Predictive value of the C-reactive protein to albumin ratio in the treatment of septic arthritis in young children: A retrospective study.

INTRODUCTION: Septic arthritis (SA) can cause lifelong disability in children due to joint dysfunction but there is controversy regarding the timing of surgery in SA. The C-reactive protein to albumin ratio (CAR) has emerged as a novel marker of inflammation and has been extensively used in predicting inflammatory bowel disease, arthritis, and systemic inflammation. Despite advancements, few studies have evaluated the role of CAR in SA. Therefore, the present study was aimed to investigate whether CAR could serve as predictive indicators for determining whether patients under four years old with SA should be managed conservatively or require surgical intervention, and to analyze its predictive accuracy. HYPOTHESIS: An increase in CAR values among patients under four years old with SA indicates the requirement of surgical intervention. MATERIALS AND METHODS: This retrospective study enrolled SA children under four years old and divided them into two groups, the surgery and conservative groups. The clinical data between the two groups were compared and multivariate logistic regression was performed to assess the independent predictors of SA requiring surgery. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to determine the predictive ability of CAR in SA requiring surgery. RESULTS: A total of 82 SA children were included, with 42 children (51.3%) in the surgery group and 40 children (48.7%) in the conservative group. CAR ≥ 1.165 [OR = 12.641, 95% CI (4.264 - 37.479),p < 0.001] was an independent predictive indicator for surgery in SA children under four years old, with a predicted sensitivity of 0.714, specificity of 0.850, and AUC of 0.793 [95% (0.694-0.893)] indicating good predictive accuracy. DISCUSSION: CAR to be an independent predictive indicator patients under four years old with SA. And a CAR value ≥ 1.165 upon admission in these patients suggests the necessity for surgical intervention. LEVEL OF EVIDENCE: IV, Retrospective study.

Predictive value of PAR and PNI for the acute complicated course of pediatric acute hematogenous osteomyelitis.

OBJECTIVE: Platelet to albumin ratio (PAR) and prognostic nutritional index (PNI) are potential indicators for evaluating nutritional and inflammatory status. This study aimed to examine the relationship between PAR and PNI and the acute complicated course of acute hematogenous osteomyelitis (AHO). METHODS: AHO patients were divided into the simple course group and the acute complicated course group. The patient's gender, age, site of infection, body temperature, laboratory results, and pathogen culture results were collected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors of the acute complicated course group. The receiver operating characteristic curve was applied to determine the optimal cut-off value. RESULTS: In total, 101 AHO patients with a median age of 7.58 years were included. There were 63 cases (62.4 %) in the simple course group and 38 cases (37.6 %) in the complicated course group. Binary logistic regression analysis revealed that PAR and PNI were independent risk factors for predicting the acute complicated course of AHO (p = 0.004 and p < 0.001, respectively). Receiver operating characteristic curve analysis demonstrated that the combination of PAR and PNI had an area under the curve of 0.777 (95 % CI: 0.680-0.873, p < 0.001) with a cut-off value of 0.51. CONCLUSIONS: The incidence of acute complicated courses was significantly higher in patients with high PAR and low PNI. A combined factor greater than 0.51, derived from PAR and PNI measurements within 24 h of admission, may be useful for predicting AHO patients who are likely to develop severe disease.

Optimization of decellularized liver matrix-modified chitosan fibrous scaffold for C3A hepatocyte culture.

Hepatocyte scaffold is an essential part in bioartificial liver device. We have designed a novel hepatocyte scaffold based on porcine liver extracellular matrix (ECM) and chitosan (CTS) fabrics. This CTS-ECM scaffold can improve cell adhesion and proliferation. In the present study, an orthogonal test was designed to optimize the CTS/ECM composite scaffold, in which ECM concentration, EDC concentration and EDC to NHS ratio were taken as factors, proportion of nitrogen element and hydroxyproline content as indicators. The cytocompatibility of the novel scaffold for C3A hepatocytes was analyzed in vitro. The orthogonal test demonstrated that the optimal scaffold should be based on ECM concentration of 5 mg/mL, EDC concentration of 5 mg/mL, and EDC to NHS ratio 1:1. C3A hepatocytes cultured on the optimized CTS-ECM scaffolds showed stronger proliferation and functionality than those on Cytodex3 microcarriers (p < 0.05). The CTS/ECM composite scaffold may be widely used as a promising hepatocyte culture carrier, especially in bioartificial liver support systems.

