Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study.

BACKGROUND: Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS. METHOD: This study focused on patients with EGS and utilized electronic medical record systems to obtain data retrospectively from five centers in China. Five ML algorithms, including Random Forest (RF), Support Vector Machine, Naive Bayes, XGBoost, and Logistic Regression, were employed to construct predictive models for postoperative mortality, pneumonia, surgical site infection, thrombosis, and mechanical ventilation >48 h. The optimal models for each outcome event were determined based on metrics, including the value of the Area Under the Curve, F1 score, and sensitivity. A comparative analysis was conducted between the optimal models and Emergency Surgery Score (ESS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and American Society of Anesthesiologists (ASA) classification. A web-based calculator was developed to determine corresponding risk probabilities. RESULT: Based on 10 993 patients with EGS, we determined the optimal RF model. The RF model also exhibited strong predictive performance compared with the ESS, APACHE II score, and ASA classification. Using this optimal model, the authors developed an online calculator with a questionnaire-guided interactive interface, catering to both the preoperative and postoperative application scenarios. CONCLUSIONS: The authors successfully developed an ML-based calculator for predicting the risk of postoperative adverse events in patients with EGS. This calculator accurately predicted the occurrence risk of five outcome events, providing quantified risk probabilities for clinical diagnosis and treatment.

RING finger ubiquitin E3 ligase CsCHYR1 targets CsATAF1 for degradation to modulate the drought stress response of cucumber through the ABA-dependent pathway.

CsCHYR1 (CHY ZINC-FINGER AND RING PROTEIN1) encodes a RING (Really Interesting New Gene) finger E3 ubiquitin ligase involved in ubiquitin-mediated protein degradation and plays an important role for cucumber to resist drought stress. Here, we obtain one of the candidate proteins CsCHYR1 that probably interacts with CsATAF1 by yeast-two hybrid screening. Subsequently, it is verified that CsCHYR1 interacts with CsATAF1 and has self-ubiquitination activity. When the cysteine residue at 180 in the RING domain of CsCHYR1 is replaced by serine or alanine, ubiquitin could not be transported from E2 to the substrate. CsCHYR1 ubiquitinates CsATAF1 and affects the stability of CsATAF1 when plants are subjected to drought stress. The expression level of CsCHYR1 is increased by 4-fold after ABA treatment at 9 h. The Atchyr1 mutants perform an ABA-hyposensitive phenotype and have a lower survival rate than Col-0 and CsCHYR1 Atchyr1 lines. In addition, CsCHYR1 interacts with CsSnRK2.6. Therefore, our study reveals a CsSnRK2.6-CsCHYR1-CsATAF1 complex to promote the drought stress response by decreasing CsATAF1 protein accumulation and inducing stomatal closure. Those findings provide new ideas for cucumber germplasm innovation from the perspective of biochemistry and molecular biology.

A NETWORK PHARMACOLOGY-BASED TREATMENT ANALYSIS OF LUTEOLIN FOR REGULATING PYROPTOSIS IN ACUTE LUNG INJURY.

ABSTRACT: Background: Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome, are complicated pulmonary inflammatory conditions for which standard therapeutics are still not well established. Although increasing research has indicated the anti-inflammatory, anticancer, and antioxidant effects of luteolin, especially in lung diseases, the molecular mechanisms underlying luteolin treatment remain largely unclear. Methods: The potential targets of luteolin in ALI were explored using a network pharmacology-based strategy and further validated in a clinical database. The relevant targets of luteolin and ALI were first obtained, and the key target genes were analyzed using a protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The targets of luteolin and ALI were then combined to ascertain the relevant pyroptosis targets, followed by Gene Ontology analysis of core genes and molecular docking of key active compounds to the antipyroptosis targets of luteolin in resolving ALI. The expression of the obtained genes was verified using the Gene Expression Omnibus database. In vivo and in vitro experiments were performed to explore the potential therapeutic effects and mechanisms of action of luteolin against ALI. Results: Fifty key genes and 109 luteolin pathways for ALI treatment were identified through network pharmacology. Key target genes of luteolin for treating ALI via pyroptosis were identified. The most significant target genes of luteolin in ALI resolution included AKT1, NOS2, and CTSG. Compared with controls, patients with ALI had lower AKT1 expression and higher CTSG expression. Luteolin simply reduced systemic inflammation and lung tissue damage in septic mice. Furthermore, we blocked AKT1 expression and found luteolin reduced the degree of lung injury and affected NOS2 levels. Conclusions: As demonstrated by a network pharmacology approach, luteolin may exert an antipyroptosis effect on ALI via AKT1, NOS2, and CTSG.

The salivary chaperone protein NlDNAJB9 of Nilaparvata lugens activates plant immune responses.

The brown planthopper (BPH) Nilaparvata lugens (Stål) is a main pest on rice. It secretes saliva to regulate plant defense responses, when penetrating rice plant and sucking phloem sap through its stylet. However, the molecular mechanisms of BPH salivary proteins regulating plant defense responses remain poorly understood. A N. lugens DNAJ protein (NlDNAJB9) gene was highly expressed in salivary glands, and the knock down of NlDNAJB9 significantly enhanced honeydew excretion and fecundity of the BPH. NlDNAJB9 could induce plant cell death, and the overexpression of NlDNAJB9 gene in Nicotiana benthamiana induced calcium signaling, mitogen-activated protein kinase (MAPK) cascades, reactive oxygen species (ROS) accumulation, jasmonic acid (JA) hormone signaling and callose deposition. The results from different NlDNAJB9 deletion mutants indicated that the nuclear localization of NlDNAJB9 was not necessary to induce cell death. The DNAJ domain was the key region to induce cell death, and the overexpression of DNAJ domain in N. benthamiana significantly inhibited insect feeding and pathogenic infection. NlDNAJB9 might interact indirectly with NlHSC70-3 to regulate plant defense responses. NlDNAJB9 and its orthologs were highly conserved in three planthopper species, and could induce ROS burst and cell death in plants. Our study provides new insights into the molecular mechanisms of insect-plant interactions.

[miR-151-3p derived from gastric cancer exosomes induces M2-phenotype polarization of macrophages and promotes tumor growth].

Objective To investigate whether exosomes derived from gastric cancer cells can affect macrophages in tumor microenvironment through miR-151-3p. Methods The expression of miR-151-3p in tumor tissues of patients with gastric cancer and normal tissues was detected by real time quantitative PCR; Gastric cancer cells overexpressing miR-151-3p were constructed, and exosomes were isolated and identified. The expression of CD11b and CD163 markers on RAW264.7 cells co-incubated with exosomes were detected by flow cytometry, and the effects of exosome carrying miR-151-3p on tumor growth and tumor-associated macrophages were evaluated in mice transplanted tumor model. Results The results of real time quantitative PCR showed that the level of miR-151-3p in gastric tumor tissues was significantly higher than that in normal tissues, and the content of miR-151-3p in gastric juice of most patients after operation was lower than that before operation; The content of miR-151-3p in exosomes of tumor cells overexpressing miR-151-3p was also significantly higher than that of untransfected cells. Exosomes carrying miR-151-3p can induce phenotypic differentiation of M2 in co-incubation with RAW264.7 cells. Similarly, tumor transplantation model also showed that exosomes carrying miR-151-3p can induce tumor-associated macrophages to polarize to M2 and promote tumor growth. Conclusion miR-151-3p derived from gastric cancer exosomes can induce the polarization of M2 macrophages and promote the growth of gastric cancer. The treatment of miR-151-3p may destroy the tumor microenvironment of immunosuppression, which assists the anti-tumor immunotherapy.

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis.

Homeobox (HOX) transcript antisense RNA (Hotair) is elevated in many cancers significantly. However, the oncogenic role of Hotair in human laryngeal squamous cell carcinoma (LSCC) is still unknown. Thus, we explored the expression profile of Hotair and its function in LSCC. We observed high expression levels of Hotair in six LSCC cell lines compared to the human nasopharyngeal epithelial cell line. Knockdown of Hotair inhibited proliferation and enhanced apoptosis of Tu212 and Hep-2 cell lines in vitro. Moreover, the overexpression of hsa-miR-30a-5p inhibited the expression of GRP78 and PD-L1, but Hotair overexpression in LSCC cells rescues both proteins. Furthermore, the impacts of hsa-miR-30a-5p upregulation on the apoptosis and proliferation of LSCC cells were rescued by overexpression of Hotair. Finally, we combined si-Hotair and a VEGF inhibitor to treat LSCC cells in vitro or in vivo and surprisingly observed a significant inhibition of LSCC growth. In summary, these results indicate that Hotair displays an oncogenic role in both malignancy and immune escape in LSCC related to hsa-miR-30a-5p/GRP78/PD-L1 signaling. Therefore, Hotair may be a potential target for treating LSCC.

