目的 探究急性脑梗死（ACI）患者血清碱性螺旋-环-螺旋转录因子40（BHLHE40）、丝氨酸蛋白酶抑制剂家族E成员1（SERPINE1）、胆绿素还原酶B（BLVRB）水平与其颈动脉粥样硬化（CAS）程度、近期预后的关系。方法 选择2023年4月—2024年8月邯郸市第一医院（以下简称“本院”）收治的112例ACI患者（研究组），另选取在本院通过健康体检的110例健康人为对照组。根据患者颈动脉内膜中层的厚度（IMT）结果，将研究组患者中的22例纳入正常组，38例纳入增厚组，52例纳入斑块组。以预后评估结果为基准，将研究组患者中的68例纳入预后良好组，44例纳入预后不良组。用ELISA法测定BHLHE40、SERPINE1、BLVRB在ACI患者血清中的表达水平；多因素Logistic回归分析ACI预后不良危险因素；ROC曲线分析BHLHE40、SERPINE1、BLVRB的预测价值。结果 与对照组比较，研究组患者血清BHLHE40、SERPINE1、BLVRB水平明显升高（P<0.05）；与正常组对比，增厚组、斑块组患者血清BHLHE40、SERPINE1、BLVRB水平明显升高，且斑块组显著高于增厚组（P<0.05）；与预后良好组比较，预后不良组血清BHLHE40、SERPINE1、BLVRB水平及NIHSS评分明显提高（P<0.05）；在ACI患者中，血清BHLHE40、SERPINE1、BLVRB水平升高，NIHSS评分提高是其预后不良的危险因素（P<0.05）；BHLHE40、SERPINE1、BLVRB联用，预测ACI预后不良的AUC为0.939；联合预测AUC优于单独预测（Z值分别为3.804、3.197、3.240，P<0.05）。结论 ACI患者血清BHLHE40、SERPINE1、BLVRB水平升高，三者不仅与病情进展相关，亦是预后的影响因素；联合检测可有效提升对ACI不良预后的预测效能。

Objective To investigate the dynamic changes in pulmonary function after allogeneic hematopoietic stem cell transplantation(HSCT)in children and compare pulmonary function differences between children with benign and malignant hematological diseases.Methods A total of 233 children who underwent allogeneic HSCT in the First Affiliated Hospital of Shandong First Medical University,Shandong Provincial Qianfoshan Hospital from June 2015 to December 2023 were selected as subjects,according to the original disease,children were divided into benign group(n=142)and malignant group(n=91).Pulmonary function examination data were collected pre-transplant and at 3,6,9,12,18 and 24 months post-transplant,dynamic trajectories of pulmonary function parameters were analyzed.Results Forced expiratory volume in one second(FEV1)recovered after reaching its lowest in benign group in 6th month post-transplantation,while in malignant group in 9th month(P＜0.001).FEV1/forced vital capacity(FVC)reached its lowest value in 18th month and then recovered(P＜0.001).FEV1,FEV1/FVC,total lung capacity(TLC)and carbon monoxide diffusing capacity(DLCO)were significantly lower in malignant group than those in benign group at most time points(P＜0.05).Reduced DLCO was most common abnormality.Kaplan-Meier analysis showed that those with negative slopes of FEV1,FEV1/FVC,and FVC changes in first 3 months post-transplantation were more likely develop to restrictive ventilatory disorder,and those with negative FEV1/FVC slopes had a significantly higher risk of obstructive ventilatory disorder(P＜0.05).Conlusion Pulmonary dysfunction is prevalent in children after allogeneic HSCT.Pulmonary function parameters of children in malignant group were significantly lower than those in benign group and children recovery was slower.Patients with negative slopes of pulmonary function changes in the first 3 months after post-transplantation are more likely develop to pulmonary dysfunction.

