Prehospital physiological parameters related illness severity scores can accurately discriminate the severe/critical state in adult patients with COVID-19.

BACKGROUND: Whether the National Early Warning Score 2 (NEWS2) can effectively discriminate the severe/critical state of patients with coronavirus disease 2019 (COVID-19) at the prehospital stage remains unknown. We aimed to assess the performance of NEWS2 in rapidly discriminating severe/critical COVID-19 and its relationship with prehospital medical services. METHODS: Six illness severity scores of 414 patients were calculated at the prehospital stage. Receiver operating characteristic curves were generated to explore the ability of these scores to discriminate severe/critical patients from mild/moderate patients. A logistic regression analysis was conducted to evaluate independent predictors associated with severe/critical state. RESULTS: The age, numbers of comorbidities, prehospital care workload, consumption of medical human resources, and illness severity scores of severe/critical patients were higher than those of mild/moderate patients (p < 0.05). When NEWS2 scores >2, the sensitivity, specificity, positive predictive value, and negative predictive value were 93.5%, 90.7%, 74.1%, and 98.0%, respectively. The C-statistic of NEWS2 (0.963) was higher than that of quick Sequential Organ Failure Assessment (0.680, p < 0.001), CRB-65 (0.879, p < 0.001), Rapid Acute Physiology Score (0.692, p < 0.001), and Rapid Emergency Medicine Score (0.879, p < 0.001). NEWS2 was positively correlated with the numbers of prehospital treatment measures (r = 0.732, p < 0.001), numbers of medical staff (r = 0.615, p < 0.001), and total transport time (r = 0.595, p < 0.001). Age ≥65 years (OR = 5.43, p = 0.016), hypertension (OR = 5.39, p < 0.001), active malignancy (OR = 5.94, p = 0.005), and NEWS2 scores >2 (OR = 124.88, p < 0.001) were independent predictors to discriminate severe/critical patients. Oxygen saturation (SpO2) (OR =1.87, p < 0.001) was the unique independent predictor to discriminate false positive patients from true positive patients. CONCLUSIONS: Prehospital NEWS2 can accurately and rapidly discriminate severe/critical COVID-19 during the Omicron variant wave. High levels of NEWS2 indicate an increase in prehospital care workload and consumption of medical human resources.

A Lower HCC Incidence in Chronic HBV-Infected Patients Recovered from Acute-on-Chronic Liver Failure: A Prospective Cohort Study.

Background: Activation of chronic hepatitis B virus (HBV) infection is an important cause of acute-on-chronic liver failure (ACLF). However, the effect of HBV-ACLF episode on hepatocellular carcinoma (HCC) occurrence remains largely unknown. Methods: A total of 769 HBV-ACLF patients and 2114 HBV-related chronic liver disease (HBV-CLD) patients diagnosed between August 1998 and December 2011 were enrolled in this prospective cohort study. Of the HBV-CLD patients, 380 received lifetime antiviral treatment with nucleos(t)ide analogues. Propensity score matching was applied to reduce baseline differences between HBV-ACLF and HBV-CLD cohorts. Results: The survival rate of HBV-ACLF patients was 53.6%, 50.3%, 47.8%, and 46.2% at 90-day, 1-year, 5-year, and 10-year, respectively. The cumulative incidence of HCC was lower in HBV-ACLF cohort with 369 eligible patients survived for >90 days than in HBV-CLD cohort with the 380 patients (5.77/1,000 vs. 9.78/1,000 person-years, p = 0.0497). HBV-ACLF episode decreased HCC risk regardless of liver cirrhosis, and in patients without family history of HCC. Multivariate Cox analyses indicated that male, increasing age, liver cirrhosis, and platelet count (≤100 × 109/L) increased, whereas HBV-ACLF episode decreased, HCC risk independently. In the propensity score-matched cohorts, HBV-ACLF episode reduced HCC incidence (10.20/1,000 vs. 4.66/1,000 person-years, p = 0.0326). The area under curve of nomogram was 0.812 for 3-year HCC probability. Conclusions: HBV-ACLF episode decreases HCC occurrence in chronic HBV patients. Older age and liver cirrhosis independently increased HCC occurrence. A nomogram-enrolled episode of ACLF reliably predicts the occurrence of HCC.

A Tale of Water Molecules in the Ribosomal Peptidyl Transferase Reaction.

The peptidyl transferase center (PTC) in the large subunit of the ribosome plays a critical role in protein synthesis by catalyzing the formation of peptide bonds with an astounding speed of about 15 to 20 peptide bonds per second. The ribosome coordinates the nucleophilic attack and deprotonation in the rate-limiting step at the PTC. However, the details of peptide bond formation within the ribosome, particularly the precise role of the two water molecules in the PTC, remain unclear. Here, we propose a novel stepwise "proton shuttle" mechanism which corroborates all the reported experimental measurements so far. In this mechanism, a water molecule close to A76 of peptidyl-tRNA 2'- and 3'-O stabilizes the transition state. The other one adjacent to the carbonyl oxygen of peptidyl-tRNA actively participates in the proton shuttle, playing the catalytic role of ribosome-catalyzed peptide bond formation.

Granulocyte Colony-Stimulating Factor Accelerates the Recovery of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure by Promoting M2-Like Transition of Monocytes.

Background and Aim: Acute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents. Methods: We performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 µg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments. Results: The survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments. Conclusion: G-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration Number: ClinicalTrials.gov, identifier (NCT02331745).

Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry.

BACKGROUND AND AIMS: Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. APPROACH AND RESULTS: We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. CONCLUSIONS: Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course.

Systematic characterisation of the structure and radical scavenging potency of Pu'Er tea () polyphenol theaflavin.

The structure, energetics and radical scavenging potency of theaflavin (TF), a natural polyphenolic antioxidant found in oxidised tea, have been characterised by a series of density functional theory (DFT) determinations. Exploratory conformational searches yielded 153 distinct neutral structures. Results showed TF's structural preferences to be regulated by its unique fused double ring benzotropolone moiety, and its degree of planarity, with structural diversity, principally arising from variations of its nine -OH groups. The distinct 3D conformational 'poses' are shown to be stabilised by a complex network of intra-system interactions, damping overall structural floppiness. This rigidification, together with stability, is shown to be coupled with radical scavenging potency in the TF system. Radical scavenging via hydrogen atom abstraction (HAB) in H2O solution was determined to be spontaneous with very low reaction barriers (ΔGrel ∼ 4 kJ mol-1).

Method to extract multiple states in F1-ATPase rotation experiments from jump distributions.

A method is proposed for analyzing fast (10 µs) single-molecule rotation trajectories in F1 adenosinetriphosphatase ([Formula: see text]-ATPase). This method is based on the distribution of jumps in the rotation angle that occur in the transitions during the steps between subsequent catalytic dwells. The method is complementary to the "stalling" technique devised by H. Noji et al. [Biophys. Rev. 9, 103-118, 2017], and can reveal multiple states not directly detectable as steps. A bimodal distribution of jumps is observed at certain angles, due to the system being in either of 2 states at the same rotation angle. In this method, a multistate theory is used that takes into account a viscoelastic fluctuation of the imaging probe. Using an established sequence of 3 specific states, a theoretical profile of angular jumps is predicted, without adjustable parameters, that agrees with experiment for most of the angular range. Agreement can be achieved at all angles by assuming a fourth state with an ∼10 µs lifetime and a dwell angle about 40° after the adenosine 5'-triphosphate (ATP) binding dwell. The latter result suggests that the ATP binding in one ß subunit and the adenosine 5'-diphosphate (ADP) release from another ß subunit occur via a transient whose lifetime is ∼10 µs and is about 6 orders of magnitude smaller than the lifetime for ADP release from a singly occupied [Formula: see text]-ATPase. An internal consistency test is given by comparing 2 independent ways of obtaining the relaxation time of the probe. They agree and are ∼15 µs.

A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection.

Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long-term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord-derived mesenchymal stem cell (UC-MSC) therapy in liver transplant patients with acute graft rejection. Twenty-seven liver allograft recipients with acute rejection were randomly assigned into the UC-MSC infusion group or the control group. Thirteen patients received one infusion of UC-MSCs (1 × 106 /kg body weight); one patient received multiple UC-MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow-up for 12 weeks after UC-MSC infusions. No side effects occurred in treated patients. Four weeks after UC-MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12-week follow-up period. Importantly, allograft histology was improved after administration of UC-MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC-MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC-MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect. Stem Cells Translational Medicine 2017;6:2053-2061.

