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IntroductionNumerous studies have demonstrated acute myeloid leukemia (AML) is one of the malignancies with high mortality worldwide. Immunogenic cell death (ICD) is a form of cell death that is specialised in that it triggers the body’s immune response, particularly the adaptive immune response. Recent evidence has confirmed that pseudogenes are implicated in multiple human tumorigenesis and progression although lacking the function of coding protein. However, the roles of ICD-associated genes in AML remain largely unascertained.MethodsTCGA-AML and GSE71014 cohorts were picked out and we combined them into a merged dataset by removing the batch effect using the sva package in the R project. A consensus clustering analysis of the ICD genes in AML was performed to define subgroups. Based on the expression of 15 prognostic-related pseudogenes, we developed a prognostic model and categorized AML samples into low and high-risk groups.ResultsAML was differentiated into two subgroups (C1 and C2 clusters). Most ICD-related genes were significantly up-regulated in the C2 cluster. The single sample gene set enrichment analysis (ssGSEA) revealed that the immune cell infiltration and immune checkpoint gene expression of the C2 cluster was strongly high, suggesting that the C2 population responded well to immune checkpoint blockade (ICB) therapy and had better survival. The C1 group was sensitive to chemotherapy, including Cytarabine, Midostaurin, and Doxorubicin. On the other hand, 15 ICD-related pseudogenes were identified to be associated with AML prognosis. The receiver operator curve (ROC) analysis and nomogram manifested that our prognostic model had high accuracy in predicting survival. However, the high-risk group was sensitive to ICB therapy and chemotherapy such as Methotrexate, Cytarabine, and Axitinib while the low-risk group benefited from 5-Fluorouracil, Talazoparib, and Navitoclax therapy.DiscussionIn summary, we defined two subgroups relying on 33 ICD-related genes and this classification exerted a decisive role in assessing immunotherapy and chemotherapy benefit. Significantly, a prognostic signature identified by critical ICD-related pseudogene was created. The pseudogene prognostic signature had a powerful performance in predicting prognosis and therapeutic efficacy, including immunotherapy and chemotherapy to AML. Our research points out novel implications of ICD in cancer prognosis and treatment approach choice.

AbstractObjectives The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) pose significant clinical challenges. This study aims to compare the efficacy and long-term outcomes of the two treatments in TD-NSAA.Methods Patients who underwent ATG-based IST or allo-HSCT between July 2011 and December 2019 were reviewed. We gathered their clinical information, treatment response, survival data, and subsequently analysed the associated risk factors.Results A total of 97 TD-NSAA patients were reviewed, and 55 patients who underwent either ATG-based IST (n = 27) or allo-HSCT (n = 28) were enrolled. We observed a significant disparity in the 12-month overall response rate (ORR) (48.1% in IST vs 78.6% in HSCT, p

Abstract As the most common modification of RNA, N6-methyladenosin (m6A) has been confirmed to be involved in the occurrence and development of various cancers. However, the relationship between m6A and castration resistance prostate cancer (CRPC), has not been fully studied. By m6A-sequencing of patient cancer tissues, we identified that the overall level of m6A in CRPC was up-regulated than castration sensitive prostate cancer (CSPC). Based on the analysis of m6A-sequencing data, we found m6A modification level of HRas proto-oncogene, GTPase (HRAS) and mitogen-activated protein kinase kinase 2 (MEK2 or MAP2K2) were enhanced in CRPC. Specifically, tissue microarray analysis and molecular biology experiments confirmed that METTL3, an m6A “writer” up-regulated after castration, activated the ERK pathway to contribute to malignant phenotype including ADT resistance, cell proliferation and invasion. We revealed that METTL3-mediated ERK phosphorylation by stabilizing the transcription of HRAS and positively regulating the translation of MEK2. In the Enzalutamide-resistant (Enz-R) C4-2 and LNCap cell line (C4-2R, LNCapR) established in the current study, the ERK pathway was confirmed to be regulated by METTL3. We also found that applying antisense oligonucleotides (ASOs) to target the METTL3/ERK axis can restore Enzalutamide resistance in vitro and in vivo. In conclusion, METTL3 activated the ERK pathway and induced the resistance to Enzalutamide by regulating the m6A level of critical gene transcription in the ERK pathway.

Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail.Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated.Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways.Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy.

Joint arthroplasty is an effective method for treating end-stage joint lesions and damages. Robotic arm-assisted arthroplasty, a rapidly developing technology that combines navigation technology, minimally invasive technology, and precise control technology of the robotic arm, can achieve accurate preoperative planning, optimal selection of implants, minimally invasive surgery, precise osteotomy, and accurate placement of the artificial joint. It has the characteristics of high accuracy and stability, and thus is more and more widely used in the field of joint surgery. In this paper, we systematically reviewed the application and clinical efficacy of robotic arm-assisted technology in hip and knee arthroplasty to provide reference for its future promotion.

With an increasing number of international students coming to China for higher education, the learning needs of academic Chinese increased sharply. However, Chinese for Academic Purposes (CAP) is still in its infancy in both academic research and teaching practice. As a result, students lack the support for their academic Chinese skills and encounter difficulties according to their feedback. Meanwhile, the studies on English for Academic Purposes (EAP) pedagogy are fruitful. Among all the pedagogies, corpus-based instruction with genre analysis were found to be an effective approach in improving students’ EAP writing abilities. This study thus applied corpus-based genre analysis teaching approach to CAP teaching and examined the effectiveness. Through the construction and analysis of a specific corpus, this paper first investigated the move structure and high-frequency words and expressions of Chinese research article (RA) abstracts in the discipline of Economics and Management Science. Afterwards, a mini learning corpus was compiled for students’ exploration. The learning materials and sample tasks were introduced and data were collected from students’ feedback and writing samples before and after the teaching intervention. The results revealed that, firstly, the conventional move structure of Chinese RA abstracts in Economics and Management Science was I-MR-D, which is similar to English RA abstracts. Method and Results are two conventional moves. Second, corpus-based genre analysis can partially improve students’ performances in academic writing. After the teaching intervention, students’ awareness of text structure and the use of academic Chinese expressions improved noticeably. Though based on a small sample size, the research findings contribute towards the understanding of linguistic conventions of Chinese RA abstracts. Moreover, the materials and pedagogy used in this project shed new light on the instruction of Chinese writing as well as CAP curriculum development.

Cancer is a debilitating disease, causing millions of deaths annually throughout the world. Due to their adaptive ability to meet nutritional demands, cancer cells often utilize more energy than normal cells. In order to develop new strategies to treat cancer, it is necessary to understand the underlying mechanisms of energy metabolism, which is yet largely unknown. Recent studies have shown that cellular innate nanodomains are involved in cellular energy metabolism and anabolism and GPCRs signaling regulation, which have a direct effect on cell fate and functions. Therefore, harnessing cellular innate nanodomains may evoke significant therapeutic impact and shift the research focus from exogenous nanomaterials to cellular innate nanodomains, which will have great potential to develop a new treatment modality for cancer. Keeping these points in view, we briefly discuss the impact of cellular innate nanodomains and their potential for advancing cancer therapeutics, and propose the concept of innate biological nano confinements, which include any innate structural and functional nano domains both in extracellular and intracellular with spatial heterogeneity.

BackgroundStaphylococcus aureus (S. aureus) is the leading cause of various infective diseases, including topical soft tissue infections. The goals of this study were to investigate the roles of YycF and CodY in the regulation of biofilm formation and pathogenicity.MethodsElectrophoretic mobility shift assay (EMSA) was conducted to validate the bound promoter regions of YycF protein. We constructed the codY up-regulated or down-regulated S. aureus mutants. The biofilm biomass was determined by crystal violet microtiter assay and scanning electron microscopy (SEM). Quantitative RT-PCR analysis was used to detect the transcripts of biofilm-related genes. The live and dead cells of S. aureus biofilm were also investigated by confocal laser scanning microscopy (CLSM). We constructed an abscess infection in Sprague Dawley (SD) rat models to determine the effect of CodY on bacterial pathogenicity. We further used the RAW264.7, which were cocultured with S. aureus, to evaluate the effect of CodY on macrophages apoptosis.ResultQuantitative RT-PCR analyses reveled that YycF negatively regulates codY expression. EMSA assays indicated that YycF protein directly binds to the promoter regions of codY gene. Quantitative RT-PCR confirmed the construction of dual- mutant stains codY + ASyycF and codY-ASyycF. The SEM results showed that the biofilm formation in the codY + ASyycF group was sparser than those in the other groups. The crystal violet assays indicated that the codY + ASyycF group formed less biofilms, which was consistent with the immunofluorescence results of the lowest live cell ration in the codY + ASyycF group. The expression levels of biofilm-associated icaA gene were significantly reduced in the codY + strain, indicating codY negatively regulates the biofilm formation. Furthermore, CodY impedes the pathogenicity in a rat-infection model. After cocultured with bacteria or 4-h in vitro, the apoptosis rates of macrophage cells were lowest in the codY + group.ConclusionsYycF negatively regulate the expression of codY. By interaction with codY, YycF could modulate S. aureus biofilm formation via both eDNA- dependent and PIA- dependent pathways, which can be a significant target for antibiofilm. CodY not only impedes the pathogenicity but also has a role on immunoregulation. Thus, the current evidence may provide a supplementary strategy for managing biofilm infections.

