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Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy., Graphical abstract, Increased LINC00941 in PDAC enhances the interaction between MST1 and PP2A, which facilities PP2A-mediated dephosphorylating of MST1, resulting in Hippo pathway activation and enhancing the glycolysis in the PDAC cell, consequently promoting the progression of pancreatic cancer.

Aim: Coronavirus disease 2019 is a life-threatening disease and how to improve survival of the patients is of great importance. Objective: To determine whether tocilizumab (TCZ) shows favorable results in coronavirus disease 2019 patients. Materials & methods: A retrospective study of four patients who received TCZ was conducted from 19 February to 31 March 2020 at Leishenshan Hospital, Wuhan, China. Clinical data of patients were compared before and after the administration of the agent. Results: There was not much difference in the clinical feature improvements and computed tomography images after TCZ administration in two mild patients. The other two severe patients died of disseminated intravascular coagulation and acute respiratory distress syndrome, respectively. Conclusion: Administration of TCZ was not shown a favorable outcome in this preliminary uncontrolled case series., Lay abstract Patients treated with tocilizumab was not indicated a favoring outcome with not much improvement in two moderate patients and two severe patients died. Early identification of cytokine release syndrome in treating coronavirus disease 2019 patients with IL-6 antagonist is required.

To investigate the relationship between serum superoxide dismutase (SOD) activity and the presence of chronic complications in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective cross-sectional study in patients with T2DM. They were assigned to three groups (Q1, Q2, and Q3) by SOD levels in both sexes. Clinical characteristics, cardiovascular disease, diabetic retinopathy, nephropathy, and peripheral neuropathy were compared. The relationship between the SOD and the prevalence of chronic complications was analyzed by binary logistic regression. Statistical analysis was performed in SPSS 26.0 (SPSS Inc., Chicago, IL). A total of 645 T2DM patients (401 men and 244 women) with complete data for SOD and medical records of complications were included. In men, patients in the Q1 group (lowest serum SOD activity) had the highest prevalence of diabetes with atherosclerosis (AS) (p

Summary It is unknown whether there is any relationship between extremity arterial macroangiopathy and osteoporosis in type 2 diabetic mellitus (T2DM) patients. We provide evidence to show the association between lower extremity arterial calcification and the presence of osteoporosis in postmenopausal T2DM women, but not in T2DM men of similar age. Purpose To investigate the relationship between lower extremity arterial calcification and the presence of osteoporosis in type 2 diabetic mellitus (T2DM) patients. Methods We performed a retrospective cross-sectional study in patients with T2DM. They were assigned into two groups (patients with or without vascular calcification) in both sexes. Clinical characteristics, presence of osteoporosis, and bone metabolic markers were compared. Arterial calcification was determined by ultrasonography examination. Osteoporosis was defined based on the measurements from dual-energy X-ray absorptiometry. The relationship between the lower extremity arterial calcification and the presence of osteoporosis was analyzed. Statistical analysis was performed in SPSS 26.0. Results A total of 933 T2DM patients (535 men ≥ 50 years old, and 398 postmenopausal women) were identified and analyzed. A significant association between arterial calcification and osteoporosis was only observed in women, with a higher prevalence of osteoporosis observed in women with calcification (40.8%) than in women without calcification (26.9%) (P = 0.004). Compared to women without calcification, women with calcification had lower bone mineral densities in the hip (P < 0.001) and femoral neck (P < 0.001). Ordinal logistic regression analysis showed that women with calcification had a nearly 2-fold increased risk for osteoporosis, even after adjusting for age, duration of T2DM, body mass index, pulse pressure, clearance of creatinine, glycosylated hemoglobin, and fasting C-peptide. Similar differences were not identified between men with and without calcification. Conclusion Calcification of lower extremity arteries is related with the presence of osteoporosis in postmenopausal T2DM women. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05775-5.

Objective Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of the trithorax and polycomb genes, which have been proven to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors has been extensively studied in recent years. However, the relationship between ASXL2 and the prognosis of CRC is still unclear. Materials and methods In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on the proliferation of CRC cells were determined by CCK8 assay. Results This study demonstrated that ASXL2 was significantly more highly expressed in CRC specimens than in normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stage. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed that ASXL2 expression could be considered an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells. Conclusion These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC.

Ovarian carcinoma is the deadliest type of gynecological cancer. The unique tumor microenvironment enables specific and efficient metastasis, weakens immunological monitoring, and mediates drug resistance. Tumor associated macrophages (TAMs) are a crucial part of the TME and are involved in various aspects of tumor behavior. Lysophosphatidic acid (LPA) is elevated in the blood of ovarian carcinoma patients, as well as in the tumor tissues and ascites, which make it a useful biomarker and a potential therapeutic target. Recent studies have shown that LPA transforms monocytes into macrophages and regulates the formation of macrophages through the AKT/mTOR pathway, and PPAR γ is a major regulator of LPA-derived macrophages. In addition, TAMs synthesize and secrete LPA and express LPA receptor (LPAR) on the surface. With these data in mind, we hypothesize that LPA can convert monocytes directly into TAMs in the microenvironment of ovarian cancer. LPA may mediate TAM formation by activating the PI3K/AKT/mTOR signaling pathway through LPAR on the cell surface, which may also affect the function of PPAR γ, leading to increased LPA production by TAMs. Thus, LPA and TAMs form a vicious circle that affects the malignant behavior of ovarian cancer.

