BackgroundSmad4,a key intracellular mediator in transforming growth factor-β (TGF-β)signaling,plays a critical role in the normal development of many tissues/organs.However,its functional role in the development of lacrimal gland has rarely been reported.ObjectiveThe aim of this study was to investigate the role that Smad4 may play in the development of lacrimal glands using Smad4 conditional knockout (CKO) mice( C57BL/6 mouse line),MethodsSmad4 in lacrimal glands,as well as in the lens,cornea and ectoderm of the eyelids,was conditionally inactivated by the Pax6 promoter-driven Cre transgenic mice and Smad4 conditional gene mice,LacZ reporter was used to visualize the developing lacrimal gland by X-gal staining,and standard histological approaches were used to reveal morphological changes.Six or more mice or embryos in each group were used for comparisons at the same stage.ResultsLacZ staining showed that E15.0,Smad4 CKO mice could still develop primary lacrimal bud,but much shorter than the wild-type ones.At E16.5,the primary lacrimal bud in wild-type mice began branching,but no branching was found in Smad4 CKO mice except that the primary lacimal bud became blunt at the tip.At E18.0,although Smad4 CKO mice develop some acini,the branching and size and number of acini were obviously less than ones in Smad4 wild-type mice.Based on histological findings,lacrimal glands in Smad4 CKO mice developed slowly,and the size was considerably smaller,and the numbers of lobes as well as the numbers of acini were much fewer than those of Smad4 wild-type mice lacrimal glands at various stages.Pigment and adipose tissue were also observed within the lacrimal glands starting from P7 in Smad4 CKO mice and increased with age growing.Lacrimal glands in mutant adult mice were eventually replaced by adipose tissue and accumulation of pigments.Conclusions These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG and may be involved in the metabolism of pigment and adipose tissue in LG.

0.05).There was a negative correlation between the EGFR expression with the expression of SSTR2A and SSTR5 in NSCLC tissues.The 3-year survival rates were 64.5% and 65.9% in patients positive of SSTR5 and SSTR2A,respectively;and were 45.2% and 22.2% for those negative of SSTR5 and SSTR2A,respectively(P

Objective:To evaluate the inhibitory effect of Herceptin on HeLa,SiHa cells and to investigate the synergistic mechanism of Herceptin and Carboplatin.Methods:HeLa and SiHa cells were treated with Herceptin(at 5,10,20,40,and 80 ?g/ml),Carboplatin(at 0.5,1,2,4,and 8 ?g/ml),and Her+CBP[(10+1),(20+2),and(40+4)?g/ml] separately.The untreated cells were taken as control.SP immunohistochemical method was used to detect the protein expression of HER-2/neu and downstream Ras oncogene.MTT method was used to study the inhibition effect of Herceptin on HeLa,SiHa cells and its synergetic effect with carboplatin.FCM was used to detect the cell apoptosis and cell cycle.The mRNA expression of her-2/neu and ras were assessed by RT-PCR;the protein expression of HER-2/neu and Ras were studied by Western blotting.Results:Herceptin significantly inhibited cervical cancer cells proliferation,and there was a synergistic effect when combined with carboplatin(P

Objective:To observe the expression and correlation of eIF4E and c-myc in laryngeal squamous cell carcinoma.Methods:Western blot was applied to examine the expression of eIF4E and c-myc on tumor core,transition core and tumor-free core from 36 laryngeal carcinoma patients.The results were statistically analyzed.Results:The overexpression of eIF4E and c-myc protein levels suggests an increasing tendency from tumor-free core,transition core and tumor core;and shows an significant correlation of eIF4E and c-myc expression.Conclusion:The overexpression of eIF4E and c-myc cause the laryngeal carcinoma cell malignant transformation;the correlation of eIF4E and c-myc may provide a basis for gene therapy of laryngeal carcinoma.

