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Objective. Gliomas are the most common and life-threatening intracranial tumors. Immune infiltration of the tumor microenvironment significantly affects tumor prognosis in glioma. Recently, PLEKHA4 was reported to be upregulated in melanoma and closely associated with tumor genesis and development, but its role in glioma is poorly understood. Our aim was to investigate the expression, functional role, and prognostic value of PLEKHA4 in glioma. Methods. The expression levels of PLEKHA4 in 33 types of cancer in the TCGA (The Cancer Genome Atlas) database were collected via the UCSC Xena browser. The clinical samples of glioma patients were downloaded from the TCGA database. Immunohistochemistry was used to verify PLEKHA4 expression in tumor tissues. We assessed the influence of PLEKHA4 on survival of glioma patients by survival module and GEPIA. Then, we downloaded datasets of glioma from TCGA and investigated the correlations between the clinical characteristics and PLEKHA4 expression using logistic regression. Moreover, we used TIMER to explore the collection of PLEKHA4 expression and immune infiltration level in glioma and to analyze cumulative survival in glioma. Gene Set Enrichment Analysis (GSEA) was performed using the TCGA dataset. Results. PLEKHA4 transcript levels were significantly upregulated in multiple cancer types, including gliomas. Moreover, immunohistochemical analysis verified that PLEKHA4 was overexpressed in gliomas compare to the corresponding normal tissues. Univariable survival and multivariate cox analysis show that increased PLEKHA4 expression significantly correlated with age, tumor grade, IDH mutation status, and 1p/19q codel status, and higher PLEKHA4 had shorter OS, DSS, and PFI. Specifically, PLEKHA4 expression level had significant positive correlations with infiltrating levels of B cell, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and DCs in glioma, and upregulation of PLEKHA4 expression was significantly related to immune cell biomarkers and immune checkpoint expression in glioma. In addition, several GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) items associated with immune response, JAK STAT signal pathway, and cell cycle were significantly enriched in the high PLEKHA4 expression phenotype pathway. Conclusions. Our findings proposed that PLEKHA4 was an independent prognostic biomarker and correlated with immune infiltrates in glioma, and targeting PLEKHA4 might improve immunotherapy in glioma. Of course, these findings also need basic experiments and further clinical trials to confirm in the future. [ABSTRACT FROM AUTHOR]

With the increasing incidence and mortality of renal cancer, it is pressing to find new biomarkers and drug targets for diagnosis and treatment. However, as one negative upstream regulator of p53, the prognostic and immunological role of NFE2L3 in renal cancer is still barely known. We investigated the expression, prognostic value, and relevant pathways of NFE2L3 using the datasets from public databases, including The Cancer Genome Atlas Program (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and UALCAN. Furthermore, we analyzed the relationship between NFE2L3 expression and the immune microenvironment using distinct methods. We found that NFE2L3 was higher expressed in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) tissues than adjacent normal tissues. Additionally, we identified NFE2L3 as one survival-related factor for KIRC and KIRP. The enrichment analyses revealed that NFE2L3 was associated with a variety of immune-relevant pathways in KIRC and related to the infiltration ratios of 17 types of immune cells in KIRC patients. Ultimately, we demonstrated nine significantly enriched mutations, such as TP53 and MET, in NFE2L3-expression-changing groups. The elevated expression of NFE2L3 in renal cancerous tissues versus normal tissues is associated with poor outcomes in patients. Besides, NFE2L3 has a role in the regulation of the immune microenvironment in renal cancer patients. The findings of our study provide a potential prognostic biomarker and a new drug target for renal cancer. [ABSTRACT FROM AUTHOR]

Background. Ferredoxin 1 (FDX1) is a newly discovered gene regulating cuprotosis. However, the effect of FDX1 expression on clear renal cell carcinoma (ccRCC) is unknown. Methods. Gene expression profiles and clinical data of ccRCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The differences in FDX1 expression between ccRCC and nonneoplastic tissues adjacent to cancer were analyzed by R software. The results were validated by GEO data, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC). Chi-square test was used to analyze the clinical pathological parameters. Kaplan-Meier survival analysis and Cox proportional hazard regression model selection were used to evaluate the effect of FDX1 expression on overall survival. Protein interaction networks were used to analyze other proteins that interact with FDX1. Signal pathway analysis was performed for possible FDX1 enrichment using GSEA and ssGSEA algorithms. Pan-cancer analysis of FDX1 was carried out through TCGA database. Results. The FDX1 expression in nontumor tissues was significantly higher than that in ccRCC, and the expression difference was verified by GEO data, qRT-PCR, WB, and IHC. The high expression of FDX1 was significantly related to the well overall survival rate (P < 0.05). The chi-square test showed that the high expression of FDX1 was related to gender, TNM stage, T stage, lymph node metastasis, and pathological grade. Additionally, the FDX1 expression level was different in groups classified based on pathological grade, gender, TNM stage, T stage, lymph node metastasis, and distant metastasis (P < 0.05). The multivariate analysis revealed the high expression of FDX1 as an important independent predictor for overall survival. STRING database results showed that LIAS and LIPT1 may interact with FDX1 in the PPI network, which are also involved in the regulation of cuprotosis. The GSEA and ssGSEA results showed that the FDX1 was enriched in the anticancer pathway. The FDX1 high expression is associated with better prognosis in many cancers, as revealed by pan-cancer analysis. Conclusion. FDX1 may play a role in the progression of ccRCC as a tumor suppressor gene. It can be used as a potential prognostic indicator and therapeutic target of ccRCC. However, the cuprotosis regulatory role in the development of ccRCC needs to be further verified. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of 12-week physical exercise (jogging, basketball, and outdoor training) on sleep quality, harmful mood, and heart rate variability (HRV) in college students with Internet addiction. Methods. 46 college students with Internet addiction were chosen and then randomly assigned to the Internet addiction group (IA, n = 23) and the Internet addiction exercise group (IA+EX, n = 23). The subjects in the IA+EX group underwent physical exercise for 12 weeks (three times per week), and the IA group did not perform regular physical exercise during the experiment. Then, the degree of Internet addiction, depression, and sleep quality were evaluated by using Young's Internet Addiction Test (IAT) scale, Center for Epidemiologic Studies Depression (CES-D) scale, and Pittsburgh sleep quality index (PSQI); HRV were measured by using Polar Team 2 before and after physical exercise intervention. Results. (1) After the 12-week exercise, compared to preexercise intervention, the scores of IAT, CES-D, and PSQI significantly decreased (t = 12.183 , 9.238, 5.660; P < 0.01) in the IA+EX group; compared with the IA group, the scores of IAT, CES-D, and PSQI significantly decreased (t = 2.449 , 3.175, 4.487; P < 0.05 , P <0.01) in IA+EX group college students with Internet addiction. (2) After the 12-week exercise, compared to preexercise intervention, LFn and the ratio of LF/HF significantly decreased (t = 5.650 , 3.493; P < 0.01) and HFn significantly increased (t = − 2.491 , P < 0.05) in the IA+EX group; there were no significant differences in the above indexes before and after the experiment in the IA group (P > 0.05). Compared with the IA group, HFn significantly increased (t = 3.616 , P < 0.01) and the ratio of LF/HF significantly decreased (t = 2.099 , P < 0.01) in IA+EX group college students with Internet addiction; there was no significant difference in LFn between the two groups. Conclusion. Long-term physical exercise could significantly reduce the degree of Internet addiction and depression, improve sleep quality, and balance sympathetic parasympathetic function of college students with Internet addiction, indicating that exercise-based intervention might be an effective way to alleviate or even eliminate Internet addiction. [ABSTRACT FROM AUTHOR]

Background. Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods. Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results. In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1β. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion. Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

COVID-19 is still prevalent in more world regions and poses a severe threat to human health due to its high pathogenicity. The incidence of COPD patients is gradually increasing, especially in patients over 45 years old. COPD patients are susceptible to COVID-19 due to the specific lung receptor ACE2 of SARS-CoV-2. We attempt to reveal the genetic basis by analyzing the expression of common DEGs of the two diseases through bioinformatics approaches and find potential therapeutic agents based on the target genes. Thus, we search the GEO database for COVID-19 and COPD transcriptomic gene expression. We also study the enrichment of signaling regulatory pathways and hub genes for potential therapeutic treatments. There are 34 common DEGs in the two datasets. The signaling pathways are mainly enriched in intercellular junctions between virus and cytokine regulation. In the PPI network of common DEGs, we extract 5 hub genes. We find that artesunate CTD 00001840, dexverapamil MCF7 UP, and STOCK1N-35696 PC3 DOWN could be therapeutic agents for both diseases. We also analyze the regulatory network of differential genes with transcription factors and miRNAs. Therefore, we conclude that artesunate CTD 00001840, dexverapamil MCF7 UP, and STOCK1N-35696 PC3 DOWN can be therapeutic candidates in COPD combined with COVID-19. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In the past decades, HCC treatment has achieved great progress; however, the overall prognosis remains poor. Therefore, it is the need of the hour to identify new prognostic biomarkers which can advance our understanding related to the underlying molecular mechanism of adverse prognosis and apply them to clinical work in prognosis prediction. In the present study, data of 576 HCC patients and 292 normal control cases from TCGA and ICGC databases were enrolled to our bioinformatic analysis. SNHG1 and SNHG3 were identified as overlapping genes in TCGA and ICGC databases using Pearson correlation analysis and univariate Cox regression analysis. Further, we used the median of the SNHG1 and SNHG3 expression values as the cutoff values to define the HCC patient groups with high or low expression level. The subsequent analysis revealed that abnormal high expression of SNHG1 or SNHG3 affected the immune infiltration patterns and the crosstalk among immune cells. Moreover, high expression of SNHG1 or SNHG3 resulted in drug resistant to AKT inhibitor VII, bexarotene, bicalutamide, dasatinib, erlotinib, and gefitinib. In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Further, we found significant relation between the aberrant upregulation of SNHG1 and SNHG3 in tumor grade and stage. We established a nomogram to systematically predict the 5- and 8-year overall survival of liver cancer patients with good accuracy. Finally, the in vitro assays suggest that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells. [ABSTRACT FROM AUTHOR]

Objective. By detecting the levels of external counterpulsation combined with exercise therapy on the levels of moesin, angiopoietin-like protein2 (Angptl 2), angiopoietin-like protein (Angptl 3), hypoxia inducible factor-1α (HIF-1α), and RNA-34a (miR-34a) in patients with coronary artery occlusive disease, the effect of external counterpulsation combined with exercise therapy on the establishment of occluded coronary collateral circulation was studied. Methods. A retrospective analysis of 166 patients with coronary heart disease was confirmed by coronary angiography results that at least one coronary artery (anterior descending branch, circumflex branch, and right coronary artery) was completely occluded and was classified into the control group (routine medication) and the treatment group (routine drug therapy plus exercise therapy and external counterpulsation) according to the treatment plan of the patient. The serum levels of moesin, Angptl 2, Angptl 3, and HIF-1α were detected by enzyme-linked immunosorbent assay (ELISA) test. The index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) of the two groups of patients were measured before and after 2 weeks of treatment. The formation of collateral circulation was analyzed according to the Rentrop classification method. Results. After treatment, the IMR levels of the two groups were significantly decreased, and the CFR levels were significantly increased. The decrease of IMR level and the increase of CFR level in the experimental group were better than those in the control group (P < 0.05). There was no significant difference in the positive detection rate of moesin antibody between the two groups, but the OD detection value of the treatment group decreased significantly (P < 0.05). The levels of Angptl 2, Angptl 3, and miR-34a in the treatment group were lower than those in the control group, while the relative expression of HIF-1α was higher than that in the control group. The difference was statistically significant (P < 0.05). External counterpulsation combined with exercise therapy improved the formation rate of collateral circulation (P < 0.05). Conclusions. External counterpulsation combined with exercise therapy can reduce moesin antibody, Angptl 2, Angptl 3, and miR-34a levels increase HIF-1α levels, and promote the establishment of occluded coronary collateral circulation. [ABSTRACT FROM AUTHOR]

Acupuncture can effectively improve the sleep state, and most PD patients have sleep disorders. In this study, we used acupuncture to intervene in the sleep state of PDSD, so as to observe the changes and dose effect of Acutreatment on PDSD. 57 patients with PDSD, during medical treatment, aged 40–70 years were recruited to enroll in this trial. Each participant completed one condition, namely, Acutreatment (n = 30) and sham Acutreatment (placebo, stick flat needle on skin, n = 27). The Acutreatment was applied for 30 min once a day for a 30-day observation. UPDRSIII scores for motor symptom assessment and sleeping quality were assessed by PDSS-2, ESS as well as ActiGraph. Scale evaluation was made on the first day of admission and the thirtieth day. There were significant differences on all outcome indicators, except UPDRSIII, on day 30 compared with day 1 (P < 0.01). Compared with sham Acutreatment therapy, Acutreatment therapy has better performance in sleep latency, total sleep time, and sleep efficiency (P < 0.01). ActiGraph indicated that sleep efficiency of sham or Acutreatment in day 6 was significantly lower than that in day 5 (P < 0.05 and P < 0.01) and Acutreatment in day 7 was significantly lower than that in day 6 (P < 0.01). The sleep efficiency of Acutreatment in days 5, 6, and 7 was significantly higher than that in sham Acutreatment (P < 0.01). Moreover, Acutreatment in days 26, 27, and 28 was significantly higher than that in sham Acutreatment (P < 0.01). There was a close correlation between the difference of UPDRSIII and PDSS-2 (r = 0.5090 , P < 0.05), sleep latency (r = 0.7201 , P < 0.01), TST (r = − 0.6136 , P < 0.01), and sleep efficiency (r = − 0.6707 , P < 0.01). The sleep condition of PDSD patients can be improved by acupuncture, which can effectively relieve sleep quality, can also be shown by ActiGraph, and shows a dose-response relationship. Future research should explore Acutreatment with a larger sample size and compare the Acutreatment protocol goal formation of the system scheme. [ABSTRACT FROM AUTHOR]

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH. [ABSTRACT FROM AUTHOR]

Background. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters. Methods. Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test. Results. Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue. Conclusions. LHPP is associated with the AFP level and acts as a good prognostic factor in HCC. [ABSTRACT FROM AUTHOR]

