More than 80% of the world’s populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.

Objective:To investigate the effects of bisphenol A(BPA)on the proliferation activity and stemness characteristics of endometrial mesenchymal stem/stromal cells(eMSCs),and to elucidate the improvement effect of human umbilical cord mesenchymal stem cell-derived supernatant(hUCMSC-Sup)on the cell injury.Methods:The eMSCs were cultured in vitro and treated with different concentrations of BPA(0,200,250,300,350,and 400 μmol·L-1).The eMSCs were divided into control group(only cultured with culture solution),BPA group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA),BPA+hUCMSC-Sup group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 50%volumetric ratio of hUCMSC-Sup),and BPA+CHIR-99021 group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 10 μmol·L-1 CHIR-99021).The survival rates of eMSCs in various groups were detected by methyl thiazolyl tetrazolium(MTT)assay.The numbers and diameters of the spheroids in various groups were detected by spheroids formation assay,the proliferation activities of the cells in eMSCs stem cell spheroids in various groups were detected by CCK-8 assay;the percentage of CD73+cells in eMSCs in various groups were detected by flow cytometry;the expression levels of sex determining region Y-box 2(Sox2),octamer-binding transcription factor 4(Oct4),and Nanog mRNA in the eMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method,the expression levels of β-catenin protein in the eMSCs in various groups were detected by Western blotting method.Results:The MTT results showed that after treated with BPA for 24 and 48 h,compared with 0 μmol·L-1 BPA group,the survival rates of eMSCs in 200,250,300,350,and 400 μmol·L-1 BPA groups were significantly decreased(P<0.01).At 24 and 48 h after treatment,compared with control group,the survival rate of the eMSCs in BPA group was significantly decreased(P<0.01);at 48 h after treatment,compared with BPA group,the survival rate of the eMSCs in BPA+hUCMSC-Sup group was significantly inereased(P<0.05).The spheroids formation assay results showed that compared with culture 3 d group,the numbers and diameters of stem cell spheroids of the eMSCs in culture 4 d group and culture 5 d group were significantly increased(P<0.05 or P<0.01);compared with control group,after 48 h of culture,the number and diameter of the cells in eMSCs stem cell spheroids in BPA group were significantly decreased(P<0.05 or P<0.01).The CCK-8 results showed that after 24 and 48 h of treatment,compared with control group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA group was significantly decreased(P<0.01);compared with BPA group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The flow cytometry results showed that compared with control group,the percentage of the CD73+cells in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the percentage of the CD73+cells in eMSCs in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA group were significantly decreased(P<0.01);compared with BPA group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression level of β-catenin protein in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the expression levels of β-catenin protein in the eMSCs in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were signifrcantly inereased(P<0.01).Conclusion:BPA can inhibit the stemness characteristics of the eMSCs,and injury the self-renewal and repair of endometrium;its mechanism may be related to down-regulating the activity of Wnt/β-catenin signal pathway in the cells.hUCMSC-Sup can promote the proliferation of injured eMSCs,and has improvement effect on the stemness injury induced by BPA.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

Objective:To evaluate the relationship between intestinal mucosal mast cells and intestinal flora during intestinal ischemia-reperfusion(I/R) in mice.Methods:Forty-eight healthy male C57BL/6 mice, aged 9-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation plus mast cell membrane stabilizer cromolyn sodium (CS) group (group Sham+ CS), I/R group and I/R+ CS group.The intestinal I/R injury was induced by clamping the superior mesenteric artery for 45 min followed by 4 h of reperfusion in I/R and I/R+ CS groups.The superior mesenteric artery was only exposed but not occluded in Sham and Sham+ CS groups.CS 50 mg/kg was intraperitoneally injected once a day for two weeks before surgery in Sham+ CS and I/R+ CS groups.The equal volume of normal saline was intraperitoneally injected once a day for two weeks before surgery in Sham and I/R groups.Mice were then sacrificed and intestinal tissues were harvested for examination of the pathological changes of intestinal mucosa with a light microscope after HE staining, and the damage to intestinal tissues was assessed and scored according to Chiu.The expression of mast cell tryptase was detected using the immunohistochemical SP staining method, and the mast cells were counted.The intestinal contents were collected, the total amount of bacteria in intestinal flora was detected by 1% agarose gel electrophoresis, and the diversity (Chao1 index and Shannon index) and relative abundance of intestinal microbial bacteria were detected by 16S rDNA sequencing method. Results:Compared with Sham group, the Chiu′s score and mast cell count were significantly increased, the expression of mast cell tryptase was up-regulated, the total amount of intestinal flora bacteria was increased, Chao1 index and Shannon index were decreased, the relative abundance of Bacteroidetes, Proteobacteria, Bacteroides and Enterobacteriaceae were increased, and the relative abundance of Firmicutes, Lactobacillus and Bifidobacteria was reduced in I/R group ( P<0.05 or 0.01), and no significant change was found in the parameters mentioned above in Sham+ CS group ( P>0.05). Compared with I/R group, the Chiu′s score and mast cell count were significantly decreased, the expression of mast cell tryptase was down-regulated, the total amount of intestinal flora bacteria was decreased, Chao1 index and Shannon index were increased, the relative abundance of Bacteroidetes, Proteobacteria, Bacteroides and Enterobacteriaceae were reduced, and the relative abundance of Firmicutes, Lactobacillus and Bifidobacteria was increased in I/R+ CS group ( P<0.05 or 0.01). Conclusion:The activation of intestinal mucosal mast cell can lead to imbalance of intestinal flora, decrease the number of probiotics and increase the number of potential pathogenic bacteria, and thus be involved in the pathophysiological mechanism of intestinal I/R injury in mice.

