Objective To carry out rigid-body inverse dynamics modelling and analysis of a self-designed 6RSS parallel bio-inspired masticatory robot.Methods Firstly,the functions of kinematic variables including translational/rotational velocities and accelerations were derived for rigid-body inverse dynamics modelling.Secondly,the rigid-body inverse dynamics model was established with the Newton-Euler's law.Finally,the chewing motion trajectories of the oral health volunteers were tracked and numerical calculations were carried out in the case where the robot was subjected to a chewing reaction force.Results Numerical calculations showed that the driving torque and the constraint force of the robot peaked when the chewing reaction force was at its maximum.Conclusion The external force has a large impact on the inverse dynamics of the robot,and theoretical references are provided for the motion control and optimal design of the robot.[Chinese Medical Equipment Journal,2024,45(3):16-22]

Objective To investigate the effect and mechanism of andrographolide(AG)on lipopolysaccharide(LPS)-induced ferroptosis in renal tubular epithelial cells(HK-2 cells).Methods HK-2 cells were treated with LPS to simulate the in vitro HK-2 injury model of sepsis.The cells were further treated with AG of 5,10,20,40 μmol/L and randomly divided into control group,LPS group,LPS+dimethyl sulfoxide group(DMSO group),and AG group.Cell viability was detected by the CCK-8 method,and the optimal concentrations of LPS and AG were screened.Cell morphological change,the levels of kidney injury markers,including neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS),as well as the expression levels of ferroptosis regulatory proteins such as solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and ferritin in each group were compared,and the pro-tective effect of AG treatment on the cells was evaluated.Results Compared with the control group,the cell viabi-lity and GSH content decreased significantly in HK-2 cells treated with 10 μg/mL LPS;cell shrinkage and adhesion ability were poor;the contents of oxidative products MDA and ROS,as well as the levels of kidney injury markers NGAL and KIM-1 increased significantly,while expression levels of SLC7A11 and GPX4 protein decreased;ferritin expression level increased;differences were all statistically significant(all P＜0.05).Compared with LPS group,the cell viability,GSH content,as well as protein expression levels of SLC7A11 and GPX4 increased significantly after AG intervention,while ferritin expression level decreased,differences were all significant(all P＜0.05).MDA content,ROS fluorescence intensity,and the levels of kidney injury markers NGAL and KIM-1 decreased sig-nificantly,difference were all significant(all P＜0.05).Conclusion AG has a protective effect on LPS-induced HK-2 cell injury,possibly by activating SLC7A11/GPX4 pathway,reducing oxidative stress,up-regulating antioxi-dant enzyme activity,and alleviating ferroptosis.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.
Animals ; Mice ; Apolipoproteins E ; Atherosclerosis/genetics* ; Beclin-1 ; Cholesterol, LDL ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 2/genetics* ; Matrix Metalloproteinase 9/genetics* ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism* ; Plaque, Atherosclerotic ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/genetics* ; Vascular Cell Adhesion Molecule-1/genetics*

Interleukin-17 (IL-17) has been proved to be closely associated with the pathogenesis of various inflammatory skin diseases. Its main source is Th17 cells, whose differentiation is evoked by interleukin-23 (IL-23). Therefore, the IL-23/Th17 axis is an emerging target for the treatment of inflammatory skin diseases. IL-17 antagonists, IL-23 antagonists and IL-12/23 antagonists have shown satisfactory efficacy and safety in the treatment of psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris and SAPHO syndrome in latest clinical trials. Accordingly, this review mainly summarizes progress in molecular signaling pathways in and pathophysiological basis of the IL-23/Th17 axis in the occurrence of inflammatory skin diseases, as well as clinical application of different biological agents targeting this axis.

