Search

Purpose To investigate the possibly predictive role of BRAF V600E mutation and thyroid-relevant indexes on papillary thyroid cancer (PTC). Methods 1139 patients of PTC were included in this retrospective study. The pathological results, demographic characteristics data, BRAF V600E mutation, and serum examination of thyroid were analyzed by Chi‐square tests and logistic regressions. Results The patients at a high level of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), or Hashimoto's thyroiditis (HT) had lower rates of BRAF V600E mutation. Elevated thyroglobulin was associated with a higher rate of macro-carcinoma regardless of the mutation statuses (P0.05). Conclusion BRAF V600E mutation and HT interfered with each other in PTC. HT manifested a protective role against the progression of this cancer in the early period, but the mutation didn't impact the features. The tumor load was reflected by thyroglobulin and body mass index.

Background Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery. Case presentation A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes. Conclusions She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.

Objective: Recently, Nonalcoholic Steatohepatitis (NASH) has become a major contributor to cirrhosis and liver cancer. Therefore, the Global Burden of Disease (GBD) 2017 was used to comprehensively analyze the global, regional, and national burden of cirrhosis and liver cancer due to NASH between 1990 and 2017. Methods: Data for cirrhosis and liver cancer due to NASH were extracted from the GBD study 2017. Socio-demographic Index (SDI) in 2017 was cited as indicators of socioeconomic status. ARIMA model was established to forecast the future health burden. Kruskal-Wallis test and Pearson linear correlation were adopted to evaluate the gender disparity and association with socioeconomic level. Results: From 1990-2017, the global disability-adjusted life years (DALYs) numbers of liver cancer due to NASH increased from 0.71 million to 1.46 million. The age-standardized DALYs rates of liver cancer due to NASH were negatively associated with SDI levels (r=0.-409, p

Diabetes mellitus is a leading cause of mortality and reduced life expectancy. We aim to estimate the burden of diabetes by type, year, regions, and socioeconomic status in 195 countries and territories over the past 28 years, which provide information to achieve the goal of World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases in 2025. Data were obtained from the Global Burden of Disease Study 2017. Overall, the global burden of diabetes had increased significantly since 1990. Both the trend and magnitude of diabetes related diseases burden varied substantially across regions and countries. In 2017, global incidence, prevalence, death, and disability-adjusted life-years (DALYs) associated with diabetes were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, with a projection to 26.6 million, 570.9 million, 1.59 million, and 79.3 million in 2025, respectively. The trend of global type 2 diabetes burden was similar to that of total diabetes (including type 1 diabetes and type 2 diabetes), while global age-standardized rate of mortality and DALYs for type 1 diabetes declined. Globally, metabolic risks (high BMI) and behavioral factors (inappropriate diet, smoking, and low physical activity) contributed the most attributable death and DALYs of diabetes. These estimations could be useful in policy-making, priority setting, and resource allocation in diabetes prevention and treatment.

Hyperglycemia is a major public health concern. An understanding of the latest trends of the global burden of noncommunicable diseases (NCDs) by high fasting plasma glucose (HFPG) is critical for determining research priorities and planning health policy.This is a comparative burden-of-disease study. We obtained global, regional, and national data on deaths and disability-adjusted life years (DALYs) of NCDs attributable to HFPG from the Global Burden of Disease Study 2017, performed a secondary analysis of deaths and DALYs by time, age, gender, location, and specific causes, and analyzed their associations.In 2017, 6.39 million deaths and 166.36 million DALYs from NCDs were attributable to HFPG, accounting for 15.6% and 10.7% of all deaths and DALYs, respectively. The burden's rate decreased with time, increased with age and was significantly higher in males. A negative association was found between the sociodemographic index (SDI) and disease burden, and a positive association was found between SDI and male superiority by gender difference and gender ratio.The burden of NCDs attributable to HFPG has increased significantly since 1990 and varied widely across regions. Greater efforts are needed to prevent and control hyperglycemia, especially in less developed countries and among males.背景: 高血糖是一个重大的公共健康问题。了解高空腹血糖导致的全球非传染性疾病负担的趋势变化对研究方向确定和卫生政策规划均有着重要作用。 方法: 这是一项关于疾病负担的对比研究, 通过从2017年全球疾病负担研究中获取全球、区域和民族的非传染性疾病死亡及伤残调整生命年(DALY)数据, 按照时间、年龄、性别、地区和特定疾病进行二次分析。 结果: 在2017年, 高空腹血糖导致的非传染性疾病共引起639万死亡和16 636万DALYs, 分别占全部死亡及DALY的15.6%和10.7%。校正年龄、人口后的疾病负担率随时间降低、随年龄增长, 且在男性中更高。此外, 疾病负担率还与社会人口指数存在显著负相关, 且该指数还与疾病负担率的男女差距呈显著正相关性。 结论: 高空腹血糖导致的非传染性疾病负担从20世纪90年代起显著增加, 且在不同地区间差异显著。对高血糖的预防和控制仍需更多努力, 尤其是在欠发达地区和男性中。.

