HnRNPAB promotes pancreatic ductal adenocarcinoma extravasation and liver metastasis by stablizing MYC mRNA.

Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) is considered a cancer-promoting heterogeneous nuclear ribonucleoprotein in many cancers, but its function in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. HnRNPAB was highly expressed in PDAC tissues compared to normal pancreatic tissues, and high expression of hnRNPAB was associated with poor overall survival and recurrence-free survival in PDAC patients. HnRNPAB promotes migration and invasion of PDAC cells in vitro. In xenograft tumor mouse models, hnRNPAB deprivation significantly attenuated liver metastasis. HnRNPAB mRNA and protein levels are positively associated with MYC in PDAC cells. Mechanistically, hnRNPAB bound to MYC mRNA and prolonged its half-life of MYC mRNA. HnRNPAB induced PDAC cells to secret CXCL8 via MYC, which promoted neutrophils recruitment and facilitated tumor cells entrancing into the hepatic parenchyma. These findings point to a novel regulatory mechanism via which hnRNPAB promotes PDAC metastasis. Implications: Hnrnpab participates in the post-transcriptional regulation of the oncogene MYC by binding and stabilizing MYC mRNA, thereby promoting liver metastasis in PDAC.

Chemoenzymatic Asymmetric Synthesis of Chiral Triazole Fungicide (R)-Tebuconazole in High Optical Purity Mediated by an Epoxide Hydrolase from Rhodotorula paludigensis.

Tebuconazole is a chiral triazole fungicide used globally in agriculture as a racemic mixture, but its enantiomers exhibit significant enantioselective dissimilarities in bioactivity and environmental behaviors. The steric hindrance caused by the tert-butyl group makes it a great challenge to synthesize tebuconazole enantiomers. Here, we designed a simple chemoenzymatic approach for the asymmetric synthesis of (R)-tebuconazole, which includes the biocatalytic resolution of racemic epoxy-precursor (2-tert-butyl-2-[2-(4-chlorophenyl)ethyl] oxirane, rac-1a) by Escherichia coli/Rpeh whole cells expressed epoxide hydrolase from Rhodotorula paludigensis (RpEH), followed by a one-step chemocatalytic synthesis of (R)-tebuconazole. It was observed that (S)-1a was preferentially hydrolyzed by E. coli/Rpeh, whereas (R)-1a was retained with a specific activity of 103.8 U/g wet cells and a moderate enantiomeric ratio (E value) of 13.4, which was remarkably improved to 43.8 after optimizing the reaction conditions. Additionally, a gram-scale resolution of 200 mM rac-1a was performed using 150 mg/mL E. coli/Rpeh wet cells, resulting in the retention of (R)-1a in a 97.0% ees, a 42.5% yields, and a 40.5 g/L/d space-time yield. Subsequently, the synthesis of highly optical purity (R)-tebuconazole (>99% ee) was easily achieved through the chemocatalytic ring-opening of the epoxy-precursor (R)-1a with 1,2,4-triazole. To elucidate insight into the enantioselectivity, molecular docking simulations revealed that the unique L-shaped substrate-binding pocket of RpEH plays a crucial role in the enantioselective recognition of bulky 2,2-disubstituted oxirane 1a.

Correlation of laminin subunit alpha 3 expression in pancreatic ductal adenocarcinoma with tumor liver metastasis and survival.

BACKGROUND: The high mortality rate of pancreatic ductal adenocarcinoma (PDAC) is primarily attributed to metastasis. Laminin subunit alpha 3 (LAMA3) is known to modulate tumor progression. However, the influence of LAMA3 on liver metastasis in PDAC remains unclear. This study aimed to elucidate whether LAMA3 expression is increased in PDAC with liver metastasis. PATIENTS AND METHODS: We extracted information related to LAMA3 expression levels and associated clinicopathological parameters from The Cancer Genome Atlas (TCGA) and four Gene Expression Omnibus (GEO) datasets. Clinicopathological analysis was performed; the Kaplan-Meier Plotter was used to evaluate LAMA3's prognostic effect in PDAC. We retrospectively collected clinicopathological data and tissue specimens from 117 surgically treated patients with PDAC at the Affiliated Hospital of Qingdao University. We assessed LAMA3 expression and investigated its correlation with the clinicopathological traits, clinical outcomes, and hepatic metastasis. RESULTS: Amplified expression of LAMA3 was observed in PDAC tissue compared with normal tissue in the TCGA and GEO databases. High LAMA3 expression was associated with poor overall survival (OS) and relapse-free survival (RFS) in patients with PDAC. LAMA3 expression was significantly enhanced in PDAC tissues than in adjacent tissues. Tumor tissues from patients with PDAC exhibiting liver metastasis showed higher LAMA3 expression than those without liver metastasis. High LAMA3 expression correlated with large tumor size and TNM stage. LAMA3 expression and liver metastasis were independent predictive factors for OS; the former was independently associated with liver metastasis. CONCLUSIONS: LAMA3 expression is elevated in patients with PDAC with liver metastasis and is a predictor of prognosis.

