Transcriptional repression by androgen receptor: roles in castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.

Effect of enteral nutrition on accidental upper gastrointestinal injury in children / 中华儿科杂志

Objective@#To evaluate the effectiveness of enteral nutrition in children with accidental upper gastrointestinal injury.@*Methods@#The medical records of 128 patients with mechanical or chemical gastrointestinal mucosal injury, who were hospitalized in Department of Gastroenterology, Children's Hospital of Zhejiang University School of Medicine from January 1, 2011 to December 30, 2017, were collected. All cases were treated with enteral nutrition. The clinical features and etiologies were retrospectively analyzed. Weight-for-age Z score and lab findings including white blood cells, C-reactive protein, neutrophils, albumin, prealbumin, urea nitrogen and hemoglobin before and after treatment were extracted. The clinical characteristics, the duration of enteral nutrition and gastrointestinal mucosal healing between different etiologies were further analyzed. Normal distribution variables and categorized variables were compared with t test and χ2 test respectively, and abnormal distribution data was compared with Wilcoxon test.@*Results@#Among all the cases, 77 were males and 51 were females. The average age was (29±22) months. The mean duration of hospitalization and enteral nutrition were (11±7)d and (27±20)d respectively. Vomiting was the most common clinical presentation (72 cases, 56.3%). In 79 cases the problems were caused by mechanical injury, among which coins were most commonly seen. The rest 49 cases were caused by chemical injury. However, the duration of hospitalization ((13±8) d vs. (10±6)d, t=-3.089, P=0.002) and enteral nutrition ((39±22) vs. (19±14) d, t=-5.365, P=0.000) were longer in children with chemical injury than those with mechanical injury. A total of 112 cases got complete blood count and C-reactive protein both before and after enteral nutrition. Inflammatory markers, including leukocytes ((7.7±2.7) ×109/L vs. (13.7±5.0) ×109/L, t=12.244, P <0.05), neutrophils ((3.4±1.9)×109/L vs. (9.4±4.6) ×109/L, t=13.655, P<0.05), and C-reactive proteins (5.0(3.0,7.8) vs. 13.5(6.0,40.5) mg/L, Z=7.776, P <0.05) were significantly decreased. The nutritional markers, including the weight-for-age z score (-0.1 ± 1.0 vs. 0.0 ± 1.0, t=-2.622, P=0.010) and the prealbumin (0.1 ± 0.1 vs. 0.2 ± 0.0 g/L, t=-3.671, P=0.001) were significantly increased. Fifty-five (82.1%) children in mechanical injury group recovered in 4 weeks, while 27 (79.4%) children in chemical injury group recovered in 7 weeks.@*Conclusion@#Enteral nutrition can provide adequate nutritional requirements for children with upper gastrointestinal injury, and may help to decrease imflammation and improve mucosal healing.

Endoscopic management of ingested foreign bodies in the upper gastrointestinal tract in childhood: a retrospective study of 1 334 cases / 中华儿科杂志

Objective@#To explore the clinical features and complications of foreign bodies in the upper gastrointestinal tract in children and to investigate the effectiveness of endoscopic management.@*Methods@#Data of patients with foreign bodies in upper gastrointestinal tract were collected retrospectively at Endoscopy Center, the Children's Hospital, Zhejiang University School of Medicine, from January 2011 to December 2016. Clinical characteristics, the types of foreign bodies, the location and duration of foreign body impaction were summarized. The risk factors of complications and endoscopic removal failure were analyzed by using Logistic regression analysis.@*Results@#A total of 1 334 patients (825 males and 509 females) were enrolled. The median age was 2.5 years, with a range from 0.25 to 15 years and peak age 1-3 years. Twenty patients had esophageal diseases. The most common foreign body ingested was coin (n=964, 72.3%). Foreign bodies were most commonly located in the esophagus (n=1 002, 75.1%), especially in the upper esophagus (n=857, 85.5%). The duration of foreign body impaction ranged from 3 hours to 5 years. Among 1 334 patients, 252 patients (18.9%) developed complications, including ulcers (n=101, 40.0%) and perforations(n=13, 5.2%). The success rate of endoscopic removal was 96.6% (n=1 288). By Logistic regression analysis, sharp foreign body ingestion (OR=6.893, 95%CI: 4.421-10.746) , esophageal impaction (OR=5.253, 95%CI:3.352-8.233) and foreign body impaction longer than 24 hours (OR=4.336, 95%CI:3.091-6.082) were risk factors of complications. Sharp foreign body ingestion was the risk factor of endoscopic failure (OR=5.372, 95%CI:2.773-10.406) .@*Conclusions@#Coin is the most common foreign body in upper gastrointestinal tract. Sharp foreign bodies impacted in the esophagus over 24 hours increase the risk of complications. Endoscopic removal of foreign bodies from the upper gastrointestinal tract in children has a high success rate. Sharp foreign body ingestion increases the risk of failure in endoscopic removing.

X-linked inhibitor of apoptosis deficiency manifested as Crohn's disease: a case report and literature review / 中华儿科杂志

Objective@#To analyze the clinical characteristics of X-linked inhibitor of apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's disease.@*Methods@#Clinical manifestations, laboratory investigations, genetic testing and therapeutic interventions of one case of XIAP deficiency who was admitted to Department of Gastroenterology in Children's Hospital, Zhejiang University School of Medicine in May 2016 were summarized. PubMed and Chinese database for articles published from January 2016 to June 2017 were searched using the key words of'Crohn's disease’and'XIAP’, and the relevant literature was reviewed.@*Results@#The case we reported was a 6-year-1-month-old boy with recurrent bloody stool for 2 months, and abdominal pain with fever for 2 weeks. The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and epilepsy in the past one year. Complete blood cell count showed mild anemia (Hb108 g/L). The patient had an elevated high-sensitivity C reactive protein (86 mg/L) and erythrocyte sedimentation rate (46 mm/1h) . White blood cells, pus cells and red blood cells were found on routine stool examination. Biochemical panel showed hypoalbuminemia (25.2 g/L) , elevated transaminase (alanine aminotransferase 175 U/L, aspartate transaminase 229 U/L) , hypertriglyceridemia (4.41 mmol/L) , and hyperferritinemia (>1 650.0 μg/L) . Magnetic resonance enterography revealed the intestinal wall thickening and increased enhancement in parts of illeum and colon. Capsule endoscopy revealed multiple ulcers in jejunum. Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of terminal ileum and colon, which was combined with partial necrosis and ulceration. Some phagocytes were seen in bone marrow smears. The patient was given multiple diagnoses, including hemophagocytic lymphohistiocytosis, Crohn's disease, sepsis, epilepsy, severe malnutrition, and hypoproteinemia. The pediatric Crohn's disease activity index (PCDAI) was 37.5. Genetic testing identified a hemizygotic mutation of c.910G>T chrX:123022501 p.G304X in XIAP. The parents had no such mutation. The patient showed response to infliximab with oral intake of mercaptopurine and corticosteroids, and had remission with PCDAI of 0. There were 9 relevant articles (Chinese 0 English 9), which showed 33.3% XIAP deficient patients manifested with inflammatory bowel disease(IBD), who might have other manifestations such as hemophagocytic lymphohistiocytosis or splenomegaly simultaneously or sequentially. Those patients showed poor response to monotherapy.@*Conclusion@#XIAP deficient patients have various clinical manifestations. Genetic testing is important to those male pediatric IBD patients who have the complicated symptoms or little response to standard therapy.

Efficacy of infliximab in treatment of pediatric Crohn's disease in China / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of infliximab versus corticosteroids in achieving clinical remission in pediatric patients with Crohn's disease in China.</p><p><b>METHOD</b>Data of all newly diagnosed active Crohn's disease pediatric cases seen from June 2009 to December 2013 in Children's Hospital, Zhejiang University School of Medicine were retrospectively recorded and reviewed.</p><p><b>INCLUSION CRITERIA</b>the age of the children was less than 18 years; pediatric Crohn's disease activity index (PCDAI) was more than 10; infliximab or corticosteroids were used for inducing remission; infliximab, immunosuppressive medications or mesalamine was prescribed for maintaining remission. Patients in steroids group were followed up for more than 1 year. The enrolled patients were divided into two groups: infliximab group and steroids group. Clinical data, laboratory findings and side effects of the medications were collected at week 2, 4, 12, 24 and 48. PCDAI and Crohn's disease endoscopic index score (CDEIS) were calculated. Clinical response rate, clinical remission rate, relapse rate, mucosal healing and growth were evaluated.</p><p><b>RESULT</b>Eleven children received infliximab therapy and 11 subjects received corticosteroids. In Infliximab group, 6, 5 and 7 patients were in clinical remission at week 2, 4, and 8, while so were 6, 9, and 9 patients in steroids group. The difference was not statistically significant (χ² = 0.00, 3.14, 0.92, P > 0.05). In infliximab group, 8, 8, and 11 patients were in clinical remission at week 2, 4, and 8, so were 8, 9, and 9 patients in steroids group. The difference was not statistically significant (χ² = 0.00,0.26, 2.20, P > 0.05). When compared with data at baseline, significant decreases were observed in the median PCDAI between the two groups at week 2, 4, and 8 (all P < 0.05). But there were no significant differences between two groups at week 2, 4, and 8 (all P > 0.05). At week 12, 24 and 48, 8/11, 7/8, 3/5 cases on infliximab versus 7/11, 9/11, 8/11 cases on steroids maintained remission. There was no significant differences between the two groups (all P > 0.05). In 7 patients and 9 patients remission was successfully induced at week 8. The relapse rate was similar at week 12, 24, and 48 (χ² = 0.83, 0.09, 1.00, all P > 0.05). Height for age Z score in infliximab group was significantly higher than that in steroids group at week 24 (P < 0.05). Body mass index Z score between the two groups at week 8, 24, and 48 were not statistically significant (all P > 0.05). Of the children treated with infliximab, 3 developed side effects. All the children treated with steroids got Cushing's syndrome.</p><p><b>CONCLUSION</b>In children with Crohn's disease, infliximab therapy is as effective as corticosteroids to induce remission.Less side effects were observed with infliximab therapy compared with immunosuppressive medication and mesalamine.</p>

EZH2, an epigenetic driver of prostate cancer

The histone methyltransferase EZH2 has been in the limelight of the field of cancer epigenetics for a decade now since it was first discovered to exhibit an elevated expression in metastatic prostate cancer. It persists to attract much scientific attention due to its important role in the process of cancer development and its potential of being an effective therapeutic target. Thus here we review the dysregulation of EZH2 in prostate cancer, its function, upstream regulators, downstream effectors, and current status of EZH2-targeting approaches. This review therefore provides a comprehensive overview of EZH2 in the context of prostate cancer.