BEX1 supports the stemness of hepatoblastoma by facilitating Warburg effect in a PPARγ/PDK1 dependent manner.

BACKGROUND: Hepatoblastoma (HB) is a highly aggressive paediatric malignancy that exhibits a high presence of cancer stem cells (CSCs), which related to tumour recurrence and chemotherapy resistance. Brain expressed X-linked protein 1 (BEX1) plays a pivotal role in ciliogenesis, axon regeneration and differentiation of neural stem cells. However, the role of BEX1 in metabolic and stemness programs in HB remains unclear. METHODS: BEX1 expression in human and mouse HB was analyzed using gene expression profile data from NCBI GEO and immunohistochemical validation. Seahorse extracellular flux analyzer, ultra-high-performance liquid-chromatography mass spectrometry (LC-MS), flow cytometry, qRT-PCR, Western Blot, sphere formation assay, and diluted xenograft tumour formation assay were used to analyze metabolic and stemness features. RESULTS: Our results indicated that overexpression of BEX1 significantly enhanced the Warburg effect in HB cells. Furthermore, glycolysis inhibition largely attenuated the effects of BEX1 on HB cell growth and self-renewal, suggesting that BEX1 promotes stemness maintenance of HB cells by regulating the Warburg effect. Mechanistically, BEX1 enhances Warburg effect through the downregulation of peroxisome proliferator-activated receptor-gamma (PPARγ). Furthermore, pyruvate dehydrogenase kinase isozyme 1 (PDK1) is required for PPARγ-induced inhibition of Warburg effect in HB. In addition, BEX1 supports the stemness of HB by enhancing Warburg effect in a PPARγ/PDK1 dependent manner. CONCLUSIONS: HB patients with high BEX1 and PDK1 expression had a poor prognosis. BEX1 promotes the stemness maintenance of HB cells via modulating the Warburg effect, which depends on PPARγ/PDK1 axis. Pioglitazone could be used to target BEX1-mediated stemness properties in HB by upregulating PPARγ.

Intestinal Autotransplantation for Locally Advanced or Locally Recurrent Colon Cancer Invading SMA.

OBJECTIVE: To examine the outcomes of intestinal autotransplantation (IATx) in patients with locally advanced or recurrent colon cancer (LACC or LRCC) invading the superior mesenteric artery (SMA). BACKGROUND: SMA Involvement in LACC or LRCC is deemed unresectable and is associated with a poor prognosis. Combined extended resections of multiple organs together with SMA, followed by IATx may offer favorable clinical outcomes. However, data on its safety and efficacy are scarce. DESIGN: This retrospective cohort study included patients undergoing IATx between May 2018 and December 2022 in intestinal transplant programs at two university-affiliated hospitals in China. Patients with LACC or LRCC concomitantly with SMA contact of more than 180° were included. Patients with a locoregional peritoneal, pelvic, or distal metastasis were excluded. RESULTS: Ten patients underwent either IATx combined with pancreaticoduodenectomy (n=8) or IATx alone (n=2). Eight patients (80%) were male, and the median age was 55 years (range, 32 - 71 y). The Kaplan-Meier estimates for recurrence-free survival and overall survival at 3 years after IATx were 68% and 80%, respectively. No perioperative deaths occurred. All ten patients experienced postoperative complications including Clavien-Dindo grade I (n=1), grade II (n=4), grade IIIa (n=1), grade IIIb (n=3) and grade IVa (n=1), which comprised acute venous thromboses, upper gastrointestinal hemorrhage, anastomotic leak, gastropareses and significant pleural effusions. With an average follow-up of 23.9 months, eight patients (80%) were currently alive without evidence of disease. CONCLUSION: Extended resection for LACC or LRCC invading SMA can be performed safely and is associated with prolonged survival.

Radical Resection Combined With Intestinal Autotransplantation for Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy: A Report of 36 Consecutive Cases.