Ruili Jiao,1,2,* Shipeng Sun,3,* Xiaoqiong Gao,1 Ran Cui,1 Guangming Cao,1 Huali Wei,4 Shuzhen Wang,1 Zhenyu Zhang,1 Huimin Bai1 1Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Department of Obstetrics and Gynecology, Maternal and Child Health Hospital, Beijing, People’s Republic of China; 3Clinical Laboratories, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Department of Obstetrics and Gynecology, Emergency General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huimin Bai; Zhenyu Zhang Email bhmdoctor@sina.com; zhenyuzhang@ccmu.edu.cnObjective: This study tried to evaluate whether 8% polyethylene glycol (PEG) 6000 precipitation combined with differential ultracentrifugation (PPDU) was an efficient and practical method for the enrichment and purification of extracellular vesicles (EVs) derived from the culture supernatant of human ovarian cancer cell line A2780 and from body fluids of patients with high-grade serous carcinoma (HGSC).Methods: PPDU was used to enrich and purify the EVs derived from body fluids of patients with HSGC and cell culture supernatant of subclones of human ovarian cancer cell line A2780 with high/low invasive capacity (named as A-H/A-L, respectively). Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) were used to identificate the EVs size and distribution. Western blots (WB) were used to detect the expression of CD9, CD63, Alix and Calnexin. The high-purity EVs derived from the cell culture supernatant of A-H/A-L were detected by the protein profile. Expression of integrins (ITGs) αV, β 1 and β 3 in the EVs derived from body fluids of HGSC patients was also evaluated.Results: The diameter of EVs was about 30– 260 nm observed under the TEM. Under the NTA identification, the peak size of EVs was ranged from 70 to 159nm. EVs derived from different specimens did not significantly differ in mean size and peak size. Presence of CD9, CD63 and Alix and absence of Calnexin were confirmed in the EVs. The protein concentrations of EVs’ sample extracted from A-H/A-L cell culture supernatant were 0.36μg/μL and 0.20μg/μL, respectively. The total amount of protein obtained from 300ul EVs was 108.02ug and 61.44ug, respectively. Totally, 2397 peptides and 952 proteins were identified by isobaric tags for relative and absolute quantitation (ITRAQ). The expression of ITGαV, β 1, and β 3 in the EVs from plasma and ascites of HGSC patients was significantly higher than the control group (plasma: all P< 0.0001; ascites: P=0.036, 0.001 and 0.004, respectively). The expression level of ITGαV and β 1 in EVs of HGSC’s ascites was significantly higher than that in plasma (P= 0.004, 0.001, respectively). The expression of ITGβ 3 was also slightly elevated in EVs-derived HGSC patients’ ascites (P=0.492).Conclusion: PPDU was an efficient and practical method to enrich EVs from body fluids and cell culture supernatant. The characteristic expression of ITGαV, β 1 and β 3 in ascites and plasma EVs of patients with HGSC provided useful information on the development of EVs in HGSC.Keywords: EVs, PEG6000 precipitation, HGSC, body fluids, cell culture supernatant

Lysophosphatidic acid (LPA) is a bioactive lipid component of ovarian cancer activating factor, which is present at a high concentration in the ascitic fluid and plasma of patients with ovarian cancer. A group of six lysophosphatidic acid receptors (LPARs), LPAR1 through LPAR6, which belong to the G protein-coupled receptor superfamily (GPCR), mediate cellular activities of LPA and activates a series of downstream molecules and cellular responses, including biological and pathological effects. LPARs are widely expressed in normal ovary, benign tumor, and ovarian cancer tissues and cancer cell lines with a broad range of levels. The LPA/LPAR axis is involved in tumorigenesis and development of ovarian cancer through mediating the cellular responses to LPA and influencing the expression and function of oncogenic molecules. In the present review, the roles of LPARs in ovarian cancer, including the expression, function, and downstream molecules, are summarized, and we discuss the implications for ovarian cancer treatment that targets LPARs.

The change of tumor vessels is an important indicator for the evolution of cancer, which largely reflects the curative degrees. Therefore, in situ monitoring of the change of tumor vessels during the course of medical treatment becomes an urgent need for the implementation of therapy. Photothermal therapy (PTT), a promising treatment for cancer, has attracted extensive attention. So far, it lacks precise methods for visualizing tumor vessels during the PTT treatment in a noninvasive way. Herein, the quantum-dot-based nanoprobes emitting in the 1500-1700 nm range of the second near-infrared region (NIR-IIb window) with good photothermal conversion performance are conjugated with arginine-glycine-aspartate peptide and successfully applied to imaging-guided photothermal therapy. Owing to the high resolution of NIR-IIb fluorescence imaging, the process of significant reduction of tumor-associated vessels and abnormal angiogenesis is clearly demonstrated. Encouragingly, the immune response can be activated after the photothermal therapy. Excellent therapeutic efficacy with suppressed recurrence is achieved under the synergistic effect of destroying tumor tissues and enhancing immunity. This work provides a noninvasive method to evaluate the changes of tumor microvessel density for anti-angiogenesis therapy and affords a powerful tool for in vivo research of preclinical animal models and precise cancer therapies.

Both anemia and osteoporosis are common in type 2 diabetes mellitus (T2DM). However, the relationship between them remains to be determined. This study showed that anemia was related to osteoporosis in male and female T2DM patients. Diabetes patients with anemia should also be wary of osteoporosis. INTRODUCTION Anemia and osteoporosis are considered complications of type 2 diabetes mellitus (T2DM). However, the relationship between anemia and osteoporosis in the T2DM population remains to be determined. Thus, we planned the present study to verify their relationship. METHODS A retrospective cross-sectional study was performed. The patients were divided into groups according to sex and hemoglobin levels (Q1: ≤ 120, Q2: 120 to ≤ 140, Q3: > 140 in men; Q1: ≤ 110, Q2: 110 to ≤ 130, Q3: > 130 in women). Clinical characteristics and bone mineral density (BMD) were compared. The relationship between anemia and osteoporosis was determined after adjusting for age, diabetic duration, body mass index, alanine aminotransferase, creatinine, HbA1c, and fasting C-peptide. Statistical analysis was performed using SPSS 26.0. RESULTS This study included 2336 patients (1150 men and 1186 postmenopausal women). The percentage of osteoporosis differed by hemoglobin status in both men (Q1: 20.2%, Q2: 15.5%, Q3: 12.4%, P = 0.031) and women (Q1: 51.4%, Q2: 38.0%, Q3: 34.5%, P

ObjectivePatients with psoriasis (PsO) have a high frequency of concomitant gout and increased risk of cardiovascular diseases (CVD). We aimed to estimate the synergistic impact of gout on the risk of CVD in patients with PsO.MethodsA population-based cohort of patients registered in the National Health Insurance Research Database of Taiwan between 2000 and 2013 was stratified according to the presence of PsO and gout. Propensity score analysis was used to match age and gender at a ratio of 1:4. Cox proportional hazard models and subgroup analyses were used to estimate the hazard ratios (HRs) for CVD adjusted for traditional risk factors. The Kaplan–Meier method was used to plot the cumulative incidence curves.ResultsPatients with combined PsO and gout (n = 97), PsO alone (n = 388), gout alone (matched, n = 388) and matched controls (n = 388) were identified. Compared with the patients with PsO alone, the patients with combined PsO and gout had a significantly higher risk of CVD (relative risk 2.39, 95% CI 1.56 to 3.65). After adjustment for traditional risk factors, the risk of CVD was higher in patients with gout alone (HR 2.16, 95% CI 1.54 to 3.04) and in patients with combined PsO and gout (HR 2.72, 95% CI 1.73 to 4.28).ConclusionsGout augments the risk of CVD independently of traditional risk factors in patients with PsO.