Squid Suckerin Biomimetic Peptides Form Amyloid-like Crystals with Robust Mechanical Properties.

We present the self-assembly of fibers formed from a peptide sequence (A1H1) derived from suckerin proteins of squid sucker ring teeth (SRT). SRT are protein-only biopolymers with an unconventional set of physicochemical and mechanical properties including high elastic modulus coupled with thermoplastic behavior. We have identified a conserved peptide building block from suckerins that possess the ability to assemble into materials with similar mechanical properties as the native SRT. A1H1 displays amphiphilic characteristics and self-assembles from the bottom-up into mm-scale fibers initiated by the addition of a polar aprotic solvent. A1H1 fibers are thermally resistant up to 239 °C, coupled with an elastic modulus of ∼7.7 GPa, which can be explained by the tight packing of ß-sheet-enriched crystalline building blocks as identified by wide-angle X-ray scattering (WAXS), with intersheet and interstrand distances of 5.37 and 4.38 Å, respectively. A compact packing of the peptides at their Ala-rich terminals within the fibers was confirmed from molecular dynamics simulations, and we propose a hierarchical model of fiber assembly of the mature peptide fiber.

Bioactivity of CD34+ cells in patients with acute-on-chronic liver failure.

Liver failure is a life-threatened serious disease with many complications and high mortality rate. Stem cells have been applied to replacement therapy, gene therapy and tissue engineering for its capacity of self-renewal and multi-lineage differentiation. To investigate the bioactivity of the peripheral blood hematopoietic stem cells (PBHSC) in patients with acute-on-chronic liver failure, we isolated CD34+ cells from peripheral blood of patients with acute-on-chronic liver failure and healthy controls. After cultured it in serum-free medium (SFEM), we studied the bioactivity of CD34+ cells by observing the morphology, recording growth curve, detecting cell cycle and cell apoptosis. CD34+ cells and culture solution were collected at the time points of 3, 5, 7, 10, 12 and 14 days, and the levels of hepatocyte growth factor (HGF), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in culture solution were detected by ELISA. Also, the expressions of pyruvate kinase muscle isoenzyme 2 (PKM2), integrin-ß1 and liver-type pyruvate kinase (LPK) were detected by RT-PCR and immunofluorescence. Our results showed the bioactivity of CD34+ cells from patients with acute-on-chronic liver failure was identified to be similar with that from healthy controls. HGF, MMP-9, TNF-α and IL-6 were found in cell culture medium. RT-PCR and immunofluorescence results indicated that PKM2, Integrin-ß1 expressed on CD34+ cells from patients with acute-on-chronic liver failure. In conclusion, bioactivity of CD34+ cells of patients with acute-on-chronic liver failure was demonstrated to be normal, which could secrete HGF, MMP-9, TNF-α and IL-6, promote the growth of hepatocytes, and differentiate along a direction to hepatocyte lineage.

Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-ß supramolecular networks.

