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Endocrine System Diseases - Top 30 Publications

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012.

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes.

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012.

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes.

Downregulation of tyrosine threonine kinase inhibits tumor growth via G2/M arrest in human endometrioid endometrial adenocarcinoma.

Endometrial cancer is the most common gynecologic malignancy, about 80% of which is endometrial endometrioid carcinoma. Dysregulation of spindle assembly checkpoint plays a vital role in endometrial endometrioid carcinoma tumorigenesis and progression. The purpose of this study was to explore how tyrosine threonine kinase, a spindle assembly checkpoint-related protein, promotes the endometrial endometrioid carcinoma progression. We found that both messenger RNA and protein levels of tyrosine threonine kinase in endometrial endometrioid carcinoma tissues are higher than those in normal endometrial tissues, and its expression is associated with tumor stages. Genetic depletion of tyrosine threonine kinase by RNA interference in two endometrial endometrioid carcinoma cell lines significantly inhibits cell proliferation and induces apoptosis. Mechanistically, depletion of tyrosine threonine kinase induces G2/M cell cycle arrest and triggers caspase-dependent cell apoptosis. Collectively, tyrosine threonine kinase is significantly upregulated in endometrial endometrioid carcinoma, and downregulation of tyrosine threonine kinase can suppress endometrial endometrioid carcinoma cell proliferation and promote apoptosis via G2/M cell cycle arrest. Our study demonstrates that tyrosine threonine kinase can be a potential therapeutic target for endometrial endometrioid carcinoma treatment.

RIZ1 and histone methylation status in pituitary adenomas.

RIZ1 displays strong tumor-suppressive activities, which has a potential histone methyltransferase activity. The objective of the study was to evaluate the level and the methylation status of RIZ1 and analyze its association with clinicopathological features and the histone in the pituitary adenomas. We found that RIZ1-positive cases were 11/50 and H-Scores 22.75 ± 11.83 in invasive pituitary adenomas and 26/53 and 66.3 ± 21.7 in non-invasive pituitary adenomas (χ(2) = 8.182, p = 0.004). RIZ1 and C-myc showed the opposite trend in these cases. The methylation levels of RIZ1 were more than 50% in 30.4% (7/23) CpG sites through MALDI-TOF Mass array. There was significant difference (p < 0.01) in 4 CpG sites between invasive pituitary adenoma group and non-invasive pituitary adenoma group; furthermore, the relieved methylation levels of H3K4/H3K9 and enhanced methylation levels of H3K27 in the patients' serum were found. Furthermore, there was statistic difference of H3K4 and H3K27 methylation between invasive pituitary adenoma and non-invasive pituitary adenoma group (p < 0.01). The average progression-free survival in high RIZ1 group was 52.63 ± 7.62 months and 26.06 ± 4.23 months in low RIZ1 group (p < 0.05). Promoter region methylation of RIZ1 may play an important role in the epigenetic silencing of RIZ1 expression in pituitary adenomas, which may translate into important diagnostic and therapeutic applications.

Cancer-associated fibroblasts secrete FGF-1 to promote ovarian proliferation, migration, and invasion through the activation of FGF-1/FGFR4 signaling.

Ovarian cancer is the most lethal gynecologic malignancy, due to its high propensity for metastasis. Cancer-associated fibroblasts, as the dominant component of tumor microenvironment, are crucial for tumor progression. However, the mechanisms underlying the regulation of ovarian cancer cells by cancer-associated fibroblasts remain little known. Here, we first isolated cancer-associated fibroblasts from patients' ovarian tissues and found that cancer-associated fibroblasts promoted SKOV3 cells' proliferation, migration, and invasion. Fibroblast growth factor-1 was identified as a highly increased factor in cancer-associated fibroblasts compared with normal fibroblasts by quantitative reverse transcription polymerase chain reaction (~4.6-fold, p < 0.01) and ELISA assays (~4-fold, p < 0.01). High expression of fibroblast growth factor-1 in cancer-associated fibroblasts either naturally or through gene recombination led to phosphorylation of fibroblast growth factor receptor 4 in SKOV3 cells, which is followed by the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase pathway and epithelial-to-mesenchymal transition-associated gene Snail1 and MMP3 expression. Moreover, treatment of SKOV3 cell with fibroblast growth factor receptor inhibitor PD173074 terminated cellular proliferation, migration, and invasion, reduced the phosphorylation level of fibroblast growth factor receptor 4, and suppressed the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase pathway. In addition, the expression level of Snail1 and MMP3 was reduced, while the expression level of E-cadherin increased. These observations suggest a crucial role for cancer-associated fibroblasts and fibroblast growth factor-1/fibroblast growth factor receptor 4 signaling in the progression of ovarian cancer. Therefore, this fibroblast growth factor-1/fibroblast growth factor receptor 4 axis may become a potential target for the treatment of ovarian cancer.

