Background and Aims:Patients with end-stage liver disease(ESLD)frequently experience persistent pruritus,which significantly impairs their quality of life.Although relief of pruritus after liver transplantation is often attributed to the normalization of bilirubin levels,the role of skin microbiota in developing pruritus remains unclear.This study aimed to investigate the dynamic changes in skin microbiota during the perioperative period of liver transplantation in ESLD patients and to explore their association with pruritic symptoms.Methods:Fifteen ESLD patients treated in the Third Xiangya Hospital between 2022 and 2023 were enrolled and skin swabs were collected from the anterior tibial region at three time points:before liver transplantation and on postoperative days 7 and 30.Skin samples from 15 age-matched healthy controls were collected at the same anatomical site.Microbial composition was analyzed using 16S rRNA sequencing.Meanwhile,pruritus severity was assessed using a visual analogue scale(VAS),and multiple serological indicators were measured to evaluate correlations between microbiota changes,pruritus severity,and liver function parameters.Results:Compared with healthy controls,ESLD patients exhibited significantly altered β-diversity in skin microbiota and an increased relative abundance of Staphylococcus(LDA>4),which was strongly correlated with VAS scores for pruritus(r=0.93,Padj=3.08×10?1?).On postoperative day 7,α-diversity decreased,and Staphylococcus abundance peaked,then gradually normalized by day 30 as pruritus improved.Further analysis revealed that Staphylococcus abundance was positively correlated with alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,total bile acids,and international normalized ratio,and negatively correlated with albumin(all Padj<0.05).Notably,Staphylococcus levels were significantly higher in patients with moderate to severe pruritus(VAS score>5).Conclusion:ESLD patients demonstrate marked dysbiosis of the skin microbiota during the perioperative period of liver transplantation,characterized by an abnormal proliferation of Staphylococcus,which may contribute to the development and exacerbation of pruritus.Targeting the skin microbiome,particularly interventions against Staphylococcus,may offer a novel therapeutic strategy for alleviating pruritus in ESLD patients.

Background and Aims:Patients with end-stage liver disease(ESLD)frequently experience persistent pruritus,which significantly impairs their quality of life.Although relief of pruritus after liver transplantation is often attributed to the normalization of bilirubin levels,the role of skin microbiota in developing pruritus remains unclear.This study aimed to investigate the dynamic changes in skin microbiota during the perioperative period of liver transplantation in ESLD patients and to explore their association with pruritic symptoms.Methods:Fifteen ESLD patients treated in the Third Xiangya Hospital between 2022 and 2023 were enrolled and skin swabs were collected from the anterior tibial region at three time points:before liver transplantation and on postoperative days 7 and 30.Skin samples from 15 age-matched healthy controls were collected at the same anatomical site.Microbial composition was analyzed using 16S rRNA sequencing.Meanwhile,pruritus severity was assessed using a visual analogue scale(VAS),and multiple serological indicators were measured to evaluate correlations between microbiota changes,pruritus severity,and liver function parameters.Results:Compared with healthy controls,ESLD patients exhibited significantly altered β-diversity in skin microbiota and an increased relative abundance of Staphylococcus(LDA>4),which was strongly correlated with VAS scores for pruritus(r=0.93,Padj=3.08×10?1?).On postoperative day 7,α-diversity decreased,and Staphylococcus abundance peaked,then gradually normalized by day 30 as pruritus improved.Further analysis revealed that Staphylococcus abundance was positively correlated with alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,total bile acids,and international normalized ratio,and negatively correlated with albumin(all Padj<0.05).Notably,Staphylococcus levels were significantly higher in patients with moderate to severe pruritus(VAS score>5).Conclusion:ESLD patients demonstrate marked dysbiosis of the skin microbiota during the perioperative period of liver transplantation,characterized by an abnormal proliferation of Staphylococcus,which may contribute to the development and exacerbation of pruritus.Targeting the skin microbiome,particularly interventions against Staphylococcus,may offer a novel therapeutic strategy for alleviating pruritus in ESLD patients.