BACKGROUND: Many studies have shown an elevated level of cholesterol in colon tumors as compared to normal tissue. Obesity and high low-density lipoprotein cholesterol (LDL-C) are known risk factors for colon cancer. However, the role of LDL-C in colon cancer patients with normal body mass index (BMI) remains elusive. METHODS: Levels of serum cholesterol and oxysterols were quantified by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) from 129 individuals with normal BMI, including 32 with solitary polyp, 36 with multiple polyps, and 31 with adenocarcinoma as well as 32 healthy controls. In vitro, colon cancer cells were treated with LDL-C and assayed for chemokines via RNA-Seq and mitochondrial morphology via transmission electron microscopy and immunofluorescence. Additionally, correlation analysis was performed between LDL-C-induced chemokines and the overall survival of colon cancer patients from the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA) database. RESULTS: The serum cholesterol level was significantly higher in colon adenocarcinoma patients with normal BMI than that in healthy controls (P

A high-fat diet (HFD) is defined as a diet that contains lipids that account for more than 30% of the total energy intake, and current research has documented cases with intakes as high as 45% and 60%. There is a view that patients who have a tendency to consume a HFD are more susceptible to various kinds of diseases, including osteoporosis, metabolic syndrome, coronary heart disease, and cancer. Thus, hypotheses have been proposed that a HFD may serve as a significant risk factor for bone loss and osteoporosis. A plethora of studies has suggested a relationship between a HFD and bone health. Moreover, high fat has a vital effect on the bone structure and bone health, and intestinal flora imbalances and intestine barrier deterioration, inflammation, oxidative stress, adipokine changes, and bone marrow fat tissue (BMFT) accumulation are thought to be potential mechanisms. Most research has demonstrated that a HFD diminishes bone mineral density and bone microstructure. Some studies, however, showed that a HFD contributes to achieving peak bone mass, which is associated with weight gain. As diet is modifiable, lifestyle changes and medication can help bone improvement, as well as alleviating bone loss associated with a HFD. This review aims to give a comprehensive understanding of the relationship between a HFD and bone health, which might provide strategies to improve bone health by varying daily dietary components and building a healthy lifestyle. We also hope that further treatments for diet-related bone loss can be put forward.

Background: Dietary risks raised attention around worldwide during the past decades. The aims of this burden-of-disease study were to evaluate the global dietary risks for non-communicable diseases (NCDs) from 1990 to 2019 and quantify their impact on mortality and disability-adjusted life-years (DALYs). Data from the 2019 Global Burden of Disease Study on deaths and DALYs from NCDs attributable to worldwide dietary risks were obtained and underwent deep analysis by year, age, gender, location, leading risks, and leading causes, and their associations were examined. The Socio-demographic Index (SDI) was used as an indicator of national socioeconomic status, and the relationships between age-standardized rates of deaths or DALYs and socioeconomic status. Results: In 2019, 7.9 million deaths and 187.7 million DALYs were attributable to dietary risk factors. High intake of sodium and low intake of whole grains and fruits were leading dietary risks for deaths and DALYs worldwide. However, both indexes showed a decreasing trend by year, an increase by age, and a higher disease burden in males. The main distribution of dietary-related NCDs was located in highly populated countries. A negative association between the SDI and disease burden, and a positive association between the SDI and male preponderance were found. Conclusions: Dietary risk factors for NCDs increased significantly and varied across regions during 1990-2019. Therefore, greater efforts are needed to raise public awareness of interventions and improve dietary practices to reduce the disease burden caused by suboptimal dietary intake, especially in developing countries and among males.

Background The ongoing outbreak of Coronavirus disease 2019 (COVID-19) has led to declaration of public health emergency of international concern by World Health Organization and the first-level public health emergency response in China. We aimed to share the Joint Prevention and Control Mechanism taken in Mainland China and evaluate the effectiveness.Methods A powerful Joint Prevention and Control Mechanism was adopted to fight against COVID-19 in Mainland China. Data were collected from the daily epidemic reports released by the national and provincial health commissions of China from January 21 to April 6, 2020. Global data were collected from daily situation reports by World Health Organization.Results As of April 6, 2020, there were 81,740 confirmed COVID-19 cases (32 new) in Mainland China. The case fatality ratio was 4.74% and 0.85% in and outside Hubei respectively. It is gratifying to see that there were up to 22 provinces reporting zero new infections, but it can’t be ignored that there were 1,196,651 confirmed cases (68,700 new) reported in over 221 countries and territories outside China and the total death number were 69,274, nowadays China is facing great challenges of imported cases.Conclusions Great achievements have been made in controlling the spread of COVID-19 in Mainland China, but it is still a major challenge worldwide. The comprehensive and powerful control measures taken by Mainland China have proved to be effective and might be applicable to other regions.

Colorectal cancer (CRC) is one of the most malignant cancers, and it tends to migrate to the liver and has a high mortality rate. Several mechanisms behind the metastasis of CRC have been identified, including hyperlipidemia. For example, hyperlipidemia can lead to enhanced stemness and neutrophil infiltration, which increases CRC metastasis. There are three primary aspects to the relationship between hyperlipidemia and CRC metastasis: hyperlipidemia (1) promotes the initial metastatic properties of CRC, (2) stimulates CRC cells to leave the vasculature, and (3) facilitates the development of CRC metastasis. In this study, we provide a comprehensive overview of the role that hyperlipidemia played in CRC metastasis to help reduce the mortality associated with CRC metastasis from the standpoint of metabolic. We also review cancer metastasis.

Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high-glucose-increased Smad1 protein content. Treatment of human MCs with ANG II at 1 µM for 15 min, high glucose for 3 days, or TGF-β1 at 5 ng/ml for 30 min increased the level of phosphorylated Smad1. However, the phosphorylation of Smad1 by those stimuli was significantly attenuated by activation of SOCE. Knocking down Smad1 reduced, but expressing Smad1 increased, the amount of Col IV protein. Furthermore, activation of SOCE significantly attenuated high-glucose-induced Col IV protein production, and blockade of SOCE substantially increased the abundance of Col IV. To further verify those in vitro findings, we downregulated SOCE specifically in MCs in mice using small-interfering RNA (siRNA) against Orai1 (the channel protein mediating SOCE) delivered by the targeted nanoparticle delivery system. Immunohistochemical examinations showed that expression of both Smad1 and Col IV proteins was significantly greater in the glomeruli with positively transfected Orai1 siRNA compared with the glomeruli from the mice without Orai1 siRNA treatment. Taken together, our results indicate that SOCE negatively regulates the Smad1 signaling pathway and inhibits Col IV protein production in MCs.

Objective To investigate the expression of apoptosis-related factors in diabetic nephropathy model rats after the intervention of dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. Methods ZDF(fa/fa) and ZDF(fa/

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD). However, the association between CKD and CVD risk in patients with type 2 diabetes mellitus (T2DM) in China has not yet been well investigated. This study aimed to determine the association of CKD with the risks of coronary heart disease (CHD) and stroke in a Chinese population with T2DM. Methods: A total of 1401 inpatients with T2DM at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2008 and November 2013 were included in this study. The CKD-Epidemiology Collaboration equation for Asians was used to classify CKD. The UK Prospective Diabetes Study risk engine was used to estimate the risks of CHD and stroke. Results: CHD risk was significantly increased with CKD stage (20.1%, 24.8%, and 34.3% in T2DM patients with no CKD, CKD Stage 1–2, and Stage 3–5, respectively; P < 0.001 for all). The stroke risk was also increased with CKD stage (8.6%, 12.7%, and 25.4% in T2DM patients with no CKD, CKD Stage 1–2, and Stage 3–5, respectively; P < 0.001 for all). Compared with no-CKD group, the odds ratios (ORs) for high CHD risk were 1.7 (P < 0.001) in the CKD Stage 1–2 group and 3.5 (P < 0.001) in the CKD Stage 3–5 group. The corresponding ORs for high stroke risk were 1.9 (P < 0.001) and 8.2 (P < 0.001), respectively. Conclusion: In patients with T2DM, advanced CKD stage was associated with the increased risks of CHD and stroke. Key words: Chronic Kidney Disease; Coronary Disease; Stroke; Diabetes Mellitus

Introduction: Diabetes insipidus can be a common cause of polyuria and hydronephrosis in the kidneys. However, there is few reported case of urinary obstruction induced nephrogenic diabetes insipidus. Patient concerns: A 60-year-old Chinese man came to our hospital with the complaints of polydipsia and polyuria for 1 month. His examination showed chronic kidney disease stage III with eGFR of 48.274 ml/min, and the plasma osmolality was 338.00 mOsm/(kg·H2O) with a urinary osmolality of 163.00 mOsm/(kg·H2O). Moreover, imagological examination of the urinary system showed benign prostatic hyperplasia and hydronephrosis. Diagnosis: He was considered with benign prostatic hyperplasia induced ureter hydronephrosis and nephrogenic diabetes insipidus. Interventions: He got the transurethral resection of the prostate to alleviate urinary retention. Outcomes: After that, the urine output gradually decreased, and the administered hydrochlorothiazide was stopped due to the improved renal function. Conclusion: Our study presents a case of nephrogenic diabetes insipidus caused by urinary obstruction. Differential diagnoses for diabetes insipidus as well as the relationship between nephrogenic diabetes insipidus and urinary obstruction are also considered in this study.

Supplementary materials, methods, figures and tables. (DOCX 30583 kb)

The ARRIVE Guidelines Checklist S1. Animal Research: Reporting In Vivo Experiments. (DOCX 623 kb)

Rationale: Hyperpigmentation is a common skin disease. However, there are few reported cases of Grave's disease with diffuse hyperpigmentation. We hereby described a rare case with diffuse hyperpigmentation induced by Grave's disease. Patient concerns: A 42-year-old Chinese woman with accumulated general pigmentation of skin was admitted to our hospital in October 2017. On examination, hyperpigmentation was observed throughout the whole body, especially on the extremities and the face. Diagnoses: The patient has elevated levels of serum free thyroxine (FT4), free triiodothyronine (FT3), reduced levels of thyroid-stimulating hormone (TSH) and positive anti-TSH receptor antibody (TRAb). She presented with grade I goiter and a diffusely increased thyroid uptake to 18.5% in thyroid scan. Histopathological examination demonstrated melanin pigmentation in the pigmented skin area. The patient was diagnosed with hyperpigmentation induced by Grave's disease. Interventions: The patient was treated with oral methimazole (15 mg/day) for thyroid dysfunction and beta blocker for symptom control. Outcomes: After a period of treatment with methimazole and beta blocker, symptoms of hyperthyroidism ameliorated and hyperpigmentation abated. Lessons: Our studies proposed that in this case the diffuse hyperpigmentation in Grave's disease was caused by elevated adrenocorticotropic hormone (ACTH) as well as anti- TSH receptor stimulating antibody instead of enhanced capillary fragility. Other potential mechanisms for skin pigmentation in hyperthyroidism still need further exploration.

The present study was carried out to investigate if hepatic nuclear factor (HNF)4α contributed to the high glucose-induced increase in stromal interacting molecule (STIM)1 protein abundance in glomerular mesangial cells (MCs). Western blot and immunofluorescence experiments showed HNF4α expression in MCs. Knockdown of HNF4α using a small interfering RNA approach significantly increased mRNA expression levels of both STIM1 and Orai1 and protein expression levels of STIM1 in cultured human MCs. Consistently, overexpression of HNF4α reduced expressed STIM1 protein expression in human embryonic kidney-293 cells. Furthermore, high glucose treatment did not significantly change the abundance of HNF4α protein in MCs but significantly attenuated HNF4α binding activity to the Stim1 promoter. Moreover, knockdown of HNF4α significantly augmented store-operated Ca2+entry, which is known to be gated by STIM1 and has recently been found to be antifibrotic in MCs. In agreement with those results, knockdown of HNF4α significantly attenuated the fibrotic response of high glucose. These results suggest that HNF4α negatively regulates STIM1 transcription in MCs. High glucose increases STIM1 expression levels by impairing HNF4α binding activity to the Stim1 promoter, which subsequently releases Stim1 transcription from HNF4α repression. Since the STIM1-gated store-operated Ca2+entry pathway in MCs has an antifibrotic effect, inhibition of HNF4α in MCs might be a potential therapeutic option for diabetic kidney disease.

Insulin resistance (IR) is a fundamental pathogenic factor shared by a myriad of metabolic disorders, including obesity and type 2 diabetes. The mechanism of IR is usually accompanied by mitochondrial dysfunction. Irisin has been proposed to act as a hormone in the regulation of energy homeostasis and metabolism. However, the effects of irisin on IR and mitochondrial function have not yet been fully investigated. Here, our research shows that irisin increases glucose uptake in C2C12 myoblast cells via the p38-mitogen-activated protein kinase (MAPK)-PGC-1α pathway. Irisin can also enhance mitochondrial function and mitochondrial respiration. Moreover, irisin stimulates autophagy via PGC-1α. Collectively, these data provide basic evidence to support the therapeutic potential of irisin for IR, which may rely on p38-MAPK-PGC-1α pathway activation and enhance mitochondrial function.

Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high-glucose-increased Smad1 protein content. Treatment of human MCs with ANG II at 1 µM for 15 min, high glucose for 3 days, or TGF-β1 at 5 ng/ml for 30 min increased the level of phosphorylated Smad1. However, the phosphorylation of Smad1 by those stimuli was significantly attenuated by activation of SOCE. Knocking down Smad1 reduced, but expressing Smad1 increased, the amount of Col IV protein. Furthermore, activation of SOCE significantly attenuated high-glucose-induced Col IV protein production, and blockade of SOCE substantially increased the abundance of Col IV. To further verify those in vitro findings, we downregulated SOCE specifically in MCs in mice using small-interfering RNA (siRNA) against Orai1 (the channel protein mediating SOCE) delivered by the targeted nanoparticle delivery system. Immunohistochemical examinations showed that expression of both Smad1 and Col IV proteins was significantly greater in the glomeruli with positively transfected Orai1 siRNA compared with the glomeruli from the mice without Orai1 siRNA treatment. Taken together, our results indicate that SOCE negatively regulates the Smad1 signaling pathway and inhibits Col IV protein production in MCs.

Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2-24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway.

Carotid atherosclerosis (CA) and carotid plaque (CP) are highly correlated with cardiovascular disease. We aimed to determine the prevalence of CA and CP and their relationship with 10-year risks of stroke and coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM). We studied 1584 T2DM patients aged 20 years and older. CA and CP were detected using ultrasonography. Ten-year stroke and CHD risk were determined using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. The prevalence of CA and CP increased gradually with age. Men had a higher prevalence of CA than women (CA: 58.18% vs 51.54%, P

Tang et al. (1) reported that the administration of insulin glargine, but not liraglutide, reduced the liver fat burden in patients with type 2 diabetes, whereas the improvement in the liver fat fraction was not significantly different from that in the liraglutide group in a 12-week randomized trial. This is an interesting clinical study on the effects of antihyperglycemic drugs on liver fat. However, there are some concerns about this study. First, given the different mechanisms by which insulin glargine and liraglutide therapies may reduce liver fat, the short observation period of 12 weeks may not be long enough to show the actual effects of the two agents, especially for liraglutide. …