Association of disease condition with changes in intestinal flora, and plasma endotoxin and vascular endothelial growth factor levels in patients with liver cancer.

OBJECTIVE: Currently, the therapeutic effect on patients with liver cancer is associated with disease development. Meanwhile, the efficacy in patients with advanced liver cancer is far from satisfactory. Therefore, the aim of this study was to explore the association of disease condition with changes in liver function indexes, intestinal flora, and plasma endotoxin (ET) and vascular endothelial growth factor (VEGF) levels in patients with liver cancer. PATIENTS AND METHODS: A total of 300 patients with primary liver cancer in our hospital were enrolled in this study. All patients were divided into three groups, including early liver cancer group, middle liver cancer group, and advanced liver cancer group. Peripheral blood was collected from each subject to detect liver function indexes, procalcitonin (PCT), plasma ET, and VEGF levels. Furthermore, mid-posterior-segment stools were collected from 15 cases in each group, and sent to the company for detection of intestinal flora. RESULTS: Liver function indexes in peripheral blood of patients with liver cancer changed with the changes in disease condition. With the progression of liver cancer, the level of aspartate aminotransferase (AST) increased significantly, and the highest was observed in advanced liver cancer patients [(91.18±10.34) U/L] (p=0.046). However, the level of plasma total protein declined significantly, which was (24.83±1.75) g/L in advanced liver cancer patients (p=0.035). The changes in total bilirubin were significantly associated with the progression of liver cancer (p=0.003). The abundance of Clostridiales, Firmicutes, and Streptococcus in the intestinal tract was high in early liver cancer group. The abundance of Ruminococcaceae, Pasteurellaceae, Tanticharoenia, and Vagococcus in the intestinal tract was high in middle liver cancer group. Meanwhile, the abundance of Bifidobacteriales, Actinobacteria, Barnesiella, Porphyromonadaceae, and Pseudomonadales in the intestinal tract was high in advanced liver cancer group. In patients with liver cancer, the level of Enterobacteriaceae was positively correlated with that of Firmicutes (r=0.36, p=0.003), whereas it was negatively correlated with Lactobacillus (r=-0.72, p=0.021). The level of Lactobacillus was positively correlated with that of Ruminococcaceae (r=0.39, p=0.043), whereas it was negatively correlated with that of Firmicutes (r=-0.27, p=0.019). In addition, the level of PCT markedly rose in advanced liver cancer group [(6.89±0.35) ng/mL] (p=0.021). The level of ET increased significantly with the development of liver cancer, with the highest level observed in advanced liver cancer group [(0.71±0.09) EU/mL] (p=0.004). The level of VEGF also increased remarkably with the aggravation of liver cancer, and the highest was found in advanced liver cancer group [(112.33±2.11) µmol/L], showing differences among groups (p<0.05). CONCLUSIONS: With the progression of liver cancer, the abundance of Barnesiella, etc., rose and that of Ruminococcaceae, etc., declined in the intestinal tract. Meanwhile, the composition of intestinal flora was changed, and the levels of plasma ET and VEGF increased.

The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis.

BACKGROUND: Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. RESULTS: A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61-0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59-0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57-1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. CONCLUSION: Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.

[Effects of infant feeding practice on eczema during early childhood in Shanghai, Hohhot, and Fuzhou].

