Construction of porous structure on the surface of PLLA/β-tricalcium scaffold and its effect on cell adhesion / 西安交通大学学报(医学版)

【Objective】 To construct a 3D printed PLLA/β-tricalcium (PLLA/β-TCP) bone tissue engineering scaffold surface porous structure through simple treatment with NaOH solution, increase the roughness and hydrophilicity of the scaffold, and promote cell adhesion on the scaffold surface. 【Methods】 The PLLA/β-TCP mesh scaffold was prepared by 3D printing melt deposition molding technology, and the scaffold was roughed by NaOH etching. The effects of NaOH concentration and time on the scaffold were observed according to the microstructure, energy spectrum, contact angle, mechanics, and cell adhesion of the scaffold. 【Results】 The PLLA/β-TCP composite scaffold constructed by melt deposition technology had a pre-set porous structure, and the pores were interconnected. After NaOH etching, a porous structure with both macroscopic and microscopic pores was formed. The increase in any of the NaOH concentration and time parameters would lead to the increase of pore diameter and surface roughness. When the NaOH treatment parameter was 0.1 mol/L (9 h), it could significantly reduce the water contact angle on the surface of the scaffold, and had no significant effect on the compressive strength of the scaffold. In vitro cell testing showed that the surface porous composite scaffold etched with NaOH had more advantages in the adhesion and proliferation of BMSCs. 【Conclusion】 Using NaOH to process 3D printing of PLLA/β-TCP bone tissue engineering scaffolds can effectively improve the surface morphology of the scaffold, and optimize its hydrophilicity and cell adhesion.

Improving the surface hydrophilicity and performance of 3D printed PCL/β-TCP mesh support by sodium hydroxide alkali etching method / 西安交通大学学报(医学版)

【Objective】 To solve the problem of insufficient hydrophilicity on the surface of polycaprolactone (PCL)/β-TCP bone tissue engineering scaffolds, NaOH etching method was used to improve the surface microstructure of 3D printed PCL/β-TCP scaffolds, further affecting their hydrophilicity and cell response. 【Methods】 PCL/β-TCP mesh scaffolds were prepared using 3D printing melt deposition molding technology, and the surface roughness of the scaffolds was modified by NaOH etching. The effects of two reaction parameters, NaOH concentration and time, on the microstructure, spectral elements, contact angle, compressive strength, and cell adhesion of the scaffolds before and after modification were observed. 【Results】 After NaOH etching, the surface microporous structure of the mesh scaffold was successfully prepared. With the increase of either NaOH concentration or time, the surface micropores of the scaffold increased while the contact angle of the material surface decreased. However, the compression strength of the etched scaffold treated with NaOH for 1 mol/L (24 h) or 10 mol/L (6 h) was not statistically significant compared to the untreated group (P>0.05). The number of cells on the etched scaffold increased, with a larger spreading area of individual cells, making it more advantageous in the adhesion and proliferation of BMSCs. 【Conclusion】 The use of NaOH etching to improve the hydrophilicity of 3D printed PCL/β-TCP bone tissue engineering scaffolds is a low-cost and effective strategy which can effectively improve the wettability and cell adhesion of the scaffolds.

Effects of canagliflozin on amino acid metabolism in atherosclerotic mice / 中华心血管病杂志

Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

Effects of canagliflozin on amino acid metabolism in atherosclerotic mice / 中华心血管病杂志

Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

Effect of orthokeratology combined with 0.01% atropine solution on adolescents with myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy and safety of orthokeratology combined with 0.01% atropine solution in adolescents with myopia.METHODS: A total of 100 adolescent myopic patients(100 right eyes)who received treatment at the Department of Ophthalmology, People's Hospital of Hengshui from January 2019 to January 2022 were enrolled. All patients were divided into two groups based on the patient's preferences and randomized controlled principles: control group(n=50)and experimental group(n=50). Patients in the control group received orthokeratology alone, while those in the experimental group received orthokeratology in combination with 0.01% atropine solution. Treatment data for both groups were collected at 1, 3, 6, 9 and 12mo after treatment. The observed indicators included refraction, corneal curvature, axial length(AL), central corneal thickness(CCT), pupil diameter(PD), lipid layer thickness(LLT), break-up Time(BUT), root-mean-square of higher-order aberration(RMSh), subfoveal choroidal thickness(SFCT), corneal endothelial cell density(CD), and hexagonal cell ratio(HEX). The adverse reactions experienced during follow-up period were also observed and recorded.RESULTS: After 12mo of treatment, the refraction, corneal curvature, and AL in the experimental group were -2.42±0.17D, 38.89±1.18D and 25.44±0.23mm, respectively, which were significantly better than the control group(-2.56±0.19D, 40.12±1.65D and 25.54±0.19 mm, all P&#x003C;0.05). The CCT of the experimental group(538±33 μm)was lower than that of the control group(545±41 μm), while the PD of the experimental group was higher than that of the control group(6.38±0.38 mm vs. 6.12±0.37 mm, P&#x003C;0.05). LLT and BUT in the experimental group was 61.14±8.41 nm and 9.24±2.05s, respectively, which were significantly higher than those in the control group(56.14±7.22 nm and 7.27±1.99s, all P&#x003C;0.05). RMSh in the experimental group was lower than that of the control group(0.73±0.21 μm vs. 0.85±0.12 μm, P&#x003C;0.05), and SFCT in the experimental group was significantly higher than that of the control group(289±55 μm vs. 282±59 μm, P&#x003C;0.05). Additionally, after 12mo of treatment, there was no significant difference in CD and HEX between the experimental group and the control group(all P&#x003E;0.05). The main adverse reactions of both groups during treatment period were photophobia, anaphylaxis, conjunctivitis and keratitis, but there was no significant difference between the two groups(all P&#x003E;0.05).CONCLUSION: Compared to orthokeratology alone, the combination of orthokeratology and 0.01% atropine solution effectively prevents and improves the development of adolescent myopia without increasing the incidence of adverse reactions.

Study on in vitro differentiation of human adenoid-derived mesenchymal stem cells into olfactory sensory neurons / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility of isolation and culture of human adenoid-derived mesenchymal stem cells (aMSCs) in vitro, and to observe the differentiation of aMSCs into olfactory sensory neurons. Methods: Adenoid tissues surgically removed from children with adenoid hypertrophy in the Second Xiangya Hospital of Central South University from September to November of 2020 were collected. The adenoid tissues were digested and isolated by trypsin and then cultured with adhesion method. The expressions of cell surface antigens CD45, CD73 and CD90 on aMSCs of P5 generation were tested by flow cytometry, and the ability of osteogenic and adipogenic induction were used to identify cell differentiation ability. Then, aMSCs were induced into differentiation by retinoic acid (RA), sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), RA+SHH, RA+bFGF, SHH+bFGF and RA+SHH+bFGF, respectively. The morphology of differentiated cells was observed under inverted microscope. The expression of β-tubulin 3, which was the specific marker of sensory neuron, the expressions of growth associated protein-43 (GAP43) and olfactory maker protein (OMP), which were the specific markers of olfactory sensory neuron, were detected by immunofluorescence antibody assay. The expression intensities were compared by Chi-square test of four-grid table data. Results: aMSCs were successively isolated and cultured from human adenoid tissues. P0 cells generation had good adhesion and proliferation performance. P2 cells were basically purified. P5 cells expressed CD73 and CD90 with the purity of 99.3% and 99.75% respectively, without CD45 expression. P5 cells had a good ability of osteogenic differentiation and adipogenic differentiation. Neuron-like morphology and expression of β-tubulin 3 were found in differentiated cells after induced by RA, SHH, or bFGF, respectively. An induction of expression of GAP43 was found in differentiated cells of bFGF+SHH group and RA+SHH+bFGF group, without expression of OMP of each group. The intensity of GAP43 expression of RA+SHH+bFGF group was stronger than that of bFGF+SHH group (χ2=17.48, P<0.005). Conclusions: aMSCs can be cultured from human adenoid tissues, with the stably passaged and good differentiation ability. As a new population of mesenchymal stem cells, aMSCs have the neuroregenerative properties and could differentiate into immature olfactory sensory neurons under the induction of RA+SHH+bFGF in vitro.

