Objective Moderate autophagy helps improve the viability of neurocytes.This study aims to investigate the effect of SP600125 on the autophagy and loss of nerve cells in the hippocampus in rats with subarachnoid hemorrhage (SHA).Methods Forty healthy male SD rats were equally randomized into a sham operation, an DMSO group, an SAH model, and an SP600125 group.The SAH model was established by vascular puncture and the rats of the SP600125 group were injected with 10 μL of SP600125 (3 μg/μL) into the lateral cerebral ventricle at 30 minutes before modeling.Sham group and SAH group were injected with equal volume of normal saline, DMSO group was injected with the same amount of DMSO.The animals were sacrificed at 24 hours after modeling for observation of the changes in the morphology and the number of neurons in the hippocampus by HE staining and qualitative and quantitative determination of the expressions of the p-JNK protein and the autophagy markers beclin-1 and LC3-II by immunohistochemistry and Western blot.Results Compared with the sham operation group, the neurons exhibited a disordered arrangement and the cells were polygonal and decreased in number in the hippocampus of the SAH models, while milder neuronal injury and more cells were observed in the rats of the SP600125 group than in the SAH models.The mean optical density values of Beclin-1, LC3-II and p-JNK in the hippocampus were significantly higher in the SAH models (14.66±4.40, 12.62±3.46, and 12.82±3.68) and DMSO (13.85±3.85、11.59±4.52、13.03±3.53), and the SP600125 group (9.86±3.14, 6.78±2.56, and 5.60±2.42) than in the sham operation group (1.56±0.28, 1.60±0.30, and 1.58±0.32) (P<0.05), but markedly lower in the SP600125 than in the SAH model group (P<0.05).The expressions of Beclin-1, LC3-II and p-JNK were remarkably increased in the SAH models (0.474±0.122, 0.668±0.130, and 0.496±0.124) and DMSO (0.432±0.102、0.628±0.113、0.416±0.094) and the SP600125 group (0.264±0.106, 0.332±0.113, and 0.219±0.104) than in the sham operation group (1.56±0.28, 1.60±0.30, and 1.58±0.32) (P<0.05), but significantly decreased in the SP600125 group as compared with the SAH models (P<0.05).Conclusion SP600125 has a protective effect on the neurocytes in the hippocampus of SAH rats, which may be associated with SP600125 moderately activating neuronal autophagy by inhibiting the activity of the JNK signaling pathway.

Objective To evaluate the schistosomiasis control effect of the measures of replacing cattle with machine for cul?tivation and forbidding depasturage of livestock on marshlands in marshland and lake regions. Methods The retrospective re?view and field survey were implemented in the Jiangling and Gongan counties of Hubei Province where were implemented with the measure of replacing cattle with machine for cultivation,and Yuanjiang and Huarong counties of Hunan Province where were implemented with the measure of forbidding the depasturage of livestock on marshlands. The schistosome infection status of hu?man,cattle,and Oncomelania hupensis snails,and schistosome?infested field excreta were surveyed from 2007 to 2013. The ef?fects of the interventions were compared before and after their implementations. Results The 6 villages of Hubei Province were implemented with the measure of replacing cattle with machine for cultivation,and 7 villages of Hunan Province were imple? mented with the measure of forbidding the depasturage of livestock on marshlands. From 2007 to 2013,the schistosome infection rates of residents declined from 3.95%to 0.70%(χ2 =128.376,P<0.05),with the descend range of 82.53%. The descend ranges of the measures of replacing cattle with machine for cultivation and forbidding the depasturage of livestock on marshlands were 83.081%and 81.62%respectively,and there was no significant difference between the two measures(χ2 =0.132,P>0.05). The infection rate of cattle decreased from 3.66%in 2007 to 0.65%in 2013,and the descend range was 82.24%(χ2=13.692,P<0.05). The field excreta was surveyed in the snail breeding place in 2013. The investigated area was 157.435 hm2, and 625 samples of field feces of cattle were collected with the density of field excreta of 3.97/hm2,and the positive rate was 1.12%(7/625). The schistosome infection rate of snails and the density of infected snails decreased successively from 2007, and no infected snails were detected from 2011 to 2013. Conclusions The schistosomiasis endemic situation are decreased sig?nificantly after the interventions of replacing cattle with machine for cultivation and forbidding the depasturage of livestock on marshlands. Therefore,schistosomiasis control effect of these measures is notable in the marshland and lake regions.

