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Background Extracellular vesicles (EVs) and their mimics from mesenchymal stem cells (MSCs) are promising drug carriers to improve cancer treatment, but their application is hindered by donor variations and expansion limitations of conventional tissue-derived MSCs. To circumvent these issues, we made EV-mimicking nanovesicles from standardized MSCs derived from human induced pluripotent stem cells (iPSCs) with a theoretically limitless expandability, and examined the targeting capacity of these nanovesicles to prostate cancer. Methods Nanovesicles are made from intact iPSC-MSCs through serial extrusion. The selective uptake of fluorescently labeled nanovesicles by prostate cancer cells vs. non-tumor cells was examined with flow cytometry. For in vivo tracing, nanovesicles were labeled with fluorescent dye DiR or renilla luciferase. In mice carrying subcutaneous or bone metastatic PC3 prostate cancer, the biodistribution of systemically infused nanovesicles was examined with in vivo and ex vivo imaging of DiR and luminescent signals. A chemotherapeutic drug, docetaxel, was loaded into nanovesicles during extrusion. The cytotoxicities of nanovesicle-encapsulated docetaxel on docetaxel-sensitive and -resistant prostate cancer cells and non-tumor cells were examined in comparison with free docetaxel. Therapeutic effects of nanovesicle-encapsulated docetaxel were examined in mice carrying subcutaneous or bone metastatic prostate cancer by monitoring tumor growth in comparison with free docetaxel. Results iPSC-MSC nanovesicles are more selectively taken up by prostate cancer cells vs. non-tumor cells in vitro compared with EVs, membrane-only EV-mimetic nanoghosts and liposomes, which is not affected by storage for up to 6 weeks. In mouse models of subcutaneous and bone metastatic PC3 prostate cancer, systemically infused nanovesicles accumulate in tumor regions with significantly higher selectivity than liposomes. The loading of docetaxel into nanovesicles was efficient and did not affect the selective uptake of nanovesicles by prostate cancer cells. The cytotoxicities of nanovesicle-encapsulated docetaxel are significantly stronger on docetaxel-resistant prostate cancer cells and weaker on non-tumor cells than free docetaxel. In mouse models of subcutaneous and bone metastatic prostate cancer, nanovesicle-encapsulated docetaxel significantly decreased the tumor growth and toxicity to white blood cells compared with free docetaxel. Conclusions Our data indicate that EV-mimicking iPSC-MSC nanovesicles are promising to improve the treatment of metastatic prostate cancer.

Aberrant activation of Notch signaling plays an oncogenic role in cancer development. Jagged1 (JAG1) is an important Notch ligand that triggers Notch signaling through cell-cell interactions. JAG1 overexpression has been reported in many different types of cancer and correlates with a poor clinical prognosis. JAG1/Notch signaling controls oncogenic processes in different cell types and cellular contexts. Furthermore, JAG1/Notch signaling cascades activate a number of oncogenic factors that regulate cellular functions such as proliferation, metastasis, drug-resistance, and angiogenesis. To suppress the severe toxicity of pan-Notch inhibitors, JAG1 is attracting increasing attention as a source of therapeutic targets for cancers. In this review, the oncogenic role of JAG1/Notch signaling in cancer is discussed, as well as implications of strategies to inhibit JAG1/Notch signaling activity.

Urinary brain-derived neurotrophic factor (BDNF), an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia (BPH). We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms (LUTS) in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score (IPSS) was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity (DO) in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine (Cr) levels. Seventy-six BPH patients were divided into moderate LUTS group (n=51, 7IPSS≤20) and severe LUTS group (n=25, IPSS20) according to the IPSS. Of the 76 BPH patients, DO was present in 34 (44.7%) according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS (8.29±3.635, P0.0001) and severe LUTS (11.8±6.44, P0.0001) than normal controls (1.71±0.555). Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS (11.8±6.44 vs. 8.29±3.635, P=0.000). The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker for the diagnosis of DO in BPH patients.

