Abstract The segmentation of athlete knee joint injury images can provide doctors with information about the location and extent of the athlete knee joint injury. Therefore, it is significant to segment the images of athlete knee joint injury. However, the traditional image segmentation method of athlete knee injury has the problems of low accuracy of mask region extraction, completion time of extraction and high error rate of segmentation. In the paper, we propose image segmentation method for athlete knee joint injury using the transformer model by the medical Internet of Things (MIoT). First, the MIoT was used as a way to obtain images of knee joint injury of athletes, and the images of knee joint injury of athletes were derived using the MIoT. Second, the exported image is input into the shadow expansion layer of the transformer model, which performs shadow expansion on the athlete knee joint injury image to obtain its mask region, and then the image is input into the patch embedding layer. Finally, after the patch embedding layer extracts the mask patch of the athlete knee joint injury image, the mask patch is input into the transformer block for down-sampling and up-sampling processing, and then the athlete knee joint injury image segmentation result is output using the end backpropagation layer. The results show that the proposed method has a low error rate in extracting the mask region from the knee joint injury image of athletes, and a short completion time for extracting the mask region, the most detailed and comprehensive segmented athlete knee joint injury image, the maximum error rate of image segmentation is only 6.8%, and the maximum value of segmentation time is only 3.96s. It has important research value in the field of athlete knee joint injury diagnosis.

Abstract Human periodontal ligament stem cells (hPDLSCs) are promising cells for dental and periodontal regeneration. Objective This study aimed to develop novel alginate-fibrin fibers that encapsulates hPDLSCs and metformin, to investigate the effect of metformin on the osteogenic differentiation of hPDLSCs, and to determine the regulatory role of the Shh/Gli1 signaling pathway in the metformin-induced osteogenic differentiation of hPDLSCs for the first time. Methodology CCK8 assay was used to evaluate hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red S staining, and the expression of osteogenic genes were evaluated. Metformin and hPDLSCs were encapsulated in alginate-fibrinogen solutions, which were injected to form alginate-fibrin fibers. The activation of Shh/Gli1 signaling pathway was examined using qRT-PCR and western blot. A mechanistic study was conducted by inhibiting the Shh/Gli1 pathway using GANT61. Results The administration of 50 μM metformin resulted in a significant upregulation of osteogenic gene expression in hPDLSCs by 1.4-fold compared to the osteogenic induction group (P < 0.01), including ALP and runt-related transcription factor-2 (RUNX2). Furthermore, metformin increased ALP activity by 1.7-fold and bone mineral nodule formation by 2.6-fold (P<0.001). We observed that hPDLSCs proliferated with the degradation of alginate-fibrin fibers, and metformin induced their differentiation into the osteogenic lineage. Metformin also promoted the osteogenic differentiation of hPDLSCs by upregulating the Shh/Gli1 signaling pathway by 3- to 6- fold compared to the osteogenic induction group (P<0.001). The osteogenic differentiation ability of hPDLSCs were decreased 1.3- to 1.6-fold when the Shh/Gli1 pathway was inhibited, according to ALP staining and alizarin red S staining (P<0.01). Conclusions Metformin enhanced the osteogenic differentiation of hPDLSCs via the Shh/Gli1 signaling pathway. Degradable alginate-fibrin hydrogel fibers encapsulating hPDLSCs and metformin have significant potential for use in dental and periodontal tissue engineering applications. Clinical Significance Alginate-fibrin fibers encapsulating hPDLSCs and metformin have a great potential for use in the treatment of maxillofacial bone defects caused by trauma, tumors, and tooth extraction. Additionally, they may facilitate the regeneration of periodontal tissue in patients with periodontitis.

Abstract To enhance the dissolution and oral bioavailability of poorly water-soluble biphenyl dimethyl dicarboxylate (BDD), the supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed by adding a water-soluble polymer PVP to prevent precipitation of the drug and maintain a supersaturate state in vivo. Ternary phase diagrams were drawn to evaluate the microemulsification domain. The formulations were characterized by testing the physical stability of the drug, particle size and zeta potential. The pharmacokinetic study in beagle dogs was performed for the S-SMEDDS, SMEDDS formulation and the market drop pills. The optimized S-SMEDDS formulation consist of 35% (w/w) Cremphor EL35, 33% (w/w) Transcutol HP, 30% (w/w) MCT and 2% (w/w) PVPK30 of each excipient showed minimum mean droplet size (37.71 ± 0.87nm) and optimal drug release profile and better physical stability in water compared with the PVP absent SMEDDS. The in vivo studies showed that S-SMEDDS had significantly increased the Cmax and area under the plasma concentration-time curve (AUC) (P < 0.01). The S-SMEDDS formulation should be an effective oral dosage form for improving oral bioavailability of water-insoluble BDD.