Background. The necessity of preoperative biliary drainage (PBD) prior to pancreaticoduodenectomy (PD) is still controversial. However, in some settings, PBD with endoscopic retrograde cholangiopancreatography (ERCP) procedure is recommended as a preferred management. Meanwhile, pancreatic duct stenting in the drainage procedure is rarely performed for selected indications, and its associated complications after PD remain quite unknown. Methods. A retrospective observational longitudinal cohort study was performed on patients who underwent PBD and PD from a prospectively maintained database at the National Cancer Center from March of 2015 to July of 2019. Patients who underwent biliary stenting alone, biliary and pancreatic stenting, were distributed into two study cohort groups, and their records were scrutinized for the incidence of postoperative complications. Results. A total of 83 patients who underwent successful PD after biliary drainage were identified. 29 patients underwent nasobiliary drainage (ENBD)/plastic or metal bile duct stenting (BS) and pancreatic duct stenting (PS group), and 54 patients underwent only ENBD/BS, without pancreatic duct stenting (NPS group). No differences were found between the two groups with respect to in-hospital time, overall complication rate, respective rate of serious (grade 3 or higher) complication rate, bile anastomotic leakage, bleeding, abdominal infection, surgical wound infection, organ dysfunction, and pancreatic anastomotic leakage. Postoperative gastrointestinal dysfunction rates differed significantly, which occurred in 3 (5.56%) cases in the NPS group, compared with 6 (20.7%) cases in the PS group (P = 0.06). In the univariate and multivariate regression model analysis, pancreatic duct stenting was correlated with higher rates of gastrointestinal dysfunction [ odds ratio OR = 4.25 , P = 0.0472 ]. Conclusion. Our data suggested that PBD and pancreatic duct stenting prior to pancreatoduodenectomy would increase the risk of postoperative delayed gastric emptying, while the overall incidence of postoperative complications and other complications, such as pancreatic leakage and bile duct leakage, showed no statistical difference. [ABSTRACT FROM AUTHOR]

Objective. In this study, the mechanical properties of the new spinal fixation system (NSFS) in the treatment of thoracolumbar fractures were evaluated by the finite element analysis method, so as to provide a mechanical theoretical basis for the later biomechanical experiments and clinical experiments. Methods. T12-L2 bone model was constructed to simulate L1 vertebral fracture, and three models of internal fixation systems were established on the basis of universal spinal system (USS): Model A: posterior short-segment fixation including the fractured vertebra (PSFFV); Model B: short-segment pedicle screw fixation (SSPF); Model C: new spinal fixation system (NSFS). After assembling the internal fixation system and fracture model, the finite element analysis was carried out in the ANSYS Workbench 18.0 software, and the stress of nail rod system, fracture vertebral body stress, vertebral body mobility, and vertebral body displacement were recorded in the three models. Results. The peak values of internal fixation stress, vertebral body stress, vertebral body maximum displacement, and vertebral body maximum activity in Model C were slightly smaller than those in Model B. Conclusions. Compared with the traditional internal fixation system, the new spinal internal fixation system may have the mechanical advantage and can provide sufficient mechanical stability for thoracolumbar fractures. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, CDCA5, CENPH, and MCM7, and 4 novel genes, namely, CDC6, CDC45, CDCA8, and MCM4, which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The CDCA8 and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis. [ABSTRACT FROM AUTHOR]

Poultries including chickens, ducks, geese, and pigeons are widely used in the biological and medical research in many aspects. The genetic quality of experimental poultries directly affects the results of the research. In this study, following electrophoresis analysis and short tandem repeat (STR) scanning, we screened out the microsatellite loci for determining the genetic characteristics of Chinese experimental chickens, ducks, geese, and pigeons. The panels of loci selected in our research provide a good choice for genetic monitoring of the population genetic diversity of Chinese native experimental chickens, ducks, geese, and ducks. [ABSTRACT FROM AUTHOR]

Background. The treatment of vertical femoral neck fractures in young patients remains a challenge. This study is aimed at comparing ordinary cannulated compression screw (OCCS) and double-head cannulated compression screw (DhCCS) fixation in vertical femoral neck fractures both clinically and biomechanically. Materials and Methods. Clinically, the radiographs of 81 patients with Pauwel's III femoral neck fractures, including 54 fractures fixed with three parallel OCCSs and 27 fractures fixed with three parallel DhCCSs, were reviewed retrospectively. Complications consisting of fixation failure (screw loosening, obvious fracture displacement, varus deformity, or femoral neck shortening), bony nonunion, and avascular necrosis (AVN) were determined. Biomechanically, twenty synthetic femur models of vertical femoral fractures with an 80° Pauwel's angle were divided into two groups and subsequently fixed with three parallel OCCSs or DhCCSs. All specimens were tested for axial stiffness, load to 5 mm displacement, and a maximum load to failure with a loading rate of 2 mm/min. Results. Clinically, 22 fractures in the OCCS group experienced fixation failure, including 19 screw loosening, 18 femoral neck shortening, 14 varus deformities, and 8 obvious fracture displacements, whereas only 4 fractures experienced fixation failure in the DhCCS group, including 3 screw loosening, 3 femoral neck shortening, 3 varus deformities, and 1 obvious fracture displacement. Additionally, 11 fractures in the OCCS group exhibited nonunion, whereas only 3 in the DhCCS group exhibited nonunion. Nine fractures with AVN were noted in the OCCS group, whereas only 1 was observed in the DhCCS group. Biomechanically, the axial stiffness of the DhCCS group was greater than that of the OCCS group (154.9 ± 6.81 vs. 128.1 ± 7.41 N/mm), and the load to 5 mm displacement was also significantly greater in the DhCCS group (646.1 ± 25.87 vs. 475.8 ± 21.46 N). Moreover, the maximum load to failure in the DhCCS group exhibited significant advantages compared with that of the OCCS group (1148 ± 39.47 vs. 795.9 ± 51.39 N). Conclusion. Our results suggested that using three DhCCSs improved the outcome of vertical femoral neck fractures compared to three OCCSs, offering a new choice for the treatment of femoral neck fracture. [ABSTRACT FROM AUTHOR]

Purpose. A hybrid pedicle screw system for minimally invasive spinal fixation was developed based on the uniplanar pedicle screw construct and a new intermediate screw. Its biomechanical performance was evaluated using finite element (FE) analysis. Methods. A T12-L2 FE model was established to simulate the L1 vertebral compression fracture with Magerl classification A1.2. Six fixation models were developed to simulate the posterior pedicle screw fracture fixation, which were divided into two subgroups with different construct configurations: (1) six-monoaxial/uniplanar/polyaxial pedicle screw constructs and (2) four-monoaxial/uniplanar/polyaxial pedicle screw constructs with the new intermediate screw. After model validation, flexion, extension, lateral bending, and axial rotation with 7.5 Nm moments and preloading of 500 N vertical compression were applied to the FE models to compare the biomechanical performances of the six fixation models with maximum von Mises stress, range of motion, and maximum displacement of the vertebra. Results. Under four loading scenarios, the maximum von Mises stresses were found to be at the roots of the upper or lower pedicle screws. In the cases of flexion, lateral bending, and axial rotation, the maximum von Mises stress of the uniplanar screw construct lay in between the monoaxial and polyaxial screw constructs in each subgroup. Considering lateral bending, the uniplanar screw construct enabled to lower the maximum von Mises stress than monoaxial and polyaxial pedicle screw constructs in each subgroup. Two subgroups showed comparable results of the maximum von Mises stress on the endplates, range of motion of T12-L1, and maximum displacement of T12 between the corresponding constructs with the new intermediate screw or not. Conclusions. The observations shown in this study verified that the hybrid uniplanar pedicle screw system exhibited comparable biomechanical performance as compared with other posterior short-segment constructs. The potential advantage of this new fixation system may provide researchers and clinical practitioners an alternative for minimally invasive spinal fixation with vertebral augmentation. [ABSTRACT FROM AUTHOR]

