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*

120 extracted maxillary first premolars were endodontically treated and randomly divided into 5 groups(n=24).The teeth in group A had 4 walls of coronal tooth structure,in group B,C,D and E had only 3 walls,missing the palatal,buccal,mesial and distal wall,respectively.The teeth in group A0-E0(n=6)were restored without post,in group A1-E1(n=6)with buccal post,in group A2-E2(n=6)with palatal post,in group A3-E3(n=6)with buccal and palatal post,respectively.The fracture resistance of group A was higher than that of B,C,D and E groups(P＜0.05).The fracture resistance of fiber posts placed in the buccal root canal was higher than that in the palatal root canal(P＜0.05).The 360° complete ferrule can provide the best fracture resistance,When the ferrule is not complete,it is recommended to place buccal fiber post for repair.

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.

ObjectiveTo investigate the role of the Wnt1/β-catenin signaling pathway in the intervention of medicated serum of Buyang Huanwutang （BYHWT） in endothelial-to-mesenchymal transition （EndMT） of human pulmonary artery endothelial cells （HPAECs） as well as its related mechanisms. MethodMedicated serum of BYHWT was prepared by gavage to New Zealand rabbits with a dosage of 53.36 g·kg^-1·d^-1 after decocting the medicine as usual. In addition， the same volume of normal saline was used to prepare blank serum. The HPAECs were cultured in vitro， and then induced by the transforming growth factor-β₁ （TGF-β₁） to establish the EndMT model. Five groups were established： blank group （10% blank serum）， model group （TGF-β₁+10% blank serum）， low-dose BYHWT group （TGF-β₁+2.5% medicated serum+7.5% blank serum）， medium-dose BYHWT group （TGF-β₁+5% medicated serum+5% blank serum） and high-dose BYHWT group （TGF-β₁+10% medicated serum）. Through Western blot， the expressions of Wnt1， β-catenin， and glycogen synthase kinase-3β （GSK-3β） were detected. In order to further clarify the mechanism of the Wnt1/β-catenin signaling pathway in the intervention of the medicated serum of BYHWT in inhibiting EndMT， the overexpression of β-catenin was confirmed by polymerase chain reaction after plasmid of overexpression β-catenin was constructed and transfected into the HPAECs. The HPAECs were intervened by 10% medicated serum with the optimal effect in previous studies. Then， they were divided into another five groups： the blank group （10% blank serum）， the model group （TGF-β₁+10% blank serum）， the BYHWT group （TGF-β₁+10% medicated serum）， the BYHWT+overexpression plasmid control group （TGF-β₁+10% medicated serum+blank plasmid） and the BYHWT+β-catenin overexpression plasmid group （TGF-β₁+10% medicated serum+β-catenin）. Apart from that， cell proliferation ability was detected by the methyl thiazolyl tetrazolium （MTT） method and cell migration ability by scratch assay and Transwell assay together. Immunofluorescence was adopted to detect the expressions of platelet endothelial cell adhesion molecule （PECAM-1/CD31）， vascular endothelial cadherin （VE-cadherin）， fibroblast-specific protein 1 （FSP1）， and α-smooth muscle actin （α-SMA）. ResultIn comparison to the blank group， the expressions of Wnt1 and β-catenin were significantly increased （P<0.01） while the expression of GSK-3β significantly decreased （P<0.01） in the model group. In comparison to the model group， the expressions of Wnt1 and β-catenin were significantly decreased （P<0.01） while the expression of GSK-3β was significantly increased （P<0.01） in the high-dose BYHWT group. The expression of β-catenin was significantly decreased （P<0.01） while the expression of GSK-3β was significantly increased （P<0.01） in the medium-dose BYHWT group. There was no significant difference in these indexes of the low-dose BYHWT group. In comparison to the blank group， proliferation and migration abilities were remarkably increased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were decreased， while those of FSP1 and α-SMA were increased in the model group. In comparison to the model group， proliferation and migration abilities were significantly decreased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were increased， while those of FSP1 and α-SMA diminished in the BYHWT group. Beyond that， the change trend of those indexes in the BYHWT+β-catenin overexpression plasmid group was consistent with that in the model group. In comparison to the BYHWT+overexpression plasmid control group， proliferation and migration abilities were significantly increased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were decreased， while those of FSP1 and α-SMA were increased in the BYHWT+β-catenin overexpression plasmid group. ConclusionMedicated serum of BYHWT can inhibit EndMT of HPAECs by the Wnt1/β-catenin signaling pathway.

