Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease.

Sensitization of hepatic immune cells from chronic alcohol consumption gives rise to inflammatory accumulation, which is considered a leading cause of liver damage. Regulatory T cells (Tregs) are an immunosuppressive cell subset that plays an important role in a variety of liver diseases; however, data about pathological involvement of Tregs in liver steatosis of alcoholic liver disease (ALD) is insufficient. In mouse models of ALD, we found that increased lipid accumulation by chronic alcohol intake was accompanied by oxidative stress, inflammatory accumulation, and Treg decline in the liver. Adoptive transfer of Tregs relieved lipid metabolic disorder, oxidative stress, inflammation, and, consequently, ameliorated the alcoholic fatty liver. Macrophages are a dominant source of inflammation in ALD. Aberrant macrophage activation and cytokine production were activated during chronic alcohol consumption, but were significantly inhibited after Treg transfer. In vitro, macrophages were co-activated by alcohol and lipopolysaccharide to mimic a condition for alcoholic liver microenvironment. Tregs suppressed monocyte chemoattractant protein-1 and TNF-α production from these macrophages. However, such effects of Tregs were remarkably neutralized when interleukin (IL)-10 was blocked. Altogether, our data uncover a novel role of Tregs in restoring liver lipid metabolism in ALD, which partially relies on IL-10-mediated suppression of hepatic pro-inflammatory macrophages.

Proteo-transcriptomic profiles reveal genetic mechanisms underlying primary hair follicle development in coarse sheep fetal skin.

Long hair trait represents a valuable genetic asset in Qinghai Tibetan sheep, with its quality and yield being contingent upon the characteristics of hair follicles (HFs). This study aims to elucidate the genetic mechanism underlying primary hair follicles (PFs) formation through an integrated analysis of proteomics and transcriptomics. Samples were collected at key stages of fetal HF formation (E65 and E85) for histological observation, revealing significant alterations in the microstructure of PF (E65) during the developmental process. In this study, a comprehensive analysis revealed a total of 217 overlapping genes that exhibited concordant expression patterns at both the proteomic and transcriptomic levels. Furthermore, to ensure the reliability of our findings, we employed parallel response monitoring (PRM) to validate the obtained proteomic data. The protein-protein interaction (PPI) network diagram highlights five hub core proteins (TTN, IGTA2, F2, EGFR, and MYH14). These differentially expressed proteins (DEPs) play crucial roles in metabolic processes, cell adhesion, and diverse biological processes. The potential synergy between transcriptional regulation and post-translational modifications plays a pivotal role in governing the initiation PF development. The findings presented in this study offer innovative insights into the molecular mechanisms underlying HFs generation and establish a robust foundation for targeted breeding strategies aimed at augmenting wool traits in sheep. SIGNIFICANCE: The composition of coarse hair primarily consists of long, myelinated fibers originating from primary hair follicles. Sheep fetal skin initiates the formation of primary hair follicles around E65, followed by the development of secondary hair follicles around E85. Conducting differential proteomic and transcriptomic analyses during these developmental stages enhances our understanding of the molecular mechanisms underlying primary hair follicle development and offers valuable insights for sustainable utilization of high-quality germplasm resources.

Salidroside attenuates LPS-stimulated activation of THP-1 cell-derived macrophages through down-regulation of MAPK/NF-kB signaling pathways.

Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside (Sal), one of the main bioactive components of Rhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activation of macrophages and the possible mechanism. The lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-1-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at both mRNA and protein levels in THP-1-derived macrophages, and the effect was dose-depedent. Moreover, NF-κB activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1ß, IL-6 and TNF-α, and the mechanism involves the inhibition of NF-κB activation and the phosphorylation of the MAPK signal pathway.

Noninvasive measurement of liver fibrosis by transient elastography and influencing factors in patients with chronic hepatitis B-A single center retrospective study of 466 patients.

