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Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Aristolochic acid I (AAI) derived from a natural herbal alkaloid is a nephrotoxicant. AAI-induced acute kidney injury (AKI), a devastating clinical disease associated with high mortality rates, is difficult for early diagnosis. To address this issue, we identified and validated early-detection biomarkers for AAI-induced acute kidney injury via profiling microRNA expression in rats. Global miRNA expression profile analysis found that 21 miRNAs were significantly dysregulated in kidney of rats treated by 40 mg/kg AAI on day 2, day 4, or day 6, among which 5 miRNAs were upregulated at all three time points. Quantitative RT-PCR confirmed that miR-21-3p on day 4 and day 6 was obviously upregulated in kidney of rats treated by 40 mg/kg AAI. Further examination found that miR-21-3p was increased in plasma early on day 2 in 10 mg/kg AAI-treated rats, but not in non-target organs. Importantly, the elevation of plasma miR-21-3p preceded the increase in blood urea nitrogen and creatinine, and the presence of renal tubular injury, characterized by differential increase before and after the presence of renal tubular lesions. Our findings thus show that miRNA expression is upregulated in kidney and plasma of AKI rat induced by AAI, and plasma miR-21-3p may be served as a new potential biomarker for early diagnosing AAI-induced acute kidney injury in rats, and possibly in humans.

Many Aristolochia species herbal drugs, used for diseases treatment since antiquity, contain active component aristolochic acid mixture, which consists of aristolochic acid I and II. However, it remains unclear whether aristolochic acid I is gastrotoxic, though evidence has shown that aristolochic acid mixture is nephrotoxic, carcinogenic, and genotoxic. The present study aimed to investigate the gastrotoxicity in rats treated with aristolochic acid I alone. Four groups of rats were orally administrated with vehicle (1% NaHCO3), or 30mg, 60mg, and 90mg/kg/day of aristolochic acid I for twelve days. The results showed that aristolochic acid I can induce obvious body weight loss, forestomach injury characterized by necrosis, ulcer, hyperkeratosis, and hyperplasia of epithelial cells. The severity of these forestomach lesions was presented in a dose-dependent mode. Meanwhile, only non-specific, slight renal tubule degeneration, and occasionally single necrotic epithelial cell were found in aristolochic acid I-treated rats' kidney. These resulst indicated aristolochic acid I had obvious gastrotoxicity, and such aristolochic acid I-induced forestomach toxicity probably presented much prior to kidney injury. Such irritation lesions may play a partial role in gastric cancer development of rats induced by aristolochic acid. Therefore, these results expanded our understanding on the digestive system toxicity of aristolochic acid I., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: To investigate the differences between emergency surgery and selective surgery treatment of ankle fractures with dislocation., Methods: In the study, 40 patients with ankle fracture and dislocation were treated and followed up from May 2013 to May 2014, and all the data were collected and analyzed. The subjects involved 29 male patients and 11 female patients. The patients were randomly separated into two groups, and the patients in group A were given surgical intervention within 6 hours after injury, while those in group B were initially given close reduction and given selective operation when the soft tissue condition got better. Group A contained 13 male patients and 7 female patients with average age of 37.10; Group B consisted of 15 male and 5 female, with average age of 37.85., Results: The Baird-Jackson score was applied for assessment of the patients' outcomes. According to the score, the outcomes were classified into excellent, good, fair, and poor. In group A (emergency group), the outcomes were 13 (65.0%), 4 (20.0%), 3 (15.0%), and 0, respectively. In group B (selective group), they were 11 (55.0%), 7 (35.0%), 2 (10.0%), and 0, respectively. The numbers of the patients from excellent to poor were 24 (55.0%), 11 (27.5%), 5 (12.5%), and 0, respectively., Conclusion: There is no significant difference in postoperative function between the two groups, however, early surgical intervention can benefit in accomplishing anatomical reduction much easier and shortening the time of hospitalization, which is cost-saving for the patients.

Pregnancy-related pelvic ring disease brings great suffering to pregnant women, including the separation of the pubic symphysis and sacroiliac joint pain. Hormonal changes leading to ligamentous laxity is the main reason for Pregnancy-related pelvic ring disease. In normal pregnant cases, and the physiologic widening at the symphysis is about 3-7 mm. When the widening of the symphysis is more than 10 mm, it may lead to symptoms and need active treatment. Currently the diagnosis of the pubic symphysis separation is based on the clinical symptoms and signs. The treatment of acute pubic symphysis separation bases on conservative therapy, includes bed rest and physical therapy. But when the widening of the symphysis is more than 4 cm, the surgery intervention may be a good treatment. If the conservative treatment is not obviously effective, the surgery consists of plate fixation in the pubic symphysis and sacroiliac screw fixation. Other indications for the surgical intervention include inadequate reduction, recurrent diastasis, intractable symptoms, and open rupture.

