[Design and application of a multiple combination portable auxiliary device for infusion].

Intravenous infusion is an important route of drug therapy, and infusion safety is an important issue for medical staff. Long-term and multiple infusion routes at the same time bring inconvenience to patients. Multiple three-way switches in parallel infusion may lead to interruption of the liquid route, which can seriously endanger the life of patients. To address these clinical issues, medical staff from the School of Basic Medical Sciences of Hebei Medical University and the Emergency Department of the Second Hospital of Hebei Medical University designed a multiple combination portable infusion assistance device and obtained the National Utility Model Patent of China (ZL 2022 2 0226073.2). The device is mainly composed of adhesive tape sticker, fixed slots and pipelines, and also includes a three-way valve and a mixing chamber, and different modes of infusion assist devices can be selected according to clinical needs. The device is simple and convenient to operate, solves the problem of multiple liquid infusion blockages, improves the safety and comfort of infusion, and can meet the needs of liquid infusion in various clinical situations.

Food-Borne Poisoning Accident from Amanitin Toxin in Wild Mushrooms - Xingtai City, Hebei Province, China, 2023.

What is already known about this topic?: Fatal poisonings caused by wild mushrooms containing amanita toxins pose a significant threat in the southern regions of China. These toxins primarily induce gastrointestinal symptoms initially, which are then followed by potentially life-threatening acute liver damage. What is added by this report?: This report contributes to the existing knowledge on these cases of poisoning by documenting the second occurrences in Hebei Province and the first occurrences in Xingtai City. Five individuals reported consuming wild mushrooms from the same origin, and laboratory tests confirmed the presence of α-amanitin in their blood samples. What are the implications for public health practice?: This underscores the risk associated with the collection and consumption of amanita toxin-containing mushrooms in Hebei. It is important to note that the identification of toxic and non-toxic mushrooms should not solely rely on personal experience or appearance.

Risk Factors for Short-Term and Long-Term Low Back Pain After Transforaminal Endoscopic Lumbar Discectomy.

Introduction: Low back pain following transforaminal endoscopic lumbar discectomy (TELD) is prevalent (15-25% incidence). Modifying TELD techniques to avoid excessive disc removal has been suggested to reduce such pain. Facet injury, re-herniation, and disc space collapse might contribute. This retrospective study aimed to explore factors linked to post-TELD low back pain. Methods: A total of 351 patients with L3/4, L4/5, and L5/S1 intervertebral lumbar disc herniations, who underwent TELD at two spine centers, were included. Patients were followed for one year. Low back and leg pain visual analogue scale (VAS) scores, Oswestry Disability Index (ODI), Pfirrmann grade, and disc height were measured at 3 months and 1 year. Correlation analyses examined links between postoperative low back pain VAS scores, age, sex, disc/vertebrae height ratio (D/V H ratio), Pfirrmann grade, cannula position grade, re-herniation grade, high-intensity zone (HIZ), disc calcification, surgical grade, and other factors. Significant variables were identified using partial least square tests, with variable importance in projection (VIP) values quantifying their impact on low back pain. Results: Univariate analysis indicated that surgical grade correlated with long-term postoperative low back pain (P = 0.023), while re-herniation (P = 0.008, P = 0.000), disc height (P = 0.001, P = 0.034), and sex (P = 0.025, P = 0.003) correlated with both short- and long-term postoperative low back pain. Trephine/cannula position is correlated with short-term low back pain (P = 0.036). Worsening low back pain was associated with female sex, improper trephine/cannula position, re-herniation, and post-surgical disc space collapse. Intradiscal irrigation was linked to decreased low back pain. Discussion: This study highlights factors influencing low back pain after TELD. Loss of disc height, extent of re-herniation, quality of trephine/cannula position, and sex were associated with low back pain at both 3 months and 1-year post-TELD. Proper techniques, like minimizing disc height loss and re-herniation, may help mitigate postoperative low back pain.

Siglec15 facilitates the progression of non-small cell lung cancer and is correlated with spinal metastasis.

