OBJECTIVETo investigate whether tri-ortho-cresyl phosphate (TOCP) and organophosphate compound that could produce organophosphate-induced delayed neuropathy (OPIDN) in hen and other sensitive species, directly affect oligodendrocytes, the myelin-forming cell of the central nervous system.

METHODSThis was achieved by a combination of measurements of cell viability (MTT) cell pathological observation in the presence and absence of the compound cultured hen brain oligodendrocytes were prepared and treated with various concentrations of TOCP.

RESULTSIn a time-course experiment TOCP showed a cytotoxic effect to oligodendrocytes and led to the oligodendrocyte processes disintegrated and membranous blebs, cytoplasmic vacuolation following exposure time of 24 h or longer, it showed a dose-depended and time-depended manner cytotoxic effect to oligodendrocytes at dose levels of 0.5 approximately 1.5 microg/ml (1.35 approximately 4.05 mol/L) concentrations of TOCP for 24 - 72 h exposure. MTT experiment indicated that TOCP inhibited cell viability by dose-depended manner at dose levels of 0.5 approximately 1.5 microg/ml (1.35 approximately 4.05 mol/L) concentrations of TOCP for an 24 h exposure.

CONCLUSIONSTOCP is cytotoxic to oligodendrocytes and leads to the oligodendrocyte processes disintegrated and membranous blebs, vacuolar degeneration, which suggests that this oligodendrocyte degeneration may involve in the pathogenesis mechanism for OPIDN.

Animals ; Cell Survival ; Cells, Cultured ; Cerebral Cortex ; pathology ; Chickens ; Dose-Response Relationship, Drug ; Oligodendroglia ; drug effects ; pathology ; Tritolyl Phosphates ; toxicity ; Vacuoles ; drug effects ; pathology

BACKGROUND: Although regulatory T cells (Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis. DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and PubMed. Articles on the role of Tregs in immune dysfunction during sepsis were identified. RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function. CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.

OBJECTIVE Lychee seed, a famous traditional Chinese medicine, recently were reported to improve the learning and memory abilities in mice. However, it is still unclear whether lychee seed saponins (LSS) can improve the cognitive function and associated mechanisms. METHODS In present studies, we established the Alzheimer disease (AD) model by injecting Aβ25-35 into the lateral ventricle of rats. Then the spatial learning and memory abilities of LSS- treated rats were evaluated with the Morris water maze, meanwhile the protein expressions of AKT, GSK3β and Tau in the hippo?campal neuron were analyzed by immunohistochemistry and Western blotting. RESULTS The results showed LSS can improve the cognitive functions of AD rats through shortening the escape latency, increasing the number across the platform, platform quadrant dwell time and the percentage of the total distance run platform quadrant. The protein expression of AKT was significantly up-regulated and that of GSK3β and Tau were decreased remarkably in the hippocampal CA1 area. CONCLUSION Our study is the first to show that LSS significantly improve the cognitive function and prevent hippocampal neuronal injury of the rats with AD by activation of the PI3K/AKT/GSK3β signaling pathway, suggesting LSS may be developed into the nutrient supplement for the treatment of AD.

Objective: To observe the effect of serum-containing Qingxin Tongmai decoction(QXTMD) on the apoptosis rate of mouse mononuclear macrophage cell line RAW264.7 induced by Acetylated low density lipoprotein (ac-LDL) and the expressions of type A scavenger receptor(SR-A), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), inositol-requiring enzyme 1α(IRE1α), exploring the possible mechanism of QXTMD in the treatment of atherosclerosis.Method: Eight New Zealand rabbits were randomly divided into the atorvastatin group (2.6 g·kg^-1) low, medium and high-dose QXTMD groups (3.33, 6.66, 13.32 mg·kg^-1). After 7 days of gavage, the carotid blood was collected to prepare drug-containing serum. The RAW264.7 cell line was stimulated with 2.5%, 5%, 10%, and 20% drug-containing serum culture for 6, 12, and 24 h, respectively. The cell proliferation rate was observed by cell counting kit-8 (CCK-8) method. The RAW264.7 cell line was cultured in vitro and divided into blank group, model group, atorvastatin group, and low, medium and high-dose QXTMY groups. The cells in blank group were cultured with bovine serum albumin(BSA). The model group was stimulated with BSA+50 mg·L^-1 ac-LDL for 24 h. The other groups were stimulated with BSA+50 mg·L^-1 ac-LDL+10% drug-containing serum for 24 h. The apoptosis rate and SR-A expression of RAW264.7 cells were detected by flow cytometry. The expressions of Bcl-2, Bax and IRE1α protein were detected by Western blot.Result: Compared with the blank group, the model group could increase the apoptosis rate of RAW264.7 cells (P<0.01) and the expressions of Bax and SR-A protein (P<0.01), but decrease the expression of Bcl-2 protein (P<0.05). Compared with the model group, low, medium and high-dose QXTMD groups could decrease the apoptosis rate of RAW264.7 cell line (P<0.05) and the expressions of SR-A and IRE1α (P<0.05,P<0.01). The low-dose QXTMD group and the high-dose QXTMD group could decrease the expression of Bax(P<0.05,P<0.01). The middle-dose group and the high-dose group could decrease the expression of Bcl-2(P<0.01).Conclusion: QXTMD can reduce the apoptosis rate of macrophages. The mechanism of atherosclerosis may be related to the expressions of Bax, IREα, SR-A and anti-apoptotic protein Bcl-2.