Shikonin Inhibits APC-mutant Colon Cancer via Wnt/β-catenin Signaling / 肿瘤防治研究

Objective To identify small molecule inhibitors of APC-mutant colon cancer and provide lead compounds for targeted therapy of colon cancer. Methods APC-mutant colon cancer cell lines that stably express 7*Tcf-GFP/SV40-Cherry (7TGC) dual fluorescence reporter system was constructed for small-molecule inhibitor screening. Cell viability, colony formation, EdU incorporation, and xenograft tumor assay were used to evaluate the inhibitory effect of these inhibitors on APC-mutant colon cancer in vitro and in vivo. Western blot and co-immunoprecipitation assays were used to explore the molecular mechanism. Results Four small molecules that inhibited Wnt activity in APC-mutant colon cancer cells were discovered. Shikonin exhibited significant inhibition of cell viability and proliferation while inducing apoptosis of APC-mutant colon cancer cells. Xenograft tumor assay demonstrated that shikonin significantly reduced tumor growth in vivo. Furthermore, Western blot and co-immunoprecipitation assays revealed that shikonin markedly decreased β-catenin levels. Conclusion Shikonin effectively inhibits Wnt activity and suppresses tumor growth in APC-mutant colon cancer.

Improvement effect of velvet antler polypeptide in osteoporosis model rats and its effect on SIRT1/FOXO1 signaling pathway / 吉林大学学报(医学版)

Objective:To discuss the protective effect of velvet antler peptide(VAP)in the osteoporosis(OP)model rats,and to clarify the possible mechanism.Methods:Sixty 12-week-old SD rats were randomly divided into control group,model group,positive drug group(treated with 1 mg·kg-1·d-1 of alendronate sodium by gavage),low dose of VAP group(treated with 100 mg·kg-1·d-1 VAP),medium dose of VAP group(treated with 200 mg·kg-1·d-1 VAP),and high dose of VAP group(treated with 300 mg·kg-1·d-1 VAP),and there were ten rats in each group.Except for control group,the rats in the other groups were injected with dexamethasone(2 mg·kg-1)to replicate the OP rat model,while the rats in control group were injected with the equivalent volume of saline twice a week for 11 consecutive weeks.Dual-energy X-ray absorptiometry was used to detect the bone mineral density(BMD)of femur tissue of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of serum calcium(Ca2+),phosphate(P),osteoprotegerin(OPG),alkaline phosphatase(ALP),and osteocalcin(OCN)in serum of the rats in various groups;biochemical method was used to detect the malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in serum of the rats in various groups;HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups;Western blotting method was used to detect the expression levels of silent information regulator 1(SIRT1),catalase(CAT),Runt-related transcription factor 2(RUNX2),and forkhead box protein O1(FOXO1)proteins in bone tissue of the rats in various groups.Results:Compared with control group,the BMD of femoral tissue of the rats in model group was decreased(P<0.05);compared with model group,the BMD of femur tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were increased(P<0.05 or P<0.01).Compared with control group,the levels of Ca2+,P,OPG,and SOD activities in serum of the rats in model group were decreased(P<0.05),and the levels of ALP,OCN,and MDA were increased(P<0.05);compared with model group,the level of OPG in serum of the rats in low dose of VAP group was significantly increased(P<0.05),the levels of Ca2+,P,OPG,and activities of SOD in serum of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01),and the levels of ALP,OCN,and MDA in serum of the rats in positive drug group and different doses of VAP groups were decreased(P<0.05 or P<0.01).The HE staining results showed that compared with control group,the rats in model group had fewer bone cells and disordered arrangements in the bone tissue,thinner bone trabeculae with large fractures,and an expanded marrow cavity;compared with model group,the rats in positive drug group,medium dose of VAP group,and high dose of VAP group had thicker bone trabeculae arranged more tightly.The Western blotting results showed that compared with control group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in model group were decreased(P<0.05);compared with model group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01).Conclusion:VAP has the protective effect against OP in the rats,and its mechanism may be related to mediating the antioxidant stress action through the SIRT1/FOXO1 signaling pathway.

Retraction: Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasion via regulation of the NF-κB signaling pathway in osteosarcoma cells.

[This retracts the article DOI: 10.1039/C8RA08973F.].

Development and validation of a ferroptosis-related lncRNAs signature to predict prognosis and microenvironment for melanoma.

Ferroptosis plays an important role in cancer. However, studies about ferroptosis-related lncRNAs (FRLs) in skin cutaneous melanoma (SKCM) are scarce. Moreover, the relationship between prognostic FRLs and tumor microenvironment (TME) in melanoma remains unclear. This study investigates the potential prognostic value of FRLs and their association with TME in SKCM. The RNA-sequencing data of SKCM were downloaded from The Cancer Genome Atlas (TCGA) database. Melanoma patients were randomly divided into training and testing groups in a 1:1 ratio. A signature composed of 19 FRLs was developed by the least absolute shrinkage and selection operator (LASSO) regression analysis to divide patients into a low-risk group with a better prognosis and a high-risk group with a poor prognosis. Multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor. The Area Under Curve (AUC) value of the risk score reached 0.768 in the training group and 0.770 in the testing group. Subsequent analysis proved that immune-related signaling pathways were significantly enriched in the low-risk group. The tumor immune cell infiltration analysis demonstrated that melanoma in the high-risk group tended to be immunologically "cold". We identified a novel FRLs signature which could accurately predict the prognosis of patients with melanoma.

Different classes of antibiotics exhibit disparate negative impacts on the therapeutic efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

It has been reported that antibiotics (ATBs) have adverse effect on the efficacy of treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Since different classes of ATBs have different antibacterial spectrum, we aimed to study whether all ATBs had similar or different negative effects on the clinical outcomes of ICIs in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who received ICIs were included in this retrospective study and grouped by the class of ATBs they had used around the ICIs treatment time. The overall survival (OS) and the progression free survival (PFS) of patients among these groups were compared using Kaplan-Meier method and Cox proportional hazards model. A total of 148 eligible patients were enrolled, and 80 patients used ATBs. The results indicated that quinolones had no significant negative consequence on the clinical outcomes, while ß-lactams significantly shortened the OS and PFS of patients. Furthermore, patients exposed to the combination of ß-lactams and quinolones suffered the worst OS and PFS. Moreover, the subgroup analysis of ß-lactams revealed that only penicillins, but not carbapenems and cephalosporins, markedly reduced both OS and PFS. In addition to the class of ATBs used, the time frame of ATBs used also affected the clinical outcomes of ICIs therapy. Patients receiving ATBs within 60 days prior to and 30 days after the initiation of ICI treatment had significantly shorter OS and PFS compared with those who did not use ATBs. This study demonstrated that different classes of ATBs had disparate negative impacts on the clinical outcomes, and the use of ß-lactams, especially penicillins, should be avoided in advanced NSCLC patients who are receiving or scheduled to receive ICIs within 60 days.

Restraint of FAM60A has a cancer-inhibiting role in pancreatic carcinoma via the effects on the Akt/GSK-3ß/ß-catenin signaling pathway.

Family with sequence similarity 60A (FAM60A) has been reported as a new cancer-related protein that affects the malignant progression of some cancers. However, whether FAM60A plays a part in pancreatic carcinoma is undetermined. This work was designed to examine the impact of FAM60A in pancreatic carcinoma. Abundant expression of FAM60A was observed in the primary tumor tissue of pancreatic carcinoma. Moreover, a high FAM60A level was related to a poor overall survival in pancreatic carcinoma patients. Malignant behaviors of pancreatic carcinoma cells, such as proliferation and invasiveness, were markedly affected by FAM60A depletion. In addition, FAM60A depletion enhanced the drug sensitivity of pancreatic carcinoma cells to gemcitabine. Further study revealed that FAM60A depletion impaired the activities of Akt and ß-catenin. Inhibiting the activity of Akt abolished FAM60A-mediated ß-catenin activation. Re-expression of ß-catenin partially diminished the FAM60A-depletion-mediated cancer suppressive effect in pancreatic carcinoma cells. In vivo experiments demonstrated that FAM60A depletion prohibited the xenograft formation of pancreatic carcinoma cells, with concurrent reductions of Akt and ß-catenin activities. Collectively, our findings indicate that FAM60A exerts a cancer-promoting role in pancreatic carcinoma through affection of the Akt/ß-catenin pathway. This work indicates that FAM60A acts as a tumor promoter in pancreatic carcinoma and can be utilized as a potential target for anti-pancreatic carcinoma therapy development.