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

Intrauterine growth restriction(IUGR),which refers to the failure of the fetus to achieve ad-equate growth potential,is a common complication of pregnancy.The disease seriously affects fetal growth and development,increases the risk of fetal and neonatal complications and death,and easily causes adverse perina-tal outcomes such as fetal distress and neonatal asphyxia.Children with IUGR have a high risk of lifelong neu-rodevelopmental consequences such as cognitive deficits,cerebral palsy,behavioral problems,learning and con-centration difficulties.Currently,there is no definite treatment method to protect neonates with IUGR from adverse neurological consequences.Early and accurate identification and intervention to promote neurodevelop-ment are essential to improve poor outcomes in neonates with IUGR.In addition,IUGR can also affect blood flow in the fetal brain,change the structure of the ventricles,affect brain functions and change molecular dy-namics indicators in the brain.The purpose of this article is to summarize the progress of research on fetal neurodevelopment of IUGR in recent years,and to review how IUGR affects fetal neurodevelopment and the corresponding diagnostic monitoring methods,so as to provide new ideas for further determining the plan to improve the long-term poor neurological prognosis.

Objective To investigate the dynamic changes in pulmonary function after allogeneic hematopoietic stem cell transplantation(HSCT)in children and compare pulmonary function differences between children with benign and malignant hematological diseases.Methods A total of 233 children who underwent allogeneic HSCT in the First Affiliated Hospital of Shandong First Medical University,Shandong Provincial Qianfoshan Hospital from June 2015 to December 2023 were selected as subjects,according to the original disease,children were divided into benign group(n=142)and malignant group(n=91).Pulmonary function examination data were collected pre-transplant and at 3,6,9,12,18 and 24 months post-transplant,dynamic trajectories of pulmonary function parameters were analyzed.Results Forced expiratory volume in one second(FEV1)recovered after reaching its lowest in benign group in 6th month post-transplantation,while in malignant group in 9th month(P＜0.001).FEV1/forced vital capacity(FVC)reached its lowest value in 18th month and then recovered(P＜0.001).FEV1,FEV1/FVC,total lung capacity(TLC)and carbon monoxide diffusing capacity(DLCO)were significantly lower in malignant group than those in benign group at most time points(P＜0.05).Reduced DLCO was most common abnormality.Kaplan-Meier analysis showed that those with negative slopes of FEV1,FEV1/FVC,and FVC changes in first 3 months post-transplantation were more likely develop to restrictive ventilatory disorder,and those with negative FEV1/FVC slopes had a significantly higher risk of obstructive ventilatory disorder(P＜0.05).Conlusion Pulmonary dysfunction is prevalent in children after allogeneic HSCT.Pulmonary function parameters of children in malignant group were significantly lower than those in benign group and children recovery was slower.Patients with negative slopes of pulmonary function changes in the first 3 months after post-transplantation are more likely develop to pulmonary dysfunction.

Objective Using meta-analysis to identify the risk factors for slow-flow or no-reflow during percutaneous coronary intervention(PCI)in patients with ST-segment elevation acute myocardial infarction(AMI).Methods A computerized retrieval of academic papers concerning the risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI from the databases of CNKI,Wanfang Database,VIP,SinoMed,PubMed,Web of Science,Embase,and Cochrane Library was conducted.The retrieval time period was from the establishment of the database to January 2024.In order to ensure the accuracy and reliability of the study,two independent reviewers screened the literature according to the preset inclusion and exclusion criteria,extracted key data,and strictly evaluated the quality of the literature.RevMan5.4 software was used to make meta-analysis.Results A total of 23 articles with a total of 9 780 cases were included in this analysis.The results of meta-analysis showed that reperfusion time ≥6 h(OR=1.52),preoperative TIMI blood flow≤level-Ⅰ(OR=1.12),heavy thrombus burden(OR=1.60),advanced age(OR=1.56),diabetes(OR=1.83),preoperative Killip grade≥Ⅲ(OR=2.52),long target vessel disease(OR=1.95),and collateral flow≤level-Ⅰ(OR=1.61)were the risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI.Preoperative systolic blood pressure＜90 mmHg(OR=1.17)and high white blood cell(WBC)count(OR=1.27)were not the risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI.Conclusion Reperfusion time ≥ 6 h,preoperative TIMI blood flow≤level-Ⅰ,heavy thrombus burden,advanced age,diabetes,preoperative Killip grade≥level-Ⅲ,long target vessel lesion,and collateral blood flow≤level-Ⅰ are the independent risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI.

