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Mirizzi syndrome is a serious complication of gallstone disease. It is caused by the impacted stones in the gallbladder neck or cystic duct. One of the features of Mirizzi syndrome is severe inflammation or dense fibrosis at the Calot's triangle. In our clinical practice, bile duct, branches of right hepatic artery and right portal vein clinging to gallbladder infundibulum are often observed due to gallbladder infundibulum adhered to right hepatic hilum. The intraoperative damage of branches of right hepatic artery occurs more easily than that of bile duct, all of which are hidden pitfalls for surgeons. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferable tools for the diagnosis of Mirizzi syndrome. Anterograde cholecystectomy in Mirizzi syndrome is easy to damage branches of right hepatic artery and bile duct due to gallbladder infundibulum adhered to right hepatic hilum. Subtotal cholecystectomy is an easy, safe and definitive approach to Mirizzi syndrome. When combined with the application of ERCP, a laparoscopic management of Mirizzi syndrome by well-trained surgeons is feasible and safe. The objective of this review was to highlight its existing problems: (1) low preoperative diagnostic rate, (2) easy to damage bile duct and branches of right hepatic artery, and (3) high concomitant gallbladder carcinoma. Meanwhile, the review aimed to discuss the possible therapeutic strategies: (1) to enhance its preoperative recognition by imaging findings, and (2) to avoid potential pitfalls during surgery., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Liver microsomal stability, a crucial aspect of metabolic stability, significantly impacts practical drug discovery. However, current models for predicting liver microsomal stability are based on limited molecular information from a single species. To address this limitation, we constructed the largest public database of compounds from three common species: human, rat, and mouse. Subsequently, we developed a series of classification models using both traditional descriptor-based and classic graph-based machine learning (ML) algorithms. Remarkably, the best-performing models for the three species achieved Matthews correlation coefficients (MCCs) of 0.616, 0.603, and 0.574, respectively, on the test set. Furthermore, through the construction of consensus models based on these individual models, we have demonstrated their superior predictive performance in comparison with the existing models of the same type. To explore the similarities and differences in the properties of liver microsomal stability among multispecies molecules, we conducted preliminary interpretative explorations using the Shapley additive explanations (SHAP) and atom heatmap approaches for the models and misclassified molecules. Additionally, we further investigated representative structural modifications and substructures that decrease the liver microsomal stability in different species using the matched molecule pair analysis (MMPA) method and substructure extraction techniques. The established prediction models, along with insightful interpretation information regarding liver microsomal stability, will significantly contribute to enhancing the efficiency of exploring practical drugs for development.

Background: Diarrhea is a prevalent complication after renal transplantation., Objective: To examine the risk factors for diarrhea after renal transplantation, evaluate their combined predictive values, and analyze the prognosis., Methods: Clinical data of patients who underwent allogeneic renal transplantation in the Second People's Hospital of Shanxi Province from January 2019 to March 2020 were retrospectively analyzed, cases were screened and grouped, independent risk factors for diarrhea after renal transplantation were analyzed by univariate analysis and multivariate analysis, and their predictive value was evaluated by receiver operating characteristic (ROC) curve. The survival time of recipient grafts in diarrhea and non-diarrhea groups were evaluated by Kaplan-Meier and log-rank test., Results: We included 166 recipients in the study and the incidence of diarrhea was 25.9%; univariate and logistic regression multivariate analyses revealed that independent risk factors for diarrhea in recipients were that the type of renal transplant donor was DCD (donation after circulatory death), immunity induction was onducted with basiliximab + antithymocyte globulin (ATG), and ATG alone, the type of mycophenolic acid (MPA) used was mycophenolate mofetil capsules, and delayed graft function (DGF) occurred after transplantation. The ROC curve indicated that the combination of the four factors had good accuracy in predicting the occurrence of diarrhea in recipients. The graft survival rate two years after the operation in the diarrhea group was significantly lower than that in the non-diarrhea group., Conclusion: Diarrhea affected the two-year survival rate of the graft. The type of donor, immunity induction scheme, and the type of MPA and DGF were independent risk factors for diarrhea in recipients, and the combination of the four factors had good prognostic prediction value.

