Clinical features and prognostic factors of duodenal neuroendocrine tumours: A comparative study of ampullary and nonampullary regions.

BACKGROUND: Duodenal neuroendocrine tumours (DNETs) are rare neoplasms. However, the incidence of DNETs has been increasing in recent years, especially as an incidental finding during endoscopic studies. Regrettably, there is no consensus regarding the ideal treatment of DNETs. Even there are few studies on the clinical features and survival analysis of DNETs. AIM: To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours. METHODS: The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected. Neuroendocrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group; neuroendocrine tumours in any part of the duodenum outside the ampullary area were divided into the nonampullary region group. Using a retrospective study, the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed. RESULTS: Twenty-nine DNET patients were screened. The male to female ratio was 1:1.9, and females comprised the majority. The ampullary region group accounted for 24.1% (7/29), while the nonampullary region group accounted for 75.9% (22/29). When diagnosed, the clinical symptoms of the ampullary region group were mainly abdominal pain (85.7%), while those of the nonampullary region groups were mainly abdominal distension (59.1%). There were differences in the composition of staging of tumours between the two groups (Fisher's exact probability method, P = 0.001), with nonampullary stage II tumours (68.2%) being the main stage (P < 0.05). After the diagnosis of DNETs, the survival rate of the ampullary region group was 14.3% (1/7), which was lower than that of 72.7% (16/22) in the nonampullary region group (Fisher's exact probability method, P = 0.011). The survival time of the ampullary region group was shorter than that of the nonampullary region group (P < 0.000). The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months. Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients (HR = 0.029, 95%CI 0.004-0.199, P < 0.000; HR = 12.609, 95%CI: 2.889-55.037, P = 0.001). Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter < 2 cm was longer than that of patients with a tumour diameter ≥ 2 cm (t = 7.243, P = 0.048). As of follow-up, 6 patients who died of nonampullary DNETs had a tumour diameter that was ≥ 2 cm, and 3 patients in stage IV had liver metastasis. Patients with a tumour diameter < 2 cm underwent surgical treatment, and all survived after surgery. CONCLUSION: Surgical treatment is a protective factor for prolonging the survival of DNET patients. Compared to DNETs in the ampullary region, patients in the nonampullary region group had a longer survival period. The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

Relationship between gastric xanthoma, gastric precancerous lesions, and gastric cancer: A retrospective study.

OBJECTIVE: To evaluate the relationship between gastric cancer and its precancerous lesions and gastric xanthoma. METHODS: Medical records of 47 736 patients who underwent gastroscopy in our center from January 2020 to December 2021 were reviewed. Patients' age, sex, endoscopic and histopathological findings, and the presence, number and location of gastric xanthoma were recorded. To investigate the detection rate of gastric xanthoma at different stages of gastric lesions, the participants were further divided into the chronic gastritis group (n = 42 758), the precancerous lesion group (n = 3672), and the gastric cancer group (n = 1306), respectively. RESULTS: The overall detection rate of gastric xanthoma was 2.85%, and it was most commonly observed in the gastric antrum (52.50%). In addition, gastric xanthoma was more common in men and more likely to be single lesion. It was most detected in the precancerous lesion group (8.39%), followed by the gastric cancer group (5.44%), and least in the chronic gastritis group (2.29%). Multivariate analysis showed that gastric xanthoma was closely related to precancerous lesions (odds ratio [OR] 3.197, 95% confidence interval [CI] 2.791-3.662, P < 0.001) and gastric cancer (OR 1.794, 95% CI 1.394-2.309, P < 0.001). CONCLUSION: Gastric xanthoma is closely related to gastric precancerous lesions and gastric cancer.

Endoscopic grading of gastric atrophy and histological gastritis staging on risk assessment for early gastric cancer: A case-control study.

