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Open access

Zeming Liu, Di Hu, Yihui Huang, Sichao Chen, Wen Zeng, Ling Zhou, Wei Zhou, Min Wang, Haifeng Feng, Wei Wei, Chao Zhang, Danyang Chen and Liang Guo

Objectives

Controversies regarding factors associated with distant metastasis in pediatric thyroid cancer remain among the scientific community. The aim of this study was to investigate factors influencing distant metastasis in pediatric thyroid cancer.

Methods

We reviewed 1376 patients (aged 2 to 18 years) with thyroid cancer treated between 2003 and 2014. Data collected and analyzed included sex, race, age at diagnosis, year of diagnosis, pathological type, number of tumor foci, tumor extension, T-stage, N-stage, surgical procedure and radiation. Univariate and multivariate analyses were conducted to evaluate factors influencing distant metastasis of pediatric thyroid cancer.

Results

In the univariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P < 0.001), N-stage (P < 0.001), number of tumor foci (P = 0.003), tumor extension (P < 0.001) and T-stage (T1 vs T2 (P = 0.803), T3 (P < 0.001) and T4 (P < 0.001)). In multivariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P = 0.001), N-stage (P < 0.001) and T-stage (T1 vs T3 (P = 0.036) and T4 (P < 0.001)). Sex, race, year of diagnosis, pathological type, number of tumor foci, tumor extension, surgical procedure and radiation had no significant influence on distant metastasis (all P > 0.05). Furthermore, according to chi-squared test, younger pediatric thyroid cancer patients with higher T- and N-stages are more likely to have distant metastasis.

Conclusion

Age at diagnosis, T-stage and N-stage influence distant metastasis of thyroid cancer patients aged 2 to 18 years; accordingly, more radical treatments may need to be used for patients with those risk elements.

Open access

Rong Huang, Jun Zheng, Shengxian Li, Lihua Wang, Tao Tao, Xiangyu Teng, Jing Ma and Wei Liu

Open access

Changwei Liu, Jingwen Wang, Yuanyuan Wan, Xiaona Xia, Jian Pan, Wei Gu and Mei Li

Background

To investigate the relationship 25-hydroxy vitamin D (25OHD) level among children and in children with type 1 diabetes mellitus (T1DM).

Methods

A case–control study was conducted to compare the serum 25OHD levels between cases and controls. This study recruited 296 T1DM children (106 newly diagnosed T1DM patients and 190 established T1DM patients), and 295 age- and gender-matched healthy subjects as controls.

Results

The mean serum 25OHD in T1DM children was 48.69 ± 15.26 nmol/L and in the controls was 57.93 ± 19.03 nmol/L. The mean serum 25OHD in T1DM children was lower than that of controls (P < 0.01). The mean serum 25OHD level (50.42 ± 14.74 nmol/L) in the newly diagnosed T1DM children was higher than that (47.70 ± 15.50 nmol/L) in the established T1DM children but the difference was not statistically significant (P = 0.16). HbA1c values were associated with 25OHD levels in established T1DM children (r = 0.264, P < 0.01), and there was no association between 25OHD and HbA1c in newly diagnosed T1DM children (r = 0.164; P > 0.05).

Conclusion

Vitamin D deficiency is common in T1DM children, and it should be worthy of attention on the lack of vitamin D in established T1DM children.

Open access

Xuechao Jiang, Yonghui Wang, Xiaoying Li, Leqi He, Qian Yang, Wei Wang, Jun Liu and Bingbing Zha

B lymphocytes are the source of autoantibodies against the thyroid-stimulating hormone receptor (TSHR) in Graves’ disease (GD). Characterization of autoimmune B-cell expression profiles might enable a better understanding of GD pathogenesis. To reveal this, the expression levels of long noncoding RNAs (lncRNAs) and mRNAs (genes) in purified B cells from patients with newly diagnosed GD and healthy individuals were compared using microarrays, which elucidated 604 differentially expressed lncRNAs (DE-lncRNAs) and 410 differentially expressed genes (DEGs). GO and pathway analyses revealed that the DEGs are mainly involved in immune response. A protein–protein interaction network presented experimentally validated interactions among the DEGs. Two independent algorithms were used to identify the DE-lncRNAs that regulate the DEGs. Functional annotation of the deregulated lncRNA–mRNA pairs identified 14 pairs with mRNAs involved in cell proliferation. The lncRNAs TCONS_00022357-XLOC_010919 and n335641 were predicted to regulate TCL1 family AKT coactivator A (TCL1A), and the lncRNA n337845 was predicted to regulate SH2 domain containing 1A (SH2D1A). TCL1A and SH2D1A are highly involved in B-cell proliferation. The differential expression of both genes was validated by qRT-PCR. In conclusion, lncRNA and mRNA expression profiles of B cells from patients with GD indicated that the lncRNA–mRNA pairs n335641–TCL1A, TCONS_00022357-XLOC_010919–TCL1A, and n337845–SH2D1A may participate in GD pathogenesis by modulating B-cell proliferation and survival. Therefore, the identified lncRNA and mRNA may represent novel biomarkers and therapeutic targets for GD.

