Objective:To investigate the clinical characteristics of a family with maturity-onset diabetes of the young type 3(MODY3) and assess its association with the novel HNF1A-c.47T>A variant.Methods:A genetic pedigree of the MODY3 family was constructed, and clinical data were collected. Whole-exome sequencing combined with Sanger sequencing was used, followed for familial co-segregation analysis. Bioinformatics tools, including multiple sequence alignment–based conservation analysis and protein structural prediction, were conducted to validate the association between the novel HNF1A-c.47T>A variant and MODY3.Results:Seven MODY3 patients were diagnosed in this family, all harboring the HNF1A-c.47T>A heterozygous variant. AlphaFold2 protein structure prediction indicated that the HNF1A-c.47T>A variant altered the conformation of the first pair of α-helices within the protein dimerization domain.Conclusion:Based on co-segregation analysis, sequence conservation assessment, protein structure prediction, and classification based on American College of Medical Genetics and Genomics(ACMG) Guidelines, the HNF1A-c.47T>A variant was determined to be pathogenic for MODY3. This study reports this novel pathogenic variant, expanding the mutational spectrum of MODY3. By revealing its disruptive effect on the protein dimerization domain, the findings provide a potential molecular basis for the diagnosis and management of patients carrying similar variants.

Objective:To investigate the clinical characteristics of a family with maturity-onset diabetes of the young type 3(MODY3) and assess its association with the novel HNF1A-c.47T>A variant.Methods:A genetic pedigree of the MODY3 family was constructed, and clinical data were collected. Whole-exome sequencing combined with Sanger sequencing was used, followed for familial co-segregation analysis. Bioinformatics tools, including multiple sequence alignment–based conservation analysis and protein structural prediction, were conducted to validate the association between the novel HNF1A-c.47T>A variant and MODY3.Results:Seven MODY3 patients were diagnosed in this family, all harboring the HNF1A-c.47T>A heterozygous variant. AlphaFold2 protein structure prediction indicated that the HNF1A-c.47T>A variant altered the conformation of the first pair of α-helices within the protein dimerization domain.Conclusion:Based on co-segregation analysis, sequence conservation assessment, protein structure prediction, and classification based on American College of Medical Genetics and Genomics(ACMG) Guidelines, the HNF1A-c.47T>A variant was determined to be pathogenic for MODY3. This study reports this novel pathogenic variant, expanding the mutational spectrum of MODY3. By revealing its disruptive effect on the protein dimerization domain, the findings provide a potential molecular basis for the diagnosis and management of patients carrying similar variants.

Objective To observe value of thin slice CT multiple signs combined with multiplanar reformation(MPR)for diagnosing tracheobronchial tuberculosis(TBTB).Methods Data of 234 TBTB patients who underwent chest thin slice CT scanning were retrospectively analyzed.MPR was performed,the direct signs and indirect signs of TBTB were observed.The diagnostic efficacy of axial plain CT images(direct observation)and of MPR combined with the former(combined observation)were compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of direct observation was 38.88％(201/517),98.13％(1 789/1 823),85.53％(201/235),84.99％(1 789/2 105)and 85.04％(1 990/2 340),respectively,of combined observation was 91.10％(471/517),98.85％(1 802/1 823),95.54％(471/493),97.51％(1 802/1 848)and 97.14％(2 273/2 340),respectively.Significant differences of sensitivity,positive predictive value,negative predictive value and accuracy were found(all P＜0.001),whereas no significant difference of specificity was found between 2 methods(P＞0.05).Conclusion Thin slice CT multiple signs combined with MPR could be used to effectively diagnose TBTB.

