No abstract available.
*Alanine Transaminase ; Antiviral Agents/therapeutic use ; Humans ; *Liver Cirrhosis

OBJECTIVE: To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages. METHODS: In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group. RESULTS: In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P < 0.05). CONCLUSION Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.
Alanine/therapeutic use* ; Alanine Transaminase/therapeutic use* ; Antiviral Agents/therapeutic use* ; DNA, Viral/therapeutic use* ; Hepatitis B/drug therapy* ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; T-Lymphocytes, Regulatory

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.
Abietanes/therapeutic use* ; Acetaminophen/therapeutic use* ; Alanine Transaminase/metabolism* ; Animals ; Antipyretics/therapeutic use* ; Aspartate Aminotransferases/metabolism* ; Benzofurans/therapeutic use* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Depsides/therapeutic use* ; Emulsions ; Glycyrrhetinic Acid/therapeutic use* ; Liver/drug effects* ; Malondialdehyde ; Mice

OBJECTIVETo determine the effect of dipeptide of glutamine and alanine on patients with severe traumatic brain injury.

METHODSA total of 46 patients (31 males and 15 females, aged 7-68 years, (47+/-9.6) years on average) with severe traumatic brain injury were randomized into two groups: Group G (n=23) and Group C (n=23). The patients in Group G received nutritional remedy with the dipeptide of glutamine and alanine, whereas the patients in Group C received routine nutritional therapy only. GCS changes, the length of stay in the neurosurgical intensive care unit (NICU), the mortality,the count of lymphocytes, related complications including lung infection and hemorrhage of alimentary tracts, etc, were examined and recorded.

RESULTSThe fatality rate and the length of stay in NICU in Group G was lower than these in Group C (P larger than 0.05), but no obvious difference was found in GCS changes of the patients between the two groups (P larger than 0.05). The patients with lung infection and alimentary tract hemorrhage in Group G were less than those in Group C (P larger than 0.05). The count of lymphocytes in Group G was more than that in Group C (P larger than 0.05), but no difference was found in other nutritional data.

CONCLUSIONSDipeptide of glutamine and alanine can increase the resisting stress and anti-infection ability of patients with severe traumatic brain injury, which can also lower the mortality and shorten the NICU stay.

Adolescent ; Adult ; Aged ; Alanine ; therapeutic use ; Brain Injuries ; drug therapy ; Child ; Dipeptides ; therapeutic use ; Female ; Glutamine ; therapeutic use ; Humans ; Male ; Middle Aged

No abstract available.
Alanine Transaminase/*blood ; Antiviral Agents/*therapeutic use ; Female ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*therapeutic use ; Male ; Polyethylene Glycols/*therapeutic use ; Recombinant Proteins/therapeutic use ; Ribavirin/*therapeutic use

OBJECTIVETo evaluate the efficacy and safety of 4 treatment options for HBeAg-positive chronic hepatitis B (CHB) patients following a suboptimal response to 24-week interferon monotherapy.

METHODSThe data of 193 HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy were collected from Nanfang Hospital between September, 2010 and January, 2013. According to the subsequent treatments, the patients were divided into group A with additional entecavir or adefovir, group B with further interferon monotherapy, group C with conversion to NAs therapy, and group D with direct therapy withdrawal, and the biochemical and virological results at weeks 24, 48 and 72 were analyzed in the 4 groups.

RESULTSAt week 48, the HBV DNA negative rates and serum alanine aminotransferase (ALT) normalization rates were both significantly higher in group A and C than in group B (P<0.05); in group A, ETV therapy subgroup had a significantly higher HBV DNA negative rate than ADV therapy subgroup at week 48 (90.3% vs 59.5%, Χ=8.255, P=0.004). At week 72, 39.7%(27/68) of the patients in group A achieved HBeAg seroconversion, a rate significantly higher than those in groups B (Χ=4.238, P=0.040) and C (Χ=7.681, P=0.006); the HBV DNA negative rate and ALT normalization rate in group A were 85.3%(58/68) and 86.8%(59/68), respectively, both significantly higher than those in group B (Χ=23.018, P<0.001; Χ=5.987, P=0.014) but comparable to those in group C (P>0.05). In the two subgroups in group A, the HBV DNA negative rate and HBeAg seroconversion rate were both significantly higher in ETV subgroup (Χ=9.823, P=0.002; Χ=5.450, P=0.020). In group D, all the patients remained HBeAg-positive with abnormal ALT levels and high level of HBV DNA.

CONCLUSIONFor HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy, combined treatment with NAs (especially ETV) and extension of the treatment course can significantly improve the HBeAg seroconversion rates, HBV DNA negative rates, and ALT normalization rates.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Drug Therapy, Combination ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferons ; therapeutic use ; Organophosphonates ; therapeutic use

Ultra-high-performance liquid chromatography-Q exactive orbitrap tandem mass spectrometry(UHPLC-QEOrbitrap-MS/MS) was used to explore the inhibitory effect and mechanism of ginkgo flavone aglycone(GA) combined with doxorubicin(DOX) on H22 cells. The effects of different concentrations of GA and DOX on the viability of H22 cells were investigated, and combination index(CI) was used to evaluate the effects. In the experiments, control(CON) group, DOX group, GA group, and combined GA and DOX(GDOX) group were constructed. Then the metabolomics strategy was employed to explore the metabolic markers that were significantly changed after combination therapy on the basis of single medication treatment, and by analyzing their biological significance, the effect and mechanism of the anti-tumor effect of GA combined with DOX were explained. The results revealed that when 30 μg·mL~(-1) GA and 0.5 μmol·L~(-1) DOX was determined as the co-administration concentration, the CI value was 0.808, indicating that the combination of GA and DOX had a synergistic anti-tumor effect. Metabolomics analysis identified 23 metabolic markers, including L-arginine, L-tyrosine and L-valine, mostly amino acids. Compared with the CON group, 22 and 17 metabolic markers were significantly down-regulated after DOX treatment and GA treatment, respectively. Compared with the DOX and GA groups, the treatment of GA combined with DOX further down-regulated the levels of these metabolic markers in liver cancer, which might contribute to the synergistic effect of the two. Five key metabolic pathways were found in pathway enrichment analysis, including glutathione metabolism, phenylalanine metabolism, arginine and proline metabolism, β-alanine metabolism, and valine, leucine and isoleucine degradation. These findings demonstrated that the combination of GA and DOX remarkably inhibited the viability of H22 cells and exerted a synergistic anti-tumor effect. The mechanism might be related to the influence of the energy supply of tumor cells by interfering with the metabolism of various amino acids.
Arginine/therapeutic use* ; Doxorubicin/therapeutic use* ; Flavones/therapeutic use* ; Ginkgo biloba/chemistry* ; Glutathione ; Humans ; Isoleucine/therapeutic use* ; Leucine/therapeutic use* ; Liver Neoplasms/drug therapy* ; Metabolomics/methods* ; Phenylalanine/therapeutic use* ; Proline ; Tandem Mass Spectrometry/methods* ; Tyrosine/therapeutic use* ; Valine/therapeutic use* ; beta-Alanine/therapeutic use*

The wide use of lamivudine in chronic hepatitis B has produced a monotonic increase in patients with lamivudine resistance. Therefore, treating lamivudine resistance in chronic hepatitis B is a major concern in clinical practice for the treatment of hepatitis B virus (HBV). There is conflicting evidence on the outcome of pegylated interferon alpha (PEG-IFN alpha) therapy against lamivudine-resistant HBV, which is due to mutations in the YMDD motif. We experienced a patient with chronic hepatitis B who was successfully treated with PEG-IFN alpha-2a after the development of virologic and biochemical breakthrough during lamivudine therapy. Virologic breakthrough was associated with the emergence of YMDD mutants 48 months after starting lamivudine therapy. Treatment with PEG-IFN alpha-2a for 12 months resulted in an undetectable serum level of HBV DNA and the resolution of hepatitis, and the virologic response was maintained over 16 months after cessation of PEG-IFN alpha-2a.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis ; Drug Resistance, Viral ; Hepatitis B, Chronic/diagnosis/*drug therapy ; Humans ; Interferon Alfa-2a/*therapeutic use ; Lamivudine/*therapeutic use ; Liver/pathology ; Male ; Polyethylene Glycols/*therapeutic use

OBJECTIVETo observe the therapeutic effects of Pegasys (pegylated interferon alpha-2a) in chronic hepatitis B (CHB) patients with low-level alanine transaminase (ALT) < 2 x upper limit of normal (ULN).

METHODSOne hundred and seven CHB patients were randomized enrolled including 52 with ALT < 2 x ULN and liver tissues inflammation activity > or = G2 as observational group and 55 with ALT > 2 x ULN as control group. All the enrolled patients received pegasys treatment for 48 weeks and the responses between two groups were compared. Measurement data were analyzed using t test and numeration data were analyzed using chi square test.

RESULTSThe reductions of HBV DNA in observational group at different time points were all less than control group (all P < 0.05). At the end of treatment, the HBV DNA negative rate, HBeAg seroconversion rate and HBsAg loss rate in the observational group were 51.9%, 48.8% and 1.9% , respectively, which were all lower than control group (67.3% , 66.7% and 7. 3% , respectivley) ( all P <0. 05). The ALT normalization rates of two groups were 75% and 76.4% (P > 0. 05).

CONCLUSIONPegasys is efficient for CHB patients with ALT < 2 x ULN and liver tissues inflammation activity > or = G2, while it is still inferior to those with ALT > 2 x ULN.

Adolescent ; Adult ; Alanine Transaminase ; metabolism ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B, Chronic ; drug therapy ; enzymology ; physiopathology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use

UNLABELLEDOBJECTIVE To observe the clinical efficacy by Qingying Huoxue Decoction (QHD) combined ursodeoxycholic acid (UDCA) in treating patients with early and mid-term primary biliary cirrhosis (PBC). METHODS Totally 78 patients were randomly assigned to the treatment group and the control group, 39 in each group. All patients received basic treatment and took UDCA (at the daily dose of 13-15 mg/kg). Patients in the treatment group took QHD, one dose per day. The treatment course for all was 6 weeks. Clinical efficacy, gamma-glutamyl transferase (γ-GGT), alkaline phospatase (ALP), TBIL, alanine aminotransferase (ALT), and aspartate transaminase (AST) were observed before and after treatment. RESULTS Totally 21 (53. 8%) patients obtained complete response in the treatment group, with statistical difference when compared with that of the control group (11 cases, 30. 8%). Levels of GGT, ALP, ALT, AST, and TBIL decreased in the two groups after treatment (P < 0.01). Levels of ALP, GGT, and TBIL were obviously lower in the treatment group than in the control group (P < 0.05).

CONCLUSIONSQHD combined UDCA in treating early and mid-term PBC patients was superior to the effect of using UDCA alone. It also could improve patients' liver function.

Alanine Transaminase ; metabolism ; Aspartate Aminotransferases ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Cirrhosis, Biliary ; drug therapy ; Ursodeoxycholic Acid ; therapeutic use ; gamma-Glutamyltransferase ; metabolism