Citrate-based mussel-inspired magnesium whitlockite composite adhesives augmented bone-to-tendon healing.

Citrate-based mussel-inspired whitlockite composite adhesives (CMWAs) were developed and administered to the bone-tendon interface in anterior cruciate ligament (ACL) reconstruction. CMWAs could improve the initial bone-tendon bonding strength, promote the bony inward growth from the bone tunnel and enhance the chondrogenesis and osteogenesis of the bone-tendon interface, thus augmenting bone-to-tendon healing.

Clinical characteristics and risk factors for symptomatic venous thromboembolism in hospitalized COVID-19 patients: A multicenter retrospective study.

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.

Kinesin Family Member C1 Increases Temozolomide Resistance of Glioblastoma Through Promoting DNA Damage Repair.

Glioblastoma (GBM) is one of the most frequent primary malignant brain tumors with a poor prognosis. Unfortunately, due to the intrinsic or acquired chemoresistance of GBM cells, it easily becomes refractory disease and tumors are easy to recur. Therefore, it is critical to elucidate the molecular mechanisms underlying the chemoresistance of GBM cells to discover more efficient therapeutic treatments. Kinesin family member C1 (KIFC1) is a normal nonessential kinesin motor that affects the progression of multiple types of cancers. However, whether KIFC1 have a function in GBM is still unexplored. Here we found that KIFC1 was upregulated in human temozolomide (TMZ)-resistant GBM tissues. KIFC1 silencing is sufficient to inhibit GBM cell proliferation and amplify TMZ-induced repression of cell proliferation. Mechanistically, KIFC1 silencing contributed to DNA damage, cell cycle arrest, and apoptosis through regulating Rad51, Akt, and DNA-PKcs phosphorylation. We also noticed that KIFC1 silencing also inhibited tumor formation and increased TMZ sensitivity through regulating Ki67, Rad51, γ-H2AX, and phosphorylation of AKT in vivo. Our findings therefore confirm the involvement of KIFC1 in GBM progression and provide a novel understanding of KIFC1-Akt axis in the sensitivity of GBM to chemotherapy.

The value of dynamic monitoring of procalcitonin in the early identification of pathogens and prognosis of bloodstream infections in the ICU.

BACKGROUND: To explore the value of dynamic monitoring of procalcitonin (PCT) for early identification of pathogens and prognosis of bloodstream infections (BSI) in the intensive care unit (ICU). METHODS: A retrospective analysis was performed on 84 patients with positive blood cultures. Patients were divided into the survival group and death group according to prognosis. Dynamic changes of PCT before and after treatment in the two groups were compared, as well as the relationship between such changes and prognosis. RESULTS: Among the 84 patients with bloodstream infections, 41 cases of Gram-negative (G-) bacteria, 40 cases of Gram-positive (G+) bacteria, and 3 cases of fungi were detected. PCT value in the G- bacteria group was significantly higher than that in the G+ bacteria group and fungus group, and the difference was statistically significant (P<0.05). PCT values on the first day of the G- bacteria group and the non-G- bacteria group were analyzed by a receiver operating characteristic (ROC) curve. When the threshold value was 3.84 ng/mL, the sensitivity, specificity, and area under the ROC curve for predicting G- bacteria bloodstream infection were 61%, 92.5%, and 0.841, respectively. The Kruskal-Wallis test (K-W test) was performed on PCT levels of each G- bacteria on the first day of bloodstream infection, and the difference was not statistically significant (P>0.05). Logistic binary regression analysis showed that the reduction rate of PCT after 5 days of treatment was an independent protective factor for patient survival. ROC curves showed that the sensitivity and specificity for predicting patient survival were 88% and 68.7%, respectively, when the PCT reduction rate (PCT(D1-D5)/D1) reached 36.02% or more. CONCLUSIONS: PCT can be used as an adjunctive method to quickly diagnose pathogenic microorganisms of bloodstream infections, and the anti-infection treatment scheme has certain guiding value. The dynamic changes in PCT have a certain role in predicting the therapeutic effect and prognosis of anti-infection treatment.

miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP.