Objective:To investigate the relationship between thyroid stimulating hormone (TSH) level and thyroid peroxidase antibody (TPOAb) status in the first trimester on pregnancy outcomes.Methods:A total of 2 095 pregnant women with complete clinical data from department of pregnancy endocrinology or department of obstetrics in Dongying People′s Hospital from January 1, 2018 to November 31, 2019.According to the TSH level detected before 12 + 6 weeks of gestation, all pregnant women were divided into normal TSH (0.1 μIU/ml≤TSH< 2.5 μIU/ml), high TSH (2.5 μIU/ml≤TSH≤4.0 μIU/ml), sub-clinical hypothyroidism during gestation (4.0 μIU/ml0.05). Multivariate logistic regression analysis of gestational diabetes mellitus and preterm delivery showed that the risk of gestational diabetes mellitus was significantly increased in group F compared with the control group. Age, gestational status, and TPOAb positivity were risk factors for gestational diabetes. The risk of premature birth in group D, group E and group F was higher than that in the control group [odds ratio ( OR)>1]. Age and TPOAb positivity were risk factors for preterm delivery in pregnant women ( OR>1, P<0.05). Conclusions:TPOAb positive in early pregnancy combined with subclinical hypothyroidism in pregnancy will increase the risk of gestational diabetes, while TPOAb positive in early pregnancy combined with TSH on the high side or subclinical hypothyroidism in pregnancy will increase the risk of premature delivery, so the management of such pregnant women should be strengthened and active treatment should be given if necessary.

Objective:To explore the expression and clinical significance of RhoGDI2 in colorectal cancer. Methods:Immuno-histochemistry was used to identify RhoGDI2 expression in clinical samples of colorectal cancer tissues,para-tumorous tissues and lymph node metastasis tissues. The relationships between CRC clinical factors and survival were analyzed. Results: RhoGDI2 expression contributed positively with tumor progression and metastasis in clinical tissues. It was associated with the stage of the tumor,lymph node metastasis, remote metastasis, venous invasion and vessel invasion. Patients with higher RhoGDI2 expression had poorer overall survival. Conclusion:RhoGDI2 showed high expression in colorectal cancer and it was associated with the stage of the tumor,lymph node metastasis,remote metastasis, venous invasion and vessel invasion. Patients with higher RhoGDI2 expression had poorer overall survival.

Objective:To study the silencing gene expression level of RhoGDI2 small interfering RNA(siRNA)and the colorectal cancer cell malignant behaviors such as cell proliferation,migration,invasion.Methods:Testing RhoGDI2 expression using Westen blot analysis and Real-time reverse transcription polymerase chain reaction(RT-qPCR)in the colorectal cancer cell lines of RKO,HT29,SW620,SW480,HCT116.The siRNA of RhoGDI2 with Lipofecta mineTM2000 was transfected into target cells,as well as negative control and normal control groups.Cell counting kits(CCK-8)to detect proliferation,Wound healing assay and the Transwell plate migration and invasion was detected.The epithelial-mesenchymal transition(EMT)relevant protein E-cadherin/Vimentin expression was detected.Results:Human colon cancer cell lines RhoGDI2 expression levels decreased in the order of RKO,HT29,SW620,SW480,HCT116:siRNA inhibited RhoGDI2 expression rate of RKO cell by 70%;in silence group,negative control group and blank contro1 group,the proliferation rates were(0.683±0.013),(0.866±0.088),(0.905±0.008),P<0.05;Wound healing assay and Transwell assay suggested RhoGDI2 silencing could inhibit migration;siRNA interference of colon cancer cells downregulated Vimentin,but upregulated E-Cadherin protein.Conclusion:RhoGDI2 down-regulation could significantly inhibit the cell proliferation,migration,invasion of colon cancer cell.

Objective To evaluate the clinical efficacy and safety of transcatheter arterial chemoembolization (TACE) with oxaliplatin (OXA), fluorouracil (5-Fu) and pirarubicin (THP) scheme in treating primary liver cancer. Methods A total of 65 patients with primary liver cancer were treated with TACE using infusion of OXA/5-Fu/THP scheme (TACE group). Other 21 patients with primary liver cancer, who were encountered at the Department of Interventional Radiology of authors’ hospital during the same period as the patients of TACE group, received simple transarterial embolization (TAE group). The therapeutic effect, the occurrence of adverse reactions, the progression-free survival time (PFS) and overall survival time (OS) of the two groups were comprehensively evaluated. The results were compared between the two groups. Results In the TACE group, the objective response rate (ORR) and disease control rate (DCR) were 55.4%and 81.5%respectively, and the median PFS and median OS were 11.5 months and 18.5 months respectively. Single factor analysis indicated that patients, who had liver function of Child-Pugh A and received more times or treatment, and who had small-sized tumor and no portal vein tumor thrombus or metastasis, usually had a better prognosis, and the differences were statistically significant (P<0.05). The prognosis of the patients with Barcelona staging (BCLC) B was better than that of the patients with Barcelona staging C, and the difference was statistically significant (P=0.000). Cox multivariate analysis revealed that the portal vein tumor thrombus and tumor metastasis were independent risk factors for the prognosis of the patients. Compared with the TAE group, TACE with OXA/5-Fu/THP scheme could effectively improve the mean progression-free survival time. Conclusion For the treatment of primary liver cancer, TACE with infusion of OXA/5-Fu/THP is clinically effective with fewer adverse reactions.

