Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective: To explore the facilitating and hindering factors of mental health promotion activities in junior and senior high schools from teachers perspectives, as well as coping strategies, so as to provide evidence for implementing teacher led mental health promotion programs. Methods: From September 2023 to September 2024, by using purposive sampling method, 5 junior high schools, 5 regular high schools, 2 vocational high schools in four provinces and municipalities (Tianjin, Shanxi, Shandong, and Jiangxi) were selected. A total of 92 teachers (78 homeroom teachers and 14 full time or part time psychological counselors) were interviewed using semi structured focus group discussions (one session per school, totaling 12 sessions). Thematic analysis was applied to code and analyze the interview transcripts. Results: The implementation of mental health promotion activities in middle schools was influenced by three levels: teachers, schools and society. Specifically, teachers exhibited a high support low capability phenomenon (81 participants supported conducting such activities, but 71 felt lacking in professional capacity); activity effectiveness and support systems were imbalanced (42 mentioned significant effects, while 78 reported insufficient support); there was a mismatch between student demand and activity content (9 mentioned students had psychological needs, but 11 indicated existing activities failed to meet these needs); administrative support and sustainability showed disparities (14 believed sufficient administrative support existed, while 37 noted sustainability issues); parental awareness and participation remained inadequate (11 highlighted parents need for mental health knowledge, and 37 perceived insufficient understanding of psychological issues among parents). Effective strategies included enhancing teachers effectiveness, providing essential skill training, focusing on the needs of teenagers,enhancing program sustainability, and eliminating misconceptions about mental health among parents. Conclusion Mental health promotion activities in junior and senior high schools should focus on enhancing teachers skills, improving activity sustainability, reducing stigma among parents, and establishing a collaborative network for school based mental health promotion.

Objective:It sorts out the relevant policies of China's public hospital salary system reform,summarizes the short-comings of public hospital salary policy in the process of formulation,and provides references for the subsequent adjustment and opti-mization of salary system.Methods:Based on Policy Modeling Consistency(PMC)index model,public hospital salary policies were collected and preprocessed,high-frequency words were extracted by text mining method,and an evaluation index system of sal-ary policies of public hospitals was constructed.By calculating the score of PMC index and first-level variables,the common prob-lems of various policies are analyzed,and specific suggestions were put forward.Results:The average PMC index of 12 public hos-pital compensation policies was 6.00,the overall quality of the policies was good,but there was still much room for improvement.The main common problems are the lack of internal and external linkage,the neglect of the incentive function of non-economic com-pensation and the unreasonable compensation structure.Conclusion:From the perspective of policy,the reform of public hospital salary system is a systematic project.It is suggested to take holistic thinking as the guide in the follow-up policy making process,en-hance the internal and extemal coordination of the policy,attach importance to the incentive role of non-economic compensation and optimize the salary structure,so as to promote the steady operation of the salary system reform of public hospitals.

Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.

Objective To establish a three-dimensional finite element model of knee joint in patients with mild knee osteoarthritis in the absence of CT and MRI with thin layer thickness,and to analyze the stress distributions of the tibial plateau.Methods A female patient with mild knee osteoarthritis was selected as the study object,and received serial CT scan from pelvis to distal tibia of fibula.The obtained files in DICOM format were imported into Mimics software for extracting the bony structures of knee joint through threshold segmentation,and then optimizing the extracted structures with Edit Masks,Cavity Fill and Region Grow.The generated model of bony structures was imported into 3-matic for smoothing and wrapping,and Geomagic Wrap was used for bony structure processing with mesh doctor inspection,surface defect repair and surface fitting.The cartilages,meniscus and ligaments were established by contour extension,and assembled with bony structures in SolidWorks in the way of origin coincidence.After defining material properties and contact relationships,meshing,and setting constraints and loads in ANSYS software,the stress distributions of the tibial plateau when standing with both legs were analyzed.Results A complete knee joint model including bony structure,cartilage and ligament was successfully established.When standing with two legs,the peak value of contact stress was about 1.21 MPa,and the maximum stress was 0.72 MPa at the medial middle of tibial plateau and lateral tibial plateau.The 62.7%and 37.3%of the total load were borne by the inner and outer compartments.Conclusion The model of the total knee joint is established with CT extraction and software rendering,and the finite element analysis results meet clinical expectations,indicating that the model established by the proposed method is reliable and can be used for follow-up research.

Objective:It sorts out the relevant policies of China's public hospital salary system reform,summarizes the short-comings of public hospital salary policy in the process of formulation,and provides references for the subsequent adjustment and opti-mization of salary system.Methods:Based on Policy Modeling Consistency(PMC)index model,public hospital salary policies were collected and preprocessed,high-frequency words were extracted by text mining method,and an evaluation index system of sal-ary policies of public hospitals was constructed.By calculating the score of PMC index and first-level variables,the common prob-lems of various policies are analyzed,and specific suggestions were put forward.Results:The average PMC index of 12 public hos-pital compensation policies was 6.00,the overall quality of the policies was good,but there was still much room for improvement.The main common problems are the lack of internal and external linkage,the neglect of the incentive function of non-economic com-pensation and the unreasonable compensation structure.Conclusion:From the perspective of policy,the reform of public hospital salary system is a systematic project.It is suggested to take holistic thinking as the guide in the follow-up policy making process,en-hance the internal and extemal coordination of the policy,attach importance to the incentive role of non-economic compensation and optimize the salary structure,so as to promote the steady operation of the salary system reform of public hospitals.

Objective:It sorts out the relevant policies of China's public hospital salary system reform,summarizes the short-comings of public hospital salary policy in the process of formulation,and provides references for the subsequent adjustment and opti-mization of salary system.Methods:Based on Policy Modeling Consistency(PMC)index model,public hospital salary policies were collected and preprocessed,high-frequency words were extracted by text mining method,and an evaluation index system of sal-ary policies of public hospitals was constructed.By calculating the score of PMC index and first-level variables,the common prob-lems of various policies are analyzed,and specific suggestions were put forward.Results:The average PMC index of 12 public hos-pital compensation policies was 6.00,the overall quality of the policies was good,but there was still much room for improvement.The main common problems are the lack of internal and external linkage,the neglect of the incentive function of non-economic com-pensation and the unreasonable compensation structure.Conclusion:From the perspective of policy,the reform of public hospital salary system is a systematic project.It is suggested to take holistic thinking as the guide in the follow-up policy making process,en-hance the internal and extemal coordination of the policy,attach importance to the incentive role of non-economic compensation and optimize the salary structure,so as to promote the steady operation of the salary system reform of public hospitals.