Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective:To explore the effect of cholesterol on the expression of genes for matrix synthesis and degradation of human meniscal fibrochondrocytes and its mechanism.Methods:Meniscal tissue was taken from patients undergoing arthroscopic surgery to extract fibrochondrocytes. The cells were divided into a control group in which the normal cells were not processed, a positive control group in which interleukin-1 β was used to create a degeneration model, and 2 treatment groups which were subjected to treatment with 15 and 30 μg/mL cholesterol respectively. Safranin O staining, β-galactosidase staining and enzymic kits were used to detect the morphology and total cholesterol (TCH) content of meniscal fibrochondrocytes in the 4 groups. Immunofluorescence and western blot were used to detect the protein expression of type Ⅰcollagen precursor α1 (COL1A1) and type Ⅱ collagen precursor α1 (COL2A1). RT-qPCR was used to detect the mRNA expression of COL1A1, COL2A1, matrix metalloproteinase (MMP) 3, MMP9, MMP13, and genes related to cholesterol efflux pathways [like liver X receptor α (LXR α), ATP binding cassette transporter A1 (ABCA1) and ABCG1]. Results:There was no significant difference between the control and the positive control groups in the TCH content in human meniscal fibrochondrocytes ( P>0.05). The treatments with 15 and 30 μg/mL cholesterol resulted in significantly increased TCH contents in human meniscal fibrochondrocytes in the treatment groups ( P<0.05). Compared with the control group, the mRNA expression of LXR α, ABCA1 and ABCG1 was significantly decreased in the treatment groups ( P<0.05), and the meniscal fibrochondrocytes in the positive group and the treatment groups presented with a lower density, chaotic distribution and obvious signs of degradation. Compared with the control groups, the mRNA expression of matrix synthesis genes (COL1A1 and COL2A1) in the meniscal fibrochondrocytes was significantly inhibited while the mRNA expression of matrix degradation metalloenzymes (MMP3, MMP9 and MMP13) was significantly promoted ( P<0.05). Conclusion:Cholesterol may inhibit the cholesterol efflux pathways of meniscal fibrochondrocytes, and thus cause accumulation of cholesterol in the meniscal fibrochondrocytes, eventually leading to degeneration of meniscus.

In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

Objective To study the influence of precision medicine-based health education on cognitive level of disease knowledge,anxiety and depression in patients with gestational diabetes.Methods Toally 84 cases of gestational diabetes patients in our hospital from September 2014 to December 2015 were divided into a study group and a control group according to the random number table,42 cases in each group.While the routine nursing intervention was done in the control group,the precision medicinebased health education program was carried out in the study group.The two groups were assessed using the cognitive questionnaire designed by our hospital.The self rating anxiety scale (SAS) and self rating depression scale (SDS) prepared by Zung were used to assess the levels of anxiety and depression in the two groups before the intervention and two weeks after the intervention.Results The cognitive level of disease knowledge in the study group after the intervention was statistically significantly higher than that of the control group (P＜0.05).Before the intervention,there were statistically insignificant differences in anxiety and depression between the two groups (P＞0.05),but after the intervention,the levels of anxiety and depression in the study group were significantly lower than those of the control group (P＜0.05).Conclusion The precision medicine-based health education is helpful for the patients with gestational diabetes to improve their diabetes-related knowledge and meanwhile it can relieve their anxiety and depression.

BACKGROUNDThe prevalence of thyroid nodules (TN) is increasing rapidly. This study analyzed the epidemiological and clinical characteristics of TN in surgically treated patients and identified the risk factors for malignant nodules (MN) to provide more understanding of the differential diagnosis of TN.

METHODSA total of 6 304 TN cases who underwent thyroid surgery were included in this retrospective study. The clinical data were collected to evaluate the clinical and epidemiological characteristics and related risk factors for MN. The nature of TN (benign nodules (BN) or MN), medical records, laboratory data, and imaging data were analyzed. The risk factors for MN were screened using Spearman's rank correlation analysis and nonconditional binary Logistic regression analysis.

RESULTSThe number of surgically treated TN cases increased yearly. A total of 34.33% of cases were MN and 65.67% were BN. Up to 56.74% of these cases underwent unnecessary surgery. Among the MN cases, papillary thyroid carcinoma accounted for 94%, in which 46.71% coexisted with benign thyroid disease and 32.28% with multiple foci. Single-related factor analysis showed that age, employment, disease duration, history of breast nodules and/or hypertension, the levels of serum thyroid-stimulating hormone (TSH), thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPoAb), and ultrasound features of TN were related to MN. Stepwise nonconditional binary Logistic regression analysis showed that 13 factors may be the independent risk factors for MN, including <40 years old, previous history of breast nodules and/or hypertension, disease duration <1 month, employment, hypoechoic nodule, irregular nodules, nodule calcification, solid echo nodule, fuzzy boundary, rich blood flow within nodules, abnormal lymph nodes around the neck, nodule diameter <1 cm, and abnormally high TgAb.

CONCLUSIONSOur results demonstrate a rapid increase in surgically treated TN cases and ratio of MN and indicate unnecessary surgeries in some cases. This study also suggest that age, duration of thyroid disease, history of breast disease and/or hypertension, the levels of serum TSH, TgAb, and TPoAb, and ultrasound features of TN are related to MN, and some of these factors may be the risk factors for MN.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Thyroid Neoplasms ; epidemiology ; Thyroid Nodule ; epidemiology

Objective To investigate the significance of hypoxia inducible factor-1(HIF-1) expression in ovarian endometriosis (Oems). Methods Elivision Tm plus Immunohistochemical and Stereology methods were used to detect HIF-1 expression in 30 cases of ectopic endometrium, 30 cases of eutopic endometrium in ovarian endometriosis and 30 cases of endometrium in ovarian teratoma as the normal control. Quantitative images analysis was performed with the aid of computer to collect and analyze the mean optical density (MOD) of HIF-1 expression. Results The MOD values of HIF-1 in ectopic and eutopic endometrium of Oems and the normal control were 0. 077 ± 0. 014, 0. 070 ± 0. 013 and 0. 061 ± 0. 007 respectively, which showed significantly differences between each other groups(F = 37. 738, P ＜ 0. 01 ＝. HIF-1 expression in proliferative phase (0.076 ±0.007) of eutopic endometrium of Oems was significantly higher than that in secretary phase (0. 059 ±0. 014) (t = 6. 918 ,P ＜0. 01 ＝; which was also significantly higher than that of the normal control in the same phase (0.060±0.007) (t=-12.724,P ＜0.01 ＝.Conclusion HIF-1 may play an important role in the pathogenesis and development of Oems.

Objective To assess the surgical effectiveness of pelvic endometriosis (EMS) by Laparoscopic. Methods Retrospective analysis was performed in 1272 pelvic EMS patients underwent laparoscopic surgical treatment. All patients were classified into four groups according to the R-AFS,63 patients of Ⅰ stage,44 patients of Ⅱ stage,475 patients of Ⅲ stage and 690 patients of Ⅳ stage. Symptoms of EMS,surgical effect and follow-up outcomes were compared. Results In all stages, there were no significant differences on moderate to severe dysmenorrhea,increase in CA125 and infertility (Ps ＞ 0. 05 ). In the EMS patients combined with AM or/and DIE, the rates of the moderate to severe dysmenorrhea, CA125 increase and infertility were 84.6% (11/13 ) ,92.3 %(12/13) and 53.8% (7/13)in stage Ⅰ ,81.8% (9/11) ,90. 9% ( 10/11 )and 54.5% (6/11) in stage Ⅱ ,84.8%(173/204) ,93. 1% (190/204) and 47.1% (96/204) in stage Ⅲ ,and 81.6% (213/261) ,91.2% (238/261) and 46.4% ( 121/261 ) in stage Ⅳ, respectively. The rates in non-consolidated AM or/and DIE patients were 46.0%(23/50),62.0% (31/50) and 22.0% ( 1 1/50) in stage Ⅰ ,45.5 % ( 15/33 ),54.5% ( 18/33 ) and 18.2% (6/33)in stage Ⅱ ,41.7% ( 113/271 ) ,62.7% ( 165/271 ) and 23.6% (64/271) in stage Ⅲ ,and 47.3% (203/429),60.1% (248/429) and 21.7% (93/429). The difference between the two groups with and without consolidated AM or/and DIE had statistical significance( P ＜ 0.05 or P ＜ 0.01 ). After the treatment, the scores of life's energy, ache,emotion,sleep,social activity and body movement of NHP were significantly superior than those before treatment in all patients ( P ＜ 0.01 ). The surgery time-consuming of Ⅲ and Ⅳ stage patients were (64.5 ± 18.4) min and (61.7 ± 17.1 ) min respectively, which were significantly higher than that of Ⅰ and Ⅱ stage ( ( 31.9 ± 12.3 ) min and (40.3 ± 10. 6) main ] ( t = 20.25, P ＜ 0.01 ). The massive hemorrhages and the internal damage organs occurred in Ⅲ and Ⅳ stage surgery [2.9% and 3.5% ,respectively] ,whereas much less in Ⅰ and Ⅱ stage (0.8% and 1.4% ) ,with no significant difference(P ＞0. 05). After treatment,the rate of symptoms recurrence of Ⅲ and Ⅳ stage patients respectively were 21.4% ,which were higher than that of Ⅰ and Ⅱ stage patients ( 2.3% ) (P ＜ 0.05 )The rate of pregnancy in Ⅲ and Ⅳ stage patients ( 15.4% ) were lower than that of Ⅰ and Ⅱ stage patients (69. 6% ) ( P ＜ 0. 01 ). Conclusions Pelvic EMS decreased the quality of life. EMS patients combined with adenomyosis or/and deep infiltrating EMS have more severe pelvic pain symptoms, less surgical effectiveness and more serious complications. Ⅲ and Ⅳ stage patients are more liable to symptoms recurrence and lower pregnancy rate.