Objective To explore the effect of α-zearalanol (α-ZAL) on β-amyloid (Aβ) induced mice and the mechanism. Methods The model was induced by intracerebroventricular injection of Aβ25-35. The mice were divided randomly into sham group, model group, estradiol benzoate (EB) group (Aβ+EB) as a positive control and α-ZAL (Aβ+α-ZAL) group. Morris water maze was used to evaluate the learning and memory ability. The levels of antioxidant enzymes and nitric oxide system in the brain tissue were detected with spectrophotometric and sotopic method. Results The escape latency was longer in the model group than in the control group (P<0.01), and was shorter in the EB group and α-ZAL group than in the model group (P<0.05). Compared with the control group, the level of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased, and the level of malonaldehyde (MDA), constitutive nitric oxide synthase (cNOS), inducible nitrous oxide synthesis (iNOS), and nitric oxide (NO) increased in the model group (P<0.05); compared with the model group, the level of SOD and GSH-Px increased, and the level of MDA, cNOS, iNOS and NO decreased in the EB group and α-ZAL group (P<0.05), except the level of SOD and cNOS in hippocampus in α-ZAL group (P>0.05). There was no significant difference between EB group and α-ZAL group (P>0.05). Conclusion α-ZAL could improve the cognitive behavior in Aβ25- 35 induced mice by increasing the antioxidant activities and decreasing the lipid peroxidation.

Objective : To understand the spatial distribution of multidrug resistant/rifampicin resistant pulmonary tuberculosis（MDR/RR PTB）in Wenzhou from 2014 to 2017,and to provide the scientific basis for MDR/RR TB control and prevention. Methods : The data of MDR/RR PTB cases in Wenzhou from 2014 to 2017 were collected from the Tuberculosis Management Information System of the Chinese Disease Prevention and Control Information System,and was associated with the geographic information database of Wenzhou Survey and Mapping Research Institute. The global spatial autocorrelation analysis was carried out by ArcGIS 10.1 to determine if there was spatial clustering of MDR/RR PTB cases in Wenzhou. The specific clustering areas of the MDR/RR PTB in Wenzhou was analyzed by SaTScan 9.3 and presented by ArcGIS. Results : There were 452 MDR/RR PTB cases reported in Wenzhou from 2014 to 2017,with a total registration rate of 4.74/100 000. The incidence rate of MDR/RR PTB in Wenzhou was unevenly distributed;the areas with registration rates of more than 7.45/100 000 were the north-central parts of Yongjia,the south-central parts of Yueqing and the east-central parts of Wencheng. The results of global spatial autocorrelation analysis showed that there were obvious clustering for MDR/RR PTB in Wenzhou（Moran's I=0.321,Z=7.352,P<0.001）. The spatial scanning found two clusters：20 towns/streets in the southeastern part of Yongjia and the south of Yueqing were the primary clustering areas（RR=2.213,LLR=22.353,P<0.001）;Yangyi Street and Shuangyu Street in Lucheng were the secondary clustering areas（RR=2.488,LLR=9.889,P=0.004）. Conclusion The MDR/RR PTB cases reported from 2014 to 2017 in Wenzhou had spatial clustering. The high-incidence areas were in the southeast of Yongjia,south of Yueqing,Yangyi Street and Shuangyu Street of Lucheng.

