Giant cell arteritis (GCA) is the most common vasculitis in elderly, with ischemic and constitutional symptoms caused by vascular involvement and systemic inflammation. Early initiation of therapy results in prompt remission, while patients may still experience flares or severe complications during glucocorticoid tapering. This study was to identify the characteristics of Chinese GCA patients with different prognosis.Ninety-one patients diagnosed with GCA in Peking Union Medical College Hospital in the last 20 years were followed up. Those who were lost to follow up or were followed up for less than 1 year were excluded. According to the prognosis, patients were divided into the group of favourable prognosis (patients who sustained disease remission for over 1 year) and unfavorable prognosis (patients who had relapses or severe complications). Clinical data at disease onset and after treatment were collected and analysed between the 2 groups.Thirty-seven patients with favourable prognosis and 40 patients with unfavourable prognosis were admitted into the study. Fever as an onset symptom was less common in favourable group (P=.016). As for presentations of GCA, fever, tenderness and abnormal pulsation of temporal artery and jaw claudication were less frequently observed in patients with favourable prognosis (P=.029, .049, .043, respectively). At onset, medium-size arteries were affected more in unfavorable prognosis group (P = .048), and involvement of branches below the aortic arch were more common in favorable prognosis group (P = .034). Erythrocyte sedimentation rate in group of favourable prognosis were significantly lower after treatment (P = .041). Compared with healthy subjects, GCA patients had increased monocytes and decreased lymphocytes at disease onset (P < .01). Monocyte counts were higher in patients with favourable prognosis at disease onset (P = .043), while no significant differences were seen between the 2 groups after treatment. Lymphocyte counts were lower in patients with unfavourable prognosis (P = .014) after treatment.Complete blood count may reflect the disease status of GCA. Little change in monocyte during treatment and lower lymphocytes after treatment may serve as potential predictors of unfavourable clinical prognosis.

Radiotherapy is the major approach and is well tolerated in locally advanced esophageal squamous cell carcinoma (ESCC). And nowadays, no effective biological markers have been identified for predicting the prognosis of patients with ESCC. Platelet-derived growth factor (PDGF) is associated with a poor prognosis of various malignancies. The present study aimed to assess the effect of PDGF-BB on radiotherapeutic responses of ESCC and the underlying mechanisms of its roles in ESCC. Serum from 68 cases that received neoadjuvant or radical radiotherapy was obtained before and during radiotherapy. Gene expression analyses were validated by enzyme linked immunosorbent assay. The prognosis of patients with significantly reduced PDGF-BB was probably better than that of the others found in the progression-free survival and overall survival groups. Depletion of PDGFB significantly suppressed the proliferation, invasion and migration of cancer cells. Inhibiting PDGFB induced cellular apoptosis and promoted the sensitivity to ionizing radiation (IR). Furthermore, IR inhibited PDGF-BB-induced migration by blocking the PI3K/AKT pathway in ESCC cells. We found that the expression of PDGF-BB provided a possible model for predicting ESCC radiotherapy. It can also be used as a prognostic indicator for locally advanced ESCC that was treated by radiotherapy.

To explore the understanding of refractory gout in Chinese rheumatologists.

Autoinflammatory phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) is a rare autoinflammatory disease caused by gain-of-function mutations in the PLCG2 gene. Here we report a rare case of APLAID patient carrying a novel heterozygous missense PLCG2 I169V mutation with gangrenous pyoderma and concomitant high serum immunoglobulin (Ig) E level.

Patulin (PAT) is a toxic fungal metabolite, and oxidative damage was proved to be its important toxicity mechanism. Selenium nanoparticles (SeNPs) were prepared by reducing sodium selenite with chitosan as a stabilizer and used for preventing PAT-induced liver, kidney and gastrointestinal damage. SeNPs have good dispersibility, in vitro antioxidant activity, and are much less cytotoxic than sodium selenite. Cell culture studies indicated that SeNPs can effectively alleviate PAT-induced excessive production of intracellular ROS, the decline of glutathione peroxidase activity, and the suppression of cell viability. Evaluation of serum biochemical parameters, histopathology, oxidative stress biomarkers and activities of antioxidant enzymes in a mouse model showed that pre-treatment with SeNPs (2 mg Se/kg body weight) could ameliorate PAT-induced oxidative damage to the liver and kidneys of mice, but PAT-induced gastrointestinal oxidative damage and barrier dysfunction were not recovered by SeNPs, possibly because the toxin doses suffered by the gastrointestinal as the first exposed tissues exceeded the regulatory capacity of SeNPs. These results suggested that a combination of other strategies may be required to completely block PAT toxicity.

Giant cell arteritis (GCA) is a medium- and large-vessel vasculitis with an onset age after 50 years. Takayasu arteritis (TA), which is also a large-vessel vasculitis with an onset age earlier than 40 years, was suggested to be associated with tuberculosis (TB). However, the association between GCA and TB was rarely reported. This study was to retrospectively analyze clinical data of GCA patients at Peking Union Medical College Hospital and elucidate the association between GCA and TB. Ninety-one patients diagnosed with GCA were included in the study. A total of 20 patients (22.0%) had a history of active tuberculosis and received anti-tuberculosis therapy. On comparing the clinical features of patients with GCA and concomitant TB and those without TB, obvious weight loss (P = 0.011), lower percentage of dyslipidemia (P = 0.042), higher percentage of anti-phospholipid antibodies (P = 0.010), and lower white blood cells (P = 0.006) were noted in the TB group. In conclusion, this study demonstrated the percentage of TB history in patients with GCA was higher than that in the Chinese general population. Clinicians should recognize the possibility of comorbid TB in patients with obvious weight loss and relatively lower white blood cell count.

In the food industry, microbiological safety is a major concern. Mycotoxin patulin represents a potential health hazard, as it is heat-resistant and may develop at any stage during the food chain, especially in apple-based products, leading to severe effects on human health, poor quality products, and profit reductions. The target of the study was to identify and characterize an excellent adsorbent to remove patulin from apple juice efficiently and to assess its adsorption mechanism. To prevent juice fermentation and/or contamination, autoclaving was involved to inactivate bacteria before the adsorption process. The HPLC (high-performance liquid chromatography) outcome proved that all isolated strains from kefir grains could reduce patulin from apple juice. A high removal of 93% was found for juice having a 4.6 pH, 15° Brix, and patulin concentration of 100 μg/L by Lactobacillus kefiranofacien, named JKSP109, which was morphologically the smoothest and biggest of all isolates in terms of cell wall volume and surface area characterized by SEM (Scanning electron microscopy) and TEM (transmission electron microscopy). C=O, OH, C-H, and N-O were the main functional groups engaged in patulin adsorption indicated by FTIR (Fourier transform-infrared). E-nose (electronic nose) was performed to evaluate the aroma quality of the juices. PCA (Principal component analysis) results showed that no significant changes occurred between control and treated juice.

Secretory immunoglobulin A (SIgA) acts as the first line of defense against respiratory pathogens. In this assay, the variable regions of heavy chain (VH) and Light chain (VL) genes from a mouse monoclonal antibody against H5N1 were cloned and fused with human IgA constant regions. The full-length chimeric light and heavy chains were inserted into a eukaryotic expressing vector and then transfected into CHO/dhfr-cells. The chimeric monomeric IgA antibody expression was confirmed by using ELISA, SDS-PAGE, and Western blot. In order to obtain a dimeric secretory IgA, another two expressing plasmids, namely, pcDNA4/His A-IgJ and pcDNA4/His A-SC, were cotransfected into the CHO/dhfr-cells. The expression of dimeric SIgA was confirmed by using ELISA assay and native gel electrophoresis. In microneutralization assay on 96-well immunoplate, the chimeric SIgA showed neutralization activity against H5N1 virus on MDCK cells and the titer was determined to be 1 : 64. On preadministrating intranasally, the chimeric SIgA could prevent mice from lethal attack by using A/Vietnam/1194/04 H5N1 with a survival rate of 80%. So we concluded that the constructed recombinant chimeric SIgA has a neutralization capability targeting avian influenza virus H5N1 infection in vitro and in vivo.

