Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

To explore the potential mechanism of frankincense volatile oil in the prevention and treatment of cardiac hypertrophy based on in vitro cell experiment and network pharmacology. METHODS: The anti-hypertrophic effect of frankincense volatile oil was investigated by isoproterenol induced H9c2 cardiomyocytes hypertrophy model. The active chemical components and targets of frankincense volatile oil and targets associated with cardiac hypertrophy were obtained by CNKI, Pubmed, Pubchem databases, etc. String database and Cytoscape 3.8.0 software were used to construct protein-protein interaction network (PPI) and a network of "drug-active component-key target-disease" of frankincense volatile oil in order to screen the key targets of frankincense volatile oil against cardiac hypertrophy. The fluorescent quantitative PCR experiments were performed to verify those key targets. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis of key target genes were performed using David online analysis tool. RESULTS: In vitro cell experiments showed that frankincense volatile oil significantly inhibited the isoproterenol induced increases in cardiomyocytes surface area and protein synthesis, and upregulations of ANP and β-MHC mRNA. A total of 87 active components and 36 ingredient-disease targets of frankincense volatile oil were screened. Network analysis showed that ESR1, NOS3, PTGS2, TNF, MAPK14, and PPARG were key targets. Fluorescence quantitative PCR experiments results indicated that frankincense volatile oil inhibited isoproterenol induced upregulations of ESR1, PTGS2, TNF, and MAPK14 mRNA levels, and downregulations of NOS3, PPARG mRNA levels, respectively. In addition, the GO functional enrichment analysis showed that its biological pathways mainly included lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthetic process, caveola, enzyme binding, etc. The KEGG pathway enrichment analysis included 22 KEGG pathways, which were closely related to VEGF signaling pathway, TNF signaling pathway, sphingolipid signaling pathway and others. CONCLUSION: The active components of frankincense volatile oil may regulate VEGF signaling pathway, TNF signaling pathway, Sphingolipid signaling pathway by acting on ESR1, NOS3, PTGS2, TNF, MAPK14 and PPARG targets, thereby affecting the regulation of lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthetic process, caveola, and enzyme binding, and improving cardiac hypertrophy.

Objective:To explore the value of low-dose CT in pregnancy with COVID-19.Methods:A retrospective analysis was performed on the clinical characteristics, laboratory tests, and chest CT findings of 12 pregnant women with COVID-19 diagnosed by nucleic acid testing in the Renmin Hospital of Wuhan University from January 20, 2020 to February 16, 2020. Two radiologists blinded to the reconstruction algorithm independently scored subjective image quality on a 5-point Likert scale. Image quality score ≥ 3 was acceptable in clinics. The CT radiation doses were recorded, including CT volume dose index (CTDI vol), dose length product (DLP), and effective radiation dose ( E). Two radiologists observed the distribution, shape, density, and other characteristics of lung lesions, and they also decided whether hilar, mediastinal lymphadenopathy, and pleural changed. Results:A total of 12 pregnant women with COVID-19, 8 had cough, 4 had fever, 2 had chest tightness, and 1 had dyspnea and diarrhea each. The CT image quality score of all patients was 3-4, with an average of 3.46, which fully met the clinical diagnosis requirements. The CTDI vol value was 1.13-4.31 mGy, with an average of 3.02 mGy. The DLP value was 34.48-75.29 mGy·cm, with an average of 55.48 mGy·cm. The Evalue was 0.48-1.05 mSv, with an average of 0.78 mSv. In all cases, chest CT examination showed abnormal manifestations after clinical symptoms, including unilateral lung lesions in 5 cases and bilateral lung lesions in 7 cases, 1 case of ground-glass opacity, 1 case of solidification, 7 cases of ground-glass and consolidation, 1 case of strip opacity, ground-glass, and consolidation and strip cable shadow coexisted in 2 cases. Conclusions:The application of low-dose CT scan in pregnant women with COVID-19 is completely feasible. CT mainly manifested as bilateral lung patchy and flaky ground-glass opacity with consolidation. Active and effective treatment can help recover and improve prognosis.

OBJECTIVETo investigate the effect of atorvastatin on platelet aggregation and activation in the acute phase following balloon-induced carotid artery injury in rabbits fed cholesterol-enriched diet.

METHODSThirty rabbits were randomly divided into 5 equal groups, namely control group, high-cholesterol group, model group, low-dose (5 mg/kg daily) atorvastatin group, and high-dose (10 mg/kg daily) atorvastatin group. Platelet aggregation rate was measured in the rabbits by turbidimetric platelet aggregometry, and the changes of serum P-selectin and thromboxane B2 (TXB2) levels were detected with enzyme-linked immunosorbent assay (ELISA).

RESULTSCompared with those in the control group, serum P-selectin level increased significantly (P<0.01) but platelet aggregation rate and TXB2 level exhibited no obvious changes in high-cholesterol group. After carotid artery balloon injury, P-selectin and TXB2 levels and platelet aggregation significantly increased in cholesterol-fed rabbits, reaching the peak level at 24 h after the injury (P<0.01). Compared with the model group, low-dose atorvastatin treatment significantly decreased P-selectin and TXB2 levels and inhibited platelet aggregation in cholesterol-fed rabbits following carotid artery balloon injury (P<0.01), and such effects of atorvastatin were more prominent at a higher daily dose of 10 mg/kg (P<0.05).

CONCLUSIONSCarotid artery balloon injury in rabbits fed cholesterol-enriched diet can induce platelet activation and aggregation, which reaches the peak level at 24 h after balloon injury and can be dose-dependently inhibited by atorvastatin in the acute phase following the injury.

