[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

ObjectiveTo explore the differences in attention to the sub-dimensions of satisfaction with the quality of assistive devices among people with different self-care abilities in China, identify the key driving factors, and provide a basis for the precision design and service provision of assistive devices. MethodsBased on the 2023 national survey data, involving 14 030 people with functional impairments, self-care ability was taken as the core independent variable, eight sub-dimensions of satisfaction as dependent variables, and variables such as gender, age, educational level and residential type were controlled. Univariate analysis was performed using Chi-square test with Bonferroni correction, and a binary Logistic regression model was constructed to identify influencing factors. Meanwhile, reliability and validity tests, endogeneity tests (instrumental variable method and propensity score matching) and heterogeneity tests were conducted. ResultsAmong the eight satisfaction sub-dimensions, six presented significant inter-group differences, with Bonferroni correction (threshold = 0.00625). Following binary Logistic regression and endogeneity correction, significant inter-group heterogeneity was confirmed in dimensions such as size and shape. For the affordability dimension, the main effect of self-care ability was not statistically significant, yet prominent urban-rural heterogeneity was observed. Specifically, taking the fully independent (self-care) group as the reference, the fully dependent group attached significantly greater importance to safety (B = 0.253, P < 0.001), comfort (B = 0.153, P = 0.001) and ease of use (B = 0.316, P < 0.001); the partially dependent group showed the highest level of attention to lightweight (B = 0.094, P = 0.027) and durability (B = 0.254, P < 0.001); and the fully independent group demonstrated a relatively stronger preference for aesthetics. ConclusionStratified functional demands, driven by self-care ability, exist in the satisfaction of individuals with functional impairments with assistive devices in China. The policy formulation and product design of assistive devices should shift to a precision-oriented paradigm: prioritize the guarantee of safety, comfort and ease of use for fully dependent groups, optimize lightweight performance and durability for partially dependent groups, enhance aesthetics and social acceptance for fully independent groups, roll out price subsidy policies for urban price-sensitive groups, and strengthen the supply of core functional services for rural groups. This approach will comprehensively improve the adaptation effectiveness of assistive devices and the well-being of users.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Objective: To understand the current status of neglect among rural preschool children in Xi an under the multi child policy and the association with family characteristics, so as to provide a reference for preventing and reducing the occurrence of child neglect. Methods: A total of 7 052 parents of preschool children were selected using stratified cluster sampling across 9 suburban counties/districts in Xi an from March to April 2025. A questionnaire survey was administered using the Chinese Norm Scale for Neglect Assessment of Rural(Preschool) Children Aged 3-6. The t-test, Chi-quare test, and analysis of variance (ANOVA) were used for inter group comparisons. Results: The overall prevalence rate and mean score of neglect among rural preschool aged children in Xi an were 32.4% and 38.27±6.70, respectively. Statistically significant differences were detected in neglect rates and neglect degrees among preschool children of different genders and grade levels ( χ 2=30.41, 15.15, t/F =4.92,7.03, all P <0.05). Statistically significant differences were also detected in neglect rates and neglect degrees among preschool children from whether only one child, different family structures, numbers of children in a family and families with different annual incomes ( χ 2=29.22, 10.41 , 31.99, 186.47, t/F =-9.96, 5.50, 33.57, 68.63, all P <0.05). In multi child families, there was a statistically significant difference in neglect degree among children with different birth orders ( F =4.25, P <0.05), but there was no statistically significant difference in neglect rate ( χ 2=5.73, P >0.05). Among all subgroups, the highest neglect rates and neglect degrees were observed in children from multi child families(35.0%,39.00±6.71), other family types(50.0%，42.38±12.34) and families with three children(39.9%，39.50±7.43). Lower annual family income was associated with higher neglect rates and neglect degrees among preschool children( χ 2 trend =186.47， F =270.68，both P <0.05). Conclusions Under the multiple child policy, the neglect of preschool children in rural areas of Xi an is quite severe, particularly in families with multiple children and low income households. Targeted interventions should be implemented for high risk groups.

Objective To assess the echogenicity of the ultrasound-guided catheter and its associated delivery system. Methods The study consisted of in vitro characterization experiments and animal studies. In the in vitro phase, the acoustic and mechanical properties of the ultrasound-guided catheter were compared with those of the traditional MPA2 catheter, including parameters such as echo intensity, recognizability, and angle dependence. In the animal experiments, a ventricular septal defect (VSD) model was established in miniature pigs to compare the procedural performance of the ultrasound-guided delivery system versus the conventional system. Evaluation indicators included the time required for the system to cross the VSD, the detection rate of the system within the right ventricle, and the occurrence of intraoperative complications. Results The ultrasound-guided catheter demonstrated a significantly higher mean echo intensity than the MPA2 catheter [(237.3±1.8) dB vs. (190.9±13.1) dB, P<0.001] and a markedly improved recognizability rate (82.3%±5.6% vs. 26.7%±3.2%, P<0.001), along with better angle independence and image quality. In animal experiments, the ultrasound-guided delivery system significantly reduced the time required to cross the VSD [(18.5±5.7) min vs. (30.3±4.5) min, P<0.001] and substantially increased the detection rate within the right ventricle (100.0% vs. 30.0%). No severe complications occurred in any experimental animal. Conclusion The ultrasound-guided catheter and its corresponding delivery system exhibite superior ultrasound visibility and operational performance in both in vitro and animal experiments, indicating strong potential for clinical application.

ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component （NUF2） and magnesium homeostasis in ovarian cancer cell apoptosis， as well as the regulatory mechanism of gypenoside L （Gyp-L） on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group， a low-concentration Gyp-L group （50 µmol·L^-1）， a high-concentration Gyp-L group （100 µmol·L^-1）， and a cisplatin （15 µmol·L^-1） group. The migration， proliferation， and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays， clonal experiments， and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus （GEO） database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes （STRING） database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource （TIMER） database， and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis （GEPIA） database. The mRNA expression levels of NUF2， magnesium homeostasis-related indicators， such as magnesium transporter 1 （MAGT1）， non-imprinted in Prader-Willi/Angelman syndrome 1 （NIPA1）， NIPA-like domain containing 1 （NIPAL1）， as well as apoptosis-related indicators B cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） in OVCAR3 cells， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NUF2， MAGT1， NIPA1， NIPAL1， Bcl-2， and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed， and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning， TUNEL staining， Real-time PCR， and ProteinSimple WES. Finally， the Mg²⁺ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis （P<0.05）. Overexpression of NUF2 markedly increased the expression levels of MAGT1， NIPA1， NIPAL1， and Bcl-2， while reducing the expression level of Bax （P<0.05）. It also significantly elevated intracellular Mg²⁺ content and protein synthesis efficiency and simultaneously inhibited apoptosis （P<0.05）. Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2， downregulating the expression levels of NUF2， MAGT1， NIPA1， NIPAL1， and Bcl-2 （P<0.05）， while upregulating the expression level of Bax （P<0.05）. ConclusionGyp-L can inhibit the occurrence of ovarian cancer， and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.

This article presents the first reported successful case of patent ductus arteriosus closure using a fully biodegradable occluder under the sole guidance of transthoracic echocardiography.Compared to traditional methods that require radiation and metal occluders,this technique,which combines echocardiography guidance with biodegradable devices,reduces iatrogenic injury and procedural risks,demonstrating favorable clinical outcomes.

Objective To discusse the application effects of the informatization of the review center and the homogeneity of pharmacists on the rationality of emergency department prescriptions.Methods Based on the system rules of the rational drug use management system and manually set custom rules,the changes in pharmacist's review quality,efficiency homogeneity,and prescription rationality were compared before(February 2023 to July 2023)and after(August 2023 to January 2024)the construction of the review center,according to the informatization and process standardization management.Results After the establishment of the review center,analysis of variance showed that the approval rate of pharmacist's review significantly increased compared to before the establishment of the review center(P＜0.05),while the average time consumption increased significantly(P＜0.01).The average review time,average approval time,and average review return time have been extended from(4.50±0.58),(4.50±0.58),and(4.75±0.96)s to(11.67±1.03),(8.50±0.55)and(13.17±0.98)s,respectively.The trend chi-square test showed that the irrationality rate of emergency department prescriptions decreased monthly from 6.27％in August 2023 to 0.93％in January 2024(P＜0.01).Correlation analysis between the number of intervention system rules since the establishment of the review center and the irrationality rate of emergency department prescriptions revealed a significant correlation(P=0.004 4).Conclusions By utilizing the platform of the review center,establishing dedicated review pharmacists and an information pharmacist team,and implementing informatization and standardized management processes,it can contribute to improving the quality and efficiency of prescription review,increasing the qualification rate of prescriptions,ensuring rational drug use,and enhancing the management level and medical quality of hospitals.

[Purpose]To analyze the trends of brain tumor incidence and age of onset in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The incidence data of brain tumors from 2009 to 2019 were obtained from 16 national cancer registration areas of Jiangsu Province.The crude incidence rate,age-standardized incidence rate by Chinese standard popula-tion(ASIRC),average age of onset,standardized age-specific incidence rate,and annual average percentage change(AAPC)by sexes and regions were calculated.[Results]The incidence rate of brain tumor in Jiangsu Province from 2009 to 2019 showed an increasing trend(AAPC=4.12％,95％CI:3.31％～4.95％),and the increase in female(AAPC=5.79％,95％CI:4.44％～7.15％)was higher than that in male(AAPC=2.31％,95％CI:1.66％～2.97％);and the increase in urban areas(AAPC=4.84％,95％CI:3.52％～6.18％)was higher than that in rural areas(AAPC=3.04％,95％CI:2.12％～3.98％).The ASIRC also showed an increasing trend(AAPC=2.14％,95％CI:1.27％～3.02％).Birth cohort analysis showed that within the same age group,the incidence rate of brain tumors increased with increasing birth years.The average age of onset for crude incidence showed a delaying trend of 0.43 years old per year(t=7.09,P＜0.001);that for ASIRC was 0.20 years old per year(t=3.33,P=0.009).The proportion of patients in the age group of 60 years old and above increased from 35.79％in 2009 to 44.18％in 2019.[Conclusion]The incidence of brain tumor in cancer registration areas of Jiangsu Province showed an increasing trend from 2009 to 2019 with a delaying trend of average age of onset.

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.