Buyang Huanwu Decoction Ameliorates Damage of Erectile Tissue and Function Following Bilateral Cavernous Nerve Injury / 中国结合医学杂志

OBJECTIVE@#To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP).@*METHODS@#The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining.@*RESULTS@#The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01).@*CONCLUSIONS@#BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.

A preliminary study of the role of neutrophil extracellular traps in patients with primary biliary cholangitis / 临床肝胆病杂志

Objective To investigate the expression level of neutrophil extracellular traps (NET) in the peripheral blood and liver tissue of primary biliary cholangitis (PBC) patients and its correlation with clinical biochemical parameters. Methods A total of 24 PBC patients who were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine, from August 2016 to August 2020 were enrolled, as well as 8 patients with primary sclerosing cholangitis (PSC) and 19 patients with autoimmune hepatitis (AIH) matched for age, and 19 healthy individuals were enrolled as healthy control group (HC group). The serum level of myeloperoxidase (MPO) was measured, and its correlation with clinical indices were analyzed. Immunofluorescence assay was used to measure the expression of NET in the liver of PBC patients, and an in vitro experiment was to compare the ability of peripheral blood neutrophils to produce NET between PBC patients and healthy controls. Normally distributed continuous data were expressed as mean±standard deviation, and the independent samples t -test was used for comparison between two groups; for the non-normally distributed continuous data expressed as M ( P 25 - P 75 ), the Kruskal-Wallis H test was used for comparison between multiple groups, and the Mann-Whitney U test was used for comparison between two groups. A correlation analysis was performed for MPO level and liver-related laboratory markers, and the Spearman's correlation coefficient was calculated. Results The serum level of MPO in the PBC group was increased to 811.21 (450.67-1 216.20) ng/mL, which was significantly higher than that in the AIH group [468.58 (142.63-812.43) ng/mL] and the HC group [357.54 (203.52-811.21) ng/mL] ( P < 0.05), suggesting that there was a significant increase in the production of NET in peripheral blood of PBC patients. The PSC patients had a serum MPO level of 763.56 (489.59-1 633.14) ng/mL, which was significantly higher than that in the HC group ( P < 0.05). MPO level was positively correlated with alkaline phosphatase ( r =0.500, P < 0.05), gamma-glutamyl transpeptidase ( r =0.426, P < 0.05), alanine aminotransferase ( r =0.521, P < 0.05), and aspartate aminotransferase ( r =0.547, P < 0.01). Confocal immunofluorescence showed colocalization of H3Cit and MPO in the liver of PBC patients. In vitro experiment showed that compared with the HC group, the PBC group had an increase in NET produced by peripheral blood neutrophils after in vitro stimulation and an increase in spontaneous production of NET. Conclusion There is an increase in NET in peripheral blood and liver of PBC patients, and the content of peripheral blood NET is positively correlated with biochemical parameters of liver function. NET may become a novel biomarker for assessing the severity of PBC.

Advances in the pathogenesis of autoimmune hepatitis and new targets for clinical intervention / 临床肝胆病杂志

Autoimmune hepatitis (AIH) is an immune-mediated liver disease with hepatocytes as the main target cells. It is characterized by the high immunoglobulin G level and the presence of autoantibodies, and histological observation shows interface hepatitis at the portal area caused by a large amount of lymphoplasmacytic infiltration. The pathogenesis of AIH has not been fully elucidated. At present, glucocorticoid combined with azathioprine is mainly used as non-specific immunosuppressive therapy, and most patients tend to have good response; however, rebound or relapse is often observed during dose reduction or after drug withdrawal, so most patients need long-term maintenance therapy. This article briefly reviews the advances in the pathogenesis of AIH and the potential new targets for clinical intervention, in order to provide a reference for clinical translational research.

Considerations on the elevation of aminotransferases in primary biliary cholangitis / 临床肝胆病杂志

Primary biliary cholangitis (PBC) is an autoimmune-mediated chronic cholestatic liver disease, with the typical biochemical manifestation of significantly elevated alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT), with or without mild-to-moderate elevation of aminotransferases. ALP and GGT play an important role in the diagnosis and monitoring of PBC. With a deeper understanding of PBC, the significance of elevated aminotransferases in diagnosis and treatment has attracted more and more attention. This article briefly summarizes the significance of elevation of aminotransferases in PBC patients.