OBJECTIVE: To achieve radical resection of locally advanced pancreatic ductal adenocarcinoma (PDAC), and tested the safety and benefits of intestinal autotransplantation in pancreatic surgery. BACKGROUND: PDAC has an extremely dismal prognosis. Radical resection was proved to improve the prognosis of patients with PDAC; however, the locally advanced disease had a very low resection rate currently. We explored and evaluated whether the combination of modern advances in systemic treatment and this macroinvasive surgery was feasible in clinical practice. METHODS: Patients diagnosed as PDAC with superior mesenteric artery involvement and with or without celiac trunk involvement were included. Patients were treated with modified-FOLFIRINOX chemotherapy with or without anti-PD-1 antibodies and were applied to tumor resection combined with intestinal autotransplantation. Data on operative parameters, pathologic results, mortality, morbidity, and survival were analyzed. RESULTS: A total of 36 consecutive cases were applied to this strategy and underwent radical resection combined with intestinal autotransplantation. Among these patients, 24 of them received the Whipple procedure, 11 patients received total pancreatectomy, and the other 1 patient received distal pancreatectomy. The median operation time was 539 minutes. Postoperative pathology showed an R0 resection rate of 94.4%, and tumor invasion of a superior mesenteric artery or superior mesenteric vein was confirmed in 32 patients. The median number of dissected lymph nodes was 43, and 25 patients were positive for lymph node metastasis. The median time of intensive care unit stay was 4 days. Two patients died within 30 days after surgery due to multiorgan failure. The severe postoperative adverse events (equal to or higher than grade 3) were observed in 12 out of 36 patients, and diarrhea, gastroparesis, and abdominal infection were the most frequent adverse events. Postoperative hospital stay was averagely of 34 days. The recurrence-free survival is 13.6 months. The median overall survival of patients after diagnosis and after surgery was 21.4 months and 14.5 months, respectively. CONCLUSIONS: Our attempt suggests the safety of this modality and may be clinically beneficial for highly selected patients with PDAC. However, the experience in multidisciplinary pancreatic cancer care and intestinal transplantation is warranted.

Successful combined auxiliary partial liver and intestinal transplantation in two highly sensitized, cross-match positive patients.

INTRODUCTION: Sensitization to human leukocyte antigen (HLA) creates an immunological barrier to intestinal transplantation (ITx). Current desensitization therapies are limited and ineffective in the most highly sensitized patients. A co-transplanted whole liver transplant can protect a kidney, heart, or intestinal allograft from antibody-mediated injury. Whether an auxiliary partial liver allograft provides effective protection for highly sensitized intestinal transplant recipients is unknown. METHODS: Two patients with strong HLA donor-specific antibody at high titer against their deceased donors underwent combined auxiliary partial liver and ITx across a positive cross-match. The left lateral lobes from the combined-graft recipients and the right liver lobes from the deceased donors were transplanted as a domino procedure to other four patients. RESULTS: Two combined-graft recipients have had an uneventful postoperative course without major complications at a 12- and 24-month follow-up, respectively. Intestinal graft function has been excellent with no evidence of humoral or cellular rejection. While a positive cross-match turned negative, titers of donor-specific HLA antibodies gradually declined over time after transplant. The left liver lobes procured from the combined-graft recipients were successfully transplanted into two pediatric patients (age 1.9, 2.4 years) and the right lobes from two deceased donors were successfully transplanted into two adult patients. All transplant procedures went well, without post-operative complications related to the splitting technique. CONCLUSION: Our results indicate that an auxiliary liver transplant can effectively protect a co-transplanted intestinal allograft against rejection and suggest that this combined procedure may serve as a useful therapeutic adjunct for a highly sensitized intestinal transplant candidate.

Magnetofection of miR-21 promoted by electromagnetic field and iron oxide nanoparticles via the p38 MAPK pathway contributes to osteogenesis and angiogenesis for intervertebral fusion.

