[Risk factors of systemic allergic reactions caused by subcutaneous allergen immunotherapy].

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.

MiR-424 Inhibits neuronal apoptosis in rats with cerebral infarction through regulating TGF-ß1/Smad3 signaling pathway.

It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-ß (TGF-ß) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-ß1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-ß1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO.

Effects of habitat fragmentation on the genetic diversity and differentiation of Dendrolimus punctatus (Lepidoptera: Lasiocampidae) in Thousand Island Lake, China, based on mitochondrial COI gene sequences.

Thousand Island Lake (TIL) is a typical fragmented landscape and an ideal model to study ecological effects of fragmentation. Partial fragments of the mitochondrial cytochrome oxidase subunit I gene of 23 island populations of Dendrolimus punctatus in TIL were sequenced, 141 haplotypes being identified. The number of haplotypes increased significantly with the increase in island area and shape index, whereas no significant correlation was detected between three island attributes (area, shape and isolation) and haplotype diversity. However, the correlation with number of haplotypes was no longer significant when the 'outlier' island JSD (the largest island) was not included. Additionally, we found no significant relationship between geographic distance and genetic distance. Geographic isolation did not obstruct the gene flow among D. punctatus populations, which might be because of the high dispersal capacity of this pine moth. Fragmentation resulted in the conversion of large and continuous habitats into isolated, small and insular patches, which was the primary effect on the genetic diversity of D. punctatus in TIL. The conclusion to emphasize from our research is that habitat fragmentation reduced the biological genetic diversity to some extent, further demonstrating the importance of habitat continuity in biodiversity protection.

[The clinical value of China Savin pollen extract used for skin prick test].

Objective:The aim of this study is to evaluate the effectiveness and safety of China Savin pollen extract which was used for skin prick test (SPT) in the diagnosis of China Savin pollen allergy. Method:Patients with diagnosis of allergic diseases were collected from Allergy Department of Peking Union Medical College Hospital. All patients were given SPT with China Savin pollen extract, and the mean wheal diameter (MWD) was measured after 15 minutes. Receiver operating characteristic curve (ROC) analysis was performed based on the results of serum specific immunoglobulin E (sIgE). The effectiveness of SPT in the diagnosis of China Savin pollen allergy was evaluated under different diagnostic cutoff values. Adverse events were also recorded to evaluate the safety. Result:A total of 1 029 patients were enrolled in this study without drop out case. There were 1 007 patients in full analysis set (FAS) and 765 patients in per protocol analysis set (PPS). The elimination rate was 25.66%. The area under the ROC curve of FAS is 0.814 (95%CI: 0.788-0.839); which of PPS is 0.829 (95%CI: 0.801-0.857). Based on the ROC curve of PPS, the optimal and the 95% specificity diagnostic cutoff values of MWD were 3.25 mm and 4.75 mm respectively. Based on different diagnostic cutoff value (3.00, 3.25 and 4.75 mm), the sensitivities of SPT with China Savin pollen extract were 0.740 0 (95%CI: 0.701 6-0.778 4), 0.700 (95%CI: 0.659 8-0.740 2) and 0.532 (95%CI: 0.488 3-0.575 7) respectively, whereas the specificity was gradually increased in sequence, which was 0.769 8 (95%CI: 0.719 1-0.820 5), 0.826 4 (95%CI: 0.780 8-0.872 0) and 0.950 9 (95%CI: 0.924 9-0.976 9) respectively. There were 7 adverse events observed among 6 patients (rate: 0.583%, 6/1 029). The manifestation was mild. There was no severe adverse event. Conclusion:SPT with China Savin pollen extract is an effective and safe tool for the diagnosis of China Savin pollen allergy. The effectiveness of diagnosis could be improved based on integration of medical history and different diagnostic threshold values of SPT.

A female patient with normosmic idiopathic hypogonadotropic hypogonadism carrying a novel mutation in FGFR1.

Mutations in the fibroblast growth factor receptor 1 gene (FGFR1) have been reported in patients with Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Here, we report an nIHH patient with a novel mutation in FGFR1. The patient was a 19-year-old female who presented the nIHH phenotype with primary amenorrhea, cleft lip and palate, mixed hearing disorders, and skeletal malformations. Coding regions of 12 genes that have been implicated in nIHH were analyzed by direct sequencing. Mutation analysis revealed a novel mutation at exon 10 of the FGFR1 gene, 1422 C>G, and a C→G transition in codon 476, which resulted in the replacement of aspartic acid with glutamic acid. The patient's family members did not possess this mutation. We briefly reviewed FGFR1 variants found in Chinese subjects. These results indicate that the mutation in FGFR1 is a cause of nIHH, which is associated with specific non-reproductive phenotypes.

Mutational spectrum and geno-phenotype correlation in Chinese families with hereditary angioedema.

BACKGROUND: Hereditary angioedema is a rare autosomal dominant disease, and its correlation between genotype and phenotype seems not to exist. So far, there are very few studies on Chinese population. We aimed to establish a Chinese genetic database of hereditary angioedema and investigated the potential correlation between genotype and phenotype. METHOD: All the eight exons and intron-exon boundaries of C1 inhibitor gene were detected in 48 unrelated families with HAE. The correlations between genotype and clinical parameters were evaluated by R statistical software. RESULTS: Thirty-five different mutations (25 of them were novel) and 7 SNPs (3 of them were novel) were identified. Significant difference was found in the level of C1 inhibitor antigen (P = 0.01793) between different groups of mutational types. The correlation between different groups of mutational types and the level of C1 inhibitor antigen (0.5047, P = 0.00027) was significant. The different groups of mutational types showed neither difference nor correlations of clinical parameters (severity score and the level of C1 inhibitor function). CONCLUSION: It appears that nonsense, frameshift, and mutations on Arg466 can cause lower level of C1 inhibitor antigen than missense and in-frame mutations; however, it does not affect severity of symptoms.

Constituents of Eugenia sandwicensis with potential cancer chemopreventive activity.

A triterpenoid, 3beta-cis-p-coumaroyloxy-2alpha,23-dihydroxyolean-12-en-28-oic acid (1), and two natural products, 3beta-trans-p-coumaroyloxy-2alpha,23-dihydroxyolean-12-en-28-oic acid (2) and 23-trans-p-coumaroyloxy-2alpha,3beta-dihydroxyolean-12-en-28-oic acid (3), were isolated from a chloroform-soluble extract of the stems of Eugenia sandwicensis, along with 10 known compounds. Of these compounds, 2 showed significant inhibitory activity (79.2% at 4 microg/ml) in a 7,12-dimethylbenz[a]anthracene-induced mouse mammary organ culture assay system of relevance to cancer chemoprevention. Gallic acid was isolated as an antioxidative constituent of an ethyl acetate-soluble extract of E. sandwicensis stems. Isolates 1-3 were characterized on the basis of spectral and chemical evidence.

A pregnane steroid from Aglaia lawii and structure confirmation of cabraleadiol monoacetate by X-ray crystallography.

The pregnane steroid, (E)-aglawone, along with four known triterpenes, and a known sterol mixture were isolated from the bark of Aglaia lawii (Wight) Saldanha ex Ramamoorty (Meliaceae). The structural determination/identification was accomplished by a combination of 1D- and 2D-NMR spectroscopic techniques. The relative stereochemistry of the known triterpene, 20S,24S-epoxydammarane-3alpha,25-diol acetate, was also unequivocally determined for the first time by X-ray crystallography. The isolates were not active against various human cancer cell lines.

[Studies on triterpenoids and their glycosides from Aralia dasyphylla Miq].

The structures of two triterpenoids and their glycosides were isolated from Aralia dasyphylla Miq. Their structures have been identified to be oleanoic acid(I), 16 beta-hydroxy-18 beta-H-oleanoic acid(II), oleanoic acid-28-O-beta-D-glucopyranoside(III) and 16 beta-hydroxy-18 beta-H-oleanoic acid-28-O-beta-D-glucopyranoside(IV), respectively, mainly through interpretation of UV, IR, MS, 1H and 13CNMR, DEPT, HMQC and HMBC spectra data. The stereochemistry of II has been confirmed by NOESY. Pharmacological experiments showed that the total saponins exerted preventative effect on CCl4-induced liver injury of male mice and hypoglycemic effect on a model of alloxan-induced diabetes in rats.