The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

ObjectiveTo construct a stable monoclonal human embryonic kidney 293 （HEK293） cell line expressing recombinant human coagulation factor Ⅶ （rhFⅦ） and evaluate the expression level and procoagulant bioactivity of rhFⅦ. MethodsThe plasmid pCDNA3.1-EGFP-FⅦ was transfected into HEK293 cells to verify the effectiveness of the transfection system. The plasmid pCDNA3.1-FⅦ was transfected into HEK293 cells， and monoclonal stable transfected cell lines were selected using geneticin （G418）. The transcription of the FⅦ gene was identified by reverse transcription polymerase chain reaction （RT-PCR）. The expression level of rhFⅦ in the supernatant of the monoclonal stable transfected cell line was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. The concentration of rhFⅦ was determined by enzyme-linked immunosorbent assay （ELISA）， and the procoagulant activity of rhFⅦ was measured by human coagulation factor Ⅶ potency assay. ResultsHEK293 cells transfected with pcDNA3.1-EGFP-FⅦ showed green fluorescence， indicating that rhFⅦ was successfully expressed in the supernatant of HEK293 cells after transient transfection with pcDNA3.1-FⅦ. The monoclonal stable transfected cell line was obtained by G418 screening. RT-PCR identified that the FⅦ gene was integrated into the genome of the monoclonal stable transfected cell line. The cell viability was good as detected by Cell Counting Kit-8， and a single band of rhFⅦ was obtained by purification of the cell supernatant. The highest rhFⅦ expression was （1.27±0.09） mg/L， and the highest procoagulant activity was （380.29±13.80）%. ConclusionThe monoclonal HEK293 cell lines which can express rhFⅦ protein efficiently and stably with excellent procoagulant bioactivity is successfully screened.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Objective:To develop an electronic information platform-based assessment tool for entrustable professional activities (EPAs) of master of nursing specialist (MNS) students.Methods:The study used the content analysis method to construct the draft of the assessment tool, which was finalized using the expert meeting method. An electronic information platform was developed based on the assessment tool. The functions of the platform was optimized using the focus group interview method.Results:Based on previous research on the EPA framework for MNS students, an EPA assessment tool was developed, including an assessment form and an assessment protocol. The assessment form consisted of three parts: description of the EPAs, supervision level, and narrative feedback. The assessment protocol covered the assessment objects, assessment initiation strategy, assessment implementation-entrustment decision making, assessment cycle, and quality control. The electronic information platform includes both web-based and mobile app interfaces, with user roles for clinical instructors, graduate students, and project administrators, and with functions such as assessment application, assessment initiation, historical assessment review, and assessment information management.Conclusions:The study developed an EPA assessment tool for MNS students. The tool relies on the convenience and efficiency of the electronic information platform, facilitates clinical instructors in observing the comprehensive performance of MNS students in multiple competencies, and promotes postgraduate students' professional development. Future research will further explore the effectiveness of this tool in assessing clinical practice competencies of MNS students, with the aim of advancing the practice of EPAs in nursing masters' education.

Objective:To analyze by bioinformatics the association between the expression of membrane-associated tyrosine/threonine protein kinase 1(PKMYT1)in glioma with its prognostic value,biological function,drug sensitivity,gene mutation,and immune infiltration.Methods:The differential expression of PKMYT1 was analyzed based on the Chinese Glioma Genome Atlas database(CGGA)and the Cancer Genome Atlas database(TCGA).Pathways likely to be enriched for PKMYT1 were predicted by gene ontology analysis(GO)and gene set enrichment analysis(GSEA).PKMYT1 was subjected to Pearson correlation and gene set variation analysis(GSVA)with cell cycle-related genes and gene sets.The survival prognosis,gene mutation,drug sensitivity and immune infiltration were further analyzed for PKMYT1 high and low expression groups of glioma patients.Results:PKMYT1 was significantly highly expressed in WHO high-grade glioma(P<0.000 1),IDH wild-type glioma(P<0.05),and glioblastoma(P<0.000 1).Overall survival(OS)of patients in the PKMYT1 low expression group was significantly higher than that of the high expression group(P<0.05).Cox regression analysis showed that PKMYT1 expression level was an independent prognostic factor for OS(P<0.05).GO and GSEA analyses showed that the gene sets co-expressed with PKMYT1 were mainly enriched in signaling pathways such as cell cycle,DNA replication and DNA damage repair.Pearson correlation and GSVA analyses showed that the expression of PKMYT1 was significantly and positively correlated with the cell cycle-related genes,gene sets and cell cycle checkpoint genes(P<0.01).Drug sensitivity analysis revealed that patients in the PKMYT1 high expression group had high sensitivity osimertinib,dabrafenib,carmustine and cediranib(P<0.05).Mutation analysis revealed that the IDH1 gene had a higher mutation frequency in the PKMYT1 low expression group.The results of immune infiltration analysis showed that PKMYT1 expression was significantly positively correlated with glioma stroma score(r=0.13,P<0.001),immune score(r=0.11,P<0.01)and ESTIMATE score(r=0.13,P<0.001);and was significantly positively correlated with immune cell infiltration level of regulatory T(Treg)cells and M2-type macrophages(P<0.05).Conclusion:Patients with high PKMYT1 expression have a poorer prognosis,and the mechanism may be related to tumor immune infiltration and cell cycle regulation.PKMYT1 is expected to be a potential target for the diagnosis and treatment of glioma.

Objective:To analyze and compare the reporting data of adverse events following immunization (AEFI) of influenza vaccines in Fujian Province from 2019 to 2023.Methods:Using the National Immunization Program Information Management System, the AEFI reports and vaccination data of influenza vaccines in Fujian Province from 2019 to 2023 were collected, and the reporting rates and clinical characteristics of AEFI of 6 types of influenza vaccines were compared. The 6 types of vaccines in the analysis were as follows: trivalent inactivated influenza vaccines (IIV3) for 6-35 months old people, IIV3 for ≥3 years old people, trivalent live attenuated nasal spray vaccine (LAIV3) for 3-17 years old people, quadrivalent inactivated influenza vaccines (IIV4) for 6-35 months old people, IIV4 for ≥6 months old people, and IIV4 for ≥3 years old people.Results:From 2019 to 2023, a total of 87 687.21 million doses of influenza vaccine were vaccinated in Fujian Province, and 510 cases of AEFI were reported, with a reporting rates of 5.82 per 100 000 doses. Among the 510 cases, 443 (86.86%) were general reactions, 56 (10.98%) were abnormal reactions, 1 (0.20%) was psychogenic reactions, and 10 (1.96%) were coincidence. There were no reports of vaccination accidents and vaccine quality accidents. The reporting rates of AEFI were relatively higher in 2019 and 2020 (18.38 and 18.00 per 100 000 doses, respectively), and lower in 2021, 2022 and 2023 (8.91, 10.68 and 2.30 per 100 000 doses, respectively); the differences were statistically significant (all P<0.05). The differences of reporting rates of AEFI between IIV3 for 6-35 months old people and IIV4 for 6-35 months old people, the injectable vaccines and nasal spray vaccines were not statistically significant. However, the reporting rates of overall AEFI, general reactions and abnormal reactions of IIV3 for ≥3 years old people were all higher than those of IIV4 for ≥3 years old people (7.77 per 100 000 doses vs. 3.88 per 100 000 doses, 6.18 per 100 000 doses vs. 3.59 per 100 000 doses, 1.41 per 100 000 doses vs. 0.19 per 100 000 doses). The reporting rates of overall AEFI and general reaction of IIV3 for 6-35 months old people were both higher than those of IIV3 for ≥3 years old (16.47 per 100 000 doses vs. 7.77 per 100 000 doses, 13.05 per 100 000 doses vs. 6.18 per 100 000 doses), and the differences were statistially significant (all P<0.05). The reporting rates of general abnormal reactions of IIV4 for 6-35 months old and ≥ 6 months old people were both higher than those of IIV4 for ≥3 years old people (14.73 per 100 000 doses and 9.52 per 100 000 doses vs. 3.88 per 100 000 doses); the reporting rates of general reactions and abnormal reactions of IIV4 for ≥6 months old people were both higher than those of IIV4 for ≥3 years old people (12.94 per 100 000 doses vs. 3.59 per 100 000 doses, 1.34 per 100 000 doses vs. 0.19 per 100 000 doses), the differences were statistcially significant (all P<0.05). In terms of clinical features, the reporting rates of fever (37.6-38.5 ℃ and ≥ 38.5 ℃), local redness and swelling (diameter 2.6-5.0 cm), and local induration (diameter ≤2.5 cm and 2.6-5.0 cm) after vaccination of IIV3 for ≥3 years old people were higher than those of IIV4 for ≥ 3 years old people (1.41 per 100 000 doses vs. 0.64 per 100 000 doses, 3.00 per 100 000 doses vs. 1.16 per 100 000 doses); the reporting rates of allergic rash and angioedema of IIV3 for ≥ 3 years old people were higher than those of IIV4 for ≥3 years old people (0.53 per 100 000 doses vs. 0.12 per 100 000 doses, 0.35 per 100 000 doses vs. 0); the differences were statistically significant (all P<0.016 7). Conclusions:The reporting rates of AEFI for influenza vaccines in Fujian Province from 2019 to 2023 was showing a downward trend. The AEFI was mainly general reactions. The reporting rates of AEFI were different among different influenza vaccines, but the overall safety was good.