OBJECTIVE: To observe the effects of Qingdan Capsule (QDC) and Yanggan Lidan Granule (YGLDG), two kinds of compound traditional Chinese herbal medicines, on biochemical parameters in guinea-pigs with pigment gallstones. METHODS: An animal model of pigment gallstones was established in male guinea-pigs by hypodermic injection of lincomycin. The guinea-pigs were randomly divided into blank control group, untreated group, QDC group and YGLDG group. There were 8 guinea-pigs in each group. After ten-day treatment, animals were sacrificed and sampled to calculate the rate of stone formation, total bilirubin (TB), unconjugated bilirubin (UCB) and Ca2+ density in bile of the four groups. RESULTS: In comparison with the untreated group, the rates of stone formation in the QDC and YGLDG groups were significantly decreased (P<0.01). TBIL, UCB and Ca2+ content of bile in both QDC and YGLD groups was also significantly decreased (P<0.05, P<0.01). CONCLUSION: QDC and YGLD have good effects on biochemical changes of animal model of pigment gallstone in reversing the lithogenesity of bile by reducing the content of TB, UCB and Ca2+, hence resulting in clinical treatment and prevention of pigment gallstone disease.

OBJECTIVE: To evaluate the efficacy and safety of Danning Tablet (DNT) in patients with non-alcoholic fatty liver disease (NAFLD) of damp-heat syndrome type. METHODS: A multicenter, randomized, double-blinded and positive drug parallel controlled trial was performed. One hundred and thirty-five patients were enrolled into the study and divided into two groups: DNT-treated group (n=102) and ursodeoxycholic acid (UDCA)-treated group (n=33). Body mass index (BMI), principal symptoms, liver function, blood lipids, iconographic, and compositional parameters were measured before and after treatment, respectively. RESULTS: In the two groups, BMI, distress in hepatic region, fatigue, anorexia, liver function, blood lipids and iconographic parameters were significantly improved, and the improvements of BMI, distress in hepatic region were better in DNT-treated group than in UDCA-treated group. The histological study also showed that DNT had positive effect in treatment of NAFLD. CONCLUSION: DNT is an effective drug to treat patients with NAFLD of damp-heat syndrome type and is more effective than UDCA.

OBJECTIVE: To study the changes of the center of cellular immune thymus and the interference of Jinhong Tablet, a compound traditional Chinese herbal medicine, during the course of cholangitis. METHODS: Twenty-four male Wistar rats were randomly divided into three groups. Ligation group, simple ligation of bile duct without producing infection and fed with normal saline; untreated group, reproduce acute cholangitis and fed with normal saline; Jinhong Tablet-treated group, reproduce cholangitis and treated with Jinhong Tablet. Five days after modeling, the rats were sacrificed and the thymus were sampled to observe the morphological changes with an electronic microscope, count the index of thymus and apoptosis and assay the expressions of Bcl-2 gene coding protein and Fas gene coding protein. RESULTS: The frequency of apoptosis of thymus in the untreated group was higher than that in the Jinhong Tablet-treated group and the ligation group, and the frequency of apoptosis of thymus in the Jinhong Tablet-treated group was higher than that in the ligation group. Compared with the Jinhong Tablet-treated group and the ligation group, the weight and index of thymus were lower and the index of apoptosis of thymus was higher significantly in the untreated group (P<0.01). The expression of Bcl-2 gene coding protein in the ligation group and the Jinhong Tablet-treated group were much higher than that in the untreated group (P<0.01), but there were no significant differences of the expression of Fas gene coding protein among the three groups. CONCLUSION: There exists a promotion of non-physiological apoptosis of cellular immune center such as decrease of the weight and the index of thymus and increase of the index of apoptosis of thymus during acute cholangitis, which may be inhibited by up-regulation of Bcl-2 gene coding protein with antipyretic and purgative herbs Jinhong Tablet.

OBJECTIVE: To observe the changes of intracellular free calcium level ([Ca(2+)]i) in gallbladder cells of guinea pigs with gallstones so as to study the mechanisms of gallstone formation and the prevention and treatment function of traditional Chinese herbs for nourishing the liver. METHODS: Eighty guinea pigs were randomly divided into four groups, which were normal control group, untreated group, nourishing-liver Chinese drug (NLCD) group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group. Gallstones were induced in the guinea pigs of the latter 3 groups by the feed of diet inducing cholelithiasis with high cholesterol, while the corresponding medicines were used in NLCD group and UDCA group for prevention and treatment for 7 weeks. Then the state of the guinea pigs, the formation of gallstones, and the changes of [Ca(2+)]i in gallbladder cells were observed. RESULTS: The [Ca(2+)]i in gallbladder cells of guinea pigs in the untreated group was decreased significantly. NLCD improved the behavioral signs of the guinea pigs, significantly decreased the formative rate of gallstones and increased the [Ca(2+)]i in gallbladder cells. CONCLUSIONS: The [Ca(2+)]i in gallbladder cells is the important factor for contractile function of gallbladder and the information of gallstones. Traditional Chinese herbs for nourishing the liver may significantly increase the [Ca(2+)]i in gallbladder cells to facilitate contraction of the smooth muscle cells of gallbladder and relieve the cholestatis. It may be one of the mechanisms of traditional Chinese herbs for nourishing the liver in preventing and treating cholelithiasis.

OBJECTIVE: To study the mechanisms of Shengqing Capsules, a compound Chinese herbal medicine for dispersing stagnated liver qi and promoting bile flow, in prevention and treatment of pigment gallstone. METHODS: Liver cells from guinea pigs with pigment gallstone were primarily cultured in vitro. The serums containing different concentrations of Shengqing Capsules were prepared by serum pharmacological method. The primary cultured hepatocytes with excessive expression of nuclear factor-kappaB (NF-kappaB) were stimulated with lipopolysaccharides (LPS) and the effects of the drug-containing serums on the NF-kappaB expression were detected by Western-blotting. RESULTS: Shengqing Capsules down-regulated the NF-kappaB expression increased by LPS stimulation. The effect is dose-dependent. CONCLUSION: Shengqing Capsules can down-regulate the NF-kappaB expression increased by LPS stimulation. It may be one of the important mechanisms of this Chinese herbal medicine in prevention and treatment for pigment gallstone formation and the inflammatory reaction in biliary tract.

OBJECTIVE: To explore the mechanism of the inhibiting effects of recipe for dispersing stagnated liver qi to promote bile flow (Danshijing Tablets) on cholesterol gallstone formation and provide experimental evidence for its clinical application. METHODS: Eighty guinea pigs were randomly divided into 4 groups, which were normal control group, untreated group, ursodeoxycholic acid (UDCA)-treated group and Danshijing Tablets-treated group. The gallstones in guinea pigs were induced by high-cholesterol diet. UDCA and Danshijing Tablets were given orally to guinea pigs in the corresponding group respectively for seven weeks. Then the physical signs of the guinea pigs, the rates of gallstone formation and the histomorphological changes of the gallbladder were examined. RESULTS: The behavior of guinea pigs in the Danshijing Tablets-treated group was obviously improved and the rate of gallstone formation was significantly decreased as compared with those in both untreated and UDCA-treated groups (P<0.05). The inflammation reaction of mucous membrane in gallbladder was evidently reduced in the Danshijing Tablets-treated group and its morphological appearance turned to be approximately normal. CONCLUSION: Recipe for dispersing stagnated liver qi to promote bile flow may decrease gallstone formation. Its mechanism may be related to reducing pathologic changes in gallbladder tissues, which will reduce the damages of cholesterol to the smooth muscle in gallbladder and enhance the contractility of gallbladder.

OBJECTIVE: To observe the protective effects of Yanggan Lidan Granules (YGLDG) on carbon tetrachloride (CCl(4))-induced liver damage in mice and to find out its mechanism. METHODS: A model of chronic liver damage was established in mice by intraperitoneal injection of CCl(4). After three weeks, those model mice were treated with low-, medium-, high-dose YGLDG, Danning Tablets and bifendate respectively for four weeks. Then the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissues were detected. RESULTS: YGLDG could significantly reduce the levels of serum ALT and AST in model mice, and the content of MDA was obviously decreased while the content of SOD was increased in liver tissue. CONCLUSION: The therapeutic effect of YGLDG on mice with CCl(4)-induced liver damage is to relieve the seriousness of liver damage, and its mechanism may relate to reducing peroxidation activity in liver tissue.

OBJECTIVE: To explore the molecular mechanisms of Shengqing Capsules in treating cholelithiasis. METHODS: Sixty female guinea pigs were randomized into 3 groups: group I (fed with normal diet), group II (fed with low-protein diet) and group III (fed with low-protein diet and Shengqing Capsules). After six-week feeding, the gallstone formation and the expressions of bilirubin UDP-glucuronosyltransferase (B-UGT) mRNA and cholesterol 7alpha-hydroxylase (CYP7A1) mRNA were observed. RESULTS: The proportions of stone-formed in groups I, II and III were 2/14, 9/12 and 4/14, respectively. There were significant differences among the three groups (P<0.05). The expressions of B-UGT and CYP7A1 mRNAs were higher in both group I and group III as compared with those in the group II (P<0.05). CONCLUSION: Shengqing Capsules can reduce the rate of stone-formation, which may be due to its interference of metabolism of bilirubin and cholesterol and up-regulation of the expressions of B-UGT and CYP7A1 mRNAs.