AIM: To investigate the efficacy of 1g/L topical cyclosporine A ( tCsA ) in preventing the recurrence of pterygium after pterygium excision and conjunctival flap rotation technique.
●METHODS:Fifty-eight patients (58 eyes) with primary pterygium were included in this prospective study. All eyes were operated with pterygium excision and conjunctival flap rotation technique, and divided into treatment and control group according to whether be treated with 1g/L tCsA eye drops after operation. The operated patients were followed up for 1y to assess the recurrence of pterygium.
●RESULTS: After surgery, the difference between the tCsA treatment and control group were statistically significant in the Schirmer l test results (9. 93 ± 1. 59mm/5min vs 8. 47±1. 53mm/5min, P<0. 001). The Schirmer l test results increased after tCsA treatment for patients assigned to the treatment group. The pterygium recurred in 3 of 28 eyes (10%) in the treatment group and 11 of 30 eyes (39%) in the control group (P=0. 029).
●CONCLUSION:tCsA eye drops are safe and effective for medical treatment to reduce rates of recurrence after pterygium surgery.

Objective To summarize the experience of orthotopic liver transplantation in pigs without veno-venous bypass.Method In general,Bama miniature pigs were used as both the donors and the recipients.Suprahepatic inferior vena cava and portal vein anastomosis was performed with running prolene sutures.After completion of the portal vein anastomosis,the graft was reperfused.Infrahepatic inferior vena cava anastomosis and hepatic artery anastomosis were performed in a similar fashion.Finally,the common bile duct was reconstructed.Result For all of the transplant procedures,the average cold ischemic time was 356.3 ± 66.4 min and anhepatic time 22.5 ± 2.6 min,and the average operative time was 185.7 ± 24.8 min.During the anhepatic phase,the central venous pressure (CVP) and the mean arterial pressure (MAP) were significantly lower than those at baseline (P＜ 0.05).Heart rate (HR),on the other hand,was increased significantly during the anhepatic phase (P＜0.05).By the time the portal vein and the hepatic artery were reperfused,and CVP and MAP were gradually elevated,and HR gradually reduced.All receptors were successfully extubated and awake after surgeries.On the third postoperative day they began to eat.All receptors survived during the intraoperative period,and the survival rate was 93.8％ (15/16) on the fifth postoperative day.One receptor was died on the third postoperative day due to abdominal infection.Conclusion This model has satisfactory stability and reproducibility.Without using any vasoactive substances,to maintain the MAP beyond 50 mmHg in the anhepatic phase and the short anhepatic time are important to perform successful liver transplantation.

AIM:To evaluate the effect of curcumin on impaired learning-memory ability and the expression of high mobility group box protein 1 ( HMGB1 ) and c-Jun N-terminal kinase ( JNK ) in a rat model of Alzheimer disease (AD).METHODS:Male Sprague-Dawley rats, weighing 250~270 g, were randomly divided into 4 groups (n=9):blank control group (group A), model group (group B), curcumin treatment group (group C, curcumin injected intraper-itoneally at 100 mg· kg-1· d-1 for 6 consecutive days) and solvent control group (group D).The rats of AD model were induced by injection of ibotenic acid into the nucleus basalis of Meynert ( NBM) bilaterally.All rats were trained in Morris maze to assess the ability of learning and memory .The expression of HMGB1 and JNK in the hippocampus was detected by the methods of immunohistochemistry and Western blotting .RESULTS:Compared with group A , the average escape laten-cy (AEL) in groups B and D were obviously longer (P<0.05), while AEL in group C in the 5th and 6th days were signif-icantly shorter (P<0.05).The releases of HMGB1 in the CA1 and CA3 areas in groups B and D from the nucleus were a-bundant.Compared with groups B and D , HMGB1 in hippocampal CA1 and CA3 areas in group C secreted out of the nu-cleus decreased obviously (P<0.05).No significant difference of the release of HMGB1 between group A and group C was observed (P>0.05).No significant difference in the expression of HMGB1 in the hippocampus among the 4 groups was found (P>0.05).However, compared with groups B and D , the expression of JNK in group C was decreased obvi-ously (P<0.05).CONCLUSION: Curcumin significantly improves the learning and memory ability of AD rats .The probable mechanisms may be related to inhibiting the release of HMGB 1 from the nucleus of hippocampal neurons and de-creasing the expression of JNK in the hippocampus .

Objective To investigate the effects of cytarabine(Ara-C) on expression of B7 molecules and immunogenicity of acute leukemia (AL) cells. Methods The expression of B7 molecules on fresh AL ceils and on the Ara-C exposed leukemia ceils was detected by FACS cytometer. B7 mRNA in Ara-C treated HL-60 cells were detected by reverse RT-PCR. The stimulation of proliferation of allogeneic PBMC by Ara-C treated HL-60 cells was detected by MTT method. Results B7-2 was weakly expressed in four and positive in three, whereas BT-1 was positive in only one of fourty AL patiens. Ara-C significantly enhanced B7 molecules expression on AL cells. Ara-C could induce higher expression of B7 mRNAs on HL-60 cells.Ara-C treated HL-60 cells could stimulate PBMC proliferation and promote their IFN -γ production.Conclusion Fresh AL cells express low level of B7 molecules. Ara-C enhances the B7 molecules expression on AL cells. The Ara-C treated leukemia cells can significantly stimulate the proliferation of allogeneic PBMC and induce their secretion of IFN-γ.

OBJECTIVETo assess the efficacy and safety of recombinant human thrombopoietin (rhTPO) on chemotherapy-induced thrombocytopenia in patients with solid tumor.

METHODSIn this randomized crossover self-controlled multi-center clinical trial, 154 patients with solid tumor were randomly divided into two groups (group A 77 cases and group B 77 cases). All patients were given the same two cycles of chemotherapy. In group A, the first cycle was treated cycle, in which patients were given rhTPO, while the second cycle was non-treated cycle as a control. In group B, the first cycle was non-treated cycle as a control, while the second cycle was treated cycle. RhTPO 1.0 microg/(kg x d) was administered subcutaneously 6-24 hours after chemotherapy for the longest 14 days. Laboratory tests included complete blood counts, urinalysis, serum chemistry, coagulant test, chest radiography, and electrocardiogram. Serum samples were screened for anti-rhTPO antibodies.

RESULTSIn both group A and group B, platelet decrease and duration had no significant difference between the treated cycle and non-treated cycle. Platelet count was higher in the treated cycle, than in the non-treated cycle: [minimal mean platelet count (64.4 +/- 45.4) x 10(9) cells/L and (52.4 +/- 30.9) x 10(9) cells/L (P=0.000), maximal mean platelet count (263.9 +/- 142.5) x 10(9) cells/L and (148.9 +/- 67.7) x 10(9) cells/L (P=0.000)]. Duration of thrombocytopenia was shorter in the treated cycle than in the non-treated cycle [days with platelet count < 50 x 10(9) cells/L, (2.5 +/- 3.9) and (3.7 +/- 5.7) (P=0.04); days with platelet count recovered > or = 75 x 10(9) cells/L, (10.3 +/- 8.7) and (14.0 +/- 8.9) (P=0.000), and days with platelet count recovered > or = 100 x 10(9) cells/L, (15.9 +/- 10.5) and (21.1 +/- 9.5) (P=0.000)]. The need for platelet transfusion was not significantly reduced in treated cycle. The effects of rhTPO on WBC, Hb, hepatic function, renal function, and coagulant function were not found. Transient low-titer non-neutralizing antibody was developed in one patient. Therapy with rhTPO was tolerated by all patients. Mild side effects were observed in individual patients, including fever, dizziness, and chill. Conclusion Administration of rhTPO after chemotherapy can significantly reduce the degree and duration of thrombocytopenia and promote platelet recovery. Therapy with rhTPO seems to be safe.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Neoplasms ; blood ; drug therapy ; Platelet Count ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; prevention & control ; Thrombopoietin ; therapeutic use

An in vitro P-glycoprotein mediated drug biliary excretion model (B-Clear model) was developed and validated using sandwich-cultured rat hepatocytes (SCRH) and a model substrate rhodamine 123 (Rh123). SCRH formed functional bile canalicular networks after 5 days of culture. Rh123 (10 micromol x L(-1)) was then incubated with the SCRH in standard Ca+ Hanks buffer or Ca(2+)-free buffer. The cumulative cell uptake and canalicular efflux of Rh123 under Ca2+ and Ca(2+)-free conditions were measured with a LC-MS/MS method. The biliary excretion index (BEI) and instinct biliary clearance (CL(bile, int)) were calculated. To assess the effect of known P-gp inhibitors on the efflux of Rh123, cyclosporine A (CyA), tariquidar (TQD) or quinidine (QND) (10, 50 and 100 micromol x L(-1)) was pre-incubated separately with SCRH for 30 min, then co-incubated with Rh123. The BEI and CL(bile, int) of Rh123 obtained from the SCRH model were (17.8 +/- 1.3) % and (10.7 +/- 0.9) mL x min(-1) x kg(-1), respectively. All the three P-gp inhibitors showed a dose-dependent inhibition on the bile clearance of Rh123, indicating that the B-Clear model with SCRH was functional properly. The biliary excretion of loperamide (LPAD) and the role of P-gp were further investigated with this validated model. The BEI and CL(bile, int) for LPAD (20 micromol x L(-1)) were obtained after it was incubated with SCRH for 30 min, and found to be (12.9 +/- 1.2)% and (6.1 +/- 0.3) mL x min(-1) x kg(-1) respectively. The dose-dependent inhibition on LPAD biliary excretion by CyA, TQD or QND confirmed the major role of P-gp in LPAD canalicular efflux. The results suggested that the B-Clear model with SCRH would be a useful tool for evaluation of P-gp mediated efflux and drug-drug interaction.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Animals ; Biliary Tract ; metabolism ; Cells, Cultured ; Chromatography, High Pressure Liquid ; Cyclosporine ; pharmacology ; Hepatocytes ; cytology ; metabolism ; Loperamide ; metabolism ; Male ; Quinidine ; pharmacology ; Quinolines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Rhodamine 123 ; metabolism ; Tandem Mass Spectrometry

