Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

The organization of the brain follows a topological hierarchy that changes dynamically during development. However, it remains unknown whether and how cognitive training administered over multiple years during development can modify this hierarchical topology. By measuring the brain and behavior of school children who had carried out abacus-based mental calculation (AMC) training for five years (starting from 7 years to 12 years old) in pre-training and post-training, we revealed the reshaping effect of long-term AMC intervention during development on the brain hierarchical topology. We observed the development-induced emergence of the default network, AMC training-promoted shifting, and regional changes in cortical gradients. Moreover, the training-induced gradient changes were located in visual and somatomotor areas in association with the visuospatial/motor-imagery strategy. We found that gradient-based features can predict the math ability within groups. Our findings provide novel insights into the dynamic nature of network recruitment impacted by long-term cognitive training during development.
Child ; Humans ; Cognitive Training ; Magnetic Resonance Imaging ; Brain ; Brain Mapping ; Motor Cortex

Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals.Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations:Minhang District of Shanghai,Haimen City of Jiangsu Province,Yuhuan City of Zhejiang Province,and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019.The subjects were subjected to physical examination as well as thyroid hormone levels;and the Pubertal Developmental Events Self-Assessment Scale(PDS)was used to evaluate the staging of pubertal development.Follow-ups were conducted after 2 years,with the same survey content.Thyroid function levels were assessed in 5 age groups between 11 to 15 years old,95%CI were calculated,and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels.Results The reference intervals for thyroid stimulating hormone(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)in adolescent females differed significantly from those of adults,with misclassification rates ranging from 2.98%to 5.17%.Statistically significant differences were found for age,pubertal development staging,and the interaction of age and pubertal staging after correcting for BMI,waist circumference(all P<0.05).TSH levels were more affected by age before the completion of pubertal development,the level of the 12-year-old group was higher than that of the 11-year-old group(P=0.001 2)and the 13-year-old group(P<0.000 1);FT3 levels showed greater variability with age during late pubertal stage,with levels significantly higher at 13 years of age than at 11 and 12 years of age(P<0.0001),and gradually decreasing after 13 years of age(P<0.000 1).In contrast,FT4 levels were generally less affected by age between 11 and 15 years of age,with levels slightly higher at 13-15 years of age than at 11-12 years of age(P<0.000 1).Conclusion The levels of TSH,FT3,and FT4,as indicators of thyroid function in adolescent females,differ significantly from those of adults,and are differently affected by age and the stages of pubertal development;further refinement of the reference intervals for age-and pubertal-development-specific thyroid indicators is necessary.

Objective To construct trajectory models of care-seeking patterns for type 2 diabetes mellitus(T2DM)patients,analyze the influencing factors of different trajectories,and explore the fasting blood glucose control levels of T2DM patients with different trajectories.Methods A retrospective cohort study was carried out on 18088 T2DM patients who had health records and been involved in the diabetic management in Community Health Service Center of Minhang District,Shanghai from 2006 to 2009.Starting from Jan 1,2010,participants were followed up until Dec 31,2019,with complete follow-up information.Group-based trajectory modelling(GBTM)was employed to identify and construct the fluctuation trajectory of fasting blood glucose in the patients.Bayesian information criterion(BIC),average posterior probability(AvePP)and other evaluation indicators were used to select the optimum subgroup number model.Then the differences in demographic characteristics,health status,family history,fasting blood glucose,BMI,etc were compared among different categories.Multinational logistic regression model was constructed to explore the influencing factors of different fluctuation trajectories.Cox regression analysis was used to examine the relationship between the long-term trajectories of care-seeking patterns and fasting blood glucose control level.Results Using GBTM analysis,we constructed the optimal Model 4 to categorize 18088 T2DM patients with community health records into five distinct trajectory subgroups:continuous non-attendance group(22.29%),low-level increasing group(15.09%),high-level slowly decreasing group(14.18%),high-level rapidly decreasing group(14.90%),and continuous regular attendance group(33.54%).With the continuous regular attendance group serving as the reference,gender,age,place of residence,baseline comorbidity of hypertension,baseline fasting plasma glucose level,and BMI were found to influence the community attendance trajectories of T2DM patients(P<0.05).After adjusting for confounding factors,Cox regression analysis revealed that compared to the continuous non-attendance group,the low-level increasing group,high-level slowly decreasing group,and continuous regular attendance group had better glycemic control,with HRs of 0.37(95%CI:0.34-0.39),0.72(95%CI:0.67-0.78),and 0.78(95%CI:0.73-0.84),respectively.The glycemic control level in the high-level rapidly decreasing group was comparable,with an HR of 1.06(95%CI:0.99-1.12).Conclusion Based on the optimal model,the community medical treatment trajectories of T2DM patients showed different dynamic characteristics.Factors such as gender,residence,hypertension,and weight loss may influence these varying trajectories.Regular community visits and follow-up may help control blood glucose levels.

OBJECTIVE To develop an artificial intelligence-based intelligent auxiliary diagnosis and treatment system for Xin'an medicine to address the challenges of integrating ancient Xin'an medical case records into modern clinical applications.METHODS The project involved structuring and standardizing case records from ancient texts of Xin'an medicine to build a compre-hensive Xin'an medicine database.Advanced techniques,such as data annotation,entity relationship extraction,and data mining,were applied to create a Xin'an medicine knowledge base.Furthermore,a knowledge graph of Xin'an medicine was constructed using techniques for knowledge acquisition,integration,storage,and graph-based question-answering,improving the efficiency of knowl-edge organization and retrieval.The LangChain framework was utilized to connect the Xin'an medicine knowledge base to a large lan-guage model,enabling a model-driven local knowledge base question-answering system.RESULTS The study successfully estab-lished a systematic and standardized knowledge base for Xin'an medical case records.The application of knowledge graph technology provided a clear visualization of Xin'an medicine's knowledge structure,and the development of an intelligent question-answering module significantly improved the efficiency of knowledge management and retrieval.The local knowledge base question-answering sys-tem,powered by a large language model and based on Xin'an medicine's theoretical and practical expertise,delivered accurate diag-nostic and treatment support,promoting the heritage and innovation of Xin'an medicine.CONCLUSION This research validates the feasibility of modernizing traditional medical texts and provides an innovative approach to knowledge development and clinical applica-tion in Chinese medicine.The findings have significant academic value and promising clinical implications.

Objective To explore the effects of cognitive behavioral therapy based on 5G internet of things(IOT)on rehabilitation and kinesiophobia in elderly patients after percutaneous coronary intervention(PCI)for coronary artery disease.Methods Sixty elderly postoperative PCI patients with coronary artery disease admitted from June to December 2023 were selected as study subjects and randomly divided into the control group and the 5G group,with 30 cases in each group.The control groupreceived conventional nursing intervention,while the 5G group receivedcognitive behavioral therapy based on 5G IOT in addition to traditional nursing.Left ventricular ejection fraction(LVEF),6-minute walking distance(6MWD),the Tampa Scale for kinesiophobia Heart(TSK-SV Heart)scores,the Seattle Angina Questionnaire(SAQ)scores,and rehabilitation compliance were compared between the two groups.Results 12 weeks afterintervention,LVEF and 6MWD in the 5G groupwere significantly improved as compared with those in the control group(P＜0.05).The TSK-SV Heart scores in the 5G group werelower than those in the control group(P＜0.05),but the SAQ scores were higher(P＜0.05).And the rate of better rehabilitation compliance in the 5G group was significantly higher than thatin the control group(P＜0.05).Conclusions Cognitive behavioral therapy based on 5G IOT helps to improve the rehabilitation effect in elderly patients with coronary artery disease after PCI,reduce kinesiophobia,improve quality of life,and enhance reha-bilitationcompliance,thus promoting the rehabilitation process of the patients.

OBJECTIVE To develop an artificial intelligence-based intelligent auxiliary diagnosis and treatment system for Xin'an medicine to address the challenges of integrating ancient Xin'an medical case records into modern clinical applications.METHODS The project involved structuring and standardizing case records from ancient texts of Xin'an medicine to build a compre-hensive Xin'an medicine database.Advanced techniques,such as data annotation,entity relationship extraction,and data mining,were applied to create a Xin'an medicine knowledge base.Furthermore,a knowledge graph of Xin'an medicine was constructed using techniques for knowledge acquisition,integration,storage,and graph-based question-answering,improving the efficiency of knowl-edge organization and retrieval.The LangChain framework was utilized to connect the Xin'an medicine knowledge base to a large lan-guage model,enabling a model-driven local knowledge base question-answering system.RESULTS The study successfully estab-lished a systematic and standardized knowledge base for Xin'an medical case records.The application of knowledge graph technology provided a clear visualization of Xin'an medicine's knowledge structure,and the development of an intelligent question-answering module significantly improved the efficiency of knowledge management and retrieval.The local knowledge base question-answering sys-tem,powered by a large language model and based on Xin'an medicine's theoretical and practical expertise,delivered accurate diag-nostic and treatment support,promoting the heritage and innovation of Xin'an medicine.CONCLUSION This research validates the feasibility of modernizing traditional medical texts and provides an innovative approach to knowledge development and clinical applica-tion in Chinese medicine.The findings have significant academic value and promising clinical implications.

Objective To explore the effects of cognitive behavioral therapy based on 5G internet of things(IOT)on rehabilitation and kinesiophobia in elderly patients after percutaneous coronary intervention(PCI)for coronary artery disease.Methods Sixty elderly postoperative PCI patients with coronary artery disease admitted from June to December 2023 were selected as study subjects and randomly divided into the control group and the 5G group,with 30 cases in each group.The control groupreceived conventional nursing intervention,while the 5G group receivedcognitive behavioral therapy based on 5G IOT in addition to traditional nursing.Left ventricular ejection fraction(LVEF),6-minute walking distance(6MWD),the Tampa Scale for kinesiophobia Heart(TSK-SV Heart)scores,the Seattle Angina Questionnaire(SAQ)scores,and rehabilitation compliance were compared between the two groups.Results 12 weeks afterintervention,LVEF and 6MWD in the 5G groupwere significantly improved as compared with those in the control group(P＜0.05).The TSK-SV Heart scores in the 5G group werelower than those in the control group(P＜0.05),but the SAQ scores were higher(P＜0.05).And the rate of better rehabilitation compliance in the 5G group was significantly higher than thatin the control group(P＜0.05).Conclusions Cognitive behavioral therapy based on 5G IOT helps to improve the rehabilitation effect in elderly patients with coronary artery disease after PCI,reduce kinesiophobia,improve quality of life,and enhance reha-bilitationcompliance,thus promoting the rehabilitation process of the patients.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.