OBJECTIVES: To assess the predictive value of endoscopic grading of gastric atrophy using Kimura-Takemoto classification, histological grading systems of operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric cancer (EGC) and other potential risk factors of EGC. METHODS: A single-center, case-control study was retrospectively conducted including 68 patients with EGC treated with endoscopic submucosal dissection and 68 age- and sex-matched control subjects. Kimura-Takemoto classification, OLGA and OLGIM systems, and other potential risk factors were evaluated between the two groups. RESULTS: Of the 68 EGC lesions, 22 (32.4%) were well differentiated, 38 (55.9%) were moderately differentiated, and 8 (11.8%) were poorly differentiated, respectively. Multivariate analysis revealed O-type Kimura-Takemoto classification (adjusted odds ratio [AOR] 3.282, 95% confidence interval [CI] 1.106-9.744, P = 0.032) and OLGIM stage III/IV (AOR 17.939, 95% CI 1.874-171.722, P = 0.012) were significantly related to a higher risk of EGC. Especially, O-type Kimura-Takemoto classification within 6-12 months before EGC diagnosis (AOR 4.780, 95% CI 1.650-13.845, P = 0.004) was independently associated with EGC risk. Areas under the receiver operating characteristic curve of the three systems for EGC were comparable. CONCLUSIONS: Endoscopic Kimura-Takemoto classification and histological OLGIM stage III/IV are independent risk factors for EGC, which may reduce the need for biopsies in risk stratification of EGC. Further multicenter prospective studies of large sizes are needed.

Increased Prevalence of Thyroid Nodules Across Nearly 10 Years in Shanghai, China.

OBJECTIVE: This study aimed to determine whether the prevalence of thyroid nodules (TNs) increased due to modern lifestyles or other factors, despite the advances in screening and diagnostic tools. METHODS: This study included 3474 pairs of participants, who were matched by gender and age (±3 years) from two cross-sectional sampling surveys: (1) the program on the iodine nutritional status and related health status of residents in Shanghai in 2009; (2) the thyroid disease screening program for adults in Shanghai between 2017 and 2018. The prevalence of TNs and thyroid diseases in 2009 and 2017-2018 were compared, and the potential risk factors of TNs were detected. RESULTS: The prevalence of TNs in 2009 was 28.9%: 22.5% in males and 34.5% in females. In 2017, this increased to 43.8%: 37.9% in males and 49.1% in females. The prevalence of TNs significantly increased from 2009 to 2017 (odds ratio, 1.486; 95% confidence interval, 1.238-1.786). In addition, female gender, thyroid disease history, and age were the main risk factors for TNs after adjusting for confounders in the logistic regression across the time period. CONCLUSION: The prevalence of TNs significantly increased across nearly 10 years in Shanghai.

Bile reflux is an independent risk factor for precancerous gastric lesions and gastric cancer: An observational cross-sectional study.

OBJECTIVE: To identify whether bile reflux on endoscopy and other related variables are risk factors for precancerous gastric lesions and gastric cancer (GC). METHODS: A multicenter, cross-sectional and observational study was conducted in five centers in China from June to October 2019, 1162 patients were recruited and divided into the chronic gastritis (CG), the precancerous lesion (low-grade intraepithelial neoplasia and intestinal metaplasia), and GC groups (including high-grade intraepithelial neoplasia). All participants underwent detailed interviews, endoscopy and biopsy, and completed questionnaires. Odds ratio and 95% confidence interval were calculated with multivariate logistic regression models with or without adjustment for Helicobacter pylori infection. RESULTS: We recruited 668 patients with CG, 411 with precancerous lesions and 83 with GC. By comparing the CG and precancerous lesion groups, independent risk factors for cancerous gastric lesions were the grade of bile reflux, patient's age, dietary habits and family history of GC. Similar results were obtained when comparing the CG and GC groups. In addition, bile reflux was confirmed as an independent risk factor for progression from precancerous lesions to cancer. CONCLUSIONS: Bile reflux on endoscopy as well as age, dietary habits and a family history of GC were independent risk factors for the development of precancerous gastric lesions and GC.

The presence of NAFLD in nonobese subjects increased the risk of metabolic abnormalities than obese subjects without NAFLD: a population-based cross-sectional study.