Abstract There are many restrictions on topical medications for the oral cavity. Various factors affect the topical application of drugs in the oral cavity, an open and complex environment. The complex physical and chemical environment of the oral cavity, such as saliva and food, will influence the effect of free drugs. Therefore, drug delivery systems have served as supporting structures or as carriers loading active ingredients, such as antimicrobial agents and growth factors (GFs), to promote antibacterial properties, tissue regeneration, and engineering for drug diffusion. These drug delivery systems are considered in the prevention and treatment of dental caries, periodontal disease, periapical disease, the delivery of anesthetic drugs, etc. These carrier materials are designed in different ways for clinical application, including nanoparticles, hydrogels, nanofibers, films, and scaffolds. This review aimed to summarize the advantages and disadvantages of different carrier materials. We discuss synthesis methods and their application scope to provide new perspectives for the development and preparation of more favorable and effective local oral drug delivery systems.

Abstract In this paper, LS-dyna software was used to simulate the charging process of cylindrical shell when EFP has different angles, and some interesting phenomena and laws were found. Cylindrical elastic wave σr was generated when the cylindrical shell was impacted by EFP. The cylindrical elastic wave σr was correlated with the time required for the cylindrical shell charge to be successfully detonated. When the EFP warhead penetration Angle θ ranges from 0° to 10°, the σr increases linearly with (cosθ)-1/2. With the increase of θ, the tangential velocity vy had an obvious effect on the impact of EFP on the cylindrical shell, and the linear relationship between the elastic wave σr and (cosθ)-1/2 does not change. When the θ was greater than 45°, EFP could not successfully impact and detonate the cylindrical shell charge. The EFP velocity was measured by velocity measurement method with an error of 1.3%. The experimental results have strong similarity with the simulation results, indicating that the parameters of the numerical simulation model have good reliability.

RESUMO OBJETIVO Explorar a associação do polimorfismo do gene fator neurotrófico derivado do cérebro (BDNF) com o endofenótipo cognitivo latente de transtorno de estresse pós-traumático (TEPT) após grandes desastres naturais na província de Hainan, China. MÉTODOS Um total de 300 doentes com TEPT e 150 controles saudáveis (HC) foi investigado pela escala de psicanálise para avaliar as suas funções cognitivas. A reação em cadeia polimerase (PCR) e a eletroforese em gel de poliacrilamida (Page) foram usadas para detectar o polimorfismo do gene BDNF. RESULTADOS Em termos de função cognitiva, as pontuações no grupo TEPT foram piores do que as do grupo HC (P<0,05 ou P<0,01). Houve uma diferença significativa na distribuição do genótipo de BDNF e frequência do alelo entre os dois grupos (P<0,05). Os endofenótipos de TEPT foram significativamente diferentes entre os genótipos de BDNF do grupo TEPT (P≤0,01). CONCLUSÃO Existe uma diferença estatisticamente significativa no polimorfismo do gene BDNF entre o TEPT e os grupos HC, e os alelos estão associados à incidência do TEPT. Assim, pode ser um fator de risco para TEPT.

SUMMARY OBJECTIVE To explore the association of brain-derived neurotrophic factor gene (BDNF) polymorphism with the latent cognitive endophenotype of posttraumatic stress disorder (PTSD) after major natural disasters in Hainan Province, China. METHODS A total of 300 patients with PTSD and 150 healthy controls (HC) were surveyed by psychoanalysis scale to assess their cognitive functions. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) were used to detect the BDNF gene polymorphism. RESULTS In terms of the cognitive function, the scores in the PTSD group were worse than those of the HC group (P < 0.05 or P < 0.01). There was a significant difference in the distribution of BDNF genotype and allele frequency between the two groups (P < 0.05). PTSD endophenotypes were significantly different among the BDNF genotypes in the PTSD group (P ≤ 0.01). CONCLUSION There is a statistically significant difference in the polymorphism of BDNF gene between PTSD and HC groups, and the alleles are associated with the incidence of PTSD. Thus, it may be a risk factor for PTSD.

Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.

The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.