Machine learning-based scoring functions (MLSFs) have become a very favorable alternative to classical scoring functions because of their potential superior screening performance. However, the information of negative data used to construct MLSFs was rarely reported in the literature, and meanwhile the putative inactive molecules recorded in existing databases usually have obvious bias from active molecules. Here we proposed an easy-to-use method named AMLSF that combines active learning using negative molecular selection strategies with MLSF, which can iteratively improve the quality of inactive sets and thus reduce the false positive rate of virtual screening. We chose energy auxiliary terms learning as the MLSF and validated our method on eight targets in the diverse subset of DUD-E. For each target, we screened the IterBioScreen database by AMLSF and compared the screening results with those of the four control models. The results illustrate that the number of active molecules in the top 1000 molecules identified by AMLSF was significantly higher than those identified by the control models. In addition, the free energy calculation results for the top 10 molecules screened out by the AMLSF, null model and control models based on DUD-E also proved that more active molecules can be identified, and the false positive rate can be reduced by AMLSF., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hematotoxicity has been becoming a serious but overlooked toxicity in drug discovery. However, only a few in silico models have been reported for the prediction of hematotoxicity. In this study, we constructed a high-quality dataset comprising 759 hematotoxic compounds and 1623 nonhematotoxic compounds and then established a series of classification models based on a combination of seven machine learning (ML) algorithms and nine molecular representations. The results based on two data partitioning strategies and applicability domain (AD) analysis illustrate that the best prediction model based on Attentive FP yielded a balanced accuracy (BA) of 72.6%, an area under the receiver operating characteristic curve (AUC) value of 76.8% for the validation set, and a BA of 69.2%, an AUC of 75.9% for the test set. In addition, compared with existing filtering rules and models, our model achieved the highest BA value of 67.5% for the external validation set. Additionally, the shapley additive explanation (SHAP) and atom heatmap approaches were utilized to discover the important features and structural fragments related to hematotoxicity, which could offer helpful tips to detect undesired positive substances. Furthermore, matched molecular pair analysis (MMPA) and representative substructure derivation technique were employed to further characterize and investigate the transformation principles and distinctive structural features of hematotoxic chemicals. We believe that the novel graph-based deep learning algorithms and insightful interpretation presented in this study can be used as a trustworthy and effective tool to assess hematotoxicity in the development of new drugs.

Traditional Chinese Medicine (TCM) has been widely used in the treatment of various diseases for millennia. In the modernization process of TCM, TCM ingredient databases are playing more and more important roles. However, most of the existing TCM ingredient databases do not provide simplification function for extracting key ingredients in each herb or formula, which hinders the research on the mechanism of actions of the ingredients in TCM databases. The lack of quality control and standardization of the data in most of these existing databases is also a prominent disadvantage. Therefore, we developed a Traditional Chinese Medicine Simplified Integrated Database (TCMSID) with high storage, high quality and standardization. The database includes 499 herbs registered in the Chinese pharmacopeia with 20,015 ingredients, 3270 targets as well as corresponding detailed information. TCMSID is not only a database of herbal ingredients, but also a TCM simplification platform. Key ingredients from TCM herbs are available to be screened out and regarded as representatives to explore the mechanism of TCM herbs by implementing multi-tool target prediction and multilevel network construction. TCMSID provides abundant data sources and analysis platforms for TCM simplification and drug discovery, which is expected to promote modernization and internationalization of TCM and enhance its international status in the future. TCMSID is freely available at https://tcm.scbdd.com ., (© 2022. The Author(s).)

Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection., (© 2021. The Author(s).)

Objective: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis., Methods: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course., Results: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results., Conclusions: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

Pyogenic liver abscess (PLA) of biliary origin in Southeast Asia mainly occurs in patients with intrahepatic bile duct stone (IBDS) and extrahepatic bile duct stone (EBDS), bilioenteric anastomosis, or biliary stent. IBDS, as an endemic to Southeast Asia, remains a frequent etiology of acute cholangitis and PLA. PLA related to IBDS is characterized by high incidences of PLA recurrence and death related to infection, and difficulties in diagnosis of concomitant cholangicarcinoma. PLA of biliary origin is more likely caused by Escherichia coli, more often presented as polymicrobial infections, and more associated with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae isolates. In this review, the authors summarize the differences on the presumed causes, pathogens, multidrug resistance, treatment, and prognosis of PLA between biliary origin and cryptogenic origin, the latter serving as a first and foremost presumed etiology of PLA. The authors also discuss the existing problems on early diagnosis of concomitant cholangicarcinoma related to IBDS., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Using an ORF1b-based astrovirus-specfic reverse transcription (RT)-PCR assay, a novel astrovirus-like was detected from domestic geese in China. Pairwise comparisons and phylogenetic analyzes suggested that a novel group of goose astrovirus, different with previously known astroviruses in the genus Avastrovirus, was found circulating in geese. This study has expanded our understanding about the role of domestic waterfowls as reservoirs for diverse astroviruses.

