Objective To investigate the risk factors for short-term prognosis in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods A retrospective analysis was performed for the clinical data of 119 patients with HBV-related ACLF who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2019 to October 2020, and according to their survival status on day 90, they were divided into death group and survival group. The patients were given antiviral therapy with entecavir or tenofovir. Related clinical data were collected, including alanine aminotransferase (ALT), aspartate aminotransferase, cholinesterase (ChE), albumin (Alb), cholesterol, alpha-fetoprotein, and HBV DNA at baseline, as well as the incidence rate of important complications. Model for End-Stage Liver Disease (MELD) score was also calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-squared test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for the 90-day prognosis of patients with HBV-related ACLF and establish a new predictive model; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the new model in predicting the prognosis of HBV-related ACLF. Results Of all patients, 33 died within 90 days, resulting in a mortality rate of 27.7%. There were significant differences between the survival group and the death group in age, ALT, Alb, ChE, MELD score, and incidence rates of hepatic encephalopathy, primary peritonitis, and hepatorenal syndrome (all P < 0.05). The logistic regression analysis showed that baseline hepatic encephalopathy (odds ratio [ OR ]=10.404, 95% confidence interval [ CI ]: 2.522-42.926, P =0.001), serum Alb at baseline ( OR =0.853, 95% CI : 0.764-0.952, P =0.005), and MELD score at baseline ( OR =1.143, 95% CI : 1.036-1.261, P =0.008) were independent predictive factors for the short-term prognosis of patients with HBV-related ACLF. A new predictive model was established based on the combination of these three indices, and the ROC curve analysis showed that this new model had an area under the curve of 0.833, while MELD score had an area under the ROC curve of 0.672. Conclusion As for the evaluation of the 90-day prognosis of patients with HBV-related ACLF, the new prognostic model established based on hepatic encephalopathy, Alb, and MELD score has a better predictive value than MELD score alone.

Objective:To investigate and analyze the energy metabolism characteristics and the correlation between energy metabolism and the risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease (HBV-CLD).Methods:Data of 183 cases admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2020 were retrospectively analyzed. 79 cases of chronic hepatitis B, 51 cases of hepatitis B-related liver cirrhosis, and 53 cases of hepatitis B-related liver failure were collected. Among them patients with liver failure and decompensated liver cirrhosis were defined as severe liver disease group. The Quark RMR indirect calorimetry (COSMED Corporation, Italy) was used to exam the patients' energy metabolism condition, and the incidences of secondary bacterial infection of the patients during hospitalization were recorded. Shapiro-Wilk test and normal QQ plot were used to analyze the normal distribution of continuous variable data, which was consistent with the normal distribution and was described by mean ± standard deviation. In addition, if it did not conform to the normal distribution, the median and interquartile distance were used to describe it. Levene’s test was used to test the homogeneity of variance of the data, which was consistent with the normal distribution. The t-test was used to compare the means of the two groups of samples. One-way analysis of variance was used to compare the mean values of the three groups of samples, and then the Tukey's test was used to compare the two groups. If the variance was uneven or did not conform to the normal distribution, the Wilcoxon rank sum test was used to compare the differences between the two groups. Kruskal-Wallis test (H test) was used to compare the differences between the three groups of samples, and then the Dunnett’s test (Z test) was used for comparison between the two groups. Categorical variable data were analyzed using chi-square test. Logistic regression analysis was used to screen independent risk factors, and the criteria for variable inclusion ( P < 0.05). Results:The respiratory entropy (RQ) and non-protein respiratory entropy (npRQ) of the three groups had statistically significant difference ( P < 0.05). Among them, the RQ and npRQ of the chronic hepatitis B group were higher than hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group. There were statistically significant differences in fat oxidation rate (FAT%) and carbohydrate oxidation rate (CHO%) between the three groups ( P < 0.05). Compared with hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group, chronic hepatitis B group ( P < 0.05) had lower FAT% and higher CHO%. There were no statistically significant differences in the measured and predicted resting energy expenditure and protein oxidation rate (PRO%) between the three groups. The incidence of secondary bacterial infection in patients with severe liver disease was 48.39% (45/93). Compared with the non-infected group, the RQ and npRQ values ??of the infected group were significantly decreased ( P < 0.05), while FAT% was significantly increased ( P < 0.05). Logistic regression analysis showed that glutamyltransferase, cholesterol, and npRQ were independent risk factors for secondary bacterial infections in patients with severe liver disease. Glutamyltransferase elevation, and cholesterol and npRQ depletion had suggested an increased risk of secondary bacterial infection. Subgroup analysis of patients with hepatitis B-related liver failure also showed that compared with non-infected group, RQ value and npRQ value of secondary bacterial infection group were significantly decreased ( P < 0.05), while FAT% was significantly increased ( P < 0.05). Conclusion:Patients with hepatitis B virus-related chronic liver disease generally have abnormal energy metabolism. Low RQ, npRQ, CHO% and high FAT% are related to the severity of the disease; while npRQ reduction is related to the risk of secondary bacterial infection in patients with severe liver disease, and thus can be used as a clinical prognostic indicator.

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 evaluate the current status of knowledge and behavior in breast milk collection and storage among nurses in the Neonatal Intensive Care Unit (NICU) , and to explore the factors influencing knowledge and behavior of nurses.Methods:By adopting the convenient sampling method, a total of 175 NICU nurses from ClassⅢ Grade A hospitals in Henan province were selected as the research objects in April 2019. A cross-sectional survey of NICU nurses was conducted using the knowledge and behavior questionnaire on breast milk collection and storage of NICU nurses. A total of 175 questionnaires were issued and 175 were recovered, with a recovery rate of 100%.Results:The total score of knowledge and behavior standards of breast milk collection and storage of 175 NICU nurses was (59.69±8.24) , which was at a low level. Among which, the score of knowledge dimension standard was (43.11±9.74) , and the score of behavior dimension standard was (33.58±5.14) . 85.1% (149/175) NICU nurses had not received special training in breast milk collection and storage, and there were great individual differences in the perception of the working environment of breast milk collection and storage among NICU nurses. The results of multivariate analysis showed that age, working environmentperception score of breast milk collection and storage and training of breast milk collection and storage were the main influencing factors of breast milk collection and storage knowledge behavior of NICU nurses ( P<0.05) . Conclusions:The knowledge and behavior of NICU nurses in breast milk collection and storage need to be improved, especially in breast milk thawing, storage temperature and other issues. Nursing managers should formulate objective and unified breast milk collection and storage systems and procedures and strengthen relevant training for nurses to improve nurses' perception of the working environment of breast milk collection and storage, strengthen relevant knowledge and improve breast milk collection and storage behavior.

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.

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.

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 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 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.