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.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective:To explore the application and clinical efficacy of functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium in the surgery of lung cancer brain metastases.Methods:Forty patients with lung cancer and brain metastasis admitted to the Department of Neurosurgery of Inner Mongolia Autonomous Region People's Hospital from January 2020 to January 2024 were collected as the observation group. Another 40 patients with lung cancer brain metastases who underwent microscopic resection at Inner Mongolia Autonomous Region People's Hospital from January 2016 to December 2019 were selected as the control group. All patients received head CT examination, head MRI examination, MRI enhanced sequence and MRA, MRV and DWI sequence scanning before operation. Functional neural navigation system was used to perform preoperative multi-modal image fusion to realize three-dimensional display of tumor lesions, and display the position relationship between tumor and functional areas, conduction bundles and large blood vessels, so as to make preoperative navigation plan. After conducting a fluorescein sodium allergy test on the patient before surgery, a small dose of fluorescein sodium (2 mg/kg) was intravenously injected during the operation. During the operation, neuro navigation was combined with fluorescein sodium to perform tumor resection by displaying the boundary between tumor tissue and normal brain tissue under a Pentero 900 Zeiss microscope 560 fluorescence mode. Both groups collected tumor tissue samples for pathological classification and immunohistochemical analysis, comparing and analyzing differences in tumor resection degree, postoperative occurrence of new neurological dysfunction, postoperative muscle strength improvement, changes in KPS scores before and after surgery, and the occurrence of complications. The metric data that conforms to normal distribution is represented by xˉ± s, and the comparison of means between two groups is conducted using independent sample t-test. Calculate the percentage based on the count data, and compare the inter group rates using the χ2 test. P<0.05 indicates statistical significance of the difference. Results:Compared with the control group, the total tumor resection rate of observation group (75.0% (30/40) ) and KPS score of 3 months after surgery (82.5% (33/40)) were better than those of the control group (52.5% (21/40) and 60% (24/40)), and the differences were statistically significant ( χ2 value was 4.94 and 4.38, P values were 0.026 and 0.036). The rate of postoperative new neurological dysfunction in the observation group (22.5% (9/40)) was lower than that in the control group (45.0% (18/40)), and the difference between the two groups was statistically significant ( χ2=4.53, P=0.033). The length of hospital stay ((21.48±3.23) days), operation time ((216.65±56.76) points) and complication rate (37.5% (15/40)) in observation group were lower than those in control group ((22.43±2.34) days, (225.62±37.68) points, 45.0% (18/40)). However, the difference was not statistically significant ( t/ χ2 values were 1.51, 0.83, and 0.46, respectively; P values were 0.136, 0.408, and 0.496, respectively). The 12-month survival rate of observation group (67.5%(27/45) respectively was significantly higher than that of control group (40.0%(16/40) respectively, and the difference was statistically significant ( χ2=6.08, P=0.014). Conclusion:Functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium can accurately locate the tumor and determine the boundary relationship between the tumor and normal brain tissue during lung cancer brain metastasis surgery, improve tumor resection rate, enhance patient quality of life, and ultimately improve patient prognosis without increasing the risk of related complications.

Compared with teenage patients,adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment,indicating the maladaptation of alveolar bone homeostasis under orthodontic force.However,this phenomenon is not well-elucidated to date,leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics.Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue,this review summarizes the current evidence and underlying mechanisms.The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism,thus hindering alveolar bone reconstruction during orthodontic treatment.To this end,periodontal surgery,physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism.We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.

Objective:To investigate the clinical effect of 3D printing combined with O-arm navigation assisted posterior hemivertebrae resection and orthopedic fixation in the treatment of congenital cervicothoracic scoliosis.Methods:A retrospective study was conducted on the clinical data of 14 patients with congenital cervicothoracic kyphosis caused by hemivertebra treated in Henan Provincial People's Hospital from January 2015 to June 2021, including 9 males and 5 females, aged 8.9±3.2 years (range, 1-15 years). Operation time, intraoperative blood loss and fusion stage were recorded. Intraoperative O-arm scanning and postoperative CT scanning were performed to evaluate the accuracy of nail placement. The cervicothoracic scoliosis Cobb angle, compensatory scoliosis Cobb angle, local kyphosis Cobb angle, torticollis angle, T 1 tilt angle and clavicular angle were measured before operation, model design, 1 week after operation and at the last follow-up to evaluate the effect of surgical design, intraoperative orthosis and the correction loss at follow-up. The Society for Scoliosis Research-22 (SRS-22) questionnaire was used to evaluate the functional and treatment effect. At the last follow-up, the osteotomy fusion was evaluated by Eck criterion. Results:All patients successfully completed the operation, the operation time was 228.5±41.8 min, the intraoperative blood loss was 355.6±46.7 ml, and the number of fusion segments was 5.5±0.8. Follow-up duration was 35.5±13.2 months. A total of 140 pedicle screws were inserted, with an accuracy of 97.1% (136/140). The Cobb angle of cervicothoracic scoliosis was 53.9°±17.9° preoperatively, 11.3°±4.4° in the model design, 10.8°±2.6° one week postoperatively, and 14.5°±3.5° at the last follow-up, with statistical significance ( P<0.001). The preoperative and postoperative one week difference was statistically significant ( P<0.001) with a correction rate of 78.6%±6.7%. The Cobb angle of compensatory scoliosis was 33.1°±12.1° before surgery, 11.9°±2.4° for model design, 10.5°±3.4° for one week after surgery, and 14.1°±2.5° for the last follow-up, with statistically significant differences ( P<0.001). The postoperative correction rate was 65.2%±16.2%. The Cobb angle of local kyphosis was 27.8°±9.8° preoperatively, 10.1°±2.1° in the model design, 9.8°±1.9° one week postoperatively, and 12.7°±1.6° at the last follow-up, with statistical significance ( P<0.001). The preoperative and postoperative one week difference was statistically significant ( P<0.001) with a correction rate of 59.2%±18.9%. The preoperative and postoperative one week difference was statistically significant ( P<0.001) with a correction rate of 78.6%±6.7%. The neck tilt angle was 20.6°±6.7° preoperatively, 6.2°±1.9° in the model design, 5.9°±2.1° one week postoperatively, and 7.1°±1.4° at the last follow-up, with statistical significance ( P<0.001). The preoperative and postoperative one week difference was statistically significant ( P<0.001) with a correction rate of 70.0%±11.1%. The T 1 inclination angle was 20.2°±5.8° preoperatively, 11.5°±3.1° in the model design, 10.2°±2.3° one week postoperatively, and 9.5°±3.0° at the last follow-up, with statistical significance ( P<0.001). The preoperative and postoperative one week difference was statistically significant ( P<0.001) with a correction rate of 53.2%±10.4%. There was no significant difference between preoperative design and actual measurement one week after surgery ( P>0.05). At the last follow-up, the scores of self-image (4.6±0.7), mental health (4.7±0.6) and treatment satisfaction (4.6±0.6)in SRS-22 scale were significantly improved compared with those before operation ( P<0.05). The symptoms of hemivertebra ipilateral C 8 nerve root injury occurred in 1 patient, who was treated conservatively with dehydration, hormones and nutraceutical drugs, and recovered to normal at 3 months follow-up. At the last follow-up, the appearance of the head, neck and shoulders of the patients was improved compared with that before surgery, the bone grafts have achieved osseous fusion in all patients. All fusion were grade I by Eck criterion. No complications such as serious neurological or vascular injury occurred during perioperative period. No pseudoarthrosis formation, internal fixation loosening or fracture occurred during follow-up. Conclusion:The application of 3D printing combined with O-arm navigation assistance technology in posterior hemivertebra resection and correctional surgery for cervicothoracic hemivertebra deformities can display the deformities in advance, stereoscopic and real-time, accurately place pedicle screws and complete hemivertebra resection, improve surgical safety and deformity correction rate.