Bone infection results in a complex inflammatory response and bone destruction. A broad spectrum of bacterial species has been involved for jaw osteomyelitis, hematogenous osteomyelitis, vertebral osteomyelitis or diabetes mellitus, such as Staphylococcus aureus (S. aureus), coagulase-negative Staphylococcus species, and aerobic gram-negative bacilli. S. aureus is the major pathogenic bacterium for osteomyelitis, which results in a complex inflammatory response and bone destruction. Although various antibiotics have been applied for bone infection, the emergence of drug resistance and biofilm formation significantly decrease the effectiveness of those agents. In combination with gram-positive aerobes, gram-negative aerobes and anaerobes functionally equivalent pathogroups interact synergistically, developing as pathogenic biofilms and causing recurrent infections. The adhesion of biofilms to bone promotes bone destruction and protects bacteria from antimicrobial agent stress and host immune system infiltration. Moreover, bone is characterized by low permeability and reduced blood flow, further hindering the therapeutic effect for bone infections. To minimize systemic toxicity and enhance antibacterial effectiveness, therapeutic strategies targeting on biofilm and bone infection can serve as a promising modality. Herein, we focus on biofilm and bone infection eradication with targeting therapeutic strategies. We summarize recent targeting moieties on biofilm and bone infection with peptide-, nucleic acid-, bacteriophage-, CaP- and turnover homeostasis-based strategies. The antibacterial and antibiofilm mechanisms of those therapeutic strategies include increasing antibacterial agents’ accumulation by bone specific affinity, specific recognition of phage-bacteria, inhibition biofilm formation in transcription level. As chronic inflammation induced by infection can trigger osteoclast activation and inhibit osteoblast functioning, we additionally expand the potential applications of turnover homeostasis-based therapeutic strategies on biofilm or infection related immunity homeostasis for host-bacteria. Based on this review, we expect to provide useful insights of targeting therapeutic efficacy for biofilm and bone infection eradication.

Objectives There is a controversy on the diagnostic reliability and accuracy of synovial fluid α‐defensin in periprosthetic joint infection (PJI). We performed this meta‐analysis to evaluate the diagnostic accuracy of the α‐defensin lateral flow test in PJI. Methods PubMed, Embase, and the Cochrane library were systematically searched, and articles (up to January 2020) on the diagnosis of hip and knee PJIs using the α‐defensin Synovasure lateral flow test were included. The diagnostic accuracy of the α‐defensin lateral flow test in PJI was evaluated using meta‐analysis. The pooled sensitivity, specificity, accuracy, positive and negative likelihood ratio, diagnostic odds ratio, and post‐test probabilities were calculated. Results Seventeen studies including 1443 cases were included. Meta‐analysis showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and a diagnostic odds ratio was 0.83 (95% CI 0.77, 0.88), 0.95 (95% CI 0.93, 0.97), 16.86 (95% CI 11.67, 24.37), 0.17 (95% CI 0.13, 0.24) and 85.30 (95% CI 47.76, 152.35), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.97 (95% CI 0.95, 0.98). Subgroup analysis also confirmed the high efficiency of α‐defensin Synovasure lateral flow test in diagnosing PJIs, irrespective of ethnicity. Fagan's nomogram analysis there was a high positive post‐test probability of 94% and a low negative post‐test probability of 15%. Conclusions We indicated that the α‐defensin lateral flow test had a high accuracy for diagnosing PJI. Large‐scale studies are needed to validate its significance in PJI diagnosis.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown. Methods In the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF. Results CHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF. Conclusions Our work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL. Trial registration Not applicable.

