Objective To evaluate the diagnosis and treatment of intestinal neuronal dysplasia type B (IND) in childhood. MethodsForty-five patients underwent preoperative barium enema examination, 23 patients underwent electromanometry, and mucosal biopsy and immunohistochemical staining for S100 protein were performed in 17 cases. All 45 patients underwent resection of the invalid segment with coloproctostomy. Whole layer was sampled on several sites of the resected segment and examined by two independent pathologists. All patients were followed up from 3 months to 9 years (mean 4.6 years).ResultsTwenty eight patients were complicated with Hirschsprung′s disease, one patient with hypogangliosis, and isolated IND was diagnosed in the other 16 children. The narrowed distal segment with proximal dilatation was merely noted in 4 children with isolated IND. Internal sphincter relaxations were missing in 6 children with isolated IND. The indicative diagnosis might be merely gained in 7 patients by the mucosa biopsy. The correct diagnosis can be established by whole layer biopsy of the resected segment. Three children with enterocolitis after operation were cured by conservative treatment. One patient suffering from postoperative sluice syndrome underwent second resection. Postoperative continence was achived in all patients. ConclusionThe correct diagnosis of IND can be obtained by biopsy of whole layer, and resection of invalid bowel segment with coloproctostomy is the choice of therapy.

0.05), but not in other brain regions. The number of GFAP-immunopositive cells of the E.coli-treated pups was markedly increased in periventricular white matter and hippocampus at P7 compared with the control group (P0.05). CONCLUSION: Intrauterine infection induces an increased expression of GFAP in the neonatal brain. [

Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Poly-adenosine diphosphate ribose polymerases (PARPs) play an important role in DNA repair and apoptosis.Among them, mono-(ADP-ribosyl) transferase (MARTs) can regulate various cell reactions by catalyzing and transferring single ADP-ribose.Most MARTs are highly expressed in cancers, which is closely related to the occurrence and progression of cancers.This review introduces the MARTs that are highly expressed in cancers, classifies them according to the differences of their structural domains, and reviews their known mechanism, their close relationship with cancers, their potential value in cancer therapy and the research progress of corresponding inhibitors.These targets are expected to provide new research ideas for cancer therapy in the era of precision medicine.

Objective To analyze the causes of revision surgery after percutaneous transforaminal endoscopic discectomy (PTED) for lumbar spinal stenosis,and to provide references for indications and operative methods.Methods From January 2015 to October 2017,206,491 and 60 patients of lumbar spinal stenosis were treated with PTED in Tianjin Hospital,Shanxi People's Hospital,Ningbo Sixth Hospital,respectively;among them,4,10 and 4 cases received revision surgery.Another 13 patients of lumbar spinal stenosis were treated with revision surgery due to poor results after PTED in other hospitals.Among 31 cases of reoperation,there were 16 males and 15 females,aged 27-82 years (average,66.2±12.7 years).The lesion segments included 1 case of L3,4,23 cases of L4,5,5 cases of L5S1,1 cases of L3-L5,and 1 cases of L4-S1.Patients were followed up after reoperation from 3 to 24 months (average,12.1 months).The causes of poor result and revision surgery were analyzed according to preoperative,intraoperative and postoperative data.Results All of 757 cases of lumbar spinal stenosis were treated with PTED in three hospitals,of which 18 cases (2.4％) were re-operated.The causes of reoperation included:bone slice displacement in 1 case;nerve injury in 4 cases;lumbar instability in 4 cases;disc protrusion in 10 cases (residual or recurrence);insufficient decompression in 21 cases;planed staging operation in 4 cases with bilateral or two-level stenosis.32 revision surgeries were performed for 31 patients,including PTED in 15 cases,microendoscopic discectomy (MED) in 1 case,mobile MED (MMED) in 5 cases,MMED assisted fusion in 2 cases,transforaminal lumbar interbody fusion (TLIF) in 4 cases,Minimally invasive TLIF (Mis-TLIF) in 2 cases,and open decompression and fusion in 3 cases.All patients experienced relieve of symptoms after revision surgery.At final follow-up,VAS leg pain deceased form 7.1±3.9 before revision surgeries to 1.9±1.2,VAS low back pain decreased form 6.3±3.2 to 1.8±1.3,ODI score decreased from 35％± 14％ to 7.6％±5％.According to the MacNab score,the result was excellent in 11 cases,good in 16 cases,and fair in 4 cases.Conclusion The treatment of lumbar stenosis with PTED has high technical requirements,the indications of PTED for lumbar stenosis should be strictly controlled according to technical conditions,and appropriate operative methods should be chosen according to the specific conditions of the lesions.Insufficient decompression,disc protrusion,lumbar instability and nerve injury are the common causes of reoperation.Suitable indications and proper operation should be selected.

Objective: To investigate the immunohistochemical staining of anaplastic lymphoma kinase (ALK; clone 1A4) in pediatric medulloblastoma (MB). Methods: Molecular subtyping was performed based on the NanoString and sequencing techniques for 44 pediatric MB cases at Children′s Hospital, Zhejiang University School of Medicine from 2014 to 2017. ALK expression was detected with EnVision immunhistochemistry using ALK clone 1A4 on whole section. Statistical analyses were performed to evaluate the correlation of protein expression with molecular subgroups. Results: The age ranged from 0.5 to 13.0 years with an average age of 5.8 years. There were 28 males and 16 females, and 31 classic, 5 desmoplastic nodular, 3 extensive nodular and 5 large cell/anaplastic MBs. Except three cases was unable classified, 41 MBs were classified into the four molecular groups: 5 in WNT group, 12 in SHH group, 9 in Group 3 and 15 in Group 4. Thirteen of 44 MB cases were positive staining for ALK, and the positive rate was 29.5%. Six cases were strong reaction, and 7 cases were weak. The expression of ALK at the protein level was associated with the WNT group (P<0.01). The characteristic perinuclear dot-like staining was only showed in WNT group. Conclusions The ALK immunhistochemistry using antibody clone 1A4 is a useful marker for the molecular subgroup detection of MB. The strong staining and perinuclear dot-like staining indicate as WNT group.