BACKGROUND: Magnetofection-mediated gene delivery shows great therapeutic potential through the regulation of the direction and degree of differentiation. Lumbar degenerative disc disease (DDD) is a serious global orthopaedic problem. However, even though intervertebral fusion is the gold standard for the treatment of DDD, its therapeutic effect is unsatisfactory. Here, we described a novel magnetofection system for delivering therapeutic miRNAs to promote osteogenesis and angiogenesis in patients with lumbar DDD. RESULTS: Co-stimulation with electromagnetic field (EMF) and iron oxide nanoparticles (IONPs) enhanced magnetofection efficiency significantly. Moreover, in vitro, magnetofection of miR-21 into bone marrow mesenchymal stem cells (BMSCs) and human umbilical endothelial cells (HUVECs) influenced their cellular behaviour and promoted osteogenesis and angiogenesis. Then, gene-edited seed cells were planted onto polycaprolactone (PCL) and hydroxyapatite (HA) scaffolds (PCL/HA scaffolds) and evolved into the ideal tissue-engineered bone to promote intervertebral fusion. Finally, our results showed that EMF and polyethyleneimine (PEI)@IONPs were enhancing transfection efficiency by activating the p38 MAPK pathway. CONCLUSION: Our findings illustrate that a magnetofection system for delivering miR-21 into BMSCs and HUVECs promoted osteogenesis and angiogenesis in vitro and in vivo and that magnetofection transfection efficiency improved significantly under the co-stimulation of EMF and IONPs. Moreover, it relied on the activation of p38 MAPK pathway. This magnetofection system could be a promising therapeutic approach for various orthopaedic diseases.

Short- and long-term complications after living donor ileal resection.

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8 months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.

Living Donor Intestinal Transplantation: Recipient Outcomes.

OBJECTIVE: To examine outcomes of living-donor intestinal transplant (LDITx) recipients. BACKGROUND: LDITx is not routinely performed because of surgical risks to the donor and the potential inferior physiologic performance of the segmental graft. However, data on the effectiveness of LDITx are scarce. DESIGN: This retrospective cohort study included patients undergoing LDITx between May 1999 and December 2021 in intestinal transplant programs in 2 university-affiliated hospitals in China. RESULTS: Actuarial survival rates were 80%, 72.7%, 66.7% for patient and 72.4%, 63.6%, 60% for graft at 1, 3, and 5 years, respectively. Recipients with >3/6 HLA-matched grafts had superior patient and graft survival rates than those with ≤3/6 HLA-matched grafts ( P <0.05). There were 12 deaths among the recipients, with infection being the leading cause (41.7%), followed by rejection (33.3%), surgical complications (16.7%), and others (8.3%). There were 16 graft losses among the recipients, with acute cellular rejection being the predominant cause (37.5%), followed by infection (25%), technical failure (12.5%), chronic rejection (12.5%), and others (12.5%). With an average follow-up of 3.7 (range, 0.6-23) years, the rates of acute and chronic rejection were 35% and 5%, and the rate of cytomegalovirus disease and post-transplant lymphoproliferative disease were 5% and 2.5%, respectively. Of the 40 patients, 28 (70%) are currently alive and have achieved enteral autonomy. CONCLUSIONS: LDITx is a valuable treatment option for patients with end-stage intestinal failure. Improved immunosuppression, better HLA matching, and shorter cold ischemia times were associated with reduced rates of rejection, viral-mediated infection and improved graft survival.

DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer.

