Among the 71 patients who received adjuvant therapy and/or remnant ablation due to suspected elevated Tg or high recurrence risk stratification or the iodine-avid metastatic lesions identified by DxWBS,87.5%(63/71)showed only residual thyroid tissue by DxWBS;Through the purpose verification by RxWBS and single photon emission computed tomography(SPECT)/CT,only 12.7%(9/71)of cases were verified as adjuvant or tumoricidal treatment due to iodine-avid cervical lymph node and/or lung metastasis identified by RxWBS,87.3%(62/71)were residual thyroid ablation.In the medium and high sTg group,the overall detection rate of functional cervical lymph node metastasis by DxWBS and RxWBS was 5.5%(5/91).For the detection of functional lung metastases,the overall detection rate of DxWBS was slightly lower than that of RxWBS(3.3%vs 5.5%).This indicates that DxWBS can be used to accurately pre-judge the purposes of 131I treatment,particularly for thyroid ablation and adjuvant therapy.Conclusion:DxWBS did not induce"thyroid stunning"effect.Integrating DxWBS as a theranostic tool into the real-time decision-making and evaluation system of 131I treatment,as well as with sTg and other biochemical indicators,may help to bridge the limitations of static evaluations based on pathology and clinical data,and provides a clear understanding and more precise objectives of 131I treatment.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective To investigate the factors influencing the severity of cerebral white matter hyperintensity in hypertensive patients with acute cerebral infarction,and focus on the independ-ent roles of treatment adherence,advanced age,and multidimensional risk factors.Methods A single-center cross-sectional study was conducted on 262 hypertensive patients with acute cerebral infarction admitted to our department from January 2020 to June 2023.According to their score of Morisky Medication Adherence Scale(MMAS-8),they were divided into an adherence group(116 cases)and a non-adherence group(146 cases).Their demographic data,medical history,and blood pressure data were collected through electronic medical records.Fazekas score was assessed blind-ly to quantify the severity of white matter hyperintensity.MMAS-8 and Montreal Cognitive Assessment Scale(MoCA)were used to assess the behavioral indicators,and modified Rankin Scale(mRS)was employed to evaluate the neurological function.Univariate and multivariate logistic regression analyses were performed to screen the risk factors.Results There were statis-tical differences in marital status,mRS score and Fazekas score between the adherence group and the non-adherence group(P＜0.05,P＜0.01).The non-adherence group had significantly higher diastolic blood pressure than the adherence group[(87.29±7.51)mm Hg(1 mm Hg=0.133 kPa)vs(83.98±8.11)mm Hg,P=0.001].Univariate logistic regression analysis showed age of≥80 years,duration of hypertension≥5 years,systolic blood pressure,and MoCA score＜10 were no-tably correlated with severity of white matter hyperintensity(P＜0.01).Multivariate logistic re-gression analysis indicted that age of≥80 years(OR=3.305,95％CI:1.560-7.001,P=0.002),systolic blood pressure(OR=1.026,95％CI:1.008-1.044,P=0.003),MoCA score＜10(OR=5.210,95％CI:2.060-13.176,P=0.000),and treatment non-adherence(OR=2.380,95％CI:1.346-4.209,P=0.003)were independent risk factors for white matter hyperintensity severity,and duration of hypertension showed no significance in the multivariate model(P＞0.05).Conclusion Poor treatment adherence and advanced age are core factors for white matter hyper-intensity progression in hypertensive patients with acute cerebral infarction.

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective:To investigate the genomic characteristics of a clinical strain of respiratory syncytial virus (RSV) causing a severe pneumonia outbreak in a maternity center in a city in northern China in 2021.Methods:The whole genome sequence of RSV from a clinical sample obtained from a child with respiratory failure and heart failure was determined and analyzed using Sanger sequencing method. Sequence splicing and alignment were performed using bioinformatics software such as Sequencher 5.0, MEGA 7.0, and BioEdit 7.0. Besides, its phylogenetic relationship with the representative strains of RSV-B genotype, amino acid variations, and glycosylation sites were analyzed.Results:The genome of the clinical strain (named RSV/SY/2021) was 15 242 bp in length, consisting of 10 genes encoding 11 proteins, and possessed all the structural features of RSV. Phylogenetic analysis showed that the RSV/SY/2021 strain belonged to BA9 genotype and had the closest genetic relationship with the 2018 Netherlands epidemic strain MZ515558/Netherlands/2018. The termination codon mutation at the end of its attachment glycoprotein (G) gene resulted in the elongation of seven amino acids "Q-R-L-Q-S-Y-A" and the introduction of two additional O-glycosylation sites.Conclusions:This study suggests that RSV BA9 genotype may cause severe clinical symptoms, and clarifies the genome-wide characteristics and nucleotide/amino acid variation patterns of the RSV/SY/2021 strain. These findings enrich both national and global genome databases of RSV, and provide crucial etiological data for tracking RSV transmission, nucleic acid testing, and the development and evaluation of vaccines, antibodies and drugs against RSV.

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:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.