Objective To explore the predictive value of methylenetetrahydrofolate reductase(MTHFR)gene C677T polymorphism and serum homocysteine(Hcy)level for adverse pregnancy outcomes.Methods The clinical data of 698 pregnant women who received antenatal care and deliv-ered at Ji'an Central People's Hospital were retrospectively collected.According to the research pur-pose,the pregnant women were divided into internal study cohort(n=483)or external validation co-hort(n=215).Each cohort was further divided into adverse pregnancy group and normal pregnancy group based on whether adverse pregnancy outcomes occurred.The MTHFR gene C677T polymor-phism and serum Hcy level of all pregnant women were detected.Binary Logistic regression analysis was used to investigate the relationships of MTHFR gene C677T polymorphism,Hcy level,and other indicators with adverse pregnancy outcomes.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive efficacy of different indicators when used alone and their combina-tion.Results In the internal study cohort,compared with the normal pregnancy group,the detection frequency of the CC genotype at the MTHFR gene C677T locus was lower,while the detection frequencies of the CT and TT genotypes were higher in the adverse pregnancy group(P＜0.001).The proportion of pregnant women with high Hcy levels was higher in the adverse pregnancy group than that in the normal pregnancy group(P＜0.001).Binary Logistic regression analysis showed that age,folic acid level during pregnancy,MTHFR gene C677T polymorphism,and Hcy level were all independ-ent influencing factors for adverse pregnancy outcomes(P＜0.05).The ROC curve indicated that the area under the curve(AUC)of the combined prediction model was 0.938,which was greater than that of each indicator.In the external validation cohort,the AUC of the combined prediction model was 0.917,validating the stability and clinical applicability of the model.Conclusion The TT and CT genotypes at the MTHFR gene C677T locus and high Hcy level are all independent risk factors for adverse pregnancy outcomes.The prediction model constructed by combining these factors with age and folic acid level during pregnancy has a high predictive efficacy for adverse pregnancy outcomes.

Objective:To investigate the changes in the white matter fiber structure of fetal brain with mild to moderate isolated ventriculomegaly (IVM) using diffusion tensor imaging (DTI) model and fixed based analysis (FBA) method of diffusion MRI (dMRI).Methods:This was a case-control study. Twenty fetuses diagnosed with mild to moderate IVM who were admitted to the Provincial Hospital Affiliated to Shandong First Medical University from August 2022 to August 2023 were included prospectively as the IVM group, with gestational age ranging from 24 to 36 (29.9±3.6) weeks. The control group included 22 normal control fetuses obtained from the dMRI atlas data of Chinese fetal brain, with gestational age ranging from 24 to 36 (30.2±3.7) weeks. The dMRI data were collected for all fetuses and the DTI model was used to obtain fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity of 7 main fiber bundles, including the genu and splenium of the corpus callosum, middle cerebellar peduncle, bilateral cortico-spinal tract, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. The FBA method was used to obtain fiber density (FD), fiber cross-sectional area (FC), and fiber density and cross-section (FDC) of the whole brain. The comparison of DTI parameters of each fiber bundle between the two groups was conducted using independent sample t test or Mann-Whitney U test. The comparison of FBA parameters between the two groups was performed using covariance analysis, and the MRtrix3 software package was used to display the brain regions with significant differences. Results:The FA values of the inferior longitudinal fasciculus in the IVM group and the control group were 0.142±0.012 and 0.133±0.015, respectively, and the difference was statistically significant ( t=2.21, P=0.033), while the DTI parameters of the other fiber bundles showed no statistically significant differences ( P>0.05). The whole brain FBA results showed that compared with the control group,FD decreased while FC increased in the corpus callosum, fornix, and sagittal stratum in IVM fetuses, while FDC decreased in the cortico-spinal tract. Conclusion:There are microstructural changes of the brain white matter fiber in intrauterine fetuses with mild to moderate IVM, which are mainly located in the white matter fiber bundles surrounding the body, atrium, and temporal horn of the lateral ventricle.

Objective:To evaluate the feasibility and the application values of quantitative susceptibility mapping (QSM) for the assessment of meniscal injury and in distinguishing meniscus degeneration and tears.Methods:The clinical and imaging data of 70 patients suspected of meniscus injury and scheduled for arthroscopy in Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University from November 2019 to June 2020 were analyzed retrospectively. Thirty age-and sex-matched healthy subjects were also examined as controls. All subjects received knee joint QSM and routine MR imaging. According to the results of arthroscopy, the patients was divided into meniscus degeneration and meniscus tear groups, respectively. The conventional MR was evaluated by two radiologists. The meniscus injury area was delineated on the original QSM magnitude images (the central area of the posterior corner of the lateral meniscus was selected in the healthy controls) and mapped to the corresponding QSM maps, and the magnetic susceptibility values were measured. Kruskal-Wallis H test was used to analyze the magnetic sensitivity values of meniscal degeneration, meniscal tear and healthy control groups; and Bonferroni was used to correct the pairwise comparison. ROC curve was established to evaluate the threshold and efficacy of magnetic susceptibility value in the diagnosis of meniscal tear. The results were compared with those of conventional MRI. Results:The magnetic susceptibility values of meniscus of healthy controls, meniscal degeneration and meniscal tear groups were (0.035±0.016)ppm, -0.031(-0.040,-0.005)ppm, and(-0.122±0.115)ppm, respectively, with significant difference found among the three groups (χ2=44.419, P<0.05). The magnetic susceptibility values of meniscus of healthy controls was significantly higher than those of meniscus degeneration patients and meniscus tear patients (χ2=-23.843, -48.253, P<0.05). The magnetic susceptibility values of meniscus of meniscus tear group was significant lower than those of meniscus degeneration group (χ2=-24.410, P<0.05). Taking magnetic susceptibility values of -0.062 5 ppm as threshold, the area under the ROC curve for the diagnosis of meniscal tears was 0.949, with the sensitivity as 87% and the specificity as 100%. The sensitivity and specificity of conventional MRI in the diagnosis of meniscal tears were 86.8% and 87.5%, respectively. Conclusion:QSM can quantitatively evaluate meniscus injury and can be used as an effective supplement method to conventional MRI, which is helpful to improve the diagnosis of meniscus tear.

Objective To explore the role of B7-H3 in the Tie2 expressing monocytes (TEMs) mediated angiogenesis of clear cell renal cell carcinoma (ccRCC).Methods Level of B7-H3 expression on TEMs surface was detected by flow cytometry in ccRCC tissues and normal renal tissues,which were obtained from April 2016 to August 2016 from 20 patients.Microvessel density (MVD) labeled by CD34 in high B7-H3 + TEMs group and low B7-H3 + TEMs group was detected by immunohistochemical examination in ccRCC specimens.B7-H3 + TEMs and B7-H3-TEMs were co-cultured with the 786-O cell lines,and B7-H3 + TEMs and B7-H3-TEMs culture supernatants were collected as conditioned medium,then the effect of B7-H3 + TEMs on angiogenesis was tested by tubule formation assay and mouse aortic ring assay.Results Flow cytometry showed that the frequency of B7-H3 expression on TEMs in ccRCC was (45.10 ± 17.78)％,and the frequency of B7-H3 expression in normal kidney tissues was (10.28 ± 4.28) ％.The frequency of B7-H3 expression on TEMs was significantly higher than that in normal renal tissues (P ＜ 0.001).The MVD of high B7-H3 + TEMs group (103.81 ± 29.28) was higher than that of low B7-H3 + TEMs group (76.55 ± 20.80) (P =0.027).The results of tube formation assay showed that the number of tubule formation of HUVEC in B7-H3 +TEMs group(55.25 ± 11.48) was significantly greater than that of B7-H3-TEMs group (31.34 ± 8.45) and blank control group (25.00 ± 6.74) (P ＜ 0.001).The results of mouse aortic ring assay showed that the number of neovascularization in B7-H3 + TEMs group(77.35 ± 18.47) was significantly greater than that of B7-H3-TEMs group (39.42 ± 8.29) and blank control group (28.79 ± 7.63) (P ＜0.001).Conclusions B7-H3 + TEMs can promote angiogenesis in ccRCC,and might act as an effective target in anti-angiogenic therapy for ccRCC.

Objective: To investigate whether cancer-associated- fibroblasts (CAF), the key component of tumor microenvironment, regulate the chemoresistant capacity of lung cancer cell line A549 through SDF-1 secretion. Methods: Primary cell isolation techniques was used to isolate cancer-associated-fibroblasts from lung cancer patients. MTT assay was applied to determine the proliferation and chemoresistance of A549 cells. Quantative PCR was used to detect the mRNA changes of Bcl-xL. Western blotting was used to detect the protein expression of Bcl-xL. ELISA was applied to detect the SDF-1 secretion from normal fibroblasts (NF) and CAF. Results: CAF promoted the proliferation of A549 cells, while NF had no significant effect on them. After 72 hrs incubation, the absorbance value of A549+ CAF medium group was 0.814±0.006, significantly different from the 0.753±0.006 of the A549+ NF medium group (P<0.05). The Q-PCR assay indicated that mRNA expressions of Bcl-xL in the A549 group, A549+ NF medium group and A549+ CAF medium group were 1.00±0.11, 1.10±0.09 and 3.50±0.30, respectively, showing a significant difference between the A549+ NF medium group and A549+ CAF medium group (P<0.05). The Western blot showed that protein expressions of Bcl-xL in the A549 group, A549+ NF medium group and A549+ CAF medium group were 1.00±0.08, 1.10±0.12 and 3.10±0.25, respectively, with a significant difference between the A549+ NF medium group and A549+ CAF medium group (P<0.05). The ELISA results showed that the SDF-1 concentrations in the A549+ NF medium group and A549+ CAF medium group were 3.23±0.02 and 9.53±0.10, respectively, significantly different from each other (P<0.05). The MTT assay indicated that the absorbance values of OD of A549 group, A549+ AMD3100 group, A549+ NF medium group, A549+ NF medium+ AMD3100 group, A549+ CAF medium and A549+ CA Fmedium+ AMD3100 group were 0.43±0.03, 0.25±0.02, 0.48±0.03, 0.31±0.03, 0.72±0.06 and 0.45±0.03, respectively. The data of A549+ NF medium group was significantly different from that of A549+ CAF medium group (P<0.05). Conclusions Cancer-associated-fibroblasts enhance the drug resistance of A549 cells through SDF-1 secretion, upregulating the expression level of Bcl-xL through interaction with CXCR4. Our study not only illustrates that tumor microenvironment is able to enhance drug resistance of tumor, but also provides experimental evidence for the cancer-associated-fibroblasts as a potential therapeutic target for the treatment of lung cancer.

Objective To evaluate the efficacy and safety of Sun's tip-flexible ureterorenoscopy (tf-URS) combined with holmium laser lithotripsy in treatment of renal and upper ureteral calculi.MethodsClinical data of 48 patients (29 males and 19 females) with renal and upper ureteral calculi treated by tf-URS with holmium laser lithotripsy in our hospital from November 2015 to May 2016 were retrospectively analyzed.Among 48 patients there were 29 males and 19 females with a mean age of (37.8±12.5) years (21-67), including 31 cases of upper ureteral calculi and 17 cases of renal calculi with a mean stone size of (1.4±0.6) cm (0.8-2.1).The tf-URS was advanced through the ureter under visual direction with rigid mode.When the endoscope reached the ueteropelvic junction, the inner flexible part was extended out to explore the pelvicaliceal stones and then the holmium laser lithotripsy was performed.The therapeutic results were evaluated by KUB 2 days after operation and color ultrasonography or CT 4 weeks after operation.Results The success rate of insertion of tf-URS was 94% (45/48).The calculi were detected in 45 cases, and laser lithotripsy succeeded in 43 cases (96%).The rate of total stone clearance was 87% (39/45).The procedure was transformed to laparoscopic or percutaneous nephrolithotomy (PCNL) in 3 patients with ureterostenosis or ureteral distortion.No serious complications occurred.Conclusion The tf-URS with holmium laser in the treatment of renal and upper ureteral calculi is safe,reliable and effective.

Cancer has become clear that not merely gene variations but also epigenetic modifications may contribute to it. Epigenetic changes refer to stable alterations in gene expression with unrelated to changes in the underlying genetic sequence,resulting in heritable. DNA methylation is one of the common epigenetic changes. It control the gene expression through changing DNA conformation and stability, chromatin structer, DNA-protein interaction. The reversal of dysregulated DNA methylation has emerged as a potential strategy for the treatment of thyroid carcinoma. The artical will provide an overview of how DNA methylation contribute to thyroid carcinoma dissemination,invasion and metastasis and we will summarize the latest epigenetic therapies for thyroid carcinoma.
Chromatin ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression ; Humans ; Neoplasm Metastasis ; Thyroid Neoplasms ; genetics

ObjectiveTo explore the relationship among 14 kinds of intolerant food by using association rules to provide evidence for more reasonable diet intake.Methods A total of 2962 adults who received medical examination at the First Affiliated Hospital of China Medical University during January 2008 and June 2010 were enrolled in this investigation.ELISA was used to detect allergen-specific IgG antibody of 14 kinds of food.An association rules model was established by SPSS Clementinel2.0.In order to find positive intolerance association rules,food frequency was recorded with SPSS 16.0.Results Five most commonly seen food intolerance were eggs,crabs,shrimp,milk,and cod (positive rates were 32.5％,26.0％,19.8％,13.8％ and 12.0％,respectively).Positive association rules were found in crab and shrimp,or milk and eggs.Single order association was found in female,while multi-order association was identified in male.Conclusions Our data show a strong positive association among animal foods.Female may be affected by milk,eggs and seafood,while male may be affected by a variety of foods.

Human enterovirus 71 (EV71) is one of the major etiological agents for the hand, foot, and month disease (HFMD) and is causing frequent, widespread occurrence in the mainland of China. The single positive-stranded RNA genome of EV71 is translated into a single polyprotein which is autocleavaged into structural and nonstructural proteins. The functions of many nonstructural proteins characterized in the life cycle of virus are potential targets for blocking viral replication. This article reviews the studies of the structures and functions of nonstructural proteins of EV71 and the anti-enterovirus 71 drugs targeting on these nonstructural proteins.

Objective To evaluate food intolerance sensitivity among 2962 health check-up receivers from the First Hospital of China Medical University.Methods Serum samples of 2962 adults were collected from January 2008 to June 2010.Serum allergen-specific IgG antibodies of 14 kinds of food were detected by ELISA.The data were analyzed by using One-way analysis of variance.Results In this study,the rate of food intolerance was 0.4%(mushrooms) to 38.0%(eggs).Higher rates of food intolerance were found in egg,crab,shrimp,milk,and cod fish(Eggs 32.5%,crabs 26.0%,shrimps 19.8%,milk 13.8%,and cod fish 12.0% respectively).However,wheat,pork,and mushroom showed relatively lower rates of food intolerance(Wheat 0.8%,pork 0.4%,and mushrooms1.4% respectively).Positive reaction to food intolerance was even stronger in women(9.4% versus 8.2%).Conclusion It is discovered by study that in general population,the diversity of intolerance among different food is associated with 4 factors: gender; age; feature of food; individual diversity.It is recommended that the status of intolerance to food in the general population be investigated by health management.