Objective:To investigate whether chlorogenic acid can inhibit the proliferation, migration, invasion and promote apoptosis of lung cancer A549 cells by causing mitochondrial dysfunction through PI3K-Akt pathway.Methods:A549 cells were treated with chlorogenic acid at concentrations of 0, 25, 50, 100, 150, and 200 μg/ml for 48 h. CCK-8 assay was used to detect the cell proliferation rate and calculate the half maximal inhibitory concentration (IC 50). A549 cells were divided into three groups: control group, chlorogenic acid group (IC 50) and chlorogenic acid + 740-YP group (IC 50 chlorogenic acid +50 μg/ml 740YP). After 48 h of intervention, the cell migration distance was detected by cell scratch assay. Cell invasion assay was used to detect cell invasion ability. Cell cycle, apoptosis and mitochondrial membrane potential were detected by flow cytometry. The content of malondialdehyde (MDA) in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein expression of p-PI3K, p-Akt and Caspase3. Results:The IC 50 of chlorogenic acid to A549 cells was 57.45 μg/ml. The results of cell scratch assay showed that the 48 h migration distances of the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (424.80±14.43), (289.67±18.93) and (402.22±17.99) μm, respectively. The results of cell invasion assay showed that the numbers of invasive cells after 48 h were 96.00±6.24, 35.33±7.64 and 83.00±2.00, and the results of flow cytometry showed that the 48 h apoptosis rates were (6.15±0.17) %, (54.63±0.72) % and (17.27±0.39) %, respectively, among the three groups with statistically significant differences ( F=105.98, P<0.001; F=90.62, P<0.001; F=8 321.99, P<0.001). Compared with the control group, the cell migration distances and invasive numbers of chlorogenic acid group and chlorogenic acid + 740YP group were decreased (all P<0.05), while the apoptosis rates were significantly increased (both P<0.001). Compared with chlorogenic acid group, the cell migration distance of chlorogenic acid + 740YP group increased ( P<0.001), the number of cell invasion increased ( P<0.001), and the apoptosis rate decreased ( P<0.001). The results of flow cytometry showed that the proportions of cells in G 0/G 1 phase in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (65.75±0.58) %, (55.84±0.78) % and (55.24±1.37) %, respectively. The proportions of G 2/M phase were (11.21±1.03) %, (20.23±0.62) % and (9.96±0.33) %, and the proportions of S phase were (23.04±0.49) %, (23.92±1.36) % and (34.80±1.15) %, respectively, with statistically significant differences ( F=111.02, P<0.001; F=181.26, P<0.001; F=113.05, P<0.001). Compared with the control group, the proportions of G 0/G 1 phase cells in chlorogenic acid group and chlorogenic acid + 740YP group decreased (both P<0.001), and the proportion of G 2/M phase in chlorogenic acid group increased ( P<0.001), and the proportion of S phase cells in chlorogenic acid + 740YP group increased ( P<0.001). Compared with chlorogenic acid group, the proportion of G 2/M phase cells decreased and the proportion of S phase cells increased in chlorogenic acid + 740YP group (both P<0.001). The results of mitochondrial membrane potential detection showed that the JC-1 fluorescence intensity of mitochondria in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were 39.51±1.32, 10.05±0.19 and 21.85±1.45, respectively, with a statistically significant difference ( F=508.82, P<0.001). Compared with the control group, the fluorescence intensity of chlorogenic acid group and chlorogenic acid + 740YP group decreased (both P<0.001). Compared with chlorogenic acid group, the fluorescence intensity of chlorogenic acid + 740YP group increased ( P<0.001). ELISA results showed that the MDA contents of the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (0.47±0.01), (0.61±0.01) and (0.56±0.01) nmol/ml, respectively, with a statistically significant difference ( F=162.30, P<0.001). Compared with the control group, MDA contents in chlorogenic acid group and chlorogenic acid + 740YP group increased (both P<0.001). Compared with chlorogenic acid group, MDA content in chlorogenic acid + 740YP group decreased ( P=0.001). Western blotting results showed that the relative protein expression levels of p-PI3K in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were 1.01±0.33, 0.28±0.14 and 0.34±0.20, respectively. The relative protein expression levels of p-Akt were 1.00±0.16, 0.43±0.05 and 0.95±0.14, and the relative protein expression levels of Caspase3 were 1.00±0.04, 1.41±0.05 and 0.70±0.13, respectively, and there were statistically significant differences ( F=8.48, P=0.018; F=19.11, P=0.002; F=57.50, P<0.001). Compared with the control group, the expressions of p-PI3K and p-Akt protein in chlorogenic acid group decreased, and the expression of Caspase3 protein increased (all P<0.05). The expressions of p-PI3K and Caspase3 protein in chlorogenic acid + 740YP group decreased (both P<0.05). Compared with chlorogenic acid group, the expression of p-Akt protein in chlorogenic acid + 740YP group increased, and the expression of Caspase3 protein decreased (both P<0.05) . Conclusion:Chlorogenic acid may inhibit the PI3K-Akt pathway by reducing the phosphorylation of PI3K and Akt proteins, resulting in the damage of mitochondrial function and the accumulation of MDA, which eventually leads to the damage of lung cancer A549 cells function and the reduction of cells activity, and then promotes cells apoptosis.