The severe bacterial infection and chronic wound healing caused by the abuse of antibiotics threaten the public health, which calls the need for the development of novel antibacterial agents and alternative therapeutic strategies. Herein, magnetic carboxymethyl cellulose-ε-polylysine hybrids (FCE) were synthesized via a facile one-pot coprecipitation method and further used as matrix to anchor silver nanoparticles (Ag NPs). The as-resulted Ag/FCE hybrids were employed to inactivate pathogenic bacteria and accelerate bacteria-infected wound healing with the assistance of H2O2. In vitro investigation revealed the combination of hydroxyl radical (·OH) originated from low concentration of H2O2 catalyzed by Ag/FCE and the antimicrobial activity of Ag NPs endowed effective antibacterial performance to the hybrids against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Investigation on antibacterial mechanism indicated antibacterial activity of the synergetic strategy was achieved by destroying bacterial cell integrity, arresting metabolic, producing intracellular ROS, and oxidizing GSH. Additionally, in vivo assay exhibited Ag/FCE possessed satisfactory biocompatibility and effectively accelerated S. aureus-infected wound healing with the presence of low concentration of H2O2. Altogether, the presented results supported the great potential application of the synergistic antibacterial strategy for the therapy of bacterial-infected wound healing.

Most macromolecular antimicrobials are ionic and thus lack miscibility/compatibility with nonionic substrate materials. In this context, nonionic hyperbranched polyesters (HBPs) with indole or isatin functionality were rationally designed, synthesized, and characterized. Antimicrobial disk diffusion assay indicated that these HBPs showed significant antibacterial activity against 8 human pathogenic bacteria compared to small molecules with indole or isatin groups. According to DSC measurements, up to 20% indole-based HBP is miscible with biodegradable polyesters (polyhydroxybutyrate or polycaprolactone), which can be attributed to the favorable hydrogen bonding between the N-H moiety of indole and the C═O of polyesters. HBPs with isatin or methylindole were completely immiscible with the same matrices. None of the HBPs leaked out from plastic matrix after being immersed in water for 5 days. The incorporation of indole into HBPs as well as small molecules facilitated their enzymatic degradation with PETase from Ideonella sakaiensis, while isatin had a complex impact. Molecular docking simulations of monomeric molecules with PETase revealed different orientations of the molecules at the active site due to the presence of indole or isatin groups, which could be related to the observed different enzymatic degradation behavior. Finally, biocompatibility analysis with a mammalian cell line showed the negligible cytotoxic effect of the fabricated HBPs.

Giant cell arteritis (GCA) is the most common systemic vasculitis in individuals aged ≥50 years. Some patients with GCA who develop fever at onset without typical ischemic manifestations may be misdiagnosed with fever of unknown origin.

Multiple joint procedures during a single anesthetic episode have been proposed for patients with hemophilia as a way to reduce cost. The postoperative 90-day complication rate and the cost distribution between multiple joint procedures and single joint procedures for patients with hemophilia have not been well studied.

Metastasis accounts for 90% of cancer-related deaths and, currently, there are no effective clinical therapies to block the metastatic cascade. A need to develop novel therapies specifically targeting fundamental metastasis processes remains urgent. Here, we demonstrate that Salmonella YB1, an engineered oxygen-sensitive strain, potently inhibits metastasis of a broad range of cancers. This process requires both IFN-γ and NK cells, as the absence of IFN-γ greatly reduces, whilst depletion of NK cells in vivo completely abolishes, the anti-metastatic ability of Salmonella. Mechanistically, we find that IFN-γ is mainly produced by NK cells during early Salmonella infection, and in turn, IFN-γ promotes the accumulation, activation, and cytotoxicity of NK cells, which kill the metastatic cancer cells thus achieving an anti-metastatic effect. Our findings highlight the significance of a self-regulatory feedback loop of NK cells in inhibiting metastasis, pointing a possible approach to develop anti-metastatic therapies by harnessing the power of NK cells.