BACKGROUND: miR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. However, its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood. METHODS: Quantitative real-time polymerase chain reaction was used to detect the relative expression of miR-431-5p in synovial tissues and FLSs. Cell proliferation assays helped examine RA FLS proliferation. Flow cytometry was performed to determine apoptosis and cell cycle progression in RA FLSs. We used dual-luciferase assays to determine the correlation between miR-431-5p and its putative target, X-linked inhibitor of apoptosis (XIAP). Quantitative real-time PCR and western blotting were used to measure XIAP levels in synovial tissues and transfected RA FLSs. RESULTS: miR-431-5p was downregulated in synovial tissues and FLSs of patients with RA. Upregulation of miR-431-5p prohibited cell proliferation and the G0/G1-to-S phase transition but promoted apoptosis in RA FLSs, while miR-431-5p inhibition showed the opposite results. miR-431-5p directly targeted XIAP in RA FLSs and reversely correlated with XIAP levels in synovial tissues. Notably, XIAP silencing partially restored the effects of miR-431-5p inhibition in RA FLSs. CONCLUSION: miR-431-5p regulates cell proliferation, apoptosis, and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA.

LncRNA NEAT1 Targets Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via the miR-410-3p/YY1 Axis.

LncRNA NEAT1 functions as an oncogene in multiple human cancers. However, its expression and role in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) remain unclear. Thus, we investigated the expression of NEAT1 in synovial tissues and FLSs in RA, to determine its role in the development of RA. Quantitative real-time polymerase chain reaction was used to measure the expression of NEAT1. FLS proliferation was evaluated using cell proliferation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis in FLSs. Binding between NEAT1 and miR-410-3p was demonstrated by dual-luciferase assays. We found that NEAT1 was upregulated in synovial tissues and FLSs in RA. Upregulation of NEAT1 promoted cell proliferation, induced S-to G2/M phase transition, and suppressed apoptosis in RA FLSs. NEAT1 directly bound to and negatively modulated miR-410-3p expression, while positively regulating YinYang 1(YY1; a miR-410-3p target). Inhibiting miR-410-3p and upregulating YY1 partially restored the inhibitory role in cell viability induced by the depletion of NEAT1 in RA FLSs. Besides pro-proliferative and anti-apoptotic roles, upregulation of NEAT1 promoted migration, invasion, and inflammatory cytokines secretion in RA FLSs. Taken together, our results suggest that the NEAT1 may serve as a novel diagnostic and therapeutic target for patients with RA.

Fasciotomy through multiple small skin incisions for the treatment of early acute osteofascial compartment syndrome in children.

BACKGROUND: The purpose of the present study is to investigate the therapeutic effect of fasciotomy through multiple small skin incisions for the treatment of early osteofascial compartment syndrome in children. METHODS: From January 2009 to May 2017, 56 pediatric patients with early osteofascial compartment syndrome in their limbs were admitted into our department and treated with multiple small skin incisions for decompression at the early stage. The skin incisions, function, and sensation of the limbs were followed up. RESULTS: The osteofascial compartment syndrome was diagnosed at 7.4 ± 2.1 h after injury, and then fasciotomy was performed at 1.4 ± 0.4 h later. The average procedure time of fasciotomy was 12.7 ± 4.8 min. No postoperative incision infections or neurovascular injuries were observed in all the patients. The incisions completely healed in 7-10 days with an average healing time of 8 days without secondary suture. The patients were followed up for an average of 5.1 years. No Volkmann's contractures in the injured limbs were found. The appearance, electromyography, and nerve conduction velocity of the affected limbs were not significantly different from that of the contralateral limbs. All the patients were free of symptoms and were fully recovered of sensation and function, being an "excellent" outcome at the latest follow-up. CONCLUSION: Fasciotomy through multiple small skin incisions, which can be useful to decompress the compartment pressure with fewer complications, is a simple and effective strategy for the treatment of early osteofascial compartment syndrome in children.

Clinical effect of manual reduction of humeroradial joint in the treatment of type â -â ¢ fresh Monteggia fracture in children.

