OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Objective To evaluate the correlation between alterations in DNase1 and DNase1L3 enzyme activities and impairment of NET degradation in patients with sporadic SLE, and to investigate the underlying mechanism. Methods 46 sporadic SLE patients and 30 age- and sex-matched healthy individuals were recruited. Serum levels of DNase1, DNase1L3 and corresponding autoantibodies were detected by ELISA. DNase1 and DNase1L3 were isolated by immunoprecipitation; NETs and enzyme degradation activities were detected using a modified immunofluorescence. DNase1L3 secretion by PBMCs was analyzed by ELISPOT, Western blotting and reverse transcription PCR. Results Levels of H3-dsDNA and Ela-dsDNA complexes were significantly elevated in SLE patients. LDGs in SLE population was significantly higher than in the control group, and LDGs was positively correlated with H3-dsDNA and Ela-dsDNA NETs complexes. The ability of SLE patients to degrade NET in vitro was significantly lower than that of the control group. Degradation experiments of DNase1 and DNase1L3 in different proportions showed that the decrease in DNase1L3 activity was the primary contributor to the elevated NET residue level. The concentration of DNase1L3 autoantibodies in SLE patients was significantly elevated compared to the control group. In addition, the capacity of PBMCs to secrete DNase1L3 was significantly lower in the SLE patients compared to the control group. Conclusion Decreased secretion of DNase1L3 and the presence of relevant autoantibodies notably impede NET degradation in patients with SLE, offering new directions for the monitoring and treatment of SLE patients.
Humans ; Autoantibodies ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Extracellular Traps ; Lupus Erythematosus, Systemic

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

Objective To investigate the effects of the Bushen Quhan Huashi Prescription(mainly composed of Drynariae Rhizoma,Eucommiae Cortex,Dipsaci Radix,Notopterygii Rhizoma et Radix,Zingiberis Rhizoma Recens,Coicis Semen,and Achyranthis Bidentatae Radix)in combination with Methotrexate on the disease activity and serum core-binding factor a1(Cbfa1)level of patients with ankylosing spondylitis(AS)of kidney deficiency and governor-vessel cold type.Methods Ninety AS patients with kidney deficiency and governor-vessel cold type were randomly divided into a trial group and a control group,with 45 patients in each group.The control group was given Methotrexate treatment,and the trial group was treated with Bushen Quhan Huashi Prescription on the basis of treatment for the control group.The course of treatment in the two groups lasted for 3 months.The changes of Bath ankylosing spondylitis disease activity index(BASDAI)scores,Bath ankylosing spondylitis function index(BASFI)scores and serum levels of Cbfa1,type I collagen carboxy-terminal peptide(CTX-Ⅰ)and Dickkopf1 protein(DKK1)of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse effects were compared between the two groups.Results(1)After 3 months of treatment,the total effective rate of the trial group was 97.78%(44/45)and that of the control group was 82.22%(37/45).The intergroup comparison by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the disease activity scores of BASDAI and BASFI in the two groups of patients were significantly decreased compared with those before treatment(P＜0.05),and the trial group's reduction of BASDAI scores and BASFI scores were significantly superior to those of the control group,and the differences were statistically significant(P＜0.01).(3)After treatment,the serum levels of serological indicators of Cbfa1,CTX-Ⅰ,and DKK1 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of Cbfa1,CTX-Ⅰ and DKK1 levels in the trial group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).(4)During the treatment,the incidence of adverse reactions in the trial group was 6.66%(3/45)and that in the control group was 11.11%(5/45),and the difference of the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Bushen Quhan Huashi Prescription combined with Methotrexate exerts certain effect in treating AS patients with kidney deficiency and governor-vessel cold type,and the therapy can effectively control the disease activity and reduce the level of serum Cbfa1 expression in the patients.