Regulation of platelet function by cantharidin via PI3K/Akt/PKC pathway / 中国药理学通报

To investigate the effect of cantharidin ( CTD) on platelet function and the mechanism of anti-platelet aggregation. Methods Washed platelets were collected from the venous blood of healthy volunteers. The effect of CTD on platelet aggregation and release was determined by aggregometer. The CTD concentration was 2.5 ,5 ,10 μmol • L

Realgar inhibits proliferation, invasion and induces cellular ferroptosis in esophageal cancer cells / 中国药理学通报

Aim To investigate the effects of realgar on the proliferation, invasion and ferroptosis of esophageal cancer cells. Methods Different concentrations of realgar(0, 10,20, 40, 60, 80, 100 μmol·L-1)or realgar 1/2IC

Dissecting the Neural Circuitry for Pain Modulation and Chronic Pain: Insights from Optogenetics / 神经科学通报·英文版

Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The processing of pain involves complicated modulation at the levels of the periphery, spinal cord, and brain. The pathogenesis of chronic pain is still not fully understood, which makes the clinical treatment challenging. Optogenetics, which combines optical and genetic technologies, can precisely intervene in the activity of specific groups of neurons and elements of the related circuits. Taking advantage of optogenetics, researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission, pain modulation, and chronic pain both in the periphery and the central nervous system. In this review, we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.

Screening of traditional Chinese medicine-derived snail control drug targets based on network pharmacology / 中国血吸虫病防治杂志

Objective To screen the targets of traditional Chinese medicine-derived potential plant molluscicides based on network pharmacology and explore the mechanisms of molluscicidal actions. Methods The traditional Chinese medicines with molluscicidal actions were screened based on retrospective literature reviews, and their molluscicidal efficiency was summarized. The active ingredients and potential targets of traditional Chinese medicines were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Unified Protein Database and literature mining using network pharmacology. The drug-active ingredient-target network was created using the software Cytoscape 3.7.2, and the key targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the Metascape software. Results A total of 27 types of snail control drugs derived from traditional Chinese medicines were screened from publications and classified into 14 categories. Network pharmacology identified 190 active ingredients, and the active ingredients with a high degree in the drug-active ingredient-target network included quercetin, linoleyl acetate, luteolin, beta-carotene, (24S)-ethylcholesta-5,22,25-trans-3beta-ol, fumarine and arctiin, with 181 corresponding potential targets screened. KEGG pathway enrichment analysis revealed that these targets were mainly located in 16 pathways, including the neuroactive ligand-receptor interactions, regulation of adipocyte lipolysis and adrenergic signal in myocardial cells. Conclusions This study preliminarily demonstrates the multi-ingredient, multi-target and multi-pathway mechanisms of action of 27 molluscicides. The screened key ingredient may provide the basis for isolation, purification and pharmacological studies of molluscicides, and the screened key targets and key pathways may facilitate the illustration of mechanisms of actions of traditional Chinese medicine-derived molluscicides and development of novel green molluscicides.