RESUMO OBJETIVO Nosso estudo teve como objetivo investigar o valor diagnóstico do lncRNA H19 para doença arterial coronariana (DAC) e explorar os possíveis mecanismos. Métodos Um total de 30 pacientes com DAC e 30 pessoas saudáveis, bem como pacientes com diferentes doenças cardiovasculares foram incluídos neste estudo. O sangue foi extraído de cada participante para preparar amostras de soro e a expressão de lncRNA H19 foi detectada por qRT-PCR. A análise da curva ROC foi utilizada para analisar o valor diagnóstico de H19 para DAC. Efeitos da informação básica dos pacientes e estilo de vida na expressão de H19 foram analisados. O nível plasmático de TGF-β1 foi medido por ELISA. A linha de células endoteliais da artéria coronária primária (HCAEC) humana de sobre-expressão de H19 foi construída e os efeitos da sobre-expressão de H19 na expressão de TGF-β1 foram analisados por Western blot. Resultados A expressão de H19 foi especificamente regulada positivamente em pacientes com DAC, mas não em pessoas saudáveis e em pacientes com outros tipos de doenças cardiovasculares. A análise da curva ROC mostrou que o nível de expressão de H19 pode ser usado para prever com precisão a DAC. Sexo, idade e estilo de vida dos pacientes não têm efeitos significativos sobre a expressão de H19, mas a expressão de H19 foi maior em pacientes com curso mais longo da doença em comparação com os controles. A expressão de H19 correlacionou-se positivamente com o nível sérico de TGF-β1 e a superexpressão de H19 aumentou significativamente o nível de proteína de TGF-β1 em HCAEC. Conclusão A superexpressão de H19 participa da patogênese da DAC aumentando o nível de expressão de TGF-β1 e o nível de expressão de H19 pode servir como marcador diagnóstico de DAC.

SUMMARY OBJECTIVE: Our study aimed to investigate the diagnostic value of lncRNA H19 for coronary artery disease (CAD) and to explore its possible mechanisms. Methods: A total of 30 CAD patients and 30 healthy individuals, as well as patients with different cardiovascular diseases, were included in this study. Blood was drawn from each participant to prepare serum samples, and the expression of lncRNA H19 was detected using qRT-PCR. The ROC curve analysis was used to analyze the diagnostic value of H19 for CAD. The effects of patients' basic information and lifestyle on H19 expression were analyzed. The plasma level of TGF-β1 was measured by ELISA. The H19 overexpression in the human primary coronary artery endothelial cell (HCAEC) line was constructed, and the effects of H19 overexpression on the TGF-β1 expression were analyzed using Western blot. The results of H19 expression were specifically upregulated in patients with CAD but not in healthy individuals and patients with other types of cardiovascular diseases. The ROC curve analysis showed that the H19 expression level could be used to predict CAD accurately. Gender, age, and patients' lifestyle had no significant effects on H19 expression, but H19 expression was higher in patients with a longer course of disease in comparison with the controls. H19 expression was positively correlated with the serum level of TGF-β1, and H19 overexpression significantly increased TGF-β1 protein level in HCAEC. Conclusion: H19 overexpression participates in the pathogenesis of CAD by increasing the expression level of TGF-β1, and H19 expression level may serve as a diagnostic marker for CAD.

Aortic dissection is characterized by the redirection of blood flow, which flows through an intimal tear into the aortic media. The purpose of this study was to find potential acute type A aortic dissection (AAAD)-related genes and molecular mechanisms by bioinformatics. The gene expression profiles of GSE52093 were obtained from Gene Expression Omnibus (GEO) database, including 7 AAAD samples and 5 normal samples. The differentially expressed genes (DEGs) were detected between AAAD and normal samples. The functional annotation and pathway enrichment analysis were conducted through the Database for Annotation, Visualization and Integration Discovery (DAVID). A protein-protein interaction network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) software. The microRNAs (miRNAs) of these differentially expressed genes were predicted using <microRNA.org> database. Moreover, DEGs were analyzed in the comparative toxicogenomics (CTD) database to screen out the potential therapeutic small molecules. As a result, there were 172 DEGs identified in patients with AAAD. These DEGs were significantly enriched in 6 pathways, including cell cycle, oocyte meiosis, DNA replication, extracellular matrix-receptor interaction, and mineral absorption pathway. Notably, CDC20, CDK1, CHEK1, KIF20A, MCM10, PBK, PTTG1, RACGAP, and TOP2A were crucial genes with a high degree in the protein-protein interaction network. Furthermore, potential miRNAs (miR-301, miR-302 family, and miR-130 family) were identified. In addition, small molecules like azathioprine and zoledronic acid were identified to be potential drugs for AAAD.