ObjectivesThis study was conducted in order to develop and validate an ultrasonic-based radiomics nomogram for diagnosing solid renal masses.MethodsSix hundred renal solid masses with benign renal lesions (n = 204) and malignant renal tumors (n = 396) were divided into a training set (n = 480) and a validation set (n = 120). Radiomics features were extracted from ultrasound (US) images preoperatively and then a radiomics score (RadScore) was calculated. By integrating the RadScore and independent clinical factors, a radiomics nomogram was constructed. The diagnostic performance of junior physician, senior physician, RadScore, and radiomics nomogram in identifying benign from malignant solid renal masses was evaluated based on the area under the receiver operating characteristic curve (ROC) in both the training and validation sets. The clinical usefulness of the nomogram was assessed using decision curve analysis (DCA).ResultsThe radiomics signature model showed satisfactory discrimination in the training set [area under the ROC (AUC), 0.887; 95% confidence interval (CI), 0.860–0.915] and the validation set (AUC, 0.874; 95% CI, 0.816–0.932). The radiomics nomogram also demonstrated good calibration and discrimination in the training set (AUC, 0.911; 95% CI, 0.886–0.936) and the validation set (AUC, 0.861; 95% CI, 0.802–0.921). In addition, the radiomics nomogram model showed higher accuracy in discriminating benign and malignant renal masses compared with the evaluations by junior physician (DeLong p = 0.004), and the model also showed significantly higher specificity than the senior and junior physicians (0.93 vs. 0.57 vs. 0.46).ConclusionsThe ultrasonic-based radiomics nomogram shows favorable predictive efficacy in differentiating solid renal masses.

A 33-year-old Chinese woman with a history of immune thrombocytopenic purpura presented with heavy menstrual bleeding. She was found to have thrombocytopenia, plasma ADAMTS13 activity of 0%, and positivity for the plasma ADAMTS13 inhibitor. She was diagnosed with the coexistence of thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura. The patient was treated by plasmapheresis, a glucocorticoid, and rituximab. Her platelet level returned to normal, and she was discharged 28 days after admission. The number of plasmapheresis sessions and the timing of rituximab administration may be the key aspects of management of patients with thrombotic thrombocytopenic purpura who have underlying immune dysfunction caused by diseases such as immune thrombocytopenic purpura.

Abstract Background The aim of this study is to evaluate the prophylactic effects of probiotic mixture BIFICO on antibiotic-induced gut dysbiosis (AIGD) and the influence on the change of the gut microbiota. Methods We conducted a prospective, randomized, controlled study and divided 196 patients who required intravenous beta-lactam antibiotics into three groups: a control group (no probiotics), a regular group (840 mg of BIFICO), and a double-dosage group (1680 mg of BIFICO). The symptoms of antibiotic-related diarrhea, bloating and abdominal pain and the incidence of AIGD were evaluated 7 days and 8–14 days after antibiotic use, with 10 patients in each group. 16S rDNA sequencing was performed to detect changes of the gut microbiota. Results Within 7 days of the initiation of antibiotic treatment, the incidences of AIGD in the control group, regular group (840 mg of BIFICO), and double-dosage group (1680 mg of BIFICO) were 21.88%, 14.93%, and 6.15% respectively. On days of 8–14th, the incidences of AIGD in the control group, regular group, and double-dosage group were 25%, 14.93%, and 4.62%, respectively. The incidence of AIGD in the double-dosage group within 7 days and 14 days were both significantly lower than that in relevant control group (P