Molecular Mechanism of "Transmission Between Lung and Brain" of Influenza and Intervention Effect of Maxing Shigantang Based on JAK1/STAT1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of "transmission between the lung and brain" of influenza based on Janus kinase 1/signal transducer and activator of transcription 1（JAK1/STAT1） signaling pathway and further investigate the intervention effect of Maxing Shigantang （MXSGT）. MethodA total of 100 SPF BALB/c mice were randomly divided into a normal group，a model group，an oseltamivir group （21.63 mg·kg-1·d-1），an antiviral granules group（3.9 g·kg-1·d-1）， and an MXSGT group（6.05 g·kg-1·d-1）， with 20 mice in each group. The pneumonia model was induced in mice except for those in the normal group by intranasal infection of influenza A virus（IAV）. Twenty-four hours after modeling，mice were treated with corresponding drugs， while those in the normal group and the model group received the same amount of normal saline by gavage， once a day for 3 and 7 days. The pathological changes in the lung and brain were observed by hematoxylin-eosin（HE）staining. The mRNA expression of IAV nucleoprotein（NP），JAK1， and STAT1 in the lung and brain was detected by real-time quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of JAK1 and STAT1 in the lung and brain was detected by Western blot. Immunohistochemical method was used to detect the expression of phosphorylated（p）-STAT1 in the lung and brain tissues， and enzyme-linked immunosorbent assay（ELISA） was used to detect the serum levels of interleukin-1β（IL-1β） and interleukin-10（IL-10）. ResultCompared with the normal group， the model group showed obvious pathological changes in the lung tissues and cerebral cortex， increased relative mRNA expression of IAV NP in the lung （P<0.01）， elevated mRNA and protein expression of JAK1 and STAT1 in the lung and brain tissues （P<0.05，P<0.01），up-regulated expression level of p-STAT1 in lung tissues and cerebral cortex （P<0.05，P<0.01）， and increased serum level of IL-1β （P<0.05）. Compared with the model group， the MXSGT group showed alleviated pathological damage to lung tissues and cerebral cortex， decreased relative mRNA expression of IAV NP in lung tissues（P<0.01），reduced mRNA and protein expression levels of JAK1 and STAT1 in lung tissues and brain tissues（P<0.05，P<0.01）， and increased serum level of IL-10（P<0.01）. ConclusionThe abnormal activation of the JAK1-STAT1 signaling pathway may be one of the molecular mechanisms of "transmission between the lung and brain" of influenza. As an effective compound prescription against the influenza virus，MXSGT can alleviate the pathological damage of brain tissues in mice infected with IAV by regulating the level of cytokines mediated by this pathway.

Neoseq for neonatal screening of fatty acid oxidation disorders / 中华围产医学杂志

Objective:To explore the value of Neoseq in screening and diagnosis of neonatal fatty acid oxidation disorders (FAOD).Methods:A retrospective case-control study was conducted on 163 500 live births in Changzhou city from April 2015 to April 2021. The following two models were adopted for FAOD screening and diagnosis. (1) Traditional mode: Heel blood samples were obtained from all subjects for initial screening using tandem mass spectrum (TMS), followed by next-generation sequencing (NGS) and other differential diagnostic testings for those with positive results. (2) Neoseq: Neoseq was performed on the true positive, negative and false positive cases according to the traditional mode screening results. The detection rate, additional discovery, reporting period, and other parameters of the two models for FAOD were described and compared.Results:(1) Detection and diagnosis of FAOD: A total of 18 confirmed cases of FAOD were detected through the traditional model, with an incidence of 1/9 083 in Changzhou city. The positive rate was 0.55% (907/163 500) for initial TMS and 0.04% (73/163 500) for the second. The positive predictive value was 2.0%(18/907), with a false positive rate of 98%(889/907) in the initial screening. (2) The results of Neoseq: ①Pathogenic mutations were detected in 16 of the 18 confirmed cases, and the coincidence rate of mutation sites between the two methods was 16/18. The other two confirmed cases were missed diagnosed by Neoseq, including one β-ketothiolase deficiency with only one detected pathogenic mutation and one medium-chain acyl-CoA dehydrogenase deficiency without any detected pathogenic mutation. ②No pathogenic mutations were detected in the 57 false-positive cases by Neoseq. ③Among the 100 negative cases in initial screening, DUOX2 heterozygous mutation, and MTTL1 hemizygous mutation were detected in one case each. ④The median period of results reporting was 43.5 d (28-104 d) for the traditional mode and 12 d (10-15 d) for the Neoseq mode. Conclusions:Neoseq has a high detection rate for FAOD. Combined with TMS screening, Neoseq reduces the false-positive rate of biochemical screening, rapidly identifies genetic causes by shortening the results waiting time and covers diseases that couldn't be detected by traditional biochemical methods.