Objective To explore the impact of patient compliance on the long-term outcomes in hypertensive patients receiving hydrochlorothiazide(HCTZ)based combination therapy with spironolactone or eaptopril.Methods A total of 853 patients with mild to moderate hypertension were recruited and randomly divided into ItCTZ group(HCTZ 12.5 mg q.d),spironolactone group(HCTZ 12.5 mg q.d and spironolactone 20 mg q.d),and captopril group(HCTZ 12.5 mg q.d and captopril 25 mg bid)after 2-week placebo washout period and 6-week loading period for HCTZ.Since the efficacy of combination therapy was proven to be better than monotherapy 1 year after therapy beginning,patients in HCTZ group were randomly assigned to spironolactone group or captopril group.The patients were followed up for 4 years.Patients were divided to compliance(n=424)or noll-compliance group(n=429)according test drug taking questionnaire.During the follow-up time,the blood pressure and the outcomes were recorded monthly,and blood biochemical parameters were determined once a year. Results At the end of follow up,incidence of cardio-cerebral vascular events was significantly lower in compliance group(2 fatat,8 non-fatal)than that in noncompliance group(7 fatal,21 non-fatal,P<0.05).Systolic blood pressure[-(19.4±20.6)mm Hg,1 mm Hg=0.133 kPa]and diastolic blood pressure[-(10.7±13.5)mm Hg]were significantly reduced compared values at baseline and noncompliance group(all P<0.001)while the reduction did not reach statistically significance in noncompliance group[-(7.3±18.2)mm Hg and-(3.5±10.2)mm Hg,all P>0.05 vs.baseline].The serum BUN,Cr and UA leveis in the compliance group were significantly hisher and the serum K+,CHO,LDI-C level were significantly lower than baseline values.The serum BUN,UA levels in the compliance group were significantly higher while the serum K+,cholesterol levels were significantly lower than those in the noncompliance group(all P<0.05).Conclusions This study indicates that patient compliance could affect the long-term outcome and antihypertensive efficacy in hypertensive patients receiving HCTZ based combination therapy with spironolactone or captopril.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

OBJECTIVE: To determine the regulating role of phosphatidylinositol 3-kinase( PI3K) / protein kinase B( Akt)signaling pathway in the autophagy activity of rat NR8383 cells exposed to silicon dioxide( SiO_2). LY294002 was used to block PI3 K pathway. METHODS: i) The normal NR8383 cells were used and divided into blank group and silica exposure group( final concentrations of SiO_2 suspension were 0 and 50 mg / L respectively). They were cultured for 3,6,12,20 and24 hours. The enzyme linked immunosorbent assay( ELISA) was used to assess the amount of tumor necrosis factor-α( TNF-α) and transforming growth factor-β1( TGF-β1) in supernatants of cultured cells,and then the optimal time of cells exposed to dust was determined. ii) NR8383 cells were divided into control group( treated with a same volume of F-12 K medium without serum),silica group( treated with SiO_2 suspension,final concentration 50 mg / L) and intervention group( treated with SiO_2 suspension and PI3 K inhibitor LY294002,final concentration 50 mg / L and 20 μmol / L,respectively).Cells were harvested following incubation. ELISA was used to detect the levels of TNF-α and TGF-β1 at the time point of20 hours after incubation. To reveal the autophagy status of cells,Western blotting was used to detect Akt and microtubuleassociated proteins 1 light chain 3( LC3) protein at time point of 20 hours; laser scanning confocal microscope( LSCM)was used to observe the immunofluorescence expression of autophagy at time points of 3,6,12 and 20 hours. The cells were also treated with the lysosomal inhibitor chloroquine diphosphate( CDP) at the same time of SiO_2 treatment. RESULTS: i) The time point of 20 hours was confirmed to be the best dust exposure time for in vitro cell model of NR8383 cells.ii) The levels of TNF-α and TGF-β1 of supernatant in the silica group were higher than those of the control group( P <0. 05). The levels of TNF-α and TGF-β1 of supernatant in the intervention group were higher than those of the control group and silica group( P < 0. 05). The Akt protein expression of the intervention group was lower than those in the control group and the silica group,respectively. The LC3 Ⅱ / Ⅰ protein level of the silica group was higher than those of the control group and intervention group( P < 0. 05),but no statistical significance was found between the control group and intervention group( P > 0. 05). LSCM results indicated that autophagy expression at time points of 3 and 6 hours were stronger than those of 12 and 20 hours in control group; autophagy expression at time point of 12 hours was stronger than those of 3 and 6 hours in the silica group,while the autophagy expression at time point of 20 hours was slightly weaker than that of 12 hours,but still stronger than those of 3 and 6 hours. Compared with the same time point in control group,autophagy expression at 3 and 6 hours were weaker in the silica group,while the expressions increased obviously at time points of 12 and 20 hours. Autophagy expression at all time points decreased in the intervention group compared with silica group,especially at the time point of 20 hours. The autophagy expression in each group increased in varying degrees after added with CDP blocking. CONCLUSION: Silica dust exposure can induce autophagy in rat NR8383 cells. PI3 K inhibitor LY294002 can reduce the autophagy expression indicating that the PI3 K / Akt signaling pathway might participate in the autophagy process of silica dust inducing autophagy in alveolar macrophages.