Abstract Background C-Myc overexpression is associated with poor prognosis and aggressive progression of natural killer/T-cell lymphoma (NKTCL). Matrine, a main alkaloid of the traditional Chinese herb Sophora flavescens Ait, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The present study investigated the effects and possible mechanisms of matrine inhibiting the growth of natural killer/T-cell lymphoma cells. Methods The effects of matrine on the proliferation, apoptosis and expression of apoptotic molecules, STAT3, LMP1, RUNX3, EZH2 and activation of CaMKIIγ/c-Myc pathway were examined in cultured NKTCL cell line NK92 cells. Results In cultured NK92 cells, matrine inhibited the proliferation in a dose and time dependent manner. The IC50 value of matrine was 1.71 mM for 72 h post exposure in NK92 cells. Matrine induced apoptosis with decreased Bcl-2 expression and the proteasome-dependent degradation of c-Myc protein in NK92 cells. c-Myc protein half-life in NK92 was reduced from 80.7 min to 33.4 min after matrine treatment, which meant the stability of c-Myc was decreased after matrine exposure. Furthermore, we found that matrine downregulated c-Myc phosphorylation at Ser62 together with the inhibition of CaMKIIγ, a key regulator of c-Myc protein in NKTCL. The downregulation of c-Myc transcription by matrine was mediated through LMP1 inhibition. We also observed that anti-proliferative activity of matrine was irrelevant to STAT3, RUNX3 and EZH2. Conclusions The results of the present study indicated that matrine inhibits the growth of natural killer/T-cell lymphoma cells by modulating LMP1-c-Myc and CaMKIIγ-c-Myc signaling pathway.

Aim. The relationship between postsurgical pain and osseointegration was evaluated and analyzed in this study. Material and method. 27 patients, ranging in age from 35 to 72 years old, 12 males and 15 females, who received dental implants and failed to achieve osseointegration from Tianjin Medical University Second Hospital, were analyzed and studied in the following aspects: bone density, initial torque, one- or two-stage surgery, postsurgical pain, postsurgical swelling, and radiographic evidence of osseointegration failure. Result. 5 patients were assessed to be D4 bone density and 7 cases were assessed to be D3 bone density, 2 patients were assessed to be D2 bone density and 13 patients were assessed to be D1 bone density. All cases were documented with clinically acceptable initial torque. Among the 27 cases, 2 of them were one-stage nonsubmerged surgery and 25 cases were two-stage submerged surgery. 25 out of 27 patients reported moderate to severe pain lasting for more than 72 hours. Radiologic examinations failed to offer any indication of poor osseointegration in the 7-day postsurgical follow-up. Conclusion. Moderate to severe postsurgical pain lasting more than 72 hours displays high odd ratio of poor osseointegrate. The radiological examinations alone failed to offer any valuable evidence for the early detection of osseointegration failure in this study.

Since the mid-1980s, there has been an academic shift toward students’ involvement in the learning process. A great number of studies have focused on the relationship between student engagement and educational achievement. They have highlighted that appropriate educational input and a supportive classroom environment are necessary, but optimum learning should occur when students are engaged with the curriculum as well as the institution, particularly in higher education institutions. Many scholars claimed that higher levels of engagement will help students deal with academic anxiety and develop a sense of belonging, which may lead to higher academic success. Educational experts and policymakers have begun to propose nationwide and international strategies and programs to promote student engagement in the classroom, which has led to the proposal of well-known programs such as the National Survey of Student Engagement, the UK Engagement Survey, and Program for International Student Assessment. Such engagement-centered international measures have been used across the globe (e.g., Germany) and translated into different languages (e.g., Chinese). Although the findings of relevant studies confirm the effectiveness of engagement on learning achievement, there is still the need to conduct further (cross-sectional) studies considering the implementation of such programs in a different context. The present study is an attempt to review the related literature regarding student engagement among Chinese and German students across a variety of disciplines. The findings suggest that researchers should devote more time and budget to investigate the significance of learner engagement, especially in Germany and China.

Intermittent fasting confers protections to various diseases including autoimmune disorders, but the specific effects of intermittent fasting on Sjögren’s syndrome (SS) remains inconclusive. The present study was undertaken to determine the specific impact of alternate-day fasting (ADF) on newly established SS-like sialadenitis using non-obese diabetic (NOD) mice. Female NOD mice were deprived of food every other day from 10 to 13 weeks of age, the early stage of established SS, and then analyzed for the disease characteristics. Mice in the ADF group had higher salivary flow rate and attenuated submandibular gland (SMG) inflammation, compared to the control mice fed with standard chow ad libitum. The improvements were accompanied with a decrease in the total leukocytes, T and B lymphocytes and activated CD4 and CD8 T cells, and a down-regulation of pro-inflammatory cytokines IFN-γ and IL-17, chemokine receptor CXCR3 and its ligands CXCL9 and CXCL11 in the SMGs. ADF also led to elevated mRNA levels of water channel protein aquaporin 5 and tight junction protein claudin-1, two factors crucial for normal salivary secretion in the SMGs. In addition, ADF reduced the proportion of IFN-γ- and IL-17- expressing CD4 T cells and diminished mRNA levels of IFN-γ, TNF-α, and IL-17 in the total submandibular draining lymph node cells. Taken together, ADF is effective in ameliorating newly established SS-associated salivary gland exocrinopathy in NOD mice.

