Aberrant Expression of a Proliferation-Inducing Ligand Underlies Autoimmune Mechanisms in Immune Thrombocytopenia.

PURPOSE: To study the relationship between surface membrane-bound APRIL and ITP. METHODS: The peripheral blood of all subjects, 50 patients diagnosed with ITP and 25 healthy controls, was collected. Flow cytometry was used to detect the expression of membrane-bound APRIL on immune cells and platelets. ELISA was used to detect the content of soluble APRIL in plasma. RESULTS: Membrane-bound APRIL was only expressed on the surface of platelets in both ITP patients and controls. APRIL expression on the platelet surface was significantly lower in newly diagnosed (P < 0.001) and chronic (P < 0.001) ITP patients than in controls. Platelet surface APRIL level was significantly enhanced in patients with complete remission after treatment (P = 0.02) but not in those with no response after treatment. Platelet surface APRIL level in ITP patients was negatively correlated with serum APRIL level (r = -0.09765, P = 0.0424). CONCLUSIONS: Platelet surface APRIL may play a key immunoregulative role. Platelet surface APRIL is likely to be one source of the excessive serum APRIL in ITP patients. The effectiveness of treatment may be measured by determining the platelet surface APRIL levels in ITP patients.

Increasing miR-150 and lowering HMGA2 inhibit proliferation and cycle progression of colon cancer in SW480 cells.

OBJECTIVE: High mobility group protein A2 (HMGA2) is a kind of oncogene that regulates cell proliferation and cycle. HMGA2 up-regulation is related to the occurrence of multiple tumors including colorectal cancer. MiR-150 is found down-regulated in colorectal cancer tissue. Bioinformatics analysis shows the complementary targeted relationship between miR-150 and the 3'-UTR of HMGA2. This study explores the role of microRNA-150 (miR-150) in regulating HMGA2 expression, colorectal cancer cell proliferation, and cycle. PATIENTS AND METHODS: Colorectal cancer patients were enrolled to collect cancer and para-carcinoma tissues. MiR-150 and HMGA2 expressions were tested in tissue. MiR-150, HMGA2, and Cyclin A levels in colorectal cancer cell line SW480, and normal colorectal epithelial cell line FHC were compared. The targeted relationship between miR-150 and the 3'-UTR of HMGA2 was evaluated by dual luciferase reporter gene assay. SW480 cells were divided into five groups, including miR-control, miR-150 mimic, small interfere normal control (si-NC), si-HMGA2, and miR-150 mimic + si-HMGA2. Cell cycle was determined by using flow cytometry. The cell proliferation was detected by using the cell counting kit 8 (CCK-8) test. RESULTS: HMGA2 expression was significantly increased, while miR-150 levels were significantly declined in colorectal cancer tissue compared with that in para-carcinoma tissue (p<0.05). HMGA2 and Cyclin A levels were higher significantly, whereas miR-150 expression was lower significantly in SW480 cells compared to that in FHC cells (p<0.05). MiR-150 targeted band to the 3'-UTR of HMGA. MiR-150 mimic and/or si-HMGA2 significantly reduced HMGA2 and Cyclin A expressions, blocked cell cycle in the G0/G1 phase, and attenuated cell proliferation. CONCLUSIONS: We observed that miR-150 down-regulated Cyclin A expression to block colorectal cancer cell cycle and inhibit proliferation through targeted inhibiting HMGA2.

Effects of preventive acupuncture on streptozotocin-induced hyperglycemia in rats.