Background: Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy, difficult-to-access surgical sites, and the relatively low incidence of such cases. Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture. The goal of this study was to assess the use of three-dimensional (3D) printing techniques for surgical management of old pelvic fractures., Methods: First, 16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data. Next, nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models. The pelvic injuries were all type C, and the average time from injury to reconstruction was 11 weeks (range: 8-17 weeks). The workflow consisted of: (1) Printing patient-specific bone models based on preoperative computed tomography (CT) scans, (2) virtual fracture reduction using the printed 3D anatomic template, (3) virtual fracture fixation using Kirschner wires, and (4) preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation. These models aided communication between surgical team members during the procedure. This technique was validated by comparing the preoperative planning to the intraoperative procedure., Results: The accuracy of the 3D printed models was within specification. Production of a model from standard CT DICOM data took 7 hours (range: 6-9 hours). Preoperative planning using the 3D printed models was feasible in all cases. Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases. The patients were followed for 3-29 months (median: 5 months). The fracture healing time was 9-17 weeks (mean: 10 weeks). No delayed incision healing, wound infection, or nonunions occurred. The results were excellent in two cases, good in five, and poor in two based on the Majeed score., Conclusions: The 3D printing planning technique for pelvic surgery was successfully integrated into a clinical workflow to improve patient-specific preoperative planning by providing a visual and haptic model of the injury and allowing patient-specific adaptation of each osteosynthesis implant to the virtually reduced pelvis.

The introduction of rotavirus vaccines Rotarix® and RotaTeq® into the Australian National Immunisation Program in July 2007 has resulted in a dramatic decrease in the burden of rotavirus disease. G2P[4] strains became the dominant genotype Australia-wide during the 2010-2011 surveillance period and for the first time since vaccine introduction, a higher proportion were isolated in jurisdictions using RotaTeq® vaccine compared to locations using Rotarix®. Phylogenetic analysis of the VP7 gene of 32 G2P[4] strains identified six genetic clusters, these distinct clusters were also observed in the VP4 gene for a subset of 12 strains. The whole genome was determined for a representative strain of clusters; A (RVA/Human-wt/AUS/SA066/2010/G2P[4]), B (RVA/Human-wt/AUS/WAPC703/2010/G2P[4]), C (RVA/Human-wt/AUS/MON008/2010/G2P[4]) and E (RVA/Human-wt/AUS/RCH041/2010/G2P[4]). All of the strains possessed the archetypal DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Three of the strains, SA066, MON008 and WAPC703 clustered together and were distinct to RCH041 for all 11 genes. The VP7 genes of 31/32 of the strains characterized in this study possessed five conserved amino acid substitutions when compared to the G2 VP7 gene present in the RotaTeq® vaccine. Three of the substitutions were in the VP7 antigenic regions A and C, the substitutions A87T, D96N and S213D have been reported in the majority of G2P[4] strains circulating globally over the previous decade. These changes may have improved the ability of strains to circulate in settings of high vaccine use., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Previous studies into electro-acupuncture (EA) treatment of irritable bowel syndrome (IBS) have principally focused on the peripheral effects of EA in a rat model of IBS. It is not known whether EA exerts central effects in this rat model. We have examined the effects of EA on hypothalamic corticotropin-releasing hormone (CRH) levels in a rat model of IBS provoked by colorectal distension (CRD) and forelimb immobilization. EA was administered once daily to IBS model rats over a period of 7 d; untreated IBS rats and controls were also studied. The behavioral response to distension was rated according to the abdominal withdrawal reflex (AWR) score; hypothalamic CRH levels were measured by radioimmunoassay. We report that EA treatment significantly decreased visceral sensitivity to CRD in this rat model. In treated animals, EA also decreased hypothalamic CRH to control levels. Reduced hypothalamic CRH levels may mediate the beneficial effects of EA in this rat IBS model.