Background. The abnormal vascular permeability is associated with the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). Previously, our study demonstrated that the nasal lavage fluid- (NLF-) derived exosomes from CRSwNP can promote the vascular permeability of human umbilical vein endothelial cells (HUVECs). miR-22-3p, a specific differentiated miRNA, is reported to regulate microvessels in some diseases. This study is purposed to explore the impact of exosomal miR-22-3p derived from CRSwNP on vascular permeability and identify the underlying targets. Methods. Exosomes were extracted from NLF of 26 CRSwNP patients and 10 control patients. Quantitative real-time PCR (qRT- PCR) was applied to evaluate the relative level of exosomal miR-22-3p. The impact of exosomal miR-22-3p on HUVECs was assessed by permeability assays in vitro. The potential molecular targets of miR-22-3p were investigated by applying such technologies as dual-luciferase reporter assay and western blot. Results. miR-22-3p was upregulated in NLF-derived exosomes from CRSwNP. Exosomal miR-22-3p derived from CRSwNP enhanced the tubule permeability of HUVECs. Vascular endothelial- (VE-) cadherin (CDH5) was identified as a direct target of miR-22-3p. miR-22-3p regulated the vascular permeability by targeting VE-cadherin in HUVECs. Conclusions. Exosomal miR-22-3p derived from NLF of CRSwNP plays an important role in regulating vascular permeability by targeting VE-cadherin. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare but clinically aggressive endocrine malignancy. Circular RNAs (circRNAs) were found to play key roles in tumorigenesis. In the current study, we aimed to investigate the functions and mechanisms of a novel circRNA, circ-CCAC1, in ACC cells. circ-CCAC1 expression levels in ACC tissue specimens and cell lines were evaluated by RT-qPCR. Kaplan-Meier analysis was applied to explore the relationship between circ-CCAC1 and patients' prognosis. Cell counting kit-8 (CCK-8), colony formation, acridine orange/ethidium bromide (AO/EB) double fluorescence staining, and Transwell assays were performed to evaluate the functions of circ-CCAC1 in ACC cells. Bioinformatics analysis and a dual-luciferase reporter assay were utilized to explore the mechanisms of circ-CCAC1. As a result, circ-CCAC1 was overexpressed in ACC tissue samples and cell lines and correlated with poor prognosis. Gain- and loss-of-function tests demonstrated that circ-CCAC1 acted as an oncogene in ACC. What is more, circ-CCAC1 enhanced C22orf46 expression by sponging miR-514a-5p in ACC cells. A rescue assay illustrated that circ-CCAC1 facilitated ACC progression through miR-514a-5p/C22orf46 signaling. To sum up, we identified a novel circRNA, circ-CCAC1, which may be used as a potential therapeutic target for ACC. [ABSTRACT FROM AUTHOR]

Background. Deciphering the immune characteristics within tumors and identifying the immune signals related to the prognostic factor are helpful for the treatment and management of tumor patients. However, systematic analysis of immune signatures in head and neck squamous cell carcinoma (HNSCC) remains largely unstudied. Methods. A total of 718 immune-related genes were extracted from RNA sequencing data from 519 HNSCC patients in the TCGA database, and survival analysis with integrated bioinformatics analyses was performed to build the final predictive prognosis model. Results. The 178 survival-associated genes (P < 0.05) participated in important immune functions, including immune cell activation and migration. Multivariate regression analysis using 93 genes (P < 0.01), together with survival-associated clinicopathological parameters, identified 35 independent prognostic factors. The most significant 8 independent factors were CD3E, CD40LG, TNFRSF4, CD3G, CD5, ITGA2B, ABCB1, and TNFRSF13b. The final prognostic model achieved outstanding predictive efficiency with the highest AUC of 0.963. Conclusion. Our prognostic model based on the immune signature could effectively predict the prognosis of HNSCC patients, providing novel predictive biomarkers and potential therapeutic targets for HNSCC patients. [ABSTRACT FROM AUTHOR]

Adiponectin (APN) is an adipokine secreted from adipose tissue and exhibits biological functions such as microcirculation-regulating, hearing-protective, and antiapoptotic. However, the effect of APN on the apoptosis of spiral arterial smooth muscle cells (SMCs) under hypoxic conditions in vitro is not clear. We used cobalt chloride (CoCl2) to simulate chemical hypoxia in vitro, and the SMCs were pretreated with APN and then stimulated with CoCl2. The viability of cells and apoptosis were assessed by CCK-8 and flow cytometry, respectively. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, cAMP level, and the activity of PKA were detected by ELISA. Protein expression and localization were studied by Western blot and immunofluorescence analysis. In the present study, we found that APN exhibits antiapoptosis effects. CoCl2 exhibited decreased cell viability, increased apoptosis and MDA levels, and decreased SOD activity in a concentration-dependent manner, compared with the control group. Moreover, CoCl2 upregulated the expression levels of Bax and cleaved caspase-3 and then downregulated Bcl-2 levels in a time-dependent manner. Compared with the CoCl2 group, the group pretreated with APN had increased cell viability, SOD activity, PKA activity, cAMP level, and PKA expression, but decreased MDA levels and apoptosis. Lastly, the protective effect of APN was blocked by cAMP inhibitor SQ22536 and PKA inhibitor H 89. These results showed that APN protected SMCs against CoCl2-induced hypoxic injury via the cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]

Objective. It is difficult to evaluate the ablation effect immediately after thermal ablation of liver cancer by clinical imaging methods, due to the immediate formation of an annular inflammatory reaction band (IRB). This study is aimed at exploring the early identification indicators of the IRB and residual tumor postmicrowave ablation (MVA) using contrast-enhanced ultrasonography (CEUS). Methods. MVA was used to inactivate part of the tumor nodules in rabbit VX2 liver cancer models, leading to the coexistence of the IRB with residual tumors. Quantitative analysis of the perfusion parameters of the tumor and ablation zone was performed using CEUS, followed by liver biopsy and VEGFR-2 immunohistochemical staining. Results. All rabbits successfully tolerated VX2 tumor inoculation and MVA operation. No statistically significant difference existed between the IRB vs. residual tumors, the IRB vs. junctional areas, and residual tumors postablation vs. VX2 tumors before ablation in regional blood volume, blood velocity, and blood flow estimated by parameters A , k , and A ∗ k of CEUS quantitative analysis. There was a statistically significant difference between the IRB and normal liver parenchyma in regional blood velocity and blood flow (p = 0.005 and p = 0.023 , respectively). Normal liver parenchyma showed nonspecific VEGFR-2 staining, while VX2 tumor before ablation and residual tumor after ablation both showed positive VEGFR-2 staining; the necrosis zone showed negative staining by VEGFR-2 immunohistochemical staining. Conclusion. MVA had no significant effect on the residual tumor hemodynamics. The blood flow in the IRB increased significantly as compared to normal liver parenchyma, resembling tumor hemodynamic patterns. CEUS can detect residual tumors immediately postablation only when they protrude from the annular-shaped IRB. In addition, VEGFR-2 targeted CEUS may have a great potential for detecting residual tumor after thermal ablation of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background. Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression. Methods. RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3 × type 1 , 3 × type 2 , and 3 × type 3). Student's t -tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results. A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. Conclusions. Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. [ABSTRACT FROM AUTHOR]