Protective effect of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress / 中国中药杂志

To explore the protective effect and mechanism of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress. Tunicamycin was used to establish the damage model in L02 cells. Methyl thiazolyl tetrazolium(MTT) colorimetric assay was used to investigate the survival rate of ethyl acetate extract from B. bipinnata in L02 cells injury induced by endoplasmic reticulum stress; the protein expressions of endoplasmic reticulum stress-related molecule glucose regulated protein 78(GRP78), PKR-like ER kinase(PERK), eukaryotic initiation factor-2(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(CHOP), B-cell CLL/lymphoma 2(Bcl-2), Bal-2 associated X apoptosis regulator(Bax) were examined by Wes-tern blot. The expressions of the above proteins were also detected after endoplasmic reticulum stress inhibitor(4-phenyl butyric acid) and CHOP shRNA-mediated knockdowns were added. The expressions of GRP78, PERK, CHOP in L02 cells were observed by immunofluorescence method. The results showed that ethyl acetate extract from B. bipinnata could significantly increase the survival rate of L02 cell injury caused by endoplasmic reticulum stress in a dose and time-dependent manner(P<0.05 or P<0.01). The expression levels of GRP78, PERK, eIF2α, ATF4, CHOP and Bax in the drug treatment groups were significantly down-regulated(P<0.05 or P<0.01), while Bcl-2 was significantly up-regulated(P<0.01). After endoplasmic reticulum stress inhibitor and CHOP shRNA-mediated knockdowns were added, the expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax in the drug treatment groups were significantly down-regulated(P<0.01), whereas Bcl-2 was significantly up-regulated(P<0.01). Immunofluorescence results showed that the expressions of GRP78, PERK, CHOP were consistent with the Western blot method. In conclusion, ethyl acetate extract from B. bipinnata has a significant protective effect on the damage of L02 cells caused by endoplasmic reticulum stress. The mechanism may be related to the inhibition of endoplasmic reticulum stress and the down-regulation of apoptosis in cells through the PERK/eIF2α/ATF4/CHOP signaling pathway.

LncRNA PVT1 induces chondrocyte apoptosis through upregulation of TNF-α in synoviocytes by sponging miR-211-3p.

Temporomandibular joint osteoarthritis (TMJ OA) is an important subtype of temporomandibular disorders (TMD). Articular cartilage destruction is considered a common pathological feature of TMJ OA, which is reported to be mainly induced by chondrocyte apoptosis. Synovial sterile inflammation is an initial factor of TMJ OA-associated articular cartilage destruction. Therefore, determining the mechanism of synovial membrane inflammation-induced articular cartilage destruction in TMJ OA is important for the TMJ OA therapy. In this study, we detected the function of synoviocytes in chondrocyte apoptosis under lipopolysaccharide (LPS)-induced inflammatory conditions and explored the underlying mechanism. We found that synoviocytes in inflammatory conditions facilitated LPS-induced chondrocytes apoptosis by secreting increased Tumor Necrosis Factor α (TNF-α), which was induced by long non-coding RNA plasmacytoma variant translocation 1 (PVT1) upregulation. PVT1 served as a competing endogenous RNA that sponged the microRNA miR-211-3p and prevented the inhibition of TNF-α expression. In conclusion, our in vitro study revealed that PVT1 has a previously unknown role in chondrocyte apoptosis, which may also be a mechanism underlying synoviocyte involvement in TMJ OA.

Reflections on the Requirements for Production Lines in Application of Chemical Drugs in China / 中国药学杂志

OBJECTIVE: The manufacturing site of drugs is a combination of a series of production factors to meet the requirements of drugs production, which is not only the material basis of drugs production, but also the evaluation basis for the review when applying for registration. The purpose of this paper is to preliminarily discuss the definition and extension of production lines for chemical drugs in China, and provide some references for standardizing new drug application. METHODS: The historical requirements for manufacturing site information in application materials of chemical drugs in China were briefly introduced, with daily pharmaceutical evaluation works and specific cases study. RESULTS: AND CONCLUSION: It should make clear the definition and extension of production lines in the application materials, strengthen the effective communication between different regulatory authorities, update the relevant information in time, and should pay continuing attention to the revision progress of the laws and regulations requirements on the production line in China.