As methods of cancer diagnosis and treatment improve, interest in metastatic brain tumors continues to increase. In the present study, we attempted to characterize genetically the dynamic changes occurring during brain metastasis formation by DNA microarray, and attempted to compare these findings with histological observations. Lewis lung carcinoma cells were injected into C57BL/6Ncrj mice carotid arteries. The mice were sacrificed at days 1-9 after injection. We performed histological observation and genome-wide expression profiling using a DNA microarray. In histological observation, tumor cells were observed in capillary vessels at day 1 after injection. At day 3, the tumor cells had begun to proliferate. At day 6, the metastatic foci showed "perivascular proliferations". Next, we performed a pairwise comparison of gene expression microarray data from day 1 to day 9 after injection. The first major change occurred between Phase Two and Phase Three. When hierarchical clustering was performed between different samples using the 867 genes, they could be classified into identical clusters for days 1 and 2, identical clusters for day 3 to day 5, and identical clusters for day 6 to day 9. For time course analysis, we extracted 623 genes by the pairwise comparison. By using the quality threshold (QT) nonhierarchical clustering method, we identified 37 expression patterns. These patterns can be separated into eight clusters by using the k-means method. The microarray results reported here strongly suggest that a large number of genes exhibit a spike pattern, which is tantamount to phase-specific expression.

Objective: To investigate the effects of arginine enriched enteral nutrition (EN) on nutritional status and cellular immunity of severely burned patients., Methods: Randomized, single blind, parallel and positive control investigation was employed in the study. Thirty severely burned patients were divided into enteral immune nutrition (EIN) group and EN group. Sixteen patients in EIN group received enteral nutrition enriched with arginine, while the other 14 patients in EN group received standard enteral nutrition. Nutritional support was continued for 14 days. Gastrointestinal reaction of patients in 2 groups was observed. Fasting venous blood was drawn from patients of both groups before receiving nutrition treatment and on the morning of 7th, 14th day of treatment. Level of serum protein, hepatic function parameters, renal function parameters, fasting-blood glucose, and subpopulations of T lymphocytes in peripheral blood were determined., Results: (1) Incidence of gastrointestinal side effect in EIN group (25.0%) was close to that of EN group (21.4% , P > 0.05). (2) Compared with pre-treatment days, levels of prealbumin and transferrin in serum of patients in 2 groups on 7th and 14th post-treatment days were significantly increased (P < 0.05 or P < 0.01), but there was no significant difference between 2 groups. The level of total serum protein on 14th day of treatment of patients was significantly increased in both groups, and that of EIN group (66 +/- 7 g/L) was significantly higher compared with that in EN group (64 +/- 11 g/L, P < 0.05). The level of serum albumin (29 +/- 5, 32 +/- 5 g/L, respectively) of patients in EIN group on 7th and 14th day of treatment were significantly higher than that (26 +/- 4 g/L, P < 0.05) in pre-treatment days, however there was no significant difference in EN group. (3) There was no significant difference in respect of hepatic function, renal function, and fasting-blood glucose between pre-treatment and post-treatment periods in both groups (P > 0.05). (4) The ratio of CD4(+), CD8(+) on 14th day of treatment in EIN group was close to that of pretreatment level. In EN group, cell percentage of CD4(+) significantly decreased, while that of CD8(+) significantly increased (P < 0.05), and CD4(+) was significantly higher [(56 +/- 8)%] in EIN group than that in EN group [(55 +/- 12)%, P < 0.05]. In both groups, cell percentage of CD3(+) was significantly higher than that in pre-treatment days (P < 0.05), while there was no obvious change in CD4(+)/CD8(+)., Conclusions: Arginine enriched enteral nutrition can effectively improve nutritional status and cellular immune function of burn patients.

As methods of cancer diagnosis and treatment progress, interest in metastatic brain tumours continues to increase. There are many studies using various methods of animal model and we considered that each model reflects different pathological processes because of the unique composition of the brain. We prepared metastatic brain tumour models using three different methods. In this study, we attempted to elucidate the roles of the pia mater in brain metastasis. The metastatic foci showed an angiocentric pattern, forming collars of neoplastic cells, and were designated 'perivascular proliferations'. Furthermore, we observed neoplastic cells that infiltrated the brain parenchyma, the border of which had become indistinct. These were labelled 'invasive proliferations'. The internal carotid artery injection model reflects haematogenous metastasis. In this model, both perivascular and invasive proliferations were observed. The intrathecal injection model reflects leptomeningeal carcinomatosis. In this model, metastasis to the meninges was observed. In the stereotactic injection model, the tumour proliferation at the injection site and the infiltration into the brain parenchyma were observed. The pia-glial membrane serves as a scaffold when neoplastic cells spread to the perivascular space forming angiocentric pattern. The pia-glial membrane is found between the brain parenchyma and blood vessels. Blood vessels penetrate the brain through tunnels known as perivascular spaces that are covered by pia mater. Three different methods which we prepared reflect three different pathological processes. Our findings suggest that the pia mater is a critical factor in brain metastasis.

