Objective To investigate the impact of subclinical hypothyroidism (SCH) on macrovascular complications in elderly type 2 diabetic patients.Methods A total of 1170 hospitalized elderly patients with type 2 diabetes mellitus were enrolled in the study through systematic sampling and underwent testing for blood biochemical indicators, thyroid function and C peptide.Parameters for macro-vascular complications, including the ankle/brachial index (ABI), transcranial Doppler vascular ultrasound (TCD), electrocardiogram (ECG), ejection fraction (EF), history of coronary heart disease, and hypertension grading were also monitored.Results All the subjects were divided into two groups based on the thyroid stimulating hormone (TSH) level: the euthyroid group (4 mU/L≥TSH＞0.4 mU/L) and the SCH group (TSH＞4 mU/L), and the latter was further sub-grouped into the mild SCH group (10 mU/L≥TSH＞4 mU/L) and the severe SCH group (TSH＞10 mU/L).ABI was significantly decreased in SCH (R/L: 0.86/0.92, P＜0.01).Levels of basal C-peptide (CP0) and post glucose-challenge C-peptide (CP1-3) were higher in the SCH group than in the euthyroid group [(2.16±0.93)pg/L vs.(1.56±1.05)pg/L, (0.53±0.25)pg/L v, (0.38±0.37),(0.72±0.23) pg/L vs.(0.56 ±0.32) pg/L, (6.21± 2.69) pg/L vs.(4.46 ± 2.62) pg/L,respectively, P＜0.01 for all].EF was higher in the SCH group than in the euthyroid group[(70.87± 6.66)％ vs.(65.10 ± 8.08％), P＜ 0.01].There were no significant differences in other biochemical indicators, ECG, TCD, history of coronary heart disease, hypertension grading and intervention treatment (P＞0.05 for all).Conclusions Lower extremity atherosclerotic disease has a higher incidence in elderly type 2 diabetic patients with SCH and occurs earlier than other macrovascular complications.Elevated TSH levels and insulin resistance may be the major causes.

Cytology in China developed from nothing and underwent a long journey from gynecologic cytology to that of all organs, laying a solid foundation for new developments in the 21st century. Thyroid fine-needle aspiration (FNA) was primarily developed in an endocrinology department and then in the clinical laboratory department or pathology department in the 1970–80s. Wrights staining is popular in endocrine and clinical laboratory departments, while hematoxylin and eosin staining is common in pathology. Liquid based cytology is not common in thyroid FNA cytology, while BRAF(V600E) mutation analysis has been the most popular molecular test. The history and practice of thyroid FNA practice in China were reviewed based on retrospective study of the practice in Qilu Hospital of Shandong University.
Biopsy, Fine-Needle* ; China* ; Endocrinology ; Eosine Yellowish-(YS) ; Hematoxylin ; Pathology ; Retrospective Studies* ; Thyroid Gland*

Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.

Objective: To investigate clinicopathological features of carcinoma showing thymus-like elements (CASTLE) in the head and neck regions. Methods: Clinicopathological data of 7 patients with CASTLE in the head and neck regions were retrospectively reviewed.Immunohistochemical staining and in situ hybridization for EBER were performed. BRAF^V600E mutation was examined by ARMS method in 6 cases. Results: There were 5 females and 2 males with age between 49 and 78 years (average of 65.6 years). All tumors were solitary nodular lesions with an infiltrative border, including 6 intrathyroid tumors and 1 extrathyroid tumor in the laryngeal pharynx.The tumors were 1.7-4.1 cm in diameter (average of 3.0 cm). Four cases demonstrated lymph node metastasis.All patients were alive without metastasis during follow-up, except one consultation case (with FNA sample) developed recurrence at the primary site. The cases showed different immunoreaction to CD5, diffuse immunoreaction with p63, CK5/6 and CD117, but negative staining for TTF1, TG and calcitonin. One case showed positive immunoreaction with Synin less than 30% tumor cells. The Ki-67 labeling index was between 3% and 90%. No BRAF^V600E mutation and EB virus infection were detected. Conclusions Extrathyroid CASTLE involving laryngeal pharynx shows the similar morphological and immunohistochemical features with intrathyroid CASTLE.Immunohistochemical markers of CD5 and CD117 are helpful in the diagnosis. Ki-67 labeling index can be high in CASTLE, especially in lymphoepithelioma type. CD5-negative CASTLE may have neuroendocrine differentiation. BRAF^V600E mutation and EB virus may not be involved in the carcinogenesis of CASTLE.

Objective:To identify the influencing factors of maternal anxiety, and explore the moderating role of co-parenting in the effect of marriage quality on maternal anxiety.Methods:Totally 522 mothers with children aged 0-12 were enrolled in the surveys and completed the Generalized Anxiety Disorder (GAD-7), Marital Adjustment Test and Co-parenting Relationship Scale.The chi-square test, the spearman correlation analysis and non-parametric percentile Bootstrap method were processed by SPSS 22.0.Results:①The detection rate of anxiety in the mothers was 48.7%, and the rate for mild, moderate, and severe anxiety was 37.4%, 8.4%, 2.9%, respectively.② The chi-square test showed that the family factors, such as mother's age, level of workload, family economic conditions, husband's level of workload, the child's age and health condition, as well as the conflicts between parents and grandparents and the grandparents’ willingness of involving in raising children, significantly affected mother’s anxiety(χ 2=4.292-23.170, P<0.05). ②The maternal anxiety was negatively correlated with marital quality ( r=-0.419, P<0.01). ③ Both positive co-parenting (PCP) and negative co-parenting(NCP) played moderating roles in the relationship between marriage quality and maternal anxiety( BPCP=0.013, P<0.01; BNCP=-0.010, P<0.05). Conclusion:Marital quality is an important factor which affects maternal anxiety, and father’s performance in co-parenting plays a moderating role in it.

Objective: To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC). Methods: The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed. Results: All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of β-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected. Conclusions CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and β-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment