Comparative efficacy and safety of the treatment by Omalizumab for chronic idiopathic urticaria in the general population: A systematic review and network meta-analysis.

BACKGROUND: Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients. MATERIALS AND METHODS: Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs). RESULTS: In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo. CONCLUSION: 300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.

Synthetic Antioxidants as Contaminants of Emerging Concern in Indoor Environments: Knowns and Unknowns.

Synthetic antioxidants, including synthetic phenolic antioxidants (SPAs), amine antioxidants (AAs), and organophosphite antioxidants (OPAs), are essential additives for preventing oxidative aging in various industrial and consumer products. Increasing attention has been paid to the environmental contamination caused by these chemicals, but our understanding of synthetic antioxidants is generally limited compared to other emerging contaminants such as plasticizers and flame retardants. Many people spend a significant portion (normally greater than 80%) of their time indoors, meaning that they experience widespread and persistent exposure to indoor contaminants. Thus, this Perspective focuses on the problem of synthetic antioxidants as indoor environmental contaminants. The wide application of antioxidants in commercial products and their demonstrated toxicity make them an important family of indoor contaminants of emerging concern. However, significant knowledge gaps still need to be bridged: novel synthetic antioxidants and their related transformation products need to be identified in indoor environments, different dust sampling strategies should be employed to evaluate human exposure to these contaminants, geographic scope and sampling scope of research on indoor contamination should be broadened, and the partition coefficients of synthetic antioxidants among different media need to be investigated.

Occurrence, Fate, Human Exposure, and Toxicity of Commercial Photoinitiators.

Photoinitiators (PIs) are a family of anthropogenic chemicals used in polymerization systems that generate active substances to initiate polymerization reactions under certain radiations. Although polymerization is considered a green method, its wide application in various commercial products, such as UV-curable inks, paints, and varnishes, has led to ubiquitous environmental issues caused by PIs. In this study, we present an overview of the current knowledge on the environmental occurrence, human exposure, and toxicity of PIs and provide suggestions for future research based on numerous available studies. The residual concentrations of PIs in commercial products, such as food packaging materials, are at microgram per gram levels. The migration of PIs from food packaging materials to foodstuffs has been confirmed by more than 100 reports of food contamination caused by PIs. Furthermore, more than 20 PIs have been detected in water, sediment, sewage sludge, and indoor dust collected from Asia, the United States, and Europe. Human internal exposure was also confirmed by the detection of PIs in serum. In addition, PIs were present in human breast milk, indicating that breastfeeding is an exposure pathway for infants. Among the most available studies, benzophenone is the dominant congener detected in the environment and humans. Toxicity studies of PIs reveal multiple toxic end points, such as carcinogenicity and endocrine-disrupting effects. Future investigations should focus on synergistic/antagonistic toxicity effects caused by PIs coexposure and metabolism/transformation pathways of newly identified PIs. Furthermore, future research should aim to develop "greener" PIs with high efficiency, low migration, and low toxicity.

Preparation of a novel metal-free polypyrrole-red phosphorus adsorbent for efficient removal of Cr(VI) from aqueous solution.

The toxicity and carcinogenicity of Cr(VI) makes it a major threat to the health of animals and people. However, how to efficiently remove Cr(VI) still faces important challenges. In this study, a new metal-free polypyrrole-red phosphorus (PPy-RP) composite is successfully synthesized by in-situ oxidation polymerization for Cr(VI) removal from wastewater. The maximum adsorption capacity (qm) of Cr(VI) on PPy-RP-1 is 513.2 mg/g when the pH value is 2, which is far superior to RP nanosheets (207.8 mg/g) and PPy (294.9 mg/g). The improved qm can be ascribe to the good dispersion and increased specific surface area of PPy-RP adsorbent. Encouragingly, PPy-RP adsorbent still exhibits excellent stability after 7 cycles tests without a significant decline in removal efficiency, and remain above 81.4%. Based on the fittings of adsorption isotherms and kinetics, the process conforms to the pseudo-first-order kinetic model and the single-layer adsorption of the Langmuir model with an R2 value of 0.98533. The adsorption process is chemical and monolayer. The experimental result demonstrates that the PPy-RP can efficient removal Cr(VI) by electrostatic attraction and complexation reaction (formation of N-Cr(VI) bond) through the PPy on the surface. The results of this study indicate that PPy-RP is a promising adsorbent to remove the Cr(IV).

Fine mapping and candidate gene analysis of CRA3.7 conferring clubroot resistance in Brassica rapa.

KEY MESSAGE: In this study, we fine-mapped a clubroot resistance gene CRA3.7 in Chinese cabbage and developed its closely linked marker syau-InDel3008 for marker-assisted selection in CR cultivars breeding. Chinese cabbage is an important leafy vegetable rich in many nutrients widely grown in China. Clubroot disease caused by an obligate biotrophic pathogen Plasmodiophora brassicae was rapidly spread and challenged to Chinese cabbage production. A clubroot resistance (CR) gene, CRA3.7, was mapped on chromosome A03 of Brassica rapa. A Chinese cabbage line 'CR510', which harbor homozygous resistance locus CRA3.7 was selected from a BC4F3 family. 'CR510' was crossed with a clubroot susceptible Chinese cabbage inbred line '59-1'. Total 51 recombinant plants were identified from an F2 population including 3000 individuals. These recombinants were selfed and the clubroot resistance of F2/3 families was evaluated. Finally, a clubroot resistance gene CRA3.7 was fine-mapped to an interval of approximately 386 kb between marker syau-InDel3024 and syau-InDel3008. According to the reference genome, total 54 genes including five encoding the TIR-NBS-LRR proteins was annotated in the fine-mapped region. Further, nine candidate's gene expression in parental lines at 7, 14 and 21 days after inoculation of P. brassicae were evaluated. Bra019376, Bra019401, Bra019403 and Bra019410 are highly expressed in 'CR510' than '59-1'. Gene sequence of Bra019410 from 'CR510' was cloned and identified different from CRa. Therefore, Bra019376, Bra019401, Bra019403 and Bra019410 are the most likely candidates for CRA3.7. Our research provides a valuable germplasm resource against P. brassicae Pb3 and CRA3.7 closely linked marker for marker-assisted selection in CR cultivars breeding.

Rare Case of Paraneoplastic Pemphigus Associated With Prostatic Cancer.

ABSTRACT: The combination of paraneoplastic pemphigus and prostate cancer is extremely unusual and has not been reported yet. Paraneoplastic pemphigus is caused by tumor-induced autoantibodies, which cause damage to the skin and mucosa. The essential treatment is active tumor control. Our patient received a robot-assisted radical prostatectomy and glucocorticoid therapy to improve his condition and relieve his skin lesions.

Thromboelastography predicting the prognosis of sudden sensorineural hearing loss.

OBJECTIVES: To explore the association between thromboelastography and the clinical features as well as the prognosis of sudden sensorineural hearing loss (SSNHL). DESIGN: Single-centre, retrospective study. SETTING: A hospital in China. PARTICIPANTS: In total, 133 patients presented with SSNHL within 2 weeks before the study, who did not receive treatment. MAIN OUTCOME MEASURES: The patients' medical history was collected. Audiological, imaging and haematological examinations were performed before treatment. Patients with abnormal thromboelastography were re-examined 1 week after treatment, and efficacy was evaluated 1 month after treatment. The chi-squared test and binary logistic regression analysis were used to analyse the association between factors, such as vertigo, degree and type of hearing loss, vestibular function, inner ear MRI results, thromboelastography and efficacy of treatment. RESULTS: Thromboelastography was correlated with prognosis (p = 0.049) and degree (p = 0.030) and type of hearing loss (p = 0.013) in patients with SSNHL. The R (p =  0.002) and angle values (p =  0.010) correlated with prognosis. The MA (p =  0.022) and G values (p =  0.020) correlated with the degree of hearing loss. The R (p =  0.033) value correlated with inner ear MRI results, and the ΔG (p =  0.010) value correlated with fibrinogen levels. ΔThromboelastography (p =  0.032) was correlated with the prognosis of patients with abnormal thromboelastography results. Logistic regression analysis showed that thromboelastography correlated with prognosis (p =  0.013), and Δthromboelastography correlated with the prognosis of patients with abnormal thromboelastography results (p =  0.013) and vertigo (p =  0.016). CONCLUSION: Thromboelastography is an independent risk factor affecting the prognosis of SSNHL with the R and angle values playing a major role.

Characteristics and prognosis analysis of bilateral sudden sensorineural hearing loss: A retrospective case-control study.