Stomach adenocarcinoma (STAD) is one of the most common cancers in the world. However, the prognosis of STAD remains poor, and the therapeutic effect of chemotherapy and immunotherapy varies from person to person. MicroRNAs (miRNAs) play vital roles in tumor development and metastasis and can be used for cancer diagnosis and prognosis. In this study, hsa-miR-100-5p was identified as the only dysregulated miRNA in STAD samples through an analysis of three miRNA expression matrices. A weighted gene co-expression network analysis (WGCNA) was performed to select hsa-miR-100-5p-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a miR-100-5p-related prognostic signature. Kaplan–Meier analyses, nomograms, and univariate and multivariate Cox regression analyses were used to evaluate the prognostic signature, which was subsequently identified as an independent risk factor for STAD patients. We investigated the tumor immune environment between low- and high-risk groups and found that, among component types, M2 macrophages contributed the most to the difference between these groups. A drug sensitivity analysis suggested that patients with high-risk scores may be more sensitive to docetaxel and cisplatin chemotherapy and that patients in the low-risk group may be more likely to benefit from immunotherapy. Finally, external cohorts were evaluated to validate the robustness of the prognostic signature. In summary, this study may provide new ideas for developing more individualized therapeutic strategies for STAD patients.

Pancreatic adenocarcinoma is one of the most lethal diseases with a 5-year survival rate of about 8%. ASXL2 is an epigenetic regulator associated with various tumors including colorectal cancer, breast cancer, and myeloid leukemia. However, the role of ASXL2 in pancreatic cancer remains unclear. This is the first research focusing on the prognostic value of ASXL2 in pancreatic cancer. In this research, we aimed to explore the correlation between ASXL2 and the prognosis, as well as other features in PAAD. We obtained gene expression profiles of PAAD and normal tissues from TCGA, GEO, and Xena databases. TIMER and CIBERSORT algorithms were employed to investigate the effect of ASXL2 on tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of ASXL2. The response to various chemotherapeutic drugs was estimated by algorithms in R package “pRRophetic”, while the sensitivity to immunotherapy was quantified by TIDE score. We found that ASXL2 was upregulated in the PAAD samples and elevated expression of ASXL2 was linked to poor overall survival. ASXL2 DNA methylation contributed to ASXL2 expression. Functional annotation indicated that ASXL2 was mainly involved in inflammatory response and epithelial mesenchymal transition. Patients with high ASXL2 expression were more likely to benefit from immune checkpoint blockade, gemcitabine, and mitomycin-C. Finally, external datasets and biospecimens were used and the results further validated the aberrant expression of ASXL2 in PAAD samples. In summary, our results highlight that ASXL2 is a potential prognostic and predictive biomarker in pancreatic cancer.

People with type 1 diabetes mellitus (T1DM) must continuously monitor their blood glucose levels and regulate them by insulin dosing to stay in a safe range. A reliable glucose prediction technique could pre-alert the risk of abnormal glycaemia in the near future. In this paper, we apply an attention-based deep network for glucose prediction, which models both the temporal dependencies and the physiological relations among glucose and glucose-related life events, including insulin and carbohydrate intake. We also propose to make use of the knowledge learned from non-target subjects with the same disease to improve the personalised prediction by applying parameters transfer. Our approach was evaluated on the standard benchmark OhioT1DM dataset, where the experiments achieved average root mean square errors over the 12 subjects of 17.82 mg/dL for 30 minutes and 28.54 mg/dL for 60 minutes. Additionally, our ablation experiments indicated that the use of transfer learning constantly improved the prediction. On this basis, we conclude that our approach achieves state-of-the-art performance with statistical significance, and data from other people with T1DM could help on improving personalised predictions. We release our codes at https://github.com/r-cui/GluPred under the MIT license.

Background: Colorectal cancer (CRC) is one of the high incidence tumors and is ranked second in cancer-related mortality. Even though great progress has been made, there are no effective therapeutic strategies for late stage and metastatic CRC patients. Acidity is one characteristic of the tumor microenvironment. However, how cancer cells respond to this acidic environment surrounding them remains largely unknown, especially in colorectal cancer. Methods: Proton sensor receptor expression was analyzed in GEO and TCGA datasets. The expression of GPR4 in CRC specimens was confirmed by western blotting and immunohistochemistry (IHC). The role of GPR4 in CRC progression was analyzed both in vitro and in vivo. Pharmacological intervention, immunofluorescence and gene set enrichment analyses were performed to reveal the underlying molecular mechanisms of GPR4. Findings: We found that GPR4 was upregulated in CRC samples. In addition, its high expression correlated with late stage tumors and poor overall survival in patients. Furthermore, loss-of-function assays proved that GPR4 promoted CRC carcinogenesis and metastatic ability. Mechanistically, GPR4 was activated by extracellular protons in the tumor microenvironment and enhanced RhoA activation and F-actin rearrangement, leading to LATS activity inhibition, YAP1 nuclear translocation and oncogene transcription. Conclusions: The expression of GPR4 is upregulated in colorectal cancer and is associated with shorter overall survival time in CRCpatients. These findings reveal the novel roles of GPR4 in CRC progression and suggest GPR4 might be a new therapeutic target for CRC treatment. Funding Statement: This work was supported by the grant from the National Natural Science Foundation of China (No.81702300 & No.81873555). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: Study protocol that strictly in line with International Ethical Guidelines for Biomedical Research Involving Human Subjects was approved by the Research Ethics Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Patients that had received no anti-tumor therapy and signed written informed consent were enrolled in this study.

Obesity is a major epigenetic cause for colorectal cancer (CRC). Leptin is implicated in obesity-associated CRC, but the underlying mechanism remains unclear. The current study identified over-expression of metallopanstimulin-1 (MPS-1) in CRC patients through microarray and histological analysis, especially in obese CRC patients. MPS-1 was correlated with advanced tumor stage, suggesting its association with CRC progression. In addition, MPS-1 over-expression was associated with poor overall survival (OS) in obese CRC patients, but not in their non-obese counterparts, suggesting its potential as a prognostic marker of obese CRC patients. MPS-1 expression was positively associated with circulating leptin levels in CRC patients, especially in obese cases. Functional experiments demonstrated that MPS-1 silencing inhibited tumor proliferation and colony formation, and induced apoptosis of CRC cells in vitro. Converse results were obtained from the experiments with MPS-1 over-expression. Mechanistically, MPS-1 executed its action through induction of c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moreover, the promotion effect of MPS-1 on CRC progression was modulated by leptin. In vivo studies demonstrated that MPS-1 silencing suppressed tumor growth of CRC via inhibiting JNK/c-Jun signaling. Collectively, this study indicates that MPS-1 promotes leptin-induced CRC via activating JNK/c-Jun pathway. MPS-1 might represent a potent candidate for the treatment and prognostic prediction of obesity-associated CRC.