BACKGROUND: With lifestyle modification and over-nutrition, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing annually. Here we aimed to assess the updated prevalence of NAFLD, and to evaluate the association of NAFLD with metabolic abnormalities according to gender, body mass index and age. METHODS: A population-based cross-sectional study was conducted in Shanghai from December 2016 to July 2017. With a three-stage stratified sampling strategy, 3,717 eligible participants were enrolled for the analysis. RESULTS: In total, 1,217 subjects (32.7%) had NAFLD. Among them, 400 (16.3%) of the nonobese and 817 (65.0%) of the obese subjects had NAFLD. The prevalence of NAFLD was increased according to the quartiles of age and waist circumference (WC) in the nonobese subjects. Females with nonobese NAFLD had 1.6-, 2.6-, 2.0-, 2.3- and 3.3-fold higher risks for metabolic syndrome, diabetes mellitus, hyperglycemia, hypertriglycerdemia (high TG) and low high-density lipoprotein cholesterol than obese subjects without NAFLD, respectively. Males had comparable metabolic profiles in both groups, except for a 2.0-fold higher risk of high TG in nonobese NAFLD subjects compared with obese subjects without NAFLD. More impressively, the homeostasis metabolic assessment insulin resistance index was comparable between the two groups. CONCLUSIONS: The increase of age and WC had significant impact on the risk of NAFLD in nonobese subjects. The presence of NAFLD in nonobese subjects increased the risk of metabolic diseases than obese subjects without NAFLD, especially in female.

Lamb's tripe extract and vitamin B12 capsule plus celecoxib reverses intestinal metaplasia and atrophy: A retrospective cohort study.

BACKGROUND: Chronic atrophic gastritis (AG) with intestinal metaplasia (IM) significantly increases the risk of gastric cancer. Some medicines have showed definite therapeutic effects in AG and IM regression. AIM: To validate the efficacy of Lamb's tripe extract and vitamin B12 capsule (LTEVB12) initial therapy and celecoxib rescue therapy for IM and AG. METHODS: A total of 255 patients were included to receive LTEVB12 initial therapy (2 capsules each time, three times daily for 6 mo) in hospital in this study. The patients with failure of IM regression continued to receive celecoxib rescue therapy (200 mg, once daily for 6 mo). After each therapy finished, the patients underwent endoscopy and biopsy examination. The regression efficiency was assessed by the operative link on gastritis assessment (OLGA) and the operative link on the gastric intestinal metaplasia assessment (OLGIM) staging system. Logistic regression analysis was applied to identify factors associated with the curative effect. RESULTS: For LTEVB12 initial therapy, the reversal rates of IM and AG were 52.95% and 48.24%, respectively. Analogously, for celecoxib rescue therapy, the effective rates for IM and AG were 56.25% and 51.56%, respectively. The IM regression rate of complete therapy was up to 85.03%. In different OLGA and OLGIM stages of IM patients, therapeutic efficiency showed a significant difference in each group (P < 0.05). For both therapies, patients with high stages (III or IV) of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages (I or II). Among patients with high stages (OLGIM III and IV), the IM regression rate was above 70% for each therapy. Eating habits, fresh vegetable intake, and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy, especially high-salt diet (odds ratio = 1.852, P < 0.05). CONCLUSION: Monotherapy could reverse IM and AG. LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect. IM may not be the point of no return among gastric precancerous lesions.

Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis.

OBJECTIVE: We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC. METHODS: An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression. RESULTS: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients. CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.

Recent advances of miRNAs in the development and clinical application of gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors. The mechanism of how GC develops is vague, and therapies are inefficient. The function of microRNAs (miRNAs) in tumorigenesis has attracted the attention from many scientists. During the development of GC, miRNAs function in the regulation of different phenotypes, such as proliferation, apoptosis, invasion and metastasis, drug sensitivity and resistance, and stem-cell-like properties. MiRNAs were evaluated for use in diagnostic and prognostic predictions and exhibited considerable accuracy. Although many problems exist for the application of therapy, current studies showed the antitumor effects of miRNAs. This paper reviews recent advances in miRNA mechanisms in the development of GC and the potential use of miRNAs in the diagnosis and treatment of GC.

A randomized, multicenter and noninferiority study of amoxicillin plus berberine vs tetracycline plus furazolidone in quadruple therapy for Helicobacter pylori rescue treatment.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is closely associated with gastric ulcers and gastric adenocarcinomas. We aimed to assess the efficacy and safety of a quadruple regimen with amoxicillin plus berberine vs tetracycline plus furazolidone in rescue therapy for H. pylori eradication. METHODS: We conducted a randomized, open-label, multicenter, noninferiority trial. Patients with previous treatment failures recruited from five centers were randomized (1:1) to receive a regimen with esomeprazole and bismuth plus either berberine and amoxicillin (the BA group) or tetracycline and furazolidone (the TF group) for 14 days. Their H. pylori infection status was confirmed 4-8 weeks after treatment. The primary outcome was the eradication rate. The secondary outcomes included the rates of symptom improvement, compliance, and adverse events. This study was registered at ClinicalTrials.gov (NCT03609892). RESULTS: Altogether 658 participants were consecutively enrolled. An intention-to-treat analysis demonstrated that the two regimens achieved a similar eradication rate (76.3% vs 77.5%; P = 0.781). The per-protocol analysis reached a similar result (81.5% vs 85.0%; P = 0.278). The eradication rate reached in the BA group was greater than the pre-established margin of noninferiority, at -10% (the lower bounds of the 95% CI were -7.66% and -9.43%, respectively). The rate of adverse events was lower for the BA group than the TF group (18.5% vs 26.1%, P = 0.024). Rates of compliance and symptom improvement were similar for the two therapies. CONCLUSION: The efficacy of both regimens in rescue treatment for H. pylori eradication was satisfactory, 14-day BA-based quadruple therapy is noninferior to the TF-based therapy.