Sporamin induces apoptosis and inhibits NF-κB activation in human pancreatic cancer cells.

Sporamin, a Kunitz-type trypsin inhibitor (TI) from sweet potato tuberous roots, has demonstrated anti-tumor activity through poorly defined mechanisms. Furthermore, the effects of sporamin on pancreatic cancer have not been explored. Herein, we studied the effects of sporamin on two human pancreatic cancer cell lines, PANC-1 and BxPC-3. Sporamin significantly inhibited the cell viability and proliferation activity and induced apoptosis in PANC-1 and BxPC-3 cells. Consistently, in sporamin-treated PANC-1 and BxPC-3 cells, the anti-apoptotic proteins Bcl-2 and Bcl-XL were downregulated and the pro-apoptotic protein Bax was upregulated. Moreover, nuclear factor kappa B activation and IκBα phosphorylation were inhibited, and total IκBα expression was increased in sporamin-treated PANC-1 and BxPC-3 cells. Thus, our results suggest that the anti-tumor effects of sporamin in pancreatic cancer cells might result partly from induction of apoptosis by downregulating nuclear factor kappa B pathway.

The Prime Diabetes Model: Novel Methods for Estimating Long-Term Clinical and Cost Outcomes in Type 1 Diabetes Mellitus.

Recent publications describing long-term follow-up from landmark trials and diabetes registries represent an opportunity to revisit modeling options in type 1 diabetes mellitus (T1DM).

Signal transducer and activator of transcription 3 (STAT3) promoter methylation and expression in pituitary adenoma.

Pituitary adenoma (PA) is a benign brain tumor that can cause neurological, endocrinological and ophthalmological aberrations. Till now there is a need to identify factors that can influence the tumor invasiveness and recurrence. The aim of this study was to evaluate the associations between the signal transducer and activator of transcription 3 (STAT3) promoter methylation, mRNA expression and the invasiveness or recurrence of PAs and patient clinical characteristics.

Diagnosis and Differential Diagnosis of Cushing’s Syndrome.

Diagnosis and Differential Diagnosis of Cushing’s Syndrome.

Diagnosis and Differential Diagnosis of Cushing's Syndrome.

Diagnosis and Differential Diagnosis of Cushing's Syndrome.

Frequency of Evidence-Based Screening for Diabetic Retinopathy.

Frequency of Evidence-Based Screening for Diabetic Retinopathy.

Metformin is associated with fewer major adverse cardiac events among patients with a new diagnosis of type 2 diabetes mellitus: A propensity score-matched nationwide study.

Early type 2 diabetes mellitus (DM) may only require lifestyle modifications for glycemic control without the need for oral hypoglycemic agents (OHAs). Metformin is believed to improve cardiovascular outcomes in patients with DM, and it is considered to be a first-line therapy. However, it is unclear whether metformin is beneficial for patients with a new diagnosis of DM compared to those who do not need OHAs for glycemic control.Data were obtained from a population-based health care database in Taiwan. Patients with a new diagnosis of DM were enrolled if they received metformin monotherapy only between 1999 and 2010. A 4:1 propensity score-matched cohort of patients with a new diagnosis of DM who did not take OHAs or insulin during follow-up was also enrolled. The primary study endpoint was the occurrence of major adverse cardiovascular events (MACEs). The time to the endpoints was compared between groups using Cox proportional hazards models.A total of 474,410 patients with DM were enrolled. During a mean 5.8 years of follow-up, the incidence of MACEs was 1.072% (1072 per 100,000 person-years) in the metformin monotherapy group versus 1.165% in the lifestyle modification group (those who did not take OHAs) (P < .001). After adjusting for confounders, metformin independently protected the DM patients from MACEs (hazard ratio: 0.83, P < .001). The metformin group also had an improved MACE-free survival profile from year 1 to year 12 (P < .001).In addition to lifestyle modifications, the patients with a new diagnosis of DM treated with metformin monotherapy had a lower MACE rate than those who did not take OHAs. Our findings suggest that metformin may be given early to patients with a new diagnosis of DM, even when they do not need OHAs for glycemic control.

Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma.

Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma is investigated.The medical records of 45 patients who had undergone radical resection for pancreatic adenocarcinoma from March 2010 to September 2013 were reviewed retrospectively. There were 34 patients in the pancreaticoduodenectomy (PD) group and 10 patients in the distal pancreatectomy (DP) group. One patient received total pancreatectomy. The endocrine function was measured using the glucose tolerance index (GTI), which was derived by dividing daily maximum serum glucose fluctuation by daily minimum glucose. Remnant pancreas volume (RPV) was estimated by considering pancreas body and tail as a column, and head as an ellipsoid, respectively. The pancreatic atrophic index (PAI) was defined as the ratio of pancreatic duct width to total pancreas width. Representative indices of each patient were compared before and after resection up to 2 years postoperatively.The area under receiver operating characteristic curve of GTI for diagnosing DM was 0.823 (95% confidence interval, 0.699-0.948, P < .001). Overall, GTI increased on postoperative day 1 (POD#1, mean ± standard deviation, 1.79 ± 1.40 vs preoperative, 1.02 ± 1.41; P = .001), and then decreased by day 7 (0.89 ± 1.16 vs POD#1, P < .001). In the PD group, the GTI on POD#14 became lower than preoperative (0.51 ± 0.38 vs 0.96 ± 1.37; P = .03). PAI in the PD group was significantly lower at 1 month postoperatively (0.22 ± 0.12 vs preoperative, 0.38 ± 0.18; P < .001). In the PD group, RPV was significantly lower at 1 month postoperatively (25.3 ± 18.3 cm vs preoperative, 32.4 ± 20.1 cm; P = .02), due to the resolution of pancreatic duct dilatation. RPV of the DP group showed no significant change. GTI was negatively related to RPV preoperatively (r = -0.317, P = .04), but this correlation disappeared postoperatively (r = -0.044, P = .62).Pancreatic endocrine functional deterioration in pancreatic adenocarcinoma patients may in part be due to pancreatic duct obstruction and dilatation caused by the tumor. After resection, this proportion of endocrine insufficiency is corrected.

Value of contrast-enhanced ultrasound in differential diagnosis of solid lesions of pancreas (SLP): A systematic review and a meta-analysis.

Contrast-enhanced ultrasound (CEUS) is considered a novel method for diagnosing pancreatic cancer, but currently, there is no conclusive evidence of its accuracy. Using CEUS in discriminating between pancreatic carcinoma and other pancreatic lesions, we aimed to evaluate the diagnostic accuracy of CEUS in predicting pancreatic tumours.

Endoscopic ultrasound guided fine needle aspiration versus endoscopic ultrasound guided fine needle biopsy in sampling pancreatic masses: A meta-analysis.

The comparison between endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound guided fine needle biopsy (EUS-FNB) for the diagnosis of pancreatic masses is still controversial. Many factors can affect the final results.

Cryptococcal meningitis after transnasal transsphenoidal pituitary microsurgery of ACTH-secreting pituitary adenoma: A case report.

Microbial infection should be regarded in the differential diagnosis of neurosurgical complications after transnasal transsphenoidal pituitary microsurgery, albeit cryptococcal meningitis is rare. This article will discuss the risk factors of cryptococcal meningitis in patients underwent transnasal transsphenoidal pituitary microsurgery, and summary the potential origins of infection.

Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial-mesenchymal transition.

Long non-coding RNAs play important roles in the regulation of cellular processes including cell proliferation, differentiation, and metastasis. The dysregulation of long non-coding RNAs, such as the SPRY4-IT1 (SPRY4 intronic transcript 1), has been associated with various types of malignancies. However, the functional roles and regulatory mechanism of SPRY4-IT1 in ovarian cancer remain to be elucidated. Here, we quantified the expression level of SPRY4-IT1 in ovarian cancer patients and found its downregulation in ovarian cancer tissues compared to the adjacent normal tissues. Patients with lower SPRY4-IT1 expression were associated with a relatively poor prognosis. In consistency, the expression of SPRY4-IT1 was found to be reduced in four human ovarian cancer cell lines compared to normal ovarian epithelial cells. Next, two ovarian cancer cell lines SKOV3 and HO8910 were employed in vitro assays to investigate biological functions of SPRY4-IT1 in ovarian cancer. The cell proliferation was reduced following SPRY4-IT1 overexpression in SKOV3/HO8910 cells based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. The SPRY4-IT1 overexpression also dramatically arrested cell cycle and promoted cell apoptosis. Both wound-healing and transwell-based assays demonstrated that cell migration and invasion were inhibited following SPRY4-IT1 overexpression. Meanwhile, overexpression of SPRY4-IT1 increased E-cadherin and decreased N-cadherin and vimentin protein levels, indicating that SPRY4-IT1 may regulate ovarian cancer cell metastasis through the inhibition of epithelial-mesenchymal transition. Taken together, our findings suggest that SPRY4-IT1 regulates various cellular processes of ovarian cancer cells and its downregulation may contribute to ovarian cancer progression and metastasis partly via affecting the epithelial-mesenchymal transition.

Struma ovarii: a rare case of giant ovarian cyst.

Struma ovarii is a rare tumor, which accounts for 2.7% of ovarian teratomas and 0.01% of ovarian tumors. It usually affects women in the fifth decades of life and is most often detected incidentally during ultrasound and then confirmed histologically. The gold standard treatment is surgery and prognosis is excellent. We here report the particular case of a young female patient with giant struma ovarii whose radiological features were classified as unusual presentation. We match patient's data with those from the literature.

Giant parathyroid carcinoma: diagnostic difficulties and therapeutic strategies.

Parathyroid carcinoma is a very rare malignancy responsible for 0.4 to 5.2% of hyperparathyroidism. Clinical diagnosis is difficult and treatment should be codified. Surgery is the only curative treatment. We report the case of a female patient treated for malignancy-associated hypercalcemia revealing parathyroid carcinoma. The patient underwent surgery; after three months she developed lymphatic recurrence. Given the absence of other secondary involvement, bilateral lymph node dissection followed by chemotherapy was performed. Parathyroid carcinoma is often suspected on the basis of biological, radiological and especially intraoperative macroscopic criteria, but definitive diagnosis is made histopathologically. Surgery is currently the only curative treatment and the role of adjuvant therapy is to establish.

Alterations to the Foveal Cone Mosaic of Diabetic Patients.

We measured localized changes occurring in the foveal cone photoreceptors and related defects in the cone mosaic to alterations in the nearby retinal vasculature.

Long-term outcome of thyroid lobectomy for unilateral multifocal papillary carcinoma.

