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BACKGROUND Acute superior mesenteric venous thrombosis (MVT) is a rare condition associated with a high mortality rate. The treatment strategy for MVT is clinically challenging due to its insidious onset and rapid development, especially when accompanied by kidney transplantation. CASE SUMMARY Here we present a rare case of acute MVT developed 3 years after renal transplantation. A 49-year-old patient was admitted with acute abdominal pain and diagnosed as MVT with intestinal necrosis. An emergency exploratory laparotomy was performed to remove the infarcted segment of the bowel. Immediate systemic anticoagulation was also initiated. During the treatment, the patient experienced bleeding, anastomotic leakage, and sepsis. However, after aggressive treatment was administered, all thrombi were completely resolved, and the patient recovered with his renal graft function unimpaired. CONCLUSION The present case suggests that accurate diagnosis and timely surgical treatment are important to improve the survival rate of MVT patients. Bleeding with anastomotic fistula needs to be treated with caution because of grafts. Also, previously published cases of mesenteric thrombosis after renal transplantation were reviewed.

Intestinal stem cells (ISCs) are essential to maintain intestinal epithelial regeneration and barrier function. Our previous work showed that glucomannan from Aloe vera gel (AGP) alleviated epithelial damage, but the mechanism was still elusive. Herein, RNA-sequencing analysis showed that proliferation and differentiation of intestinal epithelial cells as well as the canonical Wnt pathway were involved in this process. Further experiments exhibited that AGP promoted nuclear translocation of β-catenin and expression of transcription factor 7, increased the number of Lgr5+ ISCs, and differentiated epithelial cells in mice colon. Intriguingly, AGP reversed the inhibition of IEC-6 cells proliferation induced by an inhibitor of the canonical Wnt pathway. Hence, this study implied that AGP promoted proliferation and differentiation of colon stem cells via Wnt/β-catenin signaling, which subsequently facilitated the regeneration of epithelial cells and alleviated colitis in mice. It may provide new insights into the role of polysaccharides in regulating intestinal homeostasis and relieving intestinal injury.

Targeting autophagy and lysosome may serve as a promising strategy for cancer therapy. Tea polysaccharide (TP) has shown promising antitumor effects. However, its mechanism remains elusive. Here, TP was found to have a significant inhibitory effect on the proliferation of colon cancer line HCT116 cells. RNA-seq analysis showed that TP upregulated autophagy and lysosome signal pathways, which was further confirmed through experiments. Immunofluorescence experiments indicated that TP activated transcription factor EB (TFEB), a key nuclear transcription factor modulating autophagy and lysosome biogenesis. In addition, TP inhibited the activity of mTOR, while it increased the expression of Lamp1. Furthermore, TP ameliorated the lysosomal damage and autophagy flux barrier caused by Baf A1 (lysosome inhibitor). Hence, our data suggested that TP repressed the proliferation of HCT116 cells by targeting lysosome to induce cytotoxic autophagy, which might be achieved through mTOR-TFEB signaling. In summary, TP may be used as a potential drug to overcome colon cancer.

Advanced glycation end products (AGEs) are involved in delaying the wound healing of diabetic foot ulcers. The present study investigated the effects of heme oxygenase-1 (HO-1) on oxidative stress, inflammatory insult and biological behaviors in rat dermal fibroblasts in the presence of AGEs. Rat dermal fibroblasts were cultured in the presence of AGEs (100 µg/ml), glucose (1.0 g/l or 4.5 g/l), hemin (5 µM) and chromium mesoporphyrin (CrMP; 20 µM). A bilirubin kit, reverse transcription-quantitative PCR and western blotting were used to measure the activity and mRNA and protein levels of HO-1, respectively. ELISA kits were used to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), TNF-α, IL-6, IL-1β and the viability and collagen (hydroxyproline) secretion of fibroblasts. Cell proliferation and apoptosis were measured via flow cytometry. The scratch test was performed to evaluate cell migration. The results revealed that AGEs resulted in oxidative stress, inflammatory response and biological behavioral disorders in fibroblasts, while worsened functional disorders were caused by the combination of AGEs and high-glucose treatment. Hemin treatment induced sustained high HO-1 expression, decreased the levels of ROS, MDA, 8-OHdG, TNF-α, IL-6, IL-1β and cell apoptosis, and increased cellular collagen synthesis, viability, proliferation and migration, whereas CrMP abolished the effects of hemin. It was observed that high HO-1 expression reversed the AGE-induced oxidative stress, inflammatory response and biological behavioral disorders in fibroblasts, but fibroblast function did not return to that observed under normal glucose levels. In conclusion, it was demonstrated that hemin treatment induced high HO-1 expression. HO-1 reduced the AGE-induced functional disorders in fibroblasts and may accelerate the healing of diabetic wounds by improving fibroblast biological behaviors and reducing the oxidative stress and inflammatory response.

Background Hypoxia-inducible factor 1alpha (HIF-1α) is implicated in the cell’s response to hypoxia. We investigated whether serum HIF-1α concentrations are correlated with the severity and clinical outcome of severe traumatic brain injury (sTBI). Methods Serum HIF-1α concentrations were quantified in 104 sTBI patients and 80 healthy controls. Trauma severity was assessed using Glasgow coma scale (GCS). Glasgow outcome scale (GOS) score of 1–3 at post-trauma 90 days was defined as a poor outcome. Multivariate analyses were performed to discern the relationship between serum HIF-1α concentrations and outcome. Results Patients displayed significantly higher serum HIF-1α concentrations than controls (median, 294.9 versus 102.7 pg/ml). HIF-1α concentrations were intimately related to GCS scores (r = -0.62) and GOS scores (r = -0.64). 48 patients (46.2%) experienced a poor outcome. Serum HIF-1α concentrations > 280.2 pg/ml significantly distinguished patients with the development of poor outcome with 77.1% sensitivity and 69.6% specificity (AUC, 0.750; 95% CI: 0.655–0.829). Serum HIF-1α concentrations > 280.2 pg/ml emerged as an independent predictor for poor outcome (OR: 4.179; 95% CI: 1.024–17.052). Conclusions Serum HIF-1α concentrations are tightly associated with trauma severity and poor 90-day outcome, substantializing serum HIF-1α as a promising prognostic biomarker for sTBI.