The hard sucker ring teeth (SRT) from decapodiforme cephalopods, which are located inside the sucker cups lining the arms and tentacles of these species, have recently emerged as a unique model structure for biomimetic structural biopolymers. SRT are entirely composed of modular, block co-polymer-like proteins that self-assemble into a large supramolecular network. In order to unveil the molecular principles behind SRT's self-assembly and robustness, we describe a combinatorial screening assay that maps the molecular-scale interactions between the most abundant modular peptide blocks of suckerin proteins. By selecting prominent interaction hotspots from this assay, we identified four peptides that exhibited the strongest homo-peptidic interactions, and conducted further in-depth biophysical characterizations complemented by molecular dynamic (MD) simulations to investigate the nature of these interactions. Circular Dichroism (CD) revealed conformations that transitioned from semi-extended poly-proline II (PII) towards ß-sheet structure. The peptides spontaneously self-assembled into microfibers enriched with cross ß-structures, as evidenced by Fourier-Transform Infrared Spectroscopy (FTIR) and Congo red staining. Nuclear Magnetic Resonance (NMR) experiments identified the residues involved in the hydrogen-bonded network and demonstrated that these self-assembled ß-sheet-based fibers exhibit high protection factors that bear resemblance to amyloids. The high stability of the ß-sheet network and an amyloid-like model of fibril assembly were supported by MD simulations. The work sheds light on how Nature has evolved modular sequence design for the self-assembly of mechanically robust functional materials, and expands our biomolecular toolkit to prepare load-bearing biomaterials from protein-based block co-polymers and self-assembled peptides. STATEMENT OF SIGNIFICANCE: The sucker ring teeth (SRT) located on the arms and tentacles of cephalopods represent as a very promising protein-based biopolymer with the potential to rival silk in biomedical and engineering applications. SRT are made of modular, block co-polymer like proteins (suckerins), which assemble into a semicrystalline polymer reinforced by nano-confined ß-sheets, resulting in a supramolecular network with mechanical properties that match those of the strongest engineering polymers. In this study, we aimed to understand the molecular mechanisms behind SRT's self-assembly and robustness. The most abundant modular peptidic blocks of suckerin proteins were studied by various spectroscopic methods, which demonstrate that SRT peptides form amyloid-like cross-ß structures.

The Therapeutic Efficacy and Safety of Compound Kushen Injection Combined with Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma: An Update Systematic Review and Meta-Analysis.

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent medicine approved by the China Food and Drug Administration for the treatment of various types of solid tumors. CKI, combined with transarterial chemoembolization (TACE), is believed to increase the therapeutic efficacy of unresectable hepatocellular carcinoma (HCC). We report an updated and extended meta-analysis with detailed outcomes of both the efficacy and adverse events (AEs) of CKI combined with TACE therapy. MATERIALS AND METHODS: Electronic databases, including PubMed, Embase, the Cochrane Library, the Chinese Biomedical Database (CBM), Wanfang, the VIP medicine information system (VMIS) and the China National Knowledge Infrastructure (CNKI), were examined for relevant articles before November 13, 2015. An odds ratio (OR) was used to estimate tumor response (TR), Karnofsky Performance Scale (KPS) improvement, Child-Pugh (CP) improvement, survival rate (SR) and AEs. A publication bias and a subgroup analysis were also assessed. RESULTS: Eighteen studies, with a total of 1,338 HCC patients who met the criteria for the meta-analysis, were included. TR, KPS improvement and CP improvement were significantly enhanced for the combination therapy compared to TACE alone (OR = 1.84, 95% CI: [1.46, 2.33], P < 0.00001; OR = 2.37, 95% CI: [1.76, 3.18], P < 0.00001; OR = 1.81, 95% CI: [1.08, 3.03], P = 0.02, respectively). The combination therapy was associated with an improvement in 1-year and 2-year SRs but not an improved 3-year SR (OR = 2.40; 95% CI: [1.59, 3.62], P < 0.0001; OR = 2.49, 95% CI: [1.24, 5.00], P = 0.01; OR = 2.49, 95% CI: [0.94, 6.61], P = 0.07, respectively). A safety analysis indicated that AEs (including nausea/vomiting, fever, hepatalgia, increased transaminase, increased bilirubin and leukopenia) were reduced for the combination treatment compared to TACE alone. CONCLUSION: The combination treatment of TACE and CKI was associated with improved TR, KPS and CP improvement and improved 1- and 2-year SRs in patients with unresectable HCC. The 3-year SR was not improved. The combination therapy resulted in a reduction in AEs. The findings of this study should be interpreted with caution because of the small sample size and study limitations.

Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties.

Coiled coils with defined assembly properties and dissociation constants are highly attractive components in synthetic biology and for fabrication of peptide-based hybrid nanomaterials and nanostructures. Complex assemblies based on multiple different peptides typically require orthogonal peptides obtained by negative design. Negative design does not necessarily exclude formation of undesired species and may eventually compromise the stability of the desired coiled coils. This work describe a set of four promiscuous 28-residue de novo designed peptides that heterodimerize and fold into parallel coiled coils. The peptides are non-orthogonal and can form four different heterodimers albeit with large differences in affinities. The peptides display dissociation constants for dimerization spanning from the micromolar to the picomolar range. The significant differences in affinities for dimerization make the peptides prone to thermodynamic social self-sorting as shown by thermal unfolding and fluorescence experiments, and confirmed by simulations. The peptides self-sort with high fidelity to form the two coiled coils with the highest and lowest affinities for heterodimerization. The possibility to exploit self-sorting of mutually complementary peptides could hence be a viable approach to guide the assembly of higher order architectures and a powerful strategy for fabrication of dynamic and tuneable nanostructured materials.