PURPOSE: To evaluate the efficacy of closed reduction on the humeroradial joint in the treatment of Bado type Ⅰ, Ⅱ and Ⅲ fresh Monteggia fractures in children and investigate the effect of clinical factors, including Bado classification, age and time of treatment on the success rate of closed reduction. METHODS: We retrospectively studied the data of children ≤10 years old with fresh Monteggia fractures (injury within two weeks) treated by manual reduction with plaster immobilization from January 2014 to April 2019. All patients were followed up in the outpatient department every two weeks for 4-6 weeks until plaster removal and then 3, 6 and 12 months. Online or telephone interview was provided for some inconvenient patients after 6 months. Mackay criteria were used to evaluate the clinical effect. Radiographic data were collected and reviewed to assess the reduction of the humeroradial joint. Function of the elbow joint and forearm was evaluated and risk factors related to the failure of reduction were assessed. The successful manual reduction was analyzed from three aspects, respectively Bado fracture type (Ⅰ, Ⅱ, Ⅲ), patient age (<3 year, 3-6 years, >6 years) and time interval from injury to treatment (group A, <1 day; group B, 1-3 days; group C, >3 days). RESULTS: Altogether 88 patients were employed in this study, including 58 males (65.9%) and 30 females (34.1%) aged from 1 to 10 years. There were 29 cases (33.0%) of Bado type Ⅰ Monteggia fractures, 16 (18.2%) type Ⅱ and 43 (48.7%) type Ⅲ. Successful manual reduction was achieved in 79 children (89.8%) at the last follow-up. The failed 9 patients received open surgery. Mackay criteria showed 100% good-excellent rate for all the patients. The success rate of manual reduction was 89.7%, 87.5% and 90.7% in Bado type Ⅰ, Ⅱ and Ⅲ cases, respectively, revealing no significant differences among different Bado types (χ2 = 0.131, p = 0.937). Successful closed reduction was achieved in 13 toddlers (13/13, 100%), 38 preschool children (28/42, 90.5%) and 28 school-age children (28/33, 84.8%), suggesting no significant difference either (χ2 = 2.375, p = 0.305). However time interval from injury to treatment showed that patients treated within 3 days had a much higher rate of successful manual reduction: 67 cases (67/71, 94.4%) in group A, 10 cases (10/11, 90.9%) in group B, and 2 cases (2/6, 33.3%) in group C (χ2 = 22.464, p < 0.001). Fisher's test further showed significant differences between groups A and C (p = 0.001) and groups B and C (p = 0.028). CONCLUSION: Closed reduction is a safe and effective method for treating fresh Monteggia fractures in children. The reduction should be conducted as soon as possible once the diagnosis has been made.

miR-483-3p promotes cell proliferation and suppresses apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by targeting IGF-1.

Accumulating evidence suggests that miR-483-3p is implicated in maintaining biological properties in human cancers. However, its biological roles in rheumatoid arthritis (RA) remain unknown. miR-483-3p levels in synovial tissue samples and fibroblast-like synoviocytes (FLSs) were determined using quantitative real-time PCR. The CCK-8 assay and EdU staining were performed to assess cell proliferation in RA FLSs after transfection with miR-483-3p mimics or inhibitor. Flow cytometry with Annexin V-FITC staining or PI staining was performed to assess apoptosis or cell cycle progression in RA FLSs, respectively. miR-483-3p was upregulated in RA, which markedly promoted cell proliferation, induced the G0/G1-to-S phase transition, and suppressed apoptosis in RA FLSs, whereas miR-483-3p silencing yielded opposite results. Moreover, insulin growth factor 1 (IGF-1) was detected as a direct miR-483-3p target. IGF-1 silencing partially restored cell proliferation, the G0/G1-to-S phase transition, and apoptosis suppression in RA FLSs via miR-483-3p inhibition. Our results showed that miR-483-3p promotes RA FLSs proliferation by targeting IGF-1, suggesting a potential strategy for diagnostic and treatment strategy for RA.

HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.

Co-expression Network Analysis Identifies Four Hub Genes Associated With Prognosis in Soft Tissue Sarcoma.

Background: Soft tissue sarcomas (STS) are heterogeneous tumors derived from mesenchymal cells that differentiate into soft tissues. The prognosis of patients who present with an STS is influenced by the regulation of a complex gene network. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with STS (Samples = 156). Results: Among the 11 modules identified, the black and blue modules were highly correlated with STS. However, using preservation analysis, the black module demonstrated low preservation, therefore the blue module was chosen as the module of interest. Furthermore, a total of 20 network hub genes were identified in the blue module, 12 of which were also hub nodes in the protein-protein interaction network of the module genes. Following additional verification, 4 of 12 genes (RRM2, BUB1B, CENPF, and KIF20A) demonstrated poorer overall survival and disease-free survival rate in the test datasets. In addition, gene set enrichment analysis (GSEA) demonstrated that samples with a high level of blue module eigengene (ME) were enriched in cell cycle and metabolism associated signaling pathways. Conclusion: In summary, co-expression network analysis identified four hub genes associated with prognosis for STS, which may diminish the prognosis by influencing cell cycle and metabolism associated signaling pathways.