To measure the testicular volume and testicular fat deposition of middle-aged overweight men and to assess the utility of testicular fat deposition and testicular volume in determining and monitoring testicular infertility. Pelvic MRI with thin slice T2WI, T1WI and mDIXON Quant was performed on 30 middle-aged overweight patients in the treatment group and 30 middle-aged overweight men in the control group. Testicular volume and testicular fat deposition were measured separately based on thin slice T2WI and the fat fraction (FF) map of mDIXON Quant, and the testicular fat deposition observed with T1WI was used as a reference for qualitative diagnosis. Testicular volume and testicular fat deposition in middle-aged overweight individuals were compared using a t test with Bonferroni correction and receiver operating characteristic (ROC) curve. The testicular volumes (10.6–17.9 cm3) of individuals in the treatment group were smaller than those (12.6–19.0 cm3) of individuals in the control group (p

Background Platelet activation is implicated in secondary brain injury following traumatic brain injury (TBI). C-type lectin-like receptor 2 (CLEC-2) is extensively expressed on platelets and participates in platelet activation. We investigate dthe prognostic significance of plasma CLEC-2 in TBI patients. Methods One hundred and six patients with isolated severe blunt TBI and 106 healthy controls were prospectively investigated. Plasma CLEC-2 concentrations were detected and Glasgow coma scale (GCS) scores were recorded. The relationship between plasma CLEC-2 concentrations and 30-day mortality in addition to overall survival was determined using multivariate models. Results Patients exhibited a substantially higher concentration of plasma CLEC-2 than healthy controls. Among patients, plasma CLEC-2 concentrations were remarkably increased in the GCS scores- and Rotterdam computerized tomography classification- dependent manner. As compared with survivors within posttraumatic 30 days, plasma CLEC-2 concentrations were remarkably raised in non-survivors. Rising plasma CLEC-2 concentration was independently associated with an enhanced risk of 30-day mortality and short overall survival time. Plasma CLEC-2 concentrations had a significantly high area under receiver operating characteristic curve for predicting 30-day mortality. Conclusions Incremental plasma CLEC-2 concentrations are intimately related to increasing trauma severity, in close association with increased 30-day death, indicating the prognostic role of plasma CLEC-2 in TBI.

Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability with upregulation throughout axonal regeneration. Our study aims to determine the correlation of serum SPARCL1 concentrations with the severity and in-hospital mortality of severe traumatic brain injury (sTBI).A total of 102 consecutively recruited patients admitted for sTBI and 102 randomly selected healthy controls were included in this observational prospective study. Serum SPARCL1 concentrations were measured and correlated with Glasgow coma scale (GCS) scores and in-hospital mortality using multivariate analysis.Compared with controls (median, 0.22 ng/ml; interquartile range, 0.19-0.41 ng/ml), patients had significantly higher SPARCL1 concentrations (median, 3.29 ng/ml; interquartile range, 1.88-4.37; P 0.001). There was an independently correlation between SPARCL1 concentrations and GCS scores (t = -7.011, P 0.001). We found a high area under receiver operating curve (AUC) of serum SPARCL1 concentrations to predict in-hospital mortality (AUC, 0.822; 95% confidence interval, 0.734-0.891). In the multiple logistic regression analysis, serum SPARCL1 concentrations3.29 ng/ml was independently associated with in-hospital mortality (odds ratio = 10.052, 95% confidence interval = 1.918-52.686, P = 0.006).The novel findings of our study are that sTBI patients had an increase of serum SPARCL1 concentrations, and that there is an association between high serum SPARCL1 concentrations and sTBI mortality or trauma severity.

Objective The effect of lumbar traction on low back pain (LBP) patients is controversial. Our study aims to assess changes in the intervertebral disc water content after lumbar traction using T2 mapping and explore the correlation between changes in the T2 value and Oswestry Disability Index (ODI)/visual analogue scale (VAS) score. Design Lumbar spine magnetic resonance imaging was performed, and the ODI/VAS scores were recorded in all 48 patients. Midsagittal T2-weighted imaging and T2 mapping were performed to determine the Pfirrmann grade and T2 value. Then, the T2 values were compared between pre- and posttraction, and the correlation between changes in the T2 value and ODI/VAS scores were examined. Results In the traction group, the changes in the nucleus pulposus (NP) T2 values for Pfirrmann grades II-IV and the annulus fibrosus (AF) T2 values for Pfirrmann grade II were statistically significant after traction ( P < 0.05). Changes in the mean NP T2 value of 5 discs in each patient and in the ODI/VAS score showed a strong correlation ( r = 0.822, r = 0.793). Conclusion T2 mapping can be used to evaluate changes in the intervertebral disc water content. Ten sessions of traction resulted in a significant increase in quantitative T2 measurements of the NP in discs for Pfirrmann grade II-IV degeneration and remission of the patients’ clinical symptoms in the following 6 months. Changes in the mean NP T2 value of 5 discs in each patient were strongly correlated with changes in the ODI/VAS score.