Abstract: Besides stimulating vasoconstriction, Angiotensin II is also well known in inducing reactive oxygen species and promoting inflammatory phenotype switch via its type 1 receptor. In clinic, Angiotensin II type 1 (AT1) receptor blocker like candesartan has been widely applied as an antihypertensive medication. We previous have demonstrated that a higher dose of candesartan plays a protective role after kidney injury. However, whether candesartan could exhibit anti-inflammatory effects remains unclear. Here, by stimulating isolated human embryonic kidney epithelial cells with tumor necrosis factor-α (TNF-α), we observed the anti-inflammation capacity of candesartan ex vivo. It was found that pre-treat with candesartan significantly suppressed transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) expression after incubation with TNF-α. Surprisingly, silence of angiotensin II type 1 receptor has little effects on reducing TGF-β or IL-6 products. Furthermore, candesartan inhibited TNF-α-induced oxidative stress in the primary cultured tubular epithelial cells. Overall, our data indicates that candesartan suppresses TNF-α-induced inflammatory cytokine production by inhibiting oxidative stress, rather than block AT1 receptor activity.

ABSTRACT Objective: The aim of the study was to determine whether serum thymosin beta4 (Tβ4) can be a useful noninvasive biomarker to differentiate between nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver (NAFL). Methods: The study included 24 NAFL patients and 21 NASH patients. The levels of Tβ4, 8-hydroxydeoxyguanosine acid (8-OhdG), liver function parameters, blood lipid, and glucose were detected in the venous blood of all patients. The NAFLD histological activity score (NAS) was examined in biopsy specimens from all patients. Statistical analysis was performed in order to find differences between the two abovementioned groups. In addition, receiver operator characteristic (ROC) analyses for alanine aminotransferase (ALT) and Tβ4 levels were performed in NAFL and NASH patients and the cut-off value was determined. Associations between the variables were tested using correlation coefficient calculations. Statistical significance was set at a p value of < 0.05. Results: Serum Tβ4 content was 5.12 ± 1.87 mg/l in the NAFL group and 2.98 ± 1.35 mg/l in the NASH group (p < 0.001). Serum Tβ4 content and NAS, histological features of hepatic steatosis, lobular inflammation and ballooning, ALT, glucose and 8-OhdG levels were negatively correlated (p < 0.05 for all) in the NASH group. The correlation coefficient values were -0.530, -0.562, -0.574, -0.438, -0.446, -0.426 and -0.563, respectively. On the basis of ROC analysis, the best predictive Tβ4 cut-off value for detecting NASH was 3.94 mg/l (85.7% sensitivity and 79.2% specificity, which were higher than those of ALT). Conclusion: Serum Tβ4 level can be used as a biomarker for the diagnosis of NASH and was negatively correlated with the oxidation state of the liver.

Abstract Background: Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) could regulate cancer cell proliferation important for cancer cell proliferation; however, its role in Hepatocellular carcinoma (HCC) remains largely unknown. Here, we investigated the role of PIK3R1 in HCC and examined the underlying molecular mechanisms. Methods: The expression of PIK3R1 was evaluated by immunohistochemistry and qRT-PCR in a series of HCC tissues. The mRNA and protein expression of PIK3R1 was used by qRT-PCR and western blot assays in a series of human HCC cell lines, and then we choose MHCC97H and HCCLM3 cells as a model to investigate the effect of PIK3R1 on HCC progression. The effects of PIK3R1 knowdown on cell proliferation, migration, apoptosis of HCC were assessed by the MTT assay, clonogenic assays, wound healing assay and flow cytometry in vitro. Western blot assay was performed to assess the expression changes of PI3K/AKT/mTOR signaling pathway. Results: Our results found that PIK3R1 was highly expressed in HCC tissues compared with adjacent normal tissues. Knockdown of PIK3R1 inhibited the proliferation, migration and promoted apoptosis of HCC cell lines. In addition, we proved that knockdown of PIK3R1 downregulated p-PI3K, p-AKT, and p-mTOR expressions in MHCC97H and HCCLM3 cells. Conclusions: In conclusion, PIK3R1 providing potential novel targets for the treatment of HCC.

ABSTRACT PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.