Role of H2S produced by CSE in cerebral ischemia-reperfusion injury in mice and its relationship with RhoA-ROCK2 signaling pathway / 中国药理学通报

Aim To investigate the role of H2S pro¬duced by CSE in cerebral ischemia-reperfusion ( I/R) injury and its relationship with RhoA-ROCK2 signaling pathway.Methods Bilateral common carotid artery ligation was used to prepare a mouse cerebral ischemia- reperfusion injury model.Laser speckle method was used to detect cerebral blood flow, HE staining method was used to observe the pathological changes of brain hippocampus, and the activity of LDH, NSE, RhoA and ROCK,, H,S content and ROCK, protein expres¬sion were detected.Results The H,S synthase CSE substrate L-Cys ( 3(X) mg • kg-1) could significantly promote the recovery of cerebral blood flow in brain 1/ R mice, improve the pathological damage of hippocam¬pus , inhibit the increase of LDH activity in serum and NSE, RhoA and ROCK2 activity in brain tissues, and inhibit the decrease of serum H2S content and the in¬crease of ROCK2 protein expression in brain tissues.But the above effects of L-Cys could be significantly at¬tenuated by the CSE inhibitor PPG (50 mg • kg~ 1 ) ; the H2S donor NaHS (4.8 mg • kg"1 ) also had the same effect as L-Cys did.Conclusions H2S pro¬duced by CSE has a protective effect on mouse brain 1/ R injury, and its effect may be related to inhibiting RhoA-ROCK signaling pathway and increasing cerebral blood flow.

Effect mechanism of Ma Xing Gan Shi Decoction against influenza virus from JAK2/STAT3 signaling pathway by combining network pharmacology / 中国药理学通报

Aim To explore the effect of JAK2/STAT3 signaling pathway on lung tissue injury induced by influenza A virus in combination with network pharmacology and to further explore the intervention effect of Ma Xing Gan Shi Decoction.Methods Network pharmacological method was used to screen the signal pathway enriched by Ma Xing Gan Shi Decoction on the potential target of influenza virus.BLAB/c mice were intranasally infected with influenza A virus.The mice were divided into normal control group, model control group, oseltamivir group, antiviral granule group and Ma Xing Shigan decoction group.The animals were treated with corresponding drugs for 3 and 7 days.Body weight and lung index were detected by HE for observation of the pathological changes of lung tissues.Real-time PCR(RT-PCR)was used to detect the mRNA expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.Western blot and ELISA were used to detect the protein expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.AutoDock Vina software was used to conduct molecular docking between STAT3 and target compounds.Results The main active components of Ma Xing Gan Shi Decoction had 110 intersection targets with influenza virus and were enriched in 170 signaling pathways.Ma Xing Shigan decoction could up-regulate the body weight of mice infected with influenza A virus, improve the pathological injury of lung tissues, down-regulate the lung index and the expression levels of JAK2, STAT3, IL-1β mRNA and protein in lung tissues, and up-regulate the expression levels of IL-4 mRNA and protein.STAT3 had better binding activity with glycyrrhiza chalcone A, an active compound in Ma Xing Gan Shi Decoction.Conclusions Ma Xing Gan Shi Decoction, as an effective compound prescription of traditional Chinese medicine against influenza virus, can effectively reduce pulmonary inflammation and regulate the balance of cytokines.The possible mechanism is to alleviate the lung injury caused by influenza A virus infection in mice by inhibiting the activation of JAK2/STAT3 signal pathway.

Protective effect of mesenchymal stem cell-derived exosomal treatment of hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury / 世界急诊医学杂志（英文）

@#BACKGROUND: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms. METHODS: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined. RESULTS: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation (P<0.05). The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus (2.14±0.65 vs. 5.48±1.09, P<0.01) and increased the intracellular expression of antioxidative proteins, including superoxide dismutase and glutathione peroxidase (17.18±0.97 vs. 14.40±0.62, and 20.65±2.23 vs. 16.44±2.05, respectively; P<0.05 for both). OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial function-associated genes, such as PINK, DJ1, LRRK2, Mfn-1, Mfn-2, and OPA1. The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons. CONCLUSIONS: MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons. Therefore, MSC-Exo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