Background Accurate identification of Parkinson’s disease (PD) and Parkinsonism-Plus syndrome (PPS), especially in the early stage of the disease, is very important. The purpose of this study was to investigate the discriminative spatial pattern of cerebral blood flow (CBF) between patients with PD and PPS. Methods Arterial spin labeling (ASL) perfusion-weighted imaging was performed in 20 patients with PD (mean age 56.35 ± 7.56 years), 16 patients with PPS (mean age 59.62 ± 6.89 years), and 17 healthy controls (HCs, mean age 54.17 ± 6.58 years). Voxel-wise comparison of the CBF was performed among PD, PPS, and HC groups. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CBF in discriminating between PD and PPS. The relationship between CBF and non-motor neuropsychological scores was assessed by correlation analysis. Results PD group showed a significantly decreased CBF in the right cerebelum_crus2, the left middle frontal gyrus (MFG), the triangle inferior frontal gyrus (IFG_Tri), the left frontal medial orbital gyrus (FG_Med_Orb) and the left caudate nucleus (CN) compared with the HC group (P P P P Conclusion PD and PPS patients have certain discriminative patterns of reduced CBFs, which can be used as a surrogate marker for differential diagnosis.

AIM: To analyze the clinical efficacy of intravitreal injection of ranibizumab (IVR) on diabetic macular edema (DME) with multifocal electroretinography (mfERG) and optical coherence tomography (OCT). METHODS: A total of 41 patients (41 eyes) with DME were treated with IVR. The best corrected visual acuity (BCVA), mfERG results, and OCT were analyzed to compare to the baselines at 1wk, 1, and 3mo after operation. RESULTS: The BCVA was significantly improved in all eyes at each time point (P

Reduced serum omentin-1 concentrations might be related to an increased risk for poor functional outcome after acute ischemic stroke. We intended to explore whether serum omentin-1 could be a promising prognostic biomarker for acute intracerebral hemorrhage.A total of 104 consecutive patients with hemorrhagic stroke underwent 90-day follow-up. The modified Rankin scale score2 was evaluated as worse prognosis. A multivariable logistic model was conFig.d for assessing the relationship between serum omentin-1 concentrations and functional outcome.Serum omentin-1 concentrations, with the median value of 147.9 ng/ml (interquartile range, 114.7-199.8 ng/ml), were substantially declined with rising modified Rankin scale scores (P 0.001). Serum omentin-1 concentrations147.9 ng/ml was independently related to higher risk of 90-day worse prognosis (odds ratio, 3.789; 95% confidence interval, 1.819-8.608; P = 0.018). Under receiver operating characteristic curve, an optimal value of serum omentin-1 concentrations was selected as 179.7 ng/ml, which yielded 0.88 sensitivity value and 0.70 specificity value for discriminating patients at risk of 90-day worse prognosis (area under curve, 0.82; 95% confidence interval, 0.73-0.89).Lower serum omentin-1 concentrations are closely associated with poor functional outcome after hemorrhagic stroke, substantializing serum omentin-1 as a potential prognostic biomarker for acute intracerebral hemorrhage.

The objective of this study was to quantitatively assess fat deposition in the testis and epididymis by measuring the fat/water signal ratios with mDIXON Quant and to investigate its correlation with age and ejaculation. Routine pelvic magnetic resonance imaging and mDIXON Quant were performed on 120 subjects. The fat/water signal ratios of the testis and epididymis were measured based on the fat/water signal intensity on mDIXON Quant. The fat/water signal ratio values of the testis and epididymis in the early adulthood group (0.952–3.550%, p

Objective To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). Materials and Methods Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15-61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20-65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS. Results Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7-4.9%, p < 0.05 and 1.8-3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2-2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2-3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS. Conclusion The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.

Purpose: To quantitatively investigate the correlation between liver fat content and hepatic perfusion disorders (HPD) after radiofrequency ablation (RFA) for liver cancer using magnetic resonance imaging (MRI)-determined proton density fat fraction (PDFF). Materials and methods: A total of 150 liver cancer patients underwent liver MRI examination within one month after RFA and at four months after RFA. According to the liver fat content, they were divided into non-, mild, moderate, and severe fatty liver groups. The liver fat content and hepatic perfusion disorders were determined using PDFF images and dynamic contrast-enhanced MRI images. The relationship between the liver fat content and HPD was investigated. Results: At the first postoperative MRI examination, the proportion of patients in the nonfatty liver group with hyperperfused foci (11.11%) was significantly lower than that in the mild (30.00%), moderate (42.86%), and severe fatty liver (56.67%) groups (p &lt, 0.05), whereas the proportions of patients with hypoperfused foci (6.67%, 7.5%, 5.71%, and 6.67%, respectively) were not significantly different among the four groups (p &gt, 0.05). In the nonfatty liver group, the liver fat content was not correlated with hyperperfusion abnormalities or hypoperfusion abnormalities. By contrast, in the three fatty liver groups, the liver fat content was correlated with hyperperfusion abnormalities but was not correlated with hypoperfusion abnormalities. At the second postoperative MRI examination, six patients in the nonfatty liver group were diagnosed with fatty liver, including two patients with newly developed hyperperfusion abnormalities and one patient whose hypoperfusion abnormality remained the same as it was in the first postoperative MRI examination. Conclusion: There was a high correlation between the liver fat content and hyperperfusion abnormalities after RFA for liver cancer. The higher the liver fat content was, the higher the was risk of hyperperfusion abnormalities. However, there was little correlation between liver fat content and hypoperfusion abnormalities, and the increase in postoperative liver fat content did not induce or alter the presence of hypoperfused foci.