Objective:To analysis the construction of the world's top PhaseⅠclinical trial registration agencies, compare their size, composition, operation and funding, to provide further reference for the construction of clinical trial agency in China.Methods:Search for PhaseⅠclinical trial research agencies by region on clinicaltrials.gov. Collecting information about the agency’s management, staffing, implementation in Asia, America and Europe. Descriptive analysis was carried out to explore the type, proportion and operation among different regions, the organizational structure, operational management and effectiveness of each agency from different regions were compared.Results:The United States, Europe and East Asia are dense areas of PhaseⅠclinical research around the world. The types of agencies in the United States, Britain, France, Germany, South Korea, Japan, and Israel are mainly enterprises. Among other types of agencies, the organizational models are diversified. The agencies have different spatial distances from medical institutions, but possess relatively consistent scale and institutional operation. All the agencies have a stable source of funding.Conclusions:In order to strengthen the construction of clinical trial agencies in China, we should speed up the establishment of a close connection mechanism to promote deep cooperation in clinical trials. Control the construction scale and maintain stable input of the agency. Meanwhile, establish and strengthen international exchanges and cooperation.

To investigate the clinical manifestations and risk factors in patients with systemic lupus erythematosus (SLE) and cancers. From October 2010 to February 2019, 5 566 SLE patients hospitalized in the First Affiliated Hospital of Zhengzhou University were enrolled. A total of 69 cancer patients were identified, and the clinical characteristics and previous treatment were analyzed. Cervical carcinoma (21.74%, 15/69) and thyroid cancer (21.74%, 15/69) were the most common types of cancer. Most cancers were diagnosed in SLE patients with an age 40~50 years. The disease duration of SLE was from 60~120 months. SLE patients without cancers were usually diagnosed between 20~30 years with duration of symptoms less than 12 months. As to the previous treatment of SLE, the uses of glucocorticoid, cyclophosphamide, methotrexate and azathioprine were comparable between patients with cancers and without (P>0.05). However, the use of hydroxychloroquine was more frequent in SLE patients than in patients with cancers (P<0.01). Correlation analysis revealed significant correlation between disease course of SLE (OR=4.25, 95%CI 1.79~10.01,P<0.001), hydroxychloroquine (OR=0.26, 95%CI 0.12~0.59,P<0.001) and cancer risk. Long disease course may be a risk factor for SLE patients to develop cancer, whereas hydroxychloroquine could be a protective factor.

Background N6-methyladenosine (m6A) RNA methylation may play an important role in the process of malignant transformation of cells induced by environmental carcinogens. However, the specific roles and mechanisms need to be further explored. Objective To explore the role and mechanism of m6A binding protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the malignant transformation of human gastric mucosal epithelial cells GES-1 induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods Based on the GES-1 malignant transformation cells MC-30, a stable knockdown IGF2BP3 MC-30 cell line (MC30-shIGF2BP3, abbreviated as MC30-shI3) was constructed by lentiviral transfection technology, and a negative control group (MC30-NC) was also prepared. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the mRNA expression and protein levels of IGF2BP3. RNA binding protein immunoprecipitation (RIP-qPCR) was used to examine the combination between IGF2BP3 protein and MYC mRNA in malignant cells MC-30. Furthermore, the stability of MYC mRNA was detected by actinomycin D assay. CCK-8 and Transwell respectively were employed to detect cell proliferation, migration, and invasion. Western blotting was applied to detect the expression of EMT markers (N-cadherin, Vimentin, α-SMA, and Snail). The role of the downstream target gene MYC was further elucidated by a rescue assay in MC30-shI3 cells transfected with a plasmid overexpressing MYC to observe changes in cellular phenotypes (proliferation, migration, invasion) and expression of key EMT proteins. Results Compared with the control group, the expression of IGF2BP3 mRNA was up-regulated after 5, 10, 20, and 40 μmol·L⁻¹ MNNG infection of GES-1 cells (P<0.05). After 20 μmol·L⁻¹ MNNG infection, the expression level of IGF2BP3 mRNA increased with prolongation of exposure time (P<0.05). Compared with the control group, the mRNA and protein expression levels of IGF2BP3 were up-regulated in the 10th, 20th, and 30th generations of 5 μmol·L⁻¹ MNNG malignant transformation (P<0.05). The results of qRT-PCR and Western blotting showed that, compared with the MC30-NC group, the IGF2BP3 and MYC mRNA expression and protein expression decreased in the MC30-shI3 group (P<0.01). The CCK8 and transwell assay results showed that, compared with the MC30-NC group, the cell proliferation, migration, and invasion abilities significantly reduced in the MC30-shI3 group (P<0.01). The results of the Western blotting showed that, compared with the MC30-NC group, the protein levels of EMT markers N-cadherin, Vimentin, α-SMA, and Snail decreased in the MC30-shI3 group (P<0.01). The results of RIP-qPCR showed that, compared with the IgG group, the mRNA level was higher for the enriched MYC in the IGF2BP3 group (P<0.01); the results of the actinomycin D assay showed that, compared with the MC30-NC group, the stability of MYC mRNA significantly reduced in the MC30-shI3 group (P<0.01). While the rescue experiment showed that, compared with the IGF2BP3 knock-down+vector group, the MYC protein level significantly increased in the IGF2BP3 knock-down + MYC over-expression group (P<0.01), the proliferation, migration, and invasion abilities significantly enhanced (P<0.01), and the EMT key proteins (N-cadherin, Vimentin, α-SMA, Snail) increased in the MC30-shI3+MYC group (P<0.01). Conclusion Exposure to MNNG could result in up-regulation of IGF2BP3 expression in GES-1 cells. IGF2BP3 may enhance the proliferation, migration, and invasion of malignantly transformed human gastric epithelial cells by binding to MYC mRNA and increasing its stability and expression level and thus promoting the EMT process, which in turn affects the progression of malignant transformation.