Immunotherapy has been demonstrated as a promising strategy in controlling head and neck squamous cell carcinoma (HNSC). The AID/APOBEC family is well characterized as DNA mutator and considered to play critical roles in immune responses in HNSC. However, the expression pattern and deamination-dependent demethylation roles of AID/APOBECs in HNSC are unclear. In this study, the RNA-seq and DNA methylation profiles of HNSC from TCGA database and cell-based experiments were applied to analyze the relationships between AID/APOBEC expression levels, patients' clinical outcomes, methylation alterations, and immune responses. Here, we found that APOBEC3H was abnormally upregulated in HNSC patients. HPV+ patients tended to have higher APOBEC3H levels than HPV- patients. Remarkably, patients with high APOBEC3H levels showed a favorable overall survival. Furthermore, tumors with high APOBEC3H levels exhibited a genome-wide DNA hypomethylation pattern. APOBEC3H was identified to demethylate and upregulate CXCL10 and improve CD8+ T cell tumor infiltration in the tumor microenvironment. Collectively, APOBEC3H plays critical roles in CD8+ T cell immune infiltration and activation in HNSC, which may be a potential biomarker for oncoimmunotherapy in HNSC. [ABSTRACT FROM AUTHOR]

Tec kinase is an important mediator in inflammatory immune response that enhances the activity of neutrophils and macrophages. However, information on its function in lipopolysaccharide- (LPS-) induced acute kidney injury (AKI) is limited. This study is aimed at determining whether Tec kinase was a regulator in AKI. An AKI model in mice was successfully established using intraperitoneal LPS. Results showed that the serum levels of creatinine (Cr), blood urea nitrogen (BUN), and cystatin-C (Cys-C) increased after intraperitoneal LPS injection. Renal tissue sustained significantly severe injury as measured by pathological scores. Pretreatment with LFM-A13 improved the function of the kidney in mice and decreased the renal injury score. Enzyme-linked immunosorbent assay showed that LFM-A13 significantly reduced the release of IL-1β and TNF-α in mice exposed to LPS. LFM-A13 can evidently abrogate the expression of Tec protein, MyD88, TLR4, NF-κB p65, and Tec's phosphorylated protein as determined by Western blot. Immunohistochemistry analysis revealed that LFM-A13 markedly downregulated the expression of Tec kinase in renal tubular epithelial cells. In vitro, Tec kinase protein was expressed highly in NRK-52E cells after LPS exposure. Tec-siRNA also decreased IL-1β and TNF-α production and obviously abolished phospho-p65 and phospho-IκBα expression in NRK-52E cell stimulated by LPS; however, Tec-siRNA increased the IκBα level. Altogether, these data suggested that Tec kinase can be a modulating protein in AKI through TLR4/NF-κB activation. [ABSTRACT FROM AUTHOR]

To reconstruct the ceRNA biological network of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and to select an appropriate mRNA as a biomarker that could be used for CESC early diagnosis and prognosis evaluation. We downloaded CESC data from the TCGA public database, and statistical analysis was conducted with the R software to find out differential expressed genes encoding for lncRNAs, miRNAs, and mRNAs. The differentially expressed mRNAs (DEmRNAs) screened in the ceRNA network were analyzed for survival to find the mRNAs with significantly linked to the survival prognosis. These mRNAs were searched in the Pathological Atlas to identify the final appropriate mRNAs. Differential expression analysis revealed 773 lncRNAs, 94 miRNAs, and 2466 mRNAs. Survival analysis of DEmRNAs in the ceRNA network indicated that ADGRF4, ANXA8L1, HCAR3, IRF6, and PDE2A (P < 0.05) were negatively correlated with survival time. Verification of these six DEmRNAs in the Pathology Atlas indicated that PDE2A was a possible biomarker for CESC patients. PDE2A might be a biomarker for early diagnosis and prognosis evaluation of CESC patients, but due to the lack of available data, further studies may be needed for confirmation. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the effects of human bone marrow mesenchymal stem cells (hBMSCs) and osteoblasts (hFOB1.19) on PC3 prostate cancer cells. Methods. To simulate the in vivo interaction between the bone/bone marrow microenvironments and prostate cancer cells, we established cocultures of PC3 cells with hBMSC or hFOB1.19 cells and evaluated their effects on the proliferation, cell cycle distribution, cell migration, and invasion of PC3 cells. Quantitative reverse transcription polymerase chain reaction was used to detect CD59 mRNA expression in PC3 cells. The expression of receptor activator of nuclear factor- (NF-) κB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), CD59, NF-κB (p50 subunit), and cyclin D1 in PC3 cells was analyzed by immunofluorescence and western blotting. Results. hBMSCs and hFOB1.19 cells enhanced the proliferation, migration, and invasion of PC3 cells; increased the proportion of PC3 cells in the S and G2/M phases of the cell cycle; and upregulated RANK, RANKL, OPG, CD59, cyclin D1, and NF-κB (p50 subunit) expression by PC3 cells. The RANKL inhibitor, scutellarin, inhibited these effects in PC3-hFOB1.19 cocultures. Conclusion. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease which is often associated with Staphylococcus aureus (S. aureus) colonization. S. aureus ingredients are potential ligands to activate the Toll-like receptor 2 (TLR2) and drive inflammatory cytokine or chemokine production. However, the role of TLR2-mediated chemokine expression in AD development has not been systematically investigated. In this study, we sought to determine the mode of TLR2-mediated chemokine expression in AD patients. Human peripheral blood mononuclear cells (PBMCs) were isolated from AD patients and healthy controls. Upon incubation with TLR2 ligands Pam3CSK4 and PGN, mRNA expression of chemokines, including CCL1, CCL5, CCL8, CCL13, CCL17, CCL18, CCL22, and CCL27, were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The results showed that basal mRNA expression of CCL17 in PBMCs from AD patients was upregulated compared with healthy controls, while those of CCL8 and CCL13 were downregulated. When stimulated with TLR2 ligands, the mRNA expression of CCL5, CCL8, CCL13, CCL18, and CCL22 in PBMCs from AD patients was significantly higher than those from healthy controls. The different basal chemokine mRNA expression profiles indicate the different immune status in patients with AD compared with healthy controls. Excessive chemokine mRNA expression induced by TLR2 activation is associated with the development of AD. [ABSTRACT FROM AUTHOR]