Objective To explore the gray and white matter microstructures in the brain of patients with different degrees of chronic mountain sickness(CMS).Methods 30 cases of CMS (10 cases in each group divided into mild,moderate and severe groups according to the severity)were collected as experimental group,and 10 normal adults in high altitude area were collected as the normal control group.All cases underwent MRI conventional head sequences,diffusion weighted imaging (DWI)and diffusion kurtosis imaging (DKI)sequences.The values of mean kurtosis(MK),radial kurtosis(RK),kurtosis anisotropy(KA)and apparent diffusion coefficient(ADC) graphs were reconstructed by post-processing software respectively.Selected the region of interest(ROI)symmetrically and fixedly, then measured and analyzed the parameter values of ROI in the same area.Results Compared the CMS groups with normal control group,the diffusion parameters and ADC values in certain parts of deep gray matter nucleus and white matter fibers were statistically significant,and the difference was significant with the progression of the disease.Conclusion DKI combined with DWI has certain value in evaluating the gray and white matter microstructure of human brain,there are some difference in the brain microstructure between CMS patients and high altitude normal subjects,additionally,the difference in different degrees of CMS is diverse.

Objective To explore the protective effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) on AD-like neurodegenerative changes and its mechanism. Methods The human neuroblastoma cell line SH-SY5Y on the logarithmic phase was divided into six groups:control group (CON group, treated with PBS contained 1‰DMSO for 12 h), wortmannin intervention group (W group, treated with 0.03 μmol/L wortmannin for 12 h), DPP-4I intervention group (DPP-4I group, treated with 10μmol/L DPP-4I for 12 h), both DPP-4I and wortmannin intervention group (DPP-4I+W group, pre-treated with 10 μmol/L DPP-4I for 2 h, then 0.03 μmol/L wortmannin for 12 h), DPP-4I, wortmannin and Ex9-39 intervention group (DPP-4I+W+Ex9-39 group, pre-treated with 10μmol/L Ex9-39 for 2 h, then 10μmol/L DPP-4I for 2 h followed by 0.03μmol/L wortmannin for 12 h), and Ex9-39 intervention group (Ex9-39 group, treated with 10μmol/L Ex9-39 for 12 h). MTT assay was used to detect the cell vitality. Western blot assay was used to detect the level of total tau protein (tau-5) and phosphorylated tau at different sites (pSpS199/202, pT231 and pS396), the level of phosphorylated neurofilaments (NF-H, NF-M) and phosphorylation of critical enzyme in PI3K/Akt/GSK-3β signaling pathway. Results (1) The cell vitality decreased, the levels of pSpS199/202, pT231, pS396 and NF-H/M increased significantly in W group than those in CON group. However, comparing with CON group, the above mentioned parameters reversed in DPP-4I group. Comparing with W group, the cell vitality increased and phosphorylated levels of above mentioned indices were decreased in DPP-4I+W group. (2) The cell vitality showed a decline trend while the levels of phosphorylation tau at three different sites and NF-H/M were higher in Ex9-39 group than those in CON group. Comparing with DPP-4I+W group, the results of the phosphorylated levels showed the same changes in DPP-4I+W+Ex9-39 group. (3) Comparing with CON group, the expression levels of phosphorylated PI3K, Akt and GSK3β increased significantly in DPP-4I group, while those decreased in W group. Additionally, the expression levels of phosphorylated PI3K, Akt and GSK3β were significantly increased in DPP-4I+W group than those in W group. Conclusion DPP-4I can enhance the level of GLP-1 and activate PI3K/Akt/GSK-3βinsulin signaling pathway to improve the hyperphosphorylated tau and NFs induced by wortmannin, and to protect AD-like neurodegeneration.