Objective To investigate the effect of different concentrations of vinorelbine on apoptosis ,telomerase ac-tivity and expression of human telomerase-reverse transcriptase gene ( hTERT ) in human epithelial ovarian cancer cells SKOV3.Methods Ovarian cancer cells SKOV 3 were treated with vinorelbine under different concentrations . The cell proliferation was measured by cell counting kit-8 ( CCK-8) assay , and the cell apoptosis was detected by flow cytometry.The telomerase activity of SKOV3 cells was determined by TRAP-PAGE-silver staining;The mRNA expression of hTERT was performed by RT-PCR assay .Results Vinorelbine could significantly inhibited the prolifer-ation of SKOV3 cells,induce cell apoptosis (P<0.01),reduce the telomerase activity and expression of hTERT mRNA (P<0.01), in dependent of a concentration-time manner.Conclusions The detection of telomerase activity and the mRNA expression of hTERT might be vital for predicting the prognosis of patients with epithelial ovarian cancer .

OBJECTIVETo study the plasma concentration-time curve, pharmacokinetic parameters and bioavilability of oxymatrine-phospholipid complex and to compare with oxymatrine in rats.

METHODRats were given oxymatrine-phospholipid 100 mg x kg(-1). Blood samples were collected at different times after oral administration. The internal standard was cimetidine. Protein in plasma was precipitated with merhanol and centrifuged at high speed. The supernatant was directly injected and assayed by CE method. The running buffer was 0.04 mol x L(-1) Tris-10 mmol x L(-1) sodium phosphate monobasic-40% isopropanol pH to 7.6 with phosphoric acid. The wavelength of detection was 205 nm.

RESULTThe AUC of oxymatrine and oxymatrine-phospholipid complex were 4.52 mg x mL(-1) x h(-1) and 6.21 mg x mL(-1) x h(-1), respectively. The oxymatrine-phospholipid bioavailability enhanced 1.4 times.

CONCLUSIONIt is concluded that after oral administration of oxymatrine-phospholipid complex in rats the bioavailability of oxymatrine is increased greatly. This is mainly due to an obvious improvement of the lipophilic property of oxymatrine-phospholipid complex compared with oxymatrine material and an increase in gastrointestinal absorption.

Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Area Under Curve ; Biological Availability ; Male ; Phospholipids ; chemistry ; Plants, Medicinal ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Sophora ; chemistry

Objective To study the clinical characteristics and prognosis of children aged 5 or above with stage 3/4 neuroblastoma ( NB).Method Among 180 children with NB admitted from March 2007 to June 2015, 54 were aged 5 or above with stage 3 or 4.The clinical characteristics , therapeutic efficacy and prognosis of above 54 cases were analyzed.Results There were 36 boys and 18 girls with a male to female ratio of 2∶1.The most common of primary site was retroperitoneum (41/54, 75.5%), followed by mediastinum (10/54,18.5%), spine and pelvic cavity (3/545,6%).After treated by average 9 cycles of chemotherapy , 34 cases ( 63%) achieved complete remission ( CR ) , 13 ( 24.1%) achieved partial remission (PR), 5 (9.3%) presented disease progression (DP), and 2 died (3.7%).Patients were followed up for median 30 months ( 8 -99 months ) , 24 cases died and 30 survived with a overall survival (OS) rate of 55.6%.In 30 survival cases, there were 23 cases (76.7%) of event-free survival (EFS) ,and 6 cases (20.0%) of PR and 1 case (3.3%) of DP.There were significant differences in prognosis among patients with different responses to first therapy (χ2 =8.963, P =0.003 ).Among 20 children with stage 4 NB treated by autologous peripheral blood stem cell transplantation ( APBSCT ) , 13 cases died and 7 survived with an average survival time of (73.55 ±8.89)months.Among 29 cases without APBSCT, 11 cases died and 18 survived with an average survival time of(40.19 ±5.52)months.There was no significant difference in survival between APBSCT and no-APBSCT.Conclusion Children aged 5 or above with NB tend to have advanced stage , relapse and long treatment cycle , but the survival still can be improved with the appropriate treatment .

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.