Objective:To analyze clinical characteristics and high-frequency ultrasound features of localized scleroderma, and to construct and validate a non-invasive prediction model for staging of skin lesions based on the high-frequency ultrasound features.Methods:Patients with localized scleroderma were retrospectively collected from the Department of Dermatology and Venereology, Second Xiangya Hospital of Central South University from February 1, 2021 to February 28, 2023, and clinical data as well as high-frequency ultrasound and pathologic features of 85 lesions from these patients were analyzed. Lesions were divided into modeling cohort and validation cohort according to the chronological order of patient enrollment. The univariate analysis and multivariable logistic regression models were used to analyze the independent influential factors in the staging of localized scleroderma lesions in the modeling cohort, construct the regression equation, and to build a nomogram prediction model. The Bootstrap validation method was used for internal validation, and the predictive performance of the nomogram model in the modeling cohort and validation cohort was further evaluated by the calibration curve and receiver operating characteristic (ROC) curve.Results:In the modeling cohort, 60 patients with localized scleroderma, including 16 males and 44 females, were enrolled, with the age [ M ( Q1, Q3) ] being 22.0 (10.0, 39.2) years, and there were 28 lesions in the oedematous phase and 32 lesions in the fibrotic and atrophic phase; in the validation cohort, 25 patients with localized scleroderma, including 8 males and 17 females, were enrolled, with the age being 18.0 (7.0, 30.0) years, and there were 9 lesions in the oedematous phase and 16 lesions in the fibrotic and atrophic phase. Univariate analysis in the modeling cohort showed no significant differences in the age and gender of patients or the location of lesions between the oedematous phase group and the fibrotic and atrophic phase group (all P > 0.05) ; compared with the oedematous phase group, the fibrotic and atrophic phase group showed an increased proportion of patients with disease duration ≥ 2 years (20/32 cases vs. 10/28 cases, χ2 = 4.29, P = 0.038), decreased thicknesses of the subcutaneous fat layer in skin lesions (1.4 [0.0, 26.0] mm vs. 1.8 [0.1, 14.3] mm, Z = -2.14, P = 0.032), increased decrements in the subcutaneous fat layer thickness in the lesional sites compared with non-lesional control sites (1.8 [0.5, 11.0] vs. 0.3 [-1.9, 8.0] mm, Z = -4.72, P < 0.001), increased ratios of the lesional elasticity values to control elasticity values (2.9 [1.8, 6.9] vs. 1.8 [1.1, 5.9], Z = -4.34, P < 0.001), and increased ultrasound-based lesional activity scores (5.0 [3.0, 8.0] points vs. 3.0 [0.0, 5.0] points, Z = -4.76, P < 0.001). Multivariable logistic stepwise regression analysis showed that the disease duration ≥ 2 years ( P = 0.032), increased ratios of the lesional elasticity values to control elasticity values ( P = 0.019), increased ultrasound-based lesional activity scores ( P = 0.013), and increased decrements in the subcutaneous fat layer thickness in the lesions compared with the controls ( P = 0.013) helped to confirm localized scleroderma lesions in the fibrotic and atrophic phase. Based on the results of regression analysis, a total of 4 factors were included in the nomogram prediction model, including the disease duration, the decrement in the subcutaneous fat layer thickness in lesions compared with controls, the ratio of the lesional elasticity values to control elasticity values, and the ultrasound-based lesional activity score; additionally, the constructed logistic regression model formula for predicting the probability (p) of skin lesions in fibrotic and atrophic phase was "ln (p/[1 - p]) = -9.595 + 2.204 × the disease duration + 0.784 × the decrement in the subcutaneous fat layer thickness in the lesions compared with the controls (mm) + 0.887 × the ratio of the lesional elasticity values to control elasticity values + 1.374 × the ultrasound-based lesional activity score". The calibration curve showed a good predictive performance of the model through the Bootstrap validation method, and the ROC curve demonstrated good discrimination and accuracy (modeling cohort: area under the curve = 0.936, 95% CI: 0.879 - 0.994; validation cohort: area under the curve = 0.889, 95% CI: 0.748 - 1.000) . Conclusions:High-frequency ultrasound could provide essential details for staging the localized scleroderma lesions. Based on the disease duration, subcutaneous fat layer thickness, skin elasticity values, and ultrasound-based lesional activity scores, the constructed prediction model could predict the stages of localized scleroderma lesions with excellent discrimination, accuracy, and predictive performance.