Decellularized liver matrix-modified chitosan fibrous scaffold as a substrate for C3A hepatocyte culture.

A bioreactor filled with functional hepatocytes is a crucial portion of the bio-artificial liver device. However, it is a difficult task to maintain sufficient cell quantity and active hepatocellular function. In this work, we developed a promising scaffold for hepatocyte culture by coating porcine liver extracellular matrix (ECM) on chitosan (CTS) fabrics. Porcine Liver was decellularized using 1% Triton X-100. Solubilized liver ECM was immobilized on CTS fibers surface through cross linking of ECM and CTS with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS). Then the scaffold was characterized by Fourier transformed infrared spectroscopy in attenuated total reflection mode (ATR-FTIR), X-photoelectron spectroscopy (XPS) and water contact angle measurement. The efficacy of modified scaffolds to maintain C3A hepatocytes adhesion, proliferation, bioactivity and functionality in vitro was detected. FTIR spectra and XPS demonstrated the presence of ECM coating on CTS fabric surface. Covalently attached coating significantly improved the binding efficiency between ECM and CTS fabrics, in comparison to the coating by physical absorption. Furthermore, C3A hepatocytes cultured on coated scaffolds showed enhanced cell bioactivity and liver-specific function, such as albumin secretion and urea synthesis, compared with those cultured on untreated scaffolds(p < 0.05). As a promising hepatocyte culture carrier, the ECM coated CTS fabrics could be applied in the biological artificial liver reactor.

Autoimmune cholangitis and cholangiocarcinoma.

Autoimmune cholangitis, immunoglobulin G4-associated cholangitis (IAC), is a part of multiorgan IgG4-related systemic disease, which was recognized as a new clinicopathological entity in recent years. IAC is defined as a biliary stricture that responds to steroid therapy, frequently is associated with other fibrosing conditions, especially autoimmune pancreatitis and is characterized by elevation of IgG4 in serum and infiltration of IgG4 positive plasma cells in bile ducts. Since IAC shares a number of clinical, biochemical, and imaging features with cholangiocarcinoma (CCA), it is often misdiagnosed as CCA, and unnecessary surgery was performed. In this compact review, we clarify the disease of IAC, summarize criteria for diagnosis of IAC, discuss the role of CA 19-9, and provide key information to differentiate diagnosis of IAC from CCA. IAC should be highly suspected in unexplained biliary stricture associated with increased IgG4 (in serum especially in bile) and other organ involvement (kidney, retroperitoneum etc. especially pancreas in which there are abundant IgG4-positive plasmocytes infiltration). Correct diagnosis of IAC will avoid unnecessary surgery because IAC responds well to steroid therapy. In a word, increased IgG4 levels, other organ involvement and response to steroids are keys to distinguishing IAC from CCA.

[Factor V Leiden mutation leads to enhanced atherosclerosis in apolipoprotein E deficient mice].

OBJECTIVE: Factor V Leiden (FvL) causing activated protein C resistance is a genetic risk factor for venous thrombosis in humans, and it's effect on atherosclerosis is controversial. We evaluated the effect of FvL mutation on atherosclerosis in apolipoprotein E deficient mice fed with normal diet. METHODS: Degree of atherosclerosis and tissue fibrin deposition were determined in Fv+/+ApoE-/-, FvQ/+ApoE-/- and FvQ/QApoE-/- mice. RESULTS: In the presence of ApoE deficiency, homozygous FvL significantly increased atherosclerosis coverage in ApoE-/- mice (FvQ/QApoE-/- vs. Fv+/+ApoE-/-=5.0%+/-1.1% vs. 2.2%+/-0.4%, P<0.005) and tissue fibrin deposition in atherosclerotic lesion (FvQ/QApoE-/- vs. Fv+/+ApoE-/-=3.4% +/- 0.5% vs. 1.8%+/-0.4%, P<0.05). The atherosclerotic lesion of FvQ/+ApoE-/- mice was intermediate between FvQ/Q ApoE-/- and Fv+/+ApoE-/-, and there was no significant difference comparing with any of them. CONCLUSIONS: These observations demonstrate that homozygous FvL could promote atherosclerosis and fibrin deposition in apolipoprotein E deficient mice suggesting that Factor V mutation could be an important genetic risk factor for the enhanced atherosclerosis in human.

Transfection of the DAAO gene and subsequent induction of cytotoxic oxidative stress by D-alanine in 9L cells.

D-amino acid oxidase (DAAO) can catalyze the dehydrogenation of D-amino acids, such as D-alanine, to the corresponding amino acids and is then reoxidized by molecular oxygen to yield hydrogen peroxide, a reactive oxygen species, which reacts with DNA, lipids and protein, inducing cell death. This study investigated whether rat glioma 9L cells infected with the recombinant retrovirus containing the DAAO cDNA fragment can be induced in order to undergo cytotoxic oxidative stress by D-alanine. The recombinant retroviral vector, plzrus-DAAO-FLAG-GFP (pl-Dfg), was constructed and used to transfect packaged phoenix cells. The supernatant containing recombinant retroviral particles from the transfected phoenix cells was harvested and utilized to infect target 9L cells. The cytotoxic oxidative stress of infected 9L cells was induced by the DAAO substrate, D-alanine. The plasmid pl-Dfg was successfully constructed. The high titer retroviral supernatant was obtained from the transfected phoenix cells. Infected 9L cells were less viable after exposure to D-alanine compared to the control group. Anti-apoptotic proteins significantly inhibited cell death. The DAAO/D-alanine system has a potential utility for gene therapy and may be an effective strategy for the treatment of brain cancer and other malignant tumors.

Late onset of severe graft-versus-host disease following liver transplantation.

Graft versus host disease (GVHD) is an uncommon but lethal complication following liver transplantation that results from the engraftment of T lymphocytes associated with the liver graft. It usually occurs 2 to 6 weeks after the procedure. We herein report a case of late onset of severe GVHD 4 months after cadaveric liver transplantation for hepatocellular carcinoma in a 54-year-old woman, which was characterized by refractory diarrhea and abdominal pain. Moreover we discuss risk factors of GVHD including the recipient age and cytomegalovirus (CMV) infection.

High efficient mammalian expression and secretion of a functional humanized single-chain Fv/human interleukin-2 molecules.

AIM: To construct and produce a recombinant bispecific humanized single-chain Fv (sFv) /Interleukin-2 (IL-2) fusion protein by using mammalian cells. METHODS: The sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv/IL-2 with high efficiency. RESULTS: The fusion protein was constructed and high efficiently expressed with yields up to 102 +/- 4.2 mg/L in culture supernatant of the stably transfected 293 cell line. This recombinant fusion protein consisted of humanized variable heavy (V(H)) and light (V(L)) domains of monoclonal antibody (mAb) 520C9 directed against the human HER-2/neu (c-erbB2) proto-oncogene product p185, and human IL-2 connected by polypeptide linker. The fusion protein was shown to retain the immunostimulatory activities of IL-2 as measured by IL-2-dependent cell proliferation and cytotoxicity assays. In addition to its IL-2 activities, this fusion protein also possessed antigen-binding specificity against p185, as determined by indirect ELISA using p185 positive SKOV 3ip1 cells. CONCLUSION: The large-scale preparation of the recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293 cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an effective means of targeting therapeutic doses of IL-2 to p185 positive tumors without increasing systemic toxicity or immunogenicity.