Objective: The purpose of this study was to determine fat/water signal ratios using the mDIXON Quant sequence, quantitatively assess fat infiltration in the penis, and explore its possible relationship with penile hardness and erectile dysfunction. Methods: Routine pelvic MRI with the mDIXON Quant sequence was performed in 62 subjects, including 22 people in the normal group, 20 people in the normal erectile hardness group, and 20 people in the erectile dysfunction (ED) group. The fat/water signal ratio in the penis was measured using the mDIXON Quant sequence. Shear wave elastography was used to evaluate the hardness of the corpus cavernosa of the penis. Results: The fat/water signal ratio of the corpus spongiosum was significantly lower than that of the corpus cavernosa in the normal group (p = 0.03) and ED group (p < 0.01). There was no significant difference in the fat/water signal ratios between the normal group and the normal erectile hardness group. Fat infiltration was significantly lower, and erectile hardness was significantly higher in the normal erectile hardness group than in the ED group, and the fat infiltration in the left and right corpus cavernosa was inversely proportional to the erectile hardness of the penis. Conclusion: This study suggests that mDIXON Quant can be used as a non-invasive, quantitative, and objective method for evaluating penile fat infiltration. This method could help diagnose penile fat infiltration in patients with erectile dysfunction and varying body mass indexes. Our results could also allow for a more accurate diagnosis and monitoring of erectile hardness function by quantitatively measuring penile fat infiltration. Advances in knowledge: (1) The proton density fat fraction technology is a new tool for the objective, quantitative and non-invasive evaluation of penile fat infiltration. (2) The quantitative measurement of fat infiltration in the corpora cavernosa might help diagnose and monitor penile erection hardness and its function more accurately.

Iron-based nanomaterials as the main ferroptosis-inducing platforms are more promising because iron itself is a key component in the Fenton reaction to produce ROS. However, the Fe dose needs to be very high in order to induce ferroptosis-based cancer treatment using the SPIO NPs. Therefore, it is still of great challenge to enhance the efficacy of ferroptosis-based cancer therapy by associating the iron-based nanomaterials with other components and therapeutic modalities. In this study, sorafenib (SRF) and ultrasmall SPIO nanoparticles were loaded into the mesopores and onto the surface of MPDA NPs to form SRF@MPDA-SPIO nanoparticles. SPIO loading endowed the system with iron-supply for ferroptosis and made the system MRI-visible. Meanwhile, SRF was able to induce ferroptosis in cancer cells with lower Fe dose. Furthermore, the heat generated by MPDA NPs upon laser irradiation offered a moderate PTT to boost the ferroptosis effect. The SRF@MPDA-SPIO exhibited biocompatibility highly desirable for in vivo application and superior anticancer therapy via the combination of ferroptosis and photothermal therapy.

Because the primary surgical treatment options for hepatocellular carcinoma (HCC)—including hepatic resection and liver transplantation—often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin β-like protein 1–related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/β-catenin pathway. The folate-targeted theranostic small interfering RNA (siRNA) nanomedicine Fa-PEG-g-PEI-SPION/psiRNA-TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo, resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis, and angiogenesis. Because of its multi-anticancer functions against HCC, intravenous injection of the folate-targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa-PEG-g-PEI-SPION/psiRNA-TBLR1. Moreover, the SPION-encapsulated polyplexes possess high magnetic resonance imaging (MRI) detection sensitivity, which makes tumor-targeted siRNA delivery easily trackable using the clinical MRI technique. Conclusion: The theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. (Hepatology 2016;63:1240–1255)

Rationale Hepatic sinusoidal obstruction syndrome (SOS) is a rare and potentially fatal complications after hematopoietic stem cell transplantation (HSCT). Most severe SOS result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Patient concerns A 31-year-old man was diagnosed with chronic myeloid leukemia blast crisis. He presented with severe thrombocytopenia on day 42 post-HSCT (on days +42), gradually developed with painful hepatomegaly, ascites, and weight gain. Diagnoses The abdominal computerized tomography showed hepatomegaly, hepatic congestion, periportal edema, narrow hepatic vein, and ascites suggestive of SOS/hepatic vein occlusion. According to the EBMT revised diagnostic criteria, the patient was diagnosed as late-onset severe SOS. Interventions Comprehensive treatment including low molecular weight heparin was initiated. Outcomes The patient had good response with resolution of his hepatomegaly, increase of platelet, weight and transaminase loss after 4 weeks treatment. Lessons In SOS patients with nonspecific clinical and biochemical findings, computerized tomography scans can be useful in differentiating SOS from other complications after HSCT. low molecular weight heparin is effective for the treatment of SOS.

Objective: This study investigated the effects of high haem oxygenase-1 (HO-1) expression on oxidative injury and the biological behaviours of rat dermal fibroblasts, under high glucose conditions. Method: Rat dermal fibroblasts were cultured in normal glucose (1.0g/l), high glucose (4.5g/l) or haemin (5μm). A bilirubin kit, real-time polymerase chain reaction (RT-PCR) and Western blotting measured the protease activity, mRNA, and protein levels of HO-1, respectively. An enzyme-linked immunosorbent assay (ELISA) kit measured media levels of 8-hydroxydeoxyguanosine (8-OHdG), reactive oxygen species (ROS) and collagen (hydroxyproline) secretion. Cell proliferation was measured using flow cytometry. Cell apoptosis was measured using Hoechst 33258 staining and flow cytometry. The transwell method and scratch test evaluated cell migration. Results: HO-1 expression exhibited a time-dependent change that was lowest in the high glucose (HG) group at 96 hours compared with the normal glucose (NG) group. In the HG group, the 8-OHdG, ROS and cell apoptosis were increased, and collagen secretion, cell proliferation and cell migration (horizontal and vertical) were decreased compared with the NG group at 96 hours. Haemin treatment sustained high HO-1 expression for at least 96 hours, and the cells exhibited decreased 8-OHdG and ROS, increased collagen synthesis, improved proliferation and migration ability, and decreased apoptosis in the NG and haemin (NH) group/HG and haemin (HH) group compared with the NG/HG groups. These cells recovered from oxidative injury and biological behaviours dysfunction. Conclusion: Haemin induces HO-1 expression in fibroblasts and it may influence the oxidative injury and biological behaviours of fibroblasts. These findings suggest that HO-1 may accelerate the healing of diabetic wounds via alleviation of oxidative injury and improvement of biological behaviours of fibroblasts.