MicroRNA-1271 functions as a potential tumor suppressor in hepatitis B virus-associated hepatocellular carcinoma through the AMPK signaling pathway by binding to CCNA1.

Hepatocellular carcinoma (HCC) is mainly associated with hepatitis B virus (HBV) infection and characterized by metastasizing and infiltrating adjacent and distant tissues. Notably, microRNA-1271 (miR-1271) is a tumor suppressor in various cancers. Therefore, we evaluate the ability of miR-1271 to influence cell proliferation, migration, invasion, and apoptosis in HBV-associated HCC through the Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway via targeting CCNA1. HBV-associated HCC and adjacent normal tissues were collected to identify the expression of miR-1271 and CCNA1. To verify the relationship between miR-1271 and CCNA1, we used bioinformatics prediction and the dual-luciferase reporter gene assay. The effects of miR-1271 on HBV-associated HCC cell behaviors were investigated by treatment of the miR-1271 mimic, the miR-1271 inhibitor, or small interfering RNA against CCNA1. The HBV-DNA quantitative assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromid assay, scratch test, transwell assay, and flow cytometry were used to detect HBV-DNA replication, cell proliferation, invasion, migration, and apoptosis. MiR-1271 showed a low expression, whereas CCNA1 showed a high expression in HBV-associated HCC tissues. We identified that miR-1271 targeted and negatively regulated CCNA1. Upregulated miR-1271 and downregulated CCNA1 inhibited the HBV-associated HCC cell HBV-DNA replication, proliferation, migration, and invasion, while accelerating apoptosis by activating the AMPK signaling pathway. MiR-1271 promotes the activation of the AMPK signaling pathway by binding to CCNA1, whereby miR-1271 suppresses HBV-associated HCC progression. This study points to a potential therapeutic approach of downregulation of miR-1271 in HBV-associated HCC treatment.

Using co-axial electrospray deposition to eliminate burst release of simvastatin from microparticles and to enhance induced osteogenesis.

Microparticles (MPs) exhibit fast dissolution, characterized by a burst drug release pattern. In the present work, we prepared core-shell MPs of simvastatin (SIM) and zein with chitosan (CS) and nano-hydroxyapatite (nHA) as a drug carrier using the coaxial electrospray deposition method. The morphology, formation and in vitro osteogenic differentiation of these MPs were studied. The synthetic MPs have a diameter of about 1 µm and they are composed of non-toxic natural materials. They provide an effective way to enable long-term sustained-release activity, which is controlled by their double layer structures. The CS-nHA/zein-SIM MPs presented a low initial burst release (approximately 35-47%) within the first 24 h of application followed by the sustained release for at least 4 weeks. In vitro cell culture experiments were performed and the results revealed that the CS-nHA/zein-SIM core-shell MPs were beneficial to the adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The CS-nHA/zein-SIM MPs with a low SIM concentration were beneficial to cell proliferation and promotion of osteogenic differentiation.

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) in sarcoma remains controversial. We performed a meta-analysis so as to investigate the impact of PD-L1 on clinicopathlogical findings and survival outcomes in sarcoma. MATERIALS AND METHODS: A comprehensive search in PubMed, Embase and the Cochrane Library was conducted for relevant studies. The odds ratios or hazard ratios, at 95% confidence intervals were used as measures for investigation of the correlation between PD-L1 expression and clinicopathlogical features or survival outcomes. RESULTS: Fourteen eligible studies comprising 868 patients were selected for analysis. Pooled hazard ratios indicated that the association of PD-L1 expression with overall survival in bone sarcoma (osteosarcoma and chondrosarcoma) patients was statistically significant (1.987, 95% CI: 1.224-3.224, p = 0.005), as was its association with event-free survival in bone and soft-tissue sarcoma patients (3.868, 95% CI: 2.298-6.511, p = 0.000). Additionally, the expression of PD-L1 was positively correlated with the infiltration of programmed death 1 (PD-1) positive T-lymphocytes (OR: 4.012, 95% CI: 2.391-6.733, p = 0.000). CONCLUSIONS: Our meta-analysis indicated that high PD-L1 expression is likely to be a negative factor for patients with sarcomas and that it predicts worse survival outcomes.