AIM　To prepare naftopidil bioadhesive sustained-release capsule and study their pharmacokinetics and relative bioavailability in the dog. METHODS　Bioadhesive polymers such as hydroxypropyl methylcellulse (HPMC) and Carbopol 934 (CP 934) were used in capsule prescriptions. Naftopidil capsule and two formulations of bioadhesive sustained-release capsules (I and II) were given to five healthy male dogs in a cross-over test. The naftopidil concentrations in plasma were determined by a newly developed HPLC method and the pharmacokinetic parameters as well as the relative bioavailability were measured. RESULTS　The C0→∞, Cmax and Tmax of naftopidil capsule was (3728±573) h*ng*mL-1, (697±94) ng*mL-1 and (1.2±0.5) h. These parameters of bioadhesive sustained-release capsule I and II, respectively, were (5518±391) h*ng*mL-1 and (5636±427) h*ng*mL-1; (468±61) ng*mL-1 and (512±72) ng*mL-1; both (4.0±0.7) h. Results from statistics showed that there were significant difference between bioadhesive formulations and the non-bioadhesive one in C0→∞, Cmax and Tmax. The bioadhesive formulations and the non-bioadhesive one were not bioequivalent, the relative bioavailability of the two bioadhesive sustained-release capsules were respectively 150%±14% and 154%±23% when compared with the non-bioadhesive capsule. CONCLUSION　It is much improving bioavailability of naftopidil by using bioadhesion.

The UK Ebola-countering Operation in Sierra Leone from September 2014 to November 2015 called Operation Gritrock and its countermeasures were briefly introduced , such as the national strategy , aero-maritime deployment , self medical support , base-oriented training and international cooperation .A comparative analysis was made of operations of the same type between the UK and China in terms of mission-orientation, command and control , deployment timeline , past experience, deployment routes, logistics and assistance effects.Four implications for China′s military function construction in future international disaster relief operations were also summarized at the strategic , operational and tactical levels .

Objective To explore the increasing risk of herpes zoster and its possible mechanisms for hematologic disorders treated with arsenic trioxide (ATO). Methods The cases were divided into study group (with ATO) and control group (without ATO). The incidence rate of herpes zoster was compared between the two groups, and then the average cycles of chemotherapy were compared between the patients complicated with herpes zoster or not in study group. Results The rate of herpes zoster was significantly higher in study group than that in control group (χ2 =4.492, P =0.034). The rates of herpes zoster were 23.95 % (23/96) in study group and 7.89 % (3/38) in control groups. Patients in study group with herpes zoster had received 7.60 cycles and those without herpes zoster 7.72 cycles of chemotherapy on average (Z=0.976, P=0.296).Conclusion The risk of herpes zoster complication in hematologic disorders was increased after ATO treatment which probably activated varicella-zoster virus.

AIM:To study the effect of vitamin K3(VK3) on the induction of apoptosis in androgen-independent prostate cancer cell PC-3M in vitro.METHODS:Cell viability was estimated by MTT assay.AO/EB staining was performed to detect apoptotic cells.Apoptosis and the changes of cell cycle were detected by flow cytometry.NAC was used to observe the effect of growth inhibition by VK3.RT-PCR was used to confirm the changes in gene expression.Levels of intracellular peroxides were estimated by using an oxidation-sensitive fluorescent probe DCFH-DA.RESULTS:PC-3M cells growth was significantly inhibited by VK3(≥60 ?mol/L,P

OBJECTIVE To study clinical characteristics of liver failure with fungal infections in the elderly patients and risk factors associated with treatment failure.METHODS Eighty four elderly patients with liver failure followed by fungal infections since 1986 were divided into two groups: effective group and ineffective group.RESULTS The common pathogens were Candida albicans(58.33%),Aspergillus fumigatus(9.52%) and Candida tropicalis(8.33%).The lungs(43.88%),mouth(32.65%),intestinal tract(9.18%) and blood(5.10%) were the main sites of fungal infection.Among them after treatment,35 cases(41.67%) were effective compared with 49 cases(58.33%) ineffective.The risk factors for treatment failure included age,complication with multiple organ dysfunction syndrome(MODS) and aspergillosis.In multivariate analysis,we found MODS in patients was an independent factor in predicting the prognosis.CONCLUSIONS To improve the treatment outcome,important measures include preventing infection,enhancing the treatment of liver failure,monitoring and supporting multiple organs: heart,brain,lungs and kidneys,and promptly rational administration of antifungal agents in elderly patient with liver failure.

OBJECTIVE To study the feature of liver disease and liver failure complicated with fungous infection. METHODS The patients with liver disease complicated with fungous infection were collected form 1986 to 2005. The time was divided into four stages:from 1986 to 1990,from 1991 to 1995,from 1996 to 2000 and from 2001 to 2005. All patients with liver failure complicated with fungous infection in different stages were investigated for the incidence,the use of antibiotics and corticosteroids,the category and site of fungous infection and prognosis. RESULTS End-stage liver disease accounted for 82.6% and HBV infection was the main etiology in 475 cases of fungous infection. Fungous infection occurred mainly in hospital. Hospital acquired infection and community acquired infection were similar in different stages. The use of antibiotics and corticosteroids accounted for 88.8% and 48% in all patients before fungous infection,respectively. The use of antibiotics had no difference and the use of corticosteroids decreased in different stages. Candida were the main infection strains and the lungs and pharynx oralis were the main infection sites. The rate of healing and improvement of fungous infection and underlying diseases increased year by year. Healing and improvement rate of underlaying disease positively correlated with that of fungous infection. CONCLUSIONS End-stage liver disease patients are susceptible to fungous infection and Candida are the common infection strains. Lungs and pharynx oralis are the common infection sites. Anti-fungous therapy is important in the treatment of liver failure complicated with fungous infection.

OBJECTIVECell-free DNA (cfDNA) was shown to be a prognostic marker for diverse pathological states in the Intense Care Unit, but little is known of the role of cfDNA in HBV-related acute-on-chronic liver failure (ACLF). We hypothesize that cfDNA can also be a promising prognostic as well as a diagnostic marker in patients with HBV-related ACLF.

METHODSThirty-eight patients with HBV-related ACLF admitted in the Intense Care Unit were enrolled in the study. The patients were divided, according to the improvement of liver function at discharge, into favorable prognosis group (group 1, n=17) and poor prognosis group (group 2, n=19). Plasma samples were collected from each patient at hospitalization and at discharge to measure cfDNA by real-time quantitative PCR. MELD score was calculated at the same time points.

RESULTSThe average level of cfDNA of group 1 was lower than that of group 2 both at the time of hospitalization (P=0.044) and at discharge (P<0.001). There was no difference in MELD score between the two groups at hospitalization. Significant correlations were found of cfDNA levels with the MELD score, TBIL, CRE and INR both at hospitalization (γ=0.662, P<0.001; γ=0.356, P=0.033; γ=0.360, P=0.031; γ=0.570, P<0.001, respectively) and at discharge (γ=0.854, P<0.001; γ=0.821, P<0.001; γ=0.650, P<0.001; γ=0.638, P<0.001, respectively). The ROC curve showed that cfDNA level at discharge was optimal in diagnosing ACLF with an area under curve (AUC) value of 0.96, followed by δcfDNA (AUC value of 0.923) and cfDNA level at hospitalization (AUC value of 0.667). The MELD scores had an AUC value of only 0.545 at the time of hospitalization.

CONCLUSIONcfDNA may serve as a promising prognostic and diagnostic marker for predicting in-hospital prognosis of HBV-related ACLF within 2 to 8 weeks.

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Adult ; DNA, Viral ; blood ; End Stage Liver Disease ; diagnosis ; Female ; Hepatitis B ; complications ; Hepatitis B virus ; genetics ; Humans ; Male ; Middle Aged ; Pilot Projects ; Plasma ; chemistry ; Prognosis ; Severity of Illness Index

Objective: To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice. Methods: An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD₅₀) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1β (IL-1β) , and transforming growth factor-β1 (TGF-β1) using enzyme-linked immunosorbent assay. Results: The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD₅₀ values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-β1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1β (P<0.05) . After 48 hours, the expression of TNF-α, TGF-β1, and IL-1β in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) . Conclusion OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.

Objective: The present study was designed to evaluate the protective effects of oligomeric proanthocyanidins (OPC) in mice exposed to paraquat (PQ) , and to explore the molecular mechanism. Methods: Four experimental groups were designed. Control group: 10 BALB/c mice were intraperitoneally injected with normal saline) . PQ group: 10 BALB/c mice were intraperitoneally injected with PQ (100 mg/kg) . PQ+OPC group: 10 BALB/c mice were administered with OPC (100 mg/kg) for 1 h before PQ (100 mg/kg) expo-sure. OPC group: 10 BALB/c mice were intraperitoneally injected with OPC (100 mg/kg) . The peripheral blood samples or lung tissue samples were collected at the designed time points for measuring the levels of oxi-dative stress indicators, the related protein levels of nuclear factor-kappa B (NF-κB) pathway and nuclear fac-tor erythroid related factor-2 (Nrf2) pathway. Results: Compared with the control group, the level of reactive oxygen species (ROS) , the content of malondialdehyde (MDA) in the PQ group were significantly induced, and the activity of superoxide dismutase (SOD) in the PQ group was decreased in the peripheral blood. As com-pared with the PQ group, the level of ROS and the content of MDA in the PQ+OPC group were significantly re-duced, the activity SOD in the PQ+OPC group was increased in the peripheral blood; the level of ROS and the content of MDA were also reduced in lung tissues in the PQ+OPC group. Moreover, compared with the con-trol group, the phosphorylation of IκBα and the expression of NF-κB p65 were increased in lung tissues in the PQ group. The phosphorylation of IκBα and the expression of NF-κB p65 were decreased in lung tissues in the PQ+OPC group as compared with the PQ group. In addition, compared with the control group, the expressions of HO-1 and Nrf2 were increased in lung tissues in OPC group, and these were decreased in lung tissues in PQ groups. Furthermore, the expressions of HO-1 and Nrf2 were also increased in lung tissues in PQ+OPC as com-pared with the PQ group. Conclusion OPC could alleviate PQ-induced systemic toxicity in mice by regulating oxidative stress via NF-κB and Nrf2 pathway.