A cattle-yak, which is a hybrid between a yak (Bos grunniens) and cattle (Bos taurus), is an important livestock animal, but basic questions regarding its physiology and environmental adaptation remain unanswered. To address this issue, the present study examined the species composition and functional characteristics of rumen microorganisms in the cattle-yak of different ages (2 and 3 years old) by metagenomic analysis. We found that rumen microbial community composition was similar at the two ages. Firmicutes, Fibrobacteres, Euryarchaeota, Bacteroidetes, and Proteobacteria were the predominant phyla, with Firmicutes accounting for the highest percentage of bacteria in 2-year-old (48%) and 3-year-old (46%) animals. Bacterial species involved in lignocellulose degradation were detected in the rumen of adult cattle-yaks including Ruminococcus flavefaciens, Ruminococcus albus, Fibrobacter succinogenes, and Prevotella ruminicola, with F. succinogenes being the most abundant. A total of 145,489 genes were annotated according to the Carbohydrate-active Enzyme database, which identified glycoside hydrolases as the most highly represented enzyme family. Further functional annotation revealed specific microflora and genes in the adult rumen that are potentially related to plateau adaptability. These results could explain the heterosis of the cattle-yak and provide insight into mechanisms of physiologic adaptation in plateau animals. [ABSTRACT FROM AUTHOR]

In renal cell carcinoma, chromophobe renal cell carcinoma (ChRCC) is a distinct subtype, whose clinical manifestations often lack specificity, and the molecular mechanisms of ChRCC tumorigenesis remain generally vague. The target of this study was to discover novel biomarkers involved in ChRCC by integrated bioinformatics analyses. We found 2608 differentially expressed genes (DEGs), of which 1518 were upregulated and 1090 were downregulated. Gene ontology (GO) analysis of DEGs uncovered significant functional enrichment in three aspects: biological process (BP), molecular function (MF), and cellular component (CC). The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated DEGs were largely enriched in retinol metabolism, arachidonic acid metabolism, and pentose and glucuronate interconversions. Then, the protein–protein interactions (PPI) network was constructed and top three hub genes were identified by the Cytoscape plugin cytoHubba. Through calculating the degree, betweenness centrality, and Stress of mRNAs, CENPA was upregulated and KNG1 and AGT were downregulated. A survival assay performed according to Oncomine data showed only CENPA high expression exhibited a worse prognosis. This study identified crucial genes and pathways for the progress of ChRCC, and CENPA might be a novel biomarker for diagnosis, treatment, and prognosis of ChRCC. [ABSTRACT FROM AUTHOR]

Objective. Lung cancer is one of the major causes of cancer deaths worldwide, and the five-year survival still remains low despite the improvement of screening, prevention, and treatment methods. Chinese herbal medicines have been widely used for tumor prevention and treatment. Miao-Yi-Ai-Tang (Miao) is a novel herbal formulation and shows a potential anticancer effect. Materials and Methods. Human Small Cell Lung Cancer Cell was used for study in vitro. After treatments by Miao and Cisplatin (DDP), the invasion, migration, proliferation, and apoptosis of cells were detected by transwell, wound healing, CCK-8, and flow cytometry, respectively. The expression of β-catenin, AXIN, and c-myc was detected by qRT-PCR and immunohistochemistry staining. Western blotting was applied for measuring the protein expression of β-catenin. Subcutaneously transplanted tumor model of lung cancer NCI-H446 was established to investigate the influence of Miao on tumor growth. Results. We found that Miao could inhibit invasion, migration, and proliferation and promote apoptosis of human lung cancer cells. Meanwhile, Miao and DDP presented synergy regulating the proliferation and apoptosis of lung cancer cells. The percentage of lung cancer cells in S and G2 stages was increased markedly by Miao. Besides, the expression of c-myc, AXIN, and β-catenin was markedly inhibited by Miao. Tumor growth in vivo was markedly inhibited by Miao. Conclusions. Chinese herbal formulas Miao could suppress lung cancer through targeting the β-catenin/AXIN signaling pathway. Therefore, our findings may provide a novel strategy for the prevention and treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Purpose. To verify the biomechanical importance with respect to the integrity of posteromedial cortex of femoral neck fracture (FNF) and demonstrate whether the modified fixation of cannulated screws (CSs) could increase the biomechanical strength. Methods. A total of 24 left artificial femurs were randomly divided into three groups. The osteotomy was made in the center of the femoral neck at a 20° angle to the shaft axial. The posteromedial cortices of femoral neck were removed in groups B and C. In group A, 8 femurs with intact posteromedial cortex were fixed with three parallel partial thread screws (PTSs), forming a standard triangle. In group B, the femurs were stabilized with the same fixation of CSs like group A. In group C, two inferior PTSs were replaced by two fully thread screws (FTSs). Results. The lower A-P and axial stiffness and load to failure along with higher axial displacement were found in group B compared with group A (p≤0.001 for all). Between groups B and C, the modified fixation of CSs increased A-P and axial stiffness and load to failure and reduced the axial displacement (p≤0.001 for all). Conclusions. We verified that the comminuted posteromedial cortex affected the biomechanical strength adversely and resulted in higher displacement. The modified fixation of CSs characterized by two inferior FTSs could improve the biomechanical performance and buttress the femoral head fragment better. [ABSTRACT FROM AUTHOR]

Background/Aims. TRPV1 is a nonselective Ca2+ channel which has recently been observed in many cancers, while its effect on cell proliferation, apoptosis, metabolism, and cancer development in colorectal cancer (CRC) is still unclear. In this study, we hypothesized that TRPV1 is a tumor suppressor in CRC development as well as the underlying mechanism. Methods. Immunohistochemistry assay was applied to detect the expression of TRPV1 protein in CRC tissues. HCT116 cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. Cellular Ca2+ concentration was measured by Fluo-4/AM-based flow cytometer. Apoptosis-related proteins were measured by Western blotting. Results. In this study, we found that TRPV1 expression was significantly decreased in CRC tissues, compared with CRC-adjacent tissues and normal tissues, respectively. Then, we found that the TRVP1 agonist capsaicin treatment inhibited CRC growth and induced apoptosis by activating P53. Subsequent mechanistic study revealed that the TRPV1 induced cytosolic Ca2+ influx to regulate cell apoptosis and p53 activation through calcineurin. Conclusions. This study suggests that TRPV1 served as a tumor suppressor in CRC and contributed to the development of novel therapy of CRC. [ABSTRACT FROM AUTHOR]

