The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.

Objective To explore the gender heterogeneity of depression and thyroid hormone and homocysteine levels in infertile patients.Methods Totally 250 patients with infertility were selected in Tangshan Maternal and Child Health Care Hospital affiliated to North China University of Science and Technology from December 2015 to April 2017.The Self-Rating Depression Scale(SDS) was used to evaluated the patients's depression.The patients with infertility and depression were divided into infertility and depression group,and the patients with infertility but without depression were infertile and non-depressed group,patients with infertility and depression were divided into male infertility and depression group and female infertility group with depression,and the levels of thyroid hormone and homocysteine were measured respectively.Results ①The thyroid stimulating hormone and homocysteine levels in infertility patients with depression were significantly higher than those without depression ((2.045± 1.253) uIU/ml,(2.412± 1.236) uIU/ml,t=-2.287,P=0.023;(15.411 ±9.143) mmol/L,(19.129± 13.087) mmol/L,t=-2.467,P=0.014).②There was no statistically significant difference in the degree of depression between male and female infertility patients (x2=0.483,P=0.785).③ The levels of triodothyronine,thyroxine and homocysteine in male infertility patients with depression were significantly higher than those in female patients ((1.926±0.648)nmol/L,(1.712 ±0.416) nmol/L,t=2.457,P=0.015;(117.86± 19.311) nmol/L,(110.185± 18.999) nmol/L,t=2.434,P=0.016;(15.575±4.139) mmol/L,(12.277±3.921) mmol/L,t=4.982,P＜0.01),and the TSH was lower than that in the female group((2.496± 1.329) uIU/ml,(3.057± 1.583) uIU/ml,t=-2.303,P=0.023).④The TSH and Hcy levels of male and female infertility patients were significantly positively correlated with SDS indexes,and had a significant positive predictive power to SDS score.Conclusion The levels of thyroid hormone and homocysteine are different in gender in infertile patients with depression,and the thyroid hormone and homocysteine are related to the depression.so we should pay attention to the depression symptoms of infertility patients and the changes of their biological levels,especially the gender heterogeneity.

Objective To report the clinical effect of repair of significant tongue defect after tongue cancer radical resection using anterolateral thigh perforator free flap with CTA three-dimensional reconstruction technique assistance.Methods From January,2012 to November,2015,13 cases were performed using anterolateral thigh perforator free flap in the repair of significant tongue defect after tongue cancer radical resection.Preoperation CT scan of the free flap donor site was done to obtain the three-dimensional images of arterial blood area by Digital Three-dimensional Reconstruction CT Technique to determine the origin of the anterolateral thigh flaps,direction,classification,length,diameter and the position of pedicle perforator.According to the condition of the defect of the tongue,flap of area from10 cm×9 cm to 8 cm×6 cm was design,the flap arteries and veins were anastomosed with the external maxillary artery or the superior thyroid artery,anterior vein,internal jugular vein or external jugular vein respectively.The shape and recovery of function of the reconstructed tongue were observed regularly after operation.Results All the flaps in the 13 cases survived,in the postoperative 4 to 18 months followed up,the appearance of the reconstructed tongue was close to the normal one,the patients were satisfied with the mastication and feeding function.Conclusion CTA three-dimensional reconstruction technique assisted anterolateral thigh perforator free flap technique is useful in obtaining good clinical effect,and it is one of the most best methods for repairing significant tongue defect after tongue cancer radical resection.

In recent years,assisted reproductive technology(ART)is developing rapidly,especially in vitro fertilization and embryo transfer(IVF-ET)technology.The rate of clinical pregnancy in our country is about 40％,and how to improve the rate of clinical pregnancy of IVF-ET has been the focus of the scholars research content.Environmental factors including culture system,temperature,humidity,pH value and volatile organic compounds,all of these can affect the success of IVF-ET.Now the common environmental factors affecting IVF-ET research progress were reviewed as follows.

The apoptosis, necrosis, and senescence of hepatocytes are closely associated with the activation and proliferation of oval cells, and in addition, liver regeneration mediated by oval cells is an important part of regeneration after liver injury. Currently, studies have shown that a variety of cytokines, hormones, and neurotransmitters are involved in this process. This article reviews recent research findings, introduces the research advances in the association between various signaling pathways (TWEAK/Fn14, Hedgehog, and thyroid hormone) and liver regeneration mediated by oval cells, elaborates on the role of each pathway in the regeneration of hepatocytes, and investigates related mechanisms in liver regeneration.