Genes associated with Wolbachia-induced cytoplasmic incompatibility in natural populations of Culex pipiens pallens: a preliminary study / 中国血吸虫病防治杂志

Objective To investigate the genes involved in Wolbachia-induced cytoplasmic incompatibility among three natural populations of Culex pipiens pallens in eastern China, so as to provide insights into the development of preventive and control measures for mosquito-borne diseases based on Wolbachia. Methods The cytoplasmic incompatibility was tested among three natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province and Tangkou of Shandong Province using reciprocal crosses. Wolbachia infection was detected in C. pipiens pallens using a PCR assay, and the expression of Wolbachia wsp and WD0513 genes was quantified using a fluorescent quantitative real-time PCR (qPCR) assay. Results Bidirectional compatibility was found between the natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province (t = 0.57 and 0.15, both P values > 0.05), while bidirectional incompatibility was seen between the natural populations of C. pipiens pallens collected from Tangkou of Shandong Province and Wuxi of Jiangsu Province (t = 63.81 and 43.51, both P values < 0.01), and between the natural populations of C. pipiens pallens collected from Nanjing of Jiangsu Province and Tangkou of Shandong Province (t = 39.62 and 43.12, both P values < 0.01). Wolbachia wsp gene was amplified in all three natural populations of C. pipiens pallens, and qPCR assay detected no significant difference in the Wolbachia wsp gene expression among the three natural populations of C. pipiens pallens (F = 2.15, P > 0.05). In addition, there was no significant difference in the WD0513 gene expression between the natural populations of C. pipiens pallens collected from Tangkou of Shandong Province and Nanjing of Jiangsu Province (q = 8.42, P < 0.05) or between the natural populations of C. pipiens pallens collected from Tangkou of Shandong Province and Wuxi of Jiangsu Province (q = 7.84, P < 0.05); however, there was a significant difference detected in the WD0513 gene expression between the natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province (q = 0.40, P > 0.05). Conclusions Different Wolbachia numbers are detected in natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province and Tangkou of Shandong Province, and WD0513 gene may be involved in the Wolbachia-induced cytoplasmic incompatibility among three natural populations of C. pipiens pallens.

Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-ß-induced EMT.

LASP2 (LIM and SH3 protein 2), a member of the LIM-protein subfamily of the nebulin group, was first identified as a splice variant of the nebulin gene. In the past, investigators mainly focused on the impact of LASP2 on cardiac diseases because of its identification in the myocardium. Recently, several studies have reported that LASP2 is associated with the progression of various cancers. However, there have been no investigations on the expression and function of LASP2 in pancreatic cancer (PC). In this study, we performed the quantitative real-time polymerase chain reaction and Western blot analysis to detect the expression of LASP2 in PC tissues and cell lines. PC cells were transfected with LASP2 overexpression plasmid or the negative control in the presence or absence of tumor growth factor-ß (TGF-ß). The transwell assays were used to measure the effects of LASP2 on PC cell migration and invasion. The protein expression of epithelial-mesenchymal transition (EMT) markers was detected using Western blot assay. Our results demonstrated that LASP2 was downregulated in PC tissues and cell lines. In addition, upregulation of LASP2 inhibited the PC cell migration and invasion. We also found that LASP2 upregulation reversed TGF-ß-induced EMT in PC cells. Taken together, we provided novel evidence supporting the tumor-suppressor role of LASP2 in PC and suggested it as a potential therapeutic target in PC treatment.

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasion via regulation of the NF-κB signaling pathway in osteosarcoma cells.

Mitochondrial ribosomal protein S23 (MRPS23), encoded by a nuclear gene, is a participant in the translation of mitochondrial proteins. Recently, MRPS23 has been reported to be overexpressed in many types of cancers and have a close association with cancer progression. However, the specific roles of MRPS23 in osteosarcoma (OS) remain unknown. In this study, we investigated the expression pattern and biological functions of MRPS23 in OS cells. Our results demonstrated that MRPS23 was up-regulated in OS tissues and cell lines. Down-regulation of MRPS23 significantly inhibited OS cell proliferation and invasion induced by lipopolysaccharide (LPS) in vitro. Furthermore, the in vivo experiments showed that MRPS23 down-regulation markedly suppressed OS cell growth and metastasis induced by LPS. Mechanistically, down-regulation of MRPS23 inhibited the activity of NF-κB signaling pathway in OS cells. In conclusion, these findings indicated that MRPS23 may be a potential therapeutic target for OS treatment.