The National Comprehensive Cancer Network (NCCN) guidelines recommend completion thyroidectomy for patients with multifocal papillary thyroid carcinoma (PTC) diagnosed by paraffin pathology after lobectomy. However, studies for the influence of surgical range on prognosis of unilateral multifocal carcinoma are scarce. We analyzed the clinicopathological characteristics and long-term outcomes of patients with unilateral multifocal PTC to identify risk factors for recurrence and disease-related death.The clinical and pathological data of 123 cases with multifocal lesions in the unilateral thyroid lobe were retrospectively collected, including sex, age, stage, surgical range, histopathology characteristics, and follow-up data. The prognostic factors were analyzed by means of the Kaplan-Meier method.The recurrence in the contralateral residual thyroid was observed in 6 cases. The 10-year cumulative recurrence rate of the remnant thyroid was 7.0%. Extrathyroidal extension (ETE) was a significant prognostic factor, with χ equal to 4.043 and a P value of .044. One patient died from progression of pulmonary metastasis during the follow-up. The 10-year disease-specific survival rate was 96% and 14 cases experienced recurrences and underwent a second surgery (11.4%), and thus the 10-year recurrence-free survival rate was 83.2%. Multivariate analysis showed that the pathologic tumor (pT) stage was an independent prognostic factor for the recurrence-free survival rate (P <.0001, hazard ratio 2.871, 95% confidence interval 1.783-4.624).ETE is a significant prognostic factor for the recurrence of the remnant thyroid and pT stage is an independent prognostic factor for tumor recurrence-free survival. Lobectomy (with isthmectomy) is effective for most patients with unilateral multifocal PTC.

Nonfunctional pancreatic neuroendocrine tumor masked as anemia: A case report.

After a series of clinical relevant examinations. The patient was dignosed as pancreatic tomor in the pancreatic tail accompanied with the symptom of anenmia and dizziness.Until now surgery is the best treatment strategy for pancreatic tumors.So we take a joint multiple organ removal surgery.Before surgery, the main concerns of patient is whether the operation can relieve the anemia-related symptoms and improve the quality of life.The patient was dignosed as nonfunctional pancreatic neuroendocrine tumor.A joint multiple organ removal surgery including pancreaticbody and tail, spleen, part of the stomach wall, left adrenal gland,and portal splenic vein thrombosis and lymphadenectomy were performed on this patient.After surgery, the concentration of hemoglobin gradually increased and remained stable (88 g/L) on the postoperative day7. Furthermore, complete resolution of the symptom of anemia was achieved on postoperative day 30. There was no recurrence of the tumor or the symptom of anemia during the 3-month follow-up.We conclude that NF-PNETs can manifest as anemia at the time of diagnosis, and if the tumor is resectable, surgical resection is a safe and curative form of therapy not only for the anemia but also for the original tumor.

Portal vein/superior mesenteric vein resection in pancreatic cancer treatment in the elderly.

There is an increased interest in extending surgical criteria for pancreatic cancer by performing pancreaticoduodenectomy (PD) combined with portal vein (PV) or superior mesenteric vein (SMV) resection and reconstruction for borderline resectable patients. However, whether this procedure suitable for elderly patients remains unclear. Here, we studied cases of pancreatic cancer treatment in our medical center to evaluate feasibility and safety of this procedure in the elderly.Eighty-three patients 65 years of age or older who underwent PD from January 2009 to March 2014 were divided into 2 groups: PD only (Group A, 52 cases), and PD combined with PV/SMV resection and reconstruction (Group B, 31 cases). Surgical outcomes and survival rates were compared between groups. Information regarding preoperative, intraoperative and postoperative conditions, and follow-up visits were provided. The outcomes of postoperative complications and survival rates were investigated.No difference in the preoperative data was detected between 2 groups with the exception that the serum albumin level was significantly lower in Group B (P = .013), indicating more deteriorating health conditions in this group. Although intraoperative time and blood loss were higher in Group B (P < .001 and P = .048, respectively), the overall postoperative complications and survival curve showed no statistical differences between 2 groups with one exception in that there was higher incidence of intractable diarrhea in Group B (P = .034). The symptoms, however, resolved later on with conservative treatment. The median survival time for patients in this study was comparable to other reported PD treatments. There was zero postoperative mortality in both groups.PD combined with PV/SMV treatment did not lead to increased morbidity and motility in elderly patients 65 years of age and above. This procedure could provide a promising opportunity for borderline resectable elderly pancreatic cancer patients.

Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus: A meta-analysis.

Drug intensification is often required for patients with type 2 diabetes mellitus on stable metformin therapy. Among the potential candidates for a combination therapy, sodium-glucose transporter-2 (SGLT2) inhibitors have shown promising outcomes. This meta-analysis was performed to compare the efficacy and safety of SGLT2 inhibitors with non-SGLT2 combinations as add-on treatment to metformin.

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.