Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13—implications for cytogenetics and molecular biology

We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion. © 1996 Wiley-Liss, Inc.     

Phospho-Aspirin (MDC-22) inhibits pancreatic cancer growth in patient-derived tumor xenografts and KPC mice by targeting EGFR: Enhanced efficacy in combination with irinotecan

Novel therapeutic strategies are needed in the fight against pancreatic cancer. We have previously documented the chemopreventive effect of MDC-22 in preclinical models of pancreatic cancer. In the present work, we examined the therapeutic effects of MDC-22 in patient-derived tumor xenografts (PDTXs) and in LSL-Kras^G12D/+, LSL-Trp53^R172H/+, Pdx1-Cre (KPC) genetically engineered mice, two complementary and clinically relevant animal models of pancreatic cancer. In addition, we evaluated whether MDC-22 could synergize with current chemotherapeutic drugs used in the clinic. MDC-22 reduced the growth of various human pancreatic cancer cell lines in a concentration-dependent manner. In vivo, MDC-22 strongly reduced patient-derived pancreatic tumor xenograft growth by 50%, and extended survival of LSL-Kras^G12D/+; LSL-Trp53^R172H/+; Pdx1-Cre (KPC) mice by over a month (5.3 months versus 7.0 months). In both models, MDC-22 inhibited EGFR activation and its downstream signals, including ERK and FAK phosphorylation. In human pancreatic cancer cell lines, MDC-22 enhanced the growth inhibitory effect of irinotecan, and to a lesser degree those of gemcitabine and nab-paclitaxel. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of, both, MDC-22 alone or in combination with irinotecan, indicating selectivity. Furthermore, MDC-22 enhanced irinotecan''s effect on cell migration, in part, by inhibiting EGFR/FAK signaling. Collectively, our results indicate that MDC-22 is an effective anticancer drug in preclinical models of pancreatic cancer, and suggest that MDC-22 plus irinotecan as drug combination strategy for pancreatic cancer treatment, which warrants further evaluation.     

Dual specificity phosphatase 22 relates to skin lesion degree and biologics history,while its longitudinal elevation during treatment reflects better outcome in psoriasis patients

BackgroundDual specificity phosphatase 22 (DUSP22) plays an important role in the regulation of immune and inflammation, but its correlation with clinical features and treatment outcome in psoriasis patients is still unclear. This study was to investigate the longitudinal change of DUSP22 with time, as well as its association with disease activity and treatment response in psoriasis patients.MethodsTotally, 120 psoriasis patients, 50 patients with other skin inflammations as disease controls (DCs), and 50 health controls (HCs) were recruited. Serum samples were collected from psoriasis patients at baseline, month (M)1, M3, and M6 after initiation of etanercept‐based treatment as well as from DCs and HCs after enrollment to assess DUSP22 level by enzyme‐linked immunosorbent assay.ResultsDUSP22 was lower in psoriasis patients than in HCs and DCs (both p < 0.001). Besides, in psoriasis patients, DUSP22 was associated with lower psoriasis area severity index (PASI) score (p = 0.001) and systemic biological treatment history (p = 0.023), but not with other demographics, disease characteristics, or treatment history (all p>0.05). In addition, DUSP22 was increased with time (p < 0.001) in total patients. Moreover, DUSP22 at M3 (p = 0.004) and M6 (p < 0.001) was higher in response patients than in non‐response patients evaluated by PASI 75. Additionally, DUSP22 at M3 (p < 0.001) and M6 (p = 0.003) was also increased in response patients compared with non‐response patients evaluated by PASI 90.ConclusionDUSP22 decreases and negatively correlates with disease activity, while its longitudinal elevation with time reflects satisfactory treatment response in psoriasis patients.     

Allergy accelerates the disease progression of chronic rhinosinusitis

Background: The role of allergy in the development of chronic rhinosinusitis (CRS) in East Asians is not clear.

Aims/objectives: The aim was to investigate the impact of allergies in the clinical characteristics of chronic rhinosinusitis.

Material and methods: A total of 138 CRS patients who underwent endoscopic sinus surgery were included. A brief history of rhinosinusitis symptoms, blood eosinophil count, blood-specific allergen tests, computed tomography (CT) scan findings, Lund-Mackay (LM) CT scores, and Sino-Nasal Outcome Test (SNOT-22) Questionnaire scores, and sinoscopy findings at 3 and 6 months postoperatively.

Results: The ImmunoCAP test was positive in 71(51%) patients and negative in 67(49%) patients. The mean age of those who received endoscopic sinus surgery was 7-years younger in the allergic group compared with the non-allergic group (p?=?.008). The peripheral eosinophil count in the allergic group was higher than that of the non-allergic group (p?=?.008). The LM scores and SNOT-22 scores were not significantly different between the two groups. The recurrence rate of nasal polyps in the allergic group was higher but without statistical significance.

Conclusions and significance: Allergy may accelerate the disease progression of CRS. The presence of the serum-specific IgE was correlated with peripheral eosinophil percentage, especially in the CRSwNP patients.     

Retropharyngeal lipostructure in the treatment of velopharyngeal insufficiency: A prospective study and update

IntroductionRetropharyngeal lipostructure is a recent procedure in velopharyngeal insufficiency (VPI), offering an effective alternative to heavier surgery.ObjectivesTo update and assess retropharyngeal lipostructure as a treatment for VPI in the University Hospital Center of Rouen (France).Type of studySingle-center prospective study, from May 2012 to May 2014.Patients and methodsSix patients (4 girls, 2 boys) presenting with VPI were treated by retropharyngeal lipostructure. Age at surgery ranged between 6 and 12 years. Four of the patients bore a 22q11 microdeletion. Treatment was indicated in case of Borel-Maisonny type 2b (n = 2) or 2 m (n = 4) despite well-conducted speech therapy and of ≥ 50% velopharyngeal sphincter closure on nasal endoscopy. Patients were assessed preoperatively and at 3 months, by a multidisciplinary team. Borel-Maisonny type was assessed by a speech therapist. Nasality was measured on assisted vocal evaluation (EVA^®). Sphincter closure was assessed on dynamic MRI.ResultsBetween 6 and 8 cm³autologous fat was injected. At 3 months, 4 children showed 1-grade improvement in Borel-Maisonny type. Nasality decreased systematically, from a mean 14.5% preoperatively to 10.5% postoperatively. MRI showed improvement in all cases, with complete closure in occlusive vowels in 3 children.ConclusionEVA^® and MRI provide precise objective assessment of VPI. Retropharyngeal lipostructure is a simple, relatively non-invasive, reproducible technique, providing good results in VPI.     

开口箭提取物对小鼠移植性实体瘤H22的抑制作用

目的：研究开口箭提取物对小鼠移植性实体瘤H22的抑制作用及其对体重增长率、胸腺指数、脾指数的影响。方法：开口箭总提物、开口箭总皂苷和多糖分别设高、中、低3个剂量组,分别对H22实体瘤移植性小鼠连续10d灌胃给药后,测其体重增长率、抑瘤率、胸腺指数及脾指数,与模型组和阳性对照组比较。结果：总提物3个剂量组和多糖3个剂量组对小鼠移植性实体瘤H22有明显的抑制作用．抑瘤率分别为41．23％、42．58％、39．11％、42．58％、53．95％、40．27％,其中多糖中剂量组治疗效果最为显著．总皂苷组与模型组比较没有差别。3种药物不同剂量对移植性实体瘤H22小鼠的体重、胸腺和脾脏均没有抑制作用．结论：开口箭总提物和开口箭多糖有明显的抑制小鼠移植性实体瘤H22的作用,而且对胸腺、脾脏没有毒副作用．在抗肝癌方面具有广阔的前景。     