Objective: To estimate the prevalence of eczema in early childhood and effect of infant feeding practice on eczema by different regions of China with diverse climate and dietary patterns. Method: A questionnaire survey was conducted from June 2012 to October 2012 in Shanghai, Hohhot, and Fuzhou. The parent or guardian of the children aged between 2.5 to 3.5 years attending routine health visit in the chosen communities were invited to complete a modified questionnaire of the International Study of Asthma and Allergy in Childhood (ISAAC). Logistic regression model was used to analyze of the family history of allergy, duration of breastfeeding, timing of introduction of complementary foods and other potential confounders. Result: A total of 2 242 children were interviewed, 750 from Shanghai, 716 from Hohhot, and 776 from Fuzhou. The prevalence of eczema in early childhood was significantly different among Shanghai (16.9%, 95%CI 16.87-16.93), Hohhot (34.5%, 95%CI 34.46-34.54)and Fuzhou (44.3%, 95%CI 44.26-44.34). The difference was statistically significant between 3 groups (χ2=72.05, P<0.05). Introducing complementary food after the age of 6 months was associated with a decreased risk for eczema when compared to introduction between 4 to 6 months(odds ratio (OR) 0.58, 95%CI 0.41-0.81) in Fuzhou, while there was no significant association between timing of introduction of complementary foods and eczema in Shanghai and Hohhot. Conclusion: The prevalence of eczema during early childhood is various among three cities. The relationship between timing of introduction of complementary foods and eczema in Fuzhou is different from that in Shanghai and Hohhot. The role of climate and dietary patterns on prevalence of eczema needs further studies.

Vascular endothelial growth factor increases GEnC permeability by affecting the distributions of occludin, ZO-1 and tight juction assembly.

OBJECTIVE: To explore the molecular mechanism of the increased permeability of glomerular endothelial cells (GEnC) stimulated by vascular endothelial growth factor (VEGF). METHODS: We investigated the permeability-increasing effect and tight junction formation of VEGF by measuring FITC labeled BSA across GEnC monolayer. Then, immunofluorescence and western blot were employed to detect the distributions of occludin and ZO-1. RESULTS: We found that VEGF increased FITC-BSA permeability. VEGF also caused a loss of occludin and ZO-1 from the endothelial cell junctions, and changed the staining pattern of the cell boundary. Western blot analysis of GEnC lysates revealed that occludin and ZO-1 were redistributed under VEGF treatment. CONCLUSIONS: These results suggested that VEGF could increase GEnC monolayer permeability by changing distributions and organizations of occludin and ZO-1, which lead to tight junction disassembly. Occludin and ZO-1 appeared to be downstream effectors of the VEGF signaling pathway.

Effect of TIMP1 transfection on PTEN expression in human kidney proximal tubular cells.

To explore the role of metalloproteinase-1 (TIMP-1) tissue inhibitor in the mechanisms of kidney aging, we observed the effects of sense and antisense transfection of TIMP-1 and of metalloproteinase (MMP) inhibitors on phosphatase and tensin homolog (PTEN), vascular endothelial growth factor (VEGF), and Flk-1 expression in TIMP-1 transgenic human proximal tubular epithelial cells (HKCs). Transfected HKCs were co-incubated with 100 µM MMP-2 and MMP-9 inhibitor III for 24 h to affect enzyme inhibition. TIMP-1, MMP-2, MMP-9, PTEN, VEGF, and Flk-1 mRNA expression was detected by reverse transcription-polymerase chain reaction. PTEN, VEGF, and Flk-1 protein expression in cells of each experimental group was measured by indirect immunofluorescence. We found that PTEN expression was up-regulated (P < 0.05) in the sense TIMP-1-transfected group (P < 0.05) compared with the non-transfected and empty vector groups, and that expression of VEGF and Flk-1 was down-regulated (P < 0.05). In contrast, the antisense TIMP-1 transgenic group showed the opposite results (P < 0.05). No significant differences in expression of PTEN, VEGF, or Flk-1 were observed among the MMP- 2/MMP-9 inhibitor III, non-transfected, and empty vector groups (P > 0.05). These results suggest that in the progression of renal aging, high expression of TIMP-1 up-regulates PTEN expression through an MMP-independent pathway, and subsequently down-regulates the expression of VEGF and Flk-1, indicating that PTEN and TIMP-1 are involved in the aging-associated impairment of renal angiogenesis. Our study provides a theoretical basis for further exploration of the mechanism underlying TIMP- 1 participation in renal aging progression.

Gpnmb/osteoactivin, an attractive target in cancer immunotherapy.