Objective To investigate the isolation rate, distribution and trend of nontuberculous mycobacteria (NTM) in Wenzhou during 2014 to 2016.Methods Sputum or alveolar lavage specimens of patients with suspected pulmonary tuberculosis were collected for mycobacteria culture from January 2014 to December 2016.Mycobacterium culture positive strains were further identified by gene chip, 16S rRNA and hsp65 gene sequencing.SPSS 19.0 software was used to analyze the data.Results After excluding repetitive strains, 3 295 mycobacteria strains (MTB) were isolated from respiratory specimens, included 3 032 mycobacterium tuberculosis complex strains, 238 NTM strains, 20 Gordon genera strains, 3 Nocardia genera strains and 2 Tsukamurella genera strains.The proportion of NTM among confirmed mycobacteria was 8.5％ (86/1 006), 6.7％ (72/1 079) and 6.8％ (80/1 185) in 2014, 2015 and 2016, respectively (x2 =2.459,P ＞ 0.05).The overall prevalence of NTM was 7.3 ％ (238/3 270).There were 15 species of NTM, and the most common NTM strain was Mycobacterium intracellulare (52.5％,125/238), followed by Mycobacterium abscessus (22.7％, 54/238) and Mycobacterium avium (10.1％, 24/238), other species were only accounted for 14.7％ (35/238).The ranking of Mycobacterium avium went up rapidly from the fifth in 2014 to the second in 2016 (x2 =18.259, P ＜ 0.01), while proportion of Mycobacterium abscess, dropped from 34.9％ (30/86) in 2014 to 17.5％ (14/80) in 2016 (x2 =7.335, P＜0.01).Among patients from whom the NTM strains were isolated, 56.7％ (135/238) were male and most of them were aged 45 years or above (79.8％, 190/238).Conclusions In the past three years, the trend of NTM isolation rate in Wenzhou is steady.The most prevalent NTM species is Mycobacterium intracellulare, followed by Mycobacterium abscessus and Mycobacterium avium.Mycobacterium avium shows a continuously upward trend, while the separation of Mycobacterium abscessus shows a downward trend.

This study aims to explore possible effect of RNA polymerase I subunit D (POLR1D) on proliferation and angiogenesis ability of colorectal cancer (CRC) cells and mechanism herein. The correlation of POLR1D and Yin Yang 1 (YY1) expressions with prognosis of CRC patients in TCGA database was analyzed. Quantitative realtime polymerase chain reaction (qRT-PCR) and Western blot were applied to detect expression levels of POLR1D and YY1 in CRC cell lines and CRC tissues. SW480 and HT-29 cells were transfected with si-POLR1D or pcDNA3.1-POLR1D to achieve POLR1D suppression or overexpression before cell migration, angiogenesis of human umbilical vein endothelial cells were assessed. Western blot was used to detect expressions of p38 MAPK signal pathway related proteins and interaction of YY1 with POLR1D was confirmed by dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). TCGA data showed that both POLR1D and YY1 expressions were up-regulated in CRC patients. High expression of POLR1D was associated with poor prognosis of CRC patients. The results showed that POLR1D and YY1 were highly expressed in CRC cell lines. Inhibition or overexpression of POLR1D can respectively suppress or enhance proliferation and angiogenesis of CRC cells. YY1 inhibition can suppress CRC progression and deactivate p38 MAPK signal pathway, which can be counteracted by POLR1D overexpression. JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

Objective To investigate the diagnosis and treatment of adult Hirschsprung disease. Methods The clinical data of 10 patients with adult Hirschsprung disease from August 2011 to August 2017 in the Department of General Surgery of the First Affiliated Hospital of Soochow University were retrospectively analyzed. Results Among the 10 patients, 4 cases were male, and 6 cases were female, with age 21 to 65 years old, and body mass index 16.77 to 25.73 kg/m2. The patients were diagnosed with Hirschsprung disease by postoperative pathological examination. All patients had difficult defecation medical history. Barium enema examination in 3 patients before operation showed obvious narrow segment, migrating segment and dilatation segment. Four cases received emergency surgical operation, and 6 cases received selective surgical operation. Complications included intestinal obstruction in 3 cases, incisions infection in 2 cases, and incision rupture in 1 case. Conclusions Adult Hirschsprung disease is difficult to be diagnosed, and the aspect of medical history, barium enema examination, surgical findings and pathological examination has to be combined. The surgery way of AHD is diverse and ought to be individual. Laparoscopic surgery with small trauma and quick recovery has great development space.

In the original publication the Supplementary Material and Fig. 2 are incorrect. The correct version is provided in this correction article. The text HBG2 appearing in the article should be read as HBG1.

Bacterial Proteins ; genetics ; CRISPR-Cas Systems ; genetics ; Endonucleases ; genetics ; Gene Editing ; HEK293 Cells ; Humans ; Transcriptional Activation ; genetics ; p300-CBP Transcription Factors ; genetics

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.