1.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
2.A Rubric System for Evaluating the TCA-based Ideological and Political Teaching Model:Its Construction and Application
Ying WANG ; Ling-Hui LV ; Ren-Ji WEI ; Xiang ZHANG ; Yi RU ; Bo YAN ; Lan SHEN ; Mao SUN ; Liang LIANG ; Jing ZHAO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(1):53-67
The success of"New Medical Sciences"in higher education requires effective tools in evalua-ting students'performance in courses.Previously,we reported a teamwork(T),critique(C)and ap-preciation(A)(TCA)ideological and political model,a teaching model widely applied in Basic Medical courses.TCA is an abbreviation derived from Tricarboxylic Acid Cycle in Biochemistry as an analogy for nurturing the abilities of thinking and teamwork(T),critique(C)and appreciation(A),which hope-fully could provide students with moral norms for cognition,science and life.This paper further explores the tools to assess the educational outcomes of the TCA model,by which teachers can collect feedback and reflect on teaching quality and effectiveness.Addressing the challenges of individual differences in large classes,fragmented learning feedback,and the difficulty of measuring meta-cognition in educational evaluation,this study employs strategies of value-added assessment,matrix assessment and norm-transfer-able assessment to evaluate the TCA abilities from the aspects of thinking quality,thinking creativity,co-operation ability,iterative thinking,dialectical thinking and job responsibility.By modifying/using 18 e-valuation tools in Education and Psychology,we have established a rubric system composed of 30 primary indicators(with 11 newly designed,10 partly modified and 9 directly adopted),along with 49 secondary indicators and 98 tertiary indicators to enhance the feasibility of the evaluation process.This rubric sys-tem was applied to Biochemistry teaching among the five-year-program undergraduates at Air Force Medi-cal University.Specifically,thinking and teamwork are evaluated by creative works from"the magic bio-chemical-circle",while critiques are assessed in large classes under the guidance of basic and clinical teachers,coupled with appreciation measured by job responsibility in a task-driven virtual reality(VR)project.The results indicate that Biochemistry teaching not only accumulates knowledge in students,but also achieves the goals in nurturing values and cognition.The inclusion of creative performance evalua-tion,cooperative learning and clinical case studies,can enhance students'interpersonal skills,coopera-tion,quality of thinking,creative thinking,iterative thinking and dialectical thinking to varying degrees.TCA-based Biochemistry teaching has a long-lasting impact on character education,and is capable of in-ducing positive long-term changes in students'cognition and lifestyle.Taken together,with the help of this rubric system,teachers can promptly acknowledge the effectiveness of their teaching,thereby facilita-ting their teaching strategies.
3.Effect of comprehensive management intervention based on WeChat multimedia classroom on cardiac function rehabilitation and prognosis in elderly patients with acute myocardial infarction
Ge WANG ; Ning YANG ; Min YANG ; Hua BAO ; Nan LIU ; Gai-ling QIANG ; Hai-yan ZHAO
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(1):51-56
Objective:To investigate effect of comprehensive management intervention based on WeChat multimedia classroom on cardiac function and prognosis in elderly patients with acute myocardial infarction(AMI).Methods:Clinical data of 118 elderly patients diagnosed with AMI in the Second Affiliated Hospital of Chinese PLA Air Force Military Medical University between August 2021 and December 2022 were retrospectively collected.According to nursing way after operation,they were divided into control group(n=60,comprehensive management interven-tion)and intervention group(n=58,comprehensive management intervention based on WeChat multimedia class-room),both groups were intervened for 5 months.Cardiac function,exercise tolerance,compliance to rehabilita-tion management,self-efficacy and healthy behavior were compared between two groups.Kaplan-Meier survival curve was employed to compare incidence of adverse cardiovascular events during follow-up between two groups.Results:After 5-month intervention,compared with patients in control group,those in intervention group had sig-nificant higher left ventricular ejection fraction(LVEF)[(58.14±1.88)%vs.(54.48±1.34)%],6min walking distance(6MWD)[(490.41±59.59)m vs.(394.97±28.20)m],scores of compliance to rehabilitation manage-ment[(6.97±2.03)points vs.(5.03±1.40)points],General Self-Efficacy Scale(GSES)[(30.34±4.67)points vs.(23.55±4.86)points]and Health Promoting Lifestyle Profile-Ⅱ[(137.62±30.17)points vs.(115.95±22.66)points],and significant lower left ventricular end-diastolic volume(LVEDV)[(117.90±4.22)ml vs.(131.28±3.61)ml],left ventriadar end-systolic volume(LVESV)[(54.46±2.10)ml vs.(63.15±2.06)ml],serum brain natriuretic peptide(BNP)[(362.32±25.36)pg/ml vs.(567.58±21.90)pg/ml]and incidence of ad-verse cardiovascular events(6.90%vs.21.67%)(P<0.05 or<0.01).Conclusion:Comprehensive management intervention based on the WeChat multimedia classroom could significantly improve cardiac function,exercise toler-ance,compliance to rehabilitation,self-efficacy and healthy behavior,and reduce incidence of adverse cardiovas-cular events after operation in elderly AMI patients.
4.Predictive value of ox-LDL combined with ECG ischaemia grading for MACE after PCI in STEMI pa-tients
Ya-zhao SUN ; Gang LI ; Shu-yan ZHANG ; Pei SUN ; Hai-lin LI ; Ling-xiao ZHANG ; Bin LIU ; Dong-sheng LIU
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(2):199-204
Objective:The predictive value of oxidized low density lipoprotein(ox-LDL)and electrocardiogram(ECG)ischaemia grade for major adverse cardiovascular events(MACE)in patients with ST elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI)was assessed by a retrospective cohort study de-sign.Methods:A total of 336 STEMI patients admitted to Cangzhou People's Hospital between October 2019 and May 2022 were selected,and the medical record information was obtained through the hospital medical record sys-tem,and all patients received PCI and physician-recommended basic treatment.With occurrence of MACE with in 12-month follow-up as the evaluation index,they were divided into MACE group(n=65)and no MACE group(n=271).Multifactorial Logistic regression model was used to study the influencing factors of MACE after PCI in STEMI patients,and Spearman test for association of ox-LDL level,ECG ischaemia grade with MACE after PCI.ROC curve was used to evaluate the predictive efficacy of ox-LDL,ECG ischaemia grade and their combination for MACE after PCI.Results:The overall MACE incidence was 19.35%.Compared with patients in no MACE group,those in MACE group had significant higher ox-LDL level[46.34(29.46,66.29)U/L vs.33.00(23.02,50.03)U/L]and proportion of ECG grade Ⅲ ischaemia(64.62%vs.42.80%)(P<0.01 all).Multifactorial Logistic re-gression analysis showed that ox-LDL(OR=1.022,95%CI 1.011~1.033,P=0.001)and ECG grade Ⅲ ischae-mia(OR=1.878,95%CI 1.007~3.504,P=0.048)were the independent risk factors of post-PCI MACE in STEMI patients.Spearman test showed that ox-LDL and ECG grade Ⅲ ischaemia were positively correlated with post-PCI MACE(r=0.209,0.173,P<0.001 all).ROC curve analysis showed that the AUCs of ox-LDL,ECG grade Ⅲ ischaemia and their combination in predicting post-PCI MACE were respectively 0.653(95%CI 0.599~0.704),0.609(95%CI 0.555~0.662)and 0.758(95%CI 0.709~0.803),in which the predictive value of the combination of the two was significantly higher than any single detection(Z=2.030,3.097,P=0.042,0.002).Conclusion:ox-LDL combined with ECG ischaemia grading has a high predictive value for the occurrence of MACE with in 12 months after PCI in STEMI patients.
