[摘 要] 目的：制备低亲和力的CD117 CAR-T细胞，探讨其对急性髓系白血病（AML）细胞Kasumi-1的体外杀伤效应。方法：调取CD117低亲和力抗体巴佐利单抗（barzolvolimab）和Fab-79D VH和VL序列，设计VH-(G4S)3-VL结构的单链抗体，分别构建带4-1BB共刺激分子的经典二代CAR分子，经基因合成后分别亚克隆至pMFG逆转录病毒载体，获得CD117-79D CAR和CD117-0159 CAR质粒。将两种CAR质粒分别包装制备逆转录病毒，检测其滴度合格后转导活化后的T细胞，构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，采用流式细胞术检测两种CAR-T细胞的阳性率。将未转导T细胞与两种CAR-T细胞分别与CD117+ Kasumi-1细胞共培养，通过流式细胞术检测Kasumi-1细胞凋亡率，以评估两种CAR-T细胞的抗肿瘤活性。结果：成功构建CD117-79D CAR-T和CD117-0159 CAR-T细胞，其阳性率分别为（59.4 ± 2.6）%、（62.5 ± 1.2）%。未转导T细胞、CD117-79D CAR-T和CD117-0159 CAR-T细胞体外培养均能稳定增殖，且三者的增殖能力均无显著差异（均P > 0.05）。体外杀伤Kasumi-1细胞结果显示，不同效靶比条件下，CD117-79D CAR-T和 CD117-0159 CAR-T细胞较未转导T细胞展现出显著增强的杀伤能力（P < 0.05或P < 0.01），但两种CAR-T细胞的杀伤效率无显著差异（P > 0.05）。结论：成功构建低亲和力的CD117-79 CAR-T和CD117-0159 CAR-T细胞，体外实验证实其可有效杀伤CD117+ Kasumi-1细胞，为AML的靶向治疗提供了实验依据。

Objective: To analyze the status and trends of the disease burden of periodontal disease among women of reproductive age (15-49 years) in China from 1990 to 2021, and to provide a reference for the development of periodontal disease prevention and control strategies for women of reproductive age. Methods: Using the global burden of disease (GBD) data from 1990 to 2021, this study investigated the periodontal disease burden among women of reproductive age, including prevalence, incidence, disability-adjusted life years (DALYs), DALY rates, and their corresponding standardized indicators. Joinpoint 5.2.0.0 software was used for time trend analysis of DALYs, age-specific DALY rates, and annual average percentage change (AAPC) values. A log-linear regression model was used to test trends for DALYs and DALY rates. Results: Compared with 1990, the prevalence and incidence of periodontal disease among Chinese women in 2021 increased by 45.67% (per 100,000 people) and 29.29% (per 100,000 people), respectively. The distribution of periodontal disease among women (15-49 years) showed a continuous and rapid upward trend, with the growth rate increasing rapidly with age. The number of cases increased the fastest in the 45-49 age group, and the prevalence increased the fastest in the 35-44 age group. The incidence of periodontal disease continued to rise with age, with the fastest increase in the 35-44 age group among women of reproductive age. The Joinpoint regression model results showed that periodontal disease led to an expanding trend in the disease burden among women of reproductive age in China, with an AAPC of DALYs = 1.20% and an AAPC of DALY rate = 1.25% (P<0.001). Conclusion The periodontal disease burden among Chinese women aged 15-49 years showed a gradually increasing trend from 1990 to 2021.

In recent years, with the improvement of people's awareness of physical examination and the more accurate detection equipment, the detection rate of pulmonary nodules is getting higher and higher. Surgical resection is the first choice for the treatment of malignant pulmonary nodules, but multiple pulmonary nodules, nodules in complex areas and those with surgical contraindications are not suitable for surgery. As an effective, less invasive and low-cost treatment, ablation has developed rapidly in the treatment of multiple pulmonary nodules. This article introduces the progress of several common ablation techniques (radiofrequency ablation, microwave ablation, cryoablation) in the treatment of multiple pulmonary nodules, the indications and contraindications of ablation techniques, the efficacy evaluation and complications after ablation therapy, and the prospects of ablation techniques in the treatment of multiple pulmonary nodules.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

ObjectiveTo learn the density and seasonal variation of adult mosquitoes in Pudong New Area of Shanghai, and to explore the influence of meteorological factors on the density of adult mosquitoes. MethodsFrom April to November in 2017‒2021, adult mosquito density in Pudong New Area was monitored every ten days a time by using CO₂ trapping light method. Meteorological data were collected during the same time, and Pearson correlation analysis and multiple linear regression model were used to investigate the correlation between adult mosquito density and meteorological factors. ResultsThe seasonal variation of adult mosquito density showed a single-peak pattern, with the peak of 7.09 mosquitoes·(set·time)^-1 in July. The adult mosquito density was positively correlated with the monthly average temperature, monthly maximum temperature, monthly minimum temperature, and monthly average relative humidity (r=0.813, 0.793, 0.820, 0.617, all P<0.05), but negatively correlated with monthly average air pressure (r=-0.738, P<0.05). The regression equation of the adult mosquito density and monthly minimum temperature in Pudong New Area of Shanghai was Y=0.066 X₃-0.884, with a corrected R² of 0.673, indicating a good model fitting. ConclusionThe overall seasonal variation of adult mosquito density in Pudong New Area showed a single-peak pattern. The density of adult mosquitoes was correlated with the monthly average temperature, monthly maximum temperature, monthly minimum temperature, monthly average relative humidity, and monthly average air pressure, and linearly correlated with monthly minimum temperature.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.