Background: Non-small cell lung cancer (NSCLC) frequently metastasizes to bone, leading to poor prognosis. Siglec15 has been identified as a newly discovered immune checkpoint and exists in a variety of tumors. However, the expression and function of Siglec15 in NSCLC and bone metastasis remains largely unclear. Methods: Siglec15 expression in NSCLC and the correlation between Siglec15 expression and the clinicopathological factors of patients with NSCLC were analyzed using The Cancer Genome Atlas (TCGA) dataset. Correlation analysis between Siglec15 and bone metastasis-related genes expression was based on the Molecular Signatures Database (MSigDB). Western blotting and immunohistochemistry were applied to detect Siglec15 expression in NSCLC and spinal metastasis. Human A549 and mouse CMT167 cells were transfected with Siglec15 siRNA to investigate its biological functions in NSCLC proliferation, migration, and invasion. The immune-related signaling pathways and correlations between Siglec15 and tumor-infiltrating immune cells and different immune checkpoints in the NSCLC tumor microenvironment (TME) were analyzed using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and gene set enrichment analysis (GSEA). To demonstrate Siglec15 in NSCLC cell-mediated T cell suppression and investigate the potential mechanism of Siglec15 silencing in antitumor immunity, we used a T cell killing assay in vitro and the high­throughput sequencing approach. Results: Siglec15 expression was positively associated with the tumor stage and lymph node metastasis, and was markedly up-regulated in NSCLC bone metastasis. Functionally, Siglec15 knockdown inhibited the proliferation, migration, and invasion of NSCLC cells (A549 and CMT167 cell lines). A total of eight kinds of tumor-infiltrating immune cells were found to have a strong association with the Siglec15 expression in NSCLC cases. The expression of previously discovered immune checkpoints was higher in the high Siglec15 expression NSCLC group. Furthermore, an in vitro T cell killing assay showed that the down-regulation of Siglec15 in tumor cells could enhance the antitumor immune responses of CD8+ T cells. High­throughput sequencing revealed the potential molecular mechanisms underlying the Siglec15-mediated immunosuppression effect of tumor cells on immune cells. Conclusions: Siglec15 may be involved in the pathogenesis of spinal metastasis in NSCLC and provide a new potential therapeutic target for the treatment of NSCLC and bone metastasis.

Spine­specific downregulation of LAPTM5 expression promotes the progression and spinal metastasis of estrogen receptor­positive breast cancer by activating glutamine­dependent mTOR signaling.

Estrogen receptor­positive (ER+) breast cancer (BC) is a malignancy that is prone to metastasis to the spine, which is difficult to treat and often results in poor prognosis. However, the mechanism underlying the tumorigenesis and spinal metastasis of ER+ BC remains unclear. Lysosomal protein transmembrane 5 (LAPTM5) has been reported as a tumor suppressor in several types of cancer, but its role in ER+ BC has not been described. Here, by analyzing a gene sequencing dataset and ER+ BC tissues, tumor­adjacent normal tissues and spinal metastatic tissues from patients and mouse models, we found that LAPTM5 expression is negatively related to the progression and spinal metastasis of ER+ BC. Subsequently, in vitro experiments demonstrated that downregulation of LAPTM5 expression promoted the proliferation, migration, and chemoresistance of ER+ BC cells by activating glutamine­dependent mTOR signaling. A high level of CX3CL1 could inhibit LAPTM5 expression, explaining how ER+ BC metastasized to the spine. Thus, we found that LAPTM5 functions as a tumor suppressor in ER+ BC and that the CX3CL/CX3CR1/LAPTM5/glutamine axis mediates the spinal metastasis of ER+ BC. This axis may be a promising therapeutic target for ER+ BC.

Effect of dynamic stratified potassium supplementation in elderly patients with chronic heart failure and moderate to severe hypokalaemia-a randomised, controlled trial.