Purpose To investigate the expression of pro-tein of relevant evolutionary and lymphoid interest domain-con-taining 1(PRELID1)in gastric cancer tissues and to analyze its effect on prognosis,and the mechanism of influencing the prolif-eration and invasion ability of gastric cancer cells.Methods Using TCGA data and clinical data of 111 patients with gastric cancer,we analyzed the relationship between the expression of PRELID1 and clinicopathological parameters and the impact on clinical prognosis.The biological function of PRELID1 was pre-dicted by bioinformatics,and further verified by in vitro and in vivo experiments.Lentivirus was applied to regulate the level of PRELID 1 in gastric cancer cell line(MGC803)in vitro,and its effect on the proliferation,migration,and invasion of gastric cancer cells was observed.The nude mouse subcutaneous tumor-igenesis was used to observe the effect of PRELID1 on the growth of gastric cancer tissue in vivo.Results The expression of PRELID1 was significantly higher in gastric cancer tissues than that in the adjacent tissues(P＜0.001)and was positively cor-related with the cell proliferation indicator Ki67(P＜0.001).Cox regression model analysis showed that the high expression of PRELID 1 was an independent risk factor affecting the 5-year survival rate after radical gastrectomy(HR=2.336;95％CI=1.354-4.029).Gene enrichment results showed that the func-tion of PRELID1 was related to proliferation and JAK/STAT sig-naling.CCK-8 and Transwell experiments found that up-regula-tion of PRELID1 promoted the proliferation(P=0.016),mi-gration(P=0.016)and invasion(P=0.025)of gastric cancer cells,while down-regulation inhibited the proliferation(P=0.026),migration(P=0.048)and invasion(P=0.029).Subcutaneous tumor formation experiments in nude mice found that up-regulation of PRELID1 promoted the growth of gastric cancer tissue(P=0.047),while down-regulation was the oppo-site(P=0.005).Western blot detecting gastric cancer cells and gastric cancer tissues found that up-regulation of PRELID1 promoted the expression of JAK and STAT proteins(all P＜0.05),while down-regulation inhibited them(all P＜0.05).Conclusion The high expression of PRELID1 associated with poor prognosis may regulate the proliferation,migration and in-vasion of gastric cancer cells by up-regulating JAK/STAT signa-ling in gastric cancer.

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.