Objective: To explore the effect of artesunate (Art) on Akt/GSK-3β/β-catenin signal pathway.Methods: Art at different concentrations (0, 12.5, 25, 50 μg·ml-1) was used to treat human hepatic stellate cells (LX-2), and CCK-8 assay was used to detect the cell proliferation to determine the optimal concentration.Art inhibitor (MK-2206) at different concentrations (0~8 μmol·L-1) was given to LX-2 cells, and a Western Blot method was applied to determine the optimal inhibition concentration.Art, MK-2206 and MK-2206+Art were respectively given to LX-2 cells, and a Western Blot method was used to detect the levels of Akt, p-Akt, GSK-3β, p-GSK-3β and β-catenin proteins.Results: CCK-8 assay was used to detect the cell survival rate, and the survival rate was 80% after the 24-hour treatment with 25 μg·ml-1 Art.The results of Western Blot showed that MK-2206 at 6 μmol·L-1 could effectively inhibit the expression of p-Akt.Compared with those of the control group, the levels of Akt, p-Akt, p-GSK-3β and β-catenin protein were significantly different (P＜0.05) in Art (25 μg·ml-1) group, MK-2206 (6 μmol·L-1) group and MK-2206 (6 μmol·L-1) + Art (25 μg·ml-1) group.The expression of GSK-3β and Akt in MK-2206+Art group had no significant difference when compared with that in Art group and MK-2206 group (P＞0.05), while the levels of p-Akt, p-GSK-3β and β-catenin were significantly reduced (P＜0.01).Conclusion: Art exhibits the influence on the relative factors in Wnt/β-catenin signal pathway by Akt/β-catenin, subsequently inhibits the cell proliferation and alleviates the liver fibrosis process.

Objective To summarize the clinical and laboratory features of chronic manganese poisoning. Methods A retrospective analysis was conducted on the clinical data of 4 cases with chronic manganese poisoning, including gener?al information, medical history, clinical manifestations, laboratory examination such as electrophysiological and imaging. Results Patients with chronic manganese poisoning mainly presented with mild mental disorder and autonomic nerve dis?order during early stage and then gradually developed extrapyramidal symptoms and signs. The laboratory examination of chronic manganese poisoning lacked of specificity. EMG showed neurogenic damage in 3 cases and normality in 1 case. EEG showed slightly increased full guide slow wave in 1 case and normality in 3 cases. cranial MRI revealed the damag?es in bilateral symmetry of the basal ganglia nuclei in 4 cases of Chronic manganese poisoning. There was no significant correlation between the changes of urinary manganese level before or after treatment and the clinical manifestations. Conclusions Although there is lack of specific clinical manifestations of chronic manganese poisoning, the possibility of this disease should be considered when patients with mild mental disorders or autonomic nerve disorder with or without extrapyramidal symptoms. The main treatment of chronic manganese poisoning includes excretion of manganese, symp?tomatic and supportive treatment. Patients usually have the sequelae of tremor, muscle tension, and other symptoms.

Objective:To explore the effect of P-glycoprotein ( P-gp) activity on its mediated imatinib mesylate accumulation and intracellular drug membrane permeability. Methods: 1199G/wt ABCB1 and 1199A/mut recombinant plasmids were transferred into HEK293 cells, respectively, and the expression levels of mRNA in different cell models were investigated by RT-PCR. Cell Counting Kit-8(CCK-8) assay was used to detect the drug toxicity in different cell models, HPLC was applied to determine the drug concentra-tion in different cell models and evaluate the intracellular accumulation, and transmembrane resistance experiment was employed to de-tect the transmembrane permeability and evaluate the effect of P-gp activity on drug transportation. Results: Cytotoxicity test showed that the drug concentration in the transferred cells was lower than that in the control group, which proved that P-gp had the function of mediating drug out of cells. HPLC and transepithelial electrical resistance experiment showed that compared with the wild type of AB-CB1 (1199G) cells, mutation of ABCB1 1199A cells had stronger effect on P-gp mediated mesylate imatinib accumulation and drug membrane permeability. Conclusion:The experiment manifested that ABCB1 (1199G/A) site mutation can change the coding protein P-gp activity and the polymorphisms will lead to the increase of mesylate imatinib clearance rate and the decrease of effective drug con-centration in target cells. Meanwhile, the clarification of ABCB1 genetic types in clinics can guide the individualized medication of imatinib mesylate.