Considerations on the elevation of aminotransferases in primary biliary cholangitis / 临床肝胆病杂志

Primary biliary cholangitis (PBC) is an autoimmune-mediated chronic cholestatic liver disease, with the typical biochemical manifestation of significantly elevated alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT), with or without mild-to-moderate elevation of aminotransferases. ALP and GGT play an important role in the diagnosis and monitoring of PBC. With a deeper understanding of PBC, the significance of elevated aminotransferases in diagnosis and treatment has attracted more and more attention. This article briefly summarizes the significance of elevation of aminotransferases in PBC patients.

One new coumarin from seeds of Herpetospermum pedunculosum / 中国中药杂志

This paper aims to investigate the chemical constituents of the seeds of Herpetospermum pedunculosum. One new coumarin and two known lignans were isolated from the ethanolic extract of the seeds of H. pedunculosum with thin layer chromatography(TLC), silica gel column chromatography, Sephedax LH-20 chromatography, Semi-preparative high performance liquid chromatography and recrystallization, etc. Their structures were elucidated as herpetolide H(1), phyllanglaucin B(2), and buddlenol E(3) by analysis of their physicochemical properties and spectral data. Among them, compound 1 was a new compound, and compounds 2 and 3 were isolated from this genus for the first time. In vitro anti-inflammatory activity test showed that herpetolide H had certain NO inhibitory activity for LPS-induced RAW 264.7 cells, with its IC_(50) value of(46.57±3.28) μmol·L~(-1).

Studies on chemical constituents of stems of Herpetospermum pedunculosum / 中国中药杂志

This project is to study chemical compositions from the stems of Herpetospermum pedunculosum. Twenty-two compounds were isolated from the 70% acetone extract of the stems of H. pedunculosum by column chromatography on Sephadex LH-20, semi-preparative HPLC and preparative TLC. Their structures were elucidated by their physicochemical properties and spectroscopic data as N-benzyltyramine(1), α-spinasterol(2),(2S)-1-O-heptatriacontanoyl glycerol(3), 5,7-dihydroxychromanone(4), methyl 2β,3β-dihydroxy-D:C-friedoolean-8-en-29-oate(5), p-hydroxy benzyl alcohol(6), p-hydroxybenzoate(7), p-hydroxy cinnamic acid(8), 1H-indol-3-carboxylic acid(9), rhodiocyanoside B(10), rhodiolgin(11), rhodiosin(12), 9,12,13-trihydroxy-10(E)-octadecenoic acid(13), cylo-(Tyr-Leu)(14), matteflavoside A(15), loliolide(16), 1H-indol-3-carboxaldehyde(17),(+)-dehydrovomifoliol(18), 3-hydroxy-5α,6α-epoxy-β-ionone(19), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-1-propen-1-yl)-2-methoxyphenoxy]-1-propanone(20), 7-en-nonadecanoic acid monoglyceride(21), vanillic acid(22). Compound 1 is a new natural product, while compounds 3-15 were isolated from this plant for the first time.

Standard therapy and potential therapeutic targets for autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis (AIH) is a liver inflammatory disease mediated by autoimmune response and may progress to liver failure and liver cirrhosis without treatment. The goal of AIH treatment is to achieve biochemical remission and histological remission. Currently immunosuppressant therapy is the standard therapy for AIH, i.e., prednisone/prednisolone alone or combined with azathioprine. For the patients who do not tolerate or have poor response to the standard therapy, second-line treatment regimen, including mycophenolate mofetil, can be considered. Recent studies have shown that various factors participate in the development and progression of AIH, such as immune function, gut microbiota, vitamin D, and mental state, which may become the potential therapeutic targets for AIH. This article reviews related studies on the standard therapies for AIH and highlights the potential therapeutic targets for AIH treatment.

Current status and perspectives of autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis (AIH) is an autoimmune liver disease induced by environmental factors in individuals with genetic susceptibility, with the main features of positive serum autoantibody, hypergammaglobulinemia, elevated transaminases, and interface hepatitis. The pathogenesis of AIH remains unknown, high heterogeneity is observed in clinical diagnosis and treatment, and thus it is of great importance to establish individualized precise diagnosis and treatment. Therefore, this article reviews the research advances and difficult issues in this field.

Pathogenesis of cholestasis-induced liver fibrosis and thoughts for blockade / 临床肝胆病杂志

Cholestasis refers to a pathological state of disorders in the formation, secretion, and excretion of bile flow, and liver fibrosis is a process of tissue repair induced by liver injury. Cholestatic liver disease is a chronic liver disease caused by cholestasis, progressive bile duct injury, and persistent intrahepatic inflammation, and it may cause cholangiocyte and hepatocyte injury, which will gradually progress to liver fibrosis. With reference to the current research advances, this article reviews the pathogenesis of cholestasis-induced liver fibrosis and the strategies for blockade.

Research advances of autoimmune liver diseases in 2018 / 中华肝脏病杂志

Autoimmune liver disease is a group of hepatobiliary injuries mediated by abnormal immunity. It mainly includes autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. Recently, an advancement of diagnostic technology has improved the detection and treatment of autoimmune hepatitis. However, it is easy to be confused with other liver diseases. Thus, the standardization of diagnosis and treatment of autoimmune liver diseases has become a main concern. Moreover, new progress has been made in basic research and clinical treatment of autoimmune liver diseases since 2018. In this review, we have introduced the latest research advances for the diagnosis and treatment of autoimmune liver diseases.

Advances in Diagnosis and Treatment of Autoimmune Liver Diseases Overlap Syndrome / 胃肠病学

Autoimmune liver diseases include autoimmune hepatitis (AIH),primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)and so on. The simultaneous presence of features of AIH,PBC or PSC called overlap syndrome,usually has a progressive course toward cirrhosis and liver failure if without prompt management. Early diagnosis and treatment can significantly improve the prognosis. This article summarized the advances in diagnosis and treatment of autoimmune liver diseases overlap syndrome in recent years.

Advances in Diagnosis and Treatment of Autoimmune Hepatitis / 胃肠病学

Autoimmune hepatitis (AIH)is a chronic progressive immune-mediated inflammatory liver disease. Both adults and children could be involved and women are more often affected. AIH is characterized by elevation of serum IgG/hypergammaglobulinemia,autoantibodies and interface hepatitis with diverse clinical spectrum. The incidence of AIH is increasing in recent years. If not treated timely,it may lead to cirrhosis and liver failure. Immunosuppressive therapy is crucial for improving patients'survival rate. This article summarized the advances in diagnosis and treatment of AIH.

Challenges to Diagnosis and Management of Autoimmune Liver Diseases / 胃肠病学

Autoimmune liver diseases (AILDs),including mainly autoimmune hepatitis (AIH),primary biliary cholangitis (PBC),primary sclerosing cholangitis (PSC),IgG4-related sclerosing cholangitis (IgG4-SC),and overlap syndromes,are characterized by circulating autoantibodies,inflammatory liver histology,and increased level of serum immunoglobulins. Early diagnosis and management can significantly improve the prognosis of patients and their quality of life. This editorial focused on the research progress and difficulties encountered in studies on AILDs in China.

Pathogenesis of immunoglobulin G4-related hepatobiliary disease / 中华肝脏病杂志

IgG4-relaed hepatobiliary diseases (IgG4-HBD) are the hepatobiliary manifestations of IgG4-related disease, a multisystem fibro-inflammatory disorder. Previous studies on the pathogenesis of genetics and immunology have provided significant assistance in understanding the disease, rational diagnosis and treatment, but there are still many unknowns and challenges. The current research progress summarizes several factors influencing fibrosis and inflammation in the pathogenesis of disease.

Clinical observation of isolated immunoglobulin G4-related sclerosing cholangitis and immunoglobulin G4 sclerosing cholangitis combined autoimmune pancreatitis / 中华肝脏病杂志