BACKGROUND & AIMS: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) both exhibit notable cancer stem cell (CSC) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating the CSC properties of HB and a subtype of HCC with high CSC features (CSC-HCC). METHODS: Stemness scores were analyzed in 5 murine HCC models. A subpopulation of BEX1-positive cells and BEX1-negative cells were sorted from HCC cell lines, and subjected to transcriptome analysis. The expression and function of BEX1 was examined via western blotting, sphere formation assays, and xenograft tumor models. RESULTS: We identified BEX1 as a novel CSC marker that was required for the self-renewal of liver CSCs. Furthermore, zebularine, a potent DNMT1 inhibitor, can induce the reactivation of BEX1 by removing epigenetic inhibition. Notably, BEX1 was highly expressed in patients with HB and CSC-HCC, but not in patients with non-CSC HCC. Moreover, DNMT1-mediated methylation of the BEX1 promoter resulted in differential BEX1 expression patterns in patients with HB, CSC-HCC, and non-CSC-HCC. Mechanistically, BEX1 interacted with RUNX3 to block its inhibition of ß-catenin transcription, which led to the activation of Wnt/ß-catenin signaling, and stemness maintenance in both HB and CSC-HCC. In contrast, downregulated BEX1 expression released RUNX3 and inhibited the activation of Wnt/ß-catenin signaling in non-CSC-HCC. CONCLUSION: BEX1, under the regulation of DNMT1, is necessary for the self-renewal and maintenance of liver CSCs through activation of Wnt/ß-catenin signaling, rendering BEX1 a potentially valuable therapeutic target in both HB and CSC-HCC. LAY SUMMARY: Cancer stem cells (CSCs) contribute to a high rate of cancer recurrence, as well as resistance to conventional therapies. However, the regulatory mechanisms underlying their self-renewal remains elusive. Herein, we have reported that BEX1 plays a key role in regulating CSC properties in different types of liver cancer. Targeting BEX1-mediated Wnt/ß-catenin signaling may help to address the high rate of recurrence, and heterogeneity of liver cancer.

Efficacy of gelatin sponge impregnated with ropivacaine on postoperative pain after transforaminal lumbar interbody fusion: a comparative study.

BACKGROUND: The purpose of this study was to investigate the efficacy of gelatin sponge impregnated with ropivacaine on postoperative pain after transforaminal lumbar interbody fusion (TLIF) in patients with lumbar degenerative diseases. METHODS: We retrospectively reviewed patients who underwent TLIF in our department between August 2018 and January 2020. Patients were divided to ropivacaine group and saline group. A ropivacaine group whom received gelatin sponge impregnated with ropivacaine during operation, and a saline group whom were intraoperatively administered by gelatin sponge impregnated with saline. The two groups were compared in reference to postoperative hospital stay, postoperative complications and visual analog scale (VAS) scores. The consumption of postoperative diclofenac sodium suppository use was also recorded. The Oswestry Disability Index (ODI) scores and Japanese Orthopedic Association (JOA) scores were used for functional evaluation at 1 year postoperatively. RESULT: A total of 127 patients were evaluated in this retrospective study. The mean postoperative hospital stay in the ropivacaine group was significantly lower than saline group. The VAS score was significantly lower in patients receiving gelatin sponge impregnated with ropivacaine as compared with patients in saline group on postoperative day 1, 2, 3 and 4. The number of patients who need the administration of diclofenac sodium suppository and the mean consumption of postoperative diclofenac sodium suppository was significantly lower in the ropivacaine group as compared with saline group. CONCLUSION: The application of gelatin sponge impregnated with ropivacaine around the nerve root in patients undergoing TLIF can effectively control the postoperative pain and reduce postoperative hospital stay.

Enhanced osteogenesis of bone marrow stem cells cultured on hydroxyapatite/collagen I scaffold in the presence of low-frequency magnetic field.

As a non-invasive biophysical therapy, electromagnetic fields (EMF) have been widely used to promote the healing of fractures. In the present study, hydroxyapatite/collagen I (HAC) loaded with rabbit bone marrow mesenchymal stem cells (MSCs) were cultured in a dynamic perfusion bioreactor and exposed to EMF of 15 Hz/1mT. Osteogenic differentiation of the seeded cells was analyzed through the evaluation of ALP activity and osteogenesis-related genes expression in vitro. The in vivo osteogenesis efficacy of the cell laden HAC constructs treated with/without EMF was evaluated through a rabbit femur condyle defect model. The results showed that EMF of 15 Hz/1mT could enhance the osteogenic differentiation of the cells seeded on HAC scaffold. Furthermore, the in vivo experiments demonstrated that EMF exposure could promote bone regeneration within the defect and bone integration between the graft and host bone. Taking together, the MSCs seeded HAC scaffold combined with EMF exposure could be a promising approach for bone tissue engineering.