5.Trajectory of changes in electronic health literacy and its relationship with unplanned readmission in young and middle-aged patients with coronary heart disease and diabetes mellitus after PCI
Yan ZHAO ; Xiaoxia FANG ; Ling MA ; Mingming QIAO ; Ke XU
Chinese Journal of Modern Nursing 2025;31(30):4158-4163
Objective:To explore the trajectory of changes in electronic health literacy in young and middle-aged patients with coronary heart disease (CHD) combined with diabetes mellitus (DM) after percutaneous coronary intervention (PCI), and to analyze its relationship with unplanned readmission within 30 days.Methods:A convenience sample of 210 young and middle-aged CHD patients with DM who underwent PCI in the Department of Cardiology, Xinxiang Central Hospital, from February 2023 to June 2024 was selected. The e-Health Literacy Scale (eHEALS) was used to assess electronic health literacy at the 3rd day (T 1), 15th day (T 2), and 30th day (T 3) after PCI. Unplanned readmission within 30 days after discharge was recorded. Latent class growth model (LCGM) was used to identify categories and characteristics of electronic health literacy trajectories. Kaplan-Meier method was applied to plot the cumulative incidence of 30-day unplanned readmission, and the Log-Rank test was used to compare differences among different trajectory types. Results:A total of 207 patients completed the entire survey and follow-up, with a valid response rate of 98.57% (207/210). eHEALS scores gradually increased after PCI, with scores of (6.75±1.31), (11.55±3.31), and (15.56±5.75) at T 1, T 2, and T 3, respectively. Two potential categories were identified: persistent low-level type (85 cases, 41.06%) and gradually improving type (122 cases, 58.94%). Twenty-six patients experienced unplanned readmission within 30 days, with an incidence of 12.56%. The proportions of unplanned readmission within 30 days were 20.00% (17/85) in the persistent low-level group and 7.38% (9/122) in the gradually improving group, with a statistically significant difference (χ 2=7.268, P=0.007). Kaplan-Meier cumulative risk function analysis showed that the cumulative incidence of 30-day unplanned readmission in the gradually improving group was lower than that in the persistent low-level group, with a statistically significant difference (Log-Rank=7.683, P=0.006) . Conclusions:Young and middle-aged CHD patients with DM after PCI show trajectory characteristics in electronic health literacy. Although the electronic health literacy of some patients gradually improved after PCI, persistent low-level literacy was still common, and patients in the persistent low-level group had a higher risk of 30-day unplanned readmission, which deserves clinical attention.
6.Review of application scope of mobile medical devices combined with EMA method for lung cancer patient caring
Zi-dan WANG ; Hong-yue WU ; Bing LI ; Xin-tong ZHENG ; Jun-ling LIU ; Ying-nan ZHAO ; Yan LI
Chinese Medical Equipment Journal 2025;46(10):71-77
Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]
7.The synergistic effect and mechanism verification of effective components of Biejia-Ezhu against triple-negative breast cancer based on network pharmacology and component compatibility theory
Dou-dou FENG ; Xiao-shan LUO ; Yan-yun MENG ; Jing-zhe ZHAO ; Jiu-long ZHU ; Ya-zhen HUANG ; Qing XIE ; Xiang-Li LING ; Su XIE
Chinese Pharmacological Bulletin 2025;41(5):950-959
Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P<0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P<0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.
8.Analysis of influencing factors of major adverse cardio-cerebrovascular events after drug-eluting stenting in patients with coronary artery disease
Zhao-yun MENG ; Yan-qun ZHANG ; Xiu-ling WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(2):135-139
Objective:To explore the influencing factors of major adverse cardio-cerebrovascular events(MACCE)after drug-eluting stenting in patients with coronary artery disease(CAD).Methods:Retrospective study data from First Affiliated Hospital of Zhengzhou University were extracted from the Dryad database.Patients were di-vided into MACCE group(n=160)and control group(n=880)according to whether MACCE occurred during fol-low-up.Clinical data including age,gender,fibrinogen(Fg)level etc.were compared between two groups,and the variables with significant differences between two groups were substituted into Logistic regression model to screen the influencing factors of MACCE after drug eluting stenting in CAD patients.Results:Compared with pa-tients in control group,those in MACCE group had significant higher Fg level[(3.6±1.1)g/L vs.(3.4±1.0)g/L],proportions of triple-vessel coronary disease(25.6% vs.18.3%)and right coronary artery lesion(53.1% vs.41.7%)(P<0.05 or<0.01).Multivariate Logistic regression analysis indicated that Fg level(OR=1.18,95%CI 1.01~1.37,P=0.039)was the independent risk factor of MACCE after drug eluting stenting in CAD patients.The risk of MACCE after drug eluting stenting in CAD patients significantly increased when the Fg level was>3.27 g/L.Conclusion:High Fg level is the independent risk factor of MACCE after drug eluting stenting in CAD patients.
