SPA inhibits hBMSC osteogenic differentiation and M1 macrophage polarization by suppressing SETD2 in acute suppurative osteomyelitis.

To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4's inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: Up until now, no research has been reported on the association between the clinical growth rate of multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and computed tomography (CT) imaging characteristics. Our study sought to examine the correlation between them, with the objective of distinguishing unique features of MCRNLMP from renal cysts and exploring effective management strategies. AIM: To investigate optimal management strategies of MCRNLMP. METHODS: We retrospectively collected and analyzed data from 1520 patients, comprising 1444 with renal cysts and 76 with MCRNLMP, who underwent renal cyst decompression, radical nephrectomy, or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution. Detection of MCRNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology. RESULTS: Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP. Precisely, it comprises 1.48% of all cases involving simple renal cysts, 5.26% of those with complex renal cysts, and a noteworthy 12.11% of renal tumors coexisting with renal cysts, indicating a statistically significant difference (P = 0.001). Moreover, MCRNLMP constituted a significant 22.37% of the patient population whose cysts demonstrated a rapid growth rate of ≥ 2.0 cm/year, whereas it only represented 0.66% among those with a growth rate below 2.0 cm/year. Of the 76 MCRNLMP cases studied, none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis. In the remaining 67 patients, who were actively monitored over a 3-year postoperative period, only one showed suspicious recurrence on CT scans. CONCLUSION: MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators. In treating MCRNLMP, partial nephrectomy is preferred, while radical nephrectomy should be minimized. After surgery, active monitoring is advisable to prevent unnecessary nephrectomy.

Metallophthalocyanine as ideal antibiotics without light: Mechanisms and applications.

The urgent global health problem of antimicrobial resistance (AMR) calls for the discovery of new antibiotics with innovative modes of action while considering the low toxicity to mammalian cells. This paper proposes a novel strategy for designing antibiotics with selective bacterial toxicity by exploiting the positional differences of electron transport chains (ETC) in bacterial and mammalian cells. The focus is on cytochrome c (cyt C) and its maturation system in E. coli. The catalytic oxidative activity of metallophthalocyanine (MPc), which have a distinctive M-N4 structure, is being investigated. Unlike previous applications based on light-activated reactive oxygen species (ROS) generation, this study exploits the ability of MPcs to oxidize Fe2+ to Fe3+ in cyt C and catalyze the formation of disulfide bonds between cysteine residues to interfere with cyt C maturation, disrupt the bacterial respiratory chain and selectively kills bacteria. In contrast, in mammalian cells, these MPcs are located in the lysosomes and cannot access the ETC in the mitochondria, thus achieving selective bacterial toxicity. Two MPcs that showed effective antibacterial activity in a wound infection model were identified. This study provides a valuable reference for the design of novel antibiotics based on M-N4-based metal complex molecules.

ZX703: A Small-Molecule Degrader of GPX4 Inducing Ferroptosis in Human Cancer Cells.

Ferroptosis is a novel form of oxidative cell death triggered by iron-dependent lipid peroxidation. The induction of ferroptosis presents an attractive therapeutic strategy for human diseases, such as prostate cancer and breast cancer. Herein, we describe our design, synthesis, and biological evaluation of endogenous glutathione peroxidase 4 (GPX4) degraders using the proteolysis targeting chimera (PROTAC) approach with the aim of inducing ferroptosis in cancer cells. Our efforts led to the discovery of compound 5i (ZX703), which significantly degraded GPX4 through the ubiquitin-proteasome and the autophagy-lysosome pathways in a dose- and time-dependent manner. Moreover, 5i was found to induce the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, thereby inducing ferroptosis. This study provides an attractive intervention strategy for ferroptosis-related diseases.

Prognostic factors of primary intrascrotal rhabdomyosarcoma in children: a population-based study.

PURPOSE: Primary intrascrotal rhabdomyosarcoma (RMS) is a rare and aggressive tumor. The purpose of this study was to investigate the prognostic factors of intrascrotal RMS in children. METHODS: All pediatric patients with intrascrotal RMS diagnosed between 2000 and 2018 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. To compare survival curves, the log-rank test was employed. A multivariate Cox proportional hazards model was developed to investigate the effect of each factor on overall survival (OS). A nomogram was created using the outcomes of the Cox regression model. RESULTS: A total of 102 pediatric patients with intrascrotal RMS were identified. Overall survival rates for all patients were 90.6% at 3-year and 87.2% at 5-year, respectively. Survival rates differed significantly by SEER stage and surgery; however, chemotherapy and removal of lymph nodes showed no significant difference. The outcome of Cox proportional hazard regression revealed that SEER stage and surgery were important independent predictors in this model. Furthermore, we developed a nomogram for predicting OS in pediatric intrascrotal RMS based on the Cox regression model. The risk of death increased with stage in patients. Additionally, patients who underwent surgery had a lower mortality risk than those who did not. CONCLUSIONS: Our findings show that SEER stage and surgery are the most important indicators of OS in children with intrascrotal RMS, providing critical epidemiological information for clinical therapy.