Abstract: Objective To compare the differences in the expression of interleukin-8 (IL-8) and signal transducer and activator of transcription 3 (STAT3) among three groups of individuals: patients with multi-drug resistant tuberculosis (MDR-TB), patients with drug-susceptible tuberculosis (DSP-TB), and healthy controls. By analyzing the differences between these groups, the study seeks to provide a reference basis for clinical auxiliary diagnosis of new type tuberculosis. Methods The differences in mRNA expression profiles of chip from peripheral blood mononuclear cells (PBMCs) among three groups were analyzed. MDR-TB and DSP-TB patients were selected as study subjects, with healthy individuals serving as a control group, and the serum IL-8 concentration of each group was measured using an ELISA assay to compare differences between groups. Additionally, PBMCs from all groups were isolated and total RNA was extracted for analysis of IL-8 and STAT3 mRNA expression using quantitative real-time PCR(Q-PCR). Differences in STAT3 protein expression among the groups were also compared by Western blot assay. Results The serum IL-8 concentration in the MDR-TB and DSP-TB groups was significantly higher than that in the healthy control group, with a statistically significant difference (P<0.05). The relative expression level of IL-8 mRNA in PBMCs of the MDR-TB group and DSP-TB group was also significantly higher than that of the healthy control group, with a statistical significance (P<0.05). Both Q-PCR and Western Blot results revealed that the expression of STAT3 in the healthy, DSP-TB and MDR-TB groups sequentially increased, presenting statistically significant differences between the groups (P<0.05), consistent with the mRNA chip results. Conclusions The expression of IL-8 in active tuberculosis patients (ATB) is significantly increased, which can be used as a marker to distinguish ATB from healthy populations. The changes of STAT3 concentration not only serve as a reference for the diagnosis of ATB but can also distinguish between DSP-TB and MDR-TB populations. The combined detection of IL-8 and STAT3 holds promise as a clinical auxiliary diagnostic basis for different tuberculosis patients.

Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.

Objective:To investigate the clinical effect of high diffusion sensitivity coefficient(high b value)diffusion-weighted imaging(DWI),dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)combined with tumor carbohydrate antigen 125(CA125)in judging the nature of ovarian lesions.Methods:A total of 100 patients with ovarian lesions who were treated in Nantong Haimen People's Hospital from April 2020 to April 2022 were selected for retrospective study.All of them underwent CA125,DWI,DCE-MRI and pathologically qualitative examination.According to the pathological results,58 patients with malignant lesions of ovarian were divided into malignant group and patients with benign lesions of ovarian were divided into benign group.The CA125 levels of the two groups were analyzed and compared,and the results of the receiver operating characteristics(ROC)of different detection methods(DWI with high b value+CA125,DCE-MRI+CA125,DWI with high b value+DCE-MRI+CA125)also were analyzed and compared.Results:The CA125 index of the malignant group was significantly higher than that of the benign group,with a statistically significant difference(t=29.357,P＜0.05),and the CA125 positive rate of the malignant group was significantly better than that of the benign group,with a statistically significant difference(x2=34.456,P＜0.05).The apparent diffusion coefficient(ADC)value[(0.91±0.18)×103mm2/s]of the malignant group was significantly less than that[(33±0.21)×103mm2/s]of the benign group,while the contrast agent volume conversion constant(Ktrans),rate constant(Kep)and the extracellular space volume ratio outside of blood vessels(Ve)of the malignant group were significantly higher than those of the benign group,with significant differences(t=16.863,9.686,10.205,P＜0.05),respectively.The diagnostic accuracy,sensitivity,negative predictive value and positive predictive value of DWI with high b-value+DCE-MRI+CA125 examination method were higher than those of DWI with high b-value + CA125 or DCE-MRI+CA125 examination method in diagnosing malignant ovarian tumors.There were not significant differences in various indicators between DCE-MRI+CA125 examination method and DWI with high b-value +CA125 examination method(P＞0.05).ROC curve analysis showed that the area under curve(AUC)of the DWI with high b-value +DCE-MRI+CA125 examination method was the best(AUC=0.920).Conclusion:The combined examination method of DWI with high b-value + DCE-MRI + CA125 has better overall diagnostic efficiency,which can improve the screening ability of clinical diagnosis for malignant ovarian tumors.It has a certain clinical application value.