Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report.

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.

Effects of Salmonella infection on hepatic damage following acute liver injury in rats.

BACKGROUND: Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS: Oral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury. RESULTS: The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P<0.01); The peyer's patch CD3+ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group (P<0.05). S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation. CONCLUSIONS: Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines.

Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR-23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-κB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI-induced hepatocarcinogenesis.

Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients.

AIM: To investigate the microbiological characteristics and drug resistance in liver cirrhosis patients with spontaneous peritonitis. METHODS: We analyzed the data of patients with liver cirrhosis and abdominal infection at the First Affiliated Hospital of Zhejiang University between January 2011 and December 2013. Pathogens present in the ascites were identified, and their sensitivity to various antibiotics was determined. RESULTS: We isolated 306 pathogenic bacteria from 288 cases: In 178 cases, the infection was caused by gram-negative strains (58.2%); in 85 cases, gram-positive strains (27.8%); in 9 cases, fungi (2.9%); and in 16 cases, more than one pathogen. The main pathogens were Escherichia coli (E. coli) (24.2%), Klebsiella pneumoniae (18.9%), Enterococcus spp. (11.1%), and Staphylococcus aureus (7.5%). Of the 306 isolated pathogens, 99 caused nosocomial infections and 207 caused community-acquired and other infections. The E. coli and K. pneumoniae strains produced more extended-spectrum ß-lactamases in cases of nosocomial infections than non-nosocomial infections (62.5% vs 38%, P < 0.013; 36.8% vs 12.8%, P < 0.034, respectively). The sensitivity to individual antibiotics differed between nosocomial and non-nosocomial infections: Piperacillin/tazobactam was significantly more effective against non-nosocomial E. coli infections (4% vs 20.8%, P < 0.021). Nitrofurantoin had stronger antibacterial activity against Enterococcus species causing non-nosocomial infections (36.4% vs 86.3%, P < 0.009). CONCLUSION: The majority of pathogens that cause abdominal infection in patients with liver cirrhosis are gram-negative, and drug resistance is significantly higher in nosocomial infections than in non-nosocomial infections.

Administration of Lactobacillus salivarius LI01 or Pediococcus pentosaceus LI05 improves acute liver injury induced by D-galactosamine in rats.

This work investigated the effect of the intragastric administration of five lactic acid bacteria from healthy people on acute liver failure in rats. Sprague-Dawley rats were given intragastric supplements of Lactobacillus salivarius LI01, Lactobacillus salivarius LI02, Lactobacillus paracasei LI03, Lactobacillus plantarum LI04, or Pediococcus pentosaceus LI05 for 8 days. Acute liver injury was induced on the eighth day by intraperitoneal injection of 1.1 g/kg body weight D-galactosamine (D-GalN). After 24 h, samples were collected to determine the level of liver enzymes, liver function, histology of the terminal ileum and liver, serum levels of inflammatory cytokines, bacterial translocation, and composition of the gut microbiome. The results indicated that pretreatment with L. salivarius LI01 or P. pentosaceus LI05 significantly reduced elevated alanine aminotransferase and aspartate aminotransferase levels, prevented the increase in total bilirubin, reduced the histological abnormalities of both the liver and the terminal ileum, decreased bacterial translocation, increased the serum level of interleukin 10 and/or interferon-γ, and resulted in a cecal microbiome that differed from that of the liver injury control. Pretreatment with L. plantarum LI04 or L. salivarius LI02 demonstrated no significant effects during this process, and pretreatment with L. paracasei LI03 aggravated liver injury. To the best of our knowledge, the effects of the three species-L. paracasei, L. salivarius, and P. pentosaceus-on D-GalN-induced liver injury have not been previously studied. The excellent characteristics of L. salivarius LI01 and P. pentosaceus LI05 enable them to serve as potential probiotics in the prevention or treatment of acute liver failure.

Anti-hepatitis B virus effect and possible mechanism of action of 3,4-o-dicaffeoylquinic Acid in vitro and in vivo.

The anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid isolated from Laggera alata was studied using the D-galactosamine- (D-GalN-) induced hepatocyte damage model, HepG2.2.15 cells, and with HBV transgenic mice. In vitro results showed that 3,4-O-dicaffeoylquinic acid improved HL-7702 hepatocyte viability and markedly inhibited the production of HBsAg and HBeAg. At a concentration of 100 µg/mL, its inhibitory rates on the expression levels of HBsAg and HBeAg were 89.96% and 81.01%, respectively. The content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in HepG2.2.15 cells was significantly decreased after the cells were treated with the test compound. In addition, 3,4-O-dicaffeoylquinic acid significantly increased the expression of heme oxygenase-1 (HO-1) in HepG2.2.15 cells. In vivo results indicated that the test compound at concentrations of 100 µg/mL significantly inhibited HBsAg production and increased HO-1 expression in HBV transgenic mice. In conclusion, this study verifies the anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid. The upregulation of HO-1 may contribute to the anti-HBV effect of this compound by reducing the stability of the HBV core protein, which blocks the refill of nuclear HBV cccDNA. Furthermore, the hepatoprotective effect of this compound may be mediated through its antioxidative/anti-inflammatory properties and by the induction of HO-1 expression.

Xiao-Chai-Hu Tang in treating model mice with D-galactosamine-induced liver injury.

This study explored the effects of a classical Chinese medicine formula- Xiao-Chai-Hu Tang(XCHT) on the model mice with D-galactosamine -induced liver injury. Sixty male imprinting control region (ICR) mice were used in the present study, and they were separated randomly into 6 groups: a normal control group (Group A, n=10), a model control (Group B, n=10), a positive control (Group C, n=10), a low dose of XCHT group (Group D, n=10), a medium dose of XCHT group (Group E, n=10), and a high dose of XCHT group (Group F, n=10). ELISA was used to detect the IL-6 and TNF-α levels in the serum. Real-time PCR was performed to assess the expression of FasmRNA, Fas-LmRNA, Bcl-2mRNA of the liver tissues. Western blotting was used to detect the Bax protein expression of the liver tissues. The serum IL-6 and TNF-α levels of Group B were significantly higher than the other groups (P<0.05). The expression of Fas mRNA, Fas-LmRNA, and Bax protein of the liver tissues of Group B were significantly higher than those of the other groups (P<0.05). The expression of Bcl-2 mRNA of the liver tissues of Group B was significantly lower than other groups (P<0.05). Both of XCHT and biphenyl dicarboxylate significantly decreased the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increased the Bcl-2 mRNA expression of the liver tissues of model mice (P<0.05). It may be through decreasing the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increasing the Bcl-2 mRNA expression of the liver tissues that XCHT significantly relieved the D-galactosamine -induced liver injury.

Discovery of potent, orally active compounds of tyrosine kinase and serine/threonine-protein kinase inhibitor with anti-tumor activity in preclinical assays.

Traditional medicines have become the most productive source of leads for drugs development, particularly as anti-cancer agents. Various screening approaches are being applied. Sorafenib, a multikinase inhibitor, is used to treat primary kidney cancer (advanced renal cell carcinoma) and advanced primary liver cancer. A small library of compounds analogous to sorafenib were designed and screened for the treatment of liver cancer. Multiple members of the family in an assay panel of tyrosine kinase family and serine/threonine-protein kinase family, including VEGFR, Abl, Aurora A, p 38, Lck, Src, PDGFR, Flt3, c-RAF, c-KIT, MEK(MAPKK) were selected to test these compounds. Analysis of the selectivity patterns for these compounds shows specificity for many kinase families. IC50 were measured for the selected compounds. Multiple compounds have very similar kinase inhibition profiles of VEGFR, Flt3, FGFR to that of sorafenib. The IC50 of c-RAF of BB1 is lower than sorafenib. The IC50 of c-RAF of BB3-12 is higher than that of sorafenib. For Flt3, IC50 of BB1-4 is less than sorafenib. The IC50 value of KDR of BB1-10 is less than sorafenib. especially against c-RAF, PDGFR, c-KIT, KDR compared to sorafenib. These compounds are potent Raf1 and Flt4 kinase inhibitors.

Epidemiology and characteristics of antimicrobial resistance in China.