Cervical cancer is the most common malignancy of the female reproductive system. Dendritic cell (DC)-based immunological therapy is a novel treatment for this cancer. DCs are specialized antigen-presenting cells (APCs) in the human immune system, and they can activate the T cells used in tumor immunological therapy. In this study, we developed a novel immunotherapeutic peptide by linking the Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70) functional peptide to the extracellular domain of FPR1, a protein overexpressed in cervical cancer, to obtain an MTBHsp70-exFPR1 fusion protein. Our experiments confirmed that the MTBHsp70-exFPR1 protein could promote DC maturation and induce the secretion of IL-12p70, IL-1β, and TNF-α. The antitumor effect of human cytotoxic T lymphocytes (CTLs) activated by autologous DCs was assessed in NOG mice. These results indicate that DCs pulsed with MTBHsp70-exFPR1 can enhance antitumor immunity against cervical cancer, providing a novel immune therapeutic strategy.

Non-toxic and long-term fluorescent probes for tumor imaging are in urgent need for non-invasively obtaining information about tumor genesis and metastasis in vivo. Here, we present a biocompatible near-infrared fluorescent probe for in vivo long-term imaging of tumor by modifying glucose (Glc), which experiences high uptake in cancer cells, on the surface of near-infrared Ag2Se quantum dots (NIR Ag2Se QDs). The fluorescence of glucose-functionalized Ag2Se QDs (Glc-Ag2Se QDs) from the targeted tumor can be observed in vivo for at least 7 days. In addition, this probe could be excreted through kidneys and the renal excretion ability is favorable for in vivo imaging applications. Moreover, Glc-Ag2Se QDs could be used for tumor targeted imaging of not only human breast cancer cells (MCF-7), but also SW1990 pancreatic cancer cells since glucose is highly taken up in almost all kinds of tumors. Glc-Ag2Se QDs could be a promising general tool for in vivo long-term observation of tumor evolution.

Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.

ObjectivesThis study aimed to compare the prevalence of hypogonadism between male patients with latent autoimmune diabetes (LADA) and type 2 diabetes (T2DM) and investigate the risk factors for hypogonadism in these patients.MethodsThis cross-sectional study evaluated 367 male patients with LADA (n=73) and T2DM (n=294) who visited the endocrinology department of Shanghai Tenth People’s Hospital between January 2016 and October 2019 for diabetes management. Sex hormones, lipid profiles, sex hormone-binding globulin (SHBG), glycosylated hemoglobin A1c, beta-cell function, uric acid, and osteocalcin were determined in serum samples. Hypogonadism was defined as calculated free testosterone (cFT) less than 220 pmol/L along with the presence of symptoms (positive ADAM score).ResultsThe rate of hypogonadism in the LADA and T2DM group were 8.2, and 21.7%, respectively (p=0.017). After adjusting possible confounders, the rate of hypogonadism in the LADA group was comparable to those of the T2DM group. Univariate logistic regressions demonstrated that age, BMI, fasting C-peptide, triglycerides, total cholesterol and uric acid were associated with hypogonadism in men with diabetes, BMI, triglycerides and estradiol were independent risk for hypogonadism in men with diabetes.ConclusionThis is the first evidence to explore the rate of hypogonadism in male patients with latent autoimmune diabetes (LADA). In the population requiring admission to a large urban hospital in China, the rate of hypogonadism was comparable to those of the T2DM group after adjusting for possible confounders. BMI, triglycerides and estradiol were independently associated with the presence of HH in male diabetic patients.

Background: To investigate the possible association of diabetic peripheral neuropathy (DPN) and serum hemoglobin levels in type 2 diabetes mellitus (T2DM) patients with different glycosylated hemoglobin levels.Methods: A total of 995 patients were involved in this retrospective cross-sectional study. Laboratory medical data and electromyography results from the patients were collected. The patients were divided into five groups according to their HbA1c levels (Group 1: HbA1c ≤7%, Group 2: HbA1c 7% to ≤8%, Group 3: HbA1c 8% to ≤9%, Group 4: 9% to ≤10%, and Group 5: >10%). Differences in clinical data in the five groups were compared. Analysis of variance (ANOVA) and binary logistic regression analysis were used. All analyses were performed using SPSS 24 (SPSS Inc., Chicago, IL, USA). P value < 0.05 was considered to indicate statistical significance.Results: A correlation was found between the prevalence of DPN and anemia in both sex groups. Age, BMI, duration of diabetes, ALT, serum creatinine, TC, TG, LDL, FPG, FCP, and hemoglobin A1c differed to a statistically significant extent in different groups. Group 5 showed the highest prevalence of DPN in both sex groups. Hemoglobin levels were higher in Group 5 than in other groups, while composition of anemia was not statistically different. Binary logistic regression showed hemoglobin to be negatively related to the prevalence of DPN in Group 5 in men and in Group 4 in women.Conclusion: Hemoglobin level was negatively associated with the occurrence of DPN at the HbA1c level of >10% in men and 9 to 10% in women in T2DM patients. HbA1c must be considered in exploring the correlation between hemoglobin and DPN.

Background The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation. Methods A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm. Results According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P Conclusion PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.

Background: Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of trithorax and polycomb gene, which have been proved to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors have been extensively studied in recent years. However the relationship between ASXL2 and the prognosis of CRC is still unclear.Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on proliferation of CRC cells were determined by CCK8 assay.Results: This study demonstrated that ASXL2 was significantly more expressed in CRC specimens relative to the normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stages. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed ASXL2 expression could be considered as an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells.Conclusion: These results showed that ASXL2 could induce cell proliferation which is associated with poor prognosis of CRC patients and might be a new therapeutic target for CRC.