Objective To investigate the expression of cysteine rich protein 2 binding protein(CSRP2BP)mRNA and estrogen related receptors β(ESRRB)mRNA and protein in cervical cancer tissues and their correlation with epithelial mesenchymal transition(EMT)and clinical prognosis.Methods A total of 106 cervical cancer patients admitted to Yan'an Traditional Chinese Medicine Hospital from March 2018 to March 2020 were selected.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect CSRP2BP mRNA,ESRRB mRNA and EMT related indicators[E-cadherin(E-cad),N-cadherin(N-cad),snail family transcriptional repressor 1(Snail)].Immunohistochemistry was used to detect the CSRP2BP protein and ESRRB protein expression in tissues.Pearson correlation analysis was used to analyze the correlation between CSRP2BP mRNA,ESRRB mRNA and EMT related indicators.Kaplan-Meier curve and COX regression were used to analyze the effect of CSRP2BP mRNA and ESRRB mRNA expression on the prognosis of cervical cancer patients.Results CSRP2BP mRNA(3.14±0.52 vs 1.22±0.21)expression and protein positive rate(86.79%vs 9.43%),ESRRB mRNA expression(2.86±0.31 vs 1.06±0.20)and protein positive rate(92.45%vs 8.49%),N-cad mRNA(3.22±0.43 vs 1.05±0.26)and Snail mRNA(2.67±0.36 vs 0.69±0.17)expression in cancer tissues were higher than those in adjacent tissues,while E-cad mRNA(0.84±0.17 vs 2.15±0.24)expression was lower than that in adjacent tissues,and the differences were statistically significant(t/x2=34.249,127.049;50.234,149.466;44.461,51.204,45.858,all P<0.001).The expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer was positively correlated with N-cad mRNA and Snail mRNA(r=0.663,0.731;0.726,0.715,all P<0.001),and was negatively correlated with E-cad mRNA(r=-0.594,-0.669,all P<0.001).The expression of CSRP2BP mRNA(4.48±0.36,4.21±0.37,4.69±0.33)and ESRRB mRNA(4.48±0.36,4.21±0.37,4.69±0.33)in cervical cancer tissues of patients with FIGO stage Ⅰ B2～Ⅱ A,poor differentiation and lymph node metastasis was higher than that of patients with FIGO stage ⅠA～ⅠB1(2.60±0.44,2.06±0.24),medium and high differentiation(2.43±0.44,2.01±0.25)and no lymph node metastasis(2.53±0.58,2.07±0.26),and the differences were statistically significant(t=16.327,41.135;18.507,36.545;14.501,43.806,all P<0.001).The 3-year overall survival rate of patients with high expression of CSRP2BP mRNA was 66.00%(33/50),which was lower than 89.29%(50/56)in the low expression group,while the 3-year overall survival rate of the high expression group of ESRRB mRNA was 65.38%(34/52),which was lower than 90.74%(49/54)of the low expression group,and the differences were statistically significant(Log rank x2=5.401,11.400,P=0.020,0.001).Multivariate Cox regression analysis showed that,CSRP2BP mRNA high expression(HR=1.327,95%CI:1.097～1.605),ESRRB mRNA high expression(HR=1.322,95%CI:1.108～1.577),FIGO stage Ⅰ B2～Ⅱ A(HR=1.423,95%CI:1.154～1.755),lymph node metastasis(HR=1.363,95%CI:1.095～1.698)and poor differentiation(HR=1.297,95%CI:1.064～1.581)were risk factors affecting the prognosis of cervical cancer patients(all P<0.001).Conclusion The increased expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer are related to EMT related indicators and adverse clinical and pathological features,and are new tumor markers for prognostic evaluation.

IgA nephropathy is a common primary glomerular disease.Its pathogenesis is currently unclear.As an autoimmune disease, immune response is a key link in the onset of IgA nephropathy.Multiple immune cells are involved in the occurrence and development of IgA nephropathy.The impacts of different cell subpopulations of innate and adaptive immunity can lead to sustained immune damage directly or indirectly.This article elaborates on the role of immune cells in IgA nephropathy from two aspects, namely innate immunity and adaptive immunity, aiming to provide references for further research on IgA nephropathy.

A retrospective analysis was made on the clinical data and gene mutation characteristics of 2 children admitted to the Children′s Hospital of Zhejiang University School of Medicine for epilepsy without periventricular nodules caused by the ARF1 gene mutation from August 2023 to February 2024, and relevant literature was reviewed.Both patients presented with seizures and psychomotor retardation, and 1 of them was diagnosed with West syndrome.Whole exome sequencing confirmed that the 2 patients carried a missense mutation in the ARF1 gene (c.55C>A, p.R19S).Brain magnetic resonance imaging (MRI) of 2 patients revealed no obvious abnormalities.A summary analysis of 5 cases of ARF1 gene mutations reported in three foreign literatures showed that patients with ARF1 gene mutations usually presented with seizures, developmental delay, hypotonia, mental retardation, and motor stereotypies.MRI showed periventricular nodular heterotopia, corpus callosum dysplasia, subcortical white matter abnormalities, and delayed myelination.This study found for the first time that ARF1-related disorders can occur without significant brain structural malformations, indicating that there are inconsistencies in neuroimaging findings, adding valuable phenotypic information to this gene.The differences in imaging findings may be the result of genetic background or variation in ARF1-interacting proteins, or may be caused by altered regulatory mechanisms of protein activity.