The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

Objective Guided by"Medical Record Management Quality Control Indicators(2021 Edition)"(hereafter regarded as Medical Record Quality Indicators),this study aims to evaluate the quality of inpatient hospice medical records at a tertiary hospital in Guangzhou.Methods A total of 1,071 inpatient hospice medical records from the year 2023 in a tertiary gen-eral hospital in Guangzhou were selected for evaluation.The evaluation focused on three aspects:documentation compliance of documentation of critical examinations(including CT/MRI,pathology,and pathogen examinations),the compliance rate of treat-ment behavior records(encompassing antibiotic usage,chemotherapy or radiotherapy or targeted or immunotherapy for malignant tumors,and surgical records),and the incidence of unreasonable duplication within medical record.Results The compliance rate for major examination records ranged from 47.7％to 100.0％,with the lowest compliance rate(47.7％)observed in docu-mentation of pathogen culture analysis.Treatment behavior documentation compliance varied from 49.1％to 100.0％,with the lowest compliance rate of 49.1％observed in the recording of antibiotic usage.Rates of inappropriate duplication ranged from 1.0％to duplication(63.1％),with the highest rate of 63.1％occurring when initial progress notes replicated admission histo-ries without synthesis(63.1％).Conclusion The Medical Record Management Quality Control Indicators serves as an effective tool for evaluating the dimensions of medical record quality and offers a systematic framework for enhancing documentation integri-ty within hospitals.

The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

Objective To explore the diagnostic value of the radiomic model based on panoramic radiographs in differentiating single or multiple root canals in mandibular first premolars.Methods A retrospective analysis was conducted on 68 patients with CBCT and panoramic radiographs from the affiliated Stomatological Hospital of Nanjing Medical University between July 2022 and November 2023.One hundred and thirty one mandibular first premolars(105 single-root and 26 multiple-root canals)were included in this study.Using stratified random sampling,the mandibular first premolars were divided into a training cohort(104 teeth)and a test cohort(27 teeth)at a ratio of 8∶2.CBCT was used to confirm the root canal configuration,and radiomic features were extracted from panoramic radio-graphs.After feature screening,radiomic models were constructed using extratrees,LightGBM,logistic regression(LR),multi-layer perceptron(MLP),random forest,support vector machine(SVM),and XGBoost.The optimal radiomic model was selected based on receiver operating characteristic(ROC)curve,accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and decision curve analysis(DCA).Results A total of 107 radiomicfeatures were extracted from panoramic radiographs.After feature filtering,4 radiomic features were ultimately selected using the Lasso model.The XGBoost model showed higher predictive efficiency and stability,with an AUC of 0.962 in the training cohort and 0.770 in the test cohort.DCA curves also in-dicated that the XGBoost model was optimal.Conclusion The radiomic model based on panoramic radiographs demonstrates good per-formance in differentiating single or multiple root canals in mandibular first premolars.

Objective:To integrate the symptom management experiences of patients with acute decompensated heart failure (ADHF), so as to provide a basis for developing symptom management measures.Methods:Qualitative or mixed studies on the symptom management experience of ADHF patients included from establishment of the database to September 2024, were electronically retrieved in PubMed, CINAHL, Cochrane Library, Web of Science, Embase, EBSCO, China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database and other Chinese and English databases and gray literature databases. The quality of the literature was evaluated using the Critical Appraisal Skills Programme developed by the Center for Evidence-Based Medicine at the University of Oxford. The results were synthesized through the aggregative integration method.Results:A total of 14 papers were included. Thirty-four findings were distilled into eight categories and three integrative findings, namely, the multiple challenges posed by symptoms (complex and multiple symptomatic somatic experiences, symptom-induced mood changes, and reduced family and social engagement), the unmet needs of patients (insufficient healthcare resources, insufficient supply of discharge services provided by healthcare organizations, and lack of knowledge), and the co-existence of positive and negative coping styles (negative coping styles in symptomatic distress, positive debugging and diversified coping in symptomatic distress) .Conclusions:ADHF symptoms severely affect patients' physical, psychological, and social function. Healthcare professionals should focus on the unmet needs of patients with ADHF and explore patient-engaged models of active symptom management.

Objective Guided by"Medical Record Management Quality Control Indicators(2021 Edition)"(hereafter regarded as Medical Record Quality Indicators),this study aims to evaluate the quality of inpatient hospice medical records at a tertiary hospital in Guangzhou.Methods A total of 1,071 inpatient hospice medical records from the year 2023 in a tertiary gen-eral hospital in Guangzhou were selected for evaluation.The evaluation focused on three aspects:documentation compliance of documentation of critical examinations(including CT/MRI,pathology,and pathogen examinations),the compliance rate of treat-ment behavior records(encompassing antibiotic usage,chemotherapy or radiotherapy or targeted or immunotherapy for malignant tumors,and surgical records),and the incidence of unreasonable duplication within medical record.Results The compliance rate for major examination records ranged from 47.7％to 100.0％,with the lowest compliance rate(47.7％)observed in docu-mentation of pathogen culture analysis.Treatment behavior documentation compliance varied from 49.1％to 100.0％,with the lowest compliance rate of 49.1％observed in the recording of antibiotic usage.Rates of inappropriate duplication ranged from 1.0％to duplication(63.1％),with the highest rate of 63.1％occurring when initial progress notes replicated admission histo-ries without synthesis(63.1％).Conclusion The Medical Record Management Quality Control Indicators serves as an effective tool for evaluating the dimensions of medical record quality and offers a systematic framework for enhancing documentation integri-ty within hospitals.

Objective To explore the diagnostic value of the radiomic model based on panoramic radiographs in differentiating single or multiple root canals in mandibular first premolars.Methods A retrospective analysis was conducted on 68 patients with CBCT and panoramic radiographs from the affiliated Stomatological Hospital of Nanjing Medical University between July 2022 and November 2023.One hundred and thirty one mandibular first premolars(105 single-root and 26 multiple-root canals)were included in this study.Using stratified random sampling,the mandibular first premolars were divided into a training cohort(104 teeth)and a test cohort(27 teeth)at a ratio of 8∶2.CBCT was used to confirm the root canal configuration,and radiomic features were extracted from panoramic radio-graphs.After feature screening,radiomic models were constructed using extratrees,LightGBM,logistic regression(LR),multi-layer perceptron(MLP),random forest,support vector machine(SVM),and XGBoost.The optimal radiomic model was selected based on receiver operating characteristic(ROC)curve,accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and decision curve analysis(DCA).Results A total of 107 radiomicfeatures were extracted from panoramic radiographs.After feature filtering,4 radiomic features were ultimately selected using the Lasso model.The XGBoost model showed higher predictive efficiency and stability,with an AUC of 0.962 in the training cohort and 0.770 in the test cohort.DCA curves also in-dicated that the XGBoost model was optimal.Conclusion The radiomic model based on panoramic radiographs demonstrates good per-formance in differentiating single or multiple root canals in mandibular first premolars.

Objective:To integrate the symptom management experiences of patients with acute decompensated heart failure (ADHF), so as to provide a basis for developing symptom management measures.Methods:Qualitative or mixed studies on the symptom management experience of ADHF patients included from establishment of the database to September 2024, were electronically retrieved in PubMed, CINAHL, Cochrane Library, Web of Science, Embase, EBSCO, China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database and other Chinese and English databases and gray literature databases. The quality of the literature was evaluated using the Critical Appraisal Skills Programme developed by the Center for Evidence-Based Medicine at the University of Oxford. The results were synthesized through the aggregative integration method.Results:A total of 14 papers were included. Thirty-four findings were distilled into eight categories and three integrative findings, namely, the multiple challenges posed by symptoms (complex and multiple symptomatic somatic experiences, symptom-induced mood changes, and reduced family and social engagement), the unmet needs of patients (insufficient healthcare resources, insufficient supply of discharge services provided by healthcare organizations, and lack of knowledge), and the co-existence of positive and negative coping styles (negative coping styles in symptomatic distress, positive debugging and diversified coping in symptomatic distress) .Conclusions:ADHF symptoms severely affect patients' physical, psychological, and social function. Healthcare professionals should focus on the unmet needs of patients with ADHF and explore patient-engaged models of active symptom management.