A case of de novo autoimmune hepatitis.

In this study, we reported a case of de novo autoimmune hepatitis. In this case, liver puncture biopsy was carried out and the result showed autoimmune hepatitis. In this report, we described the characteristics of this patient.

[Perforated maxillofacial defect repaired by anteromedial thigh flap instead of anterolateral thigh flap: a case report].

Anterolateral thigh flap is perfect for reconstructing maxillofacial soft tissue defects. This tissue has been widely used by clinicians, but often causes operation difficulties because of vascular variation. In this paper, we report a case where anteromedial thigh was used as new donor site when the vascular anatomic variation of anterolateral thigh perforator flap induced a failure in the flap harvest. Moreover, this paper discusses the anatomy and application of anteromedial thigh flap.

Theoretical analysis of structures and electronic spectra in molecular cadmium chalcogenide clusters.

We present calculated structural and optical properties of molecular cadmium chalcogenide nonstoichiometric clusters with a size range of less than 1 nm to more than 2 nm with well-defined chemical compositions and structures in comparison to experimental characterization and previous theoretical work. A unified treatment of these clusters to obtain a fundamental understanding of the size, ligand, and solvation effects on their optical properties has not been heretofore presented. The clusters belong to three topological classes, specifically supertetrahedral (Tn), penta-supertetrahedral (Pn), and capped supertetrahedral (Cn), where n is the number of metal layers in each cluster. The tetrahedrally shaped Tn clusters examined in this work are Cd(ER)4(2-) (T1), Cd4(ER)10(2-) (T2), and Cd10E4 (')(ER)16(4-) (T3), where R is an organic group, E and E' are chalcogen atoms (sulfur or selenium). The first member of the Pn series considered is M8E'(ER)16(2-). For the Cn series, we consider the first three members, M17E4 (')(ER)28(2-), M32E14 (')(ER)36L4, and M54E32 (')(ER)48L4(4-) (L = neutral ligand). Mixed ligand clusters with capping ER groups replaced by halogen or neutral ligands were also considered. Ligands and solvent were found to have a large influence on the color and intensity of the electronic absorption spectra of small clusters. Their effects are generally reduced with increasing cluster sizes. Blueshifts were observed for the first electronic transition with reduced size for both cadmium sulfide and cadmium selenide series. Due to weakly absorbing and forbidden transitions underlying the one-photon spectra, more care is needed in interpreting the quantum confinement from the clusters' lowest-energy absorption bands.

Refractory Dyslipidemia After Liver Transplant: Case Study With Successive Histologic Investigations.

Hyperlipidemia is not unusual in liver transplant recipients, but refractory severe hyperlipidemia is unusual. We treated a 39-year-old man who had severe dyslipidemia after liver transplant. The levels of blood lipids, liver enzymes, and essential indicators of liver pathology were monitored. The first serum sample was collected from the liver recipient 56 days after transplant surgery because samples could not be obtained sooner after the transplant. The levels of liver enzymes and blood lipids were improved with symptomatic treatment but had recurrent fluctuations. Tacrolimus and cyclosporine, even at low doses, may have been the dominant factor affecting the blood lipid levels in the recipient.

Cytokine IL-6 is required in Citrobacter rodentium infection-induced intestinal Th17 responses and promotes IL-22 expression in inflammatory bowel disease.