OBJECTIVE: To compare the effectiveness of dynamic stratified potassium supplementation at high concentrations with enteral potassium supplementation in older patients with chronic heart failure and moderate to severe hypokalaemia. METHODS: We performed a single-centre, short-term, randomised, controlled, open-labelled, clinical trial, and patients were randomly allocated to the control or intervention group. The intervention group received intermittent infusions of 30 mmol/100 mL potassium chloride. In the control group, 10% potassium chloride was administered orally in a bolus dose. Short-term efficacy and adverse events were compared. RESULTS: The intervention group received less potassium than that in the control group. T-wave normalisation and U-wave disappearance occurred sooner in the intervention group than in the control group after potassium supplementation. The rate of increase in potassium concentrations gradually became similar in both groups. The initial blood potassium concentration, method of potassium supplementation, potassium supplement dose, and 24-hour urinary potassium excretion significantly affected the rate of increase in blood potassium concentrations after supplementation. CONCLUSIONS: The efficacy of enteral potassium supplementation is equivalent to that of supplementation with high intravenous potassium concentrations in elderly patients with chronic heart failure and moderate to severe hypokalaemia. High intravenous potassium concentrations may lead to a superior potassium recovery rate.

Injectable Mussel-Inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration.

In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.

[Early reperfusion strategy selection and prognosis analysis in patients with acute ST segment elevation myocardial infarction: based on the data of 49 hospitals in Hebei Province].

OBJECTIVE: To explore the selection of strategies for early reperfusion therapy and its impact on prognosis in patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: The treatment data and 3-year follow-up results of acute myocardial infarction (AMI) patients in 49 hospitals in Hebei Province from January to December 2016 were collected. Patients with STEMI who received either intravenous thrombolytic therapy (ITT) or primary percutaneous coronary intervention (PPCI) within 12 hours of onset were enrolled. Baseline data, the time from the first diagnosis to the start of reperfusion (FMC2N for ITT patients and FMC2B for PPCI patients), vascular recanalization rate, in-hospital mortality, 1-year mortality, and 3-year mortality were compared between ITT and PPCI groups. The efficacy and prognosis of ITT and PPCI at different starting time of reperfusion (FMC2N ≤ 30 minutes, FMC2N > 30 minutes, FMC2B ≤ 120 minutes, FMC2B > 120 minutes) were analyzed. RESULTS: A total of 1 371 STEMI patients treated with ITT or PPCI were selected, including 300 patients in the ITT group and 1 071 patients in the PPCI group. 1 055 patients were actually followed up (205 patients in the ITT group and 850 patients in the PPCI group), with a rate of 79.4%. There were no significant differences in age, gender, and previous history between the two groups. The time from the first diagnosis to the start of reperfusion in the ITT group was shorter than that in the PPCI group [minutes: 63 (38, 95) vs. 95 (60, 150), U = -9.286, P = 0.000], but was significantly longer than the guideline standard. Compared with the ITT group, the vascular recanalization rate in the PPCI group was higher [95.5% (1 023/1 071) vs. 88.3% (265/300), P < 0.01], and in-hospital mortality was lower [2.1% (22/1 071) vs. 6.7% (20/300), P < 0.01], but there were no significant differences in the 1-year mortality and 3-year mortality [5.3% (45/850) vs. 4.4% (9/205), 9.5% (81/850) vs. 9.3% (19/205), both P > 0.05]. Between ITT group and PPCI group with different reperfusion starting time, the FMC2N > 30 minutes group had the lowest vascular recanalization rate and the highest in-hospital mortality. Pairwise comparison showed that the vascular recanalization rate of the FMC2B ≤ 120 minutes group and the FMC2B > 120 minutes group were significantly higher than those of the FMC2N > 30 minutes group [95.5% (654/685), 95.6% (369/386) vs. 88.0% (220/250), both P < 0.008], the in-hospital mortality was significantly lower than that of the FMC2N > 30 minutes group [2.0% (14/685), 2.1% (8/386) vs. 7.6% (19/250), both P < 0.008]. There was no significant difference in 1-year mortality (χ2 = 2.507, P = 0.443) and 3-year mortality (χ2 = 2.204, P = 0.522) among the four groups. CONCLUSIONS: For STEMI patients within 12 hours of onset, reperfusion therapy should be performed as soon as possible. PPCI showed higher infarct related artery opening rate and lower in-hospital mortality compared with ITT, and had no effect on 1-year and 3-year mortality.

