[Diagnosis of allergen components in fungi and microbial communities: patient sensitization characteristics and main sensitizing proteins].

The human body, as a highly complex ecosystem, harbors diverse microbial communities, with major factors triggering allergic reactions encompassing the skin microbiome and fungi. The global diversity of fungi is estimated to range from approximately 600 000 to 1 million species, and theoretically, IgE-mediated sensitization may occur to any fungal species. As of now, the World Health Organization/IUIS official database records 113 fungal allergens originating from 30 different fungi species, covering 42 allergen families. Regarding the skin microbiome, 14 distinct Malassezia allergens have been identified, all derived from three different Malassezia fungi species--M. furfur, M. sympodialis, and M. globosa. The conditions of patients with these allergies are exceptionally complex. This article extensively discusses the latest research advancements and clinical applications related to skin microbiome and fungal allergies from the European Academy of Allergy and Clinical Immunology (EAACI) publication, "Molecular Allergology User's Guide 2.0". Additionally, it compiles information on the sources of fungal allergens, characteristics of allergen component protein families, clinical relevance, and management strategies, both domestically and internationally. The aim is to enhance the profound understanding of allergen components among relevant professionals. Through the application of advanced allergen component diagnostic techniques, the goal is to achieve precise diagnosis and treatment of fungal allergy patients and explore the mechanisms underlying fungal sensitization and pathogenesis, laying the foundation for studying the fungal allergen protein sensitization spectrum in the Chinese population.

[Research on allergen detection technology and allergic disease diagnosis strategy in China].

In China, the prevalence of allergic diseases is increasing, but allergy research and allergy diagnosis technologies are still in their infancy, posing certain hurdles to clinical diagnosis and treatment. The detection of allergen is essential for the prevention and treatment of allergic diseases. Clarifying the aetiology and risk factors of allergic diseases is critical in order to provide targeted environmental control and therapy for allergic diseases, as well as reduce patient pain and financial burden. In this study, allergen detection technologies and diagnosis strategies are described in order to provide direction for clinicians and laboratory technicians, improve allergic diseases diagnosis, and guide allergic disease therapy.

[Analysis of serum allergen-specific IgE in children with respiratory allergic disease in Guangdong].

Objective: To investigate the common allergens in children with respiratory allergic diseases in Guangdong and provide the basis for preventing and treating respiratory allergic diseases. Methods: A total of 254 serum samples were collected retrospectively from children with allergic rhinitis and (or) asthma in the pediatric clinic of the First Affiliated Hospital of Guangzhou Medical University or Boai Hospital of Zhongshan City from August 2019 to August 2020 and tested positive for at least one allergens by ImmunoCAP 1000 or skin prick test. There were 173 males and 81 females, with a median age (interquartile interval) of 7 (4.00, 9.75) years. Specific IgE against eighteen common allergen were tested by magnetic particle chemiluminescence immunoassay. Statistical analysis using χ2 test. Results: The positive rate of Dermatophagoides pteronyssinus (85.0%, 215/254) was the highest, followed by D. farinae (83.5%, 212/254), egg white (19.3%, 49/254), milk (14.6%, 37/254), German cockroach (14.2%, 36/254) and ox-eye daisy (12.6%, 32/254). Dust mites were the most common allergens in patients with allergic rhinitis / allergic asthma / allergic rhinitis and asthma. The positive rates of D. pteronyssinus (95.4% vs. 91.7% vs. 71.0%, χ2=23.257, P<0.001), D. farinae (95.4% vs. 90.6% vs. 67.7%, χ2=26.916, P<0.001), mugwort (10.8% vs. 9.4% vs. 1.1%, χ2=7.535, P=0.023), and ox-eye daisy (21.5% vs. 14.6% vs. 4.3%, χ2=10.876, P=0.004) in allergic rhinitis combined with asthma group and allergic rhinitis group were significantly higher than those in allergic rhinitis group. The positive rates of D. pteronyssinus (96.2% vs. 84.0% vs. 53.5%, χ2=46.343, P<0.001), D. farinae (96.2% vs. 81.5% vs. 48.8%, χ2=52.756, P<0.001) and German cockroach (17.7% vs. 14.8% vs. 2.3%, χ2=6.313, P=0.043) in > 6 years old group were significantly higher than those in > 3 years old group and > 3-6 years old group, while the sIgE positive rates of egg white (41.9% vs. 21.0% vs. 10.8%, χ2=20.281, P<0.001) and milk (41.9% vs. 16.0% vs. 4.6%, χ2=36.227, P<0.001) in ≤3 years old group were significantly higher than those in > 3-6 years old group and > 6 years old group. In addition, there were significant positive correlations between D. pteronyssinus and D. farinae, mugwort and ox-eye daisy, cat dander and horse dander, ox-eye daisy and dandelion, egg white and milk, timothy grass and sesame (rs≥0.511, P < 0.01). With the increase of the class of house dust mite allergen, the sIgE positive rates of mugwort (0.0% vs. 1.5% vs. 10.8%, χ2=9.714, P=0.008), ox-eye daisy (0.0% vs. 4.4% vs. 19.6%, χ2=16.195, P<0.001), cat dander (0.0% vs. 7.4% vs. 18.2%, χ2=11.459, P=0.003) and horse dander (0.0% vs. 1.5% vs. 15.5%, χ2=15.443, P < 0.001) increased significantly, while the sIgE positive rate of milk (29.0% vs. 16.2% vs. 10.1%, χ2=8.792, P=0.012) decreased significantly. Conclusions: Dust mite is the main allergen in children with respiratory allergic diseases in Guangdong, and ox-eye daisy is the main pollen allergen. The sensitization patterns of allergens varied in different ages and diseases, and children with respiratory allergic diseases should regularly detect allergens and pay attention to avoid them.

[The diagnostic value of combined specific IgG and specific IgE of Aspergillus fumigatus in allergic broncho pulmonary aspergillosis and severe asthma with fungal sensitization].

This study aims to explore the diagnostic value of specific immunoglobulin E (sIgE) and specific immunoglobulin G (sIgG) of Aspergillus fumigatus in the diagnosis of allergic broncho-pulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). A total of 17 ABPA patients and 14 SAFS patients were enrolled. The levels of sIgG [2 294.00 (1 527.00, 14 170.00) U/ml vs. 972.60 (650.90, 1 792.00) U/ml] and sIgE [8.77 (1.64, 16.85) kU/L vs. 1.04 (0.70, 2.05) kU/L] in ABPA patients were significantly higher than those in SAFS patients (P<0.05). Aspergillus fumigatus sIgG was strongly correlated with Aspergillus fumigatus sIgE (r(s)=0.797, P<0.001) in ABPA patients. When combined with Aspergillus fumigatus sIgG (>1 000.00 U/mL) and Aspergillus fumigatus sIgE (>1.00 kU/L), the sensitivity was 82.3% and specificity 78.6% for the differential diagnosis of ABPA and SAFS. It demonstrates the diagnostic value of Aspergillus fumigatus sIgG and sIgE.

[Risk factors for visual field loss progression in patients with primary open-angle glaucoma in Wenzhou area].

Objective: To evaluate risk factors for visual field (VF) loss progression in primary open-angle glaucoma patients. Methods: A prospective nested case-control study. Patients were collected from the Wenzhou glaucoma progression study in the Eye Hospital of Wenzhou Medical University during March 2014 and April 2018. In this study, the eyes were divided into a progression group and a non-progression group using the glaucoma progression analysis methods to analyze the risk factors for glaucomatous VF loss progression. Axial length (AL) and central corneal thickness (CCT) were measured using the Lenstar LS900. The baseline, fluctuation (standard deviation), mean, maximum, minimum and range of intraocular pressure (IOP) during the follow-up period were determined based on IOP measured at each follow-up. The IOP measurements were included from the baseline to the last visit (for the non-progression group), or to the visit at which VF loss progression was determined (for the progression group). The independent sample t-test, Mann-Whitney U inspection and Cox proportional hazards models were used for statistical analysis. Results: A total of 140 patients (140 eyes) were enrolled, including 67 males and 73 females. There were 19.3% of the eyes (27 of 140 eyes) showing VF loss progression. The median time to the endpoint for progression was 24.0 (16.0, 40.0) months. The AL in the progression group and non-progression group were 23.58 (23.05, 24.24) mm and 23.91 (23.10, 24.91) mm (P=0.111). The CCT in the two groups were 531.0 (512.0, 565.0) µm and 535.0 (518.5, 552.0) µm, respectively (P=0.897). The baseline age in the progression group and non-progression group was 71.0 (68.0, 74.0) years and 68.0 (58.0, 72.0) years, respectively (Z=-2.872, P=0.004). The slope of visual field index in the two groups was -3.50 (-7.10, -1.80)%/year and 0.40 (-0.60, 1.40)%/year, respectively (Z=-6.823, P<0.01). The mean IOP during the follow-up was (16.2±2.7) mmHg (1 mmHg=0.133 kPa) in the progression group and (15.1±2.4) mmHg in the non-progression group (t=-2.215, P=0.028). The IOP fluctuation in the progression group and non-progression group was (2.6±1.3) mmHg and (2.0±0.7) mmHg, respectively (t=-2.175, P=0.038). In the multivariate model, older baseline age (HR=1.080; 95%CI:1.019-1.143), higher baseline IOP (HR=1.120; 95%CI:1.016-1.236), higher mean IOP (HR=1.145; 95%CI:1.001-1.309) and higher IOP fluctuation (HR=1.750; 95%CI:1.193-2.566) were all significantly predictive risk factors for glaucomatous VF loss progression. Longer AL (HR=0.725; 95%CI:0.532-0.988) was a protective factor against VF loss progression. However, CCT was found to be not associated with VF loss progression. Conclusion: Baseline age, baseline IOP, mean IOP, IOP fluctuation and shorter AL are found to be risk factors for glaucomatous VF loss progression among eyes with primary open-angle glaucoma in Wenzhou. (Chin J Ophthalmol, 2019, 55: 777-784).

A sub-megavolt anti-scattering grid: Fabrication, testing, and Monte Carlo simulation.

X-ray flash radiography is an effective diagnostic in implosive research. While scattering reduces the contrast of radiography, the anti-scattering grids can effectively intercept the scattered radiation and acquire better images. A focused sub-megavolt grid is elaborately manufactured with the combination of lithography, etching, and laser drilling. The consistency of Monte Carlo simulations and radiographic experiments suggests a transmission of about 36% and a 1000 times improvement for the signal to scatter ratio of the grid.

A novel approach to correct the coded aperture misalignment for fast neutron imaging.

Aperture alignment is crucial for the diagnosis of neutron imaging because it has significant impact on the coding imaging and the understanding of the neutron source. In our previous studies on the neutron imaging system with coded aperture for large field of view, "residual watermark," certain extra information that overlies reconstructed image and has nothing to do with the source is discovered if the peak normalization is employed in genetic algorithms (GA) to reconstruct the source image. Some studies on basic properties of residual watermark indicate that the residual watermark can characterize coded aperture and can thus be used to determine the location of coded aperture relative to the system axis. In this paper, we have further analyzed the essential conditions for the existence of residual watermark and the requirements of the reconstruction algorithm for the emergence of residual watermark. A gamma coded imaging experiment has been performed to verify the existence of residual watermark. Based on the residual watermark, a correction method for the aperture misalignment has been studied. A multiple linear regression model of the position of coded aperture axis, the position of residual watermark center, and the gray barycenter of neutron source with twenty training samples has been set up. Using the regression model and verification samples, we have found the position of the coded aperture axis relative to the system axis with an accuracy of approximately 20 µm. Conclusively, a novel approach has been established to correct the coded aperture misalignment for fast neutron coded imaging.

Obtaining point spread function of penumbral encoding aperture with "expectation maximization" algorithm based on matched source-image pair experiment.

A source penumbral image reconstruction method with linear mapping principle for geometrical optics is established. The ideal binary point spread function (PSF) can be obtained using a geometrical optics model. The system PSF with certain sharpness was obtained using a Monte Carlo (MC) model. Considering other factors besides the transportation of the x (gamma)-rays or particles (fusion neutrons) in the penumbral encoding aperture in MC model, such as the scattering background and the systematic error, the PSF from MC model "source-image pair matching" experiments with a large area standard oval shape source were processed. A method for correcting and calibrating the PSF by the expectation maximization adaptive algorithm was established and the optimized PSF with 22.30 microm sharpness was achieved. This is more consistent with the real system PSF despite the increased noise level of the two-dimensional PSF and large irregularity in the PSF profile.

Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma.

BACKGROUND: Portal vein tumour thrombus (PVTT) is highly associated with the progression and metastasis of hepatocellular carcinoma (HCC). However, there are no appropriate cell models of PVTT with which to study the biological and physiological characteristics of PVTT. METHODS: Primary cell culture was performed by the use of a successive xenograft line called PVTT-#1, which was obtained from a 60-year-old male HCC patient accompanied by PVTT. RESULTS: A successive cell line named CSQT-2 was established. The cell line showed aggressive phenotypes in terms of cell growth, survival, migration, xenograft and metastasis. Moreover, an orthotopic transplantation assay showed that PVTT can be generated in nude mice when CSQT-2 cells were inoculated in the liver and that it shows a typical migratory tendency in the vascular branches of portal vein. Moreover, the established CSQT-2 cells also showed varied expression of tumour-initiating cell (TIC) markers such as CD133, CD90 and EpCAM. CONCLUSION: Establishment of CSQT-2 may provide a suitable model with which to investigate the molecular mechanisms of PVTT-related HCC.

X-knife stereotactic radiosurgery on the trigeminal ganglion to treat trigeminal neuralgia: a preliminary study.

BACKGROUND: Stereotactic radiosurgery is an attractive option for elderly patients and those who do not tolerate the more invasive surgical procedures available for trigeminal neuralgia (TN). In the majority of the studies, the target location was designated as the proximal nerve at the root entry zone (REZ). The purpose of this article was to evaluate the efficacy of and complications associated with X-knife stereotactic radiosurgery on the trigeminal ganglion (TG) for TN. PATIENTS AND METHODS: 40 patients with typical idiopathic TN were treated with X-knife. The maximum radiation dose was 70 Gy. A 4-mm collimator and a 9-arc technique were employed. Treatment was focused at the TG. RESULTS: At the last follow-up (mean follow-up period: 7.9 months, range: 1-19 months), pain relief for all patients was excellent in 16 (40%), good in 17 (42.5%), for a total success rate of 82.8%. The mean time to initial relief was 12.5 days ranging from immediate in onset (<24 h) to 2 months. One patient (3.0%) experienced some recurrent pain. 3 patients (7.5%) experienced noticeable subjective facial numbness. Hearing impairment was found in 1 patient (2.5%), and ulceration of the temporal skin was seen in 2 patients (5%). CONCLUSION: Similar to other TN radiosurgery reports, X-knife stereotactic radiosurgery for TN provides effective pain relief with a low complication rate.

Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity.

The PAR-3/PAR-6/atypical PKC (aPKC) complex is required for axon-dendrite specification of hippocampal neurons. However, the downstream effectors of this complex are not well defined. In this article, we report a role for microtubule affinity-regulating kinase (MARK)/PAR-1 in axon-dendrite specification. Knocking down MARK2 expression with small interfering RNAs induced formation of multiple axon-like neurites and promoted axon outgrowth. Ectopic expression of MARK2 caused phosphorylation of tau (S262) and led to loss of axons, and this phenotype was rescued by expression of PAR-3, PAR-6, and aPKC. In contrast, the polarity defects caused by an MARK2 mutant (T595A), which is not responsive to aPKC, were not rescued by the PAR-3/PAR-6/aPKC complex. Moreover, polarity was abrogated in neurons overexpressing a mutant of MARK2 with a deleted kinase domain but an intact aPKC-binding domain. Finally, suppression of MARK2 rescued the polarity defects induced by a dominant-negative aPKC mutant. These results suggest that MARK2 is involved in neuronal polarization and functions downstream of the PAR-3/PAR-6/aPKC complex. We propose that aPKC in complex with PAR-3/PAR-6 negatively regulates MARK(s), which in turn causes dephosphorylation of microtubule-associated proteins, such as tau, leading to the assembly of microtubules and elongation of axons.

Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience.

Nonmyeloablative allogeneic stem cell transplantation (NST) has considerable activity in patients with metastatic renal cell carcinoma (RCC), although there are limited long-term follow-up data. Between February 1999 and May 2003, 18 patients with metastatic RCC underwent 19 matched-sibling NSTs after conditioning with fludarabine and cyclophosphamide with tacrolimus and mycophenolate mofetil as post-transplant immunosuppression. Among the four objective responses, all were partial and have relapsed with a median response duration of 609 days (range, 107-926). All responders are alive at a median of 41 months. Median overall survival for the entire cohort was 14 months. There were four early treatment-related deaths and one late treatment-related death. Eight patients died from progressive disease and five (28%) from treatment-related mortality. Stratifying transplant outcome as early death, intermediate (no response, no early death), or response, the combination of pre-treatment anemia and decreased performance status, was associated with adverse outcome (P = 0.015) and reduced survival (HR 5.4, 95% confidence interval of 1.4 to 21, P = 0.007). Responders demonstrated prolonged survival compared to nonresponders (P = 0.002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification.

[Observation on revascularization of free flaps with the technique of microvascular corrosion]

In order to study the process of revascularization of free flap bilateral dorsal-auricular free flaps of 18 Newzealand rabbits were completed and investigated with the technique of microvascular corrosion casting at 2,4,7,10 days and 2,4 weeks postoperatively.It was discovered that scarce neovascularity appeared around the margin of flap before 2 weeks following transplantation and extensive revascularization occured at 3 weeks postoperatively.The capillaries connected through their netword expansion while central artery and vein formed recirculation by means of multiple point anastomoses of the "vascular buds" sprouting up at both ends of vessels.

Pharmacokinetic and deuterium isotope effect studies on the metabolism of formaldehyde and formate to carbon dioxide in rats in vivo.

The effect of deuterium substitution on the metabolism of formaldehyde and formate to carbon dioxide in vivo was examined. Four groups of male Sprague-Dawley rats were injected ip with carbon-14-labeled formaldehyde, formaldehyde-d2, sodium formate, or sodium formate-d at doses of 0.67 mmol/kg. Similar rates of labeled carbon dioxide exhalation were observed for the four groups of animals, the cumulative excretion of 14CO2 in breath reaching 68-71% of the theoretical value 12 hr after injection in all cases. Plots of amount remaining to be excreted showed that the metabolism was biexponential, with half-lives of approximately 0.4 and 3 hr for the two phases for each of the four compounds. Competitive experiments in which equimolar mixtures of CH2O with CD2O or HCO2- with DCO2- were injected also failed to reveal a substantial isotope effect, although the cumulative conversion of formate to carbon dioxide was significantly higher than that of its deuterated analog at four time points in the middle of the 8-hr mixed-isotope experiment. The data indicate that deuterium substitution has little or no effect on the rates and extents of in vivo oxidation of these 1-carbon species to carbon dioxide, although a small decrease of up to 10% in reactivity under the conditions employed cannot be excluded. The results support the use of carbon dioxide exhalation data in the measurement of deuterium isotope effects on oxidative demethylation reactions such as those that occur in the activation of the carcinogen, N-nitrosodimethylamine.

Low-dose in vivo pharmacokinetic and deuterium isotope effect studies of N-nitrosodimethylamine in rats.

The rates of elimination of N-nitrosodimethylamine (NDMA) and its fully deuterated analogue (N-nitrosodi[2H6]methylamine, [2H6]NDMA) were studied in vivo to explore the origins of the difference in their carcinogenicity. Male Fischer 344 rats, 7.5 weeks of age, were given nitrosamine bolus doses of 1.35 mumol/kg by tail vein injection and 2.02 or 4.05 mumol/kg by p.o. gavage. Animals were sacrificed at various time points from 2.5 to 180 min after i.v. administration or 5 to 120 min after p.o. dosage, and their blood was analyzed for NDMA by gas chromatography-high resolution mass spectrometry. After i.v. injection, blood nitrosamine concentrations declined in an apparently biexponential manner with a terminal half-life of 10 min for NDMA and 12 min for [2H6]NDMA. The apparent total systemic blood clearances for NDMA and [2H6]NDMA were 39 and 26 ml/min/kg, respectively. The apparent steady-state volumes of distribution were nearly identical (297 and 309 ml/kg, respectively). The areas under the curve after 2.02- and 4.05-mumol/kg p.o. doses were proportional to dose. The apparent bioavailability of NDMA was 8%, while that of [2H6]NDMA was 21%. Isotope effects calculated as the ratios of first-pass metabolism, total systemic clearances, bioavailabilities, and intrinsic hepatic clearances were 1.2, 1.5, 2.6, and 3.2, respectively. The isotope effect determined from blood concentrations measured after simultaneous administration of NDMA and [2H6]NDMA by steady-state infusion (each at 1.5 mumol/kg/h) was 2.6 +/- 0.9 (SD). This study thus provides quantitative reference data on the time course of the disappearance of both N-nitrosodimethylamine and its deuterated analogue from blood (over 5 to 8 half-lives) after doses similar to those used to elicit liver tumors in chronic feeding studies, confirms the first-pass effect on their metabolism using direct blood measurements, and permits estimation of their bioavailabilities from actual blood concentrations. The results suggest that elimination pathways not involving alpha-hydroxylation are more important than is currently recognized.