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Background Recent studies have shown that the microRNA-15a-5p (miR-15a-5p) plays varying roles in different malignancies. However, to date, the role and prognostic value of miR-15a-5p in patients with endometrial cancer has not been explored. This study investigated the expression level of miR-15a-5p in endometrial carcinoma and its prognostic value. Methods A total of 108 patients with endometrial cancer treated in our hospital from January 2015 to January 2016 were enrolled in this study. The patients were followed up for 5 years. Patients who experienced recurrence or metastasis after surgery were assigned into the recurrence and metastasis group (n=45) and the remaining patients were assigned into the control group (n=63). The expression level of microRNA-15a-5p in endometrial cancer was analyzed. Furthermore, the correlation between the expression of miR-15a-5p and the pathological features and prognosis was examined. Results The expression of miR-15a-5p in endometrial carcinoma was significantly lower than that in adjacent healthy tissues (2.22±0.75 vs. 2.59±0.91, P=0.000). Furthermore, the expression of miR-15a-5p in the endometrial cancer tissues of patients in the recurrence and metastasis group was significantly lower than that observed in patients in the control group (1.91±0.62 vs. 2.45±0.75, P=0.000). The receiver operating characteristic curve was used to analyze the predictive value of miR-15a-5p in endometrial cancer tissue for postoperative recurrence or metastasis in endometrial cancer patients. The area under the curve was 0.690 [95% confidence interval (CI): 0.601 to 0.798, P=0.000], the best cut-off value of diagnosis was 2.325, the sensitivity was 0.619, and the specificity was 0.733. Multivariate logistic regression analysis showed that miR-15a-5p expression

The long noncoding RNA DLGAP1‐AS2 facilitates the malignant progression of cholangiocarcinoma via miR‐505 and GALNT10 and may have potential as a novel target for cholangiocarcinoma therapy., Cholangiocarcinoma (CCA) is a highly invasive malignant tumor with high mortality. Most cases of CCA are already advanced when they are detected, resulting in poor prognosis. As such, there is an ongoing need for the identification of effective biomarkers for CCA. The long noncoding RNA DLGAP1‐AS2 has been reported to have prognostic value in glioma and Wilms' tumor. Here, we investigated the function of DLGAP1‐AS2 in CCA. The differential expression of DLGAP1‐AS2 in CCA tissues and normal tissues was first examined using data from the The Cancer Genome Atlas database and then in CCA cell lines by quantitative RT‐PCR (qRT‐PCR). The target gene was predicted by bioinformatics analysis, and the binding sites were confirmed using luciferase assay. DLGAP1‐AS2 is up‐regulated in CCA, and high DLGAP1‐AS2 expression promotes cell viability and is associated with poor prognosis. Notably, DLGAP1‐AS2 acts as a sponge to suppress miR‐505 expression, and miR‐505 reduces the expression of N‐acetylgalactosaminyltransferase 10 (GALNT10) in CCA cells. Biofunctional experiments revealed that a miR‐505 inhibitor almost completely removed the inhibitory effect of si‐DLGAP1‐AS2 on CCA cell malignant progression, whereas the malignant phenotype of cells cotransfected with si‐DLGAP1‐AS2 and si‐GALNT10 was significantly reduced as compared with the control. In summary, the DLGAP1‐AS2/miR‐505/GALNT10 axis may contribute to regulating the malignant progression of CCA and may have potential as a novel target for CCA therapy.

Background Krüppel-like factor 9 (KLF9) is one of the most important members of the KLF family, and is abnormally expressed in many tumors. However, the detailed function of KLF9 in endometrial cancer (EC) was barely investigated. Methods In this study, a total of 52 paired EC tissues were recruited to detect the KLF9 expression. Then a serial of phenotypic experiments and mechanism researches were performed. Results The results showed that KLF9 expression was decreased in EC tissues, and the reduced expression of KLF9 is associated with highly metastatic capacity of EC cells. KLF9 could inhibit the proliferation and invasion of EC cells by inhibiting the Wnt/β-catenin signaling pathway. Progesterone receptor (PR) could bind to KLF9 promoter and a positive correlation between KLF9 and PR expression was witnessed. Conclusions Taken together, the reduction of KLF9 induced by PR might participate in the development of EC and targeting KLF9 may provide a novel strategy for EC management.

We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased oestrogen levels are reported to be associated with increased BC risk. Herein, we assessed if oestrogens, including oestrone (E1), oestradiol (E2) and oestriol (E3), are associated with A-FABP in the obesity-related BC development. We collected 249 serum samples from women with or without BC and measured serum levels of E1, E2, E3 and A-FABP. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause individuals. E3 and E1 levels were higher in non-obese than in obese women. When samples were separated by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal obese than non-obese women without BC. These differences based on body mass index (BMI) were not observed among women with BC. E3 levels were higher in obese women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese women regardless of BC status. In addition, A-FABP was not associated with E1, E2 or E3. Altogether, our data suggest that A-FABP is independently regulated by obesity and menopausal status compared to oestrogens, thus playing a unique role in the development of BC.

Supplemental Digital Content is available in the text., Background: China has seen a burgeoning epidemic of obesity in recent decades, but few studies reported nationally on obesity across socio-demographic subgroups. We sought to assess the prevalence and socio-demographic associations of obesity nationwide. Methods: We assessed the prevalence of overall obesity (body mass index ≥28 kg/m2) and abdominal obesity (waist circumference ≥85/90 cm for women/men) among 2.7 million community-dwelling adults aged 35 to 75 years in the China PEACE Million Persons Project from 2014 to 2018 and quantified the socio-demographic associations of obesity using multivariable mixed models. Results: Age-standardized rates of overall and abdominal obesity were 14.4% (95% CI, 14.3%–14.4%) and 32.7% (32.6%–32.8%) in women and 16.0% (15.9%–16.1%) and 36.6% (36.5%–36.8%) in men. Obesity varied considerably across socio-demographic subgroups. Older women were at higher risk for obesity (eg, adjusted relative risk [95% CI] of women aged 65–75 versus 35–44 years: 1.29 [1.27–1.31] for overall obesity, 1.76 [1.74–1.77] for abdominal obesity) while older men were not. Higher education was associated with lower risk in women (eg, adjusted relative risk [95% CI] of those with college or university education versus below primary school: 0.47 [0.46–0.48] for overall obesity, 0.61 [0.60–0.62] for abdominal obesity) but higher risk in men (1.07 [1.05–1.10], 1.17 [1.16–1.19]). Conclusions: In China, over 1 in 7 individuals meet criteria for overall obesity, and 1 in 3 for abdominal obesity. Wide variation exists across socio-demographic subgroups. The associations of age and education with obesity are significant and differ by sex. Understanding obesity in contemporary China has broad domestic policy implications and provides a valuable international reference.

Graphical abstract, Highlights • Whole life exposure to low doses of cadmium results in a significant accumulation of metals in the testis. • Co-exposure to cadmium with a high fat diet increases cadmium levels. • Cadmium and high fat diet disrupt essential metal homeostasis in the testis., The effects of exposure to the environmental toxicant cadmium, in combination with obesity, on the metal content in mouse testis were evaluated. Starting in utero and continuing through to 10 or 24 weeks post-weaning, male mice were exposed to cadmium (0, 0.5 or 5 ppm), and fed either a low (LFD) or high fat diet (HFD) post-weaning. Testicular levels of cadmium and essential metals were determined 10 and 24 weeks post-weaning by ICP-MS. Similar to what has been previously observed in the liver, kidney, heart and brain, significant levels of cadmium accumulated in the testis under all exposure conditions. Additionally, HFD-fed animals accumulated more cadmium than did their LFD-treated counterparts. Both treatments affected essential metal homeostasis in the testis. These findings suggest that cadmium and obesity may compromise the reproductive potential in the male mouse by disrupting essential metal levels.

Immunoglobulin A nephropathy is the most common glomerular disease in China, accounting for about 20 % to 47 % of primary glomerular diseases. Xiyin liangxue decoction is a common experience in the treatment of Immunoglobulin A nephropathy in recent years. The research of this formula in the clinical treatment of Immunoglobulin A nephropathy has achieved obvious curative effect. This article aims to study the protective mechanism of xiyin liangxue decoction on Immunoglobulin A nephropathy rats and analyzes and compares the advantages of xiyin liangxue decoction and western medicine in the treatment of Immunoglobulin A nephropathy rats with Sprague dawley nephropathy rats. The results of the study showed that after treatment of Immunoglobulin A nephropathy rats with xiyin liangxue decoction, the renal function of the rats in the treatment group was significantly improved, the expressions of alanine aminotransferase and aspartate aminotransferase increased by 19 % and 5 % and the expressions of albumin and globulin increased by 19 % and 25 %. In addition, in the treatment group, the number of urine red blood cells, urine protein and urine mannose binding lectin decreased by 29 %, 13 % and 25 %, respectively. The urine volume of rats in the high dose group was significantly reduced by 13 % and the expressions of blood urea nitrogen and blood creatinine increased 22 % and 8 % respectively. After treatment with xiyin liangxue decoction, the cure rate of experimental Immunoglobulin A rats reached 24 % and 33 % had significant improvement. It can be seen that xiyin liangxue decoction has a good clinical treatment effect on Immunoglobulin A nephropathy rats.

Background With demographic and epidemiologic transitions, China has become home to the greatest number of obese individuals in the world. Effective policy intervention requires a contemporary assessment of obesity across broad socio-demographic subgroups. Purpose We aim to assess the prevalence of overall and abdominal obesity by socio-demographic characteristics and the associations of these characteristics with obesity in China. Methods Using the data of 2.7-million community-dwelling participants aged 35–75 years in the China PEACE Million Persons Project, a nationwide cross-sectional screening project from 2014 to 2018, we calculated the prevalence of overall and abdominal obesity based on national guideline definitions (body mass index ≥28 kg/m2, waist circumference ≥85/90 cm for women/men). We examined 12 available socio-demographic variables that are potentially associated with obesity, in addition to self-reported co-morbidities, and quantified the associations of these socio-demographic characteristics with obesity using multivariable mixed models. Results The prevalence of overall and abdominal obesity were 15.8% and 37.6% in women and 15.0% and 36.3% in men (Figure). Compared to individuals with normal weight, those with overall obesity had a higher prevalence of hypertension, dyslipidemia, and diabetes (in women: by 30.4, 16.1, and 6.0 percent points; in men, by 29.9, 31.2, and 5.8 percent points). A similar pattern was observed with abdominal obesity. In women, those aged 55–64 years constituted the largest age group with overall and abdominal obesity (33.7% and 35.0%), while in men, those aged 45–54 and 55–64 years constituted the largest age group with overall obesity (30.4%) and abdominal obesity (30.5%), respectively. Older women were at substantially higher risk for obesity (e.g., adjusted relative risk [95% CI] of women aged 65–75 vs. 35–44 years: 1.29 [1.27–1.31] for overall obesity and 1.76 [1.74–1.77] for abdominal obesity) while older men were not. Higher education was associated with lower risk in women (e.g., those with college or university education vs. less than primary school: 0.47 [0.46–0.48] for overall obesity and 0.61 [0.60–0.62] for abdominal obesity) but higher risk in men (1.07 [1.05–1.10] and 1.17 [1.16–1.19]). In both women and men, current smoking was associated with lower risk for obesity, and current drinking was associated with higher risk, but the magnitude of associations was smaller in women than men. Conclusions In China, over one in seven individuals meet criteria for overall obesity, and one in three for abdominal obesity. Wide variation exists across socio-demographic subgroups. The associations of age and education with obesity are significant and differ by sex. Understanding obesity in contemporary China has broad domestic policy implications and provides a valuable international reference. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): The National Key Research and Development Program from the Ministry of Science and Technology of China, the CAMS Innovation Fund for Medical Science

Exposure to the environmental toxicant cadmium (Cd) contributes to the development of obesity-associated diseases. Obesity is a risk factor for a spectrum of unhealthy conditions including systemic metabolic dyshomeostasis. In the present study, the effects of whole-life exposure to environmentally-relevant concentrations of Cd on systemic essential metal distribution in adult mice fed a high-fat diet (HFD) were examined. For these studies, male and female mice were exposed to Cd-containing drinking water for >2 weeks before breeding. Pregnant mice and dams with offspring were exposed to Cd-containing drinking water. After weaning, offspring were continuously exposed to the same Cd concentration as their parents, and divided into HFD and normal (low) fat diet (LFD) groups. At 10 and 24 weeks, mice were sacrificed and blood, liver, kidney and heart harvested for metal analyses. There were significant concentration dependent increases in Cd levels in offspring with kidney > liver > heart. Sex significantly affected Cd levels in kidney and liver, with female animals accumulating more metal than males. Mice fed the HFD showed > 2-fold increase in Cd levels in the three organs compared to similarly treated LFD mice. Cadmium significantly affected essential metals levels in blood, kidney and liver. Additionally, HFD affected essential metal levels in these three organs. These findings suggest that Cd interacts with HFD to affect essential metal homeostasis, a phenomenon that may contribute to the underlying mechanism responsible for the development of obesity-associated pathologies.

Background Mobile health interventions hold the prospect to support risk factor and lifestyle modification and are readily scalable in healthcare systems. Purpose We aim to assess whether text messaging program can improve glycemic control in high-risk patients with coronary heart disease (CHD) and diabetes mellitus (DM). Methods The study was a multi-centre randomised clinical trial conducted at 34 clinics in China. 502 individuals with both CHD and DM were recruited and randomly assigned to either the text messaging intervention (n=251) or control group (n=251). The control group received 2 thank-you messages per month in addition to usual care. The intervention group received 6 messages per week for 6 months. Messages provided educational and motivational information related to glucose monitoring, BP control, physical activity and lifestyle recommendations. The primary outcome was change in glycemic hemoglobin (HbA1C) from baseline to 6 months. Results Follow-up rate was 99%. At 6 months, HbA1C was significantly lower in intervention group compared to control group (mean HbA1C 6.7% vs. 7.2%, P Table 1. Primary and Secondary Outcomes Analyses at 6 Month Follow-up Parameter Intervention (N=251) Control (N=251) Mean Difference in Change P value for Baseline 6 Months Mean Change Baseline 6 Months Mean Change (95% CI) Difference in Change Primary Outcome HbA1C level, %, mean (SD) 6.9 (1.4) 6.7 (1.3) −0.2 (1.0) 7.1 (1.4) 7.2 (1.5) 0.1 (1.1) −0.3 (−0.5, −0.1) 0.003 Secondary Outcomes HbA1C level Conclusion Use of a simple, culturally sensitive mobile text-messaging program could be an effective and scalable way to improve disease self-management among patients with CHD and DM. Acknowledgement/Funding Research Special Fund for Public Welfare Industry of Health (201502009) from the National Health and Family Planning Commission of China

Background: Mobile health interventions may support risk factor management and are readily scalable in healthcare systems. We aim to evaluate the efficacy of a text messaging–based intervention to improve glycemic control in patients with coronary heart disease and diabetes mellitus in China. Methods and Results: The CHAT-DM study (Cardiovascular Health and Texting-Diabetes Mellitus) was a parallel-group, single-blind, randomized clinical trial that included 502 patients with both coronary heart disease and diabetes mellitus from 34 hospitals in China. The intervention group (n=251) received 6 text messages per week for 6 months in addition to usual care. Messages were theory driven and culturally tailored to provide educational and motivational information on glucose monitoring, blood pressure control, medication adherence, physical activity, and lifestyle. The control group (n=251) received usual care and 2 thank you messages per month. The primary outcome was change in glycated hemoglobin (HbA 1C [hemoglobin A 1C ]) from baseline to 6 months. Secondary outcomes were change in proportion of patients achieving HbA 1C 1C (−0.2% versus 0.1%; P =0.003) and a greater proportion of participants who achieved HbA 1C P =0.004). Change in fasting blood glucose was larger in the intervention group (between-group difference: −0.6 mmol/L; 95% CI, −1.1 to −0.2; P =0.011), but no other outcome differences were observed. Nearly all participants reported that messages were easy to understand (97.1%) and useful (94.1%). Conclusions: A text message intervention resulted in better glycemic control in patients with diabetes mellitus and coronary heart disease. While the mechanism of this benefit remains to be determined, the results suggest that a simple, culturally sensitive mobile text messaging program may provide an effective and feasible way to improve disease self-management. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02883842.

Background: Readmission after acute myocardial infarction in low- and middle-income countries like China is not well characterized. Methods and Results: We approached consecutive patients with acute myocardial infarction hospitalized within 24 hours of symptom onset and discharged alive from 53 geographically diverse hospitals in China. We described rates of unplanned 30-day readmission, their timing and admitting diagnoses, and fit Cox proportional hazards models to identify factors associated with readmission. Among 3387 patients, median (interquartile range) age was 61 (52–69) years, and 76.9% were men. The index median length of stay was 11 (8–14) days. Unplanned 30-day readmission occurred in 6.3% of the cohort; most readmissions (77.7%) were for cardiovascular diagnoses. Nearly half (41.9% of all-cause readmissions; 44.3% of cardiovascular readmissions) occurred within 5 days of discharge. Mini-Global Registry of Acute Coronary Events scores at admission (hazard ratio [HR], 1.15 for every 10-point increase; 95% CI, 1.05–1.25), longer length of stay (HR, 1.03; 95% CI, 1.00–1.06 for each extra day), and in-hospital recurrent angina (HR, 1.40; 95% CI, 1.04–1.89) were associated with higher unplanned all-cause readmission. Revascularization during the index hospitalization (70.2% of the cohort) was associated with lower risks of all-cause readmission (HR, 0.27; 95% CI, 0.18–0.42). In addition, left ventricular ejection fraction Conclusions: In China, most readmissions are for cardiovascular events, and almost half occur within 5 days of discharge. Clinical factors identify patients at higher and lower unplanned readmissions. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01624909.

Prostaglandin E2 (PGE2), a derivative of arachidonic acid, has been identified as a tumorigenic factor in many cancers in recent studies. Prostaglandin E synthase 2 (PTGES2) is an enzyme that in humans is encoded by the PTGES2 gene located on chromosome 9, and it synthesizes PGE2 in human cells. In our study, we selected 119 samples from endometrial cancer patients, with 50 normal endometrium tissue samples as controls, in which we examined the expression of PTGES2. Both immunohistochemistry (IHC) and Western blot analyses demonstrated that synthase PTGES2, which is required for PGE2 synthesis, was highly expressed in endometrium cancer tissues compared with normal endometrium. Stable PTGES2-shRNA transfectants were generated in Ishikawa and Hec-1B endometrial cancer cell lines, and transfection efficiencies were confirmed by RT-PCR and Western blot analyses. We found that PGE2 promoted proliferation and invasion of cells in Ishikawa and Hec-1B cells by cell counting kit-8 tests (CCK8) and transwell assays, respectively. PGE2 stimulation enhanced the expression of SUMO-1, via PGE2 receptor subtype 4 (EP4). Further analysis implicated the Wnt/β-catenin signaling pathway function as the major mediator of EP4 and SUMO-1. The increase in SUMO-1 activity prompted the SUMOlyation of target proteins which may be involved in proliferation and invasion. These findings suggest SUMO-1 and EP4 as two potential targets for new therapeutic or prevention strategies for endometrial cancers.

Background: We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased estrogen levels are associated with increased BC risk. Hypothesis: Estrogens (estrone: E1, estradiol: E2 and estriol: E3) are associated with A-FABP in the setting of obesity and obesity-related BC development. Methods: Immunoassays for E1, E2, E3, and A-FABP were performed using serum samples from women with and without BC. Results: Statistical analysis was conducted using the Mann-Whitney test and multiple linear regression models. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause among both non-obese and obese individuals (p Impact: 1) A-FABP expression is increased in postmenopausal obese women with and without BC; 2) E1 and E2 expression is higher in pre- than postmenopausal women, regardless of BMI; 3) E1 and E3 levels are higher in lean than obese individuals, regardless of menopausal status; 4) the influence of obesity on E1, E2 and E3 expression in postmenopause is lost in women with BC, 5) E3 is increased in obese vs. non-obese women with BC, and 6) A-FABP and estrogens are independently involved in the development of BC. Citation Format: Bing Li, Jiaqing Hao, Xiaofang Yan, Maiying Kong, Edward Sauter. A-FABP and estrogens are independently involved in the development of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4363.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell–associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

It is clear that obesity increases the risk of many types of cancer, including breast cancer. However, the underlying molecular mechanisms by which obesity is linked to cancer risk remain to be defined. Herein, we report that circulating adipose fatty acid binding protein (A-FABP) promotes obesity-associated breast cancer development. Using clinical samples, we demonstrated that circulating A-FABP levels were significantly increased in obese patients with breast cancer in comparison with those without breast cancer. Circulating A-FABP released by adipose tissue directly targeted mammary tumor cells, enhancing tumor stemness and aggressiveness through activation of the IL-6/STAT3/ALDH1 pathway. Importantly, genetic deletion of A-FABP successfully reduced tumor ALHD1 activation and obesity-associated mammary tumor growth and development in different mouse models. Collectively, these data suggest circulating A-FABP as a new link between obesity and breast cancer risk, thereby revealing A-FABP as a potential new therapeutic target for treatment of obesity-associated cancers.

Background Prostate-specific antigen screening for prostate cancer (CaP) remains controversial. This study establishes the role of microRNA 301a (miR-301a) as a supplemental biomarker that can distinguish between patients with benign prostate hyperplasia and clinically significant CaP. We evaluate the ability of miR-301a to predict the adverse pathology of CaP. Methods In the first cohort, serum and prostate tumor samples were obtained from thirteen patients with Benign prostate hyperplasia (BPH), twelve patients with Gleason 6, and sixteen patients with Gleason 7 prostate adenocarcinoma. In the second cohort, 40 prostatectomy cases were selected (BPH:12, Gleason 6:12 and Gleason 7:16). MiRNA was extracted from serum and tumor samples. Quantitative reverse transcription-polymerase chain reaction was performed for detection of miR-301a. To understand the molecular role of miR-301a, we performed cell viability, Western blots, promoter analysis, overexpression, and silencing studies in BPH and DU-145 cell lines. Results MiR-301a demonstrated a significantly higher expression in both serum and tumor tissue in patients with CaP when compared to patients with BPH (P = 0.011 and 0.013 for serum and tissue expression, respectively). Expression of miR-301a in prostatectomy specimens correlated with increased Gleason score. We demonstrated that miR-301a inhibited the pro-apoptotic function of RUNX3, and activated ROCK1-mediated pro-survival signal in CaP. Silencing miR-301a initiated the pro-apoptotic function of RUNX3 by inhibiting ROCK1 expression in CaP cells. Conclusions Expression of miR-301a could be a valuable adjunct tool for stratifying patients with elevated prostate-specific antigen, as well as those diagnosed with CaP. Including the miR-301a as an additional variable in MSKCC post-prostatectomy nomogram improved its ability in facilitating clinical decision-making.