ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

The objective of this study was to optimise the extraction process of peptide of Poecilobdella manillensis by the Box-Behnken design-response surface methodology, and to investigate its whitening and anti-aging effects. Based on single factor experiments, NaCl solution concentration, extracting time and extracting times were taken as influencing factors, and peptide yield was used as the response value. The response surface model was designed and used to obtain the optimal extraction conditions of peptides of Poecilobdella manillensis: NaCl solution concentration of 4.3%, ultrasonic time of 4 h, and ultrasonic times of 2 times (2 + 2 h), which was significant and well-fitted to the actual experiment. The tyrosinase inhibition activity of peptide of Poecilobdella manillensis was evaluated by measuring the oxidation rate of levodopa (L-DOPA) catalyzed by tyrosinase. Moreover, using Caenorhabditis elegans as a model organism, the effects of peptide of Poecilobdella manillensis on body length, locomotion, reproductive capacity, reactive oxygen species (ROS), and lipofuscin levels were determined. The results showed that peptide of Poecilobdella manillensis exhibited a significant inhibitory effect on tyrosinase, with an IC₅₀ of 0.58 mg·mL^-1, which was stronger than that of the positive control arbutin (2.24 mg·mL^-1). Compared to the control group, 0.1, 0.5 and 1.0 mg·mL^-1 peptide of Poecilobdella manillensis showed no significant differences in the body length, eggs, and body bending of Caenorhabditis elegans. However, 0.5 mg·mL^-1 peptide of Poecilobdella manillensis significantly reduced ROS levels in Caenorhabditis elegans; 0.5 and 1.0 mg·mL^-1 peptide of Poecilobdella manillensis significantly reduced lipofuscin levels in Caenorhabditis elegans. Peptide of Poecilobdella manillensis exhibits effective whitening and anti-aging activities, potentially mediated by its inhibition of tyrosinase activity and antioxidant effects.

OBJECTIVE To study different extraction fractions of Agrimonia pilosa against h epatic fibrosis. METHODS Using hepatic stellate cells HSC-T 6 of rats as objects ，the effects of different extraction fractions （total extract ，ethyl acetate fraction ， petroleum ether fraction and n-butanol fraction ）with different concentrations （0.5，5，50，500，5 000 μg/mL，calculated by raw drug）of A. pilosa on the proliferation of HSC-T 6 cells were detected （after treated for 24，48，72 h）；median inhibition concentration（IC50）was also caculated. Platelet-derived growth factor （PDGF-BB）was used to induce the activation of HSC-T 6 cells to establish hepatic fibrosis cell model. Flow cytometry was used to detect the effects of different extraction fractions of A. pilosa on apoptosis of HSC-T 6 cells. The expression of collagen Ⅰ（Col-Ⅰ）in the supernatant was detected by enzyme linked immunosorbent assay. The expressions of α-smooth muscle actin （α-SMA），Col-Ⅰ，B-cell lymphoma- 2（Bcl-2），Bcl-2-associated X protein （Bax）and caspase- 3 were detected by Western blot assay. RESULTS Total extract ，ethyl acetate fraction ，petroleum ether fraction and n-butanol fraction of A. pilosa could significantly increase the apoptotic rate of HSC-T 6 cells（P＜0.01）. After treated for 24 h，IC50 of above fractions were 50.17，20.75，5.82，4.09 μg/mL，respectively. After intervened with PDGF-BB ，the expression of Col- Ⅰ in supernatant of HSC-T 6 cells as well as protein expression of Col- Ⅰ，α-SMA，Bcl-2，Bax and caspase- 3 in HSC-T6 cells were increased significantly （P＜0.01）. After intervened with different extraction fractions of A. pilosa ，most of the expressions of above proteins in HSC-T 6 cell culture supernatant or cells were significantly reversed compared with PDGF-BB group （P＜0.05 or P＜0.01）， and the intervention effect of n-butanol fraction of A. pilosa was the most significant. CONCLUSIONS Different extraction fractions of A. pilosa can inhibite the proliferation of HSC-T 6 cells and induce their apoptosis；n-butanol fraction from A. pilosa may be an effective fraction to exert the effect of anti-hepatic fibrosis.