Stachydrine represses the proliferation and enhances cell cycle arrest and apoptosis of breast cancer cells via PLA2G2A/DCN axis.

Considering the therapeutic efficacy of Stachydrine on breast cancer (BC), this study aims to decipher the relevant mechanism. The effects of Stachydrine on BC cell viability, proliferation and apoptosis were firstly investigated. Then, Bioinformatics was applied to sort out the candidate interacting with Stachydrine as well as its expression and downstream target in BC. Relative expressions of genes of interest as well as proliferation- and apoptosis-related factors in BC cells were quantified through quantitative reverse-transcription PCR and western blot as appropriate. As a result, Stachydrine inhibited the proliferation, down-regulated the expressions of proliferating cell nuclear antigen and CyclinD1, enhanced cell cycle arrest and apoptosis, and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9 in BC cells. Phospholipase A2 Group IIA (PLA2G2A) was predicted as the candidate interacting with Stachydrine and to be lowly expressed in BC. PLA2G2A silencing reversed while PLA2G2A overexpression reinforced the effects of Stachydrine. Decorin (DCN) was the downstream target of PLA2G2A and also lowly expressed in BC. PLA2G2A silencing counteracted yet overexpressed PLA2G2A strengthened the promoting effects of Stachydrine on DCN level. Collectively, Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis.

Design, Synthesis, and Biological Evaluation of Hydrophobic-Tagged Glutathione Peroxidase 4 (GPX4) Degraders.

Ferroptosis is an iron-dependent form of oxidative cell death induced by lipid peroxidation accumulation. Glutathione peroxidase 4 (GPX4) plays a key role in the regulation of ferroptosis and is considered to be a promising therapeutic target for cancer and other human diseases. Herein, we describe our design, synthesis, and biological evaluation of a series of HyT-based degraders of the GPX4. One of the most promising compounds, 7b (ZX782), effectively induces dose- and time-dependent degradation of GPX4 protein and potently suppresses the growth of human fibrosarcoma HT1080 cells, which are highly sensitive to ferroptosis and widely used for evaluating compound specificity in ferroptosis. Mechanism investigation indicated that 7b depletes GPX4 through both the ubiquitin-proteasome and the autophagy-lysosome. Furthermore, the degradation of GPX4 induced by 7b could significantly increase the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, ultimately leading to ferroptosis. Overall, compound 7b exhibits robust potency in depleting endogenous GPX4, thereby modulating ferroptosis in cancer cells.

FBLN5 as One Presumably Prognostic Gene Potentially Modulating Tumor Immune Microenvironment for Renal Clear Cell Carcinoma in Children and Young Adults.

Objective: To investigate the role of FBLN5in renal clear cell carcinoma (KIRC), in particular on the tumor's immune microenvironment, including children and young adults. Methods: FBLN5 expression in tumor and normal samples was explored using SangerBox, TIMER2.0, GEPIA, UALCAN, HPA databases. The Linkedomics database was used to obtain FBLN5 co-expressed genes in KIRC tissue. SangerBox was also used to estimate immune infiltration of FBLN5 in KIRC. The Kaplan-Meier plotter was used to investigate the survival effects of FBLN5 expression in the presence of immune infiltration. We then collected 48 cases from 7 hospitals over a-20 year period to calculate the impact of FBLN5 on the prognosis of children and young adults with KIRC. Results: FBLN5 expression was significantly reduced in KIRC tissue compared to normal adjacent tissue. FBLN5 was potentially involved in the immune-related biological processes. In addition, FBLN5 expression has been linked to a number of immune checkpoints, cytokines, chemokines and chemokine receptors in KIRC. At the same time, the expression of FBLN5 affected the survival rates differently in KIRC patients with high or low levels of immune infiltration. High expression of FBLN5 in children and young adults with KIRC was associated with a favorable prognosis. Conclusion: This study shed light on the potential of FBLN5 as a prognostic marker in children and young adults with KIRC and as an immune-related target for clinical treatment.

