Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

Objective To explore the effect of open reading frame 66(C12ORF66)located at chromosome 12 on the viability of MYCN amplified NB cell lines.Methods DDatasets GSE16476 and GSE49710 in R2 database were analyzed for expression level of C12ORF66 in MYCN amplified and MYCN non-amplified NB cells and its potential correlation with the prognosis of pediatric patients.C12ORF66 mRNA expression level in normal tissue immortalized cell lines,MYCN amplified and MYCN non-amplified cell lines were detected by RT-qRCR.Transient or stable knockdown of C12ORF66 cell lines were constructed to compare the difference in real time cellular analysis(RTCA),colony formation,Ki67 positive cells between the control group and the C12ORF66 knockdown group.Results By analyzing R2 datasets,C12ORF66 level in MYCN amplified samples was significantly higher than that in MYCN non-amplified samples,and the expression of C12ORF66 was negatively correlated with the prognosis of pediatric patients(P＜0.05).C12ORF66 highly expressed in MYCN-amplified BE(2)-C and SK-N-BE(2)cell lines than in MYCN non-amplified CHLA-255 and SH-SY5Y cell lines(P＜0.001).Transient or stable knockdown of C12ORF66 resulted in significant slow down of proliferation of MYCN amplified NB cells(P＜0.001),the colony formation ability was significantly reduced(P＜0.001),and the proportion of Ki67 positive cells was significantly decreased(P＜0.05).Conclusions C12ORF66 was highly expressed in MYCN amplified clinical NB samples and cell lines which is believed to be correlated with poor prognosis of pediatric patients.C12ORF66 knockdown signifi-cantly inhibits cell viability of NB cells.

Objective:To delve deeply into the dynamic trajectories of cell subpopulations and the communication network among immune cell subgroups during the malignant progression of glioblastoma(GBM),and to endeavor to unearth key risk biomarkers in the GBM malignancy progression,so as to provide a more profound understanding for the treatment and prognosis of this disease by integrating tran-scriptomic data and clinical information of the GBM patients.Methods:Utilizing single-cell sequencing data analysis,we constructed a cell subgroup atlas during the malignant progression of GBM.The Mono-cle2 tool was employed to build dynamic progression trajectories of the tumor cell subgroups in GBM.Through gene enrichment analysis,we explored the biological processes enriched in genes that significant-ly changed with the malignancy progression of GBM tumor cell subpopulations.CellChat was used to identify the communication network between the different immune cell subgroups.Survival analysis helped in identifying risk molecular markers that impacted the patient prognosis during the malignant pro-gression of GBM.This methodological approach offered a comprehensive and detailed examination of the cellular and molecular dynamics within GBM,providing a robust framework for understanding the disease's progression and potential therapeutic targets.Results:The analysis of single-cell sequencing data identified 6 different cell types,including lymphocytes,pericytes,oligodendrocytes,macrophages,glioma cells,and microglia.The 27 151 cells in the single-cell dataset included 3 881 cells from the pa-tients with low-grade glioma(LGG),10 166 cells from the patients with newly diagnosed GBM,and 13 104 cells from the patients with recurrent glioma(rGBM).The pseudo-time analysis of the glioma cell subgroups indicated significant cellular heterogeneity during malignant progression.The cell interaction analysis of immune cell subgroups revealed the communication network among the different immune sub-groups in GBM malignancy,identifying 22 biologically significant ligand-receptor pairs across 12 key bio-logical pathways.Survival analysis had identified 8 genes related to the prognosis of the GBM patients,among which SERPINE1,COL6A1,SPP1,LTF,C1S,AEBP1,and SAA1L were high-risk genes in the GBM patients,and ABCC8 was low-risk genes in the GBM patients.These findings not only provided new theoretical bases for the treatment of GBM,but also offered fresh insights for the prognosis assessment and treatment decision-making for the GBM patients.Conclusion:This research comprehensively and pro-foundly reveals the dynamic changes in glioma cell subpopulations and the communication patterns among the immune cell subgroups during the malignant progression of GBM.These findings are of significant im-portance for understanding the complex biological processes of GBM,providing crucial new insights for precision medicine and treatment decisions in GBM.Through these studies,we hope to provide more ef-fective treatment options and more accurate prognostic assessments for the patients with GBM.

Objective:To Investigate the prevalence of cancer related muscle disorder (CRMD) in hospitalized lung cancer patients, and to identify the possible risk factors.Methods:This study was a cross-sectional study. The study enrolled 259 patients without missing data who met the inclusion and exclusion criteria from 347 lung cancer patients who were non-repeated hospitalized in the Department of Respiratory and Critical Care Medicine of Peking Union Medical College Hospital from March 2023 to August 2023. Bioimpedance analysis was used to measure muscle mass in patients, and dietary information was collected using the food frequency questionnaire. Disease information and laboratory test results were obtained by consulting Hospital Information System. According to AWGS 2019, patients were divided into five groups: possible sarcopenia (PS), sarcopenia (S), severe sarcopenia (SS), low muscle mass (LMM), and non-muscle disorder (non-MD). The analysis of variance, Kruskal-Wallis test, and χ 2 test were used to compare differences in baseline data, energy and macronutrient intake, and laboratory test indicators among different groups, and ordered logistic regression analysis was applied for multivariate analysis to identify the influencing factors of CRMD in lung cancer patients. Results:This study included 259 hospitalized lung cancer patients who met the inclusion and exclusion criteria. The prevalence of CRMD among 259 patients was 64.5%, PS was 27.4%, S was 13.5%, SS was 14.3%, and LMM was 5.4%. plant protein intake ( OR=0.969, 95% CI: 0.942-0.996) and regular exercise ( OR=0.485, 95% CI: 0.269-0.869) were found to be protective factors for CRMD in hospitalized lung cancer patients, while age ( OR=1.056, 95% CI: 1.013-1.101), weight loss of more than 5% in the last six months ( OR=4.546, 95% CI: 1.363-15.563), and diabetes ( OR=2.342, 95% CI: 1.137-4.866) were identified as risk factors. Conclusion:The prevalence of CRMD in hospitalized lung cancer patients is relatively high, and is closely related to age, weight changes, exercise, comorbidities, and dietary intake.

AIM:To investigate the therapeutic effect of raddeanin A(RA)on prostate cancer xenograft mouse model,and to explore its potential mechanisms.METHODS:(1)Western blot analysis was used to investigate the effects of different concentrations(0,0.5,1,2 and 4 μmol/L)of RA on the expression of programmed cell death li-gand 1(PD-L1)protein in prostate cancer cell lines PC-3,DU145 and RM-1.(2)Thirty C57BL/6J mice were randomly divided into blank group,low-dose RA group,and high-dose RA group,with 10 mice in each group.The mice in low-and high-dose RA groups were intraperitoneally injected with 2 and 4 mg/kg RA continuously for 24 d,respectively.Mouse body weight was recorded,and tumor volume and weight were measured.Immunohistochemistry experiments were con-ducted to detect the expression of Ki67 and PD-L1 proteins in mouse tumor tissues.Flow cytometry was used to determine the percentages of CD8+T cells,CD4+T cells and regulatory T cells(Treg),as well as the levels of interferon-γ(IFN-γ)and granzyme B(GzmB)in tumor tissues.RESULTS:Treatment with RA significantly reduced the expression of PD-L1 in PC-3,DU145 and RM-1 cells(P<0.05 or P<0.01).In vivo experiments showed that RA treatment led to significant decreases in tumor volume and weight(P<0.05 or P<0.01).Additionally,the expression levels of Ki67 and PD-L1 in tu-mor tissues were significantly reduced(P<0.05 or P<0.01).Furthermore,RA treatment significantly increased the per-centages of CD8+T cells and CD4+T cells within mouse tumors,elevated the levels of IFN-γ and GzmB,and reduced the number of activated Treg(P<0.05 or P<0.01).CONCLUSION:The RA exhibits potent inhibitory effects on tumor growth in a prostate cancer xenograft mouse model.Its mechanism may be associated with the inhibition of PD-L1 expres-sion,increased infiltration of tumor-infiltrating T cells,and suppression of Treg.

Objective:This study aims to assess the effects of soy and whey protein on body composition and muscle function in hospitalized lung cancer patients with cancer-related sarcopenia.Methods:Paired comparison method was adopted for data collected before and after intervention. All enrolled non-small cell lung cancer patients with cancer-related sarcopenia were assigned to either the soy protein (30 g/d) or the whey protein (30 g/d) group to receive the 12-week intervention. Changes in muscle mass (MM) and muscle function before and after intervention were observed to assess intra-group and inter-group differences.Results:The study included 48 patients, 32 of whom completed the intervention and follow-up (16 from the whey protein group and 16 from the soy protein group). After 12 weeks of intervention with whey protein, significant increases were observed in trunk muscle mass (TMM, P=0.014) and TMM adjusted for height (TMM/Ht 2, P=0.011). After 12 weeks of intervention with soy protein, significant increases were noted in appendicular muscle mass (AMM, P=0.049), AMM adjusted for body mass index (AMM/BMI, P=0.044), fat free mass (FFM, P=0.041), and MM ( P=0.038). After adjustment using generalized estimating equations, only TMM/Ht 2 ( P=0.049) showed a significant increase in the whey protein group, while TMM ( P=0.040) and TMM/Ht 2 ( P=0.005) significantly increased in the soy protein group. Despite that all MM-related indices increased in both groups, there were no significant inter-group differences after adjusted by covariate analysis. Conclusions:Interventions with soy protein and whey protein can help maintain and improve muscle mass and muscle function in patients with lung cancer-related sarcopenia. Soy protein and whey protein may have comparable benefits in patients with lung cancer-related sarcopenia.

Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

Objective:To identify characteristic genes in sarcopenia patients through bioinformatics and machine learning, and to explore the clinical relevance of characteristic genes in the diagnosis of sarcopenia.Methods:The microarray data of GSE25941, GSE38718 and GSE9103 associated with sarcopenia were downloaded from the GEO database, followed by identification of differentially expressed genes (DEGs) associated with sarcopenia. Subsequently, functional analysis of the DEGs was performed using gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, while biomarkers of sarcopenia were identified using LASSO regression and random forest analysis. The diagnostic performance of the characteristic gene was assessed by employing receiver operating characteristic (ROC) curve analysis. Furthermore, the expression levels of biomarkers for sarcopenia were validated using the external validation dataset of GSE28422. Finally, CIBERSORT was employed to analyze the infiltration of immune cells.Results:124 DEGs were identified between control and sarcopenia populations, which were primarily involved in growth factor receptor binding and cytokine activity. KEGG analysis revealed that the DEGs were predominantly associated with signaling pathways such as peroxisome proliferator-activated receptor signaling pathway, adipokine signaling pathway, Jak-STAT signaling pathway, and adenosine 5'-monophosphate (AMP)-activated protein kinase signaling pathway. Through machine learning techniques validated by ROC curve analysis and external datasets, three characteristic genes, namely DMRT2, FAM171A1, and ARHGAP36, were discovered. The infiltration analysis of immune cells revealed the potential involvement of mast cells, CD4 memory T cells, CD8 cells, γδT cells, and neutrophils in the pathophysiology of sarcopenia.Conclusion:DMRT2, FAM171A1 and ARHGAP36 can serve as diagnostic biomarkers of sarcopenia, and are closely related to the pathophysiological process of sarcopenia.

An on-line HPLC-DPPH system was developed to determine the antioxidant activity of 16 batches of Polygoni Multiflori Radix Praeparata. By analyzing the chromatographic and biological activity fingerprints of 16 batches of Polygoni Multiflori Radix Praeparata, the dose-effect relationship was established and the total antioxidant activity was quantified by activity addition.The results suggested that the online HPLC-DPPH method can evaluate the antioxidant activity of different bathches of Polygoni Multiflori Radix Praeparata, with different processing methods, aiming to provide datasupport and scientific basis forquality evaluation of Polygoni Multiflori Radix Praeparata.

Objective:To translate the English version of Collaborative Practice Assessment Tool (CPAT) into Chinese and test the reliability and validity of the Chinese version.Methods:In accordance with Brislin translation principles, two rounds of expert consultation were used for cross-cultural adaption, and the Chinese version of CPAT was formed. Using the random cluster sampling, a total of 620 medical staff from 8 tertiary hospitals in Shanghai were selected from April to July 2020 to conduct a survey to measure reliability and validity of the scale.Results:The Chinese version of CPAT consisted of 56 items in 8 dimensions. Exploratory factor analysis extracted a total of 8 common factors and the cumulative variance contribution rate was 82.473%. The Cronbach's α coefficient of the total scale was 0.984 and the Cronbach's α coefficients of each dimension were 0.934 to 0.971. The split-half reliability was 0.869, and the test retest reliability was 0.857. The content validity index at the item level of the scale was from 0.80 to 1.00 and the content validity index at the scale level was 0.96.Conclusions:The Chinese version of CPAT has good reliability and validity, which can be used as an evaluation tool for the domestic interprofessional medical team collaboration practice level.