Animals ; Atorvastatin Calcium ; Blood Platelets ; Carotid Artery Injuries ; drug therapy ; Cholesterol ; Enzyme-Linked Immunosorbent Assay ; Heptanoic Acids ; pharmacology ; P-Selectin ; metabolism ; Platelet Activation ; Platelet Aggregation ; Pyrroles ; pharmacology ; Rabbits ; Thromboxane B2 ; metabolism

Objective To assess the effectiveness of Z-axis automatic tube current modulation ( ATCM) technique with respect to dose reduction and image noise in the thyroid regional tissues during neck computed tomography angiography (CTA). Methods A total of 140 patients underwent neck CTA with 64-slice spiral CT, and were randomized into fixed-tube current group and ATCM group. Objective noise, CTDIw, DLP and mA of each group were recorded. Results The image qualities of all the patients were diagnostically acceptable, though the objective noise of neck in the ATCM group was higher than that in the group of fixed-tube current (P＜ 0.05 ). The radiation doses in the ATCM group [ CTDIw (35.99±1.31 ) mGy, DLP (11 121.39 ±5.51) mGy·cm] were significantly inferior to those in the group of fixed tube current [ CTDIw (43.22±1.42) mGy, DLP (1514.45±5.56) mGy·cm]. Conclusions Compared with fixedtube current technique, ATCM technique could significantly reduce the radiation dose in neck CT with diagnostic acceptability of the image quality.

AIM: To investigate the effects of adenovirus-mediated human tissue kallikerin (Ad-hKLK1) gene delivery on the proliferation, migration of VSMC_(SHR) induced by platelet derived growth factor-BB (PDGF-BB). METHODS: The VSMC_(SHR) proliferation induced by PDGF-BB was accessed by cell counting and methyl thiazolyl tetrazoliuin (MTT). The migration was assessed by modified Boyden chamber assay. Western blotting was used to determine the expressions of the cycle-independent kinase inhibitors p27~(Kip1) and p21~(Cip1).RESULTS: Proliferation of VSMC_(SHR) induced by PDGF-BB was inhibited after transfection of Ad-hKLK1 (20-100 MOI) in a MOI-dependent manner. The peak inhibition titer of Ad-hKLK1 fell on 100 MOI, with the peak inhibition rate of 39.3% (cell counting, n=3, P<0.01), 30.2% (MTT, n=3, P<0.01), peak stunning rate of cell-cycle in phase G0/G1 at 36.4%. The inhibitory effects of proliferation and cell-cycle caused by hKLK1 gene delivery were significantly abolished by Hoe140, a bradykinin B2 receptor antagonist. Migration of VSMC_(SHR) induced by PDGF-BB was inhibited after hKLK1 gene delivery, with the peak inhibitory rate of 34.6% (n=6, P<0.01). However the inhibitory effects of migration were not blocked by Hoe140. The protein expression of p27~(Kip1) and p21~(Cip1) increased significantly after the hKLK1 gene delivery, whereas Hoe140 nearly completely blocked these effects (n=3, P<0.01, respectively).CONCLUSION: The hKLK1 gene delivery may inhibit the proliferation and migration of VSMC_(SHR) induced by PDGF-BB. Bradykinin B2 receptor probably mediates the up-regulating expression of p27~(Kip1) and p21~(Cip1) that contributes to the inhibitory effects of proliferation of hKLK1. However, the inhibitory effects of migration by hKLK1 gene delivery may not be mediated by bradykinin B2 receptor.

0.05). However, monocrotaline significantly increased WT% and WA% of pulmonary arterioles (WT:39.1%?2.8% vs 50.8%?3.1%, WA:51.2%?3.0% vs 74.5%?2.9%, P

Objective To investigate the influence of Angiopoietin-1(Ang1)gene modified mesenchymal stem cells on the expression of adhension factors from endothelial cells,to clarify the feasibility of modulating inflammation reaction by gene modification after stem cells transplantation.Methods Genetic engineering rMSCs were constructed by lentivirally-tranduced Ang1 gene,the expressions of ICAM-1 and VCAM-1 at different time points after 20 ?g/L VEGF stimulating were investigated,the supernatants of gene modified rMSC were collected and then added into HUVEC culture with different concentrations of Ang1,the expressions of adhension factors after VEGF stimulated were observed at the same time.Results Genetic engineering rMSCs were successfully constructed,the expressions of ICAM-1 and VCAM-1 mRNA were significantly increased after VEGF stimulated,the maximal value was at 8 h,the ICAM-1 and VCAM-1 mRNA expressions were decreased after incubation with Ang1 at different concentrations,Ang1 suppressed the VEGF-stimulated protein levels of ICAM-1 and VCAM-1.Conclusion The supernatants of Ang1 gene modified stem cells can suppresse VEGF-stimulated inflammation reaction of HUVEC.

[Objective] To study the effect on the growth of mouse Lewis lung carcinoma and on the expression of VEGF in tumor tissue.[Methods] C57BL/6 mice were inoculated the Lewis lung carcinoma cell at right armpit and divided into groups.Different groups were administered by MAALC(low,normal and high dose),CTX or saline.After 15 days,all mice were put to death to detach the tumors then weighed them.After that,we treated tumor tissue with VEGF immunohistochemistry stain,detected the integral optical density of VEGF expression with image analytical technique.[Results] Compared with model group,the average weight and VEGF expression level of the tumors of the high dose group were less and statistically significant(P