Study on insecticide resistance of Culex pipiens pallens in southwest region of Shandong Province / 中国血吸虫病防治杂志

Objective To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. Methods The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. Results The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43–557.54, 118.17–445.33, 6.44–19.00, 2.37–8.10, and 0.88–2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 – 456.95, 190.56 – 292.37, 123.32 – 319.24, and 192.31 – 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87–108.36) . Conclusions After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Analysis of population genetic diversity of mosquitoes from Shandong Provincebased on mitochondrial DNA cytochrome oxidase subunit Ⅰgene fragment / 中国血吸虫病防治杂志

Objective To explore the characteristics of gene sequence of mtDNA-COⅠof Culex pipiens pallens from differ-ent geographical regions in Shandong Province and different resistant strains from the lab and five common mosquito species, and analyze the genetic diversity of these mosquitoes.Methods Adult mosquitoes were collected from Jinan,Jining,Qingdao cities and other places in Shandong Province.The sensitive,dichlorvos-resistant,pyrethroid-resistant and propoxur-resistant strains were reared in the lab.Five species of mosquito(Cx.pipiens pallens,Cx.tritaeniorhynchus,Anopheles sinensis,Aedes al-bopictus,and Armigeres subalbatus)were collected from Jining City and identified in the lab.mtDNA-COⅠwas specifically am-plified by PCR and sequenced.The gene sequences were compared and analyzed by the biological information systems,and the phylogenetic tree was constructed.Results The amplified mtDNA-COⅠfragments of Cx.pipiens pallens from eight different cit-ies and four different resistant strains were 528 bp in length,with 67.4% A+T contents and two mutation sites.The nucleotide se-quence homology among the different geographic strains was 99.95% and the gene sequences of the four resistant strains were the same,showing a high homogeny.The amplified mtDNA-COⅠfragments of the five species of mosquitoes were 528 bp with 408 conserved sites,120 variable sites,42 parsimony informative sites and 78 singleton sites. The A+T contents were between 65.7% and 68.0%.The nucleotide sequence homology among the different mosquito species was between 86.17% and 92.05%,and the molecular identification was consistent with the traditional morphological identification. The molecular phylogenetic study showed that the different species were clustered at their own branch at the species and genus levels,while genera Armiger-es was distantly related to the others.Conclusion mtDNA-COⅠcould not serve as the molecular marker to analyze the popula-tion genetic variation and phylogenesis of Cx.pipiens pallens from different geographical regions and different resistant strains, but it has species and genus specificities,which could be used for the identification of the mosquito species and genus.

Multivariate analysis of corneal endothelial cell count reduction after cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To investigate the factors related to the decrease of corneal endothelial cell number after phacoemulsification in cataract patients. ·METHODS: We selected 98 patients (120 eyes) in Ophthalmic Center from July 2014 to July 2016 underwent phacoemulsification and they were retrospectively analyzed. According to the central corneal endothelial cell density before and 2mo after the operation, they were divided into serious loss group of 52 cases (67 eyes, density of central corneal endothelial cells loss rate no less than 12.3%),the general loss group of 46 cases (53 eyes, the density of central corneal endothelial cell loss rate <12.3%). Relevant indicators of general information, operation of the two groups were compared, the influence factors of non conditional Logistic regression analysis method was used to investigate the effect for corneal endothelial cell loss in cataract patients. ·RESULTS:Serious loss group and the general group on gender, rate with hypertension, rate with diabetes, rate with high blood lipids, with shallow anterior chamber, corneal diameter and suction time comparison, had no statistically significant differences (P > 0. 05). Nuclear hardness classification of Emery lens, ultrasonic power, ultrasonic emulsification time, age between groups were significantly different(P<0.05). By using Logistic analysis method, the results showed that increased Emery lens nucleus grading, ultrasonic energy, phacoemulsification time, age were independent risk factors for corneal endothelial cells after phacoemulsification (P<0.05). ·CONCLUSION: The main factors that influence the decrease of corneal endothelial cell number after phacoemulsification are Emery lens, higher grade of nucleus of lens, increase of ultrasonic energy, longer time of phacoemulsification and increased age.

GABA Receptor Activity Suppresses the Transition from Inter-ictal to Ictal Epileptiform Discharges in Juvenile Mouse Hippocampus / 神经科学通报·英文版

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg-free ACSF for 10 min-20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 μmol/L of the GABA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 μmol/L muscimol abolished all the epileptiform discharges. When the GABA receptor antagonist bicuculline was applied at 10 μmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.