The noninvasive measurement of liver stiffness (LS) was evaluated by transient elastography (FibroScan) and the possible influencing factors from the patients' clinical situations including age, gender, liver inflammation represented by alanine transaminase (ALT) and total billirubin (TBIL) level, HBV replication (HBV DNA loads), portal vein pressure (portal vessel diameter, PVD), splenic thickness (SPT) and body mass index (BMI) were analyzed in patients with chronic hepatitis B (CHB). A total of 466 patients including 31 patients with acute-on-chronic liver failure (ACLF), and 435 patients with chronic hepatitis B (CHB) among which 82 patients were diagnosed with liver cirrhosis (LC) by clinical manifestations and liver B-type ultrasonic inspection were enrolled at Tongji Hospital from April to December 2009. LS was measured by a FibroScan device (EchoSens, France). Simultaneously, ALT and TBIL levels, HBV DNA loads, PVD, SPT and BMI in all patients were also tested. Forty-one healthy volunteers served as controls. The values of LS were correlated positively with ages of CHB patients and significantly higher in males than in females. In patients with BMI>28 kg/m(2) (obesity) and abnormal levels of ALT and TBIL, LS values were significantly increased as compared with those having normal levels of ALT and TBIL. The patients with ACLF had the highest LS value. Furthermore, LS values in the patients with LC were significantly higher than those in patients without LC. It is concluded that noninvasive measurement of liver fibrosis by FibroScan provides an alternative method to evaluate liver fibrosis of patients with CHB. In order to properly illustrate the stiffness value taken by transient elastography, patients' gender should be taken into consideration and it is also suggested to avoid possible influencing factors including liver inflammation (high levels of ALT and TBIL) and obesity (high BMI).

Association Between Proton Pump Inhibitor Therapy and Spontaneous Bacterial Peritonitis Occurrence in Cirrhotic Patients: A Clinical Review.

Spontaneous bacterial peritonitis (SBP) is one of the most common complications in patients with end-stage liver disease (ESLD), which increases the risk of short-term mortality. Proton pump inhibitors (PPIs) are frequently used in patients with ESLD, in which controversies about the risk of PPI treatment in the occurrence of SBP are largely raised and the pathogenic mechanism of PPI-associated SBP remains unclear. We conducted a systematic literature search through PubMed/MEDLINE for publications mainly from 1 January 2000 to 1 January 2021. Our narrative review summarized the adverse effect of specific PPI therapy on the occurrence and prognosis of SBP in cirrhotic patients, described the potential mechanisms by which PPI induces the development of SBP, and discussed the risk factors associated with the development of SBP and the strategy of PPI therapy in cirrhotic patients. Although controversy regarding the association between PPI use and the occurrence of SBP exists, PPIs use should be restricted to patients with clear benefit indications, and be cautious for elderly patients with severe liver damage.

Case Report: "Area of Focus" Atypical Trichinellosis and Fascioliasis Coinfection.

Parasitic co-infection is commonly observed in natural populations, yet rare in the laboratory. Multiparasitism can have negative effects on the host, ranging from the atypical manifestations to increased mortality, consequently, it may be misdiagnosed and treated with unsuitable anthelmintic medicines. Therefore, reliable diagnosis is critical for appropriate treatment of parasitic co-infection. Herein, we report a case of a 31-year-old woman with persistent eosinophilia and hypoechoic liver lesion on ultrasound. The microscopic examination of multiple stool specimens did not find any pathogens. The patient had serum specific anti-Trichinella IgG antibody by Dot enzyme-linked immunosorbent assay (Dot-ELISA). After treatment with albendazole, contrast-enhanced magnetic resonance imaging (MRI) revealed more lesions in the liver. Subsequently, liver biopsy was performed in this patient and Fasciola hepatica was identified using metagenomic next-generation sequencing (mNGS) as well as polymerase chain reaction. After treatment with triclabendazole, which is the only anthelmintic drug specifically available against this fluke, her eosinophil count returned normal, and the liver lesions were significantly regressed. This case highlights the diagnostic challenge posed by parasitic co-infection, which merits more in-depth evaluation to confirm the diagnosis.

Proton Pump Inhibitor Therapy Increases the Risk of Spontaneous Bacterial Peritonitis in Patients with HBV-Related Acute-on-Chronic Liver Failure.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a common infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). SBP significantly increases the mortality rate and medical costs. The association between proton pump inhibitor (PPI) use and SBP remains unclear. We conducted a retrospective study to investigate the association between PPI use and SBP in patients with HBV-related ACLF and to explore the risk factors for SBP. METHODS: We compared the SBP incidence between the PPI and non-PPI groups before and after propensity score matching and explored the association between the duration and type of PPI and SBP occurrence. Risk factors for SBP occurrence were determined by univariate and multivariate logistic regression analysis. RESULTS: The SBP incidence was higher in the PPI group than in the non-PPI group before and after propensity score matching. The SBP incidence increased for elevated MELD scores in PPI users. There was a similar SBP incidence in both different types and durations of PPI users. MELD score, old age, male sex, and high WBC count were significant independent risk factors for SBP in PPI users with HBV-related ACLF in the hospital. CONCLUSIONS: PPI therapy increases the risk of SBP development in patients with HBV-related ACLF. MELD score, old age, male sex, and high WBC count could serve as predictors of SBP in PPI users. Caution should be taken regarding PPI use, especially for patients with MELD scores > 30.

Compound heterozygous UGT1A1*28 and UGT1A1*6 or single homozygous UGT1A1*28 are major genotypes associated with Gilbert's syndrome in Chinese Han people.

Gilbert's syndrome (GS) is a mild condition characterized by periods of hyperbilirubinemia, which results in variations in the UDP-glucuronosyltransferase 1 (UGT1A1) gene. Variant genotypes of UGT1A1 vary in different populations in the world. The present study aimed to determine the genotype of the UGT1A1 promoter and exon that are related to the serum total bilirubin (STB) level in the Chinese Han population. A total of 120 individuals diagnosed with GS (GS group) and 120 healthy individuals (non-GS group) were enrolled. Routine blood, liver function tests, and antibodies associated with autoimmune liver diseases were assessed. Blood samples were collected for DNA purification. Sequencing of the UGT1A1 promoter and exons was conducted for post segment amplification by PCR. Compound heterozygous UGT1A1*28 and UGT1A1*6 (25/120, 20.83%), single homozygous UGT1A1*28 (24/120, 20.00%) and single heterozygous UGT1A1*6 (18/120, 15.00%) were the most frequent genotypes in the GS group. However, single heterozygous UGT1A1*6 (30/120, 25.00%) and single heterozygous UGT1A1*28 (19/120, 15.83%) were the most frequent genotypes in the non-GS group. Further, the frequencies of single homozygous UGT1A1*28, compound heterozygous UGT1A1*28 and UGT1A1*6, and compound heterozygous UGT1A1*28, UGT1A1*6 and UGT1A1*27 were significantly higher in the GS group than those in the non-GS group. The STB levels of GS patients with the homozygous UGT1A1*28 genotype were remarkably higher than those of patients with other genotypes. Homozygous UGT1A1*28 and heterozygous UGT1A1*6 variants were associated with the highest and lowest risks of hyperbilirubinemia, respectively. Our study revealed that compound heterozygous UGT1A1*28 and UGT1A1*6, or single homozygous UGT1A1*28 are major genotypes associated with GS in Chinese Han people. These findings might facilitate the precise genomic diagnosis of Gilbert's syndrome.

Anaplastic large cell lymphoma with primary involvement of skeletal muscle: a rare case report and review of the literature.

Primary skeletal muscle ALCL is very rare. Here the authors report a case of skeletal muscle ALCL that was proven pathologically. A 14-year-old boy presented with a persistent fever, chills, night sweats, headache, and significant weight loss. A CT scan of the abdomen showed a hazy mass about 3.2 x 1.2 cm in his left sacrospinalis. Ultrasonography revealed a low-echo and irregular mass in the left lumbar muscle measuring 8 x 1.4 x 3.6 cm in size and a similar mass 8 x 3.5 x 3.7 cm in size in the femoral muscle of the left thigh. MRI demonstrated an abnormal mass signal 4 x 3 x 9 cm in size infiltrating the left sacrospinalis muscle. The biopsy specimen was taken from the femoral muscle of the left thigh at surgery. Histopathological examination revealed a diffuse infiltration of large and atypical cells with pleomorphic nuclei and abundant cytoplasm. Immunohistological staining showed these atypical cells were positive for CD30 (Ki-l), anaplastic lymphoma kinase (ALK), epithelial membrane antigen (EMA), CD3, CD45RO, and CD68. The morphology and immunophenotype were consistent with CD30-positive, ALK-positive, and ALCL of T-cell lineage. The patient's condition was diagnosed as CD30-positive primary skeletal muscle ALCL.