RNA sequence analysis reveals pathways and candidate genes associated with liver injury in a rat pancreatitis model.

BACKGROUND: The morbidity and mortality associated with acute pancreatitis (AP) are largely attributable to abnormalities that occur in distant organs, such as liver and lungs. Pancreatitis-associated liver injury (PALI) remains a serious and even fatal complication during the progression of AP. However, the exact pathophysiological mechanism is still unclear. METHODS: In the present study, we used, for the first time, RNA-seq method to reveal pathways and candidate genes associated with PALI in rats. AP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. The RNA-seq results of selected genes were validated by RT-PCR and immunohistochemistry assay. RESULTS: GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis indicated that Toll like receptor 4 (TLR4) signaling pathway and transforming growth factor ß1 (TGF-ß1) and p38 mitogen-activated protein kinase (MAPK) signaling pathway (TGF-ß1-p38 MAPK) were involved in the course of PALI. In addition, other factors were also found to be involved in the course of PALI, such as the decreased antioxidant activity, excessive production of inflammatory mediators and alterations in liver metabolism. CONCLUSIONS: The study sheds some new insight on our understanding of the pathophysiology of PALI and provides some clues to the identification of potential therapeutic targets.

Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma.

BACKGROUND AND AIM: The mammalian AlkB homolog protein family has been reported to promote tumor cell invasion and metastasis of human cancer. However, the expression status and clinical significance of AlkB homolog 3 (ALKBH3) in hepatocellular carcinoma (HCC) have not been reported yet. METHODS: In the present study, we investigated the protein expression of ALKBH3 by immunohistochemistry assay and evaluated its association with tumor progression, recurrence, and prognosis in 272 patients with HCC. In addition, we explored ALKBH3 function via gene overexpression and knockdown of ALKBH3. RESULTS: AlkB homolog 3 was overexpressed in HCC compared with adjacent non-tumorous specimens. Moreover, ALKBH3 expression was closely related to tumor differentiation and tumor-node-metastasis stage. Interestingly, the ALKBH3 high expression in tumor tissues of HCC patients had more poor disease-free survival and overall survival than low-expression patients. Consistently, we found that knockdown of ALKBH3 inhibits HCC cell proliferation in vitro and xenograft tumor formation in vivo and overexpressing ALKBH3 showed the opposite results. ALKBH3 knockdown may inhibit cell proliferation, presumably through p21/p27-mediated cell-cycle arrest at G1 phase in human HCC. ALKBH3 may also play some role on chemosensitivity to certain genotoxic reagents, such as cisplatin (CDDP) and epirubicin. CONCLUSIONS: These findings reveal an important role of ALKBH3 in HCC, indicating that ALKBH3 could be used as a new therapeutic target in future.