Cancer is a complex disease with interactions between normal and neoplastic cells. Since current therapies for cancer largely rely on drugs or radiation that kill dividing cells or block cell division, these treatments may have severe side effects on normal proliferating cells in patients with cancer. Recently, immunotherapeutic approaches for cancer therapy, by which monoclonal antibodies (Mabs) target tumor specific antigens, have shown great potential. Glycoprotein non-metastatic melanoma protein B(Gpnmb)/Osteoactivin (OA) is a transmembrane glycoprotein highly expressed in various types of cancer. Gpnmb/OA promotes the migration, invasion and metastasis of tumor cells. CR 011-vcMMAE is a Mab-drug conjugate being developed for the treatment of Gpnmb/OA-expressing cancers. Gpnmb/OA represents an attractive target in cancer immunotherapy and CR011-vcMMAE holds promise as a reagent in targeted therapy for Gpnmb/OA-expressing malignancies.

A new non-uremic rat model of long-term peritoneal dialysis.

Together with the development of peritoneal dialysis (PD), appropriate animal models play an important role in the investigation of physiological, pathophysiological and clinical aspects of PD. However, there is still not an ideal experimental PD animal model. In this study, 45 Sprague-Dawley rats were divided into three groups. Group 1 (n=15) was receiving daily peritoneal injection through the catheter connected to the abdominal cavity, using PD solution containing 3.86 % D-glucose. Group 2 (n=15) was receiving daily peritoneal injection of 0.9 % physiological saline through a catheter. Group 3 (n=15), which was subjected to sham operation, served as controls. Our results showed that WBC counts in peritoneal effluent of Group 1 were slightly higher than those of Group 2 and control group, respectively (p<0.05). However, there was no episode of infection in any group. In addition, there was no significant difference in neutrophils fractions among these three groups. Hematoxylin-eosin and Masson's trichrome staining demonstrated a dramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum exposed to high glucose (Group 1) compared to Group 2 and controls (p<0.01). These data indicated that we established a novel rat model of PD with a modified catheter insertion method. This model is more practical, easy to operate, not too expensive and it will facilitate the investigate of long-term effects of PD.

The relationship between the TGF-beta1 gene -509C/T polymorphism and tubulointerstitial damage resulting from primary nephrotic syndrome.

BACKGROUND: The aim of this study was to investigate the correlation between the transforming growth factor (TGF)-beta1 gene -509C/T polymorphism and the susceptibility to primary nephrotic syndrome (PNS), and in particular to the severe degree of tubulointerstitial damage (TID) seen in Chinese. METHODS: Ninety-eight PNS patients and 128 normal controls were studied. The extent of tubulointerstitial changes was evaluated and patients were divided into two groups according to the severe or mild degree of TID. The TGF-beta1gene -509C/T polymorphism was detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and the serum level of TGF-beta1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: No statistical differences in genotype or allele frequency of the TGF-beta1 gene -509C/T were found between PNS and normal subjects. However, T allele and CT + T T genotype frequency were higher in the PNS with severe TID than the mild TID and controls. Additionally, the serum concentration of TGF-beta1 was significantly higher in the PNS with severe TID group than the other two groups and in the T T genotype individuals than the CC and CT genotype individuals. A logistic regression analysis demonstrated that TGF-beta1 gene -509C/T genotype was the risk factor of TID in PNS patients [OR (odd ratio) 2.34, confidence interval (CI) 0.98-3.46, p = 0.012]. CONCLUSION. TGF-beta1 gene -509C/T polymorphism was associated with severe TID. The higher value in serum concentration of TGF-beta1 was also associated with severe TID and the T T genotype/T allele. T allele gene might be the important risk factor for susceptibility.

Activated T cells inhibit NK cell-mediated tumour rejection.