A Diagnostic Tool for Identification of Etiologies of Fever of Unknown Origin in Adult Patients.

The diagnosis and treatment of fever of unknown origin (FUO) are huge challenges to clinicians. Separating the etiologies of FUO into infectious and non-infectious disease is conducive to clinical physicians not only on making decisions rapidly concerning the prescription of suitable antibiotics but also on further analysis of the final diagnosis. In order to develop and validate a diagnostic tool to efficiently distinguish the etiologies of adult FUO patients as infectious or non-infectious disease, FUO patients from the departments of infectious disease and internal medicine in three Chinese tertiary hospitals were enrolled retrospectively and prospectively. By using polynomial logistic regression analysis, the diagnostic formula and the associated scoring system were developed. The variables included in this diagnostic formula were from clinical evaluations and common laboratory examinations. The proposed tool could discriminate infectious and non-infectious causes of FUO with an area under receiver operating characteristic curve (AUC) of 0.83, sensitivity of 0.80 and specificity of 0.75. This diagnosis tool could predict the infectious and non-infectious causes of FUO in the validation cohort with an AUC of 0.79, sensitivity of 0.79 and specificity of 0.70. The results suggested that this diagnostic tool could be a reliable tool to discriminate between infectious and non-infectious causes of FUO.

Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin.

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes. From January 2014 to September 2017, 431 patients with FUO were prospectively enrolled in the study population. This study established a list of 26 variables from the following 4 aspects: host factors, epidemiological factors, behavioral factors, and iatrogenic factors. Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model. The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified. These factors were incorporated into the predictive model. This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72, sensitivity of 0.71, and specificity of 0.63. The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

The effect of HBx gene on the apoptosis of hepatic cells.

To study the effect of HBx gene on the apoptosis of the cell lines (L02, HepG2) and the interaction between HBx and X-linked inhibitor of apoptosis protein (XIAP), the apoptosis of pcDNA3.1-HBx transiently transfected cell lines (L02, HepG2) was detected by flow cytometry and the mRNA expression of XIAP was assayed by real-time RT-PCR. Our study showed (1) the morphology of L02/pcDNA3.1-HBx was changed and the appearance of the cells mimicked that of HepG2 cells; (2) HBx gene could be detected in L02/pcDNA3.1-HBx and HepG2/ pcDNA3.1-HBx; (3) the apoptosis rate of L02/pcDNA 3.1-HBx was higher than that of L02 cells (P<0.01) and the apoptosis rate of HepG2/pcDNA3.1-HBx was lower than that of HepG2 cells (P<0.05); (4) the XIAP expression in L02 was about 3 times that in L02/pcDNA3.1-HBx cells (P<0.01), and the expression of XIAP in HepG2/pcDNA3.1-HBx was about 4 times that in HepG2 (P<0.01). It is concluded that HBx gene may promote the apoptosis of normal hepatocytes and inhibit the apoptosis of cells of hepatic carcinoma by regulating the expression of XIAP.

Baseline HBV load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of >3, 5, and 10 times the upper limit of normal (ULN) were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (>171 µmol/L) with or without decreased (<40%) prothrombin activity (PTA) were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8% (n=52) and 25.3% (n=22), respectively. The following variables were correlated with the severity of hepatotoxicity: albumin (ALB) levels, PTA, platelet counts (PLT), and the use of antiretroviral therapies (P<0.05). Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Leptin administration exacerbates thioacetamide-induced liver fibrosis in mice.