OBJECTIVES: To evaluate the clinical characteristics and prognostic factors of simultaneous and sequential bilateral sudden sensorineural hearing loss (Si-BSSNHL and Se-BSSNHL, respectively). DESIGN: Retrospective case-control study. SETTING: A single tertiary referral centre. PARTICIPANTS: Patients diagnosed with unilateral sudden sensorineural hearing loss (USSNHL), Si-BSSNHL, or Se-BSSNHL between September 2018 and November 2019. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, audiological features, laboratory results and hearing recovery were analysed for intergroup comparisons. Prognostic factors for BSSNHL were analysed using univariate and multivariate logistic analyses between the overall and no-recovery groups. RESULTS: Compared to the USSNHL group, a larger final pure-tone average (PTA) (H = 38.0 and 53.8, respectively, both adjusted p-value (p adj) <.05), lower hearing gain (H = -70.8 and - 74.6, respectively, both p adj <.001) and higher homocysteine levels (H = 46.8, 58.8, respectively, both p adj <.05) were observed in the Si-BSSNHL and Se-BSSNHL groups, while the rate of positive vestibular tests and proportion of tinnitus were lower in the Se-BSSNHL group (χ2  = 8.5 and 38.1, respectively, both p adj <0.05). The USSNHL group showed a significant difference in the degree of deafness and therapeutic outcome in the Se-BSSNHL and Si-BSSNHL groups, respectively (χ2  = 12.4, p adj <.05; χ2  = 13.6; p adj <.05). Hypertension (95% confidence interval, 1.014-28.623, p < .05) and onset days (95% confidence interval, 0.007-0.626, p < .05) were associated with the therapeutic effects of BSSNHL. CONCLUSIONS: Higher homocysteine levels in BSSNHL may implicate microvascular disorders as a causative factor of BSSNHL. Hypertension and onset days were associated with the prognosis of BSSNHL.

The flavonoid luteolin suppresses infantile hemangioma by targeting FZD6 in the Wnt pathway.

Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in treating infantile hemangioma. We first tested the effect of luteolin on cell proliferative potential and VEGFA expression in hemangioma-derived stem cells (HemSCs). We then examined the efficacy of systemic application of luteolin in a murine hemangioma model. We then identified the downstream factor regulated by luteolin in HemSCs and validated its causative relationship with knock-down method in both in vitro and in vivo models. We also investigated the protein expression change of this targeting factor in proliferating hemangiomas. Luteolin inhibited HemSC growth and suppressed VEGF-A expression in a dose-dependent manner. Luteolin inhibited microvessel formation and de novo vasculogenesis in the murine model. FZD6 was induced by luteolin and exerted the anti-angiogenesis effect in our tumor models. Lastly, FZD6 level was repressed in the clinical tissues of human proliferating hemangiomas. Luteolin is a promising new agent to treat infantile hemangioma. Targeting the Wnt pathway may represent a potential therapeutic strategic to inhibit angiogenesis in proliferating hemangiomas.

CircADARB1 serves as a new biomarker in natural killer T-cell lymphoma and a potential regulator of p-Stat3.

BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive subtype of Non-Hodgkin's Lymphoma. CircRNA has shown great potential to become a biomarker in plasma. In this study, we aimed to determine circRNA for its diagnostic and prognostic value and biological function in NKTCL. METHOD: The circRNA microarray of plasma from NKTCL patients and healthy donors were conducted. The relative expressions of target circRNA were verified by qRT-PCR. We conducted function experiments in vitro and in vivo. Bioinformatics predicted the target miRNA of the target circRNA and the binding site was detected by the dual luciferase report assay. Downstream target protein was predicted and detected by western blot in vitro and immunohistochemistry in vivo. RESULT: By analyzing the plasma circRNA microarrays in NKTCL, 6137 circRNAs were up-regulated and 6190 circRNAs were down-regulated. The relative expressions of circADARB1 were significantly higher in NKTCL patients. The knockdown of circADARB1 inhibited proliferation of NKTCL cells in vitro and in vivo. CircADARB1 could bind to miR-214-3p in the downstream and regulate the expression of p-Stat3. In nude mice tumor tissue, p-Stat3 was under-expressed in the circADARB1 knockdown group. CONCLUSION: CircADARB1 was highly expressed in NKTCL plasma and circADARB1 was a potential biomarker to assist diagnosis and predict the response in NKTCL. CircADARB1 bound up to miR-214-3p and regulated p-Stat3.

Long-Term Investigation of the Temporal Trends and Gas/Particle Partitioning of Short- and Medium-Chain Chlorinated Paraffins in Ambient Air of King George Island, Antarctica.

The presence of anthropogenically emitted chlorinated paraffins (CPs) has been reported in the pristine regions, providing evidence of their long-range transport. This study comprehensively analyzed the short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in both gas and particle phases at King George Island, West Antarctica (the Chinese Great Wall Station), from 2014 to 2018. The atmospheric levels of CPs ranged between 71.4 and 4230 pg/m3, with an increasing temporal trend during the sampling time. Three different models (J-P model, H-B model, and L-M-Y model) were built to estimate the progress of gas/particle partitioning of CPs at the measurement site. Furthermore, we compared the measured data of the gas/particle partitioning with the data estimated using three different models. We found that the steady-state model (L-M-Y model) was more suitable for investigating the gas/particle partitioning of CPs instead of equilibrium state models (J-P model and H-B model). The result indicated that steady-state approximation rather than the equilibrium state represents the most predominant contribution to the transport of CPs to the Antarctic region. The steady-state further made it conducive to sustaining the levels of CPs for a more extended period in the atmosphere of West Antarctica.

Wide spread and diversity of mutation in the gyrA gene of quinolone-resistant Corynebacterium striatum strains isolated from three tertiary hospitals in China.

BACKGROUND: Corynebacterium striatum was confirmed to be an important opportunistic pathogen, which could lead to multiple-site infections and presented high prevalence of multidrug resistance, particularly to quinolone antibiotics. This study aimed to investigate the mechanism underlying resistance to quinolones and the epidemiological features of 410 quinolone-resistant C. striatum clinical strains isolated from three tertiary hospitals in China. METHODS: A total of 410 C. striatum clinical strains were isolated from different clinical samples of patients admitted to three tertiary teaching hospitals in China. Antibiotic susceptibility testing was performed using the microdilution broth method and pulsed-field gel electrophoresis (PFGE) was used for genotyping. Gene sequencing was used to identify possible mutations in the quinolone resistance-determining regions (QRDRs) of gyrA. RESULTS: In total, 410 C. striatum isolates were sensitive to vancomycin, linezolid, and daptomycin but resistant to ciprofloxacin. Depending on the antibiotic susceptibility testing results of 12 antimicrobial agents, the 410 C. striatum strains were classified into 12 resistant biotypes; of these, the three biotypes R1, R2, and R3 were dominant and accounted for 47.3% (194/410), 21.0% (86/410), and 23.2% (95/410) of the resistant biotypes, respectively. Mutations in the QRDRs ofgyrA were detected in all quinolone-resistant C. striatum isolates, and 97.3% of the isolates (399/410) showed double mutations in codons 87 and 91 of the QRDRs of gyrA. Ser-87 to Phe-87 and Asp-91 to Ala-91 double mutation in C. striatum was the most prevalent and accounted for 72.2% (296/410) of all mutations. Four new mutations in gyrA were identified in this study; these included Ser-87 to Tyr-87 and Asp-91 to Ala-91 (double mutation, 101 isolates); Ser-87 to Val-87 and Asp-91 toGly-91 (double mutation, one isolate); Ser-87 to Val-87 and Asp-91 to Ala-91 (double mutation, one isolate); and Ser-87 to Ile-87 (single mutation, one isolate). The minimum inhibitory concentration of ciprofloxacin for isolates with double (96.5%; 385/399) and single (72.7%; 8/11) mutations was high (≥ 32 µg/mL). Based on the PFGE typing results, 101 randomly selected C. striatum strains were classified into 50 genotypes (T01-T50), including the three multidrug-resistant epidemic clones T02, T06, and T28; these accounted for 14.9% (15/101), 5.9% (6/101), and 11.9% (12/101) of all genotypes, respectively. The multidrug-resistant T02 clone was identified in hospitals A and C and persisted from 2016 to 2018. Three outbreaks resulting from the T02, T06, and T28 clones were observed among intensive care unit (ICU) patients in hospital C between April and May 2019. CONCLUSIONS: Quinolone-resistant C. striatum isolates showed a high prevalence of multidrug resistance. Point mutations in the QRDRs of gyrA conferred quinolone resistance to C. striatum, and several mutations in gyrA were newly found in this study. The great clonal diversity, high-level quinolone resistance and increased prevalence among patients susceptible to C. striatum isolates deserve more attention in the future. Moreover, more thorough investigation of the relationship between quinolone exposure and resistance evolution in C. striatum is necessary.

Unrestrained markerless trait stacking in Nannochloropsis gaditana through combined genome editing and marker recycling technologies.

Robust molecular tool kits in model and industrial microalgae are key to efficient targeted manipulation of endogenous and foreign genes in the nuclear genome for basic research and, as importantly, for the development of algal strains to produce renewable products such as biofuels. While Cas9-mediated gene knockout has been demonstrated in a small number of algal species with varying efficiency, the ability to stack traits or generate knockout mutations in two or more loci are often severely limited by selectable agent availability. This poses a critical hurdle in developing production strains, which require stacking of multiple traits, or in probing functionally redundant gene families. Here, we combine Cas9 genome editing with an inducible Cre recombinase in the industrial alga Nannochloropsis gaditana to generate a strain, NgCas9+Cre+, in which the potentially unlimited stacking of knockouts and addition of new genes is readily achievable. Cre-mediated marker recycling is first demonstrated in the removal of the selectable marker and GFP reporter transgenes associated with the Cas9/Cre construct in NgCas9+Cre+ Next, we show the proof-of-concept generation of a markerless knockout in a gene encoding an acyl-CoA oxidase (Aco1), as well as the markerless recapitulation of a 2-kb insert in the ZnCys gene 5'-UTR, which results in a doubling of wild-type lipid productivity. Finally, through an industrially oriented process, we generate mutants that exhibit up to ∼50% reduction in photosynthetic antennae size by markerless knockout of seven genes in the large light-harvesting complex gene family.

A Microarray Screening Platform with an Experimental Conditions Gradient Generator for the High-Throughput Synthesis of Micro/Nanosized Calcium Phosphates.

Calcium phosphates (CaP) represent an impressive kind of biomedical material due to their excellent biocompatibility, bioactivity, and biodegradability. Their morphology and structure highly influence their properties and applications. Whilst great progress has been made in research on biomedical materials, there is still a need to develop a method that can rapidly synthesize and screen micro/nanosized biomedical materials. Here, we utilized a microarray screening platform that could provide the high-throughput synthesis of biomedical materials and screen the vital reaction conditions. With this screening platform, 9 × 9 sets of parallel experiments could be conducted simultaneously with one- or two-dimensions of key reaction condition gradients. We used this platform to establish a one-dimensional gradient of the pH and citrate concentration and a two-dimensional gradient of both the Ca/P ratio and pH to synthesize CaP particles with various morphologies. This screening platform also shows the potential to be extended to other reaction systems for rapid high-throughput screening.

Long noncoding RNA LINC00342 promotes growth of infantile hemangioma by sponging miR-3619-5p from HDGF.

Infantile hemangiomas (IH) are a type of benign vascular neoplasm that may cause permanent scarring. Hemangioma-derived endothelial cells (HemECs) are commonly used as an in vitro model to study IH. Long noncoding RNA is a type of RNA transcript longer than 200 nucleotides that does not encode any protein. LINC00342 was discovered to regulate proliferation and apoptosis in nonsmall cell lung cancer. However, the role of LINC00342 in IH has never been reported before. Expressions of LINC00342 and miR-3619-5p were detected in proliferating versus normal skin tissues. Colony formation and Cell-Couting Kit 8 assays were carried out to study the effects on cell proliferation after knockdown and overexpression of LINC00342, respectively. Meanwhile caspase-3 activity and nucleosomal fragmentation assay were applied to detect cell apoptosis. Micro-RNA binding sites on LINC00342 and hepatoma-derived growth factor (HDGF) were predicted and confirmed via dual-luciferase reporter assay. Biotin RNA pulldown assay was used to verify the direct binding between RNA molecules. LINC00342 enhanced proliferation and inhibited apoptosis in HemECs. MiR-3619-5p targeted both LINC00342 and HDGF, where LINC00342 sponged miR-3619-5p and positively regulated HDGF. HDGF knockdown rescued the effects of LINC00342 on HemECs. The LINC00342-miR-3619-5p-HDGF signaling pathway could regulate cell proliferation and apoptosis in HemECs.NEW & NOTEWORTHY The role of LINC00342 in infantile hemangiomas has not yet been elucidated. This paper highlights the regulatory role of LINC00342 in cell proliferation and apoptosis in hemangioma-derived endothelial cells and the underlying molecular mechanisms. The findings would provide potential target for treatment of infantile hemangiomas.

Identification of diagnostic biomarkers in patients with gestational diabetes mellitus based on transcriptome gene expression and methylation correlation analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) has a high prevalence in the period of pregnancy. However, the lack of gold standards in current screening and diagnostic methods posed the biggest limitation. Regulation of gene expression caused by DNA methylation plays an important role in metabolic diseases. In this study, we aimed to screen GDM diagnostic markers, and establish a diagnostic model for predicting GDM. METHODS: First, we acquired data of DNA methylation and gene expression in GDM samples (N = 41) and normal samples (N = 41) from the Gene Expression Omnibus (GEO) database. After pre-processing the data, linear models were used to identify differentially expressed genes (DEGs). Then we performed pathway enrichment analysis to extract relationships among genes from pathways, construct pathway networks, and further analyzed the relationship between gene expression and methylation of promoter regions. We screened for genes which are significantly negatively correlated with methylation and established mRNA-mRNA-CpGs network. The network topology was further analyzed to screen hub genes which were recognized as robust GDM biomarkers. Finally, the samples were randomly divided into training set (N = 28) and internal verification set (N = 27), and the support vector machine (SVM) ten-fold cross-validation method was used to establish a diagnostic classifier, which verified on internal and external data sets. RESULTS: In this study, we identified 465 significant DEGs. Functional enrichment analysis revealed that these genes were associated with Type I diabetes mellitus and immunization. And we constructed an interactional network including 1091 genes by using the regulatory relationships of all 30 enriched pathways. 184 epigenetics regulated genes were screened by analyzing the relationship between gene expression and promoter regions' methylation in the network. Moreover, the accuracy rate in the training data set was increased up to 96.3, and 82.1% in the internal validation set, and 97.3% in external validation data sets after establishing diagnostic classifiers which were performed by analyzing the gene expression profiles of obtained 10 hub genes from this network, combined with SVM. CONCLUSIONS: This study provided new features for the diagnosis of GDM and may contribute to the diagnosis and personalized treatment of GDM.

Optic perineuritis secondary to hyaluronic acid injections: a case report.

BACKGROUND: Although a safe, excellent administration method for hyaluronic acid derivatives has been documented; improper injections can lead to devastating and irreversible consequences. Here, we present the first known case of optic perineuritis caused by hyaluronic acid. CASE PRESENTATION: A young female experienced sudden orbital pain in the right eye after receiving hyaluronic acid injections to the eyebrows. She presented to the eye clinic two weeks later, after developing blurred vision in the right eye. Visual acuity was reduced significantly in the right eye. Automated visual field examination showed defects in both eyes. Fundus examination revealed bilateral swelling of optic discs. Magnetic resonance imaging of the brain demonstrated bilateral perineural enhancement consistent with optic perineuritis. The patient was treated with retrobulbar injection of hyaluronidase and oral prednisolone. Her vision improved with treatment. CONCLUSIONS: The prognosis for visual outcomes in patients with optic perineuritis is generally excellent. However, a poor prognosis is associated with delays to the initiation of treatment. Recognizing this condition is important, and treatment with corticosteroids should be initiated early.

Platelet-derived growth factor receptor alpha (PDGFRα) is overexpressed in NK/T-cell lymphoma and mediates cell survival.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin lymphoma (NHL) that is clinically aggressive and has a poor prognosis. Platelet-derived growth factor receptors (PDGFRs) and their ligands (PDGFs) play important roles in angiogenesis, cancer cell proliferation, survival, migration and poor prognosis in various tumours. However, the significance of PDGFRs in NKTCL remains unknown. Herein, the present study aimed to investigate the important role of PDGFRα in pathogenesis, progression and prognisis of NKTCL. Firstly, we performed immunohistochemical staining, qRT-PCR and western blotting to determine PDGFRα expression in formalin-fixed, paraffin-embedded tissue sections from 78 NKTCL cases and in cell lines. Secondly, correlations between PDGFRα expression and NKTCL clinical parameters and prognosis were analysed. Moreover, a biological assessment of PDGFRα blockade in two NKTCL cell lines was conducted through proliferation assay, cell-cycle evaluation and apoptosis detection by flow cytometry analyses. Furthermore, we detected in vivo activity of imatinib in mouse model of NKTCL. We found that the expression of PDGFRα was significantly higher in NKTCL tissues compared to the reactive lymphoid hyperplasia of the nasopharynx (P = 0.028). High PDGFRα expression was strongly associated with a high LDH level (P = 0.028) and III-IV stage (P = 0.013). NKTCL patients with high PDGFRα expression displayed a reduced median overall survival time and progression-free survival time when compared with those with low PDGFRα expression (P = 0.011, P = 0.005, respectively). Cox multivariate analysis showed that III-IV stage (P = 0.024) and high PDGFRα expression (P = 0.003) were independent prognostic factors in NKTCL patients. Biological assessment assays in two NKTCL cell lines revealed that a specific PDGFR antagonist, imatinib, inhibited cell viability, blocked cell cycle progression at G0/G1 stage and induced apoptosis. Similarly, the in vivo assay showed that imatinib delayed mouse model tumour growth. In conclusion, NKTCL tumour cells have prominent PDGFRα expression, which can serve as a candidate prognostic marker. PDGFR antagonists have significant biological effect on NKTCL and may be useful therapeutic agents for treatment of NKTCL.

Role of Ninth Type-III Domain of Fibronectin in the Mediation of Cell-Binding Domain Adsorption on Surfaces with Different Chemistries.

The orientation and conformation of adhesive proteins after adsorption play a central role in cell-binding bioactivity. Fibronectin (Fn) holds two peptide sequences that favor cell adhesion: the Arg-Gly-Asp (RGD) loop on the tenth type-III domain (Fn-III10) and the Pro-His-Ser-Arg-Asn (PHSRN) synergy site on the ninth type-III domain (Fn-III9). Herein, adsorption of Fn fragments (Fn-III10 and Fn-III9-10) on self-assembled monolayers (SAMs) carrying various functional groups (-COOH, -NH2, -CH3, and -OH) was investigated by the Monte Carlo method and molecular dynamics simulation in order to understand its mediation effect on cell adhesion. The results demonstrated that Fn-III9 could enhance the stiffness of the Fn molecule and further fix the adsorption orientation. The RGD site of the Fn fragment appeared to be deactivated on hydrophobic surfaces (CH3-SAM) because of the binding of adjacent nonpolar residues on surfaces, whereas charged surfaces (COOH-SAM and NH2-SAM) and hydrophilic surfaces (OH-SAM) were conducive to the formation of cell-binding-favorable orientation for Fn fragments. The cell adhesion capability of Fn fragments was highly improved on positively charged surfaces (NH2-SAM) and hydrophilic surfaces because of the advantageous steric structure and orientation of both RGD and PHSRN sites. This work provides an insight into the interplay at the atomic scale between protein adsorption and surface chemistry for designing biologically responsive substrate surfaces.

Weak Hydrogen Bonds Lead to Self-Healable and Bioadhesive Hybrid Polymeric Hydrogels with Mineralization-Active Functions.

Hydrogels with self-healing features that can spontaneously repair themselves upon mechanical damage are increasingly attractive for biomedical applications. Many attempts have been made to develop unique hydrogels possessing this property, as well as stimuli-responsiveness and biocompatibility; however, the hydrogel fabrication strategies often involve specific design of functional monomers that are able to optimally provide reversible physical or chemical interactions. Here, we report that weak hydrogen bonds, provided by oligo(ethylene glycol) methacrylate (OEGMA) and methacrylic acid (MAA), a monomer combination that is commonly used to prepare chemically cross-linking hydrogels, can generate self-healable hydrogels with mechanically resilient and adhesive properties through a facile one-step free radical copolymerization. The hydrogen bonds break and reform, providing an effective energy dissipation mechanism and synergic mechanical reinforcement. The physical properties can be simply tuned by OEGMA/MAA ratio control and reversible pH adjustment. Furthermore, the hydrogel can serve as a robust template for biomineralization to produce hydrogel composite that facilitate cell attachment and proliferations. This work is synthetically simple and dramatically increases the choice of amendable and adhesive hydrogels for industrial and biomedical applications.