Knockdown of IOP1 Induces Premature Senescence in Primary HUVECs / 中国生物化学与分子生物学报

Iron-only hydrogenase-like protein 1 (IOP1) is a component of the cytosolic iron-sulfur protein assembly (CIA) machinery. IOP1 has been suggested to be a negative regulator of the hypoxia-inducible transcription factor 1(HIF-1). We previously reported that loss of one copy of NAR1 (the yeast homolog of IOP1) in diploid yeast cells leads to increased sensitivity to oxidative stress and decreased replicative lifespan‚ however‚ the underlying mechanism is still unclear. Recently‚ we found that the IOP1 protein was upregulated in late-passaged primary human umbilical vein endothelial cells (HUVECs) compared with that in early-passaged primary HUVECs‚ which indicated a potential association of IOP1 with cellular senescence. The aim of this study was to investigate the potential function of IOP1 in aging in mammalian cells. The primary HUVECs were transfected with IOP1-specific siRNA and subjected to premature senescence assays. We found that IOP1 knockdown leads to premature senescence and decreased cell proliferative ability (P < 0. 01) in primary HUVECs. Further studies revealed that downregulation of IOP1 resulted in upregulated ROS levels (P < 0. 01)‚ enhanced DNA damage (P<0. 05) and decreased mitochondrial respiration (P<0. 01) along with cell cycle arrest at the G

Biomechanical Study of Three-Dimensional Printed Titanium Root-Analogue Implant with Porous Surface / 医用生物力学

Objective To investigate biomechanical properties of personalized titanium root-analogue implants with porous surface, so as to provide theoretical basis for the design and clinical implantation of such implants. Methods Based on CT data, the personalized model of root-analogue implant with porous surface was designed by using 3-matic software, and after registering it with the mandible model, the mesh was divided and material parameters were attributed. The implant was applied with 200 N loading, and the maximum stress of the implant and the stress and strain of the bone around the implant were analyzed. An appropriate clinical case was selected and the implant was implanted immediately after tooth extraction for conducting clinical evaluation. Results The peak stress of the personalized root-analogue implant with porous surface was mainly concentrated on the interface between the solid structure and the porous structure of the implant. The maximum stresses of the solid structure and porous structure were 137.710 and 37.008 MPa, respectively, which were smaller than its yield strength. The three-dimensional (3D) printed porous root-analogue implants had good initial stability immediately after implantation, with minimal trauma and similar mechanical transmission to natural teeth. This simplified the surgical process, shortened the treatment time, and had high patient satisfaction. Conclusions The 3D printed root-analogue implant with porous surface explores a new method for immediate implantation after tooth extraction.

Biomechanical Study of PEEK Condyle Prosthesis Printed by Fused Deposition Modeling and Selective Laser Sintering / 医用生物力学

Objective To make finite element analysis and compressive performance test on three-dimensional (3D) printed personalized poly-ether-ether-ketone (PEEK) condyle prosthesis, so as to analyze stress distribution characteristics and mechanical properties of the prosthesis, and to evaluate its clinical value and prospect. Methods The finite element models of PEEK condyle prosthesis, mandible and fixation screw were established by software such as CBCT, Mimics, Geomagic Studio, SolidWorks and ANSYS Workbench. The maximum mastication force was applied, and the maximum stress of the condyle prosthesis and screw, as well as the stress and strain of the mandible were recorded. In order to simulate the actual clinical situation, a special fixture was designed to test compression performance of the condyle prosthesis prepared by the fused deposition modeling (FDM) and selective laser sintering (SLS) at the rate of 1 mm/min. Results The peak stress of the PEEK condyle prosthesis was 10.733 MPa, which was located at the back of the condyle neck. The peak stress of 5 fixing screws was 9.707 5 MPa, which appeared on the 2# and 5# screws near the trailing edge of the mandibular ascending branch. The peak stress of both the prosthesis and the screw was smaller than its yield strength. The maximum pressure of the condyle prosthesis prepared by FDM and SLS was (3 814.7±442.6) N and (1 193.970±260.350) N, respectively. Compared with the SLS preparation, the FDM prepared prosthesis not only had higher compression strength but also better toughness. Conclusions The 3D printed personalized PEEK condyle prosthesis shows uniform stress distributions and good mechanical properties, which can provide the theoretical basis for PEEK as reconstruction material for repairing temporomandibular joint.