Th22及其细胞因子在斑秃患者外周血的表达和意义

目的：探讨Th22及其细胞因子在斑秃患者外周血中的表达及其临床意义,分析T淋巴细胞在斑秃发病机制中的作用。方法选取上海市闵行区中心医院2015年1月至2016年5月收治的38例斑秃患者作为研究对象,设为斑秃组;同时取同期健康体检38例作为健康对照组,用流式细胞仪检测Th22细胞水平,用酶联免疫吸附检测血清中IL?22、IL?17的水平。结果斑秃组外周血Th22、Th17、IL?17+IL?22+CD4+、IFN?γ+IL?22+CD4+T细胞表达水平均高于健康对照组（P<0.01）。斑秃组血清IL?22、IL?17水平均高于健康对照组（P<0.05）;与轻型斑秃患者和稳定期患者相比,重型斑秃和活动期患者Th22、Th17、IL?17+IL?22+CD4+、IFN?γ+IL?22+CD4+T细胞及血清IL?22、IL?17的表达进一步升高（P<0.05）。结论 Th22及其细胞因子可能参与斑秃的发生、发展、预后。     

药疹患者血清Th22细胞相关细胞因子和补体蛋白水平变化研究

目的 了解药疹患者治疗前后血清中Th22细胞相关因子及补体相关指标表达水平的变化,探索其在药疹发生发展中的可能作用。方法 35例药疹患者,以1∶1的比例匹配性别、年龄一致的健康对照者,分别采集药疹患者治疗前后及对照组外周血5 ml。采用酶联免疫吸附试验（ELISA）和流式液相多重蛋白定量技术（CBA）检测血清中白细胞介素22（IL?22）、IL?13、肿瘤坏死因子α（TNF?α）及补体蛋白C3a、C4a、C5a。结果 治疗前,药疹患者血清中IL?22［（40.85 ± 14.56） ng/L］、IL?13［（869.94 ± 463.39） ng/L］、TNF?α［（1.03 ± 0.64） ng/L］及补体C3a［（55.21 ± 32.98） ng/L］、C4a［（285.11 ± 123.91） ng/L］、C5a表达水平［（279.68 ± 127.72） ng/L］明显高于对照组（分别为29.09 ± 8.66、372.92 ± 151.75、0.44 ± 0.31、42.44 ± 14.26、237.00 ± 63.57和215.98 ± 65.38 ng/L）,差异均有统计学意义（t值分别为5.549、6.071、4.321、2.832、2.257、2.495,均P < 0.05）。治疗后,药疹患者血清IL?22［（32.72 ± 11.77） ng/L］、IL?13［（456.21 ± 123.22） ng/L］、TNF?α［（0.64 ± 0.39） ng/L］、C3a［（45.47 ± 21.11） ng/L］、C4a［（241.86 ± 84.12） ng/L］、C5a表达水平［（239.61 ± 103.51） ng/L］均低于治疗前,差异均有统计学意义（t值分别为4.443、5.197、3.572、3.213、2.728、4.772,均P ≤ 0.01）,且除IL?22、IL?13水平仍高于对照组外（P < 0.05）,TNF?α及补体C3a、C4a、C5a水平与对照组差异无统计学意义（均P > 0.05）。相关性分析显示,药疹患者治疗前血清补体C3a与C4a（r = 0.660）、C5a（r = 0.404）,C4a与C5a（r = 0.501）表达水平呈正相关,均P < 0.05,IL?22表达水平与补体C3a水平呈负相关（r = -0.490,P = 0.005）,与TNF?α表达水平呈正相关（r = 0.573,P = 0.005）。结论 Th22细胞相关细胞因子及补体活化在药疹发生发展过程中可能起重要作用,且IL?22可能参与补体蛋白的调控。     

Resolvin D1 attenuates imiquimod-induced mice psoriasiform dermatitis through MAPKs and NF-κB pathways

Background

Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported.