[Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen].

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

Taxonomy, phylogeny and identification of Chaetomiaceae with emphasis on thermophilic species.

Chaetomiaceae comprises phenotypically diverse species, which impact biotechnology, the indoor environment and human health. Recent studies showed that most of the traditionally defined genera in Chaetomiaceae are highly polyphyletic. Many of these morphology-based genera, such as Chaetomium, Thielavia and Humicola, have been redefined using multigene phylogenetic analysis combined with morphology; however, a comprehensive taxonomic overview of the family is lacking. In addition, the phylogenetic relationship of thermophilic Chaetomiaceae species with non-thermophilic taxa in the family is largely unclear due to limited taxon sampling in previous studies. In this study, we provide an up-to-date overview on the taxonomy and phylogeny of genera and species belonging to Chaetomiaceae, including an extensive taxon sampling of thermophiles. A multigene phylogenetic analysis based on the ITS (internal transcribed spacers 1 and 2 including the 5.8S nrDNA), LSU (D1/D2 domains of the 28S nrDNA), rpb2 (partial RNA polymerase II second largest subunit gene) and tub2 (ß-tubulin gene) sequences was performed on 345 strains representing Chaetomiaceae and 58 strains of other families in Sordariales. Divergence times based on the multi-gene phylogeny were estimated as aid to determine the genera in the family. Genera were delimited following the criteria that a genus must be a statistically well-supported monophyletic clade in both the multigene phylogeny and molecular dating analysis, fall within a divergence time of over 27 million years ago, and be supported by ecological preference or phenotypic traits. Based on the results of the phylogeny and molecular dating analyses, combined with morphological characters and temperature-growth characteristics, 50 genera and 275 species are accepted in Chaetomiaceae. Among them, six new genera, six new species, 45 new combinations and three new names are proposed. The results demonstrate that the thermophilic species fall into seven genera (Melanocarpus, Mycothermus, Remersonia, Thermocarpiscus gen. nov., Thermochaetoides gen. nov., Thermothelomyces and Thermothielavioides). These genera cluster in six separate lineages, suggesting that thermophiles independently evolved at least six times within the family. A list of accepted genera and species in Chaetomiaceae, together with information on their MycoBank numbers, living ex-type strains and GenBank accession numbers to ITS, LSU, rpb2 and tub2 sequences is provided. Furthermore, we provide suggestions how to describe and identify Chaetomiaceae species. Taxonomic novelties: new genera: Parvomelanocarpus X.Wei Wang & Houbraken, Pseudohumicola X.Wei Wang, P.J. Han, F.Y. Bai & Houbraken, Tengochaeta X.Wei Wang & Houbraken, Thermocarpiscus X.Wei Wang & Houbraken, Thermochaetoides X.Wei Wang & Houbraken, Xanthiomyces X.Wei Wang & Houbraken; New species: Botryotrichum geniculatum X.Wei Wang, P.J. Han & F.Y. Bai, Chaetomium subaffine Sergejeva ex X.Wei Wang & Houbraken, Humicola hirsuta X.Wei Wang, P.J. Han & F.Y. Bai, Subramaniula latifusispora X.Wei Wang, P.J. Han & F.Y. Bai, Tengochaeta nigropilosa X.Wei Wang & Houbraken, Trichocladium tomentosum X.Wei Wang, P.J. Han & F.Y. Bai; New combinations: Achaetomiella gracilis (Udagawa) Houbraken, X.Wei Wang, P.J. Han & F.Y. Bai, Allocanariomyces americanus (Cañete-Gibas et al.) Cañete-Gibas, Wiederhold, X.Wei