High-dose hypofractionated radiotherapy (HRT) is an important anticancer treatment modality that activates antitumor host immune responses. However, HRT for oligometastases of colorectal cancer (CRC) has shown frustrating results in the clinic. As part of immune evasion, myeloid cells express signal regulatory protein α (SIRPα) to inhibit phagocytosis by phagocytes in the tumor microenvironment (TME). We postulated that SIRPα blockade enhances HRT by alleviating the inhibitory action of SIRPα on phagocytes. We demonstrated that SIRPα on myeloid cells was upregulated in the TME after HRT. When SIRPα blockade was administered with HRT, we observed superior antitumor responses compared with anti-SIRPα or HRT alone. When anti-SIRPα was administered to local HRT, the TME could become a tumoricidal niche that was heavily infiltrated by activated CD8+ T cells, but with limited myeloid-derived suppressor cells and tumor-associated macrophages. While CD8+ T cells were required for the effectiveness of the anti-SIRPα + HRT combination. The triple therapy with anti-SIRPα + HRT + anti-PD-1 had superior antitumor responses compared with the combination of any two therapies and established a strong and long-lasting adaptive immunological memory. Collectively, SIRPα blockade provides a novel way to overcome HRT resistance in oligometastatic CRC patients. Our results herein provide a valuable cancer treatment strategy that has the potential to be translated into clinical practice.

This study aimed to determine the reaction kinetics of the regioselective glucuronidation of diosmetin and chrysoeriol, two important methylated metabolites of luteolin, by human liver microsomes (HLMs) and uridine-5'-diphosphate glucuronosyltransferase (UGTs) enzymes. This study also investigated the effects of breast cancer resistance protein (BCRP) on the efflux of diosmetin and chrysoeriol glucuronides in HeLa cells overexpressing UGT1A9 (HeLa-UGT1A9). After incubation with HLMs in the presence of UDP-glucuronic acid, diosmetin and chrysoeriol gained two glucuronides each, and the OH-in each B ring of diosmetin and chrysoeriol was the preferable site for glucuronidation. Screening assays with 12 human expressed UGT enzymes and chemical-inhibition assays demonstrated that glucuronide formation was almost exclusively catalyzed by UGT1A1, UGT1A6, and UGT1A9. Importantly, in HeLa-UGT1A9, Ko143 significantly inhibited the efflux of diosmetin and chrysoeriol glucuronides and increased their intracellular levels in a dose-dependent manner. This observation suggested that BCRP-mediated excretion was the predominant pathway for diosmetin and chrysoeriol disposition. In conclusion, UGT1A1, UGT1A6, and UGT1A9 were the chief contributors to the regioselective glucuronidation of diosmetin and chrysoeriol in the liver. Moreover, cellular glucuronidation was significantly altered by inhibiting BCRP, revealing a notable interplay between glucuronidation and efflux transport. Diosmetin and chrysoeriol possibly have different effects on anti-cancer due to the difference of UGT isoforms in different cancer cells.

Chronic gouty arthritis, caused by a persistent increase in, and the deposition of, soluble uric acid (sUA), can induce pathological chondrocyte destruction; however, the effects of urate transport and intracellular sUA on chondrocyte functionality and viability are yet to be fully determined. Thus, the aim of the present study was to investigate the presence and functionality of a urate transport system in chondrocytes. The expression profiles of two primary urate reabsorptive transporters, glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), in human articular cartilage and chondrocyte cell lines were examined via western blotting, reverse transcription‑quantitative PCR, immunohistochemistry and immunofluorescence. Then, chondrocytes were incubated with exogenous sUA at increasing concentrations. Negative control assays were conducted via the specific knockdown of GLUT9 and URAT1 with lentiviral short hairpin (sh)RNAs, and by pretreatment with benzbromarone, a known inhibitor of the two transporters. Intracellular UA concentrations were measured using colorimetric assays. The expression levels of GLUT9 and URAT1 were determined in cartilage tissues and chondrocyte cell lines. Incubation of chondrocytes with sUA led to a concentration‑dependent increase in intracellular urate concentrations, which was inhibited by GLUT9 or URAT1 knockdown, or by benzbromarone pretreatment (27.13±2.70, 44.22±2.34 and 58.46±2.32% reduction, respectively). In particular, benzbromarone further decreased the already‑reduced intracellular UA concentrations in HC‑shGLUT9 and HC‑shURAT1 cells by 46.79±2.46 and 39.79±2.22%, respectively. Cells overexpressing GLUT9 and URAT1 were used as the positive cell control, which showed increased intracellular UA concentrations that could be reversed by treatment with benzbromarone. In conclusion, chondrocytes may possess an active UA transport system. GLUT9 and URAT1 functioned synergistically to transport UA into the chondrocyte cytoplasm, which was inhibited by specific gene knockdowns and drug‑induced inhibition. These results may be fundamental in the further investigation of the pathological changes to chondrocytes induced by sUA during gouty arthritis, and identified UA transport processes as potential targets for the early control of chronic gouty arthritis.

Currently, there is an intensive development of bio-based aromatic building blocks to replace fossil-based terephthalates used for poly(ethylene terephthalate) production. Indole is a ubiquitous aromatic unit in nature, which has great potential as a bio-based feedstock for polymers or plastics. In this study, we describe the synthesis and characterization of new indole-based dicarboxylate monomers with only aromatic ester bonds, which can improve the thermal stability and glass-transition temperature (T g) of the resulting polyesters. The new dicarboxylate monomers were polymerized with five aliphatic diols to yield 10 new polyesters with tunable chemical structures and physical properties. Particularly, the T g values of the obtained polyesters can be as high as 113 °C, as indicated by differential scanning calorimetry and dynamic mechanical analysis. The polyesters showed decent thermal stability and distinct flow transitions as revealed by thermogravimetric analysis and rheology measurements.

Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome.

This research aims to investigate nonionic hyperbranched polyesters (HBPs) derived from indole and lignin resources as new nontoxic antimicrobial coatings. Three nonionic HBPs with zero to two methoxy ether substituents on each benzene ring in the polymer backbones were synthesized by melt-polycondensation of three corresponding AB2 monomers. The molecular structures and thermal properties of the obtained HBPs were characterized by gel permeation chromatography, nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry analyses. These HBPs were conveniently spin-coated on a silicon substrate, which exhibited significant antibacterial effect against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis). The presence of methoxy substituents enhanced the antimicrobial effect, and the resulting polymers showed negligible leakage in water. Finally, the polymers with the methoxy functionality exhibited excellent biocompatibility according to the results of hemolysis and MTT assay, which may facilitate their biomedical applications.

Staphylococcus aureus infection is a severe public health concern with the growing number of multidrug-resistant strains. S. aureus can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasion strategies developed by S. aureus is thus crucial for its infection control. In this study, we exploited the SpyCatcher-SpyTag system to engineer bacterial outer membrane vesicles (OMVs) for the development of a multitargeting S. aureus click vaccine. We decorated OMVs with surface exposed SpyCatcher via a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused S. aureus antigens to generate an OMV-based click vaccine. Compared with antigens mixed with alum adjuvant, the click vaccine simultaneously induced more potent antigen-specific humoral and Th1-based cellular immune response, which afforded protection against S. aureus Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging S. aureus clinical isolates.