ObjectiveTo provide a new idea for exploring the molecular genetic approach to the pathogenesis of schizophrenia via construction of microRNA-messenger RNA （miRNA-mRNA） regulatory network in schizophrenia. MethodsThe microarray datasets of GSE54578 miRNA expression profiles in peripheral blood and GSE145554 mRNA expression in the anterior cingulate in postmortem brain of schizophrenic subjects were downloaded from Gene Expression Omnibus （GEO） database since July 2021. The GEO2R was used to identify the differentially expressed miRNAs and mRNAs， screen the miRNA with target differentially expressed mRNA， and predict their potential upstream transcription factors. The overlapping genes from the mRNA targeted by the differentially expressed miRNA and the mRNA differentially expressed in GSE145554 dataset were collected. Then the biological features of hub genes were analyzed via Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis， and the protein-protein interaction （PPI） network and miRNA-mRNA regulatory network of hub genes were constructed. ResultsA total of 8 up-regulated differentially expressed miRNAs with targeted mRNA were screened out in GSE54578 datasets regarding schizophrenia， which involved in the regulation of 10 transcription factors， 247 down-regulated differentially expressed mRNAs were screened out in GSE145554 datasets， and 17 overlapping mRNAs were obtained. GO analysis showed that the target mRNAs were mainly involved in astrocyte differentiation and development. KEGG pathway enrichment analysis showed that the target mRNAs were mainly involved in Rap1 and Ras signaling pathways. PPI network analysis showed that the mRNAs （KRAS and CD28） might be key genes in schizophrenia. ConclusionThe integrated bioinformatics analysis based on GEO database can identify potential susceptibility genes in schizophrenia， and it also contributes to the construction of miRNA-mRNA regulatory network in schizophrenia.

BACKGROUND: The pathogenesis of osteosarcoma (OS) is still unclear, and it is still necessary to find new targets and drugs for anti-OS. This study aimed to investigate the role and mechanism of the anti-OS effects of miR-296-5p. METHODS: We measured the expression of miR-296-5p in human OS cell lines and tissues. The effect of miR-296-5p and its target gene staphylococcal nuclease and tudor domain containing 1 on proliferation, migration, and invasion of human OS lines was examined. The Student's t test was used for statistical analysis. RESULTS: We found that microRNA (miR)-296-5p was significantly downregulated in OS cell lines and tissues (control vs. OS, 1.802 ± 0.313 vs. 0.618 ± 0.235, t = 6.402, P < 0.01). Overexpression of miR-296-5p suppressed proliferation, migration, and invasion of OA cells. SND1 was identified as a target of miR-296-5p by bioinformatic analysis and dual-luciferase reporter assay. Overexpression of SND1 abrogated the effects induced by miR-296-5p upregulation (miRNA-296-5p vs. miRNA-296-5p + SND1, 0.294 ± 0.159 vs. 2.300 ± 0.277, t = 12.68, P = 0.003). CONCLUSION Our study indicates that miR-296-5p may function as a tumor suppressor by targeting SND1 in OS.
Bone Neoplasms/genetics* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Endonucleases/genetics* ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; MicroRNAs/genetics* ; Osteosarcoma/genetics*

Objective: To investigate the feasibility of echocardiography-guided closed-chest repeated intraventricular blood sampling in mice, and to clarify the maximum blood volume that can be collected by this method, and whether the method can be used for long-term repeated blood collection in mice. Methods: Twenty-four male C57BL/6J mice (10-14 weeks old) were divided into the terminal experiment group (n=4, for investigating the maximum blood amount that could be sampled at one time), the repeated 0.5 ml blood collection group (n=10, sampling 0.5 ml whole blood each time, once every two days for consecutive 4 weeks), and the repeated 0.75 ml blood collection group (n=10, sampling 0.75 ml whole blood each time, once every two days for consecutive 4 weeks). High-frequency echocardiography was used to display the largest section of the left ventricle, guiding the insulin syringe needle through the thorax into the left ventricle for blood collection. In the repeated 0.5 ml blood collection group, echocardiography was used to detect the cardiac structure and function before blood collection, three minutes after blood collection, and one week after the last (the 14th) blood collection. Results: We successfully performed echocardiography-guided closed-chest intraventricular blood sampling, with an average operating time (88±19)s per mouse, and a maximum blood volume (1.43±0.11)ml per mouse. In the repeated 0.5 ml blood collection group, heart rate, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension and left ventricular posterior wall end-diastolic thickness remained uncganged before the first blood collection and after 4 weeks of repeated blood collection (all P>0.05). No death in the repeated 0.5 ml blood collection group. However, in the 0.75 ml blood collection group, two mice died before the end point. Conclusions: The echocardiography-guided closed-chest intraventricular blood sampling is a safe, minimally invasive, convenient and efficient method, and can be used repeatedly for long-term blood collection in mice.
Animals ; Echocardiography ; Feasibility Studies ; Heart Ventricles ; Male ; Mice ; Mice, Inbred C57BL ; Ventricular Function, Left