β-Galactosidase (E.C.3.2.1.23) catalyzes the hydrolysis of lactose into glucose and galactose and the synthesis of galacto-oligosaccharides as well. The β-galactosidases from bacteria, especially lactobacilli, and yeast have neutral pH and are much more likely to be developed as food additives. However, the challenges of cumbersome purification, product toxicity, and low yield in protein production have limited the commercialization of many excellent candidates. In this study, we identified a β-galactosidase gene (bg42-106) in Bifidobacterium animalis ACCC05790 and expressed the gene product in Escherichia coli BL21(DE3) and Pichia pastoris GS115, respectively. The recombinant bG42-106 purified from E. coli cells was found to be optimally active at pH 6.0 and 60°C and had excellent stability over a wide pH range (5.0–8.0) and at high temperature (60°C). The specific activity of bG42-106 reached up to 2351 U/mg under optimal conditions. The galacto-oligosaccharide yield was 24.45 g/L after incubation with bG42-106 at 60°C for 2 h. When recombinant bG42-106 was expressed in Pichia pastoris GS115, it was found in the culture medium but only at a concentration of 1.73 U/ml. To increase its production, three strategies were employed, including codon optimization, disulfide formation, and fusion with a Cherry tag, with Cherry-tag fusion being most effective. The culture medium of P. pastoris that expressed Cherry-tagged bG42-106 contained 24.4 U/mL of β-galactosidase activity, which is 14-fold greater than that produced by culture of P. pastoris harboring wild-type bG42-106. [ABSTRACT FROM AUTHOR]

Intermittent hypoxia (IH) that resulted from obstructive sleep apnea (OSA) has been found to be a risk factor of coronary artery disease. IH and the receptor for advanced glycation end products (RAGE) expression are known to activate monocyte/macrophage and associated with atherosclerosis development, while their effects on monocyte adhesion, chemotaxis to the endothelium, and macrophage polarization remain unknown. In the present study, RAGE in THP-1 monocytes was inhibited by shRNA lentiviral particles, followed by exposure to IH. Cell adhesion assay, transwell migration assay, and macrophage polarization assays were performed to study the effects of IH and RAGE. The mRNA and protein expression levels were investigated by RT/real-time PCR and western blot analysis, respectively. We found that IH increased RAGE expression and activated NF-кB signalling in THP-1 monocytes. The results also revealed that IH enhanced the MCP-1-mediated THP-1 monocyte adhesion and chemotaxis and promoted macrophage polarization toward a proinflammatory phenotype, which was mediated by RAGE activity. Additionally, inhibition of chemokine receptor type 2 (CCR2) suppressed the IH-induced monocyte adhesion and chemotaxis. These results demonstrated a potential role of monocyte adhesion, chemotaxis, and macrophage polarization in the development cardiovascular diseases induced by IH and identified that RAGE could be a promising therapeutic target to prevent atherosclerosis in patients with OSA. [ABSTRACT FROM AUTHOR]

Escherichia coli (E. coli) strains, from the gut of animals and humans, harbor wide range of drug resistance genes. A comparative study is conducted on the intestinal E. coli from fecal samples of healthy chicken from China and Sudan in order to monitor the antimicrobial sensitivity pattern. A number of 250 E. coli isolates from chicken farms, including 120 from China and 130 from Sudan, were isolated and identified. All isolates were subjected to susceptibility tests against 10 antibiotics and the distribution of antibiotic resistant genes was confirmed by PCR amplification, involving genes such as ampC, tetA, pKD13, acrA, ermA, ermB, ermC, tetB, mphA, aadA14, aadA1, aac3-1, and aac3- III. Many isolates were found to exhibit resistance against more than one antibiotic. However, the Chinese isolates showed more antibiotics resistance and resistance genes compared to the Sudanese isolates. For better understanding of the multidrug resistance factors, we conducted whole genome analyses of E. coli D107 isolated from China, which revealed that the genome possesses multiple resistance genes including tetracycline, erythromycin, and kanamycin. Furthermore, E. coli D4 isolate from Sudan was more sensitive to antibiotics such as erythromycin, tetracycline, and gentamicin. After analysis by RAST and MAUVE, the two strains showed 89% average nucleotide identity. However, the genomes mostly differed at the number of antibiotics-related genes, as the genome of D107 revealed a considerable number of antibiotics resistance genes such as ermA and mphD which were found to be absent in D4 genome. These outcomes provided confirmation that the poultry farms environment in different countries (China and Sudan) may serve as a potential reservoir of antimicrobial resistance genes and also indicated the evolutionary differences of strains in terms of resistant genes expression. [ABSTRACT FROM AUTHOR]

Objective. This study investigated the characteristics of carotid atherosclerosis in patients with atrial fibrillation (AF) and determined the feasibility and significance of the CHADS2 score in predicting the degree of carotid atherosclerosis. Methods. Consecutive patients (n = 109) with nonvalvular AF were registered and classified into two groups, the paroxysmal AF group (n = 59) and persistent AF group (n = 50). Fifty healthy patients, matched by sex and age, were considered the control group. All patients were examined using carotid ultrasound and velocity vector imaging (VVI). Results. Compared with the control group, the mean intimal-medial thickness in the paroxysmal AF group (0.56 ± 0.11 versus 0.61 ± 0.10, respectively, P < 0.05) and the persistent AF group (0.56 ± 0.11 versus 0.64 ± 0.13, respectively, P < 0.001) was significantly increased. The plaque index (PI) in the persistent AF group was significantly higher than that observed in the paroxysmal AF group (1.05 ± 1.33 versus 1.42 ± 1.47, respectively, P < 0.001). Regarding the VVI indices, those reflecting the long-axis longitudinal motion function of carotid arteries were significantly decreased in both AF groups. Compared with the control group, a significantly lower total longitudinal displacement (tLoD) index was observed in the persistent AF group (0.73 ± 0.66 versus 0.31 ± 0.23, respectively, P < 0·0001) and the paroxysmal AF group (0.73 ± 0.66 versus 0.34 ± 0.17, P < 0·0001). The CHADS2 score was related to indicators reflecting the structure and function of the carotid artery. Conclusions. Carotid arterial structure and function were significantly altered in patients with AF. The degree of carotid atherosclerosis depended on the duration of AF. The CHADS2 score may be useful as a predictor of the extent of carotid atherosclerosis in patients with AF. [ABSTRACT FROM AUTHOR]

Objectives. We evaluated the biomechanical outcome of different plate fixation strategies (the single plate construct, 45° double-plate construct, 90° double-plate construct, 135° double-plate construct, and 180° double-plate construct) used for the fixation of the femoral shaft nonunion with no cortical support opposite the primary lateral plate. This may help surgeons choose the optimal therapy to the femoral shaft nonunion. Methods. The femoral shaft nonunion with no medial support and the models of lateral plate and medial plate was constructed in 3-matic software and UG-NX software, respectively. We then assembled the single plate and different double plates to the fracture model separately to form the fixation models. After meshing the models’ elements, we used the ABAQUS software to perform the finite element analysis. Values of the von Mises Stress (VMS) distribution of the implant, peak VMS, and model displacement and deformation were used to capture the mechanical factors in this study. Results. Our results indicated that the peak von Mises Stress (VMS) of the lateral plate was concentrated in middle surface of the lateral plate near the fragment of each group. The peak VMS was 5201.0 MPa (the single-plate construct), 3490.0 MPa (45° double-plate construct), 1754.0 MPa (90° double-plate construct), 1123.0 MPa (135° double-plate construct), and 816.5 MPa (180° double-plate construct). The additional short plate dispersed some stress leading to the decrease in the peak VMS of the lateral plate. As angle formed by the double plates increased, the dispersed function of the additional plate was becoming obvious. The bending angles of the lateral plate were 18° versus 12° versus 3° versus 2° versus 1° (the single-plate construct versus 45° double-plate construct versus 90° double-plate construct versus 135° double-plate construct versus 180° double-plate construct). Conclusions. Our study indicated that increasing the angle between the plates in a double-plate construct improves the stability of the construct over a single lateral plate when there is no cortical support opposite to the lateral plate. The strongest fixation occurred when the angle between the two plates was greater than ninety degrees. [ABSTRACT FROM AUTHOR]

