Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.
Male ; Humans ; Female ; Biomarkers, Tumor/analysis* ; Gastrointestinal Neoplasms/pathology* ; S100 Proteins/analysis* ; Melanoma

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.
Humans ; Neuroendocrine Tumors ; Pituitary Neoplasms/pathology* ; Pituitary Hormones ; Growth Hormone/metabolism* ; Keratins

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype-phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.
Humans ; Phenotype ; Wnt Proteins

In previous studies, a Trichinella spiralis serine protease (TsSP) was identified in excretion/secretion (ES) products from intestinal infective L1 larvae (IIL1) using immunoproteomics. The complete cDNA sequence of TsSP gene was 1372 bp, which encoded 429 amino acids with 47.55 kDa. The TsSP was transcribed and expressed at all T. spiralis life cycle phases, as well as mainly located at the cuticle and stichosome of the parasitic nematode. Recombinant TsSP bind to intestinal epithelial cells (IEC) and promoted larva invasion, however, its exact function in invasion, development and reproduction are still unknown. The aim of this study was to confirm the biological function of TsSP during T. spiralis invasion and growth using RNA interference (RNAi) technology. The results showed that on 1 day after electroporation using 2.5 µM siRNA156, TsSP mRNA and protein expression of muscle larvae (ML) was suppressed by 48.35 and 59.98%, respectively. Meanwhile, silencing of TsSP gene by RNAi resulted in a 61.38% decrease of serine protease activity of ML ES proteins, and a significant reduction of the in vitro and in vivo invasive capacity of IIL1 to intrude into the IEC monolayer and intestinal mucosa. When mice were infected with siRNA 156-transfected larvae, adult worm and muscle larva burdens were decreased by 58.85 and 60.48%, respectively. Moreover, intestinal worm growth and female fecundity were evidently inhibited after TsSP gene was knockdown, it was demonstrated that intestinal adults became smaller and the in vitro newborn larval yield of females obviously declined compared with the control siRNA group. The results indicated that knockdown of TsSP gene by RNAi significantly reduced the TsSP expression and enzymatic activity, impaired larvae intrusion and growth, and lowered the female reproductive capacity, further verified that TsSP might participate in diverse processes of T. spiralis life cycle, it will be a new prospective candidate molecular target of anti-Trichinella vaccines.

Family-based cohort study is a special type of study design, in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted. Family-based cohort study can be applied to explore the effect of genetic factors, environmental factors, gene-gene interaction, and gene-environment interaction in the etiology of complex diseases. This paper summarizes the objectives, methods and results, as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.
China/epidemiology* ; Chronic Disease/ethnology* ; Cohort Studies ; Female ; Gene-Environment Interaction ; Humans ; Male ; Middle Aged ; Noncommunicable Diseases/ethnology* ; Research Design ; Rural Population

Objective: To explore the association between fatty liver and type 2 diabetes mellitus (T2DM) in the baseline-population of Jinchang cohort study. Methods: Data from all the participants involved in the baseline-population of Jinchang cohort study was used, to compare the risks of T2DM in fatty liver and non fatty liver groups and to explore the interaction between family history or fatty liver of diabetes and the prevalence of T2DM. Results: Among all the 46 861 participants, 10 574 were diagnosed as having fatty liver (22.56%), with the standardized rate as 20.66%. Another 3 818 participants were diagnosed as having T2DM (8.15%) with standardized rate as 6.90%. The prevalence of T2DM increased in parallel with the increase of age (trend χ(2)=2 833.671, trend P<0.001). The prevalence of T2DM in the fatty liver group was significantly higher than that in the non-fatty liver group, both in men or women and in the overall population. Compared with the group of non-fatty liver, the risks of T2DM in fatty liver group were seen 1.78 times higher in males, 2.33 times in women and 2.10 times in the overall population, after adjustment for factors as age, levels of education, smoking, drinking, physical exercise, BMI, family history of diabetes and some metabolic indicators (pressure, TC, TG, uric acid, ALT, AST, gamma-glutamyl transferase). Date from the interaction model showed that fatty liver and family history of diabetes present a positive additive interaction on T2DM (RERI=1.18, 95%CI: 0.59-1.78; AP=0.24, 95%CI: 0.14-0.34; S=1.43, 95%CI: 1.21-1.69). Conclusions: Fatty liver could significantly increase the risk of T2DM and a positive additive interaction was also observed between fatty liver and family history of diabetes on T2DM. It was important to strengthen the prevention program on T2DM, in order to effectively control the development of fatty liver.
China/epidemiology* ; Cohort Studies ; Diabetes Mellitus, Type 2/ethnology* ; Fatty Liver/ethnology* ; Female ; Humans ; Male ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Prevalence ; Risk Factors