Background Aedes albopictus is the dominant mosquito species in residential areas in Shanghai. There are many types of small containers with accumulated water in residential areas, providing a large number of breeding environments for Aedes alpopicuts and leading to an increasing transmission risk of mosquito-borne diseases. Objective To use random forest to predict breeding of Aedes mosquitoes in small aquatic container habitat in two concentrated reconstruction communities of rural areas in Shanghai, and to understand associated influence of environmental factors on the breeding of Aedes mosquitoes in the process of urbanization.Methods Small-scale habitat surveys of Aedes mosquitoes were carried out in two suburb concentrated reconstruction communities (Community A and B) in Shanghai, and the environment where the habitat was located was recorded and analyzed in both communities. The habitat where eggs, larvae, or pupae were found was recorded as positive. Spatial weight matrix was applied on a household basis, and global Moran's I index was used to carry out spatial autocorrelation analysis on the small-scale habitat and positive habitat in the environment of the two communities. When Moran's I is greater than 0, it means that the data present a positive spatial correlation; when Moran's I is less than 0, it means that the data are spatially negatively correlated; when Moran's I is 0, the spatial distribution is random. Combining the results of P and Z values, we explored the spatial distribution characteristics of small-scale habitat and positive habitat in the community environment. Random forest algorithm in machine learning was used to classify and sort environmental-related factors, and predict the breeding of Aedes mosquitoes in small aquatic habitat; receiver operating characteristic (ROC) curve was used to carry out model fitting evaluation. Results The environmental factors including building location (χ²=23.35, P<0.001), open space (χ²=8.83, P=0.003), and having trees (χ²=11.02, P=0.001) had a significant impact on the positive rate of small-scale habitat. The results of spatial characteristics analysis showed that the global Moran's I index of small-scale habitat was −0.092 (Z=−1.09, P=0.274) in Community A and 0.034 (Z=0.52, P=0.602) in Community B, and the global Moran's I index of positive habitat was −0.092 (Z=−1.14, P=0.255) in Community A and 0.070 (Z=0.95, P=0.342) in Community B. Since the P values of Community A and B were greater than 0.1 and the Z values were between −1.65 and 1.65, for both small-scale habitat and positive habitat the spatial characteristics were randomly distributed and no significant spatial aggregation was found. In the fitted random forest algorithm classification prediction model with the top 10 characteristic factors of importance, the area under curve (AUC) value was 0.95, and the prediction fitting effect was satisfactory. The results of classification and sorting indicated that counts of household small-scale habitat and positive habitat were the most important factors for breeding. Conclusion The random forest model constructed by environmental factor indicators can be used to predict the breeding situation of Aedes mosquitoes in small-scale aquatic habitat, and provide a basis for scientific prevention and control of mosquito breeding for the target area.