Background and Aim: Cholangitis, bacteremia, and pyogenic liver abscess (PLA) can be often caused by intrahepatic bile ducts stone (IBDS), which is endemic to South-East Asia. The association between IBDS and cholangiocarcinoma has been well recognized. Concomitant cholangiocarcinoma in the PLA related to IBDS is often missed., Methods: A case-control study consisting of 64 patients with PLA related to IBDS and 256 control patients with PLA not related to IBDS was used to investigate clinical features of PLA and incidence of concomitant cholangiocarcinoma in patients with PLA related to IBDS., Results: The main imaging manifestations of PLA related to IBDS was cystic-solid lesions and solid lesions. Of seven patients (10.9%) with pathology-proven cholangiocarcinoma in the same area of PLA related to IBDS among 64 patients, only two patients were initially diagnosed as having concomitant cholangiocarcinoma by biopsy, and other five patients diagnosed as acute inflammatory lesion. Within 60 days after onset, the infection-related death rate and recurrence rate in patients with PLA related to IBDS were 12.9% and 20.3%, respectively, whereas in patients with PLA not related to IBDS were 3.9% and 3.1%, respectively. Only 25% of patients with PLA related to IBDS underwent surgery after admission. The main pathogens in PLA patients related to IBDS were Escherichia coli and extended-spectrum beta-lactamase-producing Enterobacteriaceae., Conclusions: The imaging manifestations of PLA related to IBDS often present cystic-solid or solid lesions. PLA related to IBDS is characterized by high rate of recurrence and infection-related death, difficulty in diagnosis of concomitant cholangicarcinoma., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Goose parvovirus (GPV) continues to be a threat to goose farms and has significant economic effects on the production of geese. Current commercially available vaccines only rarely prevent GPV infection. In our study, Lactobacillus (L.) plantarum NC8 was selected as a vector to express the VP2 gene of GPV, and recombinant L. plantarum pSIP409-VP2/NC8 was successfully constructed. The molecular weight of the expressed recombinant protein was approximately 70 kDa. Mice were immunized with a 2 × 10 9 colony-forming unit/200 μL dose of the recombinant L. plantarum strain, and the ratios and numbers of CD11c + , CD3 + CD4 + , CD3 + CD8 + , and interferon gamma- and tumor necrosis factor alpha-expressing spleen lymphocytes in the pSIP409-VP2/NC8 group were higher than those in the control groups. In addition, we assessed the capacity of L. plantarum SIP409-VP2/NC8 to induce secretory IgA production. We conclude that administered pSIP409-VP2/NC8 leads to relatively extensive cellular responses. This study provides information on GPV infection and offers a clear framework of options available for GPV control strategies.

Avian influenza virus (AIV) is spreading worldwide and is a serious threat to the health of poultry and humans. In many countries, low pathogenic AIVs, such as H9N2, have become an enormous economic burden on the commercial poultry industry because they cause mild respiratory disease and decrease egg production. A recombinant Lactobacillus plantarum NC8 strain expressing NP-M1-DCpep from H9N2 AIV has been studied in a mouse model. However, it remains unknown whether this L. plantarum strain can induce an immune response and provide protection against H9N2 AIV in chickens. In this study, chickens that were orally vaccinated with NC8-pSIP409-NP-M1-DCpep exhibited significantly increased T cell-mediated immune responses and mucosal sIgA and IgG levels, which provided protection against H9N2 AIV challenge. More importantly, compared with oral administration of NC8-pSIP409-NP-M1-DCpep, intranasal administration induced stronger immune responses and provided effective protection against challenge with the H9N2 virus by reducing body weight loss, lung virus titers, and throat pathology. Taken together, these findings suggest that L. plantarum expressing NP-M1-DCpep has potential as a vaccine to combat H9N2 AIV infection.

Background & Aims: Little is known about aetiology and morbidity and clinical characteristics of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae., Methods: An analysis between pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates and those caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae was performed., Results: Among 817 pyogenic liver abscess patients, there were 176 patients (21.5%) with pyogenic liver abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (mainly Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess patients related to biliary disorders, there were 48 pyogenic liver abscess patients (27.3%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by Enterobacteriaceae expressing extended-spectrum beta-lactamases, the occurrences of 48 pyogenic liver abscess patients (71.6%) were associated with biliary disorders. When compared with pyogenic liver abscess patients caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae, there were significantly greater incidences of polymicrobial infections, bacteremia, pulmonary infection, recurrence and death in pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Carbapenems remain mainstay drugs against extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae. Independent risk factors for occurrence of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae were biliary disorders including extra- and intrahepatic cholangiolithiasis and an abnormal bilioenteric communication between bile and gut, a treatment history of malignancy such as operation and chemotherapy, pulmonary infection, and diabetes mellitus., Conclusions: Pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates mainly occurs in patients with biliary disorders or with a treatment history of malignancy. The mainstay of treatment remains carbapenems in combination with adequate aspiration or drainage., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination. The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8 + T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection. In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs.