Objective To investigate se rum concentration of tumor necrosis factor(TNF)-? and its correlation with insulin resistance in pregnant women with gestational diabetes mellitus (GDM). Methods Enzyme-linked immunosorbent assay was used to measure th e fasting serum TNF-? levels of 42 women with GDM (28～39 gestational weeks), a n d 40 cases of normal pregnant women in the third trimester. Fasting plasma gluc ose, insulin, C-peptide and glycosylated hemoglobin (HbA1c) were also measured at the same time. Insulin sensitive index (ISI) was calculated. Res u lts (1)Significantly elevated serum TNF-? was found in the women w i th GDM(5.2?1.6) ng/L as compared with the healthy pregnant women in third t rimester (4.5?0.5)ng/L(P

Objective:To compare the volatile chemical constituents from the shell and kernel of Caesalpinia minax Hance.Methods:The volatile chemical compositions of Caesalpinia minax Hance were obtained by organic solvent-wet distillation and were analyzed by GC-MS equipped with a elastic quartz capillary column HP-5MS 5%Phenyl Methyl Siloxane(30m?0.25mm?0.25?m).The constituents were identified by their mass spectra.The relative percentage of the volatile constituents was calculated from the GC peak areas.Results:One hundred and fifteen kinds of chemical constituents in the shell of Caesalpinia minax Hance were separated and sixty-three of them,which accounts for 54.7%of total volatile constituents, were characterized.There are five kinds whose relative contents were more than 2.0%.One hundred and two kinds of chemical constituents in the kernel of Caesalpinia minax Hance were separated and fifty-one of them,which accounts for 50.0%,were characterized.There are seven kinds whose relative contents were more than 2.0%.Form the shell and kernel of Caesalpinia minax Hance there were forty kinds of chemical constituents the same.The most relative contents were Limonene(5.31%,shell)and 1-Hexanol(12.94%,kernel).Conclusion:This paper reports,for the first time,the comparison of volatile constituents from shell and kernel of Caesalpinia minax Hance.It is helpful for controlling the quality and further researching of Caesalpinia minax Hance.

Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.

ObjectiveTo explore the effect of personality and psychosocial factors on irritable bowel syndrome (IBS).MethodsPersonality and psychological status of 46 IBS patients and 32 healthy individuals were evaluated with Eysenck Personality Questionaire (EPQ), Symptom Checklist-90 (SCL-90) and Life Events Scale (LES).ResultsIn EPQ, E (extroversion-introversion) scores of IBS group were lower than those of control group; N (neuroticism) scores of IBS group were significantly higher than those of control group (P<0.01). In SCL-90, the scores of somatization, compulsion, anxiety, depression and etc. were higher than those of control group (P<0.05). The frequency of meeting negative life events, the quantity of stimulus of meeting negative life events and the total quantity of stimulus of meeting life events of IBS patients within one year until episode were significantly higher than those of control group (P<0.01).ConclusionPersonality psychological characteristics and life events before illness are associated with the morbidity of IBS.

New drug research and development is a technology-intensive industry with high investment, high cycle and high risk. In recent years, with the rapid development of modern disciplines such as omics technology, bioinformatics, high-throughput and high-content screening, and artificial intelligence, the research and development of small-molecule drugs has presented a new paradigm characterized by "integrated medicinal chemistry". This review summarizes new enabling drug discovery technologies, the emergence of new subfields formed through integration innovations and practical chemistry toolbox in the field of medicinal chemistry.

Objective:To research the distribution features of HLA-A,B and DRB1 high resolution alleles and haplotypes in Heilongjiang population.Methods:PCR-SBT methods was applied for HLA-A,B,DRB1 high resolution genotyping of 13 670 unrelated and healthy donors in region of Heilongjiang,and haplotype frequencies were calculated by counting and maximum likelihood method. Results:A total of 286 HLA alleles were observed and the most frequent alleles(>0.1)were A*02∶01,A*24∶02,A*11∶01,DR*07∶01,DR*09∶01 and DR*15∶01.Among 1 087 kinds of HLA-A-B haplotype ,there were 22 kinds frequency higher than 0.01,and 267 kinds with statistically significant and positive linkage disequilibrium(ALD>0,HF≥1.09×10-4,χ2>3.84).Moreover,among 1 329 kinds of HLA-B-DRB1 haplotype,there were 19 haplotypes frequency higher than 0.01,and 357 kinds with statistically significant and positive linkage disequilibrium.1 348 kinds of A-B-DR Haplotype were informative with frequency≥1.66 ×10-4 in 4 428 haplotypes, and a total of 17 kinds of A-B-DR haplotype frequency higher than 0.005.Conclusion: Get the distribution features of HLA high resolution allele and haplotype in Heilongjiang population, and associated genetic parameters, Distribution of alleles and haplotypes close to northern Han population,but have their own distribution.