The objective of this study is to improve the overall prognosis of patients with hepatocellular carcinoma (HCC); therefore, new therapeutic methods that can be used in vivo are urgently needed. In this study, the relationship between the quantities of microRNA (miR)‐125b‐5p in clinical specimens and clinicopathological parameters is analyzed. A folate‐conjugated nanocarrier is used to transfect miR‐125b‐5p in vivo and to observe the therapeutic effect on HCC. The inhibitory effect and mechanism of miR‐125b‐5p on hepatoma cells are also studied. Data from clinical specimens and in vitro experiments confirm that the miR‐125b‐5p quantity is negatively correlated with progression, and the target protein that regulates the epithelial–mesenchymal transition (EMT)/cancer stem cells (CSC) potential in HCC is STAT3. The miR‐125b‐5p/STAT3 axis inhibits the invasion, migration, and growth of HCC via inactivation of the wnt/β‐Catenin pathway. miR‐125b‐5p‐loaded nanomedicine effectively inhibits the EMT/CSC potential of hepatoma cells in vivo together with their magnetic resonance imaging (MRI) visualization characteristics. An HCC‐therapeutic and MRI‐visible nanomedicine platform that achieves noninvasive treatment effect monitoring and timely individualized treatment course adjustment is developed.

Background Our previous study showed that overexpression of hepatocyte nuclear factor 4α (HNF4α) could directly promote mesenchymal stem cells (MSCs) to differentiate into hepatocyte-like cells. However, the efficiency of hepatic differentiation remains low. The purpose of our study was to establish an MSC cell line that overexpressed HNF4α and FOXA2 genes to obtain an increased hepatic differentiation efficiency and hepatocyte-like cells with more mature hepatocyte functions. Methods Successful establishment of high-level HNF4α and FOXA2 co-overexpression in human induced hepatocyte-like cells (hiHep cells) was verified by flow cytometry, immunofluorescence and RT-PCR. Measurements of albumin (ALB), urea, glucose, indocyanine green (ICG) uptake and release, cytochrome P450 (CYP) activity and gene expression were used to analyze mature hepatic functions of hiHep cells. Results hiHep cells efficiently express HNF4α and FOXA2 genes and proteins, exhibit typical epithelial morphology and acquire mature hepatocyte-like cell functions, including ALB secretion, urea production, ICG uptake and release, and glycogen storage. hiHep cells can be activated by CYP inducers. The percentage of both ALB and α-1-antitrypsin (AAT)-positive cells was approximately 72.6%. The expression levels of hepatocyte-specific genes (ALB, AAT, and CYP1A1) and liver drug transport-related genes (ABCB1, ABCG2, and SLC22A18) in hiHep cells were significantly higher than those in MSCs-Vector cells. The hiHep cells did not form tumors after subcutaneous xenograft in BALB/c nude mice after 2 months. Conclusion This study provides an accessible, feasible and efficient strategy to generate hiHep cells from MSCs.

There exists an urgent medical demand at present to develop therapeutic strategies which can improve the treatment outcome of hepatocellular carcinoma (HCC). Here, we explore the biological functions and clinical significance of PBOV1 in HCC in order to push forward the diagnosis and treatment of HCC. Using theranostical nanomedicines, PBOV1 is verified to be a key oncogene which greatly promotes HCC proliferation, epithelial-to-mesenchymal transition, and stemness by activating the Wnt/β-catenin signaling pathway. Therefore, single-chain antibody for epidermal growth factor receptor (scAb-EGFR)-targeted nanomedicine effectively silencing the PBOV1 gene exhibits potent anticancer effects. In vivo HCC-targeting siRNA delivery mediated by the theranostical nanomedicine remarkably inhibits the tumor growth and metastasis. In addition, the superparamagnetic iron oxide nanocrystals (SPION)-encapsulated nanomedicines possess high MRI detection sensitivity, which endows them with the potential for MRI diagnosis of HCC. This study shows that PBOV1 represents a prognostic biomarker and therapeutic target for HCC., Novel therapeutic strategies are needed to improve the treatment outcome of hepatocellular carcinoma. Here, the authors develop a theranostical targeted nanomedicine platform that reveals the key oncogenic role of PBOV1 in hepatocellular carcinoma.

The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF). Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology. The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology. The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

Lipocalin-2 is related to acute brain injury. We assessed the prognostic value of serum lipocalin-2 in head trauma.Blood samples were collected from 115 controls and 115 patients with severe traumatic brain injury. Trauma severity was assessed by Glasgow Coma Scale (GCS) scores at baseline. Thirty-day mortality and overall survival time were recorded.Compared with the controls, serum lipocalin-2 concentrations were significantly increased in the patients. Lipocalin-2 concentrations were independently associated with GCS scores (t=-7.271, P0.001) and serum C-reactive protein concentrations (t=4.325, P0.001). Under receiver operating characteristic curve for 30-day mortality, sensitivity and specificity were 85.7% and 63.2% respectively for lipocalin-2 concentrations at a cutoff value of 591ng/ml. Additionally, area under curve (AUC) of lipocalin-2 concentrations [AUC, 0.825; 95% confidence interval (95% CI), 0.743-0.889] was equivalent to that of GCS scores (AUC, 0.869; 95% CI, 0.793-0.925; P=0.413). Moreover, serum lipocalin-2 concentrations591ng/ml emerged as an independent predictor for 30-day mortality (odds ratio, 4.360; 95% CI, 1.908-12.430) and overall survival (hazard ratio, 3.820; 95% CI, 1.935-10.500).Enhanced serum concentration of lipocalin-2 at admission is associated with trauma severity and neuroinflammation as well as is a predictor of mortality after head trauma.