During a study of ornithophilous viruses in China, a new densovirus (DNV) was isolated from the lung tissue of Parus major (PmDNV-JL). The complete genome of PmDNV-JL was cloned and sequenced. Five open reading frames (ORFs) were identified in the 5166nt sequence, on the basis of deduced amino acids. It was further shown that this virus caused cytopathic effects (CPE) in Feline kidney cells. The NS1 gene sequence of PmDNV-JL shares 70-99% nucleotide sequence identity with isolates of the Blattella germanica densovirus (BgDNV) and BgDNV-like virus. Phylogenetic analysis indicated that the predicted amino acid sequences of capsid (VP) and non-structural domain (NS1) of PmDNV-JL clustered with the BgDNV and were similar to BgDNV-HB within the genus Densovirus., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A restriction fragment length polymorphism combined with direct PCR technique to differentiate goose and Muscovy duck parvoviruses (GPV and MDPV) was developed based on comparison of the NS gene of GPV and MDPV. Both GPV and MDPV genomic DNA can be amplified with 641 bp using the specific PCR primers. The PCR fragments can be cut into 463 bp and 178 bp only in the case of MDPV-derived PCR products, whereas the GPV-derived PCR products cannot. The method established in this study can be used to differentiate GPV and MDPV with high specificity and precision, by using a direct PCR kit and QuickCut enzyme, as quickly as conventional PCR.

The effects of β-glucans from Coriolus versicolor (CVP), which are extracted from a well-known immune stimulator C. versicolor, have been demonstrated extensively in vitro and in vivo. However, until now, the phagocytic activity has not been elucidated. Hence, the objective of the present study was to identify the antibacterial activity of CVP or CVP-treated macrophages by an analysis of cell cytotoxicity, phagocytic activity, intracellular bacterial survival, macrophage activation, production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in CVP-treated macrophages using flow cytometry, RT-PCR, a gentamicin protection assay, a Nitric oxide assay and an iNOS enzymatic activity assay. The results indicate that CVP-treated macrophages can phagocytize and kill bacteria, probably due to the production of NO and iNOS. More importantly, CVP-treated macrophages are effective at protecting mice against the challenge of Salmonella typhimurium. The results of this study suggest that the antibacterial effects of CVP are probably caused by the activation of innate immune cells, especially macrophages, because the activated macrophage produces NO, which kills bacteria. These phenomena indicate the possibility of CVP as a potential alternative for antibiotics against resistant bacteria., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8-pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The pathogenesis of hypogonadism in male patients with cirrhosis is complex and not well explained. Systemic infection and inflammation can inhibit testicular functions of endocrine and spermatogenesis. The acute inflammation induced by lipopolysaccharide can cause testicular acute inflammation. Both clinical and animal experimental data indicate that the developing process of cholestasis/cirrhosis can lead to endotoxemia. Little is known about the long-term effects of cholestasis on the intratesticular macrophage population, cellular proliferation and apoptosis. A rat model of secondary cholestasis caused by common bile duct ligation (CBDL) was used to evaluate the impact of cholestasis on them, and the influence of biliary decompression (choledochoduodenostomy). Endotoxemia occurred in animals at 20 days CBDL (20dCBDL) and 30 days CBDL (30dCBDL), but disappeared after 30 days biliary decompression in rats with CBDL. There was a considerable increase in the numbers of intratesticular CD68(+) and CD163(+) macrophages following CBDL. After biliary decompression, CD68(+) macrophage numbers decreased, but remained higher than that of controls; meanwhile, CD163(+) remained elevated only in rats with 30dCBDL. After CBDL, there was a progressive decrease in the expression of Bcl-2 protein and in proliferating cell nuclear antigen (PCNA(+)) cells, and a dramatic increase in the expression of Bax, active caspase-3 and apoptotic cells. These data suggest that secondary cholestasis expands the population of CD68(+) and CD163(+) macrophages in the testicular interstitium, decreases testicular proliferative activity, and promotes testicular apoptosis, which may be one of the mechanisms of biliary cirrhosis-related hypogonadism., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Problem: Cholestasis can cause translocation of gut bacteria, and endotoxemia, and systemic inflammation. Now, little is known about the effects of cholestasis on the testicular inflammation and autophagy., Methods: A rat biliary cholestasis model caused by common bile duct ligation (CBDL), together with biliary decompression (choledochoduodenostomy), was used., Results: The magnitude of MCP-1 expression and CD68(+) macrophage infiltration within testes was progressively up-regulated in rats along with increasing duration of CBDL and was maintained at relatively high level in rats with biliary decompression. The large up-regulation of testicular ATG-12, LC3II, and autophagic vacuoles was found with the extending duration of CBDL and kept at 5 weeks following biliary decompression. The autophagic contents were a large accumulation of mitophagy in testes in rats with CBDL, and cytosol components in rats with biliary decompression., Conclusion: Secondary biliary cholestasis can promote inflammatory reaction and the activation of mitophagy and autophagy in testes., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The H9N2 avian influenza virus (AIV) has become increasingly concerning due to its role in severe economic losses in the poultry industry. Transmission of AIV to mammals, including pigs and humans, has accelerated efforts to devise preventive strategies. To develop an effective oral vaccine against H9N2 AIV, a recombinant Lactobacillus plantarum NC8 strain expressing the hemagglutinin (HA) gene of H9N2 AIV was constructed in this study. Mice were orally immunized with the recombinant NC8-pSIP409-HA strain, and sIgA, IgG and HI antibodies were produced by the NC8-pSIP409-HA strain, which also induced CD8(+) T cell immune responses. Most importantly, oral administration produced complete protection against challenge with mouse-adapted H9N2 virus. These results indicate that the recombinant NC8-pSIP409-HA was more effective at inducing the mucosal, humoral and cellular immune responses. Therefore, L. plantarum NC8-pSIP409-HA could become a promising oral vaccine candidate against H9N2 AIV., (Copyright © 2014. Published by Elsevier Inc.)