Reconstruction of Segmental Mandibular Defects Restored by Prosthesis with Support and Porous Structure: A Biomechanical Study / 医用生物力学

Objective To design a personalized titanium mandibular prosthesis with porous and support structure, and analyze its stress distribution characteristics through finite element analysis, so as to evaluate clinical value and prospect of the prosthesis. Methods The fourth mandibular premolar and molar from the right mandible of Beagle dogs were removed. The spiral CT was taken after three-month healing, and the three-dimensional (3D) model of the mandible was established. Resection of 3 cm mandible with simulated surgical procedure and reconstruction with personalized restoration were conducted. The prosthesis consisted of abutment, pillar, solid unit, porous unit and retention unit. A personalized titanium mandibular prosthesis finite element model A was established, to analyze the prosthesis stress under loading, and further study was proceeded when the maximum stress of each part constituting the prosthesis was smaller than yield strength of its material. The finite element model B with the assembly of the prosthesis, mandible and screw was constructed and loaded with the mastication force, and the stress, strain and displacement distributions of the mandible were recorded. Results When the abutment was under 100 N vertical loading, the peak stress of the prosthesis with solid structure and porous structure was 147.03 and 75.36 MPa, respectively, which was smaller than yield strength of its material; the peak stress of the cortical bone and cancellous bone was 53.713, 4.216 7 MPa, and the strain was 3.753 6, 3.562 5, respectively; the maximum displacement of the restoration was 338.3 μm. ConclusionsTaking the canine mandible as an example, the personalized prosthesis with porous and support structure shows the uniform stress distribution and good mechanical properties through finite element analysis. The results provide a new method for the design of prosthesis for repairing mandibular defects.

Correlation between thyroid function and serum visfatin in patients with acute pancreatitis / 中华地方病学杂志

Objective:To investigate the correlation between thyroid function index and serum visfatin in patients with acute pancreatitis (AP).Methods:Using a prospective design, 65 patients with AP treated in Binzhou People's Hospital from December 2017 to December 2019 were selected as the research subjects. They were divided into mild acute pancreatitis (MAP) group ( n = 35) and severe acute pancreatitis (SAP) group ( n = 30) according to the acute physiology and chronic health Ⅱ (APACHE Ⅱ) score ( < 8, ≥8 scores). At the same time, 40 healthy people were selected as the control group. The serum levels of free thyroxine (FT 4), free triiodothyronine (FT 3) and thyrotropin (TSH) were measured by chemiluminescence immunoassay. Radioimmunoassay was used to measure serum reverse triiodothyronine (rT 3) level, and enzyme-linked immunosorbent assay was used to measure serum visfatin level. Pearson method was used to analyze the correlation between thyroid function index and serum visfatin in patients with AP. Results:The FT 4 [(14.02 ± 3.63), (15.68 ± 3.05) pmol/L], FT 3 [(2.34 ± 0.80), (3.66 ± 0.65) pmol/L], and TSH levels [(2.78 ± 0.85), (3.10 ± 0.57) mU/L] in SAP and MAP groups were significantly lower than those in control group [(17.03 ± 3.96), (6.04 ± 1.55) pmol/L, (4.88 ± 2.30) mU/L, P < 0.05], but the rT 3 levels [(1.63 ± 1.12), (1.23 ± 0.26) nmol/L] were significantly higher than that in control group [(0.97 ± 0.28) nmol/L, P < 0.05]. There was significant difference in serum FT 3 levels between SAP and MAP groups ( P < 0.05). The serum visfatin levels of SAP, MAP and control groups were (10.75 ± 2.92), (3.70 ± 1.73), (2.30 ± 1.31) ng/ml, the difference between the three groups was statistically significant ( F = 67.174, P < 0.05). The serum visfatin levels in SAP and MAP groups were higher than that in control group, and that in SAP group was higher than that in MAP group ( P < 0.05). There were negative correlations between serum FT 3 level and visfatin level in SAP and MAP groups ( r = - 0.672, - 0.610, P < 0.05). Conclusions:The serum visfatin level and thyroid function index of AP patients are abnormal. The levels of FT 3 and visfatin are correlated with the severity of AP patients, and there is a negative correlation between the levels of FT 3 and visfatin. Detection of thyroid function index is helpful to judge the AP patient's condition.