Previous studies have described the regulation of some T-cell subsets toward natural killer (NK) cells. Naturally occurring CD4(+)CD25(+) T regulatory cells can inhibit NK cell cytotoxicity, while activated interleukin-2 (IL-2) secreting T cells can stimulate NK cells. However, little is known about the impact of the integrity T-cell population on the final outcome of NK cell cytotoxicity. We thus examined the possible role of activated T cells in affecting NK cell cytotoxicity by mixed lymphocyte co-cultures in vitro and a B16 melanoma tumour model in vivo. In our study, activated T cells were found to be able to significantly inhibit NK cell cytotoxicity in vitro and blunt NK cell-mediated tumour rejection in vivo. The inhibition of NK cell function is a cell-cell contact dependent way. Results suggest that activated T cells may play an important role in limiting NK cell functions, which might be very significant for the design of biotherapy against tumour or infection in future.

Arkadia regulates TGF-beta signaling during renal tubular epithelial to mesenchymal cell transition.

Transforming growth factor-beta (TGF-beta) signaling has been linked with tubular epithelial to mesenchymal cell transition. In this study, we examined the role of Arkadia, an E3 ubiquitin ligase that is critically required for TGF-beta signaling during epithelial to mesenchymal cell transition. We found that when normal human renal tubular epithelial cells in culture were stimulated with TGF-beta1, which increased their levels of Arkadia, Smurf2, TGF-beta type I receptor (TbetaRI), and Smad7 mRNA, but had low levels of Smad7 protein. When these cells were preincubated with Arkadia siRNA (small interfering RNA) and lactacystin (an inhibitor of proteasomal degradation), the TGF-beta(1) induced expression of Smad7, alpha-smooth muscle actin, and E-cadherin was partly reversed, but the expression of TbetaRI protein and Smad7 mRNA was not affected. In contrast, Smurf2 siRNA had no influence on the expression of these targets. Our studies suggest that Arkadia stimulates renal tubular epithelial to mesenchymal cell transition through degradation of Smad7.

Fatty acid composition in breast milk and serum phospholipids of healthy term Chinese infants during first 6 weeks of life.

AIM: To compare the fatty acid (FA) pattern in early and mature breast milk with that in plasma phospholipids of cord blood and breast-fed infants. METHODS: Forty-five mother-infant pairs from western Shanghai were studied. All infants, born at term with normal weight and length, were examined at birth and days 5 and 42. FA was analyzed by capillary gas-liquid chromatography. RESULTS: Cord blood showed higher concentration of long-chain polyunsaturated FA (LCPUFA) but lower saturated (SFA) and monounsaturated (MUFA) FA than postnatal infants' plasma. SFA decreased with age in the infants, but MUFA and linoleic acid (LA, 18:2omega6) increased. LCPUFA were lower in the plasma of 5-day-old infants than in cord blood, but LA was 80%, alpha-linolenic acid (ALA, 18:3omega3) 33% and the ratio omega-6/omega-3 42% higher. At day 42, LA increased further, LCPUFA remained similar, and was in breast milk lower than at day 5, while ALA and gamma-linolenic acid (18:3omega6) were higher. The activity index of desaturases indicated high Delta9 activity in breast milk and high activity of Delta5 desaturase in the infants. CONCLUSION: Breast milk FA composition changed markedly from day 5 to 42 with increasing correlation to infants' plasma. Calculation of desaturase activities suggested high capacity of LCPUFA synthesis.

Effect of tacrolimus and cyclosporine A on suppression of albumin secretion induced by inflammatory cytokines in cultured human hepatocytes.