Background: Q fever endocarditis, a chronic illness caused by Coxiella burnetii, can be fatal if misdiagnosed or left untreated. Despite a relatively high positive rate of Q fever serology in healthy individuals in the mainland of China, very few cases of Q fever endocarditis have been reported. This study summarized cases of Q fever endocarditis among blood culture negative endocarditis (BCNE) patients and discussed factors attributing to the low diagnostic rate. Methods: We identified confirmed cases of Q fever endocarditis among 637 consecutive patients with infective endocarditis (IE) in the Peking Union Medical College Hospital between 2006 and 2016. The clinical findings for each confirmed case were recorded. BCNE patients were also examined and each BCNE patient’s Q fever risk factors were identified. The risk factors and presence of Q fever serologic testing between BCNE patients suspected and unsuspected of Q fever were compared using the Chi-squared or Chi-squared with Yates’ correction for continuity. Results: Among the IE patients examined, there were 147 BCNE patients, of whom only 11 patients (7.5%) were suspected of Q fever and undergone serological testing for C. burnetii. Six out of 11 suspected cases were diagnosed as Q fever endocarditis. For the remaining 136 BCNE patients, none of them was suspected of Q fever nor underwent relevant testing. Risk factors for Q fever endocarditis were comparable between suspected and unsuspected patients, with the most common risk factors being valvulopathy in both groups. However, significantly more patients had consulted the Infectious Diseases Division and undergone comprehensive diagnostic tests in the suspected group than the unsuspected group (100% vs. 63%, P = 0.03). Conclusions: Q fever endocarditis is a serious yet treatable condition. Lacking awareness of the disease may prevent BCNE patients from being identified, despite having Q fever risk factors. Increasing awareness and guideline adherence are crucial in avoiding misdiagnosing and missed diagnosing of the disease. Key words: Blood Culture; Endocarditis; Q Fever

Irreversible hypofunction of salivary glands is common in head and neck cancer survivors treated with radiotherapy and can only be temporarily relieved with current treatments. We found in an inducible sonic hedgehog (Shh) transgenic mouse model that transient activation of the Hedgehog pathway after irradiation rescued salivary gland function in males by preserving salivary stem/progenitor cells and parasympathetic innervation. To translate these findings into feasible clinical application, we evaluated the effects of Shh gene transfer to salivary glands of wild-type mice on irradiation-induced hyposalivation. Shh or control GFP gene was delivered by noninvasive retrograde ductal instillation of corresponding adenoviral vectors. In both male and female mice, Shh gene delivery efficiently activated Hedgehog/Gli signaling, and significantly improved stimulated saliva secretion and preserved saliva-producing acinar cells after irradiation. In addition to preserving parasympathetic innervation through induction of neurotrophic factors, Shh gene delivery also alleviated the irradiation damage of the microvasculature, likely via inducing angiogenic factors, but did not expand the progeny of cells responsive to Hedgehog/Gli signaling. These data indicate that transient activation of the Hedgehog pathway by gene delivery is promising to rescue salivary function after irradiation in both sexes, and the Hedgehog/Gli pathway may function mainly in cell nonautonomous manners to achieve the rescue effect.

The aim of study was to evaluate the association between serum DHEAS levels and depression with a case-control study together with a meta-analysis. Radioimmunoassay (RIA) was performed to measure the serum DHEAS levels of all participants before and after treatment. Depression Patients were divided into mild depression and severe depression based on Hamilton depression scale (HAMD24) and received 5-hydroxytryptamine (5-HT) and citalopram (20mg/d) for 8 weeks. Case-control studies related to our study theme were enrolled for meta-analysis and Comprehensive Meta-analysis 2.0 (CMA 2.0) was used for statistical analysis. After treatment, DHEAS levels in depression patients were significantly increased, while before and after treatment, DHEAS levels were all lower in depression patients than in controls (all P0.001); further analysis on age revealed that DHEAS levels were decreased with the rising of age. Meta-analysis results suggested that serum DHEAS levels (ng/mL) were significantly higher in healthy controls compared to depression patients (SMD=0.777, 95%CI=0.156-1.399, P=0.014). In conclusion, our study suggests that serum DHEAS levels are associated with the development of depression and it decreased with the rising of age.