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.

This case report describes a foreign body retained in the liver long after perihepatic gauze packing. A 64-year-old female patient had suffered a rib fracture and liver rupture during a traffic accident in 1973. She discovered a mass in her right hypochondrium. Her hepatic ultrasonography showed a round mass (20.3 cm × 17.3 cm × 16.0 cm in size) with fluid echogenicity in the right lobe of her liver, and a hepatic cystic-solid mass (19.7 cm × 18.5 cm × 15.6 cm in size) was identified in an abdominal computerized tomography scan. Several pieces of gauze were extracted, and brown pus from the hepatic mass was suctioned during her exploratory laparotomy. Histology documented gauze remnants with necrotic material inclusions and fibrotic capsules. To our knowledge, this patient's case represents the longest time for which a foreign body has been retained in the liver. In addition, we conducted a comprehensive literature review of foreign bodies retained in the liver. Foreign bodies may be introduced into the liver via penetrating trauma, surgical procedures or the ingestion of foreign bodies (which then migrate from the gut). Thus, they can be classified into the following three categories: penetrating, medical and migrated foreign bodies. The details of the case are thoroughly described.

Aim: To further investigate the role of human B7 homolog 1 (B7-H1) in the mechanism of persistent hepatitis B virus (HBV) infection., Methods: Peripheral and intra-hepatic B7-H1 expression were compared by flow cytometry and immunochemical staining between two 2 distinct groups, one being chronic HBV tolerance patients (CHB-T) and the other being acute hepatitis B patients (AHB). B7-H1 mRNA expression level was also compared by real time polymerase chain reaction between CHB-T and AHB patients. The location of intra-hepatic B7-H1 and CD40 expression were analyzed by immunofluorescence. The levels of B7-H1 and CD40 expression on cultured myeloid dendritic cells (mDCs) with or without hepatitis B surface antigen (HBsAg) treatment were analyzed dynamically by flow cytometry. Intracellular interferon-γ (IFN-γ) staining and the stimulatory capacity of mDC of cultured mDC with or without HBsAg treatment were also compared by flow cytometry., Results: Peripheral B7-H1 expression on mDCs was increased significantly in AHB compared to CHB-T patients (P < 0.05). In the liver tissues from CHB-T patients, B7-H1 positive cells were almost absent despite a persistently elevated serum HBsAg load. In contrast, there were indeed increased B7-H1-positive cells in situ in the liver tissue from AHB. In vitro analysis showed the parallel upregulation of B7-H1 and CD40 on CD11c+ mDCs after the onset of stimulation. Addition of recombinant hepatitis B surface antigen (rHBsAg) significantly decreased CD40 expression (P < 0.05 at 16 h, 20 h and 24 h time points). B7-H1 expression was also inhibited by rHBsAg, and the inhibition rate of CD40 was greater than that of B7-H1. This preferential inhibition of CD40 expression on mDCs by rHBsAg resulted in the dysfunction of mDCs and T cells in the mixed leucocyte reaction (MLR) system. With rHBsAg pretreatment, in a carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled MLR system at a ratio of 1:5 responder cell-stimulator cell (R/S), the CFSE(dim) percentage of T cells decreased from 85.1% to 25.4% and decreased from 30.3% to 12.0% at 1:10 R/S. IFN-γ production by CD8+ T cells, in the MLR system, was reduced significantly by HBsAg pretreatment. At ratios of 1:5 R/S, the percentage of IFN-γ and CD8 dual positive T cells decreased from 55.2% ± 5.3% to 15.1% ± 3.1% (P < 0.001), and decreased from 35.0% ± 5.1% to 7.3% ± 2.7% at ratios of 1:10 R/S (P < 0.001)., Conclusion: B7-H1 is not a signature of immune dysfunction, but an inflammation marker. HBsAg regulate immune response by tipping the balance between B7-H1 and CD40.