A comprehensive surveillance system for bacterial resistance in tertiary hospitals has been established in China that involves tertiary hospitals in distinct regions nationwide, enabling the collection of a large amount of antimicrobial surveillance data. Antimicrobial resistance in China has become a serious healthcare problem, with high resistance rates of most common bacteria to clinically important antimicrobial agents. Methicillin-resistant S. aureus, ESBL-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii represent more than 50% of microbial isolates. Additionally, bacterial resistance to fluoroquinolones, macrolides and third-generation cephalosporins is of serious concern. The molecular epidemiology and resistance mechanisms of the antimicrobial strains in China exhibited regional specificity, as well as the influence of dissemination of international clonal complexes. The molecular characteristics of MRSA, ESBL- and carbapenemase-producing Enterobacteriaceae, and macrolide-resistant gram-positive Streptococci in China were significantly different from those in other countries and regions, while S. pneumoniae serotypes appear to have been affected by the global spread of prevalent clones in other parts of the world. Moreover, important antimicrobial resistant bacteria such as community-acquired-MRSA, multidrug-resistant P. aeruginosa and extensive-resistant A. baumannii, and the antimicrobial resistance in primary healthcare and outpatient setting should be intensely monitored and investigated in the future.

[Regulating effects of Paecilomyces cicadae polysaccharides on immunity of aged rats].

OBJECTIVE: To investigate the effects of Paecilomyces cicadae polysaccharide (PCPS) on the immunological function of aged rats in vivo. METHOD: The young and old rats were administered with normal saline as control groups, and the rats from test group were sc given 50, 100, 200 mg x kg(-1) x d(-1) dosage of PCPS for 3 weeks. The phagocytizing rate and index of PMphi, AMphi to S. aureas were observed, and the colorimetric MTI was used to analyze the proliferative activity of spleenocytes which had been stimulated with ConA or LPS. We also inspected the ability varing of ACP, LDH, ARG of spleen, and observed the ultramicro structure of spleen under the SEM. RESULT: The phagocytosis of Mphi was lower in aged group than that in young' s group, and the proliferative activity of spleenocytes was lower too. The activities of ACP, LDH, ARG of spleen were extremely decreased (P < 0.01) in aged rats as well. The proliferative activity and phagocytotic rate were both extremely increased in PCPS groups (P < 0.01), and the mitochondrion and endoplasmic reticulum of spleen were accrementition as well (P < 0.01). CONCLUSION: PCPS could enhance the phagocytizing function of PMphi, AMphi of aged rats in vivo, and strengthen the immune function of spleen and its proliferative activity as well. Then the immunity of aged rats could be improved. The PCPS may be an anti-aging agent.

Protective role of supplement with foreign Bifidobacterium and Lactobacillus in experimental hepatic ischemia-reperfusion injury.

BACKGROUND AND AIM: Intestinal microflora play a crucial role in some severe liver diseases. The purpose of this study was to evaluate the effects of a Lactobacillus strain and a Bifidobacterium strain on ischemia-reperfusion (I/R) liver injury. METHODS: Rats were divided into six groups. Each group received either Bifidobacterium Catenulatum ZYB0401; Lactobacillus Fermentum ZYL0401; a mixture of these two bacterial strains; gentamicin; or saline by daily gavage for 7 days. On the sixth day, all rats, except those in the control group, were subjected to 20 min of liver ischemia. After 22 h of hepatic reperfusion, liver enzymes and histology, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxemia, serum tumor necrosis factor-alpha (TNF-alpha), intestinal bacteria, intestinal mucosal ultrastructure, and bacterial translocation were studied. RESULTS: All administered bacteria increased intestinal Bifidobacterium and Lactobacillus, decreased endotoxemia (P < 0.01), alanine aminotransferase (ALT) (P < 0.01), and markedly ameliorated liver histology and intestinal mucosal ultrastructure. Only rats treated with Bifidobacterium Catenulatum ZYB0401 and Lactobacillus Fermentum ZYL0401 showed reduced incidence of bacterial translocation to the kidney (P < 0.05), associated with decreased serum TNF-alpha and liver MDA (P < 0.05) and increased liver SOD (P < 0.05) compared to the I/R group. Gentamicin decreased almost all kinds of intestinal bacteria (P < 0.01) and decreased ALT (P < 0.01) and serum TNF-alpha, but failed to reduce both endotoxemia and the incidence of bacterial translocation and had no effects on liver MDA and SOD. CONCLUSION: Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.