Inflammation caused by chronic liver is primarily responsible for the occurrence and pathological progression of liver fibrosis. In the process of liver fibrosis, a large number of activated inflammatory signals promote the transformation of hepatic stellate cells (HSC) into myofibroblasts (MF), which eventually leads to the massive secretion and deposition of extracellular matrix (ECM) and the formation of scar tissue in the liver. To provide literature references for clinical diagnosis and treatment, this paper reviews the roles of HSC, Kupffer cells (KC), inflammasomes and inflammatory signaling in liver fibrosis.

Objective To study the clinical significance of globus pallidus signal intensity and the intensity ratio of globus pallidus and putamen (G/P ratio) on magnetic resonance T1WI for the early recognition of neonatal bilirubin encephalopathy.Method From January to December 2017,full-term neonates with hyperbilirubinemia admitted to the neonatology department of our hospital were enrolled in the case group,and full-term neonates without hyperbilirubinemia in the control group.The clinical data,globus pallidus T1WI signal intensity,G/P ratio and the follow-up data were collected.According to the level of hyperbilirubinemia,the neonates in the case group were further assigned into mild hyperbilirubinemia group (serum bilirubin:222 to ＜256 μmol/L),moderate hyperbilirubinemia group (serum bilirubin:256 to ＜342 μmol/L),and severe hyperbilirubinemia group (serum bilirubin:≥ 342 μmol/L).According to the injury score of ABE,the neonates with ABE were assigned into mild ABE group,moderate ABE group and severe ABE group.The correlation of globus pallidus T1WI and T2WI signal values,G/P ratio and the serum bilirubin level and ABE degree were analyzed;receiver operating characteristic (ROC) curve was drawn to explore the predictive value of the T1WI signal value and G/P ratio for the diagnosis of ABE;the changes of globus pallidus T1WI and T2WI signal values during the first 6 months after birth and the results of follow-up to 1 year after discharge were also analyzed.Result A total of 175 neonates were included in the case group (65 in the mild hyperbilirubinemia group,71 in the moderate hyperbilirubinemia group and 39 in the severe hyperbilirubinemia group) and 43 neonates in the control group.39 neonates were diagnosed as ABE (21 mild ABE,12 moderate ABE,and 6 severe ABE).The first T1WI signal value and G/P ratio of neonates in the severe hyperbilirubinemia group was higher than the moderate hyperbilirubinemia group,the mild hyperbilirubinemia group and the control group;the T1WI signal value and G/P ratio in the moderate hyperbilirubinemia group was higher than the mild hyperbilirubinemia group and the control group (P ＜ 0.05).No significant difference existed between the mild group and the control group(P ＞ 0.05).T2WI values showed no differences among neonates with different bilirubin levels (P ＞ 0.05).The first T1WI signal value and G/P ratio in the severe ABE group were significantly higher than the moderate and mild ABE group,and the moderate ABE group higher than the mild ABE group (P ＜ 0.05).The ROC curve indicated the optimal cut-off value of T1WI signal and G/P ratio were 628 and 1.38,respectively.Among all the 175 neonates,9 had a decrease in T1WI signal value and an increase in T2WI signal value at 6 months after birth.After 1 year of follow-up visits,7 children were finally diagnosed as chronic bilirubin encephalopathy.All these children had increased signal intensity on T1WI in the acute phase,plus a decreased T1WI signal and an increased T2WI signal in 1 ～ 6 months after birth.Conclusion The globus pallidus T1WI signal and G/P ratio are closely related to the serum bilirubin level and ABE severity.If T1WI signal value ＞ 628 or G/P value ＞ 1.38,ABE should be considered.The T1WI signal value and G/P ratio play important roles as indicators for the early recognition of neonatal bilirubin encephalopathy.

Objective To investigate the traditional Chinese medicine(TCM) syndromes distribution rule of nonalcoholic fatty liver disease(NAFLD) and its correlation with related clinical indexes.Methods The general condition,TCM four diagnostic methods,biochemical and CT results in 1950 cases of NAFLD in Chongqing City were investigated for analyzing the TCM syndromes distribution rule and its correlation with biochemistry and CT.Results In 1950 cases,the accumulation and binding of damp-heat,congestion of dampness turbidity,stagnation of liver-QI with spleen deficiency,intermin-gled phlegm and blood stasis and yin deficiency of both liver and kidney accounted for 36.62 ％,27.69 ％,19.38 ％,10.10 ％ and 6.21 ％ respectively;there was statistically significant difference in age among different TCM syndromes(P＜0.05);the vin deficiency syndrome of both liver and kidney and intermin-gled phlegm and blood stasis in severe fatty liver were maximal;glutamic-pyruvic transaminase(ALT) and glutamic-oxalacetic transaminase(AST) level was higher in the accumulation and binding of damp-heat;the level of fasting plasma gluco se(FBG) was higher in the yin deficiency syndrome of both liver and kidney;the total cholesterol(TC),triglyceride(TG) and FBG levels were lower in the stagnation of liver-QI with spleen deficiency,the differences were statistically significant(P＜0.05).Conclusion In NAFLD patients,the accumulation and binding of damp-heat distribution is maximal,the proportion of severe fatty liver with vin deficiency syndrome of both liver and kidney is higher.Different dialectical types may play an important role in the clinical indexes and disease development.

Interleukin-17 (IL-17) is a proinflammatory factor produced by T helper 17 cells and can induce a variety of chemokines which participate in the body's immunoregulation and inflammatory response.IL-17 can activate various liver cells to produce inflammatory mediators and secrete proinflammatory factors and thus regulate liver inflammation.IL-17 is upregulated in many liver diseases,such as virus hepatitis,fatty liver disease,autoimmune liver diseases,and parasite infection in the liver,and it can promote the development and progression of liver cirrhosis and liver cancer and is associated with liver failure and rejection reaction in liver transplantation.This article reviews the research advances in the role of IL-17 in liver diseases.

Objective To determine the relationship between the viral load of cerebrospinal fluid (CSF) and sensorineural hearing loss (SNHL) in newborns with symptomatic congenital cytomegalovirus (CMV) infection.Methods The study cohort comprised 36 newborns with symptomatic congenital CMV infection.CSF from all of the patients were analyzed for the presence of CMV DNA by PCR.Audiological function were performed on them by brain stem auditory evoked potential at birth,at 6 and 12 months of age.Results (1)Of the 36 newborns,15 cases (41.7％) had positive CSF PCR result,17 cases (47.2％) had SNHL.(2) The prevalence of SNHL in the group of newborns with positive CSF PCR result was 60.0％ (9/15),and it was 38.1％ (8/21) in the group of newborns with negative CSF PCR result,there was no significant difference of the prevalence of SNHL between the two groups (P =0.194).(3) In newborns with positive CSF PCR result,the amounts of CSF CMV DNA was not different between the newborns with SNHL and normal hearing (3.35 ± 0.68 vs.3.17 ± 0.56,P =0.36).Conclusion A positive CSF PCR result and the CMV viral load of CSF did not correlate with SNHL.

Objective To investigate the clinical effect of traditional Chinese medicine(TCM)for treating HBeAg positive chron-ic hepatitis B virus(HBV)carriers with liver stagnation and spleen deficiency syndrome.Methods The patients with HBeAg and HBV DNA positive,normal serum ALT and AST for successive 3 times within 1-year follow up,complicating different degrees of symptoms were included.Among them,the patients with liver stagnation and spleen deficiency syndrome according to the TCM dif-ferentiation were selected as the treatment obj ects and treated by the prescription of soothing the liver,tonifying spleen and detoxifi-cation.The changes of clinical symptoms and HBV markers after 6-month therapy were observed and followed up for 3 months for evaluating the effect persistance.348 cases were recruited,161 cases in the control group and the other 187 cases in the treatment group.Treatment group underwent traditional Chinese medicine treatment.Results 168 cases finished the therapy with the total effective rate of 80.3%(135/168),6 cases were HBeAg negative conversion and 14 cases were HBV DNA decrease greater than or equal to 2 logarithmic grades;157 patients finished 3-month follow-up and the effective rate was 80.9%(127/157),4 cases were HBeAg negative conversion and 1 1 cases were HBV DNA decrease greater than or equal to 2 logarithmic grades.The curative effect of treatment group was higher than that of control group.Conclusion The TCM prescription of soothing the liver,tonifying spleen and detoxification has definite effect for treating HBeAg positive chronic HBV carriers with liver stagnation and spleen deficiency syndrome,the symptoms can be significantly improved.