Objective To investigate the relationship between clinical presentation and pathological characteristics in HBeAg negative chronic hepatitis B(CHB) patients with steatosis, and to find out the predictors of hepatic inflammation and fibrosis. Methods HgeAg negative CHB patients with (n=56) or without (n=60) steatosis confirmed clinically and pathologically were enrolled in the study. All patients were examined for fasting blood glucose(FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyhransferase (GGT), alkaline phosphatase (ALP) albumin (Alb), globulin(Glb), homeostatic model assessment of insulin resistance (HOMA-IR), HBV-DNA and body mass index(BMI). The association of above parameters with hepatic inflammation, fibrosis and fatty deposition were analyzed statistically. Results It was demonstrated that BMI, FBG, FINS, TG, TC, GGT, ALP , Glb and HOMA-IR were significantly higher in HBeAg negative CHB patients with steatosis than those without steatosis (P<0.05). Whereas the levels of HBV-DNA, Alb, ALT and AST were significantly lower in HBeAg negative CHB patients with steatosis compared with those without steatosis (P<0.05). The hepatic inflammation and fibrosis were aggravated in patients with steatosis. It was implicated that BMI,FBG, FINS, TG, TC, GGT and HOMA-IR(all P values 0.05) were significant predictors for hepatic steatosis, while ALT, AST, Glb and HBV-DNA(all P values <0.05) were significant predictors for hepatic inflammation. And the predictors for hepatic fibrosis were ALT, AST, Alb, Glb and HBV-DNA(all P values <0.05). Conclusions Hepatic steatosis is common in HBeAg negative CHB patients which is positively associated with parameters including BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. Besides steatosis, the hepatic inflammation and fibrosis are also aggravated in these patients.

Objective To prepare loratadine nanoparticle suspension and investigate the stability of it. Methods Loratadine nanoparticle suspension was prepared by anti-tumor agent precipitation method,the nanosuspension was characterized by particle size analyzer and transmission electron microscopy, the optimal prescription was screened, and the stability of nanosuspension was investigated by HPLC. Results The optimal prescription stablizer was SDS and organic phase was ethanol. The drug loading radio was 1:2 and the proportion of organic phase to water was 5:10 and the time of high shear was 5 min. Loratadine suspension was pale blue with a uniform emulsion.The nanoparticles were spherical,with an average particle size of 112.8 nm,the PDI of 0.095 and the Zeta potential of -38.6 mV.The suspension had the best physical and chemical stability at room temperature. Conclusion The preparation method of loratadine suspension with good stability is simple, and it’s expected to become the new nano-drug delivery system of loratadine.

[Objective] To summarize Dr. SHEN Yiping's clinical experience of integrated traditional Chinese and western medicine in treating elderly acute myeloid leukemia (AML). [Methods]By examining with cases of illness and warding round,collecting the medical records of elderly AML patients treated by Dr. SHEN, learning the latest diagnosis and treatment guidelines, reading a large number of related papers and a large number of classical books, from the aspects of etiology and pathogenesis, therapeutic principles and methods, the clinical experience of the treatment of elderly AML were analyzed and summarized, and one medical record was provided.[Results]Dr. SHEN believes that the pathogenesis is deficiency syndrome accompanied with excess syndrome. Mostly due to congenital deficiency and poor basic functions, deficiency of spleen and kidney, heat poison intrusion, burning Jin as sputum, forcing blood going in wrong line, phlegm and blood stasis, evil accumulating in bone marrow and then suffered. Dr. SHEN uses heat-clearing, detoxifying and anti-cancer drugs to suppress and eliminate leukemia cells on the basis of chemotherapy and supplements beneficial drugs to achieve the goal of chemotherapy without harming the positive effect, he uses "Kangbai Yannian Tang" combined with decitabine and chemotherapy as a basic solution and changes flexibly by according to the clinical manifestations, changes of syndrome types of the patients, the clinical effect is remarkable, and the case had good results. [Conclusion]Dr. SHEN is good at integrated traditional Chinese and western, combining of syndrome differentiation and disease differentiation, using the combination of heat-clearing method and complement in the treatment of elderly AML, the experience and wonderful methods are worth learning and spreading.

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Objective:To investigate the potential mechanism of microRNA (miRNA) in hepatitis B virus (HBV) infection.Methods:The peripheral blood samples were collected from four chronic hepatitis B (CHB) patients who visited Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017, and those were also collected from four healthy controls. Affymetrix GeneChip microRNA 4.0 was applied to detect the expressions of miRNA between CHB patients and healthy controls. The CHB relative differential expressions of miRNA were obtained. The functions of CHB relative miRNA were analyzed by the combination of bioinformatics tools and public database data.Results:A total of seven miRNA were differentially expressed in the peripheral blood of CHB patients. Among them, miRNA-122-5p (log 2 fold change (log 2FC)=7.78, P=0.007 3), let-7c-5p (log 2FC=3.52, P=0.019 6), miRNA-6794-5p (log 2FC=1.15, P=0.033 2), and miRNA-1226-5p (log 2FC=0.68, P=0.034 3) were up-regulated, while miRNA-619-5p (log 2FC=-1.83, P=0.002 6), miRNA-1273g-3p (log 2FC=-2.69, P=0.025 1), and miRNA-4440 (log 2FC=-3.99, P=0.047 8) were down-regulated. Further analysis showed that these miRNA could directly interact with HBV gene sequence and impact the replication of the virus. Among them, miRNA-122-5p, miRNA-6794-5p and miRNA-1226-5p could negatively regulate target genes expression to influence the formation of ficolin-1 rich granule, ficolin-1 rich granule lumen, podosome and membrane ruffle, which participated in the cell membrane movement and cell-matrix adhesion. Conclusion:MiRNA could impact the molecular movement in the cell membrane and facilitate HBV entry to liver cells, playing an important supporting role in HBV infection process.

Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine.Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months.The patients were observed for survival at month 1,3,6,12,and 24 after treatment.The baseline biochemical index,coagulant function,model for end-stage liver disease (MELD) score,HBV DNA level as well as comorbidities were analyzed in this study.The count data were compared with kappa test or Fisher's exact test.For the normal distributed measurement data,the homogeneity test of variances (Levene test) was firstly used for comparison between groups.Further,the group t test was applied for variance homogeneity,while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data.Results A total of 41 patients were enrolled,including 3 drop-outs and 38 accomplishments.Among these 38 patients,there were 3 females (7.9 ％) and 35 males (92.1％),with ages (38.5 ± 11.1) years.There were 32 patients alive and 6 dead during 1 month's follow-up,while baseline MELD score was the independent prognostic factor (RR=1.864,95％CI:1.151-3.019) for survival.There were 31 patients alive and 7 dead during 3 months' follow-up,while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR =2.053,95％CI:1.163-3.625;RR=394.939,95％CI:1.880-82 948.817).There were both 26 patients alive and 12 dead during 6 and 12 months' follow-up,while baseline MELD score was the independent prognostic factor (RR=1.761,95％ CI:1.230-2.523).At the end of 24 months' follow-up,there were 15 patients alive and 23 dead.Viral rebounds were observed in 6 patients and 3 of them were dead.Baseline HBV DNA level,MELD score and electrolyte imbalance were the independent prognostic factors (RR-9.722,95％ CI:1.607-58.821;RR=l.518,95％ CI:1.066-2.162;RR=87.505,95％ CI:2.263-3 384.232) for 24 months'survival.Conclusions Although telbivudine is not recommended as the first-line treatment,ACLF patients with low MELD score and low HBV DNA level at baseline,individualized treatment may improve patient's survival rate.UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient.

Objective To investigate the clinical features of Parkinson disease (PD)with constipation.Methods From October 2013 to August 2015,a total of 204 PD patients were consecutively recruited from the Departments of Geriatrics and Neurology,Beijing Tiantan Hospital,Capital Medical University,and were evaluated by Rome Ⅲ diagnostic criteria for functional constipation and other related scales of motor symptoms(MS)and non-motor symptoms(NMS),the activity of daily living(ADL)and quality of life.Results Overall,131 of 204(64.2％)PD patients with constipation were assigned to the PD-C group and 73 of 204 (35.8％)PD patients without constipation were assigned to the PD-NC group.In the PD-C group,38 of 131(29％)PD patients had constipation before motor symptoms occurred.The mean age and age of onset in the PD-C group were significantly older than those in the PD-NC group (64.13 ± 9.67 vs.58.35 ± 11.37;60.07 ± 10.46 vs.55.10±12.97;F=2.287,4.948;t=3.827,-2.788;P＜0.01 for both).Meanwhile,compared with the PD-NC group,the PD-C group was associated with dramatically longer disease duration (2.25,range:1.00-5.00 vs.2.00,range:1.00-3.13;Z =-2.254;P ＜ 0.05),increased scores of the Unified Parkinson Disease Rating Scale (UPDRS) Ⅲ (26.00 scores,range:18.00 37.50 vs.19.00,range:12.50-31.00;Z =-2.349,P ＜ 0.05),more advanced stages on the Hoehn-Yahr (H-Y) scale (2.00 stage,range:1.50-2.50 vs.1.50,range:1.00-2.50;Z=-2.334,P＜0.05),higher total numbers of NMS(11.00,range:6.00-15.00 vs.6.00,range:3.00-11.00;Z=-3.715,P＜0.05),and higher numbers of NMS occurring before and after MS(before,2.00,range:0.00-4.00 vs.1.00,range:0.00-2.00;after,8.00,range:3.00-14.00 vs.5.00,range:2.00-9.50;Z =-2.612,-2.630,respectively;P＜0.05 for both).Additionally,there were significant differences between the groups in the scores of the Hamilton depression scale (HAMD),the Hamilton anxiety scale (HAMA),the Pittsburgh sleep quality index (PSQI),the scales for outcomes in Parkinson disease-autonomic (SCOPA-AUT),the Fatigue severity scale (FSS),the Apathy scale,the Montreal Cognitive Assessment(MoCA)scale,the UPDRS Ⅱ and ADL Scale,and the PDQL-39 (all P＜0.05).Binary Logistic regression analysis showed that age,SCOPA-AUT,HAMA and HAMD were risk factors for PD-C(OR=1.091,1.107,1.10 and 1.080;P＜0.05 for all).Conclusions PD patients have a high incidence of constipation,and more than a quarter of patients have constipation before MS occurs.Meanwhile,PD patients with constipation are usually associated with old age and late age of onset,long disease duration,severe MS,frequent and severe NMS,bad cognition,emotional state and sleep,severe fatigue,and apathy.Moreover,advanced age,autonomic dysfunction,anxiety and depression increase the risk of PD with constipation.Constipation has a serious negative impact on the activity of daily living and quality of life in PD patients.