Objective. The aim of this study was to evaluate the safety and efficacy of intra-arterial versus intravenous neoadjuvant chemotherapy for the management of patients with locally advanced cervical cancer. Methods. The PubMed, EMBASE, PMC, Web of Science, and Cochrane databases were searched to identify correlational studies published in English. Prospective controlled studies that evaluated the treatment effect of intra-arterial neoadjuvant chemotherapy or intravenous neoadjuvant chemotherapy in patients with locally advanced cervical cancer were pooled for a meta-analysis. Results. A total of three eligible studies with 112 patients with locally advanced cervical cancer were eventually included in this analysis. The baseline regimen of neoadjuvant chemotherapy was platinum-based chemotherapy. The total clinical response rate was 71.4%, and the overall pathological complete response (CR) rate was 11.5%. The grade 3/4 toxicity rate was 27.2%. In the intra-arterial group, the response rate was 83.1% (CR, 22.0%; partial response (PR), 61.0%), which was significantly higher than 58.5% (CR, 11.3%; PR, 47.2%) in the intravenous group (P=0.01). The pathological CR rate was 15.5% in the intra-arterial group, which was higher than 6.5% in the intravenous group. The grade 3/4 toxicity rate was 17.2% in the intra-arterial group, which was higher than the rate of 13.8% in the intravenous group. Conclusion. Platinum-based neoadjuvant chemotherapy was well tolerated in patients with locally advanced cervical cancer and showed moderate response activity. Compared to intravenous neoadjuvant chemotherapy, intra-arterial neoadjuvant chemotherapy had an evident advantage in terms of the clinical response while maintaining a similar toxicity rate. The clinical efficacy of intra-arterial neoadjuvant chemotherapy deserves further evaluation.

Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers.

Signal transducer and activator of transcription (STAT)3 expression is correlated with neoplasm growth, metastasis, and prognosis; it has also been implicated in the regulation of autophagy, which may in turn contribute to tumor chemoresistance. However, it is unknown whether STAT3 is involved in cancer cell survival in response to chemotherapy. In this study, we show that autophagy is triggered during chemotherapy and that inhibiting autophagy increased chemosensitivity of castration-resistant prostate cancer (CRPC) cells. Meanwhile, docetaxel induced autophagy was inhibited by STAT3 activation, which increased mitochondrial damage and decreased CRPC cell viability. These results suggest that STAT3 contributes to CRPC cell survival and chemoresistance by modulating autophagy.

Background Acanthosis nigricans (AN) has a close relationship with obesity. It is believed that obesity and AN have the common pathophysiological basis such as hyperinsulinism. This study is aimed to observe the effect of laparoscopic sleeve gastrectomy (LSG) on body composition and insulin resistance in Chinese obese patients with acanthosis nigricans. Methods A total of 37 obese patients who underwent LSG in our hospital were selected for analysis. They were divided into simple obesity (OB n = 14) and obesity with acanthosis nigricans (AN n = 23) group respectively. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements and glucolipid metabolism before and 3 months post LSG were collected for analysis. Results Patients with AN got noticeable improvement in skin condition and their AN score was significantly decreased (3.52 ± 0.79 vs. 1.48 ± 0.73, P

Objective. Recent studies have shown that hyperuricemia (HUA) is associated with hypertension, dyslipidemia, insulin resistance, and metabolic syndrome (MetS). We aimed to examine the relationship of serum UA with Acanthosis nigricans (AN) and related metabolic indices in obese patients. Methods. A cross-sectional study with 411 obese patients recruited from our department was analyzed in this study. Weight, body mass index (BMI), UA, lipid profile, liver function, and renal function were measured in all participants. Oral glucose tolerance tests were performed, and serum glucose, insulin, and C peptide were measured at 0, 30, 60, 120, and 180 min. Results. AN group had higher serum UA levels than OB group. Circulating UA levels were associated with BMI, dyslipidemia, hypertension, IR, and AN. In logistic regression analyses (multivariable‐adjusted), a high serum UA level was associated with high odds ratios (ORs) (95% confidence interval [CI]) for AN in females (ORs = 3.00 and 95% CI [1.02–8.84]) and males (ORs = 6.07 and 95% CI [2.16–17.06]) in the highest quartile (Q4) of serum UA. Conclusions. Serum UA levels were positively associated with multiple metabolic abnormalities including obesity, hypertension, hyperglycemia, hyperlipidemia, and AN and may be an important risk factor in the development of AN; further evidences in vitro and in vivo are needed to investigate the direct or indirect relationship.

Objective: To evaluate the feasibility of conservative management for patients with morbidly adherent placenta (MAP) accidentally encountered after term vaginal delivery. Methods: Medical records of patients with MAP who were accidentally encountered after term vaginal delivery and treated in our hospital from January 2009 to December 2015 were retrospectively reviewed. Results: A total of 8 eligible patients were included in this analysis. Primary postpartum hemorrhage occurred in 5 (62.5%) cases. Emergent uterine artery embolization, intrauterine balloon occlusion, and blood transfusion were performed in 5 (62.5%), 2 (25%), and 2 (25%) cases, respectively. Placentas were left in situ in all these 8 cases. Subsequent adjunctive medication treatments, including methotrexate, mifepristone, and traditional Chinese medicine, were administered in 7 (87.5%), 4 (50%), and 3 (37.5%) cases, respectively. The retained placenta spontaneously passed out in 4 (50%) patients. Additional curettage operation was performed in 3 (37.5%) patients. Emergent hysterectomy was performed in 1 (12.5%) patient due to cardiac insufficiency and acute pulmonary edema caused by sepsis. No other severe adverse events were identified. Conclusions: Conservative management is feasible for patients with MAP accidentally encountered after vaginal delivery with close follow-up.

Odontogenic ameloblast-associated protein (ODAM), an acidic matricellular protein, has been implicated in several epithelial neoplasms. However, its biological functions and molecular mechanisms in cancer progression, particular colorectal carcinoma (CRC), remain unknown. Here we demonstrated that ODAM was significantly down-regulated in CRC tissues compared with their normal counterparts. Then, we established that ODAM expression level was closely correlated with CRC development and patient prognosis. The abnormal expression of ODAM dramatically affected CRC cell growth in vitro and in vivo. We further revealed that the inhibitory effects of ODAM on CRC cell growth were associated with PTEN elevation and PI3K/AKT signaling inactivation. Furthermore, we determined that silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing CRC cells. Our study suggests matricellular protein ODAM may serve as a novel prognostic marker and act as a CRC growth suppressor.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in the world, after Alzheimer's disease (AD), affecting approximately 1% of people over 65 years of age. Exosomes were once considered to be cellular waste and functionless. However, our understanding about exosome function has increased, and exosomes have been found to carry specific proteins, lipids, functional messenger RNAs (mRNAs), high amounts of non-coding RNAs (including microRNAs, lncRNAs, and circRNAs) and other bioactive substances. Exosomes have been shown to be involved in many physiological processes in vivo, including intercellular communication, cell migration, angiogenesis, and anti-tumor immunity. Moreover, exosomes may be pivotal in the occurrence and progression of various diseases. Therefore, exosomes have several diverse potential applications due to their unique structure and function. For instance, exosomes may be used as biological markers for the diagnosis and prognosis of various diseases, or as a natural carrier of drugs for clinical treatment. Here, we review the potential roles of exosomes in the pathogenesis, diagnosis, treatment, and prognosis of PD.