Objective To explore the differences between patients withchronic mountain sickness (CMS) and healthy people in the microstructure of brain gray and white matter by using diffusion kurtosis imaging (DKI). Methods 21 CMS patients were recruited to a study group and 20 healthy volunteers were assigned to a control group. Both groups received conventional MRI and DKI sequence scans. The mean kurtosis (MK) values ,radial kurtosis (RK) values and kurtosis anisotropy (KA) values in each region of interest (ROI) in the cerebral gray and white matter were measured and the same part of the left and right side ROI parameters was counted. The data satisfied the normal distribution and the paired samples t?test was used;the ROI parameters between the two groups in the same parts of the same side followed the normal distribution and the two independent samples t?test was used. Results The KA values in both sides of the anterior limb of internal capsule ,the MK values and RK values in bilateral caudate nucleus head and thalamus had side difference in CMS group. In both sides of the anterior limb of the internal capsule′s MK values,KA values and thalamus′s MK values,RK values existed side difference in the control group. The KA values of the right anterior limb in internal capsule were lower than those in the left in both groups;the right thalamus′s MK values and RK values were higher than the other side. The RK value in genu of corpus callosum differed significantly ,and it was lower the CMS group than in the control group. The difference of the KA values in corpus callosum ,the MK value in the left anterior limb of internal capsule ,the RK values in the left posterior limb of internal capsule ,the MK values in the right caudate nucleus head ,the MK values in bilateral lenticular nucleus and the MK values and KA values in the right thalamus were significant ,and they were higher inthe CMS group than in the control group. Conclusions The left and right cerebral hemispheric micro?structure is not exactly symmetrical between patients with CMS and healthy people living in high altitude areas , there are differences in some brain areas. The sensitivity and reactivity of brain tissue to high altitude hypoxia are different in patients with CMS ,there are various degrees of difference between the CMS and the normal in the corpus callosum,basal ganglia region and thalamus.

Objective:To explore the proportions of Th17 cells in the peripheral blood and levels of IL-17,IL-23 in the serum of patients with Graves′disease ( GD ) and their clinical significance.Methods: We studied 29 patients with GD ( GD group ) , and reevaluated the GD group after therapy ( euthyroid GD group ).29 gender-and age-matched volunteers were selected as the normal control ( NC group).The proportions of Th17 cells were investigated by flow cytometry.The levels of IL-23,IL-17 in the serums were measured by ELISA.The levels of FT3,FT4,TSH were determined by ECLIA and the levels of TrAb were tested by RRA.Results:There were no significant difference among 3 study groups in sex and age match ( F=0.0075 , P>0.05;χ2=0.4213 , P>0.05 ).The proportions of Th17 cells and the levels of IL-17 , IL-23 were increased in the GD and euthyroid GD patients compared with the control group (respectively,P<0.05).The proportions of Th17 cells and the concentrations of IL-23 in euthyroid GD group were significantly lower than those of GD group ( respectively , P<0.05 ) , but there were no significance in the concentrations of IL-17 between euthyroid GD group and GD group(P>0.05).Correlation analysis revealed that the proportions of Th17 cells ,and the levels of IL-17,IL-23 were positively correlated with the levels of FT3,FT4,TrAb(r=0.588 2,0.337 2,0.371 0;0.549 6,0.287 5,0.342 7;0.361 0,0.420 8, 0.330 8;P<0.05 ,for all parameters ) ,and were negatively correlated with the levels of TSH ( r=-0.319 7 ,-0.472 8 ,-0.428 2;P<0.05,for all parameters).Conclusion:Th17 cells and their related cytokines IL-17,IL-23 are highly expressed in the serum of patients with GD.Th17 cells and their relative cytokines have certain relevance with 4 thyroid function parameters of the patients with GD , which can be used as biological markers for GD.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Objective To investigate the effects of type 2 diabetes on learning and memory of APP/PS1/Tau triple transgenic (3 × Tg) mice of Alzheimer’s disease, and the protective mechanism of liraglutide (LIR) thereof. Methods One month old C57BL/6 mice were set to be control group (WT). One month old 3×Tg mice were divided into control group (Tg), liraglutide group (Tg+LIR), type 2 diabetes group (Tg+T2DM) and liraglutide treatment group (Tg+T2DM+LIR). The model of T2DM was established by feeding the high fat and sugar fodder, and then injecting streptozotocin (STZ) in mice, making sure the fasting blood glucose was more than 7 mmol/L. Then the subcutaneous injection of LIR was administered for 2 months. The values of body weight and fasting blood glucose were detected at age of 5-month. Morris water maze was applied to evaluate the spatial learning and memory ability. Western blotting assay was used to measure the levels of phosphorylated Tau, neurofilament (NFs) and insulin receptor substrates. ELISA was used to detect the human Aβ42 to evaluate the effect of LIR on-amyloid. Results LIR can reduce body weight and blood glucose, can alleviate spatial learning and memory damaging caused by T2DM, and also can improve phosphorylated Tau levels, NFs and insulin receptor substrates caused by T2DM, and finally can reduce the deposition ofβ-amyloid of 3 × Tg mice. Conclusion T2DM can aggravate symptoms of AD in 3×Tg mice, and LIR has a protective effect on it.