OBJECTIVE AND DESIGN: To investigate the effect of tacrolimus (FK506) and cyclosporine A (CSA) on albumin secretion and on the IL-6 -induced suppression of albumin synthesis in cultured human hepatocytes. METHODS: HepG2 cells were cultured separately with IL-6, IL-10 (0-10 ng/ml) and FK506, CSA (0-100 ng/ml) for 48 h. In another experiment, HepG2 cells were incubated with different amounts of FK506 and CSA (0-10 ng/ml) in the presence of IL-6 (5 ng/ml). The albumin levels in these groups of hepatic cultures were measured by radioimmunoassay. The concentration of LDH secreted by cells stimulated with FK506 and CSA was detected by spectrophotometry. RESULTS: IL-6 decreased the levels of albumin in a dose-dependent manner (P < 0.01), maximal inhibition was observed at 5 ng/ml. Neither IL-10 nor FK506 modulated albumin production. However, FK506 decreased LDH levels in the supernatant of cells (P < 0.05) and prevented the IL-6-induced suppression of albumin synthesis (P < 0.01) in a dose dependent manner. In contrast, CSA caused only a slight decrease in albumin levels (P < 0.05). In addition, CSA slightly increased the amount of LDH in HepG2 cells and did not interfere with the IL-6-induced decrease in albumin synthesis. CONCLUSIONS: These findings suggest that IL-6, but not IL- 10, may play an important role in the suppression of hepatic albumin secretion. FK506 but not CSA protects against the suppression of hepatic albumin synthesis caused by IL-6.

A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia.

To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human papillomavirus (HPV) typing was done to determine whether lesion regression was related to HPV. Micronutrient levels were measured to determine whether levels were predictive of regression. Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women were randomized to beta-carotene or placebo, with cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze response to treatment. Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had persistent or progressive disease, and 25 women did not complete the study and were considered nonresponders in the final analysis. The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivided into indeterminate-, low-, and high-risk categories; the response rate was highest for women with no HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high-risk (18%; P =.001). CIN regression was negatively correlated with retinol levels. In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.

[Protective effect of ginsenosides on human peritoneal mesothelial cell against lactate-based peritoneal dialysis solutions--induced injury in vitro].

OBJECTIVE: The aim of this research was to observe the influence of ginsenosides (GS) on viability and proliferation of human peritoneal mesothelial cell (HPMC) which were inhibited by L-PDS in vitro. METHOD: Mesothelial cells were isolated from human omental specimens by trypsin disaggregation and established a stable HPMC culture model. The viability and capacity of proliferation of HPMC were assessed by lactate dehydrognase (LDH) release and tetrazolium salt colorimetry assay (MTT assay). RESULTS: Compared with the control group, the release of LDH in L-PDS groups (2.5%, 4.25% glucose) significantly increased. But there was no difference between the two glucose concentrations. As HPMC pre-exposed to L-PDS prolonged, the viability of cells decreased gradually. GS decreased the release of LDH and increased the cells viability (P < 0.01), as well as enhanced the proliferation of HPMC. CONCLUSION: The results suggest that GS has some protective effects on cell viability and proliferation of HPMC inhibited by L-PDS in vitro.

A phase I trial of AUC-directed carboplatin with infusional doxorubicin and ifosfamide plus G-CSF in patients with advanced gynecologic malignancies.

The effect of the addition of G-CSF to carboplatin, ifosfamide and doxorubicin (CIA) at the maximally tolerated dose (MTD) was studied in a phase I clinical trial. Nine patients with incurable solid tumors were treated: six endometrial and epithelial ovarian cancers, one colon cancer with pelvic masses and two unknown primary cancers. The carboplatin dose was calculated using the Calvert formula and administered in a standard 30-min intravenous infusion. The initial carboplatin dose was AUC 4.0 mg/ml per min. Fixed doses of ifosfamide (1.25 g/m2 per day), mesna (1.0 g/m2 per day, and doxorubicin (15 mg/m2 per day) were combined and given as a 4-day continuous intravenous infusion in an attempt to decrease nonhematologic toxicity. The dose-limiting toxicity of CIA was myelosuppression, mainly neutropenia and thrombocytopenia. Nonhematologic toxicities were hemorrhagic cystitis, weakness, fatigue, and nausea and vomiting. The MTD for CIA was established at the first dose level of carboplatin (4.0 mg/ml per min). Following this, G-CSF was added to the regimen in an unsuccessful effort to escalate the carboplatin dose. Free and total carboplatin pharmacokinetics were determined using flameless atomic absorption spectroscopy. There was one complete response and one partial response among eight evaluable patients. Both responding patients had advanced ovarian cancer. We conclude that carboplatin dose intensification beyond an AUC of 4.0 mg/ml per min is not made feasible by the addition of G-CSF to infusional doxorubicin and ifosfamide in patients with advanced gynecologic cancer.

Nephrotoxicity of high- and low-osmolar contrast media. The protective role of amlodipine in a rat model.

PURPOSE: To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. The protective role of amlodipine was studied. MATERIAL AND METHODS: Forty rats of both sexes were randomly divided into 5 groups (n=8/group) and glycerine for inducing renal failure was given to all rats except controls. RESULTS: In diatrizoate-injected rats, blood urea nitrogen (BUN) and serum creatinine (SCr) were increased; levels of phospholipase A2 (PLA2), lipid peroxide (LPO) and calcium were also increased in renal tissues. There was no significant difference between LOCM (iohexol) animals and glycerol controls either in the renal levels of PLA2, LPO and calcium or in the levels of BUN and SCr. The histologic changes were milder in the LOCM animals than in the HOCM animals. In the group pretreated with amlodipine, no increase in the levels of BUN or SCr was discovered and the renal content of PLA2, LPO and calcium were significantly lower than in the HOCM group; the renal injuries induced by diatrizoate were alleviated. CONCLUSION: The HOCM, diatrizoate, was more toxic to rat kidneys than the LOCM iohexol; PLA2, LPO and calcium load played a role in producing renal function impairment induced by diatrizoate meglumine; amlodipine protected the renal tissue from nephrotoxicity induced by diatrizoate.

Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.

Alpha-2-(Difluoromethyl)-dl-ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to suppress skin carcinogenesis in murine models after oral or topical administration. We designed a randomized, placebo-controlled study using a topical hydrophilic ointment formulation with or without 10% (w/w) DFMO. Forty-eight participants with moderate-severe actinic keratoses (AKs) on their forearms (i.e., at least 10 well-circumscribed lesions on the lateral surface) completed a 1-month run-in on placebo ointment. Before randomization, all lateral forearm AKs were circled, counted, photographed, and skin biopsies were obtained for DFMO and polyamine levels. Then participants were randomized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months. DFMO was not detected in the blood of any subject, and there were no systemic toxicities. None of a subsample of 17 placebo forearms had measurable concentrations of DFMO, whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels. As compared with placebo, the 6-month DFMO treatment caused a 23.5% reduction in the number of AKs (P = 0.001) as well as significant suppression of AK biopsy spermidine levels (26%; P = 0.04). Seven of the 48 (14.6%) participants experienced severe (2; 4.2%) or moderate (5; 10.4%) inflammatory reactions on their DFMO-treated arms which required dosing modification. Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent.

[The effect of increasing ventral movement on the small solutes transport during peritoneal dialysis].

OBJECTIVE: To investigate whether the small solutes transport and the efficiency of peritoneal dialysis can be improved through ventral movement. METHODS: Eighteen continuous ambulatory peritoneal dialysis (CAPD) patients and 6 male New Zealand rabbits peritoneal dialysis models were observed. Through self and pre-post control, we compared the concentration ratio of the solutes in effluent dialyste(D) to the solutes in plasma(P), mass transfer area coefficient and the drained volume. RESULTS: The animal experiments showed that the D/P value for BUN was different prominently when comparing the vibration and non-vibration groups in 45 min and 60 min separately(P < 0.05). On the contrary, no obvious difference existed between the two groups when comparing the D/P values for protein and drained volume. The clinical study showed: D/P value for BUN at the 2 and 4 hr and D/P value for creatinine at the 2 hr increased obviously either in the low or high frequency group when compared with the control group(P < 0.01, P < 0.01, P < 0.05, respectively). D/P for protein and drained volume had no difference compared with the control group(P > 0.05). CONCLUSION: The ventral movement and vibration could efficiently increase the transport of small solutes such as BUN and creatinine while had no influence on the transport of large molecular solutes such as protein and the ultrafiltration volume. It suggested that increasing the movement of CAPD patients can improve the efficiency of peritoneal dialysis.