Zhu H.-D.,Nanjing Southeast University |
Guo J.-H.,Nanjing Southeast University |
Mao A.-W.,Shanghai St Lukes Hospital |
Lv W.-F.,Interventional Imaging |
And 19 more authors.
The Lancet Oncology | Year: 2014
Background: The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. Methods: In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with 125iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. Findings: Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0·0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). Interpretation: In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with 125iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent. Funding: National High-tech Research Foundation of China, National Basic Research Program of China, Jiangsu Provincial Special Program of Medical Science, National Scientific and Technical Achievement Translation Foundation, and National Natural Science Foundation of China. © 2014 Elsevier Ltd.
Qiu Y.-L.,Women and Childrens Hospital of Suqian |
Zhu H.,Suqian Peoples Hospital |
Ma S.-G.,Xuzhou Medical College |
Liu H.,Xuzhou Medical College |
And 2 more authors.
Journal of Pediatric Endocrinology and Metabolism | Year: 2015
Objective: To investigate well-controlled congenital hypothyroidism on the markers associated with early kidney injury and oxidative DNA damage. Methods: Twenty-three children with euthyroid congenital hypothyroidism aged 3-6 years and 19 age- and gender-matched controls were enrolled. Serum levels of albumin, C-reactive protein, cysteine C, globulin, pre-albumin, and total protein were detected. Urine levels of albumin, fibrin degradation products, IgG, β2-microglobulin, and 8-hydroxydeoxyguanosine (8-OHdG) were also measured. Clinical and biochemical characteristics were evaluated between the two groups. Results: Serum levels of C-reactive protein were higher, but pre-albumin was lower in patients with congenital hyperthyroidism compared with the controls (all p<0.001). Urinary levels of IgG were higher in patients with congenital hyperthyroidism than in the controls (p=0.011). However, urinary levels of albumin excretion and 8-OHdG were similar to those in the controls. Serum pre-albumin levels were negatively correlated with urinary 8-OHdG levels (r=-0.479, p=0.016) in patients with congenital hypothyroidism. Conclusion: It is concluded that inflammatory and oxidative markers were slightly altered in well-controlled congenital hypothyroidism. The levels of urinary 8-OHdG and albumin excretion were not significantly different. © 2015 by De Gruyter.
Fan H.,Nanjing Southeast University |
Liu D.,Nanjing Southeast University |
Liu D.,Suqian Peoples Hospital |
Qiu X.,Nanjing Southeast University |
And 7 more authors.
BMC Medicine | Year: 2010
Background: DNA-methyltransferase (DNMT)-3A plays an important role in the development of embryogenesis and the generation of aberrant methylation in carcinogenesis. The aim of this study was to investigate the role of a DNMT3A promoter genetic variant on its transcriptional activity and to evaluate the association between DNMT3A gene polymorphism and the susceptibility to gastric cancer (GC) and oesophagus carcinoma (EC) in the Chinese population.Methods: We selected one of the single nucleotide polymorphisms (SNPs) -448A>G in the DNMT3A promoter region and evaluated its effect on activity using a luciferase assay. -448A>G polymorphisms of DNMT3A were determined by polymerase chain reaction/restriction fragment length polymorphism and confirmed by sequencing. The distribution of -448A>G polymorphisms was detected in 208 GC patients and 346 healthy controls matched for age and gender. The distribution of -448A>G polymorphisms was also detected in 96 EC patients and matched 241 healthy controls. The association of -448A>G polymorphisms of DNMT3A and the risk of GC and EC was evaluated by stratified analysis according to the patient's age and gender.Results: In a promoter assay, carriage of the -448 A allele showed a significantly higher promoter activity (> two fold) compared with the -448G allele (P < 0.001). The allele frequency of -448A among GC patients and controls was 32.9% versus 19.9%, respectively. Overall, we found that, compared with GG carriers, the DNMT3A -448AA homozygotes has a > six fold increased risk of GC. Stratification analysis showed that AA homozygotes have a more profound risk in the subgroups of individuals at the age range ≤ 60 years in GC. However, individuals with -448AG and -448AA were not statistically significantly associated with an increased risk of EC compared with those carried the -448GG genotype.Conclusions: The DNMT3A -448A>G polymorphism is a novel functional SNP and contributes to its genetic susceptibility to GC. -448A>G can be used as a stratification marker to predict an individual's susceptibility to GC, especially in the subgroups of individuals at the age range ≤ 60 years. However, the relative distribution of -448A>G in EC can not be used as a prediction marker in order to evaluate an individual's susceptibility to EC. © 2010 Fan et al; licensee BioMed Central Ltd.
PubMed | Suqian Peoples Hospital, Ningxia Medical University, No 215 Hospital and Taian Hospital of Traditional Chinese Medicine
Type: Journal Article | Journal: Nutrition journal | Year: 2016
To study the association between the expression of H3K27me3 and ACat2 (a folate metabolic protein), in order to elucidate the protective mechanism of folic acid (FA) in neural tube defects (NTDs).Eighteen female SD rats were randomly divided into normal, NTD and FA group. NTD group was induced by all-trans retinoic acid (ATRA) at E10d. FA group was fed with FA supplementation since 2weeks before pregnancy, followed by ATRA induction. At E15d, FA level in the embryonic neural tube was determined by ELISA. Neural stem cells (NSCs) were isolated. Cell proliferation was compared by CCK-8 assay. The differentiation potency was assessed by immunocytochemical staining. H3K27me3 expression was measured by immunofluorescence method and Western blot. ACat2 mRNA expression was detected by qRT-PCR.Cultured NSCs formed numerous Nestin-positive neurospheres. After 5days, they differentiated into NSE-positive neurons and GFAP-positive astrocytes. When compared with controls, the FA level in NTD group was significantly lower, the ability of cell proliferation and differentiation was significantly reduced, H3K27me3 expression was increased, and ACat2 mRNA expression was decreased (P <0.05). The intervention of FA notably reversed these changes (P <0.05). H3K27me3 expression was negatively correlated with the FA level (rs=-0.908, P <0.01) and ACat2 level (rs=-0.879, P <0.01) in the neural tube.The increased H3K27me3 expression might cause a disorder of folate metabolic pathway by silencing ACat2 expression, leading to reduced proliferation and differentiation of NSCs, and ultimately the occurrence of NTD. FA supplementation may reverse this process.
Yin H.,Central University of Costa Rica |
Zhou Y.,Central University of Costa Rica |
Wen C.,Central University of Costa Rica |
Zhou C.,Central University of Costa Rica |
And 5 more authors.
Oncology Reports | Year: 2014
Temozolomide (TMZ), a DNA alkylating agent, represents the most important chemotherapeutic option for the treatment of glioblastoma in the clinic. Despite its frequent use, the therapeutic efficacy of TMZ remains very limited due to its frequent resistance in glioblastoma. Previous evidence suggested that curcumin (CUM), an ingredient of the Indian spice turmeric, is able to sensitize glioblastoma to TMZ treatment. However, the underlying molecular mechanism remains elusive. In the present study, we performed in vitro and in vivo experiments to evaluate the interaction of CUM and TMZ on the inhibition of glioblastoma and to investigate its potential mechanisms of action using U87MG cell lines and xenograft mouse models. We demonstrated that CUM enhanced the therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis. We then proceeded to investigate the potential apoptotic signaling pathways that are involved. We observed a synergistic effect of the combination of CUM and TMZ in generating reactive oxygen species (ROS) production, suggesting that ROS may contribute to the impact of CUM on sensitizing TMZ treatment. We also showed that CUM and TMZ treatment alone significantly suppressed phosphorylated AKT and mTOR, whereas their combination achieved a more pronounced inhibitory effect. These data indicated that blockage of AKT/mTOR signaling appeared to contribute to the elevated apoptosis caused by the combination treatment with CUM and TMZ. In conclusion, this study provided molecular insights into the effects of CUM on the therapeutic response of glioblastoma to TMZ and opened new avenues for optimizing the therapeutic effects of TMZ-based therapies.
Pan F.,Nanjing Medical University |
Dong H.,Nanjing Medical University |
Ding H.,Nanjing Medical University |
Ye M.,Nanjing Medical University |
And 6 more authors.
Parkinsonism and Related Disorders | Year: 2012
Background: Over the last decades, increasing knowledge about the genetic architecture of Parkinson's disease(PD) has provided novel insights into the pathogenesis of the disorder. Recently, several studies in different populations have found a strong association between idiopathic PD and the single-nucleotide polymorphism (SNP) rs356219, which is located in the 3'UTR of the SNCA gene. In this study, we aimed to verify these findings and to explore further the nature of the association in a subset of Chinese Han PD patients. Methods: Four hundred and three unrelated patients with sporadic PD and 315 healthy ethnically matched control subjects were recruited consecutively for the study. Patients and normal controls were genotyped for SNCA rs356219 variant by ligase detection reaction (LDR). Results: A statistically significant difference was found in the frequencies of the single alleles of rs356219 (χ 2 = 12.986,P = 0.002) between PD patients and normal subjects. The distribution of A > G genotypes was different between patients and controls (χ 2 = 13.243, P < 0.001). The OR for subjects with the variant genotypes (AG and GG) was 1.88 (95%CI = 1.27-2.78, P = 0.001). The frequencies of the homozygous genotype for this variant was 42.2% (170 patients), which was significantly higher than that in controls (32.4%, P < 0.001). Conclusion: The results suggested that SNCA rs356219 variant might have an increased risk of susceptibility to PD in a Chinese Han population. Further studies are needed to replicate the association that we found. © 2012 Elsevier Ltd.
PubMed | Suqian Peoples Hospital and Nanjing Medical University
Type: Journal Article | Journal: International psychogeriatrics | Year: 2016
This is a case-control study to investigate the prevalence, characteristics, and risk factors of pain in patients with Parkinsons disease (PD).A total of 200 PD patients from eastern China were enrolled in our study. Accordingly, 200 healthy elderly adults were recruited as controls. The characteristics of pain were collected by using the Visual Analog Scale, Brief Pain Inventory (BPI), SF-36 Bodily Pain Scale, Unified Parkinsons Disease Rating Scale, Hoehn-Yahr Scale (H-Y), Hamilton Depression Scale, and Leeds Assessment of Neuropathic Symptoms and Signs.Of the 200 PD patients, pain was complained by 106 patients (53%). According to the SF-36 Bodily Pain Scale, pain morbidity in PD patients was significantly higher than in the control group. The average pain during last 24 h measured by the BPI was 2.67. About 76% of PD patients were found to have one pain type, 21.7% were having two pain types, and 1.9% had three pain types. Further, 69.8% of these patients were presented with musculoskeletal pain, 4.7% with dystonic pain, 22.6% with radicular-neuropathic pain, 20.8% with central neuropathic pain, and 9.4% with akathisia pain. The onset age and depression were the most significant predictors of pain in PD patients (p < 0.05). However, there was no significant association between pain and gender, age, disease duration, or severity of the disease. Only 5.7% of PD patients with pain received treatment in this study.Pain is frequent and disabling, independent of demographic and clinical variables, and is significantly more common in PD patients.
PubMed | Suqian Peoples Hospital and Zhejiang University
Type: Journal Article | Journal: Endocrine | Year: 2016
Recent animal studies support close associations of Periostin with hepatosteatosis and steatohepatitis. This study is to evaluate the role of serum periostin in non-alcoholic fatty liver disease (NAFLD). A hospital-based age-/sex-matched case-control study was conducted. Binary logistic regression and receiver operating characteristic (ROC) curve were performed. Serum adipokines were measured by Adipokine Magnetic Bead Panel kits. The serum concentration of Periostin in NAFLD (1914.16 [1323.59-2654.88] ng/ml, P < 0.001) was higher than it in control (1244.94 [837.87-2028.55] ng/ml). The frequency of NAFLD grew (29.8, 52.6, and 67.2%, P < 0.001), as Periostin concentration increased among its tertiles. Compared with the 1st tertile, the 2nd and the 3rd tertiles of Periostin indicated significant associations with higher odds of NAFLD [adjusted odds ratio = 2.602 (95% confidence interval (CI) 1.030-6.575), P = 0.043 and 2.819 (95% CI 1.629-4.878), P < 0.001]. ROC curve of Periostin was developed to predict the presence of NAFLD (area under ROC = 0.693 [95% CI 0.614-0.771], P < 0.001). Lastly, Periostin correlated with several adipokines, including Resistin (r = 0.269, P = 0.018), Adiponectin (r = -0.352, P = 0.002), Interleukin (IL)-6 (r = 0.359, P = 0.001), IL-8 (r = 0.364, P = 0.001), Lipocalin-2 (r = 0.623, P < 0.001), Hepatocyte growth factor (r = 0.522, P < 0.001), and Nerve growth factor (r = 0.239, P = 0.036). It suggests Periostin as a potential biomarker in the management of NAFLD.
Zhu H.,Suqian Peoples Hospital |
Peng Y.-G.,Xuzhou Medical College |
Ma S.-G.,Xuzhou Medical College |
Liu H.,Xuzhou Medical College
Cancer Biomarkers | Year: 2015
BACKGROUND: The thyroperoxidase (TPO) genetic variants in thyroid carcinoma is scarcely reported. OBJECTIVE: We report on a pedigree of thyroid papillary carcinoma and hypoechoic thyroid nodules with the TPO gene mutations. METHODS: The compound heterozygotic mutations of the TPO gene (c.2268-2269 insT and c.2090 G>A) in two patients with congenital goiters hypothyroidism were demonstrated. Fifteen family members of the proband and 105 control individuals were enrolled. The participants underwent clinical examination and molecular screening for TPO mutation. The hypoechoic thyroid nodules underwent fine needle aspiration biopsy. RESULTS: The mutation c.2268-2269 insT was detected in the four family members with normal thyroid hormone levels. The other two members harbored the c.2090 G>A mutation. The heterozygotes had degeneratively hypoechoic thyroid nodules. The control individuals showed no mutation. The maternal grandfather developed a multifocal papillary thyroid carcinoma with lymph gland and nerve invasion in the left lobe of the thyroid gland. The maternal grandfather harbored the TPO c.2268-2269 insT mutation but without BRAFV600E mutation. Malignant cells were not observed in other members by fine needle aspiration biopsy. CONCLUSION: TPO genetic variants may be associated with thyroid carcinoma and hypoechoic thyroid nodules in a few cases. Long-term follow-up in the pedigree with congenital goiter is reasonable. © 2015 - IOS Press and the authors. All rights reserved.
PubMed | Suqian Peoples Hospital and Xuzhou Medical College
Type: Case Reports | Journal: Cancer biomarkers : section A of Disease markers | Year: 2015
The thyroperoxidase (TPO) genetic variants in thyroid carcinoma is scarcely reported.We report on a pedigree of thyroid papillary carcinoma and hypoechoic thyroid nodules with the TPO gene mutations.The compound heterozygotic mutations of the TPO gene (c.2268-2269 insT and c.2090 G>A) in two patients with congenital goiters hypothyroidism were demonstrated. Fifteen family members of the proband and 105 control individuals were enrolled. The participants underwent clinical examination and molecular screening for TPO mutation. The hypoechoic thyroid nodules underwent fine needle aspiration biopsy.The mutation c.2268-2269 insT was detected in the four family members with normal thyroid hormone levels. The other two members harbored the c.2090 G>A mutation. The heterozygotes had degeneratively hypoechoic thyroid nodules. The control individuals showed no mutation. The maternal grandfather developed a multifocal papillary thyroid carcinoma with lymph gland and nerve invasion in the left lobe of the thyroid gland. The maternal grandfather harbored the TPO c.2268-2269 insT mutation but without BRAFV600E mutation. Malignant cells were not observed in other members by fine needle aspiration biopsy.TPO genetic variants may be associated with thyroid carcinoma and hypoechoic thyroid nodules in a few cases. Long-term follow-up in the pedigree with congenital goiter is reasonable.