Objective:To investigate the dynamic trend of platelet（PLT）count and mean platelet volume（MPV）in children with severe community-acquired pneumonia（SCAP）in PICU and their correlation with prognosis.Methods:A retrospective study was conducted in 215 SCAP children who were admitted to the PICU of Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to December 2019.According to the disease outcome，the patients were divided into improvement group ( n=184) and unrecovered group ( n=31).The changes of PLT count and MPV at admission，on the 2nd，3rd，and 7th days of hospitalization and before discharge were observed，and the relationship between changes in PLT parameters and poor prognosis was analyzed. Meanwhile，the correlation between thrombocytopenia on admission and on the 7th day of hospitalization and prognosis was further explored. Results:The PLT count of improvement group at admission，on the 2nd，3rd，and 7th days of hospitalization and at discharge[(328±159, 329±137, 362±159, 439±168, 510±171)×10 9/L] were significantly higher than those of unrecovered group [(210±142, 207±152, 267±143, 260±162, 343±159)×10 9/L]（ P＜0.05）.Although the MPV of improvement group [(10.9±1.9)fL] on admission was significantly lower than that of the unrecovered group[(12.7±2.5) fL]（ P＜0.05），there was no significant difference in MPV between two groups on the 2nd，3rd，7th days of hospitalization and discharge（ P＞0.05）.In addition，compared with the admission，children in improvement group had significantly higher PLT count on the 7th day of hospitalization and before discharge（ P＜0.05），but there was no significant change in unrecovered group（ P＞0.05）.Compared with SCAP patients with thrombocytopenia at admission (PLT＜100×10 9/L)( n=22),those with thrombocytopenia on 7th day of hospitalization had a significant higher rate of non recovery( P＜0.05). Conclusion:The occurrence of thrombocytopenia on admission and after 7 days of hospitalization in children with SCAP is associated with poor prognosis.No significant increase or decrease in PLT count after 7 days of hospitalization is often indicative of poor prognosis.Dynamic monitoring of PLT parameter changes may help to better judge the prognosis of severe pneumonia.

AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.

Objective To investigate the prevalence of Enterobius vermicularis infections among children in China from 2016 to 2021, so as to provide insights into enterobiasis control and formulation of the enterobiasis control strategy among children. Methods Publications pertaining to the prevalence of E. vermicularis infections among children were retrieved from Wanfang Data, CNKI, VIP and PubMed databases published from January 2016 to June 2023. Eligible publications were screened according to inclusion and exclusion criteria, and the publication bias was evaluated using the assessment tool for prevalence studies proposed by the Joanna Briggs Institute Evidence-Based Practice Resources in Australia. The study period, study areas, study subjects, sample size and number of infections were extracted from publications, and a pooled analysis was performed using a meta-analysis. A meta-regression analysis was performed with the prevalence of E. vermicularis infections as an independent variable, and sample size, source of samples, study area, study method, geographical area and province as dependent variables to identify the source of the study heterogeneity. Results A total of 66 studies were included, covering 23 provinces (municipalities, autonomous regions) in China, and with the investigations conducted between 2016 and 2021. Meta-analysis showed that the pooled prevalence of E. vermicularis infections was 4.5% [95% confidence interval (CI): (3.1%, 6.0%)] among children in China from 2016 to 2021, and the annual prevalence was 4.1% [95% CI: (2.2%, 6.5%)], 4.2% [95% CI: (2.4%, 6.6%)], 4.2% [95% CI: (2.2%, 6.8%)], 3.2% [95% CI: (1.5%, 5.4%)], 2.3% [95% CI: (0.9%, 4.3%)] and 1.1% [95% CI: (0.4%, 2.1%)] from 2016 to 2021. The pooled prevalence of E. vermicularis infections was 4.9% [95% CI: (3.4%, 6.8%)] in studies with a sample size of < 5 000 cases, which was higher than that in studies with a sample size of 5 000 cases and higher [2.1%, 95% CI: (0.2%, 3.6%)], and the pooled prevalence of E. vermicularis infections was 5.2% [95% CI: (2.9%, 8.2%)] among subjects from schools, which was higher than that among subjects from communities [4.2%, 95% CI: (2.7%, 6.0%)]. The pooled prevalence of E. vermicularis infections was 4.4% [95% CI: (2.8%, 6.2%)] among children included in comprehensive surveillance, which was higher than that among children included in specific surveillance [4.8%, 95% CI: (2.6%, 7.7%)], and the pooled prevalence of E. vermicularis infections was 5.7% [95% CI: (3.8%, 7.8%)] among children included in county-level surveys, which was higher than that among children included in city-[4.8%, 95% CI: (2.3%, 8.0%)] and province-level surveys [1.8%, 95% CI: (0.3%, 4.7%)]. In addition, the pooled prevalence of E. vermicularis infections was higher among children in southern China [11.3%, 95% CI: (7.5%, 15.7%)] than that in central China [5.2%, 95% CI: (2.8%, 8.2%)], eastern China [5.2%, 95% CI: (2.8%, 8.2%)] and southwestern China [2.6%, 95% CI: (1.4%, 4.1%)]. Meta-regression analysis identified geographical area and survey province as factors affecting the study heterogeneity. Conclusions Currently, the overall prevalence of E. vermicularis infections is moderate among children in China, and the prevalence varies greatly in regions, with a high prevalence rate in southern China and presence of small-scale clusters. Enterobiasis surveillance and health education pertaining to enterobiasis control are required with adaptations to local circumstance to reduce the prevalence of E. vermicularis infections among children.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.