Open access

Qiuli Liu, Lin-ang Wang, Jian Su, Dali Tong, Weihua Lan, Luofu Wang, Gaolei Liu, Jun Zhang, Victor Wei Zhang, Dianzheng Zhang, Rongrong Chen, Qingyi Zhu and Jun Jiang

Congenital adrenal hyperplasia (CAH) is one of the most prevalent, and potentially severe, genetic inborn errors of steroid synthesis directly affecting metabolism. Most patients are diagnosed and treated at an early age. There have been very limited reports of adults with CAH-associated adrenal myelolipomas. We aimed to analyze two families with CAH-associated giant adrenal myelolipomas caused by defects in CYP21A2 and CYP17A1 genes. A total of 14 individuals from two unrelated families were identified with either CYP21A2 or CYP17A1 mutations. Of note, five patients were found with adrenal myelolipomas. Total DNA isolated from the peripheral blood of the two probands was screened for potential mutations in the following susceptibility genes of CAH: CYP21A2, CYP11B1, CYP17A1, HSD17B3, HSD3B2, ARMC5, and STAR using target capture-based deep sequencing; and Sanger sequencing was conducted for the family members to detect the potential mutations. The following results were obtained. In family 1, molecular genetics sequencing revealed a compound heterozygous mutation (c.293-13C>G/c.518T>A, p.I173N) in CYP12A2 in the patient and his brother. In family 2, all three female patients with adrenal myelolipomas were found to have a compound heterozygous mutation (c.1118A>T, p.H373L/c.1459_1467del9, p.D487_F489del) in CYP17A1. To avoid giant CAH-associated adrenal myelolipomas in adults, it is important to identify CAH early so that appropriate treatment can be initiated to interrupt the chronic adrenal hyperstimulation resulting from increased ACTH. Genetic testing and counseling could be useful in CAH.

Open access

Guoquan Zhu, Yuying Deng, Liqin Pan, Wei Ouyang, Huijuan Feng, Juqing Wu, Pan Chen, Jing Wang, Yanying Chen and Jiaxin Luo

The goal of this study was to explore the relationship of the BRAFV600E mutation with clinicopathologic factors and evaluate the effect of radioactive iodine (RAI) therapy in a large group of intermediate- and high-risk papillary thyroid cancer (PTC) patients with the BRAFV600E mutation and without distant metastases. We collected data for PTC patients who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2014–December 2017. There were 1220 PTC patients who met the criteria, and the BRAFV600E mutation was observed in 979 of them (80.2%). Multivariate analysis identified that the BRAFV600E mutation remained independently associated with age at diagnosis, and bilaterality (OR = 1.023, 95% CI = 1.012–1.039, P < 0.001; OR = 1.685, 95% CI = 1.213–2.341, P = 0.002, respectively). In addition, the patients with bilateral PTCs had a higher prevalence of extrathyroid invasion, capsular invasion and fusion of metastatic lymph nodes than the unilateral PTC patients. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk; no significant difference was discerned between the BRAFV600E mutation and the wild-type groups (P = 0.237 and P = 0.498, respectively). To summarize, our results confirmed that PTC patients with the BRAFV600E mutation exhibit more aggressive characteristics. In addition, the patients with bilateral PTC have a higher incidence of extrathyroid invasion. Moreover, BRAFV600E mutation PTC patients did not show a poorer clinical response after postsurgical RAI therapy, suggesting that RAI therapy may improve the general clinical outcome of these patients.

Open access

Weiwei He, Bin Wang, Kaida Mu, Jing Zhang, Yanping Yang, Wei Yao, Sheli Li and Jin-an Zhang

Background

Accumulating data have shown that interleukin-27 (IL27) polymorphisms are linked to the susceptibility of some autoimmune diseases. We assessed whether there was an association between three single-nucleotide polymorphisms (SNPs) of IL27 gene and autoimmune thyroid diseases (AITDs).

Methods

Three SNPs (rs153109, rs17855750 and rs181206) of IL27 gene were genotyped by Hi-SNP high-throughput genotyping in 843 patients with AITDs (516 Graves’ disease (GD) and 327 Hashimoto’s thyroiditis (HT)) and 677 healthy controls in Chinese Han population.

Results

Compared with controls, rs153109 displayed significant associations with GD in allele and genotype frequencies (P = 0.002 and P = 0.008, respectively) and rs17855750 displayed significant associations with HT in allele frequencies (P = 0.02), whereas no differences in genotype or allele frequencies were found between AITD patients and controls at rs181206.

Conclusion

Our study, for the first time, showed the significant association of the IL27 gene SNPs with AITD.

Open access

Wei Sun, Boyuan Zheng, Zhihong Wang, Wenwu Dong, Yuan Qin and Hao Zhang

Summary

Background

In patients with papillary thyroid cancer (PTC) with clinical negative central lymph nodes (cN0), the use of prophylactic central lymph node dissection remains controversial. Contralateral central lymph node metastasis (CCLNM) occurs in 3.88–30.63% of patients with cN0 PTC. Therefore, the present meta-analysis aimed to obtain evidence for CCLNM risk factors in unilateral cN0 PTC.

Materials and methods

Relevant studies were identified in the PubMed, SCIE, and Wanfang databases up to Oct 31, 2019. The included patients had undergone lobectomy or total thyroidectomy with bilateral central lymph node dissection and were diagnosed pathologically with PTC. Revman 5.3 software was applied for statistical analysis.

Results

Thirteen studies comprising 2449 patients were included. The factors associated with increased CCLNM risk in patients with cN0 disease were: age <45 years (odds ratio (OR) = 1.89, 95% CI = 1.43–2.49, P < 0.00001), male sex (OR = 1.67, 95% CI = 1.24–2.24, P = 0.0007), extrathyroidal extension (OR = 1.63; 95% CI = 1.17–2.28; P = 0.004), tumor size ≥1 cm (OR = 2.63, 95% CI 1.85–3.74, P < 0.00001), lymphovascular invasion (OR = 4.27, 95% CI = 2.47–7.37, P < 0.00001), and ipsilateral central lymph node metastasis (OR = 11.42, 95% CI = 5.25–24.86, P < 0.00001). However, no association was found for capsular invasion, multifocality, or Hashimoto thyroiditis.

Conclusion

The meta-analysis identified that age <45 years, tumor ≥1 cm, male sex, lymphovascular invasion, extrathyroidal extension, and ipsilateral central lymph node metastasis are related to CCLNM in patients with unilateral CN0 PTC. These factors should influence the use of prophylactic central lymph node dissection in this group of patients.

Open access

Yang Lv, Ning Pu, Wei-lin Mao, Wen-qi Chen, Huan-yu Wang, Xu Han, Yuan Ji, Lei Zhang, Da-yong Jin, Wen-Hui Lou and Xue-feng Xu

Aim

We aim to investigate the clinical characteristics of the rectal NECs and the prognosis-related factors and construct a nomogram for prognosis prediction.

Methods

The data of 41 patients and 1028 patients with rectal NEC were retrieved respectively from our institution and SEER database. OS or PFS was defined as the major study outcome. Variables were compared by chi-square test and t-test when appropriate. Kaplan–Meier analysis with log-rank test was used for survival analysis and the Cox regression analysis was applied. The nomogram integrating risk factors for predicting OS was constructed by R to achieve superior discriminatory ability. Predictive utility of the nomogram was determined by concordance index (C-index) and calibration curve.

Results

In the univariate and multivariate analyses, tumor differentiation, N stage, M stage and resection of primary site were identified as independent prognostic indicators. The linear regression relationship was found between the value of Ki-67 index and the duration of OS (P < 0.05). Furthermore, the independent prognostic factors were added to formulate prognostic nomogram. The constructed nomogram showed good performance according to the C-index.

Conclusions

Contrary to WHO classification guideline, we found that the rectal NEC diseases are heterogeneous and should be divided as different categories according to the pathological differentiation. Besides, the nomogram formulated in this study showed excellent discriminative capability to predict OS for those patients. More advanced predictive model for this disease is required to assist risk stratification via the formulated nomogram.

Open access

Jing Wang, Leishen Wang, Huikun Liu, Shuang Zhang, Junhong Leng, Weiqin Li, Tao Zhang, Nan Li, Wei Li, Andrea A Baccarelli, Lifang Hou and Gang Hu

Previous studies found conflicting results about the associations between the exposure to hyperglycemia in utero and the later risks of childhood overweight and obesity. The aim of the present study is to compare the children’s BMI growth between offspring exposed to maternal gestational diabetes mellitus (GDM) and those not exposed and assess the associations between maternal GDM and their offspring’s overweight and obesity risk. We performed a large observational study in 1156 women and their offspring (578 GDM and 578 non-GDM mother–child pairs, matched by their offspring’s gender and age). Maternal GDM was diagnosed according to the World Health Organization criteria. Childhood height, weight, waist circumference, body fat and skinfold were measured using standardized methods. After adjustment for maternal and children’s characteristics, children born to mothers with GDM during pregnancy had higher mean values of Z scores for BMI-for-age, Z scores for weight-for-age, waist circumferences, body fat, subscapular skinfold and suprailiac skinfold, in comparison with their counterparts born to mothers with normal glucose during pregnancy (all P values <0.05). Moreover, maternal GDM was associated with a higher risk of childhood overweight and obesity with multivariate-adjusted odds ratios of 1.42 (95% confidence interval (CI): 1.02–1.97) and 1.18 (95% CI: 1.11–1.24), respectively, compared with the children of mothers without GDM during pregnancy. This study demonstrates that maternal GDM is an independent risk factor of childhood overweight and obesity and is associated with higher BMI in the offspring.