9.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
10.Multicenter survey on the co-occurrence patterns of psychosocial and behavioral problems in children
Minjun LI ; Feiyong JIA ; Yunjing ZHAO ; Xiaoyan KE ; Wenli WANG ; Li CHEN ; Yan HAO ; Ling LI ; Yu LING ; Jie ZHANG ; Lin WANG ; Tingyu LI
Chinese Journal of Pediatrics 2025;63(9):985-991
Objective:To investigate the co-occurrence patterns of psychosocial and behavioral problems among children and to identify associated influencing factors.Methods:A multicenter cross-sectional survey was conducted in 2023. A cluster random sample of 19 176 children aged 6-16 years was recruited from middle-income areas across 10 provincial capitals and municipalities in China. Psychological and behavioral problems, including anxiety, compulsive behavior, social withdrawal, depression, somatic complaints, social problems, schizoid, delinquent behaviors, hyperactivity, sexual issues, and aggression, were assessed using the Achenbach Child Behavior Checklist parent version. Co-occurrence was defined as ≥2 concurrent problems. Children were divided into 4 groups by gender and age: boys aged 6-11 years, girls aged 6-11 years, boys aged 12-16 years, and girls aged 12-16 years. Those children who had psychosocial and behavioral problems were further categorized into the single-problem group, and the co-occurrence group based on assessment results. High-frequency co-occurrence phenotypes of children′s psychosocial and behavioral problems were identified. Demographic factors, such as parental employment, education, as well as psychosocial factors like parent-child relationship, screen time and outdoor activity, were investigated. χ 2 test was used to analyze differences between groups. Multivariate Logistic regression modeling was conducted to identify potential factors. Results:Among 14 711 children (7 501 boys, 7 210 girls) who provided effective questionnaires, the detection rates of single problem in the boys aged 6-11 years, girls aged 6-11 years, boys aged 12-16 years, and girls aged 12-16 years groups were 4.9% (171/3 461), 6.2% (193/3 120), 3.9% (158/4 040), and 5.1% (208/4 090), respectively; the detection rates of co-occurrence were 7.6% (262/3 461), 7.7% (241/3 120), 4.9% (199/4 040), and 5.7% (234/4 090), respectively. The overall detection rates of co-occurrence was higher than that of single problem ( χ2=25.47, P<0.001). Among children with co-occurrence, there were varied manifestations: in the boys aged 6-11 years group, the detection rates of social withdrawal (69.8% (183/262)), schizoid-like behavior (68.3% (179/262)), and compulsive behavior (67.6% (177/262)) were relatively high; in the girls aged 6-11 years group, the detection rates of schizoid-compulsive behavior (69.3% (167/241)), delinquent behavior (65.6% (158/241)), and hyperactivity (58.9% (142/241)) were relatively high; in the boys aged 12-16 years group, the detection rates of hyperactivity (78.9% (157/199)), compulsive behavior (67.3% (134/199)), and immature behavior (57.3% (114/199)) were relatively high; in the girls aged 12-16 years group, the detection rates of schizoid-like behavior (89.7% (210/234)), immature behavior (59.0% (138/234)), and cruelty (57.7% (135/234)) were relatively high. Maternal bachelor′s degree or higher ( OR=0.78, 95% CI 0.61-0.99, P=0.038) served as co-occurrence protective factors, whereas having 1 or more siblings, increased parent-child conflict and decreased parent-child interaction time ( OR=1.24, 1.41, 1.36; 95% CI 1.02-1.52, 1.15-1.73, 1.02-1.82, all P<0.05) were co-occurrence risk factors. Conclusions:Children exhibit strong co-occurrence tendencies in psychosocial and behavioral problems. Compulsive and schizoid traits are the predominant co-occurring phenotypes for childhood and girls respectively. ?Familial environment plays a critical role, necessitating ?multidimensional clinical assessments and ?family-centered interventions.

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