Design, synthesis, and biological evaluation of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives as TRPM4 inhibitors for the treatment of prostate cancer.

Transient receptor potential melastatin 4 (TRPM4) is considered to be a potential target for cancer and other human diseases. Herein, a series of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives were designed and synthesized as new TRPM4 inhibitors, aiming to improve cellular potency. One of the most promising compounds, 7d (ZX08903), displayed promising antiproliferative activity against prostate cancer cell lines. 7d also suppressed colony formation and the expression of androgen receptor (AR) protein in prostate cancer cells. Furthermore, 7d can concentration-dependently induce cell apoptosis in prostate cancer cells. Collectively, these findings indicated that compound 7d may serve as a promising lead compound for further anticancer drug development.

Clinical characteristics and prognostic factors for primary pediatric and adolescent Non-Hodgkin Lymphomas of the gastrointestinal tract: a population-based study.

PURPOSE: To investigate the clinical features and survival outcomes of primary gastrointestinal non-Hodgkin lymphomas (PGINHL) in pediatric and adolescent population, we conducted a population-based cohort study. METHODS: All pediatric and adolescent patients with PGINHL diagnosed between 2000 and 2019 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplane-Meier estimations were used to generate survival curves based on various criteria. To compare survival curves, the log-rank test was applied. A multivariate Cox proportional hazards model was developed to investigate the effect of each component on overall survival. RESULTS: A total of 334 pediatric and adolescent with PGINHL patients were identified. The median age at diagnosis was 12 years (range 1.0-19 years). Tumors were most commonly found in the small bowel (47.3%), followed by the large bowel (42.8%) and the stomach (9.9%). Overall, the most common histological subtype was Burkitt lymphoma (56.9%), followed by diffuse large B-cell lymphoma (DLBCL) (27.8%). Overall survival rates for all patients were 92.2% at 5- year and 91.6% at 10- year, respectively. The Cox proportional hazard regression revealed that only chemotherapy was an important independent predictor in this model. Patients with chemotherapy have a higher survival rate than those without. CONCLUSIONS: Our study revealed that only chemotherapy was found to be the most important predictor of the OS in pediatric and adolescent PGINHL, providing critical information for therapeutic care.

hsa-miR-199b-3p suppresses osteosarcoma progression by targeting CCDC88A, inhibiting epithelial-to-mesenchymal transition, and Wnt/beta-catenin signaling pathway.

The present study investigated microRNA (miR)-199b-3p expression in osteosarcoma (OS) and aimed to identify its potential mechanism of action contributing to the development of this disease. Firstly, miR-199b-3p and coiled-coil domain containing 88A (CCDC88A) expression data were evaluated from Gene Expression Profiling Interactive Analysis and Kaplan Meier plotter was used to assess the survival data. By analyzing the GSE65071 dataset from gene expression omnibus, it was found that miR-199b-3p was expressed at a low level. By using reverse transcription-quantitative PCR analysis in OS cells and tissues, CCDC88A was found to be expressed at a high level. Moreover, TargetScan predicted CCDC88A to be a downstream target of miR-199b-3p. Luciferase reporter assays were used to verify this prediction. In vitro overexpression of miR-199b-3p decreased the invasive and proliferative activity of OS cells. Mechanistic studies indicated that decreased miR-199b-3p resulted in increased expression of CCDC88A. Concomitantly, it impeded the Wnt/beta-catenin pathway and the epithelial-to-mesenchymal transition process. Overall, the results of the present study emphasized the pivotal role of the miR-199b-3p in the formation and progression of OS, suggesting that it could be used as a potential tumor biomarker.

Oncogenic role of copper­induced cell death­associated protein DLD in human cancer: A pan­cancer analysis and experimental verification.