Objective To evaluate the mid-term and long-term effects of early endovascular emboli-zation in treating ruptured posterior communicating artery aneurysm. Methods Early endovascular embolization therapy was carried out in 36 patients with ruptured posterior communicating artery aneurysm (36 aneurysms in total), and the effects of embolization therapy were evaluated by using Raymond grading method. The unified imaging review program was formulated, and the mid-term and long-term effects were evaluated at half, 1, 2, 3 and 5 years after the treatment. Results The technical success rate was 100% in 36 patients (36 aneurysms in total). Raymond grading evaluation showed that gradeⅠwas seen in 32 patients, gradeⅡ in 2 patients, and grade Ⅲ in 2 patients. Recurrence of aneurysm was found in 5 patients (13.89%) at half (n=1), 2 (n=1), 3 (n=1) and 5 years (n=2) after the treatment. Re-rupture of the recurrent aneurysm was seen in one patient (2.78%). No death occurred during the following-up period. Conclusion Early endovascular embolization for ruptured posterior communicating artery aneurysm can effectively improve the prognosis of subarachnoid hemorrhage, and regular imaging examination can promptly detect the recurrence of aneurysm. Effective interventions are helpful for preventing deterioration and rupture of aneurysm.

Objective To investigate the Sedative effect and safety of intravenous Sufentanil combined with Propofol in painless gastroscopy.Methods 270 patients with ASA Ⅰ-Ⅱ were randomly divided into three groups:Group A (the Propofol group),Group B (the Fentanyl combined with Propofol group) and Group C (the Sufentanil combined with Propofol group).HR,MAP and SpO2 were monitored at three different time points:before placement of the gastroscope,during and 5 minutes after gastroscopy.The time required for consciousness recovery,the time required for regaining orientation,the operating time for gastroscopy and the dosage of Propofol were recorded.Results HR,MAP and SpO2 were obviously lower during operation than before or after operation in each group (P＜0.05) and were significant different among the groups (P＜ 0.05).The times required for consciousness recovery and for regaining orientation,respectively,were significantly longer in Group A than in Group B or C,and there was a significantly difference between Group B and Group C (P＜0.05).The total dose of Propofol in Group A was significantly larger than that in Group B or C (P＜0.05).Conclusions Compared with Propofol alone or Fentanyl combined with Propofol,Sufentanil can be used in combination with lower does of Propofol in painless gastroscopy to produce rapid and effective Sedation,with fewer side effects and higher patient satisfaction.

Aphosphorbasedonsilicananoparticleswaspreparedusingasol-gelmethod.Thecontrollable synthesis, spectroscopic properties, cytotoxicity and cell imaging of these nanomatericals were examined by using photoluminescence spectra, TEM, XRD, confocal microscopy and other characterized measurements. The results demonstrated that the obtained sample was silica with diameter about 50 nm. The maximum fluorescence excitation and emission wavelengths of the silica nanomatericals were 280 nm and 335 nm, and the maximum phosphorescence excitation and emission wavelengths of the silica nanomatericals were 280 nm and 440 nm. The obtained silica sample possessed room temperature phosphorescence that was stable against environmental changes. The obtained sample was stored in air at ambient conditions and its phosphorescence remained unchanged after 3 month demonstrated its long-term stability. The result of methyl thiazolyl tetrazolium ( MTT) and cell imaging experiments suggested that the synthesized silica nanoparticles were feeble cytotoxicity and could be uptaken by cells at the lysosomal compartment. Therefore these nanoparticles could serve as bioprobes for cell imaging.