Objective: To explore the developmental characteristics of circadian rhythms in hypothalamus-pituitary-adrenal (HPA) axis during puberty. Methods: A total of 1 070 students from Grade 2-3 in 3 primary schools in Ma'anshan city, Anhui province, were selected for physical examination and circadian rhythm of HPA axis checked from 2015 to 2017. Saliva samples were collected at each of the following three time points: immediately upon wakening, 30 minutes after wakening and bedtime, with the index of circadian rhythm of HPA axis calculated, which including cortisol awake response (CAR), cortisol in puberty priming and diurnal cortisol slope (DCS). Testicular volume, palpation and visual inspection of breast development were used to assess the state of purbety development on boys and girls. Information on gender, date of birth, time to fall asleep, wake-up time and weekly physical activity were gathered through questionnaire survey. Non-parametric test was used to compare the differences of baseline, follow-up period and different adolescent developmental processes of each index on circadian rhythm of HPA axis. Results: During the period of follow-up program and comparing with the continuous undeveloped group, CAR and the changes of CAR showed significantly increase, both in the puberty priming group and continuous development group, with statistically significant differences (CAR: Z=8.551, 4.680, respectively; P<0.01; the changes of CAR: Z=4.079, 2.700, respectively, P<0.01). There were no significant differences noticed in CAR and the changes of CAR between puberty priming group or continuous development group. The area under the curve (AUC) of cortisol in puberty priming group was slightly higher than that in the persistent undeveloped group (Z=2.591, P=0.010). Both the changes of daily cortisol slope (DCS) in puberty priming group and continuing developed group decreased significantly, when comparing with those in continuous undeveloped group (Z=-2.450, Z=-2.151; all P<0.05). There was no significant difference noticed in the changes of cortisol in puberty priming and DCS between different puberty development stages (the changes of AUC: χ(2)=2.747, P=0.253; DCS: χ(2)=4.554, P=0.032). Conclusions: The indexes of circadian rhythm of HPA axis were associated with the development of puberty. Both the cortisol awakening response and the total amount of diurnal cortisol secretion showed an increase, along with the puberty development. The change of diurnal cortisol slope declined with the development of puberty.
Adolescent ; Area Under Curve ; Circadian Rhythm ; Female ; Humans ; Hydrocortisone ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Pregnancy ; Saliva ; Sexual Maturation/physiology* ; Surveys and Questionnaires ; Wakefulness

Objective: To describe the situation of insufficient sleep and the association between insufficient sleep and physical exercise, among Chinese Han students aged 9-18 years. Methods: We selected 172 197 Chinese Han students aged 9-18 years from the project 2014 Chinese National Survey on Students Constitution and Health. The average sleep duration per day of less than 9 h for children aged 9-12 years and of less than 8 h for adolescents aged 13-18 years, were defined as insufficient sleep. We described the distribution of sleep duration and the prevalence rates of insufficient sleep for each subgroup. Logistic regression models were established to assess the association between insufficient sleep and physical exercise. Results: In 2014, 6.6%, 30.8%, 26.3%, 20.8%, 13.8% and 1.8% of the Chinese Han students self-reported sleep duration were <6, 6-, 7-, 8- and ≥10 h, respectively. The overall prevalence rate of insufficient sleep was 77.2%, with 75.8% for boys and 78.6% for girls. No gender disparity was found at each 9-11 age groups. However, in the 12-18 age groups, the prevalence rates for girls were significantly higher than that for boys. The prevalence rates of insufficient sleep for primary school, middle school and high school students were66.6%, 74.1% and 93.8%, respectively. Rates were increasing with age for children aged 9-12 years and adolescents aged 13-18 years respectively. The three provinces with the lowest prevalence rates of insufficient sleep were Zhejiang (68.8%), Jiangsu (66.7%) and Shaanxi (65.2%). Data from the logistic regression models revealed that, when comparing to those students with only exercise of <0.5 h per day, the exercise hours of 0.5-1 h (OR=0.72, 95%CI: 0.69-0.74) or ≥1 h (OR=0.46, 95%CI: 0.44-0.47) per day seemed as protective factors for insufficient sleep. When compared with physical exercise frequency <2 times per week, the 2 times (OR=0.82, 95%CI: 0.78-0.86) or >2 times (OR=0.65, 95%CI: 0.62-0.68) frequencies also appeared as protective. Conclusions: The prevalence rate of insufficient sleep prevailing among students aged 9-18 years was high, in China. Our data called for setting up effective measures to deal with this situation.
Adolescent ; Asian People/statistics & numerical data* ; Child ; China ; Exercise ; Female ; Humans ; Male ; Schools ; Sleep ; Sleep Deprivation ; Students ; Surveys and Questionnaires

Objective: To carry out a quantitative estimate that related to the effects of short-term exposure to PM(2.5) on all-cause mortality and emergency visits in China by using the systematic review and Meta-analysis. Methods: We selected all the studies published before March 2018 from China National Knowledge Infrastructure, Wanfang database, PubMed and EMBASE and data on relative risk (RR), excess risk (ER) and their 95%CIs: appeared in these papers were extracted. According to the differences in the size or direction (heterogeneity) of the results, we computed summary estimates of the effect values using a random-effect or fixed effect model. We also conducted the subgroup analysis and Meta-analysis to have assessed the selected studies for the evidence of study bias. Results: A total of 33 original studies, indexed in databases, were identified. Among those studies, 39 sets of data on mortality and 4 sets of data on emergency were valid to show that within the daily concentration range from 47.7 to 176.7 μg/m(3), for 10 μg/m(3) increases in PM(2.5) concentrations, it would increase the daily numbers of deaths by 0.49% (95%CI: 0.39%-0.59%) and 0.30% (95%CI: 0.10%-0.51%) for all-cause deaths and all-cause emergency-room visits, respectively. For subgroup analysis, the combined effect of PM(2.5) in causing short-term all-cause deaths in the northern areas (ER=0.42%, 95%CI: 0.30%-0.54%) seemed lower than that in the southern areas (ER=0.63%, 95%CI: 0.44%-0.82%). The combined effect of PM(2.5) concentration below 75 μg/m(3) (ER=0.50%, 95%CI: 0.37%-0.62%) was higher than that of PM(2.5) concentration ≥75 μg/m(3) (ER=0.39%, 95%CI: 0.26%-0.52%). Conclusion: Within the concentration range from 47.7 to 176.7 μg/m(3), short-term exposure to current level of PM(2.5) might increase both the all-cause daily mortality and daily emergency visits in China.
Air Pollutants ; Air Pollution/statistics & numerical data* ; China ; Databases, Factual ; Emergency Service, Hospital/statistics & numerical data* ; Environmental Exposure/statistics & numerical data* ; Female ; Humans ; Male ; Particulate Matter/toxicity* ; Time Factors