Wang & Houbraken, Amesia dreyfussii (Arx) X.Wei Wang & Houbraken, Amesia raii (G. Malhotra & Mukerji) X.Wei Wang & Houbraken, Arcopilus macrostiolatus (Stchigel et al.) X.Wei Wang & Houbraken, Arcopilus megasporus (Sörgel ex Seth) X.Wei Wang & Houbraken, Arcopilus purpurascens (Udagawa & Y. Sugiy.) X.Wei Wang & Houbraken, Arxotrichum deceptivum (Malloch & Benny) X.Wei Wang & Houbraken, Arxotrichum gangligerum (L.M. Ames) X.Wei Wang & Houbraken, Arxotrichum officinarum (M. Raza & L. Cai) X.Wei Wang & Houbraken, Arxotrichum piluliferoides (Udagawa & Y. Horie) X.Wei Wang & Houbraken, Arxotrichum repens (Guarro & Figueras) X.Wei Wang & Houbraken, Arxotrichum sinense (K.T. Chen) X.Wei Wang & Houbraken, Botryotrichum inquinatum (Udagawa & S. Ueda) X.Wei Wang & Houbraken, Botryotrichum retardatum (A. Carter & R.S. Khan) X.Wei Wang & Houbraken, Botryotrichum trichorobustum (Seth) X.Wei Wang & Houbraken, Botryotrichum vitellinum (A. Carter) X.Wei Wang & Houbraken, Collariella anguipilia (L.M. Ames) X.Wei Wang & Houbraken, Collariella hexagonospora (A. Carter & Malloch) X.Wei Wang & Houbraken, Collariella pachypodioides (L.M. Ames) X.Wei Wang & Houbraken, Ovatospora amygdalispora (Udagawa & T. Muroi) X.Wei Wang & Houbraken, Ovatospora angularis (Yu Zhang & L. Cai) X.Wei Wang & Houbraken, Parachaetomium biporatum (Cano & Guarro) X.Wei Wang & Houbraken, Parachaetomium hispanicum (Guarro & Arx) X.Wei Wang & Houbraken, Parachaetomium inaequale (Pidopl. et al.) X.Wei Wang & Houbraken, Parachaetomium longiciliatum (Yu Zhang & L. Cai) X.Wei Wang & Houbraken, Parachaetomium mareoticum (Besada & Yusef) X.Wei Wang & Houbraken, Parachaetomium muelleri (Arx) X.Wei Wang & Houbraken, Parachaetomium multispirale (A. Carter et al.) X.Wei Wang & Houbraken, Parachaetomium perlucidum (Sergejeva) X.Wei Wang & Houbraken, Parachaetomium subspirilliferum (Sergejeva) X.Wei Wang & Houbraken, Parathielavia coactilis (Nicot) X.Wei Wang & Houbraken, Parvomelanocarpus tardus (X.Wei Wang & Samson) X.Wei Wang & Houbraken, Parvomelanocarpus thermophilus (Abdullah & Al-Bader) X.Wei Wang & Houbraken, Pseudohumicola atrobrunnea (X.Wei Wang et al.) X.Wei Wang, P.J. Han, F.Y. Bai & Houbraken, Pseudohumicola pulvericola (X.Wei Wang et al.) X.Wei Wang, P.J. Han, F.Y. Bai & Houbraken, Pseudohumicola semispiralis (Udagawa & Cain) X.Wei Wang, P.J. Han, F.Y. Bai & Houbraken, Pseudohumicola subspiralis (Chivers) X.Wei Wang, P.J. Han, F.Y. Bai & Houbraken, Staphylotrichum koreanum (Hyang B. Lee & T.T.T. Nguyen) X.Wei Wang & Houbraken, Staphylotrichum limonisporum (Z.F. Zhang & L. Cai) X.Wei Wang & Houbraken, Subramaniula lateralis (Yu Zhang & L. Cai) X.Wei Wang & Houbraken, Thermocarpiscus australiensis (Tansey & M.A. Jack) X.Wei Wang & Houbraken, Thermochaetoides dissita (Cooney & R. Emers.) X.Wei Wang & Houbraken, Thermochaetoides thermophila (La Touche) X.Wei Wang & Houbraken, Xanthiomyces spinosus (Chivers) X.Wei Wang & Houbraken; New names: Chaetomium neoglobosporum X.Wei Wang & Houbraken, Thermothelomyces fergusii X.Wei Wang & Houbraken, Thermothelomyces myriococcoides X.Wei Wang & Houbraken; Lecto- and / or epi-typifications (basionyms): Botryoderma rostratum Papendorf & H.P. Upadhyay, Botryotrichum piluliferum Sacc. & Marchal, Chaetomium carinthiacum Sörgel, Thielavia heterothallica Klopotek. Citation: Wang XW, Han PJ, Bai FY, Luo A, Bensch K, Meijer M, Kraak B, Han DY, Sun BD, Crous PW, Houbraken J (2022). Taxonomy, phylogeny and identification of Chaetomiaceae with emphasis on thermophilic species. Studies in Mycology 101: 121-243. doi: 10.3114/sim.2022.101.03.

[Analysis of COL1A1 gene variation and clinical prevention and treatment in patients with Van der Hoeve syndrome].

Objective: To investigate the clinical phenotype, treatment and prevention of Van der Hoeve syndrome, and analyze the variation characteristics of its related gene COL1A1. Methods: Hearing and sequencing data of syndromic deafness patients who had undergone genetic testing for deafness at the Chinese People's Liberation Army General Hospital since January 2008 to October 2020 were retrospectively reviewed. The variation of the COL1A1 gene and return visits to traceable patients and families were summarized, the disease progress and clinical treatment effects were analyzed, and the prevention strategies were discussed. Results: A total of 7 patients with COL1A1 gene mutation underwent clinical intervention. The mutation sites were c.1342A>T (p.Lys448*), c.124C>T (p.Gln42*), c.249insG(p.Ala84*), c.668insC(p.Gly224*), c.2829+1G>C, c.1081C>T (p.Arg361*), c.1792C>T (p.Arg598*), of which c.1081C>T and c.1792C>T had been previously reported, and the remaining 5 were novo mutations that have not been reported. All the 7 probands underwent stapes implantation and received genetic counseling and prevention guidance. Conclusions: Van der Hoeve syndrome belongs to osteogenesis imperfecta type Ⅰ. The disease has high penetrance. Timely surgical intervention for hearing loss can improve the life quality in patients. Accurate genetic counseling and preimplantation genetic diagnosis can achieve the primary prevention for the disease.

[Clinical diagnosis and surgical management of 110 cases of facial nerve schwannomas].

Objective: To elucidate the clinical behavior, causes of misdiagnosis, surgical management, and outcomes of facial nerve schwannomas (FNS). Methods: A retrospective review in Chinese People's Liberation Army General Hospital from January 1, 2002 to December 31, 2015 was carried out and evaluated 110 patients with FNS, including 50 males and 60 females, aged 16-67 years old. The appropriate surgical strategy was selected based on each patient's clinical manifestations, facial nerve function, and imaging characteristics. After surgery, patients received follow-up visits to assess their facial nerve functions, with the effect of treatment compared to the reality before surgery. The Kruskal-Wallis H test was used to distinguish between the pre- and post-operation facial nerve functions in patients who had different facial nerve functions before the operations. Results: 110 cases of FNS mainly presented with facial paralysis, hearing loss, tinnitus, otalgia, dizziness, and facial spasm. 20 of the cases were misdiagnosed as Bell's Palsy, 6 were mistaken for chronic otitis media/cholesteatoma with radical mastoidectomy, 3 were mistaken for Meniere's disease, 1 was misdiagnosed as petrous bone cholesteatoma, and 4 were mistaken for acoustic neuroma. 81.8 % (90/110) of the patients had multiple segments of the facial nerve, including the vertical segment of the facial nerve, accounting for 65.5% (72/110), followed by the labyrinthine/geniculate segment, for 61.8% (68/110), and the horizontal segment, for 55.5% (61/110). The appropriate surgical approaches were chosed based on the sizes and scopes of the tumors evaluated by imaging: transmastoid approach in 73 cases, translabyrinthe approach in 14 cases, middle cranial fossa approach in 13 cases, retrosigmoid approach in 3 cases, transmastoid-middle cranial fossa approach in 3 cases, and transmastoid-neck approach in 4 cases, with all the patients undergoing a total/subtotal resection of the tumor. Eighty-seven patients had their facial nerves reconstructed. Among them, 6 received facial nerve end-to-end anastomosis, 55 received great auricular nerve graft, and 26 were subjected to facial nerve-hypoglossal nerve anastomosis. Because of long histories, facial muscle atrophies, or other reasons, the remaining patients were not received facial nerve reconstruction. The House-Brackmann(H-B) grading scale was used to evaluate the facial nerve function pre- and post-operation. Patients with better facial nerve functions and shorter history of facial paralysis before operation would get relatively better facial nerve function. The before and after operation comparisons revealed that the recovery of the facial nerve functions in patients with H-B Ⅰ-Ⅲ was better than the improvement in patients with H-B Ⅳ-Ⅴ. The difference was statistically significant (Kruskal-Wallis H test, H=8.508, P<0.05). Conclusions: The diagnosis of patients with unknown facial paralysis, hearing loss, and tinnitus should take into account the possibility of FNS. CT and other imaging examinations of the temporal bone can avoid misdiagnosis and determine the tumor size and extent of lesions, as well as provide the basis for the choice of the surgical approach. After tumors have been completely resected, facial nerve reconstruction can be performed simultaneously, according to the defect of the nerve.

[Petrous bone cholesteatoma: surgery approach and outcomes].

Objective: To investigate the choice of surgical approach of petrous bone cholesteatoma (PBC)and surgical outcomes. Methods: A retrospective study was performed on 90 patients diagnosed and treated for PBC from January 2000 to December 2014 by the Chinese People's Liberation Army General Hospital otolaryngologists. According to Sanna's classification, 40 out of the 90 cases were supralabyrinthine, five infralabyrinthine, four infralabyrinthine-apical, 25 massive and 16 apical. Five cases underwent transmastoid and retrolabyrinthine approach, translabyrinthine approach was performed on six patients, 19 cases underwent subtotal petrosectomy, seven cases underwent transotic approach, 41 cases underwent middle fossa approach, combined transmastoid/middle fossa approach was performed on 11 cases, translabyrinthine and sphenoid sinus approach were performed on one case. Supralabyrinthine cases mainly applied middle fossa approach (77.5%, 31/40) and combined transmastoid and middle-fossa approach(20.0%, 8/40). Combined transmastoid-retrolabyrinthine approach were applied for all the infralabyrinthine cases (100.0%, 5/5). Infralabyrinthine-apical cases mainly applied subtotal petrosectomy (75.0%, 3/4). Massive cases mainly applied subtotal petrosectomy (60.0%, 15/25), transcochlear approach (20.0%, 5/25), and translabyrinthine approach (16.0%, 4/25). Apical cases mainly applied middle fossa approach (62.5%, 10/16). Results: Ninty percent (18/20) of the patients who had preoperative grade Ⅰ facial nerve function maintained in the postoperative period. Out of 90 cases, only 11 cases received open cavity, and the rest cases received cavityobliteration. There were three cases of recurrence, four cases of cavity infection, three cases of cerebrospinal fluid leakage, and one case of epidural hematoma, who all received surgeries. Conclusions: Sanna's classification should be used to classify different kinds of PBC cases, choose the best surgical approach for different cases, and preserve or repair facial function during removal of PBC, and thus reduce recurrence and complications.

[The surgical treatment of middle ear cholesteatoma complicated with peripheral facial paralysis (with 22 cases)].

Objective:To summarize the clinical characteristics, the surgical methods and the recovery of facial nerve function outcomes in patients with the middle ear cholesteatoma complicated with peripheral facial paralysis.Method:Retrospective analysis method was used on patients treated for middle ear cholesteatoma associated with peripheral facial paralysis. Facial nerve decompression and great auricular nerve grafting were performed for restoration of facial nerve. Facial nerve function was assessed with the House-Brackmann (H-B) grade scale. Spearman test was employed for statistic analysis.Result:Surgical exploration revealed that the cholesteatoma was mainly located in epitympanic cavity, mastoid and sinus tympani, which mainly damaged the tympanic segment of facial nerve. Nineteen cases with facial nerve edema, including complete sheath (n=15) and sheath defect (n=4), were performed decompression. Among which 15 recovered to H-B Ⅰ, 3 recovered to H-B Ⅱ, 1 recovered to H-B Ⅳ. Three cases with facial nerve disrupt underwent great auricular nerve grafting, 1 recovered to H-B Ⅳ, 2 recovered to H-BⅤ. The rate of recovery to H-B Ⅰ or Ⅱ in patients underwent surgery within 2 weeks was 92.3%(12/13).Conclusion:When the middle ear cholesteatoma complicated with peripheral facial paralysis, surgery should be carried out as soon as possible. After removed the cholesteatoma completely, facial nerve decompression could acquire a better facial nerve function recovery compared to great auricular grafting.

[Effects of PSMB5 on proliferation and bortezomib chemo-resistance in human myeloma cells and its related molecular mechanisms].

Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot. Results: ①PSMB5 overexpression and knockdown were successfully constructed in RPMI 8226 and BTZ100 cells. ②PSMB5 expression was positively correlated with cell proliferation of RPMI 8226 and BTZ100 cells (P<0.05) . ③The cell viability was lower after PSMB5 knockdown in RPMI 8226 cells than control cells under the same concentration of BTZ[IC(50) at 24 h: (7.01±0.47) and (9.64±0.55) nmol/L respectively, t=6.289, P=0.003]. The cell viability was higher after PSMB5 overexpression in RPMI 8226 cells than control cells under the same concentration of BTZ[IC(50) at 24 h: (10.99±0.58) and (9.51±0.37) nmol/L respectively, t=3.724, P=0.020) . PSMB5 expression was negatively correlated with the sensitivity of RPMI 8226 cells to BTZ. The results of BTZ100 cells were similar. ④The expression of PSMB5 was negatively correlated with the apoptosis of RPMI 8226 and BTZ100 under the treatment of BTZ. ⑤Meanwhile, PSMB5 knockdown could increase the expression of pro-apoptosis gene Bax and cleaved caspase-3 and decrease the expression of anti-apoptotic gene Bcl-2 and p-Akt. PSMB5 over-expression has the opposite results. Conclusion: PSMB5 knockdown could improve the bortezomib sensitivity of MM cells via activation of apoptosis signaling. PSMB5 may be a potential therapeutic target for MM.

Expression of maspin in invasive fungal rhinosinusitis.

OBJECTIVE: This study aimed to test the expression of maspin in invasive fungal rhinosinusitis and explore its value in diagnosing invasive fungal rhinosinusitis. METHODS: Forty-two fungal rhinosinusitis cases (12 invasive and 30 non-invasive) were selected as the experimental group, and 30 chronic rhinosinusitis cases comprised the control group. Maspin expression was assessed in nasal mucous membrane specimens by immunohistochemical staining. RESULTS: Compared with the control group, maspin expression was down-regulated in the fungal rhinosinusitis group (p < 0.05). Furthermore, the staining score for maspin was lowest in the invasive fungal rhinosinusitis group, as compared with both the non-invasive fungal rhinosinusitis group and the control group (p < 0.05). A maspin staining score of 5.70 was the critical value for diagnosis of invasive fungal rhinosinusitis, with sensitivity and specificity of 91.7 per cent and 88.3 per cent, respectively. CONCLUSION: The results of this study suggest that the maspin staining score may be a biomarker for effective and rapid diagnosis of invasive fungal rhinosinusitis.

Brachial artery flow-mediated dilatation and carotid intima-media thickness in young ED patients with insulin resistance.

The evidence of a close relationship between cardiovascular disease and erectile dysfunction (ED) is well documented. The aim of this study is to investigate whether there is an early asymptomatic impairment of the peripheral vasculature in young ED patients without obvious cardiovascular disease. We studied a total of 261 ED patients (19-40 years old) and 40 age-matched healthy controls. All participants received questionnaires of cardiovascular risk factors and erectile function assessment, were subjected to lab tests of fasting blood sample, and underwent the ultrasonographic examination of brachial artery flow-mediated dilation (FMD) and carotid intima-media thickness (c-IMT). Insulin resistance (IR) was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Compared with normal human controls, FMD was significantly lower, whereas the average c-IMT was significantly greater in ED patients. An inverse correlation was found between FMD and mean c-IMT. The ED patients had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index, but showed relatively lower total testosterone and prolactin levels than the controls. Both FMD and c-IMT showed a significant correlation with International Index of Erectile Function-5 questionnaire (IIEF-5) score, age and HOMA-IR. Multivariate stepwise regression analysis demonstrated that age, HOMA-IR and IIEF-5 score were the risk factors associated with FMD and c-IMT. In conclusion, young ED patients in association with IR display diminished FMD and increased c-IMT. Furthermore, ED, HOMA-IR and age are independent predictors of the two subclinical atherosclerotic markers.

Influence of Constant Temperature on Development and Reproduction of Encarsia guadeloupae Viggiani (Hymenoptera: Aphelinidae), a Parasitoid of the Spiraling Whitefly Aleurodicus dispersus Russell (Hemiptera: Aleyrodidae).

Encarsia guadeloupae Viggiani is an important parasitoid of Aleurodicus dispersus Russell. The effects of temperature (16, 20, 24, 28, and 32°C) on development and reproduction of this parasitoid on A. dispersus were studied in laboratory experiments. The developmental duration of E. guadeloupae varied from 14.9 (32°C) to 54.4 days (16°C). The developmental threshold and thermal constant for an entire generation were 10.52°C and 308.85 degree-days, respectively. The highest survival rate (63.8%) of immature E. guadeloupae was recorded at 28°C. The average adult longevity ranged from 6.0 (32°C) to 15.1 days (16°C). The highest fecundity was observed at 28°C. The intrinsic rate of increase (r m ), net reproduction rate (R o ), and finite rate of increase (λ) were the highest at 28°C, which were 0.18, 54.25 and 1.21, respectively. We concluded that 28°C is the most suitable temperature for development and reproduction of E. guadeloupae.

Efficacy of intratumoral chemotherapy using arsenic trioxide (As2O3) sustained release tablets for the treatment of neurogliocytoma in nude mice.

OBJECTIVE: This study aimed to investigate the inhibiting effect of arsenic trioxide (As2O3) on neurogliocytoma in nude mice and the mechanism responsible for this effect. MATERIALS AND METHODS: Neurogliocytoma implantation models were constructed in nude mice, which were assigned to three groups: the control group, the sustained release tablet-polylactic acid-glycolic acid polymer (50:50) group (PLGA group) and the As2O3-polylactic acid-glycolic acid polymer (50:50) (As2O3-PLGA group). One tablet of As2O3-PLGA was implanted in the tumor of the As2O3-PLGA group. Intratumoral implantation was also performed in the other groups using a different type of tablet. The sustained releasing As2O3 had an inhibiting effect on the tumors. The TUNEL assay was used to determine the apoptosis rates in the implanted tumors. Immunohistochemical staining and Western blotting was carried out to determine the expression levels of caspase-3 and Bcl-2. RESULTS: No inhibitory effect was observed on the tumor in the PLGA group, and there was no significant difference between this group and the control group. Subcutaneous tumor growth in nude mice was significantly inhibited in the As2O3-PLGA group relative to that in the control group, and the difference was statistically significant (p < 0.01). The tumor inhibition rate was 60.8%. The percentage of apoptotic tumor cells in the As2O3-PLGA group was 30.8%, which was significantly higher than that in the control group (3.92%) and that in the PLGA group (4.08%). The expression of Bcl-2 in the implanted tumor tissue was significantly reduced, but the expression of caspase-3 increased significantly. CONCLUSIONS: As2O3 has a potent inhibiting effect on the growth of neurogliocytoma in vivo and can induce the apoptosis of tumor cells. The molecular mechanism of this effect may be related to the downregulation of Bcl-2 expression and the upregulation of caspase-3 expression.

Differential modification of genetic susceptibility to childhood eczema by two probiotics.

BACKGROUND: In a double-blind, randomized, placebo-controlled birth cohort, we have recently shown a beneficial effect of Lactobacillus rhamnosus HN001 (HN001) for the prevention of eczema in children through to 6 years of age but no effect of Bifidobacterium animalis subsp lactis HN019 (HN019). OBJECTIVE: Among this cohort of children, we aim to investigate whether these probiotics could modify the expression of genetic predisposition to eczema conferred by genetic variation in susceptibility genes. METHODS: Thirty-three eczema susceptibility SNPs (in eleven genes) were genotyped in 331 children of European ancestry. RESULTS: Children who carried a genetic variant that put them at a high risk of developing eczema were less likely to develop eczema if they had been randomized to the HN001 intervention group compared to those in the placebo group. HN019 was also able to protect against the effects of some SNPs. As well as modifying genetic susceptibility to childhood eczema, HN001 was also found to modify genetic susceptibility to eczema severity and atopy risk. CONCLUSION AND CLINICAL RELEVANCE: This is the first study to show an effect of a probiotic on reducing eczema risk amongst those with particular eczema-associated genotypes. Our findings suggest that Lactobacillus rhamnosus HN001 may be particularly effective in preventing eczema in children with specific high-risk genotypes.

PTPN2 but not PTPN22 is associated with Crohn's disease in a New Zealand population.

Recent genome-wide association studies have provided evidence for the involvement of the genes PTPN2 and PTPN22 in the pathogenesis of Crohn's disease (CD). We investigated whether genetic variants in these genes were associated with CD in a New Zealand population. Single-nucleotide polymorphisms (SNPs) rs2542151 (PTPN2) and rs2476601 (PTPN22) were genotyped in 315 CD cases and 481 controls. In this sample, we were able to confirm an association between CD and PTPN2 (genotypic P = 0.019 and allelic P = 0.011), and phenotypic analysis showed an association of this SNP with late age at first diagnosis, inflammatory and penetrating CD behaviour, requirement of bowel resection and being a smoker at diagnosis. There was no evidence for an association with PTPN22.

Falling asleep: the determinants of sleep latency.

BACKGROUND: Difficulty falling asleep (prolonged sleep latency) is a frequently reported problem in school-aged children. AIMS: This study aimed to describe the distribution of sleep latency and factors that influence its duration. METHODS: 871 children of European mothers were recruited at birth. 591 (67.9%) children took part in the follow-up at 7 years of age. Sleep and daytime activity were measured objectively by an actigraph worn for 24 h. RESULTS: Complete sleep data were available for 519 children (87.8%) with a mean age of 7.3 years (SD 0.2). Median sleep latency was 26 minutes (interquartile range 13-42). Higher mean daytime activity counts were associated with a decrease in sleep latency (-1.2 minutes per 102 movement count per minute, p = 0.05). Time spent in sedentary activity was associated with an increase in sleep latency (3.1 minutes per hour of sedentary activity, p = 0.01). CONCLUSIONS: These findings emphasise the importance of physical activity for children, not only for fitness, cardiovascular health and weight control, but also for promoting good sleep.

A novel DFNA5 mutation, IVS8+4 A>G, in the splice donor site of intron 8 causes late-onset non-syndromic hearing loss in a Chinese family.

We report here the clinical, genetic, and molecular characteristics of a large Chinese family exhibiting non-syndromic, late-onset autosomal dominant sensorineural hearing loss. Clinical evaluation revealed variable phenotypes of hearing loss in terms of severity and age-at-onset of disease in these subjects. Genome-wide linkage analysis mapped the disease gene to the DFNA5 locus with a maximum two-point log odds score of 5.39 at [theta] = 0 for marker D7S2457. DNA sequencing of DFNA5 revealed a novel heterozygous IVS8+4 A>G substitution in the splice donor site of intron 8. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed skipping of exon 8 in the mutant transcript. This mutation faithfully cosegregated with hearing loss in the family. In addition, the mutation was absent in 100 unrelated control DNA samples of Chinese origin. The IVS8+4 A>G mutation is predicted to create a shift in the reading frame and introduce a stop codon at position 372, thereby resulting in a prematurely truncated DFNA5 protein. Up to date, a total of four mutations in DFNA5 have been reported to lead to hearing impairment, all of them result in skipping of exon 8 at the mRNA level. Our findings provide further support for the hypothesis that DFNA5-associated hearing loss is caused by a very specific gain-of-function mutation.