Autophagy regulates exosome secretion in rat nucleus pulposus cells via the RhoC/ROCK2 pathway.

Our present study investigated whether exosome secretion of nucleus pulposus cells (NPCs) is regulated by autophagy. Different autophagic states of NPCs were induced by rapamycin (Rap), bafilomycin A1 (Baf) and other agents, and it was found that exosomes were secreted in an autophagy-dependent manner. Activation or inhibition of autophagy increased or decreased, respectively, the amount of exosomes that were released into the extracellular space. In addition, in order to confirm that Rap-promoted release of exosomes was mediated by autophagy rather than other pathways, we used autophagy associated gene 5 (ATG5) small-interfering RNA (siRNA) to silence the expression of ATG5 gene, which is indispensable for autophagy. The results showed that siRNA against ATG5 (siATG5) induced an accumulation of intraluminal vesicles (ILVs) in NPCs and a concomitant decrease in the amount of exosomes isolated from supernatant. Ras homolog gene (Rho) and Rho-associated coiled-coil forming protein kinase (ROCK) family molecules are capable of cytoskeletal remodeling and affecting vesicle transport. Therefore, we carried out targeted interventions and evaluated the effects of the RhoC/ROCK2 pathway on the secretion of exosomes within autophagic environment. Knockdown of RhoC and ROCK2 with corresponding siRNA significantly inhibited the secretion of exosomes originating from ILVs in NPCs, even when NPCs were subsequently treated with Rap. Taken together, our findings suggest that autophagy positively regulates expression levels of RhoC and ROCK2, and that the RhoC/ROCK2 pathway exerts a key function on NPCs-derived exosome secretion.

The effects of ω-3 fish oil emulsion-based parenteral nutrition plus combination treatment for acute paraquat poisoning.

OBJECTIVE: To investigate the effects of parenteral nutrition (PN) including ω-3 fish-oil emulsion on nutritional state, inflammatory response, and prognosis in patients with acute paraquat poisoning. METHODS: Patients randomized to receive medium chain triglycerides (MCT)/long chain triglycerides (LCT)-based PN (control group) or MCT/LCT-based PN containing ω-3 fish-oil emulsion (intervention group) were compared for 90-day survival and short-term treatment efficacy. RESULTS: Tumour necrosis factor-α levels were significantly lower in the intervention group ( n = 101) versus controls ( n = 73) on treatment days 4 and 7. Intervention group C-reactive protein (CRP) levels were significantly increased on day 4, decreased to baseline (day 1) levels on day 7, and were significantly lower than baseline on day 10. Control group CRP levels were significantly increased on days 4 and 7 versus baseline, and returned to baseline levels on day 10. On day 7, retinol binding protein had recovered to baseline levels in the intervention group only. Intervention group mortality rate (36.6%) was significantly lower than controls (57.5%). ω-3 fish-oil PN was associated with reduced risk of death (hazard ratio 0.52; 95% confidence interval 0.33, 0.82). CONCLUSION: In patients with acute paraquat poisoning, MCT/LCT with ω-3 fish-oil emulsion PN plus combination treatment advantageously attenuated the inflammatory response, modified the nutritional state, and was associated with significantly improved 90-day survival versus treatment without ω-3 fish oil.

The effects of TRAF6 on proliferation, apoptosis and invasion in osteosarcoma are regulated by miR-124.