AIM: To investigate the effects of leptin administration on liver fibrosis induced by thioacetamide (TAA). METHODS: Twenty-four male C57Bl/6 mice were randomly allocated into four groups, which were intra-peritoneally given saline (2 mL/kg), leptin (1 mg/kg), TAA (200 mg/kg), TAA (200 mg/kg) plus leptin (1 mg/kg) respectively, thrice a week. All mice were killed after 4 wk. The changes in biochemical markers, such as the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were determined. For histological analysis, liver tissues were fixed with 10% buffered formalin, embedded with paraffin. Hematoxylin-eosin (HE) staining and picric acid-Sirius red dyeing were performed. The level of alpha1(I) procollagen mRNA in liver tissues was analyzed by RT-PCR. RESULTS: Apparent liver fibrosis was found in TAA group and TAA plus leptin group. Compared to saline group, the levels of ALT and AST in serum and MDA in liver increased in TAA group (205.67+/-27.69 U/L vs 50.67+/-10.46 U/L, 177.50+/-23.65 U/L vs 76.33+/-12.27 U/L, 2.60+/-0.18 nmol/mg pro vs 1.91+/-0.14 nmol/mg pro, P<0.01) and in TAA plus leptin group (256.17+/-22.50 U/L vs 50.67+/-10.46 U/L, 234.17+/-27.37 U/L vs 76.33+/-12.27 U/L, 2.97+/-0.19 nmol/mg pro vs 1.91+/-0.14 nmol/mg pro, P<0.01). The level of SOD in livers decreased (51.80+/-8.36 U/mg pro vs 81.52+/-11.40 U/mg pro, 35.78+/-6.11 U/mg pro vs 81.52+/- 11.40 U/mg pro, P<0.01) and the level of alpha1(I) procollagen mRNA in liver tissues also increased (0.28+/-0.04 vs 0.11+/- 0.02, 0.54+/-0.07 vs 0.11+/-0.02, P<0.01). But no significant changes were found in leptin group and saline group. Compared to TAA group, ALT, AST, MDA, and alpha1(I) procollagen mRNA and grade of liver fibrosis in TAA plus leptin group increased (256.17+/-22.50 U/L vs 205.67+/- 27.69 U/L, P<0.05; 234.17+/-27.37 U/L vs 177.50+/-23.65 U/L, P<0.05; 2.97+/-0.19 nmol/mg pro vs 2.60+/-0.18 nmol/mg pro, P<0.05; 0.54+/-0.07 vs 0.28+/-0.04, P<0.01; 3.17 vs 2.00, P<0.05), and the level of SOD in liver decreased (35.78+/-6.11 U/mg pro vs 51.80+/-8.36 U/mg pro, P<0.05). There were similar changes in the degree of type I collagen deposition confirmed by picric acid-Sirius red dyeing. CONCLUSION: Leptin can exacerbate the degree of TAA-induced liver fibrosis in mice. Leptin may be an important factor in the development of liver fibrosis.

Analysis of AmpC beta-lactamase gene in Pseudomonas aeruginosa .

The gene and the amino acid sequence of the structural and regulatory region of the Pseudomonas aeruginosa with different resistance patterns were analyzed. Six strains with different resistance patterns were selected and the AmpC beta-lactamase was identified. The objective gene fragment was amplified by colonies PCR. The sequences of the PCR-products were analyzed. The DNA sequence of the structural gene ampC and the regulatory genes ampR, ampD and ampE was detected. The 6 strains and the wild-type Pseudomonas aeruginosa are highly homogeneous in structural and regulatory region. Some new mutant points were found.

The mechanism of resistance of Pseudomonas aeruginosa to beta-lactam antibiotics and clinical significance.