Acute hepatic encephalopathy has significant morbidity and mortality in liver transplant recipients unless it is promptly treated. We evaluated the brain magnetic resonance (MR) imaging findings associated with acute hepatic encephalopathy in transplant recipients. We retrospectively reviewed the clinical and imaging data and outcomes of twenty-five liver transplant patients (16 male; mean age, 49.3 years) with clinically diagnosed acute hepatic encephalopathy and forty liver transplant patients (20 males; mean age, 45.5 years) without neurological symptoms suggestive of hepatic encephalopathy at our institution. Bilateral symmetric hyperintensities of the insular cortex and cingulate gyrus were observed in twenty-one patients (84.00%), bilateral symmetric extensive increased cortical signal intensity (involving two or more regions) was observed in 72.00% of the patients, leptomeningeal enhancement in 73.68%, and visualization of prominent venules in 52.00%. The most common symptom at diagnosis was rigidity (n = 14), and the plasma ammonia levels ranged from 68.63 to 192.16 μmol/L. After active treatment, 17 patients gradually recovered, four patients suffered from mild or moderate neurologic deficits, and four patients with widespread brain edema died. The specific brain MR imaging features were bilateral symmetric increased cortical signal intensity, especially in the insular cortex and cingulate gyrus, leptomeningeal enhancement, visualization of the prominent venules, and widespread brain edema. These features may indicate poor prognosis and should alert radiologists to the possibility of acute hepatic encephalopathy in liver transplant recipients and encourage clinicians to prepare appropriate treatment in advance.

To quantitatively assess fat infiltration in the sacroiliac joints (SIJs) of patients with ankylosing spondylitis (AS) by measuring the fat/water signal ratios of periarticular bone marrow with iterative decomposition of water and fat with echo asymmetry and least square estimation (IDEAL).Routine SIJ magnetic resonance imaging (MRI) and IDEAL were performed on 40 patients with AS and 30 healthy subjects. The fat infiltration regions (FIRs) and normal-appearing regions (NARs) of patients were measured based on the fat/water signal intensity on IDEAL.AS patients had higher fat/water signal ratios on FIRs and NARs (65.4-85.4%, p0.05, and 44.1-70.7%, p0.05, respectively) compared to healthy controls (38.3-43.3%). After treatment, the fat/water signal ratios of FIRs and NARs decreased (42.1-53.7% and 41.5-50.3%, respectively), but they remained higher than in the healthy controls (p0.05). The fat infiltration was detected more effectively with a fat fraction map of the IDEAL sequence (95%) than other sequences, including the T1-weighted sequence (65%), and the fat/water signal ratios of the sacrum and ilium between the left and right sides of SIJs were approximately the same.The findings of this study suggest that IDEAL may be useful as a quantitative and objective method for evaluating the fat infiltration in the periarticular bone marrow of SIJs with AS; additionally, the sensitivity of IDEAL is better than that of routine sequences in detecting micro-fat infiltration of SIJs, and IDEAL can be used to quantitatively measure the adipose content and monitor patient follow-up after AS treatment.

Adiponectin plays an important role in the regulation of tissue inflammation. There is a paucity of data on circulating plasma adiponectin concentrations in human traumatic brain injury. This study is designed to investigate the potential associations between plasma adiponectin levels and clinical outcomes after traumatic brain injury.Plasma adiponectin levels of 86 patients with severe traumatic brain injury and 86 healthy subjects were determined. Clinical outcomes included in-hospital mortality, 6-month mortality and 6-month unfavorable outcome (Glasgow Outcome Scale score of 1-3).Plasma adiponectin levels were significantly higher in patients compared to controls (20.5±5.9 vs. 7.7±2.0μg/ml; P0.001) and emerged as an independent predictor of in-hospital mortality [odds ratio (OR), 1.318; 95% confidence interval (CI), 1.049-1.629; P=0.008], 6-month mortality (OR, 1.328; 95% CI, 1.082-1.657; P=0.007) and 6-month unfavorable outcome (OR, 1.240; 95% CI, 1.066-1.443; P=0.005) in a multivariate analysis. For predicting these clinical outcomes, areas under receiver operating characteristic curve of plasma adiponectin level were similar to those of Glasgow Coma scale scores (all P0.05). However, adiponectin did not improve predictive values of Glasgow Coma scale scores (all P0.05).Plasma adiponectin level may represent a novel biomarker for predicting clinical outcomes of traumatic brain injury.

Purpose To investigate in vivo MRI tracking mesenchymal stem cells (MSCs) in peripheral nerve injures using a clinically available paramagnetic contrast agent (Gd-DTPA) and commercially available rhodamine-incorporated transfection reagents (PEI-FluoR). Materials and Methods After bone marrow MSCs were labeled with Gd-DTPA and PEI-FluoR complex, the labeling efficacy and longevity of Gd-DTPA maintenance were measured and cell viability, proliferation, and apoptosis were assessed. Thirty-six rabbits with acute sciatic nerve traction injury randomly received 1 × 106 labeled (n = 12) or unlabeled MSCs (n = 12) or vehicle alone injection. The distribution and migration of implanted cells was followed by MRI and correlated with histology. The relative signal intensity (RSL) of the grafts was measured. Results The labeling efficiency was 76 ± 4.7% and the labeling procedure did not influence cell viability, proliferation, and apoptosis. A persistent higher RSL in grafts was found in the labeled group compared with the unlabeled and vehicle groups until 10 days after transplantation (P < 0.05). The distribution and migration of labeled cells could be tracked by MRI until 10 days after transplantation. Transplanted MSCs were not found to transdifferentiate into Schwann-like cells within 14-day follow-up. Conclusion Labeling MSCs with the dual agents may enable cellular MRI of the engraftment in the experimental peripheral nerve injury. J. Magn. Reson. Imaging 2010;32:1076–1085. © 2010 Wiley-Liss, Inc.

Implantation of embryonic stem cells (ESC)-derived insulin-producing cells has been extensively investigated for treatment of diabetes in animal models. However, the in vivo behavior and migration of transplanted cells in diabetic models remains unclear. Here we investigated the location and migration of insulin-producing cells labeled with superparamagnetic iron oxide (SPIO) using a dynamic MRI tracking method. SPIO labeled cells showed hypointense signal under the kidney subcapsules of diabetic mice on MRI, and faded gradually over the visiting time. However, new hypointense signal appeared in the spleen 1 week after transplantation, and became obvious with the time prolongation. Further histological examination proved the immigrated cells were insulin and C-peptide positive cells which were evenly distributed throughout the spleen. These intra-spleen insulin-producing cells maintained their protective effects against hyperglycemia in vivo, and these effects were reversed upon spleen removal. Transplantation of insulin-producing cells through spleen acquired an earlier blood glucose control as compared with that through kidney subcapsules. In summary, our data demonstrate that insulin-producing cells transplanted through kidney subcapsules were not located in situ but migrated into spleen, and rescues hyperglycemia in diabetic models. MRI may provide a novel tracking method for preclinical cell transplantation therapy of diabetes continuously and non-invasively.

As the final life-saving treatment option for patients with terminal organ failure, organ transplantation is far from an ideal solution. The concomitant allograft rejection, which is hardly detectable especially in the early acute rejection (AR) period characterized by an intense cellular and humoral attack on donor tissue, greatly affects the graft survival and results in rapid graft loss. Based on a magnetic resonance imaging (MRI)-visible and T-cell-targeted multifunctional polymeric nanocarrier developed in our lab, effective co-delivery of pDNA and superparamagnetic iron oxide nanoparticles into primary T cells expressing CD3 molecular biomarker was confirmed in vitro. In the heart transplanted rat model, this multifunctional nanocarrier showed not only a high efficiency in detecting post-transplantation acute rejection but also a great ability to mediate gene transfection in T cells. Upon intravenous injection of this MRI-visible polyplex of nanocarrier and pDNA, T-cell gathering was detected at the endocardium of the transplanted heart as linear strongly hypointense areas on the MRI T(2)*-weighted images on the third day after cardiac transplantation. Systematic histological and molecular biology studies demonstrated that the immune response in heart transplanted rats was significantly suppressed upon gene therapy using the polyplex bearing the DGKα gene. More excitingly, the therapeutic efficacy was readily monitored by noninvasive MRI during the treatment process. Our results revealed the great potential of the multifunctional nanocarrier as a highly effective imaging tool for real-time and noninvasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.

To observe the longitudinal changes of nerve repair in rats after tissue-engineered construct implantation at magnetic resonance (MR) imaging and to determine whether the enhanced nerve regeneration with use of tissue-engineered constructs could be monitored with gadofluorine M-enhanced MR imaging or nerve T2 relaxation time measurement.All experimental protocols were approved by the institutional Animal Use and Care Committee. Tissue-engineered constructs were prepared by seeding mesenchymal stem cells (MSCs) into chitosan nerve tubes. Thirty-six rats with sciatic nerve transection injury underwent nerve tube implantation with (n = 18) or without (n = 18) MSC seeding. Sequential T2 measurement, gadofluorine M-enhanced MR imaging, and sciatic function index measurement were performed over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and signal intensity at gadofluorine M-enhanced T1-weighted imaging were measured and were compared by using repeated-measures analysis of variance followed by the Student-Neuman-Keuls post-hoc test for multiple pairwise comparisons.Nerve T2 relaxation times and gadofluorine M enhancement, as well as functional changes, showed a similar time course. Nerves implanted with MSC-seeded tubes achieved slightly better functional recovery and enhanced nerve regeneration while showing a slower return to baseline T2 relaxation time and a more rapid decline in gadofluorine M enhancement compared with nerves implanted with chitosan tubes alone. T2 values of the distal portion of transected nerves showed a more rapid return to baseline level than did gadofluorine M enhancement.Peripheral nerve repair with use of tissue-engineered constructs can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting nerve regeneration.

To investigate the feasibility of highly efficient and controllable stem cell labelling for cellular MRI.A new class of cationic, superparamagnetic iron oxide nanoparticle (SPION)-loaded nanovesicles was synthesised to label rat bone marrow mesenchymal stem cells without secondary transfection agents. The optimal labelling conditions and controllability were assessed, and the effect of labelling on cell viability, proliferation activity and multilineage differentiation was determined. In 18 rats, focal ischaemic cerebral injury was induced and the rats randomly injected with 1 × 10(6) cells labelled with 0-, 8- or 20-mV nanovesicles (n = 6 each). In vivo MRI was performed to follow grafted cells in contralateral striata, and results were correlated with histology.Optimal cell labelling conditions involved a concentration of 3.15 μg Fe/mL nanovesicles with 20-mV positive charge and 1-h incubation time. Labelling efficiency showed linear change with an increase in the electric potentials of nanovesicles. Labelling did not affect cell viability, proliferation activity or multilineage differentiation capacity. The distribution and migration of labelled cells could be detected by MRI. Histology confirmed that grafted cells retained the label and remained viable.Stem cells can be effectively and safely labelled with cationic, SPION-loaded nanovesicles in a controllable way for cellular MRI.• Stem cells can be effectively labelled with cationic, SPION-loaded nanovesicles. • Labelling did not affect cell viability, proliferation or differentiation. • Cellular uptake of SPION could be controlled using cationic nanovesicles. • Labelled cells could migrate along the corpus callosum towards cerebral infarction. • The grafted, labelled cells retained the label and remained viable.

The purpose of our study was to monitor neural stem cells (NSCs) transplanted in acute peripheral nerve traction injury and to use MRI to assess the ability of NSCs to promote nerve regeneration.After labeling with gadolinium-diethylene triamine pentaacetic acid (gadopentetate dimeglumine) and fluorescent dye (PKH26), 5 × 10(5) NSCs were grafted to acutely distracted sciatic nerves in 21 New Zealand White rabbits. In addition, 5 × 10(5) unlabeled NSCs (n = 21) and vehicle alone (n = 21) subjects were injected as a control. Serial MRI was performed with a 1.5-T scanner to determine the distribution of grafted cells. Sequential T1 and T2 values of the nerves and functional recovery were measured over a 70-day follow-up period, with histologic assessments performed at regular intervals.The distribution and migration of labeled NSCs could be tracked with MRI until 10 days after transplantation. Compared with vehicle control, nerves grafted with labeled or unlabeled NSCs had better functional recovery and showed improved nerve regeneration but exhibited a sustained increase of T1 and T2 values during the phase of regeneration.Gadopentetate dimeglumine-based labeling allowed short-term in vivo MRI tracking of NSCs grafted in injured nerves. NSCs transplantation could promote nerve regeneration in acute peripheral nerve traction injury as shown by a prolonged increase of nerve T1 and T2 values.

Objective To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI. Materials and methods 1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5 × 10 5 MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals. Results Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration. Conclusion MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves.

Purpose To retrospectively review CT and MRI findings in a series of six intraspinal primitive neuroectoderal tumors and to find out their radiological features. Methods CT and MRI of six patients with surgically and pathologically proved intraspinal primitive neuroectoderal tumor were retrospectively reviewed. The tumor location, morphological features, signal intensity, calcification, contrast enhancement characteristics, involvement of paraspinal soft tissues and adjacent bony structures were assessed. Results Of six patients, four had extradural lesions and two had intradural, extramedullary lesions. Most lesions were well defined and manifested heterogeneous iso- or hypo-intense signal on T1-weighted imaging and hyper-intense signal on T2-weighted imaging and moderate attenuation on CT, and were heterogeneously enhanced after contrast enhancement. The lesion extending through the intervertebral foramen with a large paraspinal soft tissue mass formed was found in four patients and vertebral bone involvement was seen in four patients. Conclusions Although imaging findings are not specific of intraspinal primitive neuroectoderal tumor, this diagnosis could be suggested when MR imaging depicts an intradural, extramedullary or extradural large well-circumscribed mass which extends out from intervertebral foramen and invades paraspinal soft tissues or vertebral bones in a young patient.

To prospectively evaluate magnetic resonance (MR) signal abnormalities and the time course of T1 and T2 values in a rabbit model of acute nerve traction injury with histologic and functional recovery correlation.All experimental protocols were approved by the institutional animal use and care committee. Acute traction injury was produced in the sciatic nerve of one hind limb in each of 28 rabbits. The contralateral sham-operated nerves served as controls. Sequential MR imaging and T1 and T2 measurements, as well as measurements of functional changes, were obtained over a 70-day follow-up period, with histologic assessments performed at regular intervals. Signal abnormalities and the time course of T1 and T2 values were observed in the proximal, traction, and distal portions of the injured nerves and the sham-operated nerves, and were compared with each other.Nerves with acute traction injury showed visible hyperintense signals on T2-weighted images and had prolonged T1 and T2 values. Differences of T1 and T2 values were dependent on the sites along the same injured nerve, with the most pronounced and prolonged phase of T1 and T2 increases (peak values of 1333 msec +/- 46 and 79 msec +/- 3.7, respectively) observed in the most severely damaged portion of the injured nerve. T1 and T2 values and functional changes after nerve injury showed a similar time course. A return of T1 and T2 signals to normal values correlated with functional improvement.MR imaging could be used to help predict the degree of nerve damage and monitor the process of nerve recovery in acute peripheral nerve traction injury. (c) RSNA, 2010.

The aim of this study is to label rabbit neural stem cells (NSCs) by using standard contrast agents (Gd-DTPA) in combination with PKH26 and in vitro track them with MR imaging.NSCs from prenatal brains of rabbits were cultured and propagated. Intracellular uptake of Gd-DTPA was achieved by using a non-liposomal lipid transfection reagent (Effectene) as the transfection agent. After labeling with Gd-DTPA, cells were incubated with cellular membrane fluorescent dye PKH26. The labeling effectiveness and the longevity of Gd-DTPA maintenance were measured on a 1.5T MR scanner. The influence of labeling on the cellular biological behaviors was assessed by cellular viability, proliferation and differentiation assessment.The labeling efficiency of Gd-DTPA was up to 90%. The signal intensity on T1-weighted imaging and T1 values of labeled cells were significantly higher than those of unlabeled cells (P0.05). The minimal number of detectable cells for T1-weighted imaging was 5×10(3). Cellular uptake of Gd-DTPA was maintained until 15 days after initially labeling. There was no significant difference in the cellular viability and proliferation between the labeled and unlabeled NSCs (P0.05). Normal glial and neuronal differentiation remained in labeled NSCs like unlabeled NSCs.Highly efficient labeling NSCs with Gd-DTPA could be achieved by using Effectene. This method of labeling NSCs allows for tracking cells with MR imaging, and without alterations of cellular biological behaviors.