[Effects of Gardenia-aweto compound by different extraction method on antagonizing acute respiratory distress syndrome].

OBJECTIVE: To study the effect of Gardenia-Aweto compound (GAC) and two component on preventing acute respiratory distress syndrome (ARDS) by the rabbit model of ARDS induced by intravenous injection of oleic acid. To detect the efficiency component of GAC in preventing ARDS. METHOD: GAC was divided into two compounts, ethanol-soluble components (ESC) and ethanol-deposition components (EDC), based on polarity. Forty-three new zealand rabbits were randomly divided into five groups, the blank control group, the model group, the GAC groups, the ESC group, and the EDC group. The ARDS model was induced by intravenous injection of oleic acid. Dynamic changes of arterial blood gas, lung index, albumin in bronchoalveolar lavage fluid (BALF) in different groups and lung histological changes were observed and compared. RESULT: As compared with the blank group, in the model group, GAC group, ESC group, EDC group the arterial PO2 and oxygen saturation deprived continuously. While SO2 in GAC group at time points 30, 60, 90, 120 min (P < 0.05 or 0.01) and SO2 in ESC group at time points 30, 60, 90 min were higher than those in ARDS group. PO2 in ESC group at time points 30, 60 min (P < 0.05) were higher than those in ARDS group. The value of LI and W/D were higher in ARDS group than in sham group (P < 0.01), they were much lower in HD group than in ARDS group (P < 0.01). Concentration of BALF-albumin increased markedly in ARDS group and pre-treatment groups compared with sham group, but it was much lower in GAC group and ESC group, there was a significant difference between GAC group (P < 0.01), ESC group (P < 0.05) and ARDS group. The lung histological changes had been improved in GAC group and ESC group. But no significantly difference between above-mentioned parameters was found in comparison in the model group and in the EDC group. CONCLUSION: Preventive administration of GAC or ESC an protect the damaged lung function in ARDS rabbits induced by oleic acid. The efficiency component of GAC in preventing ARDS is ESC. GAC antagonizing ARDS may relate to its anti-inflammatory, immuno-modulatory, anti-oxidant and antithrombotic effects.

Effects of Salvia miltiorrhiza on intestinal microflora in rats with ischemia/reperfusion liver injury.

BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the present study was to determine the effects of Salvia miltiorrhiza on intestinal microflora, endotoxemia, and bacterial translocation in rats with hepatic I/R injury. METHODS: Sprague-Dawley rats in specific pathogen free grade were divided into 3 groups: group I(n=6) for sham operation; groups II(n=10) and III(n=7) for liver ischemia for 20 minutes and reperfusion for 22 hours. Group III was also pretreated with 4 ml/day of Salvia miltiorrhiza solution (250 mg/kg) by daily gavage for 7 days. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and superoxide dismutase(SOD) in liver tissues, serum endotoxin, intestinal bacterial counts, intestinal mucosal histology and bacterial translocation were studied. RESULTS: The levels of ALT, AST, plasma endotoxin and MDA in liver tissues were decreased more markedly in group III (57.57+/-18.08 U/L, 147.57+/-40.84 U/L, 0.42+/-0.144 EU/ml and 0.52+/-0.19 nmol/mg-prot respectively) in group II(122.8+/-80.12 U/L, 295.9+/-216.92 U/L, 0.80+/-0.262 EU/ml and 0.72+/-0.12 nmol/mg-prot; P<0.05-0.01 respectively). Liver SOD activity was increased more significantly in group III (318.47+/-64.62 U/mg-prot) than in group II(240.76+/-63.67 U/mg-prot, P<0.05). The counts of Bifidobacteria and Bacteroides increased more significantly in group III than in group II, but were similar to those in group I. Bacterial translocation to the kidney in group II was 50%(5/10), whereas no bacterial translocation to the kidney occurred in the other two groups (P<0.01). Ileal mucosal structure was markedly ameliorated in group III as compared with group II. CONCLUSIONS: Salviae miltiorrhiza could partially restore intestinal microflora balance, improve intestinal mucosal integrity, and reduce bacterial translocation and plasma endotoxin in rats with hepatic ischemia/reperfusion injury.