BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

Objective: To explore the cross sectional and longitudinal associations between 24 hour movement behaviors and physical fitness in preschool children, and to adopt the method of equal time substitution analysis to evaluate the impact of time redistribution of different activity behaviors on physical fitness scores,so as to provide a scientific basis for promoting the health of preschool children. Methods: A total of 193 preschool children aged 3-6 years were selected from three Shanghai districts (Jing an, Baoshan, Jiading) from October to December 2023 by the stratified cluster random sampling method. The 24 hour movement behaviors were monitored via 7 day accelerometry, and physical fitness was measured according to the National Physical Fitness Measurement Standards (Revised 2023, preschool section). From October to December 2024, the follow up of physical fitness among preschool children used the same testing method. The comparison between groups was conducted by t-test. Compositional regression analyses evaluated the relationship of 24 hour movement behaviors and physical fitness among preschool children. Results: At baseline, moderate to vigorous physical activity (MVPA) time was significantly higher in boys [(84.10±25.78)min/d] than in girls [( 70.44± 25.98)min/d]; the composite physical fitness score was significantly higher in boys (71.65±8.69) than in girls (68.84±9.89), and the differences were statistically significant ( t =3.65, 2.10, both P <0.01). After adjusting for gender, age and body mass index, the results of component multiple linear regression analysis showed that MVPA time proportion was positively correlated with the composite physical fitness score at baseline among preschool children ( β =6.61), but was negatively correlated with two legged continuous hopping time at 1 year ( β =-1.12) (both P <0.05). Light physical activity (LPA) time proportion was negatively correlated with walking on the balance beam time at 1 year ( β =-4.44), and sedentary behavior (SB) time proportion was negatively correlated with the composite score of physical fitness at baseline ( β =-6.55) (both P <0.05). Isotemporal substitution analysis revealed that replacing 10 minutes of sleep (SP), SB, and LPA with MVPA increased the baseline physical fitness composite score by 0.750, 0.689 and 0.575 units, respectively; at 1 year follow up, the composite score increased by 1.440, 1.419 and 1.430 units, respectively (all P <0.05). Conversely, replacing MVPA with 10 minutes of SP, SB, and LPA,resulted in decreases in baseline physical fitness composite scores of 0.836, 0.777 and 0.669 units, and reductions of 1.613, 1.592 and 1.598 units at 1 year follow up (all P < 0.05 ). Conclusions Preschool children s 24 hour movement behaviors, especially MVPA, are closely related to physical health. Implementing appropriate strategies to increase physical activity and reduce sedentary time may improve the physical fitness of preschoolers.

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective:To investigate the degree of satisfaction with education of undergraduates majoring in medical technology in medical universities in China and associated problems, and to put forward countermeasures and suggestions for student training.Methods:A questionnaire was distributed to undergraduates majoring in medical technology selected by stratified sampling from Shanghai Jiao Tong University, Tianjin Medical University, and Shanghai University of Medicine & Health Sciences. The questionnaire covered demographic characteristics, major choice motivation, education satisfaction, and various aspects, including a total of 54 variables (21 nominal variables and 33 continuous variables). Statistical analysis was performed by using SPSS 27.0 One-way analysis of variance was used for group comparison.Results:The mean degree of satisfaction with education of the students of medical technology was 4.02 points, with the highest score for curricula and teaching and the lowest score for academic atmosphere. Cultivation and management showed the strongest correlation with the degree of satisfaction with education. The degree of satisfaction with education differed significantly for different institutions and different major choice motivations ( P<0.05). Conclusions:Undergraduates of medical technology are generally satisfied with their education, and the degree of satisfaction is lower in double first-class universities than in application-oriented ordinary universities. Attention should be paid to student training and management, creating a positive academic atmosphere, and enhancing the attractiveness of colleges/universities and majors. Compared with application-oriented undergraduate colleges/universities, double first-class universities should well coordinate training goals with students' expectations, industry needs, and even national strategic needs. Colleges and universities can make appropriate adjustments in terms of curricula, teaching, and teaching resources, to promote the diverse and orderly development of medical technology talents based on their personal strengths.

Objective Liver cancer is the second leading cause of tumor-related death.The efficacy of local thermal ablation is comparable to surgical resection for the early hepatocellular carcinoma(HCC),and the ablation technique is minimally invasive,repeatable,and has a low complication rate.However,early recurrence((2 years)is the main cause of death after HCC ablation,but there is still a lack of accurate and reliable prediction models for early recurrence.Therefore,this survey intended to construct prediction models for early recurrence of HCC after ablation by using preoperative gadoxetic acid disodium-enhanced magnetic resonance(MR)images data combined with radiomics methods,evaluate and verify their predictive efficacy.To explore the application value of contrast-enhanced MRI imaging before ablation in the prognosis assessment of HCC patients,and to provide reliable data and theoretical basis for clinical treatment decisions.Methods A retrospective study was performed on 120 patients with HCC who underwent ablation and all the patients were underwent contrast-enhanced MRI examination within 1 month.A total of 1318 radiomic features were extracted from each patient by using preoperative T2-weighted sequence(T2WI)images of contrast-enhanced MRI.After feature selection,six machine learning algorithms would be used for construction of models and comparison.Finally,Logistic regression analysis was used to establish a clinical model,a radiomics model and a combined model which included the above risk factors and radiologic features.The nomogram was constructed based the combined model to evaluate the differentiation,accuracy and clinical benefit.Results Five radiomic features most closely related to early recurrence were identified and selected for model construction.The radiomic model had effective predictive performance,with AUC of 0.80 in the training sets.Two clinical risk factors associated with early recurrence,including tumor number and peritumoral hypodensity on the hepatobiliary phase,were selected to established a clinical-radiological-radiomics(CRRM)model,with AUC as high as 0.92 in the validation sets.The nomogram of CRRM model was constructed and the calibration curves indicated the goodness of fit.Decision curve analysis further confirmed the clinical usefulness of CRRM model.Conclusion The radiomics model of preoperatively contrast-enhanced MRI-T2WI image features was identified be effective to predict HCC early recurrence.In contrast,the CRRM model could be used as a more comprehensive and superior tool to predict individual probability of early recurrence.Patients at high risk of early recurrence could be identified and the appropriate and effective preoperative treatments could also be taken,to improve the prognosis and long-term survival rate of HCC patients the individualized treatment strategies should be formulated.

Objective To explore the expression of serum fatty acid-binding protein 4(FABP4)and fibroblast growth factor 19(FGF19)in patients with β-thalassemia and their relationship with clinical prognosis.Methods A total of 112 cases ofβ-thalassemia patients diagnosed and treated in Qianjiang Hospital Affiliated to Chongqing University from January 2018 to August 2020 were selected as the case group,and 60 healthy individuals who underwent physical examinations during the same period were taken as the control group.Enzyme-linked immunosorbent assay was used to detect levels of serum FABP4 and FGF19 expression.Multivariate logistic regression analysis was used to analyze factors affecting the prognosis of patients with β-thalassemia.Receiver operating characteristic curve was used to analyze the prognostic value of FABP4 and FGF19 in patients with β-thalassemia.Results The serum FABP4 level(67.13±11.35 μg/L)in the case group was higher than that in the control group(22.01±4.16μg/L),while the serum FGF19 level(104.24±21.46 ng/L)was lower than that in the control group(218.01±36.79 ng/L),with significant differences(t=29.708,25.620,all P＜0.05).The serum FABP4 levels(54.20±12.63 μ g/L,66.83±10.5 μ g/L,79.72±11.05 μ g/L)in the mild group,intermediate group,and severe group were increased sequentially,while FGF19 levels(122.53±22.36 ng/L,103.16±20.37 ng/L,86.53±18.14 ng/L)were decreased sequentially,and the differences were significant(F=39.701,24.231,all P＜0.05).Compared to the survival group,serum FGF19 level(62.80±22.09 ng/L vs 110.16±20.69 ng/L),Hb and the proportion of heterozygous genotypes in the death group patients(β CD17/β N,β CD41-42/β N)was lower,while serum FABP4(116.69±12.30 ng/L vs 60.05±10.17 ng/L),ferritin and the proportion of cardiac enlargement were higher,with significant differences(t/x2=4.436～18.981,all P＜0.05).FGF19(OR=0.634,95％CI:0.451～0.891)was an independent protective factor for β-thalassemia patients(P＜0.001),and serum FABP4(OR=1.840,95％CI:1.193～2.838)was an independent risk factor for prognosis(P＜0.001).The area under the curve(95％CI)of serum FABP4 and FGF19 combination in prognosis evaluation for β-thalassemia patients was 0.897(0.853～0.951),which was greater than the single serum indicator detection of 0.842(0.801～0.879)and 0.814(0.762～0.858),with significant differences(Z=4.864,5.270,P=0.002,0.001).Conclusion The serum FABP4 expression is increased,but serum FGF19 expression is decreased in patients with β-thalassemia.The combination of serum FABP4 and FGF19 may have a high predictive value for the prognosis of patients with β-thalassemia.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.