It is unknown whether a relationship exists between bone mineral density (BMD) and atherosclerosis with or without vascular calcification. In our study, a negative correlation between carotid atherosclerosis and BMD was found in female T2DM patients with vascular calcification, but not in those without calcification and males. Atherosclerosis is considered associated with low bone mineral density (BMD). However, most previous studies focus on patients with arterial atherosclerosis with vascular calcification. It is still unknown whether a relationship exists between atherosclerosis and BMD in patients without calcification. It is also unknown if sex plays a role in this relationship. We performed a retrospective cross-sectional study, which included 1459 type 2 diabetes mellitus (T2DM) patients (648 males ≥ 50 years old, and 811 postmenopausal females). They were assigned to three groups: group 1 (patients without carotid plaques and without carotid calcification), group 2 (patients with carotid plaques but without carotid calcification), and group 3 (patients with carotid plaques and with carotid calcification). Clinical characteristics and BMD were compared. The relationship between atherosclerosis and BMD was determined by binary logistic regression analysis. Statistical analysis was performed using SPSS 25.0. Significant differences were only observed in women. The percentage of osteoporosis was higher in group 3 (43.64%) than in groups 1 (34.82%) and 2 (32.14%) (P = 0.016). Low BMD was found in the lumbar (P = 0.032), hip (P

Preeclampsia (PE) is the major cause of maternal, fetal and neonatal mortality affecting approximately 2-7% of pregnancies. Transthyretin (TTR) is down-regulated in PE pregnancies serum and placenta. Our bioinformatic analysis showed that TTR is a predicted target for miR-200a-3p and miR-141-3p. The aim of this study was to determine whether miR-200a-3p and miR-141-3p are involved in preeclampsia through its targeting of TTR in human placental trophoblasts. In human PE placenta, TTR transcript and protein levels were significantly lower associated with high expression of miR-141-3p and 200a-3p. We found that miR-200a-3p and miR-141-3p inhibited TTR expression by directly binding to the 3'UTR of TTR, which is reversed by mutation in the microRNA binding site. In preeclamptic plasm, TTR levels were significantly downregulated. TTR was validated as a direct target of miR-200a-3p and miR-141-3p using dual luciferase assays in JEG3 cells. Transwell insert invasion assays showed that TTR mediated the invasion-inhibitory effect of miR-200a-3p and miR-141-3p in JEG3 cells. These data provides new insight into physiological role of miR-141-3p and miR-200a-3p in regulating TTR during trophoblast dysfunction and PE development.

Background: Robot-assisted surgical techniques have been introduced in recent years as an alternative minimally invasive approach for colorectal surgery. In practice, we found that the mon...

The tumor microenvironment is replete with cells that evolve with and provide support to tumor cells during the transition to malignancy. The hijacking of the immune system in the pancreatic tumor microenvironment is suggested to contribute to the failure to date to produce significant improvements in pancreatic cancer survival by various chemotherapeutics. Regulatory T cells, myeloid derived suppressor cells, and fibroblasts, all of which constitute a complex ecology microenvironment, can suppress CD8+ T cells and NK cells, thus inhibiting effector immune responses. Tumor-associated macrophages (TAM) are versatile immune cells that can express different functional programs in response to stimuli in tumor microenvironment at different stages of pancreatic cancer development. TAM have been implicated in suppression of anti-tumorigenic immune responses, promotion of cancer cell proliferation, stimulation of tumor angiogenesis and extracellular matrix breakdown, and subsequent enhancement of tumor invasion and metastasis. Many emerging agents that have demonstrated efficacy in combating other types of tumors via modulation of macrophages in tumor microenvironments are, however, only marginally studied for pancreatic cancer prevention and treatment. A better understanding of the paradoxical roles of TAM in pancreatic cancer may pave the way to novel preventive and therapeutic approaches. Here we give an overview of the recruitment and differentiation of macrophages, TAM and pancreatic cancer progression and prognosis, as well as the potential preventive and therapeutic targets that interact with TAM for pancreatic cancer prevention and treatment.

Both oncoprotein and tumor-suppressor activity have been reported for SIRTUIN1 (SIRT1) and p38 in many types of cancer. The effect of SIRT1 on p38 phosphorylation (p-p38) remains controversial and may be organ- and cell-specific. We found that SIRT1 is essential for maintaining liver size and weight in mice. SIRT1 levels were elevated in human HCC compared to adjacent normal liver tissue, and its expression correlated positively with p-p38 levels. Additionally, SIRT1-activated p38 increased liver cancer malignancy. SIRT1 increased phosphorylation and nuclear accumulation of p38, possibly by increasing MKK3 expression. SIRT1 also induced YAP expression, which in turn increased MKK3 transcription. Positive correlations between SIRT1, YAP, MKK3, and p-p38 levels indicate that blocking their activity may prove helpful in treating HCC.

We read with great interest the published paper by Xia et al 1 which provided an in-depth analysis regarding the relationship between psoriasis, psoriatic arthritis (PsA) and osteoporosis. By comprehensively analysing the datasets from three Genome-Wide Association Studies and UK Biobank, the authors concluded that the association between PsA and estimated bone mineral density (eBMD)/osteoporosis/fracture was not genetically determined but secondary (eg, treatment with methotrexate or ciclosporin). Although the conclusion was drawn based on very stringent confounders controlling, there are a few points in this study that are worth mentioning. First, typically, many background characteristics should be controlled in an observational study, especially with large datasets. In association analysis part, only seven confounders (ie, age, height, weight, smoking, drinking, regular physical …

The 2019 European League against rheumatism/American College of Rheumatology classification criteria (EULAR/ACR 2019 criteria) for systemic lupus erythematosus (SLE) has introduced a new scoring system to classify SLE.1 The EULAR/ACR 2019 criteria include positive antinuclear antibody at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical and three immunological domains and weighted from 2 to 10. Patients fulfilling at least one clinical criterion and accumulating ≥10 points are classified. In validation cohort, a classification threshold score of ≥10 yielded a sensitivity similar to that of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria (96.1% vs 96.7%) and a specificity similar to that of the ACR 1997 criteria (93.4% vs 93.4%), demonstrating both excellent sensitivity and specificity. However, we have two concerns about its additive criteria and methodology. First, some gastrointestinal injuries related to SLE, especially lupus enteritis, may be underestimated. Gastrointestinal symptoms are reported to occur in more than 50% of patients with SLE at some point in the course of their disease; …