The present study aimed to verify tumor necrosis factor receptor­associated factor 6 (TRAF6) as the target gene of microRNA-124 (miR-124). In addition, the expression of miR­124 was investigated in osteosarcoma tissues and cells, and its effects on the biological characteristics of osteosarcoma cells were determined, in order to provide an experimental and theoretical basis for the application of TRAF6 in the treatment of osteosarcoma. A fluorescence reporter enzyme system was used to verify TRAF6 as a target gene of miR­124, and western blotting was used to detect the effects of miR­124 on the protein expression levels of TRAF6 in cells. The expression levels of miR­124 were detected in osteosarcoma tissues and an osteosarcoma cell line (MG­63) by quantitative polymerase chain reaction (qPCR). In addition, a total of 48 h post­transfection of MG­63 cells with a miR­124 mimic, qPCR was used to detect the expression levels of miR­124, and the effects of miR­124 on the viability of MG­63 human osteosarcoma cells was determined using the MTT method. The effects of miR­124 on the cell cycle progression and apoptosis of MG­63 cells were analyzed by flow cytometry, whereas the effects of miR­124 on the migration of MG­63 cells was detected using the Transwell invasion chamber analysis method. A TRAF6 recombinant expression plasmid (pcDNA3.1­TRAF6) was also constructed, and MG­63 cells were transfected with the recombinant plasmid and a miR­124 mimic, in order to further validate the biological role of miR­124 via the regulation of TRAF6. The results of the present study indicated that, compared with in the normal control group, the expression levels of miR­124 were significantly increased in MG­63 cells transfected with a miR­124 mimic (P<0.01). In addition, the luciferase reporter gene system demonstrated that, compared with in the control group, relative luciferase activity was significantly reduced in the miR­124 mimic group (P<0.01). The results of MTT analysis indicated that cell viability was also significantly reduced in response to the overexpression of miR­124 in MG­63 cells (P<0.01). Flow cytometric analysis demonstrated that the proportion of cells in S phase and G2/M phase was significantly decreased (P<0.01) in cells overexpressing miR­124, and the number of apoptotic cells was significantly increased (P<0.01). Furthermore, the results of the Transwell invasion assay suggested that the number of invasive cells was significantly decreased following enhanced expression of miR­124 (P<0.01). In MG­63 cells overexpressing miR­124 and TRAF6, the results of MTT, flow cytometric and Transwell assay analyses demonstrated that the overexpression of TRAF6 had the opposite biological effects compared to miR­124 overexpression. In conclusion, the present study indicated that the expression levels of miR­124 were downregulated in human osteosarcoma tissues and cells, and that miR­124 is associated with negative regulation of TRAF6 expression; therefore, the role of TRAF6 in primary osteosarcoma may be regulated by miR­124. Therapeutic strategies that enhance miR­124 expression or inhibit TRAF6 expression may be beneficial for the treatment of patients with osteosarcoma.

MicroRNA-19 contributes to the malignant phenotypes of osteosarcoma in vitro by targeting Pax6.

This study was conducted to detect the expression of miR-19 and Pax6 (Paired box protein 6) in human osteosarcoma cells and the effects on biological characteristics of osteosarcoma cells. Quantitative real-time polymerase chain reaction was used to detect the expression of Pax6 and miR-19 in normal human osteoblasts (hFOB 1.19) and osteosarcoma cell lines (U2OS, Saos-2, and MG-63). Results showed that miR-19 was significantly upregulated in osteosarcoma cell lines compared with that in hFOB 1.19 cells, while the expression of Pax6 messenger RNA was significantly downregulated. Pax6 was defined as the target gene of miR-19 which was validated by luciferase reporter gene analysis. Results indicated that miR-19 had an interaction with Pax6 3'-untranslated region. At the same time, the protein expression of Pax6 was significantly decreased in the MG-63 cells transfected with miR-19 mimic and was notably enhanced in osteosarcoma MG-63 cells transfected with miR-19 inhibitor. These data suggested that Pax6 was a target of miR-19 in osteosarcoma MG-63 cells. The effects of miR-19 on the biological behavior of MG-63 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Transwell assay. Results showed that the downregulation of miR-19 inhibited cell viability, reduced the percentage of cells in S phase and the number of cells passing through the Transwell chamber, and increased the number of apoptotic cells. Western blot analysis showed that the inhibition of miR-19 significantly increased the expression of epithelial proteins (E-cadherin and ß-catenin) and decreased the expression of mesenchymal protein (Vimentin), extracellular signal-regulated kinase, and phosphorylated extracellular signal-regulated kinase in MG-63 cells. MiR-19 inhibitor and Pax6 small interfering RNA were simultaneously transfected into MG-63 cells. Results from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Transwell assay demonstrated that the inhibition of Pax6 expression in MG-63 cells could reverse the cell biological effects induced by the inhibition of miR-19 expression. Based on these findings, it was suggested that miR-19, upregulated in osteosarcoma cells, negatively regulated the expression of Pax6, which can promote the malignant phenotypes of osteosarcoma cells via activation of the extracellular signal-regulated kinase signaling pathways. Therefore, miR-19/Pax6 may offer potential for use as a target for the treatment of osteosarcoma.

Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema.

The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease.

Downregulation of HMGA2 inhibits cellular proliferation and invasion, improves cellular apoptosis in prostate cancer.

Prostate cancer is the most commonly diagnosed cancer among men and is the second leading cause of cancer-associated deaths among men in the world. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence has indicated that the deregulation of DNA-binding protein High Mobility Group A2 (HMGA2) is associated with the development and progression of cancer. This study aimed to explore the expression of HMGA2 in prostate cancer tissues and its correlation to the clinical pathology of prostate cancer, and to discuss the role of HMGA2 in the development of prostate cancer. The results showed that the expression of HMGA2 messenger RNA (mRNA) in the prostate cancer tissues and cells was significantly higher than that in normal prostate tissues and cells (p < 0.05), and the positive expression rate of HMGA2 mRNA in the prostate cancer tissues from patients with positive lymph node metastasis or with high Gleason grade was significantly higher than that from patients with negative lymph node metastasis or with low Gleason grade (p < 0.05). In order to explore the role of HMGA2 in prostate cancer, the expression of HMGA2 in the human prostate cancer PC3 cell line was downregulated by RNA interference. Then, the changes in proliferation, apoptosis, invasion, and migration of PC3 cells were examined by MTT test, PI staining, Annexin V-FITC staining, and Transwell chamber assay. Results showed that the abilities of proliferation, invasion, and migration were suppressed in HMGA2 knockdown PC3 cells, and the abilities of apoptosis were enhanced in HMGA2 knockdown PC3 cells. The expression of cyclin A and vimentin was downregulated in HMGA2 knockdown PC3 cells, and the expression of caspase 3 and E-cadherin was upregulated in HMGA2 knockdown PC3 cells. Taken together, the overexpression of HMGA2 in prostate cancer might be related to the tumorigenesis, invasion, and metastasis of prostate cancer, the downregulation of HMGA2 could inhibit cellular proliferation, invasion, and metastasis, and improve cellular apoptosis in prostate cancer, which might be a potential target for the treatment of prostate cancer.

HMGB1 promotes cellular proliferation and invasion, suppresses cellular apoptosis in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the deregulation of DNA-binding protein high-mobility group box 1 (HMGB1) was associated with the development of cancer. This study aimed to explore the expression of HMGB1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the role of HMGB1 in the development of osteosarcoma. The results from RT-PCR and Western blot showed that the expression rate of HMGB1 messenger RNA (mRNA) and the expression of HMGB1 in the osteosarcoma tissues were significantly higher than those in normal bone tissue (p < 0.05), the expression rate of HMGB1 mRNA and the expression of HMGB1 in the carcinoma tissues with positive lung metastasis were significantly higher than those without lung metastasis (p < 0.05), and with increasing Enneking stage, the expression rate of HMGB1 mRNA and the expression of HMGB1 also increased (p < 0.05). In order to explore the role of HMGB1 in osteosarcoma, the expression of HMGB1 in the human osteosarcoma MG-63 cell line was downregulated by the technique of RNA interference. Western blot results showed that the protein expression of HMGB1 was significantly decreased in the MG-63 cells from HMGB1-siRNA transfection group (p < 0.05), which suggested that HMGB1 was successfully downregulated in the MG-63 cells. Then the changes in proliferation, apoptosis, and invasion of MG-63 cells were examined by MTT test, PI staining, annexin V staining, and transwell chamber assay. Results showed that the abilities of proliferation and invasion were suppressed in HMGB1 knockdown MG-63 cells, and the abilities of apoptosis were enhanced in HMGB1 knockdown MG-63 cells. The expression of cyclin D1, MMP-9 was downregulated in HMGB1 knockdown MG-63 cells, and the expression of caspase-3 was upregulated in HMGB1 knockdown MG-63 cells. Taken together, the overexpression of HMGB1 in osteosarcoma might be related to the tumorigenesis, invasion, and metastasis of osteosarcoma, which might be a potential target for the treatment of osteosarcoma.

SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell.

SASH1, a member of the SLY-family of signal adapter proteins, is a candidate tumor suppressor in breast and colon cancer. The SASH1 protein possesses both the SH3 and SAM domains, indicating that it may play an important role in intracellular signal transduction. Reduced expression of SASH1 is closely related to tumor growth, invasion, metastasis, and poor prognosis. However, the biological role of SASH1 remains unknown in osteosarcoma. To unravel the function of SASH1, we explored the expression of SASH1 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and analyzed the relationship between SASH1 expression and cell cycle, apoptosis and invasion of osteosarcoma MG-63 cells, using the flow cytometry analysis and transwell invasion chamber experiments. Furthermore, the effect of SASH1 on the expression of cyclin D1, caspase-3, matrix metalloproteinase (MMP)-9 were observed by western blot. Our results showed that the expression rate of SASH1 mRNA in osteosarcoma tissues was significantly lower than that in normal bone tissue (p = 0.000), that the expression rate of SASH1 mRNA in the carcinoma tissues from patients with lung metastasis was significantly lower than that from patients without lung metastasis (p = 0.041), and that the expression rate of SASH1 mRNA also decreased with increasing Enneking stage (p = 0.032). However, the mRNA expression of SASH1 in osteosarcoma was independent of the patient's gender, age, and tumor size (p = 0.983, 0.343, 0.517, respectively). The SASH1 protein displayed a down-regulation in osteosarcoma tissues compared to normal bone tissue (p = 0.000), displayed a down-regulation in osteosarcoma tissues from patients with lung metastasis compared to from patients without lung metastasis (p = 0.000), and displayed a gradual decrease with increasing Enneking stage (p = 0.000). In addition, the MG-63 cells from pcDNA3.1-SASH1 group exhibited significantly reduced cell viability, proliferation, and invasive ability compared to the empty vector group and blank control group (p = 0.023, 0.001, respectively), and there was no difference between the empty vector group and blank control group. The pcDNA3.1-SASH1 group displayed significantly more apoptotic cells than the empty vector group and blank control group (p = 0.004). The expression of cyclin D1, MMP-9 displayed a down-regulation in MG-63 cells from pcDNA3.1-SASH1 group compared to the empty vector group and blank control group (p = 0.000, 0.001, respectively) and the expression levels of caspase-3 displayed an up-regulation in MG-63 cells from pcDNA3.1-SASH1 group compared to the empty vector group and blank control group (p = 0.000). Taken together, these data indicated that the overexpression of SASH1 might be associated with the inhibition of growth, proliferation, and invasion of MG-63 cells and the promotion of apoptosis of MG-63 cells.

TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell.

TRAF6, a unique tumor necrosis factor receptor-associated factor (TRAF) family member, possesses a unique receptor-binding specificity that results in its crucial role as the signaling mediator for TNF receptor superfamily and interleukin-1 receptor/Toll-like receptor superfamily. TRAF6 plays an important role in tumorigenesis, invasion and metastasis. This study aimed to explore the expression of TRAF6 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the relationship between TRAF6 expression and osteosarcoma invasion. These data will provide the experimental base for the biological treatment of osteosarcoma in the future. Using RT-PCR and Western blot, the results showed that the expression rate of TRAF6 mRNA in osteosarcoma tissues was significantly higher than that in normal bone tissue (p < 0.05), that the expression rate of TRAF6 mRNA in the carcinoma tissues from patients with lung metastasis was significantly higher than that from patients without lung metastasis (p < 0.05), and that the expression rate of TRAF6 mRNA also increased with increasing Enneking stage (p < 0.05). However, the mRNA expression of TRAF6 in osteosarcoma was independent of the patient's gender, age, and tumor size (p > 0.05). The TRAF6 protein displayed an up-regulation in osteosarcoma tissues compared to normal bone tissue (p < 0.05), displayed an up-regulation in osteosarcoma tissues from patients with lung metastasis compared to from patients without lung metastasis (p < 0.05), and displayed a gradual increase with increasing Enneking stage (p < 0.05). By the technique of RNA interference, the expression of TRAF6 in the human osteosarcoma MG-63 cell line was down-regulated, and the invasive ability of MG-63 cells was examined. The results showed that TRAF6 protein expression was significantly decreased in the MG-63 cells from TRAF6 siRNA-transfected group (p < 0.05), and the proliferation ability of MG-63 cells and the number of MG-63 cells that passed through the Transwell chamber were significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). In addition, the percentage of MG-63 cells undergoing apoptosis was significantly higher in the TRAF6 siRNA-transfected group compared with the non-transfected control group as well as the transfected control group (p < 0.05). The expression of p-p65, cyclin D1, MMP-9 was down-regulated in the MG-63 cells from TRAF6 siRNA-transfected group. The expression of caspase 3 was up-regulated in the MG-63 cells from TRAF6 siRNA-transfected group compared to the non-transfected control group as well as the transfected control group (p < 0.05). To make a long story short, the overexpression of TRAF6 in osteosarcoma might be related to the tumorigenesis, invasion of osteosarcoma.

Regulation of inflammatory response in human chondrocytes by lentiviral mediated RNA interference against S100A10.

OBJECTIVE: The aim of the present study was to evaluate the effects of S100A10 silencing on the inflammatory response in human chondrocytes (HCs).The inflammation induced by lipopolysaccharide (LPS) was investigated in HCs in which the S100A10 was blocked with a lentiviral shRNA vector. METHODS: A lentiviral shRNA vector targeting S100A10 was constructed and packaged to effectively block S100A10 expression in HCs. HCs were infected with the lentivirus. S100A10 expression levels in HCs were detected by western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate the change of cytokine secretion levels. The effects of S100A10 silencing on the activation of mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathway were also determined by western blot analysis. In addition, fluo-3-AM was used to demonstrate the change in calcium mobilization. RESULTS: Lentivirus effectively infected the HCs and inhibited the expression of S100A10. HCs with downregulated S100A10 showed significantly decreased production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-10. S100A10 silencing markedly suppressed the activation of MAPKs induced by LPS. Furthermore, the calcium concentration increase in HCs stimulated by LPS was also inhibited by S100A10 knockdown. CONCLUSION: Our investigation demonstrated that S100A10 might be considered as a potential target for anti-inflammatory treatment.

Treatment of fractures of the ulnar coronoid process.

OBJECTIVE: To discuss the classification, management and outcome of fractures of the ulnar coronoid process. METHODS: Retrospective analysis was carried out in 31 patients (19 men and 12 women of average age 29.8 years [range, 18-52 years]) with fractures of the ulnar coronoid process. The fractures were classified into four major groups based on the extent of injury to the ulnar coronoid process, the state of the anterior bundle of the ulnar collateral ligaments (UCL) and elbow stability. A fracture of the coronoid process less than halfway up was defined as type I (eleven cases); of the middle of the coronoid process with injury of the UCL as type II (nine cases); of the base of coronoid process with dislocation of the elbow joint, sometimes with injury of the UCL, as type III (six cases); and severe comminuted fracture of the coronoid process with elbow instability as type IV (five cases). We chose treatment according to the type of injury. RESULTS: Follow-up was 18-72 months (average 28.6 months). All patients achieved fracture union without inflammation, neural injuries or elbow instability. One type III and two type IV patients had traumatic osteoarthritis, and two type III and two type IV developed heterotopic ossification. There was a statistically significant difference between the ranges of movement of the two-side joints in type IV. CONCLUSION: We choose conservative treatment for type I fractures unless the bone fragment affected movement of the elbow joint, in which case we chose operative treatment so that elbow stability was not affected. Type II and type III fractures with elbow instability were reduced by internal fixation and the ligament repaired or reconstructed. In type IV cases, bone reconstruction was necessary to recover elbow stability. Proper post-operative rehabilitation can decrease the occurrence of traumatic osteoarthritis.