Elevated Serum Triglycerides in the Prognostic Assessment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Hypertriglyceridemia has been positively associated with the risk of acute pancreatitis (AP), but whether increased triglyceride (TG) levels are associated with the severity of AP remains unknown. To this, a meta-analysis was conducted to assess the effect of elevated serum TG on the prognosis of AP. METHODS: We searched PubMed, EMBASE, and the Cochrane library to identify all eligible studies (up to September 2016). We pooled the odds ratios (ORs) or standardized mean difference from individual studies using a random-effects model to investigate associations between levels of TG and the prognosis of AP. RESULTS: A total of 15 studies were included in the meta-analysis, including a total of 1564 patients with triglyceride-related acute pancreatitis (TGAP) and 5721 patients with nontriglyceride-related acute pancreatitis (NTGAP). The occurrence of renal failure [OR=3.18; 95% confidence interval (CI): 1.92, 5.27; P<0.00001], respiratory failure (OR=2.88; 95% CI: 1.61, 5.13; P<0.0001), and shock (OR=3.78; 95% CI: 1.69, 8.44; P<0.0001) was statistically significantly higher in TGAP group than in NTGAP group. Furthermore, mortality (OR=1.90; 95% CI: 1.05, 3.45; P<0.01), systemic inflammatory response syndrome (OR=2.03; 95% CI: 1.49, 2.75; P<0.00001), and Acute Physiology and Chronic Health Evaluation (APACHE-II) scores (standardized mean difference=2.72; 95% CI: 1.00, 4.45; P<0.001) were also statistically significantly higher in TGAP group than in NTGAP group. CONCLUSION: Elevated serum TGs are related to a worse prognosis of AP.

Effects of electromagnetic fields on bone loss in hyperthyroidism rat model.

Optimal therapeutics for hyperthyroidism-induced osteoporosis are still lacking. As a noninvasive treatment, electromagnetic fields (EMF) have been proven to be effective for treating osteoporosis in non-hyperthyroidism conditions. We herein systematically evaluated the reduced effects of EMF on osteoporosis in a hyperthyroidism rat model. With the use of Helmholtz coils and an EMF stimulator, 15 Hz/1 mT EMF was generated. Forty-eight 5-month-old male Sprague-Dawley rats were randomly divided into four different groups: control, levothyroxine treated (L-T4), EMF exposure + levothyroxine (EMF + L-T4), and EMF exposure without levothyroxine administration (EMF). All rats were treated with L-T4 (100 mg/day) except those in control and EMF groups. After 12 weeks, the results obtained from bone mineral density analyses and bone mechanical measurements showed significant differences between L-T4 and EMF + L-T4 groups. Micro CT and bone histomorphometric analyses indicated that trabecular bone mass and architecture in distal femur and proximal tibia were augmented and restored partially in EMF + L-T4 group. In addition, bone thyroid hormone receptors (THR) expression of hyperthyroidism rats was attenuated in EMF + L-T4 group, compared to control group, which was not observed in L-T4 group. According to these results, we concluded that 15 Hz/1 mT EMF significantly inhibited bone loss and micro architecture deterioration in hyperthyroidism rats, which might occur due to reduced THR expression caused by EMF exposure. Bioelectromagnetics. 38:137-150, 2017. © 2016 Wiley Periodicals, Inc.

Effects of electromagnetic fields on the metabolism of lubricin of rat chondrocytes.

Electromagnetic fields (EMFs) can improve pain, stiffness and physical function in osteoarthritis (OA) patients and have been proposed for the treatment of OA. However, the precise mechanisms involved in this process are still not fully understood. In the present study, we investigated the effects of exposure for different durations with 75 Hz, 2.3 mT sinusoidal EMFs (SEMFs) on the metabolism of lubricin of rat chondrocytes cultured in vitro. Our results showed that SEMFs exposure promoted lubricin synthesis in a time-dependent manner, and the expression of transforming growth factor (TGF)-ß1 was also enhanced after SEMFs treatment. The up-regulation effect of the expression of lubricin under SEMF was partly reduced by SB431542, an inhibitor of TGF-RI kinase. The Smad pathway was also investigated in our study. Smad2 synthesis was higher in EMF-exposed condition than in controls, whereas no effects were observed on inhibitory Smads (Smad6 and Smad7) production. Altogether, these data suggest that SEMF exposure can promote lubricin synthesis of rat chondrocytes in a time-dependent manner and that the TGF-ß/Smads signaling pathway plays a partial role.

Gastrointestinal Factor GDDR Attenuates Epithelial-Mesenchymal Transition in Gastric Cancer via Inhibiting AKT Signal.