BackgroundBoth omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells.MethodsCell counting kit-8 (CCK-8), Ki67 immunofluorescence and transwell assays were used to assess the viability, proliferation and migration of U937 and Raji cells respectively. In addition, tube formation assay was used to determine the effects of HHT/curcumin combination on angiogenesis in human umbilical vein endothelial cells (HUVECs).ResultsIn this study, we found that HHT/curcumin combination significantly inhibited the proliferation, migration and invasion in U937 and Raji cells (all P < 0.01). In addition, combination treatment markedly inhibited the secreted levels of vascular endothelial growth factor (VEGF)-(A-D) (all P < 0.01) in Raji cells. Moreover, combination treatment exhibited anti-tumor effects in Raji cells, as shown by the decreased signals of phosphorylated VEGF receptor 2 (p-VEGFR2) and phosphorylated protein kinase B (p-Akt) (all P < 0.01). Meanwhile, combination treatment inhibited VEGFA levels (P < 0.01) in exosomes derived from Raji cells. Application of exosomes with downregulated VEGF to HUVECs notably inhibited proliferation, migration and tube formation of HUVECs, evidenced by the decreased signals of p-Akt, angiogenin-1, matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) (all P < 0.01).ConclusionOur findings indicated that combination of HHT and curcumin could inhibit lymphoma cell growth and angiogenesis via inhibition of VEGF/Akt signaling pathway. These results suggested that HHT combined with curcumin might be regarded as a promising therapeutic approach for the treatment of lymphoma.

Abstract Background Although several anesthesia procedures have been explored for orthopedic surgery, the complications of anesthesia remain not well resolved. This study aimed to explore the influence of different anesthesia methods on the complications after orthopedic surgery. Methods According to the searching strategy, anesthesia associated studies in orthopedic surgery were screened from Pubmed, Embase, and the Cochrane Library up to Mar. 10th, 2018. Then, complications and demographic data were extracted and quality of studies was assessed using Cochrane Collaboration recommendations. ADDIS software was used to perform the network meta-analysis. Pooled effect size was calculated using random effective model or consistency model, and presented with odds ratio (OR) and 95% confidence interval (CI). Results According to the selective criteria, a total of 23 studies with 2393 patients were enrolled in this study. Quality assessment revealed all studies had an ordinary quality. Network meta-analyses revealed that nerve block analgesia (NBA) presented a lower effect on the occurrence of post-operative nausea or vomiting (PONV; OR = 0.17, 95% CI: 0.06–0.39) and urine retention (OR = 0.07, 95% CI: 0.01–0.37) compared with epidural anesthesia (EA). Interscalene block (ISB) and local infiltration analgesia (LIA) could significantly reduce the occurrence of back pain compared with EA (OR = 0.00, 95% CI = 0.00–0.30; OR = 0.00, 95% CI = 0.00–0.25). Conclusion NBA presented an effective role in reliving the occurrence of PONV and urine retention, and ISB and LIA relieved the back pain compared with EA after orthopedic surgery.

To make accurate and comprehensive evaluation of the catenary and diagnose the causes of the catenary fault, a method of catenary state evaluation and diagnosis based on the principal component analysis control chart was proposed, which can make full use of the multidimensional detection parameters of the catenary. The principal component analysis was used to reduce the dimension of catenary parameters, the principal component T2 control chart was calculated to show the change of principal component of catenary state data, the residual SPE control chart was calculated to show the change of their correlation, and the contribution rate control chart was calculated to show the cause of abnormal state data. The method can not only transform the multidimensional detection parameters of the catenary into a statistic to realize the simple and intuitive evaluation of the catenary state but also can accurately determine the cause of the abnormal state, so as to provide technical support for the targeted condition-based maintenance of the catenary.