Proanthocyanidin (PC) has attracted wide attention on cosmetics and pharmaceutical due to its antioxidant, anticancer, antimicrobial, antiangiogenic, and anti-inflammatory activities. However, PC applications are limited because of its sensitivity to thermal treatment, light, and oxidation and the poor absorption in the gastrointestinal tract. Thus, a novel dosage form of PC needs to be designed to improve its stability and bioavailability for drug delivery. The objective of this study is to fabricate proanthocyanidins/chitosan/lecithin (PC/CTS/LEC) microspheres and investigate various characteristics. In the current study, PC/CTS/LEC microspheres were prepared by spray-drying technology. The yield (61.68%), encapsulation efficiency (68.19%), and drug loading capacity (17.05%) were found in the results. The scanning electron microscope demonstrated that the microspheres were spherical in shape with wrinkled surfaces. DSC study displayed that the microspheres stability was greatly improved when comparing with bare PC. The in vitro release study showed that the 76.92% of PC was released from microspheres within 48 h. The moisture contents of microspheres ranged from 8% to 13%. The swelling rate and tapped density of microspheres were elevated with increasing the concentration of chitosan in the formulations. The moisture uptake of microspheres was saturated at 40°C/RH75% within 12 h. Our results indicated that the stability of PC/CTS/LEC microspheres was enhanced, and it is a promising carrier for sustained drug delivery system. [ABSTRACT FROM AUTHOR]

Schistosomiasis is one of the world’s major public health problems. Praziquantel is currently the only effective drug against schistosomiasis. As resistance of praziquantel has emerged in some endemic areas, development of new antischistosomal agents should be a high priority. In this study, a phage display peptide library was used for screening for peptide antagonists of thioredoxin glutathione reductase of Schistosoma japonicum (SjTGR), which has been identified as an alternative drug target. Three rounds of panning produced four different fusion phages. ELISA proved that all four phages could bind to SjTGR. One peptide, JIPDys1 (aa, WPHNWWPHFKVK), reduced enzyme activity of SjTGR by more than 50%. 2 μM of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC50 values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67 μM, 0.11 μM, and 0.97 μM, respectively. Based on computer simulation, it appeared that JIPDys1 binds to the substrate binding sites of glutathione reductase (GR) and glutaredoxin (Grx). Our data show that the peptide, JIPDys1 (aa, WPHNWWPHFKVK), is a promising candidate to develop novel drugs against S. japonicum which acts by binding with SjTGR and reduces enzyme activity of SjTGR. [ABSTRACT FROM AUTHOR]

As a proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α) plays a pivotal role in various autoimmune diseases such as rheumatoid arthritis (RA). Thus, TNF-α has been defined as a therapeutic target for RA. Although some TNF-α antagonists including neutralizing monoclonal antibodies and soluble receptors have been approved to be successful in attenuating symptoms in patients suffering from RA, the long-term use of these passive immunization reagents could cause some problems like a variable degree of immunogenicity. In the present study, in order to wake up active immune responses of RA patients, we developed a recombinant TNF-α therapeutic vaccine (named mrTNF-PADRE) by coupling a 12-amino acid universal Pan HLA-DR Epitope (PADRE) to the protein. Codon optimization was performed to improve the secondary structure of mrTNF-PADRE mRNA to ensure its heterologous expression. As a result, a single codon synonymous mutation greatly elevated recombinant protein expression (about 30% of the total bacteria proteins) in E. coli as compared with the undetectable expression of the unoptimized gene. Although expressed as insoluble inclusion bodies (IBs), the vaccine can be effectively prepared with a purity of over 95% by IBs washing and one-step gel-infiltration chromatography. By this strategy, a stable yield of 5.2 mg purified mrTNF-PADRE per gram of cell paste could be obtained. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study is to verify whether the headless cannulated compression screw (HCCS) has higher biomechanical stability than the ordinary cannulated compression screw (OCCS) in the treatment of vertical femoral neck fractures. Materials and Methods. 30 synthetic femur models were equally divided into 2 groups, with 50°, 60°, and 70° Pauwels angle of femoral neck fracture, under 3D printed guiding plates and C-arm fluoroscopic guidance. The femur molds were fixed with three parallel OCCSs as OCCS group and three parallel HCCSs as HCCS group. All specimens were tested for compressive strength and maximum load to failure with a loading rate of 2 mm/min. Results. The result showed that there was no significant difference with the compressive strength in the Pauwels angle of 50° and 60°. However, we observed that the maximum load to failure with the Pauwels angle of 50°, 60°, and 70° and the compressive strength with 70° of HCCS group showed better performance than the OCCS group. Conclusion. HCCS performs with better biomechanical stability than OCCS in the treatment of vertical femoral neck fracture, especially with the Pauwels angle of 70°. [ABSTRACT FROM AUTHOR]

Background. The Optical Surface Management System (OSMS) is a simple, fast, reproducible, and accurate solution for patient set-up and can minimize random day-to-day set-up errors. However, studies in breast cancer patients are rare. Objective. To analyze 200 patient set-ups in 20 patients with breast cancer by comparing the OSMS with the conventional cone-beam computed tomography (CBCT). Method. Displacements from concurrent OSMS and CBCT registrations were compared in a total of 200 setups of 20 patients to analyze the interfractional displacement and positioning displacement in three dimensions (lateral, longitudinal, and vertical directions). Results. The interfractional displacement on the lateral, longitudinal, and vertical directions for OSMS versus CBCT was 0.049±0.254 versus 0.041±0.244 centimeters (cm); 0.018±0.261 versus 0.040±0.242 cm; 0.062±0.254 versus 0.065±0.240 cm, respectively, without any significant difference (all P>0.05). The duration for CBCT scan was about 60 seconds (s), while that for image processing, matching, and couch displacement was at least 5 minutes (min). The average scanning time with OSMS was less than 20 s, and the total duration for positioning was less than 1 min. Conclusion. OSMS is an efficient tool to improve the accuracy and increase the speed for verifying the patient positioning in radiotherapy for breast cancer. [ABSTRACT FROM AUTHOR]

Zoledronic acid (ZOL) is the third generation of bisphosphonates, which can inhibit many tumors growth, especially to inhibit the growth of colon cancer. However, the molecular mechanism is still very mysterious. In this study, we observed that ZOL could regulate CT26 colon cancer cells autophagy, promote CT26 cells apoptosis, and inhibit CT26 cells proliferation. Western blotting analysis showed that proapoptosis protein caspase-3 was basically unchanged, whereas the expression of the activated caspase-3 was significantly increased, after CT26 cells were treated with different doses of zoledronic acid. Western blot also showed that ZOL could significantly affect the expression of p-p53 and autophagy-related proteins beclin-1 and p62. In conclusion, the antitumor effect of ZOL on CT26 colon cancer cells in vitro is achieved by apoptosis induction and autophagy regulation, resulting in inhibition of cell proliferation. [ABSTRACT FROM AUTHOR]