BACKGROUND: The gastric dramatic down-related gene (GDDR) is an abundantly expressed secretory protein in normal gastric epithelia, while its expression is distinctly decreased in gastric cancer. However, the role of GDDR in gastric cancer remains poorly understood. AIMS: This study aims to detect the expression and clinical significance of GDDR in gastric cancer and investigate its effects on epithelial-mesenchymal transition. METHODS: The expression of GDDR in gastric cancer was examined by immunohistochemistry, immunoblotting, and Western blotting. The relationships between GDDR expression and clinicopathological factors were evaluated. The effects of GDDR on epithelial-mesenchymal transition of gastric cancer cells were investigated in vitro. RESULTS: GDDR was absent in gastric cancer tissue or dramatically downregulated in gastric cancer cell lines. Loss of GDDR expression in gastric cancer was strongly correlated with clinicopathological factors, such as tumor differentiation (p = 0.037), T stage (p < 0.001), lymph node metastasis (p = 0.008) and TNM stage (p < 0.001). Patients with decreased GDDR expression presented shortened overall survival (p = 0.033). Functional studies demonstrated that GDDR elevation augmented cell-cell adhesion and suppressed cell motility, concomitant with increased expression of E-cadherin and decreased expression of ß-catenin and vimentin. Conversely, GDDR depletion increased cell motility, concomitant with decreased expression of E-cadherin and increased expression of ß-catenin and vimentin. Moreover, GDDR had an inhibitory effect on PI3K/Akt signaling pathway. CONCLUSIONS: Our findings suggested that GDDR expression was significantly associated with the progression of gastric cancer and GDDR may function as a tumor suppressor via inhibiting the epithelial-mesenchymal transition.

Early classic hemofiltration exhibits no benefits in severe acute pancreatitis with early organ failure: a retrospective case-matched study.

Continuous venovenous hemofiltration (CVVH) is an important organ supportive technique. This study aimed to evaluate the impact of early classic CVVH on the outcomes of severe acute pancreatitis (SAP) patients with early organ failure (EOF). Between 2008 and 2012, a total of 44 SAP patients with EOF were admitted to our department. The 44 patients were classified into two groups according to whether they received early classic CVVH (2 L/h, initiated within 24 h after admission): 25 patients received early CVVH (ECVVH group), and 19 patients did not receive early CVVH (control group). The two groups were matched for age and Acute Physiology and Chronic Health Evaluation II scores. The severity of organ dysfunctions was evaluated by Sequential Organ Failure Assessment (SOFA) scores. Each group included 19 patients. The baseline characters between the two groups were balanced. The SOFA scores in the ECVVH group increased compared with those in the control group. The time to weaning from mechanical ventilation was significantly longer in the ECVVH group (log-rank test: χ(2) = 4.007, P = 0.045). Renal support was also significantly prolonged in the ECVVH group (the number of patients receiving CVVH 72 h after admission: 10 vs. 3, respectively, P = 0.038). Nine patients died in the ECVVH group versus six patients in the control group (P = 0.508). In conclusion, our study failed to prove that early classic CVVH had any benefits on the outcomes of SAP patients with EOF. Unexpectedly, early classic CVVH worsened organ functional capacity. However, it is possible that CVVH using advanced techniques may be beneficial in SAP patients with EOF.

The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone.

Although glucocorticoids provide benefits for inflammation or autoimmune disorders, high-dose and long-term use could cause osteonecrosis or osteoporosis as adverse effect for patients. Electromagnetic field (EMF) treatments have been clinically used for many years to promote fracture healing, but whether EMF can attenuate the deleterious effects of glucocorticoids is not clear. In this study, the effects of different concentrations of dexamethasone (DEX) on proliferation and adipogenic or osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were detected and compared, and the effects of EMF treatment (15 Hz, 1 mT, 4 h/day) on 0.1 µM DEX-modulated BMSCs' proliferation and adipogenic or osteogenic differentiation were investigated. Higher concentrations of DEX (0.1 and 1 µM) inhibited proliferation of BMSCs but promoted expression of adipogenic-related genes, increasing the number of lipid droplets. In the early stage of differentiation, DEX restrained expression of RUNX2 and alkaline phosphatase (ALP), but amplified expression of ALP and osteopontin (OPN) in the late stage. EMF treatment of BMSCs influenced by 0.1 µM DEX inhibited the high expression of adipogenic-related genes, stimulated the expression of RUNX2, ALP, OPN, and osteocalcin, and increased the activity of ALP. EMF exposure augmented the expression of p-ERK, which DEX reduced. After using mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway inhibitor, U0126, the effect of EMF was reduced. In conclusion, EMF exposure accelerates BMSCs proliferation, inhibits adipogenic differentiation, and promotes osteogenic differentiation of BMSCs modulated by DEX, and these effects are mediated at least in part by MEK/ERK signaling pathway.

Osteogenic differentiation of bone mesenchymal stem cells regulated by osteoblasts under EMF exposure in a co-culture system.

This study examined the osteogenic effect of electromagnetic fields (EMF) under the simulated in vivo conditions. Rat bone marrow mesenchymal stem cells (BMSCs) and rat osteoblasts were co-cultured and exposed to 50 Hz, 1.0 mT EMF for different terms. Unexposed single-cultured BMSCs and osteoblasts were set as controls. Cell proliferation features of single-cultured BMSCs and osteoblasts were studied by using a cell counting kit (CCK-8). For the co-culture system, cells in each group were randomly chosen for alkaline phosphatase (ALP) staining on the day 7. When EMF exposure lasted for 14 days, dishes in each group were randomly chosen for total RNA extraction and von Kossa staining. The mRNA expression of osteogenic markers was detected by using real-time PCR. Our study showed that short-term EMF exposure (2 h/day) could obviously promote proliferation of BMSCs and osteoblasts, while long-term EMF (8 h/day) could promote osteogenic differentiation significantly under co-cultured conditions. Under EMF exposure, osteogenesis-related mRNA expression changed obviously in co-cultured and single-cultured cells. It was noteworthy that most osteogenic indices in osteoblasts were increased markedly after co-culture except Bmp2, which was increased gradually when cells were exposed to EMF. Compared to other indices, the expression of Bmp2 in BMSCs was increased sharply in both single-cultured and co-cultured groups when they were exposed to EMF. The mRNA expression of Bmp2 in BMSCs was approximately four times higher in 8-h EMF group than that in the unexposed group. Our results suggest that Bmp2-mediated cellular interaction induced by EMF exposure might play an important role in the osteogenic differentiation of BMSCs.

Severe traumatic dislocation of the lower cervical spine with mild neurological symptoms: Case reports and literature review.

CONTEXT: Severe traumatic fractures and dislocations of the lower cervical spine are usually accompanied by irreversible spinal cord injuries. Such patients rarely have mild or no neurological symptoms. FINDINGS: We report three cases of severe lower cervical dislocation without spinal cord injury and discuss the mechanisms underlying this type of injury. All three patients had severe lower cervical dislocation, but their neurological symptoms were mild. In all cases, the fractures occurred at the bilateral junctions of the lamina and pedicle, resulting in severe cervical spondylolisthesis, whereas the posterior structure remained in place, thereby increasing the cross-sectional area of the spinal canal. After preoperative skull traction for a few days, the patients underwent anterior or combined anterior and posterior cervical surgeries. All surgeries were successfully completed and the patient's symptoms disappeared at the last follow-up. CONCLUSION: Severe traumatic dislocation of the lower cervical spine with an intact neurological status is rare in clinical practice. Pathological canal enlargement preserves neurological function, and the most commonly injured segment is C7. Preoperative traction for closed reduction remains controversial. We suggest that if no obvious anterior compression is observed, closed reduction should be pursued. Anterior or combined anterior and posterior cervical surgeries can provide rigid fixation with satisfactory results.