A virulent Riemerella anatipestifer bacteriophage, RAP44, belonging to the Siphoviridae family of tailed phages, was previously isolated from feces of healthy Muscovy ducks in China. A complete genomic sequence analysis indicates that the phage's genome consists of a linear, double-stranded DNA molecule of 49,329 nucleotides. Eighty open reading frames (ORF) were identified. Putative functions could be assigned to 24 of the ORFs. The location of these genes was consistent with organization of the genome in a modular format which includes modules for host cell lysis, tail morphogenesis, head morphogenesis, and DNA replication and modification modules. Until now, no R. anatipestifer phage genome sequence has been reported in the literature. Therefore, this study represents the first complete genomic and molecular description of the R. anatipestifer phage.

To demonstrate the phylogenetic evolution, the molecular characteristics of the motif of HA protein cleavage site and the varieties at the receptor binding sites of the hemagglutinin gene of the duck-origin H9N2 subtype avian influenza viruses, sequence alignment and phylogenetic analysis were performed by MEGA 4.1 Neighbor-Joining method.. The results revealed that the duck-origin H9N2 AIV viruses originated from CK/BJ/1/94-like and North-Ame-like, all the duck-origin H9N2 AIV viruses from mainland China belonged to CK/BJ/1/94-like and formed multiple genotypes through complicated re-assortment, while other duck-origin H9N2 AIV, isolated from other countries in Aisa, American and European such as Korea, Japan, Alberta, Austria, Switzerland, Iran, belonged to the North-Ame-like phylogenetic lineage. The amino acids at positions 183, 190, and 226 of the receptor binding sites of North-Ame-like group isolates had highly conserved H, E and Q respectively. In contrast with duck-origin H9N2 AIV viruses isolates from mainland China, the amino acids had N at positions 183, A, T, or V at 190, L or Q at 226, which was the same as the chicken-origin H9N2 AIV from mainland China. Most newly isolated chicken-origin H9N2 AIV in Fujian Province in Southern China had L at position 226 emphasized the higher risk of cross-infection between the chicken-origin and duck-origin H9N2 AIV in China.

This report describes a one-step real-time polymerase chain reaction assay based on SYBR Green I for detection of a broad range of duck circovirus (DuCV). Align with all DuCV complete genome sequences and other Genus Circovirus download from the GenBank (such as goose circovirus, pigeon circovirus), the primers targets to the replicate gene of DuCV were designed. The detection assay was linear in the range of 1.31 × 102-1.31 × 107 copies/μL. The reaction efficiency of the assay using the slope (the slope was -3.349) and the Y-intercept was 37.01 from the linear equation was estimated to be 0.99 and the correlation coefficient (R2) was 0.993. A series of experiments were carried out to assess the reproducibility, sensitivity, and specificity of the assay, following by the low intra-assay and inter-assay CVs for CT values obtained with the standard plasmids. The intra-assay CVs were equal or less than 1.89% and the inter-assay CVs were equal or less than 1.26%. There was no cross-reaction occurred with nucleic acids extracted from RA (Riemerella anatipestifer), E. coli (Escherichia coli), Duck Cholera (Pasteurella multocida), Avian influenza virus, avian paramyxovirus, Muscovy duck parvovirus, Duck reovirus, Duck hepatitis A virus as control templates. The nucleic acids extracted from samples of healthy ducks were used as negative controls. The assay was specific and reproducible. The established real time PCR was used to detect 45 DuCV-negative samples, which were tested using conventional PCR under the developed optimal conditions, each 15 for embryonated eggs, non-embryonated budgerigar eggs, newly hatched duck, the mixture of the lung, liver, spleen which were analysis for the presence of DuCV DNA, to conform that whether the DuCV can be transmitted vertically. Meanwhile, no positive result was shown by the real-time PCR method. The SYBR Green I-based quantitative PCR can therefore be practically used as an alternative diagnostic tool and a screening method for ducks infected with duck circovirus.