BACKGROUND: Diabetes prevention has received increasing attention recently. Clinical and experimental studies showed that acupuncture could produce hypoglycemic effect. However, little is known about the effectiveness of acupuncture in diabetes prevention. AIM: To investigate the preventive effects of acupuncture on streptozotocin (STZ)-induced hyperglycemia in rats. METHODS: Hyperglycemia was induced by a single intraperitoneal injection of STZ (60 mg/kg). Rats were randomly divided into six groups (no.=8 each group): control, diabetes, preventive acupuncture plus STZ injection, STZ injection plus therapeutic acupuncture, STZ injection plus preventive and therapeutic acupuncture, and preventive and therapeutic acupuncture control. Body weight, blood glucose, serum insulin, lipid peroxidation, and antioxidant enzymes were measured by routine standard methods. Histological analysis of pancreatic islets was conducted. RESULTS: Preventive acupuncture significantly relieved hyperglycemia, insulin deficiency, weight loss, and pancreatic islet damage in rats with STZ injection; it also significantly reduced serum lipid peroxidation and enhanced superoxide dismutase in the serum and the pancreas without significantly affecting serum glutathione peroxidase and catalase. Therapeutic acupuncture exhibited a hypoglycemic effect in the late stage, but did not significantly improve other parameters. CONCLUSIONS: These results indicate that preventive acupuncture is beneficial to the control of STZ-induced hyperglycemia in rats.

Clinical dosimetric study of three radiotherapy techniques for postoperative breast cancer: Helical Tomotherapy, IMRT, and 3D-CRT.

This paper is to investigate the dosimetric characteristics of Helical Tomotherapy (HT), step-and-shoot intensity-modulated radiation therapy (SaS-IMRT) and three-dimensional conformal radiation therapy (3D-CRT) for the postoperative breast cancer as well as their dosimetric comparison of the normal tissues. CT images of 10 postoperative patients with early stage breast cancer were transferred into HT, SaS-IMRT and 3D-CRT planning systems respectively after the target region and normal tissues were outlined by the same physician to assure the contour consistency. Each prescribed dose for three different modalities of plans was given to a total of 50 Gy in 25 fractions. Doses and irradiated volumes in heart, lungs, as well as conformity index (CI) and homogeneity index (HI) were evaluated for detailed comparison. All three plans showed appropriate coverage for the prescribed target dose in the dosimetric comparison. The CI in HT and SaS-IMRT as well as 3D-CRT was 0.68 ± 0.12, 0.58 ± 0.08 and 0.40 ± 0.08, respectively. The HI were 1.10 ± 0.03, 1.14 ± 0.02 and 1.17 ± 0.04, which appeared intergroup significant differences (p < 0.05). V5, V10, as well as V20 of the heart were smallest in 3D-CRT than HT and SaS-IMRT. V5 of the ipsilateral lung was the smallest in 3D-CRT than HT and SaS-IMRT (p < 0.05); However, V20 and V30 were smaller in HT and SaS-IMRT than 3D-CRT (p < 0.05). V5 of the contralateral lung was the smallest in 3D-CRT than other groups, with V10~V30 were basically similar in numeric values with not obvious discrepancy. Comparing with SaS-IMRT and 3D-CRT, HT technique in treating breast cancer had the best conformity and homogeneity index as well as steepest dose gradient due to its highly modulated beamlets with rotational technique. The heart volume irradiated was the smallest in conventional 3D-CRT, with SaS-IMRT was the largest among the three techniques, as expected. The volume of the contralateral lung irradiated was the smallest in 3D-CRT than other groups. V5 of the ipsilateral lung was the smallest in 3D-CRT than other two groups. V10~V30 in HT and SaS-IMRT were similar and better than 3D-CRT dosimetrically. We conclude that HT technique had advantages over SaS-IMRT and 3D-CRT based on the dosimetric comparison in this study, especially in the high dose region of ipsilateral lung, target homogeneity and dose uniformity.

Association of methylenetetrahydrofolate reductase and thymidylate synthase promoter polymorphisms with genetic susceptibility to esophageal and cardia cancer in a Chinese high-risk population.