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, is recognized as an independent risk factor for atherosclerosis, cardiovascular diseases, and diabetic vascular diseases. Our recent studies revealed that the single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors (PPARα/δ/γ) gene are involved in the regulation of lipid storage and metabolism. In order to investigate the relationships between the SNPs of PPARα/γ gene and plasma levels of Lp(a), 644 participants were randomly selected from Chinese Han population in the present study. As the results shown, Lp(a) was significantly associated with L162V (rs1800206) in PPARα. Compared with those subjects with widetype (LL), significantly higher Lp(a) concentration was determined in the individuals with mutant (LV + VV) (mean difference: 49.07 mg/l, 95% CI 23.32-74.82 mg/l, p = 0.0002). Moreover, with generalized multifactor dimensionality reduction analysis, our present results indicated that there was a significant association between plasma Lp(a) level and gene-gene interaction among the polymorphisms rs1800206, rs135539 in PPARα and rs10865710, rs1805192, and rs4684847 in PPARγ. Therefore, our presented study indicated that PPARα/γ polymorphisms should be involved in the regulation of plasma Lp(a) in independently and/or in an interactive manner, suggesting that PPARα/γ gene may influence the risk of hypertension, cardiovascular diseases, and dyslipidemia by regulating Lp(a) level.

The safety and effectiveness of a novel Chinese one-shot dilation technique based on stimulated diuresis for percutaneous nephrolithotomy (PCNL) were investigated. After the feasibility of the Chinese one-shot dilation based on stimulated diuresis was verified by an animal study, this technique was applied in the clinical practice. A total of 67 patients in our department underwent the modified PCNL from July 2014 to June 2015. After the renal infundibulum was distended by stimulated diuresis, the kidney was punctured under the ultrasonographic guidance via the fornix of the target calyx. The working channel was dilated using a special designed pencil-shaped fascial dilator. The successful access rate, nephrostomy tract creation time, pre- and postoperative hemoglobin values and serum creatinine concentrations, stone-free rate and complications were recorded and analyzed. The renal infundibulum was successfully distended in all of the patients by the diuresis treatment. Under the ultrasonographic guidance, the successful access rate was 100% and the mean tract creation time was 2.0 min (range: 1.5-5.0 min). The stone-free rate right after surgery was 91.0%. Although the postoperative hemoglobin was significantly reduced (P0.01), transfusion was not clinically necessary. There was no significant difference in serum creatinine concentrations before and after operation (P0.05). No severe complication occurred during or after the PCNL. It was suggested that this Chinese one-shot dilation technique based on stimulated diuresis is an efficient and safe innovation for PCNL, and is even helpful for those patients with non-dilated pelvicaliceal systems.

We present our initial experience and 9-month outcomes of the novel technique of laparoscopic onlay lingual mucosal graft ureteroplasty for proximal ureteral stricture. In June 2015, transperitoneal laparoscopic onlay lingual mucosal graft ureteroplasty was performed on a male patient with proximal stricture of the left ureter. The patient complained with left frank pain. Severe hydronephrosis and proximal ureteral dilatation were noted through ultrasonography and CT scan. The length of upper ureteral stricture was 30 mm including 10-mm occlusion. A 46 mm in length and 15 mm in width lingual mucosa graft was harvested from the ventral of the tongue and placed in the strictured ureter as a ventral onlay for laparoscopic ureteroplasty. Operative time, intraoperative, and postoperative complications were well recorded. Follow-up was performed with renal ultrasound, CT scan, and nuclear scan renography as well as clinical assessment of symptoms. The new technique was performed successful without intraoperative and postoperative complications. Neither hydronephrosis nor proximal ureteral dilatation in the left side was found through ultrasonography 3, 6, 9 months and CT scan 6 month postoperatively. The left renal function, glomerular filtration rate, had a recovery from 9.6 ml/min preoperatively to 14.0 ml/min at 6-month follow-up, and the patient has no complaints about the donor site and flank pain. To our knowledge, we present the initial experience with laparoscopic onlay lingual mucosal graft ureteroplasty for proximal ureteral stricture. With 9-month outcomes, the new technique appears to be an excellent option for proximal ureteral stricture.

Background Gene transfer to salivary glands for use in treating both systemic and upper gastrointestinal tract diseases shows considerable potential. Numerous studies in rodents demonstrate that salivary glands can secrete transgenic secretory proteins either into saliva, primarily via the regulated secretory pathway (RSP), or into the bloodstream, primarily by the constitutive secretory pathway (CSP). The purpose of the present study was to assess the sorting characteristics of human growth hormone (hGH), a RSP protein, and human erythropoietin (hEpo), a CSP protein, in a large animal model of salivary gland gene transfer, the miniature pig. Methods Recombinant serotype 5 adenoviral (Ad5; 1011 particles/gland) vectors encoding either hGH (AdCMVhGH) or hEpo (AdCMVhEpo) were administered to both parotid glands of male miniature pigs by intraductal cannulation. The secretion of hGH or hEpo was measured in both saliva and serum on days 3, 7 and 14 following administration. Detailed serum chemistry and hematological analyses were performed, and the presence of serum antibodies to hGH and hEpo was measured. For AdCMVhEpo-treated minipigs vector distribution in multiple tissues was determined by quantitative polymerase chain reaction (QPCR). Results The RSP protein hGH was secreted entirely into saliva, while the CSP protein hEpo was secreted into both saliva and serum. Most hEpo was found in saliva, but serum hEpo levels were sufficient to significantly increase hematocrit levels in treated animals by ∼10%. Expression of both transgenes was maximal on day 3 and declined to near background by day 14. The amount of vector found in the targeted glands was 100× more than in other tissues. Conclusions Secretion of transgenic hGH from minipig parotid glands occurred principally into saliva via the RSP, as seen in rodents, while hEpo was secreted into both saliva and serum, the latter presumably via the CSP. Even though hEpo secretion into the bloodstream was not to the extent previously observed in rodents, serum hEpo levels were considerable and the hEpo was biologically active. Ad5 vector distribution was highly restricted to the parotid glands with little vector detected elsewhere. While the results in this large animal model support the established notion that salivary gland gene transfer can be used for treating systemic single protein deficiency disorders, they also highlight differences in transgenic CSP protein sorting between rodents and miniature pigs. Copyright © 2007 John Wiley & Sons, Ltd.

A total of 1,345 Ixodes persulcatus ticks collected from northeastern China were investigated for the presence of Anaplasma phagocytophila and Borrelia burgdorferi by a nested polymerase chain reaction (PCR). Sixty-two (4.6%) ticks were positive for A. phagocytophila and 454 (33.8%) were positive for B. burgdorferi. Seven (0.5%) were coinfected with both agents. Sequence analysis of 919-basepair PCR amplicons revealed three types of A. phagocytophila. Type 1 was identical to the published sequences of A. phagocytophilas responsible for human granulocytic ehrlichiosis (HGE). The other two variants differed from the HGE agent sequence at one and four positions, respectively. These findings imply that infection with A. phagocytophila poses a potential health threat to both humans and animals in northeastern China, and that ehrlichiosis should be considered in the differential diagnosis of febrile patients with a history of tick bite, particularly when clinical manifestations are atypical for Lyme disease.

Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling with the direction of stretch force. Inclined force led to inclined finger-like bones formation and deflection of bilateral maxillae. Additionally, heavily compressive force caused fracture of finger-like bones in the sutures. These data together proposed the special finger-like pattern of bone formation in sutures guided by stretch force, providing important implications for maxillary expansion.

The aim of this study was to investigate the association between three single-nucleotide polymorphisms (SNP) of in the peroxisome proliferator-activated receptor (PPAR) α gene and the level of lipoprotein (a) [Lp(a)].Participants were recruited under the framework of a cohort populations survey from the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) which was conducted in the urban community of Jiangsu province from 1999 to 2007. 644 subjects (234 males, 410 females) were randomly selected and genotyped for three polymorphisms which were used as genetic marker for PPARα gene (rs1800206, rs4253778 and rs135539). Data related to individual polymorphism and haplotype were available for analysis. χ² test was used to determine if the whole population was in Hardy-Weinberg genetic equilibrium. Linear regression models were used to analyze the association between SNPs in PPARα gene and the level of Lp(a). Associations between PPARα haplotypes and serum Lp(a) levels were analyzed by the SNPstats software.In the dominant model, after factors as sex, age, smoking, alcohol and BMI were adjusted, the presence of the V162 allele of L162V appeared associated with a high level of Lp(a) (mean difference was 57.70 mg/L (95% CI: 32.03-83.37 mg/L), P0.001. Data from the haplotype analysis revealed that A-G-V and C-G-V haplotype (established by 1AC, 7GC L162V) were significantly associated with a higher level of Lp(a) (P = 0.012 0 and 0.009 7).Results from our study might help to clarify the role of PPARα gene in regulation of Lp(a) and the evaluation of its polymorphisms and haplotypes which were characterized as genetic factors for Lp(a).