To study the resistant mechanism and clinical significance of pseudomonas aeruginosa to beta-lactam antibiotics, the outer membrane permeability rate of 30 P. aeruginosa strains to 5 beta-lactam antibiotics was measured and their production of beta-lactamase and the beta-lactamase genes they carried detected. Furthermore, the relationship between the permeability, beta-lactamase and the clinical effects of beta-lactam antibiotics was observed. By using 14C-penicillin and liquid-scintillant isotope assay, the affinity of penicillin binding proteins (PBPS) was measured and their roles in the resistant mechanism studied. It was revealed that the permeability rate was higher in sensitive strains than in resistant ones (P < 0.05). All strains harbored 1-4 beta-lactamase genes and produced beta-lactamase. Higher permeability rate and higher degree of stability to beta-lactamase indicated better clinical therapeutic effects. The affinity of PBPs changed little without regard to the permeability and beta-lactamase. These results suggested that the permeability of outer membrane and beta-lactamase, but not PBPs, played important roles in the resistant mechanism of P. aeruginosa to beta-lactam antibiotics and affected the clinical therapeutic effectiveness of some patients.

Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: validation of the TPPM model.

PURPOSE: This study aimed to evaluate the efficacy and safety of entecavir, lamivudine and telbivudine for treating patients with HBV-ACLF and to validate the Tongji prognostic predictor model (TPPM) in these patients. METHODS: In this retrospective study, we enrolled 283 patients with HBV-ACLF (100 treated with entecavir, 98 treated with lamivudine and 85 treated with telbivudine). There were no significant differences in baseline clinical and virological characteristics among patients treated with entecavir, telbivudine or lamivudine. RESULTS: There were no significant differences in the 4- and 12-week survival rates of entecavir-, telbivudine- and lamivudine-treated patients (79.00, 81.18 and 86.73 %, respectively, at 4 weeks; 67.00, 65.88 and 73.47 %, respectively, at 12 weeks). Patients in all three groups achieved an improvement in the model for end-stage liver disease (MELD) score. Using the Hosmer-Lemeshow test, the validation of the TPPM score for HBV-ACLF demonstrated a good degree of fit with disease prognosis. Based on this unique group of patients, the TPPM score with an AUC of 0.787 was superior to the MELD score, which had an AUC of 0.736 in the prediction of 12-week mortality. The TPPM had an AUC of 0.733, and the MELD score had an AUC of 0.672 in the prediction of 4-week mortality. Using a cutoff value of 0.22 for 12-week mortality prediction by the TPPM, the positive predictive value was 49.66 %, with a negative predictive value of 89.55 %. CONCLUSION: Treatment with nucleoside analogs including entecavir, lamivudine and telbivudine prevented disease progression and increased the survival of patients with HBV-ACLF. Validation of the established TPPM scoring system in this study confirmed its superior predictive value for HBV-ACLF patients when compared with the MELD system.

siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa.

To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa-induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P＜0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections.

Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure: establishment of a novel logistical regression model.

BACKGROUND: Hepatitis B-related acute-on-chronic liver failure (ACLF) has a poor prognosis with very high mortality. Unfortunately, most prognostic predictive models of liver failure are complicated and offer suboptimal sensitivity. Experience in entecavir (ETV)-treated patients with hepatitis B virus (HBV)-ACLF is limited. AIMS: This study was designed to evaluate the efficacy and safety of ETV in patients with HBV-ACLF and to develop a novel model (Tongji prognostic predictor model, TPPM) for prognostic prediction of HBV-ACLF patients. METHOD: In this retrospective study, 248 patients with HBV-ACLF were enrolled. There were no significant differences in baseline clinical and virologic characteristics between patients treated with and without ETV. RESULTS: The 1- and 3-month survival rates of patients in the ETV-treated group (n = 124) were 72.58 and 61.29%, respectively, significantly higher than that in NA-free group (n = 124), which were 53.23 and 45.97%, respectively. By Hosmor and Lemeshow test, TPPM for HBV-ACLF had a very good degree of fit with disease prognosis. Based on this unique group of patients, the TPPM scoring offered a better prediction value in both specificity and sensitivity for 3-month mortality of patients with HBV-ACLF compared with MELD scoring system with statistically significant difference. In the patients with HBV-ACLF, using a cutoff of 0.22 for 3-month predicted mortality by TPPM, the positive predictive value was 93.6% and negative predictive value 91.3%. CONCLUSION: ETV treatment prevented disease progression and increased the survival of patients with HBV-ACLF. The established TPPM scoring system offers superior predictor value in both specificity and sensitivity for HBV-ACLF patients when compared with MELD.