The relationship between gastric cancer, its precancerous lesions and bile reflux: A retrospective study.

OBJECTIVE: To evaluate the relationship between gastric cancer (GC) and precancerous lesions and bile reflux. METHODS: Medical records of 30 465 participants who underwent gastroscopy between January and December 2018 in our center were reviewed. Their age, sex, time of endoscopy, endoscopic/histologic diagnosis and grade of bile reflux were recorded. The participants were further divided into the chronic gastritis group (n = 27 807), a precancerous lesion group (n = 1943) and a GC group (n = 715). The χ2 tests and hierarchical analyses were performed. RESULTS: Patients aged 18-27 years had a higher bile reflux rate than those aged 28-37 and 68-75 years (P < 0.001), while it did not differ between patients aged <50 years and those over 50 years (P = 0.639). It was lower in men than in women (P < 0.001). The bile reflux rate did not differ in terms of months, seasons and half of the year (all P > 0.05), but differed between morning and afternoon when they underwent the endoscopy (P = 0.000). There was an interrelationship between the severity of gastric mucosal disease and bile reflux grade (r = 0.171). After excluding the effects of sex, age and time of endoscopy on bile reflux, bile reflux rate in chronic gastritis and precancerous lesions was lower than in gastric cancer (P < 0.01). CONCLUSIONS: Bile reflux may be a risk factor for gastric cancer and precancerous lesions. A high grade of bile reflux may be associated with the progression of gastric mucosal diseases.

Efficacy and safety of dulaglutide monotherapy compared with glimepiride in Chinese patients with type 2 diabetes: Post-hoc analyses of a randomized, double-blind, phase III study.

AIMS/INTRODUCTION: To investigate the efficacy/safety of dulaglutide once-weekly monotherapy versus glimepiride in Chinese patients with type 2 diabetes. MATERIALS AND METHODS: This was a post-hoc analysis of a Chinese randomized, double-blind, non-inferiority, phase III study. Patients (n = 572) with inadequate glycemic control received dulaglutide 1.5 mg (n = 189) or 0.75 mg (n = 194) once-weekly or glimepiride (1-3 mg/day; n = 189) for 26 weeks. The primary objective of the study was to investigate the non-inferiority of dulaglutide 1.5 mg versus glimepiride by the change from baseline to week 26 in glycated hemoglobin (non-inferiority margin 0.4%). RESULTS: Dulaglutide 1.5 mg and 0.75 mg were non-inferior (P < 0.001) and superior (P ≤ 0.002) versus glimepiride for the change in glycated hemoglobin from baseline to week 26. The least-squares mean differences (95% confidence interval) versus glimepiride were dulaglutide 1.5 mg, -0.53% (-0.74, -0.32) and dulaglutide 0.75 mg, -0.32% (-0.53, -0.12). Significantly more patients attained glycated hemoglobin <7.0% at week 26 in the dulaglutide 1.5 mg (71.7%) versus the glimepiride (57.5%; P = 0.005) group. The decrease from baseline to week 26 in fasting blood glucose was significantly more pronounced in both the dulaglutide groups versus the glimepiride group (P < 0.01). The overall incidence and rate of hypoglycemia were lower in both of the dulaglutide groups versus the glimepiride group. At week 26, bodyweight had increased from baseline in the glimepiride group and decreased from baseline in both dulaglutide groups. The most frequent gastrointestinal drug-related adverse events with dulaglutide were diarrhea, abdominal distension, nausea and vomiting. CONCLUSIONS: These findings support once-weekly dulaglutide monotherapy as a treatment for Chinese patients with early stage type 2 diabetes.

Modified human uterus transplantation using ovarian veins for venous drainage: the first report of surgically successful robotic-assisted uterus procurement and follow-up for 12 months.

OBJECTIVE: To report the 12-month results of the first human uterus transplantation case using robot-assisted uterine retrieval. This type of transplantation may become a treatment for permanent uterine factor infertility. DESIGN: Case study. SETTING: University hospital. PATIENT(S): A 22-year-old woman with complete müllerian agenesis who underwent a previous surgery for vaginal reconstruction. The live uterine donor was her mother. INTERVENTION(S): The uterus transplantation procedure consisted of robot-assisted uterine procurement, orthotopic replacement and fixation of the retrieved uterus, revascularization, and end-to-side anastomoses of bilateral hypogastric arteries and ovarian-uterine vein to the bilateral external iliac arteries and veins. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery, and follow-up (12 months). RESULT(S): The duration of the donor and recipient surgeries were 6 and 8 hours, 50 minutes, respectively. No immediate perioperative complications occurred in the recipient or donor. The recipient experienced menarche 40 days after transplant surgery, and she has had 12 menstrual cycles since the surgery. No rejection episodes occurred in the recipient. CONCLUSION(S): These results demonstrate the feasibility of live-donor uterine transplantation with a low-dose immunosuppressive protocol and the role of DaVinci robotic assistance during human uterine procurement. CLINICAL TRIAL REGISTRATION NUMBER: XJZT12Z06.

Deletion of HNF1α in hepatocytes results in fatty liver-related hepatocellular carcinoma in mice.

Hepatocyte nuclear factor 1α (HNF1α) is a liver-enriched transcription factor that is critical for the maintenance of hepatocyte function. Our previous studies have demonstrated the therapeutic effects of HNF1α on hepatic fibrosis and hepatocellular carcinoma (HCC) in animals. In this study, we created hepatocyte-specific Hnf1α knockout mice using the Cre-loxP recombination system. The knockout mice display increased fatty acid synthesis in the liver. Moreover, these mice spontaneously develop HCC through fatty liver without cirrhosis. Inflammatory cytokines, such as tumor necrosis factor α and IL-6, are upregulated and accompanied by increased phosphorylation of Akt, p-65 and STAT3 in the livers of HNF1α knockout mice. Our findings suggest that HNF1α plays a crucial role in hepatocyte lipid metabolism and hepatocarcinogenesis.

Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces ß-cell proliferation in diabetic mice.

Recent progress in regenerative medicine has suggested that mesenchymal stem cell (MSC)-based therapy is a novel potential cure for diabetes. Betatrophin is a newly identified hormone that can increase the production and expansion of insulin-secreting ß-cells when administered to mice. In this study, we evaluated the effect of betatrophin overexpression by human adipose-derived MSCs (ADMSCs) by in vitro experiments, as well as following their transplantation into a mice with streptozotocin (STZ)-induced diabetes. The overexpression of betatrophin did not affect the ADMSCs in terms of proliferation, differentiation and morphology. However, the co-culture of human islets with ADMSCs overexpressing betatrophin (ADMSCs-BET) induced islet proliferation, ß-cell specific transcription factor expression, and the islet production of insulin under the stimulation of glucose or KCl and Arg. In addition, ADMSCs-BET enhanced the anti-inflammatory and anti-apoptotic effects of the co-cultured islets compared with ADMSCs cultured alone. In mice with STZ-induced diabetes, the transplantation of ADMSCs-BET ameliorated the hyperglycemia and weight loss associated with STZ-induced diabetes; ADMSCs-BET also significantly enhanced the ratio of ß-cells per islet compared to the transplantation of ADMSCs alone. Thus, our study demonstrates a novel strategy for inducing ß-cell regeneration. ADMSCs-BET may replace insulin injections by increasing the number of endogenous insulin-producing cells in patients with diabetes. This combined strategy of ADMSC transplantation and gene therapy may prove to be a useful therapy for the treatment of diabetes.

MicroRNA-7/NF-κB signaling regulatory feedback circuit regulates gastric carcinogenesis.