To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARα, δ, γ) with lipid accumulation product (LAP) and the additional role of a gene-gene interactions among the 10 SNPs.Participants were recruited under the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu province) cohort populations survey in the urban community of Jiangsu province of China. A total of 820 subjects were randomly selected and no individual was related. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806 and rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. A linear regression model was used to analyze the relations between ten SNPs in the PPARs and LAP. Mean difference (Difference) and 95% confident interval (95%CI)were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction (GMDR).After adjusting the factors as age, gender, smoking status, occupational physical activity, educational level, high-fat diet as well as low-fiber diet, both rs1800206, s1805192 and rs3856806 were significantly associated with the increased level of LAP. Difference (95% CI) values were 32.47 (22.62-42.31), 12.97 (4.61-21.33) and 12.49 (4.24-20.75). Whereas rs2016520 was significantly associated with the decreased level of LAP. Difference (95%CI) values was -14.67 ( -22.97--6.55). GMDR analysis showed a significant gene-gene interaction among rs135539, rs1800206 of PPARα, rs2016520 of PPARδ and rs10865710, rs3856806, rs709158, rs1805192, rs4684847 of PPARγ for eight-dimension models (P0.05), in which prediction accuracy was 0.5902 and cross-validation consistency was 10/10.The rs1800206 of PPARα and rs1805192, rs3856806 of PPARγ were significantly associated with the increased level of LAP; rs2016520 of PPARδ was associated with the decreased level of LAP. There was a gene-gene interaction between multiple SNPs.

Purpose: To examine the effects and mechanisms of transient activation of the Hedgehog pathway on rescuing radiotherapy-induced hyposalivation in survivors of head and neck cancer. Experimental Design: Mouse salivary glands and cultured human salivary epithelial cells were irradiated by a single 15-Gy dose. The Hedgehog pathway was transiently activated in mouse salivary glands, by briefly overexpressing the Sonic hedgehog (Shh) transgene or administrating smoothened agonist, and in human salivary epithelial cells, by infecting with adenovirus encoding Gli1. The activity of Hedgehog signaling was examined by the expression of the Ptch1-lacZ reporter and endogenous Hedgehog target genes. The salivary flow rate was measured following pilocarpine stimulation. Salivary stem/progenitor cells (SSPC), parasympathetic innervation, and expression of related genes were examined by flow cytometry, salisphere assay, immunohistochemistry, quantitative reverse transcription PCR, Western blotting, and ELISA. Results: Irradiation does not activate Hedgehog signaling in mouse salivary glands. Transient Shh overexpression activated the Hedgehog pathway in ductal epithelia and, after irradiation, rescued salivary function in male mice, which is related with preservation of functional SSPCs and parasympathetic innervation. The preservation of SSPCs was likely mediated by the rescue of signaling activities of the Bmi1 and Chrm1–HB-EGF pathways. The preservation of parasympathetic innervation was associated with the rescue of the expression of neurotrophic factors such as Bdnf and Nrtn. The expression of genes related with maintenance of SSPCs and parasympathetic innervation in female salivary glands and cultured human salivary epithelial cells was similarly affected by irradiation and transient Hedgehog activation. Conclusions: These findings suggest that transient activation of the Hedgehog pathway has the potential to restore salivary gland function after irradiation-induced dysfunction. Clin Cancer Res; 20(1); 140–50. ©2013 AACR.

Purpose Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/β-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after, or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results Radiation damage did not significantly affect activity of Wnt/β-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/β-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion These results suggest that concurrent transient activation of the Wnt/β-catenin pathway could prevent radiation-induced salivary gland dysfunction.

To study protective effect and pathogenesis of complex salvia miltiorrhiza (DanShen) on acute mercury poisoning in rabbits.Models of acute mercury poisoning was made in rabbits. The effect of complex salvia miltiorrhiza on blood urea nitrogen (BUN), copper-protein (CP), lactate dehydrogenase (LDH), acid phosphatase (ACP) and the malondialdehyde (MDA) in plasma, superoxide dismutase (SOD) in erythrocyte and MDA, SOD in tissues homogenate were observed.The administration of complex salvia miltiorrhiza after mercury injection 0.5 h and 9.5 h, decreased BUN, CP, MDA, LDH and ACP, and prevented the reduction of SOD. Compared with mercury poisoning group, the difference was statistical significant (P0.05, P0.01).It is suggested that acute mercury poisoning may result in renal damage but also multiple organ tissues, and complex salvia miltiorrhiza possesses protective effect, through stabilized membranes.

Aim To evaluate the effect of single or dual field irradiation (IR) with the same dose on damage to miniature pig parotid glands. Methodology Sixteen miniature pigs were divided into two IR groups (n=6) and a control group (n=4). The irradiation groups were subjected to 20 Gy X-radiation to one parotid gland using single-field or dual-field modality by linear accelerator. The dose-volume distributions between two IR groups were compared. Saliva from parotid glands and blood were collected at 0, 4, 8 and 16 weeks after irradiation. Parotid glands were removed at 16 weeks to evaluate tissue morphology. Results The irradiation dose volume distributions were significantly different between single and dual field irradiation groups (t=4.177, P=0.002), although dose volume histogramin (DVH) indicated the equal maximal dose in parotid glands. Saliva flow rates from IR side decreased dramatically at all time points in IR groups, especially in dual field irradiation group. The radiation caused changes of white blood cell count in blood, lactate dehydrogenase and amylase in serum, calcium, potassium and amylase in saliva. Morphologically, more severe radiation damage was found in irradiated parotid glands from dual field irradiation group than that from single field irradiation group. Conclusion Data from this large animal model demonstrated that the radiation damage from the dual field irradiation was more severe than that of the single field irradiation at the same dose, suggesting that dose-volume distribution is an important factor in evaluation of the radiobiology of parotid glands.

To study the ultrastructure of parotid glands, lacrimal glands and pituitary glands between miniature pig and mouse.Five adult miniature pigs and 5 mice were studied. Ultrastructure of their parotid glands, lacrimal glands, and pituitary glands was observed.The secretary granules in acinar cell of miniature pig parotid glands showed higher density and more aequalis than those of mice. The cell apparatus in acinar cell of mouse parotid glands were more plentiful than those of miniature pigs. The secretary granules on blood vessel wall were richer in parotid gland of miniature pigs compared with mouse parotid gland. Lacrimal gland had the similar ultrastructure to parotid gland in these two animals. Many blood vessel antrum were found in pituitary glands of these two animals.Compared with mouse parotid glands, there are more secretary granules in acinar cells and vascular endothelial cells in miniature pig parotid glands, which might enter blood stream and have function of endocrine secretion.

Background Previously, using an adenoviral vector, we showed that miniature pigs could provide a valuable and affordable large animal model for pre-clinical gene therapy studies to correct parotid gland radiation damage. However, adenoviral vectors lead to short-term transgene expression and, ideally, a more stable correction is required. In the present study, we examined the suitability of using a serotype 2 adeno-associated viral (AAV2) vector to mediate more stable gene transfer in the parotid glands of these animals. Methods Heparan sulfate proteoglycan was detected by immunohistochemistry. β-galactosidase expression was determined histochemically. An AAV2 vector encoding human erythropoietin (hEpo) was administered via Stensen's duct. Salivary and serum hEpo levels were measured using an enzyme-linked immunosorbent assay. Serum chemistry and hematological analyses were performed and serum antibodies to hEpo were measured throughout the study. Vector distribution was determined by a quantitative polymerase chain reaction. Results Transgene expression was vector dose-dependent, with high levels of hEpo being detected for up to 32 weeks (i.e. the longest time studied). hEpo reached maximal levels during weeks 4–8, but declined to approximately 25% of these values by week 32. Haematocrits were elevated from week 2. Transduced animals exhibited low serum anti-hEpo antibodies (1 : 8–1 : 16). Vector biodistribution at animal sacrifice revealed that most copies were in the targeted parotid gland, with few being detected elsewhere. No consistent adverse changes in serum chemistry or hematology parameters were seen. Conclusions AAV2 vectors mediate extended gene transfer to miniature pig parotid glands and should be useful for testing pre-clinical gene therapy strategies aiming to correct salivary gland radiation damage. Copyright © 2009 John Wiley & Sons, Ltd.