Copper ions can bind directly to lipoylated components of the tricarboxylic acid (TCA) cycle, triggering the aggregation of mitochondrial lipoylated proteins and the destabilization of Fe-S cluster proteins, resulting in copper-dependent cell death. Dihydrolipoamide dehydrogenase (DLD) is a key protein of the TCA cycle and constitutes the E3 component of the α-ketoglutarate dehydrogenase complex, which is deeply interconnected with the mitochondrial electron transfer chain in the TCA cycle. Tumor cells demonstrate dependency on glutaminolysis fuelling to carry out the TCA cycle and essential biosynthetic processes supporting tumor growth. Therefore, DLD plays an important role in the tumor biological process. However, to the best of our knowledge, no pan-cancer analysis is currently available for DLD. Therefore, the present study first explored the DLD expression profile in 33 tumors in publicly available datasets, including TIMER2, GEPIA2, UALCAN, cBioPortal and STRING. TIMER2, GEPIA2 and UALCAN were used for exploring gene expression; survival prognosis was detected by GEPIA2; genetic alteration was analysed by cBioPortal; immune infiltration data was obtained from TIMER2; interacting proteins of DLD were detected by STRING. DLD was found to be highly expressed in colon, liver, lung, stomach, renal, corpus uteri endometrial and ovarian cancers compared with normal tissues, and its high expression was associated with poorer prognosis in ovarian cancer. To the best of our knowledge, the present study provided the first comprehensive pan-cancer analysis of the oncogenic role of DLD across different tumors types. As the expression of DLD in ovarian cancer was high, and high expression is associated with poor prognosis, experimental verification of DLD in ovarian cancer was conducted. In the present study, DLD expression was found to be high in the ovarian cancer OC3 cell line, compared with the normal ovarian epithelial IOSE80 cell line by reverse transcription-quantitative PCR analysis. After knockdown of DLD expression, it was found that DLD regulated metabolic pathways by suppressing the intracellular NAD+/NADH ratio, which then in turn suppressed tumor cell proliferation detected by MTT assay. In conclusion, the present pan-cancer analysis of DLD demonstrated that DLD expression was associated with the clinical prognosis, immune infiltration and tumor mutational burden in 33 tumor types, and experimental verification in ovarian cancer was conducted. These results may contribute to the understanding of the role of DLD in tumorigenesis.

Open versus closed reduction internal fixation for lateral condyle humeral fractures in children: a systematic review and meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to illustrate the clinical outcomes and safety of two different management options for Song stage 2-4 lateral condyle humeral fractures in children. METHOD: In January 2023, a systematic computer-based search was conducted. Data were retrieved for patients with two different management options for lateral condyle humeral fractures in children. The primary endpoints were clinical outcomes based on infection, avascular necrosis, and nonunion. After testing for publication bias and heterogeneity between studies, the data was aggregated for stochastic effect models when necessary. RESULTS: Eight clinical studies with 742 patients were eventually included in the meta-analysis. There was no significant difference between the closed reduction and percutaneous pinning, and open reduction and internal fixation in terms of the clinical outcomes based on infection, avascular necrosis, and nonunion (P > 0.05). CONCLUSIONS: Closed reduction and percutaneous pinning, as well as open reduction and internal fixation of lateral condyle humeral fractures in children, resulted in similar structural stability and functional outcomes. More high-quality randomized controlled trials are needed to determine this conclusion.

Thioredoxin-1 Promotes Mitochondrial Biogenesis Through Regulating AMPK/Sirt1/PGC1α Pathway in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Increasing studies suggest that mitochondrial dysfunction is closely related to the pathogenesis of AD. Thioredoxin-1 (Trx-1), one of the major redox proteins in mammalian cells, plays neuroprotection in AD. However, whether Trx-1 could regulate the mitochondrial biogenesis in AD is largely unknown. In the present study, we found that Aß25-35 treatment not only markedly induced excessive production of reactive oxygen species and apoptosis, but also significantly decreased the number of mitochondria with biological activity and the adenosine triphosphate content in mitochondria, suggesting mitochondrial biogenesis was impaired in AD cells. These changes were reversed by Lentivirus-mediated stable overexpression of Trx-1 or exogenous administration of recombinant human Trx-1. What's more, adeno-associated virus-mediated specific overexpression of Trx-1 in the hippocampus of ß-amyloid precursor protein/presenilin 1 (APP/PS1) mice ameliorated the learning and memory and attenuated hippocampal Aß deposition. Importantly, overexpression of Trx-1 in APP/PS1 mice restored the decrease in mitochondrial biogenesis-associated proteins, including adenosine monophosphate -activated protein kinase (AMPK), silent information regulator factor 2-related enzyme 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). In addition, Lentivirus-mediated overexpression of Trx-1 in rat adrenal pheochromocytoma (PC12) cells also restored the decrease of AMPK, Sirt1, and PGC1α by Aß25-35 treatment. Pharmacological inhibition of AMPK activity significantly abolished the effect of Trx-1 on mitochondrial biogenesis. Taken together, our data provide evidence that Trx-1 promoted mitochondrial biogenesis via restoring AMPK/Sirt1/PGC1α pathway in AD.

Efficacy of three types of circumcision for children in the treatment of phimosis: A retrospective study.

Phimosis is a common condition of the urinary system in children and often requires surgical treatment. However, the optimal method of circumcision for children has not been determined. Herein, we analyzed the efficacy of 3 circumcision methods for children with phimosis. A retrospective analysis of 112 cases of pediatric phimosis after circumcision was conducted at our hospital. Among them, 36 cases were subjected to conventional operation (group A), 43 cases to ring circumcision (group B), and 33 cases to suturing device circumcision (group C). The duration of operation, amount of bleeding, pain, complications, healing time, and the satisfaction of the guardians were calculated. The operation time of group B and C was (6.26 ±â€…1.31) min and (7.67 ±â€…1.29) min, respectively, which was shorter than group A (27.42 ±â€…2.42) min (P < .05); besides, group A had the most blood loss volume, (9.67 ±â€…1.67) mL, and group B was the least (1.26 ±â€…0.44) mL (P < .05); group B had the strongest postoperative pain (4.05 ±â€…0.37), the longest pain time (6.84 ±â€…1.29) days, and the longest healing time (21.84 ±â€…4.23) days (P < .05). Postoperative complications were lowest in group C (11.11% vs 20.93% vs 6.06%), satisfaction of guardians was highest in group C (86.11% vs 85.27% vs 89.99%), but the difference was not statistically significant (P > .05). Three types of surgical procedures present with advantages and disadvantages. The conventional surgery led to longer operation time and more bleeding but did not require special medical equipment and was easy to carry out; ring surgery had the shortest operation time, the least bleeding, accompanied by the longest recovery time and pain duration; the complications of the suturing device were the least, the parents had the highest degree of satisfaction, however, it also needs a specific suturing device. Therefore, each type had its distinctive characteristics and may be flexibly selected based on their own conditions.

Incidence and Epidemiological Characters of Developmental Dysplasia of the Hip in Lianyungang: Based on Ultrasound Screening: A Retrospective Study.

Objective: To explore the incidence and epidemiological characteristics of developmental dysplasia of hip (DDH) in Lianyungang and provide a basis for early detection, early diagnosis and early treatment. Methods: Ultrasound screening was performed on aged 4-6 weeks to collect the incidence and epidemiological profiles of DDH. Graf hip ultrasound imaging was used for screening. DDH was diagnosed with a classification of ≥IIa-. Results: Of the 9803 babies, 4999 were boys and 4687 were girls. There were 117 babies diagnosed with DDH, incidence rate of 1.19%. The incidence of DDH rate at left was higher than that at right (0.89%, 87/9803) vs (0.37%, 36/9803) and the difference was statistically significant (P < 0.001). Multivariate logistic regression analysis indicated that female (OR = 5.059, 95% CI: 3.012-9.109) and first child (OR = 1.871, 95% CI: 1.169-2.832) were the risk factors of DDH. Due to the small number of relevant cases and the absence of DDH cases, improper swaddling, abnormal amniotic fluid volume and confluent malformation could not be included for statistical comparison. Conclusion: The incidence of DDH in infants aged 4-6 weeks in Lianyungang was 1.19% (117/9803). DDH was more prone to occur on the left side. Girl and first-borns were the risk factors of DDH.

TPX2 regulated by miR-29c-3p induces cell proliferation in osteosarcoma via the AKT signaling pathway.

The present study aimed to investigate the significance of targeting protein for Xenopus kinesin-like protein 2 (TPX2) expression in osteosarcoma. First, the TPX2 expression and survival analysis data were evaluated from The Cancer Genome Atlas (TCGA) database. Next, reverse transcription-quantitative PCR was used to explore the expression of TPX2 in osteosarcoma tissues. The observed potential target relationship between TPX2 and microRNA (miR)-29c-3p was verified using TargetScan and luciferase reporter assays. Kaplan-Meier survival analysis was used to determine associations between TPX2 expression levels and survival prognosis. TPX2 small interfering RNA was successfully constructed and transfected into osteosarcoma cell lines. The effects of TPX2 on osteosarcoma cell proliferation were then detected by MTT assay. In addition, the expression levels of AKT signaling pathway-associated proteins were identified by western blot analysis. The expression of TPX2 was upregulated and the expression of miR-29c-3p was downregulated in osteosarcoma. High expression of TPX2 was linked to a poor prognosis. Using luciferase assay and the miRNA mimic and inhibitors, miR-29c-3p was able to target and repress TPX2, and siRNA knockdown of TPX2 resulted in the inhibition of osteosarcoma cell proliferation by affecting the AKT pathway. Overall, the study showed that miR-29c-3p could inhibit the proliferation of osteosarcoma cells via TPX2 downregulation, and that TPX2 and miR-29c-3p may serve as promising prognostic indicators.

MiR-181a-5p facilitates proliferation, invasion, and glycolysis of breast cancer through NDRG2-mediated activation of PTEN/AKT pathway.

Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of breast cancer. In this research, we explored the involvement of miR-181a-5p in the progression of breast cancer and investigated potential molecular mechanisms. Firstly, the miR-181a-5p and N-myc downstream-regulated gene (NDRG) 2 expression was detected by real-time quantitative polymerase chain reaction. Cellular processes were assessed using Cell Counting Kit 8, Bromodeoxyuridine, colony formation and transwell assays. HK2, PKM2 and LDHA activities were assessed by ELISA. The combination between miR-181a-5p was assessed by dual-luciferase reporter assay and RNA pull-down assay. The results indicated that miR-181a-5p levels were upregulated and NDRG2 levels were downregulated in breast cancer, leading to poor prognosis. Silencing of miR-181a-5p inhibited cell proliferation, invasion, glycolysis, and xenograft tumor growth, while enhanced miR-181a-5p got the opposite results. Furthermore, NDRG2 acts as a target of miR-181a-5p. Knockout of NDRG2 facilitated biological behaviors and meanwhile enhanced phosphorylation (p)-PTEN and p-AKT levels. Rescue experiments showed that restoring NDRG2 abolished the effects caused by miR-181a-5p in breast cancer cells. In conclusion, miR-181a-5p facilitated tumor progression through NDRG2-induced activation of PTEN/AKT signaling pathway of breast cancer, suggesting that focusing on miR-181a-5p may provide new insight for breast cancer therapy.Abbreviations Brdu: Bromodeoxyuridine; CCK-8: Cell Counting Kit-8; miRNA: microRNAs; mut: mutant; RT-qPCR: real-time quantitative polymerase chain reaction; UTR: untranslated region; WT: wild-type.

Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway.

The present study aimed to explore the prognostic value and role of kinesin family member 4A (KIF4A) expression in human osteosarcoma. KIF4A expression was evaluated in human osteosarcoma tissues from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Reverse transcription-quantitative PCR was then applied to assess KIF4A level in both osteosarcoma cell lines and tissues. The association between KIF4A expression and clinical results in patients with osteosarcoma was detected by survival analysis. MTT assays and colony formation assays were used to evaluate the effects of KIF4A on osteosarcoma cell proliferation. The results indicated that the level of KIF4A was increased and associated with a poor prognosis in osteosarcoma tissues. Knockdown of KIF4A was shown to inhibit osteosarcoma cellular proliferation by affecting the MAPK pathway. The level of KIF4A was high in the human osteosarcoma tissues and this could be considered as a tumor induction gene, which may be used as an indicator of prognosis.

Titanium elastic nailing can be used in 6 to 10 years old pediatric with Delbet IV femoral neck fractures.

ABSTRACT: The purpose of this study was to analyze the outcomes of titanium elastic nail (TEN) for the children in 6 to 10 years old who sustained a Delbet IV femoral neck fracture.A total of 56 children aged 6 to 10 years old with Delbet IV femoral neck fracture treated with TEN or cannulated screw (SC) were identified at our hospital from January 2009 to December 2019. Of which 24 were treated with TEN, and 32 with SC. All of them were followed up for 1 year after operation, and the differences in operation time, intraoperative blood loss, hospitalization time, hip joint function, and complication between the 2 groups were compared. Harris and Ratliff hip score were used to evaluate the hip function.All 56 fractures united properly. No major complications were noted in both groups. The intraoperative blood loss and operation time in TEN group and SC group were (11.42 ±â€Š3.41) mL, (19.66 ±â€Š4.05) mL (P = .000) and (33.58 ±â€Š7.89) min, (40.22 ±â€Š7.48) min (P = .002), respectively. There was no significant statistical difference between hip regarding range of motion and femoral neck-shaft angle in both groups, as well as Harris and Ratliff hip score between the 2 groups.TEN represent safe and effective methods in the treatment of Delbet IV femoral neck fracture in 6 to 10 years old children. TEN internal fixation is a minimal invasive and simpler technique and suitable for young children of Delbet IV femoral neck fracture.