The brain is frequently affected by the spread of lung cancer, and haematogenous metastasis is a common route to brain metastasis. We therefore developed an isogenic brain metastasis model of lung cancer to use the Lewis lung carcinoma cell line and analysed dynamics of neoplastic cells after extravasation. Histological analysis revealed two characteristic patterns: metastatic foci exhibiting an angiocentric pattern were designated 'perivascular proliferations'; neoplastic cells infiltrating the brain parenchyma were designated 'invasive proliferations'. Electron microscopic observation of perivascular proliferations showed that neoplastic cells were confined to the perivascular space. In invasive proliferations, however, fragments of collagen fibre were observed in the gaps between neoplastic cells, indicating that the neoplastic cells had disintegrated the pia-glial membrane. We analysed the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 by using both immunohistochemical analysis and real-time polymerase chain reaction analysis. MMP-2 expression was significantly higher in invasive proliferations. MMP-9 expression was significantly higher in day 7, but there was no significant difference in day 11. The pia-glial membrane and perivascular space are the barriers that neoplastic cells must overcome to infiltrate the brain. In conclusion, our findings suggest that brain metastasis requires two distinct processes.

Differential expression of the desired gene product in the target tissue is central to the concept of gene therapy. One approach is to use a tissue-specific promoter to drive therapeutic genes. To investigate the feasibility of tissue-specific gene therapy for bladder cancer using the mouse uroplakin II (UPII) promoter and its transcriptional control, the efficacy of this promoter as well as fragments in regulating gene expression were qualitatively and quantitatively analyzed in bladder and non-bladder tissue cell lines using DNA transfection. Our results demonstrate that the mouse UPII promoter actively drives gene expression in BIU-87, a bladder cancer cell line. Little promoter activity was detected in the non-bladder tissue cell lines. Furthermore, deleting the 5' end 1.5 kb of the UPII promoter by PCR, the activity was significantly decreased but was bladder-specific. However, deleting the 3' end 143-bp of the UPII promoter, the activity was hardly detected in any tissue cell lines. The activity of the 3' end 143-bp of the UPII promoter was detected in both bladder cancer and stomach cancer cell lines. These data demonstrate that the mouse UPII promoter has a high activity in human bladder cells and a low basal activity in human non-bladder cells. This suggests that targeting the gene expression of the mouse UPII promoter could be used to treat human bladder cancer. The enhancer was contained in the region of the 1.5 kb of the 5' end of the mouse UPII promoter. The core promoter was located in the region of the 143 bp of the 3' end.

This paper describes the production of divalent K88, K99 antigens by high cell density fermentation and gene overexpression. The cell density reached above 40 at A600nm and the antigens were at 2(12) level. The thousands dosage of the vaccine can be made by using 10 I broth of the fermentation. The stability of the plasmid showed that about 30 percent of the bacteria lost its plasmid after 20 h fermentation. It was found that the antigens were overexpressed and located in both the pili of E. coli and in the medium in equal quantities. It means that the expression and regulation of the genes of K88, K99 may be different from the wild type of enterotoxingenic E. coli. A large number of the vaccinated pregnant sow showed that the piglets were effectively protected from the infection of enterotoxingenic E. coli. The results indicated that the large quantities requirement of the vaccine could be provided by using a small fermenter. This vaccine consists of two forms of the antigen K88, K99 which, when present in the pili as well as the medium, is more favorable to stimulate the production of antibody in the colostrum of pregnant sow.

Oxidative stress in malaria infected human erythrocytes is augmented and the anti-oxidant system is attenuated as compared with normal RBC's. Exacerbation of intra-erythrocytic oxidative stress might provide a means to kill the parasites. Sodium artesunate (SA), an effective Chinese anti-malaria drug, markedly increased the levels of active oxygen species and production of malonyldialdehyde in normal red blood cells and, to a greater extent, in malaria infected red blood cells. SA caused a remarkable decrease of unsaturated fatty acids content in normal red blood cell membrane. These suggest that the anti-oxidative system in red blood cells infected with malaria is jeopardized. Certain active oxygen species generated and accumulated in such red blood cells might in turn kill the parasites. SA augmented intracellular O2-. and H2O2 production, and this may partly account for its antimalaria action.