Citrobacter rodentium (C. rodentium) infection is a widely used murine model to mimic human enteric bacteria infection and inflammatory bowel disease (IBD). In this model, interleukin (IL)­17A plays critical roles in increasing chemokine and cytokine production in various tissues to recruit innate cells, including monocytes and neutrophils, to the local site of infection. However, the source of IL­17A remains unclear, as the majority of cell types produce IL­17A, including intestinal endothelium cells, innate immune cells and CD4+ T cells in disease development. In the current study, wild­type B6 mice were treated with C. rodentium and the CD4+ Th17 cell subset was observed as being specifically increased in Peyer's patches (PP), but not in mesenteric draining lymph nodes. Furthermore, the research suggested that the differentiation and activation of Th17 cells in PP were dependent on the inflammatory cytokine IL­6, as blocking IL­6 signaling with neutralizing antibodies decreased Th17 cells and resulted in the mice being more susceptible to C. rodentium infection. These results confirmed that the Th17 cell subset was specifically activated in PP and demonstrated that IL­6 is required in Th17 cell activation, which are important to the clinical treatment of IBD.

Clinical-pathological analysis of hepatitis B virus recurrence after liver transplantation in Chinese patients.

BACKGROUND AND AIM: Liver transplantation (LT) for hepatitis B virus (HBV)-related disease can be complicated by HBV recurrence. The aim of this study was to evaluate the risk factors, prophylaxis treatment, and histological characteristics of HBV recurrence after LT when using long-term, low-dose hepatitis B immunoglobulin (HBIG) plus nucleoside analog (lamivudine [LAM] or entecavir [ETV]). METHODS: Retrospective data from 253 adult LT patients using long-term, low-dose HBIG plus nucleoside analog after LT, for a mean treatment duration of 1-72 months, were collected from a single center in Beijing, China. Univariate analyses were conducted to determine the association among gender, age, hepatocellular carcinoma, hepatitis B e antigen-positive status, HBV-DNA level and tyrosine-methionine-aspartate-aspartate (YMDD) mutations on HBV recurrence in these patients. RESULTS: Overall, the HBV recurrence rate was 6.32% (16/253). There was no significant difference in the survival rate between the HBV recurrence and non-recurrence groups. Risk factors for HBV recurrence were: hepatitis B e antigen positivity, HBV-DNA > 10(5) copies/mL, hepatocellular carcinoma, and YMDD mutation. Sixteen patients receiving LAM had HBV recurrence (16/169; mean treatment duration: 61.8 ± 18.3 months). No HBV recurrence occurred in patients receiving ETV after LT (0/84; mean treatment duration: 57.1 ± 15.9 months). Differences in rate of mortality and HBV recurrence were not significant between the two groups. CONCLUSIONS: LT is an effective treatment for HBV-related end-stage liver disease. The combination of ETV and intramuscular HBIG for HBV recurrence prophylaxis after LT was more effective than LAM, especially in Chinese patients with HBV recurrence risk factors.

Autoantibody and human leukocyte antigen profiles in children with autoimmune liver disease and their first-degree relatives.

OBJECTIVE: Familial clustering of juvenile autoimmune liver disease (AILD), including autoimmune hepatitis and autoimmune sclerosing cholangitis (ASC), is rare, despite a high prevalence of autoimmune disorders in AILD families. METHODS: To investigate this discrepancy, we measured autoantibodies diagnostic for AILD, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, and anti-soluble liver antigen antibodies, and human leukocyte antigen profiles in 31 patients and 65 of their first-degree relatives (FDR). The autoantibody profile was compared with that of 42 healthy subjects (HS). RESULTS: Autoantibodies were detected in 71% (22/31) patients. Anti-nuclear antibody or anti-smooth muscle antibody were present in 4/65 FDR (6.2%). HS were negative for all autoantibodies. The frequencies of homozygous HLA DRB1*0301 (DR3) genes and haplotype A1-B8-DR3 were higher in the patients (25% and 43%) than in FDR (9% and 27%) and HS (0% and 16%). The frequencies of disease-protective genes DR4 and/or DR15 were lower in the patients (25%) than in FDR (42%) and HS (42%). Only 1 family contained 2 patients with AILD, 1 with ASC and 1 with primary sclerosing cholangitis. Both patients possessed A1-B8-DR3 genes, the ASC being homozygous and the primary sclerosing cholangitis heterozygous. Six FDR had nonhepatic autoimmune disorders, none being autoantibody positive. CONCLUSIONS: Homozygosity for DR3 plays a major role in the predisposition to juvenile AILD. Diagnostic autoantibodies for AILD are rare among patients' FDR and not linked to clinical manifestation of AILD.