Duck circovirus (DuCV), a potential immunosuppressive virus, was investigated in Southern China from March 2006 to December 2009 by using a polymerase chain reaction (PCR) based method. In this study, a total of 138 sick or dead duck samples from 18 different farms were examined with an average DuCV infection rate of ∼35%. It was found that ducks between the ages of 40∼60 days were more susceptible to DuCV. There was no evidence showing that the DuCV virus was capable of vertical transmission. Farms with positive PCR results exhibited no regularly apparent clinical abnormalities such as feathering disorders, growth retardation or lower-than-average weight. The complete genomes of 9 strains from Fujian Province and 1 from Zhejiang Province were sequenced and analyzed. The 10 DuCV genomes, compared with others genomes downloaded from GenBank, ranged in size from 1988 to 1996 base pairs, with sequence identities ranging from 83.2% to 99.8%. Phylogenetic analysis based on genome sequences demonstrated that DuCVs can be divided into two distinct genetic genotypes, Group I (the Euro-USA lineage) and Group II (the Taiwan lineage), with approximately 10.0% genetic difference between the two types. Molecular epidemiological data suggest there is no obvious difference among DuCV strains isolated from different geographic locations or different species, including Duck, Muscovy duck, Mule duck, Cheery duck, Mulard duck and Pekin duck.

Pneumonia caused by multidrug-resistant (MDR) Gram-negative bacilli is associated with a higher mortality rate. The appropriate empiric therapy is based on the understanding of local etiology and MDR pattern. This study was to evaluate the spectrum of Gram-negative bacilli, MDR rate, risk factors and mortality in 475 liver transplantation (LT) recipients. In the first six months after LT, the incidence of bacterial pneumonia was 21.3% (101/475). The overall infectious incidence during the first post-transplant month was 80.2%. The most frequent pneumonia isolates were Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. Gram-negative bacilli accounted for 69.6% of all pneumonia pathogens. Of the main 124 Gram-negative bacilli isolates, MDR rate was 58.9%. Four risk factors for post-LT pneumonia caused by MDR Gram-negative bacilli were LT candidates with grade II-IV encephalopathy (OR 2.275, 95%CI 1.249-4.124, p = 0.006), prolonged duration of endotracheal intubation (OR 8.224, 95%CI 4.276-15.815, p = 0.013), tracheostomy (OR 4.929, 95%CI 1.099-18.308, p = 0.027) and post-LT episode(s) of reoperations (OR 10.597, 95%CI 3.726-30.134, p < 0.001). MDR Gram-negative bacterial pneumonia-related mortality was significantly higher than that because of antibiotic-susceptible bacilli (45.6% vs. 11.4%, p = 0.010). Our data suggest that pneumonia caused by MDR Gram-negative bacilli after LT is common, and associated with the severity of underlying disease, prolonged mechanical ventilation and upper abdominal surgery., (© 2009 John Wiley & Sons A/S.)

Background: Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant (MDR) Gram-positive coccal bacteremia after LT., Methods: A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients., Results: In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic episodes occurred in the first post-LT month. The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46 isolates), methicillin-resistant Staphylococcus aureus (MRSA, 13) and enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were: LT candidates with encephalopathy grades II - IV (P = 0.013, OR: 16.253, 95%CI: 1.822 - 144.995), pre-LT use of empirical antibiotics (P = 0.018, OR: 1.029, 95%CI: 1.002 - 1.057), post-LT urinary tract infections (P < 0.001, OR: 20.340, 95%CI: 4.135 - 100.048) and abdominal infection (P = 0.004, OR: 2.820, 95%CI: 1.122 - 10.114). The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli., Conclusions: Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.

To reveal the molecular biological characteristics of genome of circovirus in infected ducks, two nucleotide fragments were amplified by overlapping PCRs using DNA extracted from various tissues of ducks. After they had been assembled together, the nucleotide components, the genome organization and the phylogenetic scale of the sequence were analyzed. The results showed that the obtained sequence is a circular DNA with a total length of 1995nt. It contains 6 open reading frames (ORFs), and shares a high identity of 97.4% with the MuDCV circovirus sequence presented in GenBank (AY228555). These results indicate that the amplified product stems from duck circovirus sequence.

Background: Invasive fungal infections are an important cause of posttransplant mortality in solid-organ recipients. The current trend is that the incidence of invasive candidiasis decreases significantly and invasive aspergillosis occurs later in the liver posttransplant recipients. The understanding of epidemiology and its evolving trends in the particular locality is beneficial to prophylactic and empiric treatment for transplant recipients., Methods: A retrospective analysis was made of recorded data on the epidemiology, risk factors, and mortality of invasive fungal infections in 352 liver transplant recipients., Results: Forty-two (11.9%) patients suffered from invasive fungal infection. Candida species infections (53.3%) were the most common, followed by Aspergillus species (40.0%). There were 21 patients with a superficial fungal infection. The median time to onset of first invasive fungal infection was 13 days, first invasive Candida infection 9 days, and first invasive Aspergillus infection 21 days. Fifteen deaths were related to invasive fungal infection, 10 to Aspergillus infection, and 5 to Candida infection. Invasive Candida species infections were associated with encephalopathy (P = 0.009) and postoperative bacterial infection (P = 0.0003) as demonstrated by multivariate analysis. Three independent risk factors of invasive Aspergillus infection were posttransplant laparotomy (P = 0.004), renal dysfunction (P = 0.005) and hemodialysis (P = 0.001)., Conclusions: The leading etiologic species of invasive fungal infections are Candida and Aspergillus, which frequently occur in the first posttransplant month. Encephalopathy and postoperative bacterial infection predispose to invasive Candida infection. Posttransplant laparotomy and poor perioperative clinical status contribute to invasive Aspergillus infection. More studies are needed to determine the effect of prophylactic antifungal therapy in high risk patients.

Objective: To investigate the effects of tacrolimus-based immunosuppression regimens after orthotopic liver transplantation and search a reasonable regimen of combination therapy and suitable blood concentration of tacrolimus., Methods: Ninety-four adult recipients of cadaveric livers were randomly divided into 3 groups to undergo different tacrolimus-based immunosuppression regimens: dual (tacrolimus + glucocorticoid), triple [tacrolimus + mycophenolate mofetil (MMF) + glucocorticoid]; quadruple [tacrolimus + MMF + glucocorticoid in addition of induction treatment by daclizumab]. The efficacy and safety of the 3 groups 6 months after the transplantation were compared., Results: The frequencies of acute rejection were 25.9%, 11.1%, and 7.5% for the dual, triple, and quadruple therapy groups, that of the quadruple therapy group being significantly lower than that of the dual therapy group (P = 0.038). There were no significant differences in the rates Three months after transplantation, the levels of ALT and total cholesterol of the dual therapy groups were significantly higher than those of the quadruple therapy group (P(ALT) = 0.011, P(Tch) = 0.002). Within the first month post-operatively the concentration of tacrolimus of the triple therapy group could be controlled at the level 8 ng x ml(-1)-13 ng x ml(-1)., Conclusions: Quadruple tacrolimus-based immunosuppression regimen is the most effective and safest, followed by the triple therapy and dual therapy. Low-dose tacrolimus combination therapy provides an effective protection to the liver graft with mild drug toxicity to the patient.

Objective: To investigate the relation between the activity of nuclear factor kappaB (NF-kappaB) and the expression of interferon (IFN)-gamma gene transcription with or without ciclosporin treatment after liver transplantation., Methods: Orthotopic liver transplantation was performed in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar); Group III: acute rejection treated with ciclosporin by intramuscular route (SD-to-Wistar + ciclosporin). Electrophoretic mobility shift assay and reverse transcriptase polymerase chain reaction were used to analyze NF-kappaB activity of splenocytes and IFN-gamma gene transcription expression of grafted liver with or without ciclosporin treatment after liver transplantation. Histopathological examination was also used in this study., Results: Low NF-kappaB activity was only detected at day 5 and day 7 in Wistar-to-Wistar group after transplantation, meanwhile low IFN-gamma mRNA expression was detected at any time in this group. In contrast, high NF-kappaB activity was detected in SD-to-Wistar group and high level IFN-gammamRNA expression was detected at all time points in this group. The activity of NF-kappaB and IFN-gammamRNA expression were significantly inhibited in SD-to-Wistar + ciclosporin group which was significantly lower than that of SD-to-Wistar group (P < 0.001). A good correlation was found between activity of NF-kappaB and IFN-gamma mRNA expression in this study (r=0.815, P <0.01)., Conclusions: The change of expression IFN-gamma mRNA is at least partially due to the activity change of NF-kappaB after orthotopic liver transplantation. CsA down-regulates NF-kappaB activity and further inhibit IFN-gamma gene transcription.

Aim: To investigate the inhibitory effect of tea polyphenols (TP) on the transforming growth factor-beta1 (TGF-beta1) expression in rat model of cyclosporine A (CsA)-induced chronic nephrotoxicity., Methods: The rat model of CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively treated with vehicle (0.1 mL/kg/d sc), TP (80 mg/kg/d ig), CsA (15 mg/kg/d sc) and TP plus CsA (CsA 15 mg/kg/d sc+TP 80 mg/kg/d, ig). At the end of day 28 of treatment, serum and urine are analyzed for creatinine clearance, kidney tissue for pathologic analysis. The TGF-beta1 mRNA and its protein expression were detected by RT-PCR, immunohistochemistry, and Western blot., Results: CsA-treated rats had increased renal expression of TGF-beta1 mRNA and its protein, compared with the vehicle- or TP-treated controls. The renal function and interstitial fibrosis were ameliorated and renal expression of TGF-beta1 mRNA and its protein was decreased in animals treated with CsA plus TP, compared with animals treated with CsA alone (P<0.05)., Conclusion: TP significantly inhibits renal expression of TGF-beta1 in rat model of cyclosporine-induced chronic nephrotoxicity, suggesting that the decreased renal expression of TGF-beta1 exerted by TP is one of mechanisms to protect renal function and tissue structure.