MicroRNAs play essential roles in gene expression regulation during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer (GC). We used genome-wide screenings and identified RELA and FOS as novel targets of miR-7. Overexpression of miR-7 repressed RELA and FOS expression and prevented GC cell proliferation and tumorigenesis. These effects were clinically relevant, as low miR-7 expression was correlated with high RELA and FOS expression and poor survival in GC patients. Intriguingly, we found that miR-7 indirectly regulated RELA activation by targeting the IκB kinase IKKε. Furthermore, IKKε and RELA can repress miR-7 transcription, which forms a feedback circuit between miR-7 and nuclear factor κB (NF-κB) signaling. Additionally, we demonstrate that down-regulation of miR-7 may occur as a result of the aberrant activation of NF-κB signaling by Helicobacter pylori infection. These findings suggest that miR-7 may serve as an important regulator in GC development and progression.

XRCC1 gene polymorphisms and the risk of differentiated thyroid carcinoma (DTC): a meta-analysis of case-control studies.

BACKGROUND: Previous studies investigating the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and thyroid cancer risk have yielded inconsistent results. This meta-analysis was performed to derive a more precise estimation of the relationship between three XRCC1 polymorphisms and thyroid cancer risk. METHODS/PRINCIPAL FINDINGS: PubMed and EMBASE database were systematically searched to identify relevant studies. 10 publications were selected for this meta-analysis, including 11 studies for Arg399Gln polymorphism (1726 cases and 3774 controls), 7 studies for Arg194Trp polymorphism (1037 cases and 2487 controls) and 8 studies for Arg280His polymorphism (1432 cases and 3356 controls). The results in total population did not show any significant association between these three polymorphisms and the risk of DTC for all genetic models. However, when stratified by ethnicity, the results showed that Arg280His polymorphism was associated with an increased risk of DTC among Caucasians (Arg/His vs. Arg/Arg: OR = 1.45, 95% CI = 1.09-1.93; dominant model: OR = 1.43, 95% CI = 1.08-1.89; additive model: OR = 1.38, 95% CI = 1.05-1.80), whereas individuals carrying Arg/His genotype have a significantly reduced risk of DTC among Asians (Arg/His vs. Arg/Arg: OR = 0.71, 95% CI = 0.51-0.98). We also detected that 399Gln variant allele carriers might presented an overall decreased risk of DTC in mixed population. Furthermore, subgroup analyses by histological subtype revealed that Arg194Trp polymorphism was significantly associated with reduced risk for papillary thyroid carcinoma (PTC) (dominant model: OR = 0.71, 95% CI = 0.50-0.99). CONCLUSIONS: This meta-analysis suggests that Arg280His polymorphism might contribute to the susceptibility of DTC among Caucasians, whereas it might provide protective effects in Asians against the risk of DTC. Additionally, our results support the protective role of Arg194Trp polymorphism in developing PTC, and show evidence of an association between Arg399Gln polymorphism and decreased risk of DTC in mixed population.

[The derivation and validation of a prediction rule for differential diagnosis of thyroid nodules].

OBJECTIVE: To set up a prediction rule for the pro-operative differential diagnosis of thyroid nodules and evaluate its clinical value. METHODS: All patients of thyroid nodules underwent thyroid operations in Changzheng hospital from June, 1997 to July, 2012 were included in this study. They were randomly divided into the derivation cohort (2/3) and the validation cohort (1/3). A prediction rule was developed based on the logistic regression model and the scoring system was established in accordance with assigning of the value of each variable ß in the model. The prediction consistency, discriminatory power and diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. RESULTS: A total of 13 980 patients were enrolled in the study with 9195 in the derivation cohort and 4785 in the validation cohort. The prediction rule consisted of 18 variables, which were gender, clinical manifestations including fever, neck sore, neck mass, palpitation and sweating, serum level of thyroid stimulating hormone (TSH) , free triiodothyronine (FT3) , thyroid peroxidase antibody (TPOAb) , thyroglobulin antibody (TgAb) , thyroglobulin (Tg) , calcitonin and carcinoembryonic antigen (CEA) , ultrasonography features including nodules number, location, size, boundaries and ethological patterns and the presence and patterns of lymph nodes. The model showed good calibration consistency (P = 0.437) and discrimination power (area under the receiver operating characteristic curve was 0.928) in the derivation cohort. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the model were 89.3%, 81.5%, 83.2%, 56.8%, 96.6%, 4.83 and 0.13, respectively. CONCLUSION: The prediction rule and its scoring system established in the study are efficacious for the calibration and discrimination of thyroid nodules in Chinese population, which could be a useful tool for the pro-operative risk stratification.