OBJECTIVETo investigate the effects of the furin inhibitor α1-PDX on the growth, invasion, and tumorigenicity of cervical cancer cells and explore the mechanisms.

METHODSThe changes in the growth, migration and invasion of α1-PDX-transfected HeLa cells were observed using MTT assay, Boyden migration and invasion assay. The protein levels of furin and MT1-MMP were measured using Western blotting and furin activity was detected by enzyme activity assay in the transfected cells. HeLa cells were seeded subcutaneously in nude mice and the tumor volume changes were recorded.

RESULTSCompared with the control cells, α1-PDX-treated cells showed a significant growth inhibition by 18.4% at 24 h (P<0.01) with obviously lowered migration ability and cell invasiveness (P<0.01). Treatment with α1-PDX significantly reduced furin enzyme activity and MTI-MMP protein levels in HeLa cells. In nude mice, α1-PDX-treated HeLa cells exhibited a delayed and lowered tumorigenicity with reduced size of the tumors.

CONCLUSIONα1-PDX can inhibit the growth, metastasis and tumorigenicity of HeLa cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.

Animals ; Female ; Furin ; antagonists & inhibitors ; HeLa Cells ; drug effects ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Transfection ; Uterine Cervical Neoplasms ; pathology ; alpha 1-Antitrypsin ; pharmacology

Objective To investigate the effects of the furin inhibitor α1-PDX on the growth, invasion, and tumorigenicity of cervical cancer cells and explore the mechanisms. Methods The changes in the growth, migration and invasion of α1-PDX-transfected HeLa cells were observed using MTT assay, Boyden migration and invasion assay. The protein levels of furin and MT1-MMP were measured using Western blotting and furin activity was detected by enzyme activity assay in the transfected cells. HeLa cells were seeded subcutaneously in nude mice and the tumor volume changes were recorded. Results Compared with the control cells, α1-PDX-treated cells showed a significant growth inhibition by 18.4% at 24 h (P<0.01) with obviously lowered migration ability and cell invasiveness (P<0.01). Treatment withα1-PDX significantly reduced furin enzyme activity and MTI-MMP protein levels in HeLa cells. In nude mice, α1-PDX-treated HeLa cells exhibited a delayed and lowered tumorigenicity with reduced size of the tumors. Conclusionα1-PDX can inhibit the growth, metastasis and tumorigenicity of HeLa cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.

Objective To investigate the effects of the furin inhibitor α1-PDX on the growth, invasion, and tumorigenicity of cervical cancer cells and explore the mechanisms. Methods The changes in the growth, migration and invasion of α1-PDX-transfected HeLa cells were observed using MTT assay, Boyden migration and invasion assay. The protein levels of furin and MT1-MMP were measured using Western blotting and furin activity was detected by enzyme activity assay in the transfected cells. HeLa cells were seeded subcutaneously in nude mice and the tumor volume changes were recorded. Results Compared with the control cells, α1-PDX-treated cells showed a significant growth inhibition by 18.4% at 24 h (P<0.01) with obviously lowered migration ability and cell invasiveness (P<0.01). Treatment withα1-PDX significantly reduced furin enzyme activity and MTI-MMP protein levels in HeLa cells. In nude mice, α1-PDX-treated HeLa cells exhibited a delayed and lowered tumorigenicity with reduced size of the tumors. Conclusionα1-PDX can inhibit the growth, metastasis and tumorigenicity of HeLa cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.

Objective To compare the dissolution of Chuangxiong powder in different medium and discuss the dissolution characteristics in vitro of Changxiong powder. Methods The paddle method was adopted, the UV spectrophotometric method was developed to determine the in vitro dissolution quantity of Changxiong powder in five medium (water, 0.1 mol/L hydrochloric acid, acetate buffer of pH 4.5, phosphate buffer of pH 6.8, phosphate buffer of pH 7.4) with ferulic acid as index, and evaluated by drawing the dissolution curve and using the similar factor method and Weibull model. Results The dissolution quantity of Changxiong oral powder in five medium was different. The dissolution quantity in water, 0.1 mol/L hydrochloric acid, acetate buffer of pH 4.5 and phosphate buffer of pH 6.8 was similar and fit Weibull model, but it mutated in phosphate buffer of pH 7.4 and reached the maximum amount at 30 min. Conclusion The dissolution quantity of Changxiong powder is gradually increasing and the time is shorted in the medium from acidic to neutral then to alkaline. Dissolution curve is similar in the acidic and neutral medium. Changxiong powder dissolves out fast and completely in the alkaline medium.