Objective@#To compare and analyze patient’s general condition, laboratory testing and therapeutic responses of isolated immunoglobulin G4- related sclerosing cholangitis (IgG4-SC) and immunoglobulin G4 sclerosing cholangitis combined autoimmune pancreatitis (IgG4-SC/AIP).@*Methods@#A retrospective study was conducted on IgG4-SC patients who attended outpatient and inpatients department of our hospital from April 2014 to March 2018 and their demographic characteristics, laboratory testing, and therapeutic responses were statistically analyzed. Normal distribution of continuous variables was compared with t-test, non-normal distribution of continuous variables was compared using the Mann-Whitney U test, and the categorical variables were compared with χ 2 test.@*Results@#29 IgG4-SC patients were included, including 19-isolated IgG4-SC and 10 IgG4-SC combined AIP (IgG4-SC/AIP). The average age of onset in the isolated IgG4-SC group was (46.06±19.03) years which was lower than IgG4-SC/AIP group (62.60±15.11), t = -2.360, P < 0.05. The median IgG4 in IgG4-SC/AIP patients is higher than that in isolated IgG4-SC, respectively 10.87 (3.73 ~ 20.13) and 3.14 (2.37 ~ 4.78)g/L(U = 159.000, P < 0.05). IgG4/IgG ratio is higher in IgG4-SC/AIP, than that in isolated IgG4-SC, respectively 0.62(0.23 ~ 0.86) and 0.16(0.10 ~ 0.21), U = 130.000, P < 0.05. Liver cirrhosis was more common in isolated IgG4-SC group (47%) than the IgG4-SC/AIP group (0), χ 2 = 9.637, P < 0.05. The median biochemical response time of isolated IgG4-SC group was 3.00 (2.00 to 4.00) months, which was longer than 1.00 (1.00 to 1.25) months of IgG4-SC/AIP group, U = 30.000, P < 0.05. The biochemical recurrence rate of isolated IgG4-SC group was 32%, which was lower than that of IgG4-SC/AIP (χ 2 = 6.461, P < 0.05).@*Conclusion@#Serum IgG4 level and IgG4/IgG ratio were higher in patients with IgG4-SC/AIP group, and therapeutic responses in isolated IgG4-SC patients were worse than that of IgG4-SC/AIP patients. The efficacy of glucocorticoid monotherapy and immunosuppressive agents combined with glucocorticoid therapy demonstrated no considerable difference in IgG4-SC patients.

Research status and challenges in immunoglobulin G4-related hepatobiliary disease / 中华肝脏病杂志

IgG4-associated hepatobiliary diseases are group of autoimmune diseases characterized by lymphoplasmacytic infiltrates with an elevated serum IgG4 levels, affecting pancreas and biliary tract. In addition, it mainly includes IgG4-related sclerosing cholangitis, IgG4-related autoimmune pancreatitis and IgG4-related autoimmune hepatitis. An accurate diagnosis helps to avoid unnecessary surgery. Notably, an early diagnosis and treatment can improve the prognosis and enhance the quality of life. This review will focus on research advances and difficulties encountered in the study of IgG4 related hepatobiliary diseases.

Differential diagnosis of drug-induced liver injury and autoimmune hepatitis and related therapeutic strategies / 临床肝胆病杂志

Drug-induced liver injury ( DILI) and autoimmune hepatitis ( AIH) have many similar clinical and histological manifestations , which brings difficulties to clinicians in differential diagnosis .This article elaborates on the association between DILI and AIH and their simi-larities and differences in clinical and histological manifestations , in order to help clinicians with the differential diagnosis of DILI and AIH . This article reviews the selection of therapeutic regimens for DILI and AIH and introduces how to select therapeutic strategies based on patient conditions and make a definite diagnosis when there are difficulties in differential diagnosis .

Advances in the treatment of primary biliary cholangitis / 中华肝脏病杂志

Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapeutic drug for PBC and can delay disease progression, but as high as 40% of patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment. Other drugs such as fibrates, glucocorticoids, immunosuppressants, biological agents, and mesenchymal stem cells are gradually used in clinical practice and bring new hope to patients with refractory PBC.

Transglutaminase-based antibody-drug conjugation: antibody site-specific mutation and identification / 药学学报

Transglutaminase (TG) posttranslational modification of antibody permits more precisely conjugating. Based on the amino acid sequence of an anti-CD24 antibody (cG7), this article is aimed to generate a deglycosylated cG7 mutant (cG7Q). Firstly, we introduced additional glutamines at position 297 (N297Q) by site-directed mutagenesis, and then transfected the recombinant plasmids into CHO-s cells via electroporation method and screened by Dot blot assay. Subsequently, cG7Q was expressed and purified through Protein A affinity chromatography, further identified by SDS-PAGE electrophoresis and Western blot. Its affinity was detected with surface plasmon resonance and flow cytometry assay, and ADCC effect was determined by lactate dehydrogenase (LDH) release. Eventually, a cG7 mutant, cG7Q was successfully expressed with sequence-specific conjugation sites for further study.