Background:Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy affecting 6~30% of patients with skin or nail psoriasis. If PsA is not identified early and managed appropriately, progressive joint damage with deformities and disability may occur. Preliminary efforts to develop screening tools for the identification of PsA have met with variable success. Whether the tools function well or not in Chinese patients remains unknown.Objectives:We aimed to validate and compare the performance of 4 PsA screening tools in Chinese psoriasis patients.Methods:Consecutive psoriasis patients (dermatology cohort) attending dermatology clinics without previous diagnosis of inflammatory arthritis and consecutive newly diagnosed PsA patients (rheumatology cohort) attending rheumatology clinics were invited to complete the questionnaires: early arthritis for psoriatic patients (EARP), psoriatic arthritis screening and evaluation(PASE), psoriasis and arthritis screening questionnaire(PASQ), and psoriasis epidemiology screening tool (PEST). Receiver operating characteristic (ROC) curves were utilized to calculate diagnostic accuracy, least absolute shrinkage and selection operator(lasso) and binary logistic regressions to identify the most discriminative questions.Results:In this multicenter study, 379 patients in the dermatology cohort and 72 in the rheumatology cohort were recruited. In the dermatology cohort, 7.9% (30/379) were newly diagnosed with PsA. The EARP and PASQ tools demonstrated better discriminating ability for identifying PsA from psoriasis patients (yielded sensitivities/specificities were: 93.3%/92.3% and 90.0%/90.5%, while optimal cut-off values were: 3 and 5, respectively), and the good performance of EARP and PASQ was further confirmed in the rheumatology cohort. However, all these tools demonstrated low sensitivities (about 30%) with regard to screening the axial PsA. Based on the questions, a risk prediction model of PsA was established.Conclusion:The prevalence rate of undiagnosed PsA in the patients with psoriasis is 7.9%. Both EARP and PASQ tools show better favorable trade-off between sensitivity and specificity than PASE and PEST, while all the 4 tools are not sensitive to identify axial PsA.References:[1] Villani AP, Rouzaud M, Sevrain M, et al. Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and meta-analysis.Journal of the American Academy of Dermatology2015;73(2): 242-8.[2] Tinazzi I, Adami S, Zanolin EM, et al. The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.Rheumatology (Oxford, England) 2012;51(11): 2058-63.[3] Majed Khraishi IL, Gerry Mugford. The Self-Administered Psoriasis and Arthritis Screening Questionnaire (PASQ): A Sensitive and Specific Tool for the Diagnosis of Early and Established Psoriatic Arthritis.Psoriasis Forum2010;16(2): 9-16.[4] Husni ME, Meyer KH, Cohen DS, Mody E, Qureshi AA. The PASE questionnaire: pilot-testing a psoriatic arthritis screening and evaluation tool.Journal of the American Academy of Dermatology2007;57(4): 581-7.[5] Ibrahim GH, Buch MH, Lawson C, Waxman R, Helliwell PS. Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire.Clinical and experimental rheumatology2009;27(3): 469-74.Acknowledgments:This project was supported by grants from National Natural Science Foundation of China (81771746 and 81471604).Disclosure of Interests:None declared

Background and objective Previous studies about the prognostic value of the HIPEC have yielded controversial results. Therefore, this study aims to assess the impact of HIPEC on patients with ovarian cancer. Results We included 13 comparative studies, and found that the overall survival (OS) and progression-free survival (PFS) in HIPEC groups were superior to groups without HIPEC treatment in the all total population (HR = 0.54,95% CI:0.45 to 0.66, HR = 0.45, 95% CI: 0.32 to 0.62). Additionally, the subgroup analysis showed that patients with advanced primary ovarian cancers also gained improved OS and PFS benefit from HIPEC (HR = 0.59,95% CI:0.46 to 0.75, HR = 0.41,95% CI:0.32 to 0.54). With regard to recurrent ovarian cancer, HIPEC was associated with improved OS (HR = 0.45,95% CI:0.24 to 0.83), but for the PFS, no correlation was observed between HIPC group and the non-HIPEC group (HR = 0.55,95% CI:0.27 to 1.11). HIPEC also led to favorable clinical outcome (HR = 0.64,95% CI:0.50 to 0.82, HR = 0.36,95% CI:0.20 to 0.65) for stage III or IV ovarian cancer with initial diagnosis. Conclusion The review indicated that HIPEC-based regimens was correlated with better clinical prognosis for patients with primary ovarian cancers. For recurrent ovarian cancers, HIPEC only improved the OS but did not elicit significant value on the PFS. Electronic supplementary material The online version of this article (10.1186/s13048-019-0509-1) contains supplementary material, which is available to authorized users.

Objectives: This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received progestin therapy to spare fertility and, thus, improve the management of this patient group. Materials and methods: The PubMed, PMC, EMBASE, Web of Science, and Cochrane databases were searched for correlational studies published in English. Studies that evaluated the prognosis of patients with CAH or early-stage EC were pooled for a systematic review and meta-analysis. Results: In total, 31 eligible studies, including 8 prospective and 23 retrospective studies involving 1099 patients, were included in this analysis. The most commonly used progestin agents were medroxyprogesterone acetate (MPA, 47.0%) and megestrol acetate (MA, 25.5%). The total complete response (CR) rate was 75.8% (833/1099), and the median time to CR with first-line progestin therapy was 6 months. In total, 294 (26.8%) patients who achieved CR became pregnant spontaneously (28 cases) or through assisted reproductive technology (127 cases). During the median follow-up of 39 months, 245 (22.3%) women developed recurrence. Only one patient (0.09%) died of the disease. The meta-analysis showed that compared to a BMI

The aim of the study was to investigate the longitudinal bone mineral density(BMD) and bone metabolic related markers changes in obese patients with acanthosis nigricans (AN) and without AN(OB) after Laroscopic Sleeve Gastrectomy (LSG). 41 obese patients (AN group:n=29,OB group:n=12) were recruited in this study. Areal BMD (aBMD) and lumbar spine volumetric BMD (vBMD)were measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Insulin and markers of bone metabolism including 25-OHD, calcium, intact parathyroid hormone (iPTH), osteocalcin (OC), and type I collagen cross-linked C-terminal telopeptide (CTX) ] were assessed; Insulin area under the curve(AUCins) and HOMA-IR were computed. Results showed that the AN group had a higher fasting serum insulin (42.80±28.52 vs. 22.55±8.94mU/L,p=0.006), AUCins (522.42±280.32 vs. 263.87±195.75mU/L,p=0.008)and BMI(40.6±5.1 vs. 36.7±4.1kg/m2,p=0.024) compared to the OB group at baseline. The both groups did a obvious decrease in HOMA-IR after LSG; In AN group, there was a significant decrease in Lumbar vBMD(-4.4%,p=0.011), pelvic aBMD (-6.48%,p In conclusion, Insulin resistance was improved, and bone turnover was activated one year after LSG in both groups, but the bone loss was more likely to occur in the obese patients with acanthosis nigricans. Disclosure Y. Zhang: None. Z. Zhang: None. C. Zhu: None. S. Sun: None. Y. Yin: None. R. Cui: None. H. Sheng: None. S. Qu: None.