SUMMARY: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are key enzymes in folate metabolism, which is essential for normal DNA methylation and synthesis. Common polymorphisms at the MTHFR nucleotides position 677 (C-T) and a 28-bp tandem repeat polymorphism (2R or 3R) in the TS promoter enhancer region (TSER) have been reported to be functional and are supposed to disturb the normal DNA methylation and synthesis leading to carcinogenesis. To investigate the association between these polymorphisms and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA), we conducted a case-control study in the Anyang area where the incidence of ESCC is highest in northern China. Subjects consisted of 275 cases with ESCC, 129 cases with GCA and 310 sex- and age-matched cancer-free controls. The risk was evaluated in terms of age-sex adjusted odds ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression model. The ORs for the MTHFR677TT genotype compared with the MTHFR677CC/CT genotype were 1.62 (95% CI = 1.15-2.30) and 1.81 (1.17-2.81) for ESCC and GCA, respectively. The ORs for the TSER 2R/2R genotype relative to the other genotypes were 2.44 (0.89-6.73) and 3.94 (1.29-12.0) for SCC and GCA, respectively. These findings indicated that the folate metabolism plays an important role in carcinogenesis of ESCC and GCA and the common functionally polymorphisms MTHFRC677T and TSER have substantial influence in this metabolic pathway.

Death in the burn unit: sterile multiple organ failure.

It has been our impression over the years that the most common cause of death in our burn patients is multiple organ failure, despite the clinical absence of uncontrolled infection at the time of death. A six year review of all deaths in our unit confirmed this impression, revealing that multiorgan failure is indeed the most common cause of death (48 patients, 67 per cent), followed rather distantly by early withdrawal of support (15 patients, 21 per cent), resuscitation failure (4 patients, 6 per cent) and isolated pulmonary failure (4 patients, 6 per cent). Finally, we found that our patients dying of multiorgan failure, although often having had multiple small infections during their course, were indeed clinically uninfected at the time of death. These findings are consistent with the supposition that uncontrolled systemic inflammation, initially triggered by tissue injury and isolated infection, persists despite control of these infections and leads to multiple organ failure and death.

Inhaled nitric oxide in burn patients with respiratory failure.

BACKGROUND: Inhaled nitric oxide (NO) has the potential to improve ventilation/perfusion matching and decrease pulmonary artery pressure in patients with profound respiratory failure. METHODS: Eight patients, average age of 35 years (range, 2.5-77 years) and burn size 49% (range, 19-80%), with inhalation injury and respiratory failure failing conventional management (average Pao2/FiO2 ratio (PFR) 85) were given inhaled NO at 20 ppm. RESULTS: An immediate mean increase in PFR of 10% and a decrease in pulmonary artery mean pressure of 7.8% was noted. At 24 hours, the average improvement in PFR was 28% and that in pulmonary artery mean pressure was 7.7%. Although not reaching statistical significance, these changes were more pronounced in those patients who went on to survive. There was no hypotension attributed to NO administration, and maximum methemoglobin levels averaged 0.9%. CONCLUSIONS: Inhaled NO can be safely administered to selected burn patients with severe respiratory failure who are perceived to be failing conventional support. Although current data are not adequate to support its general use, an immediate and sustained improvement in PFR and pulmonary artery mean pressure may correlate with eventual recovery of pulmonary function. Continued evaluation in controlled settings seems warranted and is in progress.

Burn depth estimation by use of indocyanine green fluorescence: initial human trial.

Indocyanine green dye (ICG) fluoresces when illuminated by infrared light. After successful trials in a porcine model and with approval of the Massachusetts General Hospital's human studies committee, 10 adult patients with burn injuries were given 0.2 mg/kg ICG intravenously, and 825 nm fluorescence images were obtained with 780 nm excitation at 5 minutes after injection in the initial five patients and at 1, 2, 3, 4, 5, and 10 minutes in the subsequent five patients. Fluorescence intensities at burned and unburned sites were determined and images were correlated with burn depth as determined by healing or intraoperative assessment. In the latter five patients, seven sites were imaged (six that were of partial thickness and one that was of full thickness). The burn/normal skin fluorescence ratio was greater than 1 for superficial burns and less than 1 for deep burns. Imaging within 5 minutes of injection resulted in optimal contrast between injured and uninjured tissue. In this initial pilot trial it is apparent that ICG fluorescence has potential value as an aid in the early estimation of burn depth. In subsequent trials we will attempt to refine our ability to correlate ICG fluorescence images with burn depth.