Abstract Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. Objective: This study aimed to explore whether such effect is dependent on TLR9 signaling. Material and Methods: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses. We determined B cell numbers using a hemocytometer at 24 h and 48 h. Percentages of CD1dhiCD5+ B cells were detected by flow cytometry. Interleukin-10 (IL-10) mRNA expression and protein secretion were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and by ELISA, respectively. The silk ligature was tied around the maxillary second molars for 14 days, during which the CpG+CD40L mixture or PBS was injected into palatal gingiva on days 3, 6, and 9. Results: For both WT and TLR9 KO mice, CpG significantly induced B cell proliferation, increased IL-10 mRNA expression and protein secretion of IL-10 but reduced CD1dhiCD5+ B cells population; local injection of CpG+CD40L mixture significantly decreased alveolar bone loss and the number of TRAP-positive cells adjacent to the alveolar bone surface, and significantly increased the gingival mRNA expression of IL-10 and decreased RANKL and IFN-γ mRNA expression. Conclusions: These results indicated that CpG plus CD40L decreased periodontal inflammation and alveolar bone loss in a TLR9-independent manner in ligature-induced experimental periodontitis.

The cyclic resistance of ProTaper Universal (size 25/08) and ProTaper Next (size 25/06) instruments was compared in artificial canals with different curvatures in this study. A total of 30 ProTaper Universal and 30 ProTaper Next instruments were divided into 6 groups (n = 10) and were operated into artificial canals with 3 different angles of curvature (45°, 60°, 90°). The canal length was kept consistent in this study. The number of cycles to fracture (NCF) was counted until file fracture occurred, at which point, the length of the fragment was measured. The data were analyzed statistically using ANOVA complemented by the Tukey test (p < 0.05). Cross sections of the fractured files were scanned by an electron microscope. In the fatigue test, the ProTaper Next displayed more resistance in 45° and 60° canals (p < 0.05), whereas ProTaper Universal exhibited a better operability in 90° canals (p < 0.05). The average length of the fragments from ProTaper Next was significantly shorter than that from ProTaper Universal in 90° canals (p < 0.05). The cross sections of the fractured surfaces became flatter when the curvature angles decreased from 90° to 45°. ProTaper Next was more reliable when shaping in curved canals, whereas ProTaper Universal was more sui for the preparation of root canals with severe curvatures.

Thelaziosis is a zoonosis with regional epidemics, mainly present in oriental countries, with a majority of cases reported from China. We report a pediatric case of thelaziosis and present a literature review of Chinese case reports. The epidemiological features and clinical characteristics of thelaziosis in China are presented.

Lysosomes are crucial in the tumour immune microenvironment, which is essential for the survival and homeostasis in multiple myeloma (MM). Here, we aimed to identify lysosome-related genes for the prognosis of MM and predicted their regulatory mechanisms. Gene expression profiles of MM from the GSE2658 and GSE57317 datasets were analysed. Lysosome-related differentially expressed genes (DEGs) were identified and used for molecular subtyping of MM patients. A prognostic model was constructed using univariate Cox regression and LASSO regression analyses. The relationship between prognostic genes, immune cell types, and autophagy pathways was assessed through correlation analysis. RT-qPCR was performed to validate the expression of prognostic genes in MM cells. A total of 9,954 DEGs were identified between high and low immune score groups, with 213 intersecting with lysosomal genes. Molecular subtyping revealed two distinct MM subtypes with significant differences in immune cell types and autophagy pathway activities. Five lysosome-related DEGs (CORO1A, ELANE, PSAP, RNASE2, and SNAPIN) were identified as significant prognostic markers. The prognostic model showed moderate predictive accuracy with AUC values up to 0.723. Prognostic genes demonstrated significant correlations with various immune cell types and autophagy pathways. Additionally, CORO1A, PSAP and RNASE2 expression was up-regulated in MM cells, while ELANE and SNAPIN were down-regulated. Five lysosomal genes in MM were identified, and a new risk model for prognosis was developed using these genes. This research could lead to discovering important gene markers for the treatment and prognosis of MM. [ABSTRACT FROM AUTHOR]