Background: Gut uses variety of pathways to establish closely contact with obesity and obesity related diabetes, including gut-brain cross-talk, gut microbiota, immune pathway and gastrointestinal hormones. In this study, we aimed to identify the key pathways and genes of gastric mucosa in obesity patients with or without type 2 diabetes. Methods: Our study was divided into three groups, healthy control group with normal BMI, patients with simple obesity(OB) and obesity with type 2 diabetes mellitus(OD), three cases in each groups. Gastric mucosal tissues were isolated then analyzed by gene microarray. The differentially expressed genes were screened by functional enrichment analysis and pathway analysis. Results: 262 up-regulated genes and 265 down-regulated genes were differentially expressed between OB and normal-BMI patients. Besides, 1756 up-regulated genes and 1053 down-regulated genes were differentially expressed between OD and control subjects (fold change>2 p < 0.05). For DEGs comparisons in each group, 13 genes were co-up regulated, 10 genes were co-down regulated, and an additional 12 genes showed different trends. After analyzing the biological process and molecule function of differential expression genes, these genes were found to play crucial roles mainly in cellular metabolic, protein binding and other biological process. The analysis of KEGG showed that the relevant genes participate in Citrate cycle, NF-kappa B and PI3K-Akt signaling pathway. Conclusions: During the process of obesity and obesity related diabetes, in gut there is not only one specific gene or pathway, but multiple genes and pathways that change. The effects of genes expressed in gastric mucosa mainly influence cellular metabolic processes, NF-kappa B and other proinflammatory signaling pathway. Disclosure X. Wen: None. Y. Zhang: None. R.J. Wu: None. C. Zhu: None. R. Cui: None. Y. Hui: None. F.Y. Mei: None. J. Gao: None. S. Qu: None. L. Bu: None.

Objective: Type 2 diabetes mellitus complicated with microvascular diseases can be used as a model to study the relationship between bone health and the microvascular situation. Methods: A total of 2,170 patients with type 2 diabetes mellitus (1,188 postmenopausal females and 982 males aged ⩾50 years) were included in our cross-sectional study. These patients were grouped according to 24-hour urine protein level: Group I (Results: Group III had the lowest bone mineral density level in both genders. Multivariate analysis revealed that microangiopathy was negatively correlated with bone mineral density in females (lumbar: r = –0.522, p < 0.001; hip: r = –0.301, p = 0.010; femoral neck: r = –0.314, p = 0.009), but not in males, after adjustment for age, body mass index, hypertension, hyperlipidemia, diabetic status, hepatic function, kidney function, sex hormones and 25(OH) vitamin D. Conclusion: These results demonstrate an independent negative correlation between microangiopathy and bone mineral density in postmenopausal female type 2 diabetes mellitus patients.

The clinical significance of the chloride intracellular channel 1 (CLIC1) protein in ovarian cancer is yet to be determined. The present study aimed to investigate the association between CLIC1 expression, and clinicopathological features and prognosis of patients with epithelial ovarian cancer. In this retrospective study, CLIC1 level was determined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The association between CLIC1 expression and clinicopathological characteristics were evaluated. Progression-free survival and overall survival were assessed by univariate, and multivariate analyses. mRNA and protein levels of CLIC1 were significantly higher in cancerous tissues than in healthy ovarian tissues (P

An increasing number of studies have reported that immunotherapy serves a significant role in ovarian cancer treatment. In recent years, blockade of checkpoint pathways, including programmed death-ligand 1 (PD-L1)/programmed death-1 and cytotoxic T-lymphocyte-associated protein 4, has demonstrated significant clinical and preclinical benefits in the treatment of ovarian cancer. Additionally, tumor-associated angiogenesis and homologous recombination deficiency frequently occurs in patients with high-grade ovarian cancer, which makes cancer cells more susceptible to targeted therapies, including therapies targeting poly (ADP-ribose) polymerase inhibitor, and anti-angiogenic approaches. Additionally, targeted therapy has been associated with elevated PD-L1 expression in tumor cells, increased T-cell infiltration in tumors and dendritic cell stimulation. This synergistic effect provides the rationale for the joint application of targeted therapy and immunotherapy. Checkpoint blockades are able to elicit durable antitumor immune reactions and complement the transient antitumor effect of targeted therapies. The current review discusses the underlying mechanism of these therapies and novel developments in combined therapy for the treatment of ovarian cancer.

We previously demonstrated that long non-coding RNA cytoskeleton regulator RNA (CYTOR), also known as Linc00152, was significantly overexpressed in colon cancer and conferred resistance to oxaliplatin-induced apoptosis. At the same time, elevated CYTOR expression was also reported in gastric cancer and exerted influences on epithelial-mesenchymal transition (EMT) markers. However, the precise mechanism by which CYTOR promotes the EMT phenotype and cancer metastasis remains poorly understood. Here, we showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression. Knockdown of CYTOR attenuated colon cancer cell migration and invasion. Conversely, ectopic expression of CYTOR induced an EMT program and enhanced metastatic properties of colon cancer cells. Mechanistically, the binding of CYTOR to cytoplasmic β-catenin impeded casein kinase 1 (CK1)-induced β-catenin phosphorylation that enabled it to accumulate and translocate to the nucleus. Reciprocally, β-catenin/TCF complex enhanced the transcription activity of CYTOR in nucleus, thus forming a positive feed-forward circuit. Moreover, elevated CYTOR, alone or combined with overexpression of nuclear β-catenin, was predictive of poor prognosis. Our findings suggest that CYTOR promotes colon cancer EMT and metastasis by interacting with β-catenin, and the positive feed-forward circuit of CYTOR-β-catenin might be a useful therapeutic target in antimetastatic strategy.