Objective:To develop an electronic information platform-based assessment tool for entrustable professional activities (EPAs) of master of nursing specialist (MNS) students.Methods:The study used the content analysis method to construct the draft of the assessment tool, which was finalized using the expert meeting method. An electronic information platform was developed based on the assessment tool. The functions of the platform was optimized using the focus group interview method.Results:Based on previous research on the EPA framework for MNS students, an EPA assessment tool was developed, including an assessment form and an assessment protocol. The assessment form consisted of three parts: description of the EPAs, supervision level, and narrative feedback. The assessment protocol covered the assessment objects, assessment initiation strategy, assessment implementation-entrustment decision making, assessment cycle, and quality control. The electronic information platform includes both web-based and mobile app interfaces, with user roles for clinical instructors, graduate students, and project administrators, and with functions such as assessment application, assessment initiation, historical assessment review, and assessment information management.Conclusions:The study developed an EPA assessment tool for MNS students. The tool relies on the convenience and efficiency of the electronic information platform, facilitates clinical instructors in observing the comprehensive performance of MNS students in multiple competencies, and promotes postgraduate students' professional development. Future research will further explore the effectiveness of this tool in assessing clinical practice competencies of MNS students, with the aim of advancing the practice of EPAs in nursing masters' education.

Objective To explore the differential diagnostic value of three-dimensional CT values in active pulmonary tuberculosis(APTB)and inactive pulmonary tuberculosis(IPTB).Methods A retrospective analysis was conducted on 96 patients with pulmonary tuberculosis.According to whether the pulmonary tuberculosis lesions were active,the patients were divided into APTB group(n=61)and IPTB group(n=35).The baseline data,CT signs,and three-dimensional CT values were compared between two groups.Additionally,the results of three-dimensional CT values and conventional CT reading method in evaluating the activity of pulmonary tuberculosis were compared,and the accuracy,sensitivity and specificity of using three-dimensional CT values and conventional CT reading method to evaluate the activity of pulmonary tuberculosis were further analyzed.Results APTB group showed a higher incidence of bilateral pulmonary lesions than IPTB group(P<0.05).Compared with IPTB group,APTB group had higher proportions of blurred boundaries,parenchymal cavities,ground-glass opacities,and tree-in-bud signs(P<0.05),but lower proportions of parenchymal bronchiectasis,parenchymal calcifications,and fibrous strip shadows(P<0.05).The three-dimensional CT values in APTB group were lower than those in IPTB group(P<0.05).Significant differences were observed between conventional CT reading method and three-dimensional CT values in evaluating the activities of pulmonary parenchymal calcifications and thick-wall cavities(P<0.05).Specifically,three-dimensional CT values correctly identified 92 cases of tuberculosis lesions,including 59 cases of APTB and 33 cases of IPTB,and the remaining 4 misidentified lesions were calcified,consolidated and nodular lesions.Conventional CT reading method correctly identified 68 cases of tuberculosis lesions,including 43 cases of APTB and 25 cases of IPTB.The sensitivity,specificity,and accuracy of three-dimensional CT values were all higher than those of conventional CT reading method(P<0.05).Conclusion Three-dimensional CT values can effectively determine the activity of pulmonary tuberculosis,exhibiting high sensitivity,specificity,and accuracy.

Objective:To evaluate the clinical safety of Fufang E'jiao syrup and provide reference for its rational and safe clinical use. Methods:The literature involving Fufang E'jiao syrup in domestic and international databases, as well as the relevant clinical trials on ClinicalTrials.gov and the Chinese Clinical Trial Registry website were searched up to June 1, 2024. Those literature and clinical trials reporting drug adverse events were included, and the basic information about literature/clinical trials (title, publication year, study design, etc.), patients (age, gender, primary diseases, and dosage of Fufang E'jiao syrup), and adverse events (time of occurrence, clinical manifestations, and outcomes) was extracted. The adverse events were standardized and classified using the Medical Dictionary for Regulatory Activities version 25.0, and were also analyzed based on traditional Chinese medicine theory. Results:A total of 19 literature were included in the analysis, including 16 observational/experimental clinical studies, and 3 case reports. The 19 literature reported a total of 430 adverse events involving 398 patients, and the patients were mainly with malignant tumors and anemia. The 430 adverse events involved 11 system organ classes, which mainly included gastrointestinal disorders (260 events, 60.47%, with the most common symptom being dry mouth), respiratory, thoracic, and mediastinal disorders (119 events, 27.67%, with the most common symptom being dry throat), and skin and subcutaneous tissue disorders (16 events, 3.72%, with the most common symptom being mucosal ulcers). Based on traditional Chinese medicine theory, the 430 adverse events were mainly manifested as symptoms of indigestion (nausea, epigastric discomfort, and decreased appetite) and symptoms of "heat" (dry mouth and dry throat).Conclusions:Fufang E'jiao syrup has a relatively good overall safety profile, with the most common adverse events being symptoms of "heat" and gastrointestinal reactions. Patients should not use it blindly, and it should be used with syndrome differentiation in clinical practice.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*