Objective To study the value of MR three-dimensional volumetric interpolated breath-hold examination(3D-VIBE)and conventional MR imaging (including MRCP) in diagnosing cholangiocarcinoma early and evaluating the respectability of cholangiocarcinoma. Methods 20 patients with malignant obstruction of bile duct were scaned by conventional MR imaging(including MRCP) and dynamic-enhanced 3D-VIBE triple-phase acquisitions. MR imaging features of the tumors were analysed and the re-spectability of cholangiocarcinoma was also evaluated. The differences between conventional MR imaging and 3D-VIBE in displaying the tumors and the infiltration extent of the tumors were compared. Results The sensitivity ratio in showing the tumors were 85 and 95% with conventional MR imaging and 3D-VIBE, respectively, and there was statistically significant difference between two sequences in displaying infiltration of adjacent organs by the tumors(P<0.05). Conclusion 3D-VIBE is superior to conventional MR imaging in the early diagnosis,preoperative assessment of the infiltration extent and the tumor respectability of cholangiocarcino-ma.

Objective We screened for mutations in an autosomal dominant congenital cataract pedigree by gene sequence analysis to provide a basis for genetic diagnosis of congenital cataract.Methods A Chinese family with congenital nuclear cataract was recruited for mutational screening of candidate genes by direct sequencing.We analyzed the differences between the CRYGD gene mutant and wild-type in terms of protein conformation and structural domains using bioinformatics methods.Results We detected a novel heterozygous variant c.451_452insGACT in exon 3 of CR YGD.Bioinformatics analysis showed that the mutated CRYGD protein structural domain became shorter,the conformation became simpler,and protein inner repeatability was altered,affecting protein function.Conclusion We found that the Tyr1 51X gene mutation of CRYGD can lead to congenital hereditary cataract.To date,this is the only detected frameshift mutation caused by an insertion in CRYGD gene mutations.

Objective To investigate the correlation between the polymorphisms in GLIS3 and diabetic retinopathy in patients with type 2 diabetes in Northeast China.Methods Based on the case-control study,polymorphisms in GLIS3 were examined by PCR-RFLP in 120 cases of diabetic retinopathy in patients with type 2 diabetes (DR),120 cases of patients with type 2 diabetes without diabetic retinopathy (DNR),and 120 healthy individuals (NC).The odds ratio (OR) and 95％ confidence interval (C I) were calculated using unconditional logistic analysis.Results The resuhs demonstrated that GLIS3 rs7041847 AG,AG/GG genotype,or G allele was associated with an increased risk of DR and DNR (P ＜ 0.05).Moreover,GLIS3 rs7034200 CC,AC/CC genotype,or C allele was associated with an increased risk of DR and DNR (P ＜ 0.05).Conclusion In the patients in Northeast China,the polymorphisms in GLIS3 rs7041847 and rs7034200 were correlated with type 2 diabetes mellitus,while GLIS3 may not be associated with the susceptibility to diabetic retinopathy.

Objective To establish the CTRP4 transgenic mouse model and investigate the function of the novel adipocytokine CTRP4.Methods CTRP4 overexpressing vector in pCAGGS was firstly constructed and then microinjected into zygote to establish the founder transgenic mice .F1 heterozygotes were generated by founder mice mating with wildtype mice, and the CTRP4 transgenic homozygotes were generated by F 1 littermates.The genotype was confirmed by PCR and test cross method .The expression level of CTRP 4 in transgenic mice was detected by western blot .Result The human CTRP4 transgenic homozygote mice line was established , and the expression level of CTRP 4 was confirmed raletively high in detected tissues including heart , liver, brain and kidney . Conclusion The human CTRP4 transgenic mice was successfully established .

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.