Prevalence and related factors of abdominal obesity among urban adults aged 35 to 79 years in southwest China.

Objectives: This study aimed to investigate the prevalence and related factors of abdominal obesity among urban adults aged 35 to 79 years in southwest China. Methods: From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,981 people aged 35-79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. Abdominal obesity was defined as waist circumference ≥ 90 cm for men and ≥ 85 cm for women. Results: The prevalence of abdominal obesity was 30.7%, 24.8% in males and 33.9% in females (p < 0.001). The prevalence of abdominal obesity increased with BMI. The prevalence of abdominal obesity was positively correlated with age, sex, marriage, alcohol consumption, hypertension and diabetes, and negatively correlated with high education level, smoking and Physical activity. Conclusion: The prevalence of abdominal obesity among adults aged 35-79 in urban communities in southwest China is high, which is close to that of adults in urban communities in China. We should strengthen health education among the population, adopt healthy diet, maintain moderate physical activity and other measures to curb the prevalence of abdominal obesity in urban communities in southwest China.

IL-7 promotes CD19-directed CAR-T cells proliferation through miRNA-98-5p by targeting CDKN1A.

CAR-T targeting CD19 have achieved significant effects in the treatment of B-line leukemia and lymphoma. However, the treated patients frequently relapsed and could not achieve complete remission. Therefore, improving the proliferation and cytotoxicity of CAR-T cells, reducing exhaustion and enhancing infiltration capacity are still issues to be solved. The IL-7 has been shown to enhance the memory characteristics of CAR-T cells, but the specific mechanism has yet to be elaborated. miRNAs play an important role in T cell activity. However, whether miRNA is involved in the activation of CAR-T cells by IL-7 has not yet been reported. Our previous study had established the 3rd generation CAR-T cells. The present study further found that IL-7 significantly increased the proliferation of anti-CD19 CAR-T cells, the ratio of CD4 + CAR + cells and the S phase of cell cycle. In vivo study NAMALWA xenograft model showed that IL-7-stimulated CAR-T cells possessed stronger tumoricidal efficiency. Further we validated that IL-7 induced CAR-T cells had low expression of CDKN1A and high expression of miRNA-98-5p. Additionally, CDKN1A was associated with miRNA-98-5p. Our results, for the first time, suggested IL-7 could conspicuously enhance the proliferation of CAR-T cells through miRNA-98-5p targeting CDKN1A expression, which should be applied to CAR-T production.

TEAD4 predicts poor prognosis and transcriptionally targets PLAGL2 in serous ovarian cancer.

The oncogenic function of TEA domain transcription factor 4 (TEAD4) has been confirmed in multiple human malignancies, while its potential role and regulatory mechanism in serous ovarian cancer progression are left unknown. By the gene expression analyses from Gene Expression Profiling Interactive Analysis (GEPIA) database, TEAD4 expression is shown to be up-regulated in serous ovarian cancer samples. Here, we confirmed the high expression of TEAD4 in clinical serous ovarian cancer specimens. In the following functional experiments, we found that TEAD4 overexpression promoted serous ovarian cancer malignant phenotypes, including proliferation, migration and invasion in serous ovarian cancer SK-OV-3 and OVCAR-3 cells, while TEAD4 knockout exerted the opposite function. The tumor growth inhibition of TEAD4 depletion was also affirmed by a Xenograft model in mice. In addition, this phenotypic deterioration induced by TEAD4 overexpression was diminished by PLAG1 like zinc finger 2 (PLAGL2) silencing. More importantly, combined with the results of the dual-luciferase assay, the transcriptional regulation of TEAD4 on PLAGL2 promoter was evidenced. Our results showed that the cancer-promoting gene TEAD4 was involved in serous ovarian cancer progression via targeting PLAGL2 at the transcriptional level.

[Clinical Characteristics and Prognosis of Diabetic Foot Ulcers Patients of Different Renal Function Statuses].

Objective: To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. Methods: A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Results: Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). Conclusions: As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.

The prevalence of obesity-related hypertension among middle-aged and older adults in China.

Objective: The aim of our study was to assess the prevalence and geographic variation of obesity-related hypertension in China among adults aged 45 years or older. Methods: Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015. Stratified sample households covered 150 counties/districts and 450 villages/urban communities from 28 provinces by using household questionnaires, clinical measurements, and blood-based bioassays. A multivariable non-conditional logistic regression model was used to analyze the risk factors correlated with obesity-related hypertension. Results: The prevalence of obesity-related hypertension was 22.7%, ~120 million people, among adults aged 45 years or older in China. For people in the age ranges of 45-54, 55-64, 65-74, and ≥75 years, the prevalence of obesity-related hypertension was 16.7, 24.3, 27, and 26.7%, respectively, and the prevalence of obesity-related hypertension among hypertensive participants was 66.0, 60.9, 54.2, and 47.3%, respectively. Compared with non-obesity-related hypertension, the obesity-related hypertensive patients had a higher prevalence of diabetes mellitus, dyslipidemia, and hyperuricemia (all P < 0.0001). The prevalence of obesity-related hypertension showed a decreasing gradient from north to south and from east to west. Multivariate logistic regression analysis showed that female gender, living in urban areas, diabetes mellitus, dyslipidemia, and hyperuricemia were positively correlated with obesity-related hypertension. Conclusion: The prevalence of obesity-related hypertension among adults aged 45 years or older was high in China. Among hypertensive participants, older age was negatively correlated with obesity-related hypertension. Obesity-related hypertensive participants are more prone to aggregation of risk factors of atherosclerotic cardiovascular disease.

Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/ß-catenin pathway.

Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreover， western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.

[A Case of Pseudohypoaldosteronism Type â ¡ (PHA2) Caused by a Novel Mutation of KLHL3].

The patient, a 41-year-old woman, was admitted because "it was found out she had elevated serum potassium levels for 18 days". Eighteen days prior to admission at our hospital, the patient was found to have elevated serum potassium during hospitalization at another hospital, where the patient received symptomatic treatment and was discharged after her serum potassium returned to a normal level. However, the patient still had elevated serum potassium repeatedly and was referred to our hospital for further examination. The patient had a history of acute nephritis and gestational hypertension. Six months prior to admission at our hospital, it was found out that the patient had slightly elevated blood pressure, but no intervention was done. The patient's father has a history of hypertension and diabetes. After admission, laboratory results showed that the patient had hyperkalemia, hyperchloremia and metabolic acidosis. The level of plasma renin was obviously below the normal range, but the concentration of plasma aldosterone was within the normal range. A new mutation locus (c.1115delG) in KLHL3 (Kelch like family member 3) gene was revealed by genetic testing, leading to the diagnosis of pseudoaldosteronism type Ⅱ (PHA2). The patient was given regular treatment of oral hydrochlorothiazide hydrochloride at set intervals. Subsequently, her blood electrolyte level, blood pH, BE and BEB have returned to normal levels. The patient was followed up for 12 months and did not feel unwell during the follow-up period.

Prevalence and related factors of dyslipidemia among urban adults aged 35 to 79 years in Southwestern China.

This study aimed to investigate the prevalence of dyslipidemia and its related factors among urban adults aged 35 to 79 years in Southwestern China. From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,221 people aged 35-79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. The prevalence of high triglycerides (≥ 2.3 mmol/L), high total cholesterol (≥ 6.2 mmol/L), high low-density lipoprotein cholesterol (≥ 4.1 mmol/L), low high-density lipoprotein cholesterol (< 1.0 mmol/L), and dyslipidemia were 15.7% (95% confidence interval, 15.0-16.4%), 5.4% (4.9-5.8%), 2.5% (2.2-2.8%), 5.7% (5.3-6.2%), and 27.4% (26.5-28.2%), respectively. The prevalence of dyslipidemia was positively correlated with higher education level, monthly income over 2000 CNY, smoking, hypertension, diabetes, overweight and obesity, and central obesity, and negatively correlated with daily physical exercise. The prevalence of dyslipidemia in Southwestern China is lower than the national average level, with high triglycerides being the most common form of dyslipidemia.

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named "Tong Feng", which is described as "ache in bones and joints" with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. AIM OF THE STUDY: Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). MATERIALS AND METHODS: Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine, phellodendrine, magnoflorine, jatrorrhizine, berberrubine, palmatine, and tetrahydropalmatine, in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. RESULTS: PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. CONCLUSIONS: The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.

Evaluation of piggyBac-mediated anti-CD19 CAR-T cells after ex vivo expansion with aAPCs or magnetic beads.

Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.

Study on Network Pharmacological Analysis and Preliminary Validation to Understand the Mechanisms of Plantaginis Semen in Treatment of Gouty Nephropathy.

Plantaginis Semen (PS) has been used to promote diuresis and clear away dampness. Recent reports have shown that PS can be used to treat gouty nephropathy (GN). However, the action and mechanism of PS have not been well defined in treating GN. The present study aimed to define the molecular mechanisms of PS as a potential therapeutic approach to treat GN. A combination of network pharmacology and validation experiments in GN is used to understand the potential mechanism. Information on pharmaceutically active compounds in PS and gene information related to GN was obtained from public databases. The compound target network and protein-protein interaction network were constructed to study the mechanism of action of PS in the treatment of GN. The mechanism of action of PS in the treatment of GN was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment. Validation experiments were performed to verify the core targets. The GN rat model was prepared by the method of combining yeast and adenine. Hematoxylin-eosin (HE) staining was used to observe the morphology of renal tissue in rats. ELISA was applied to detect TGF-ß1, TNF-α, and IL-1ß levels in renal tissue. The expressions of TGF-ß1, TNF-α, and IL-1ß were determined using immunohistochemistry. Through the results of network pharmacology, we obtained 9 active components, 118 predicted targets, and 149 GN targets from the public database. Based on the protein-protein interaction (PPI), 26 hub genes for interaction with PS treating for GN were screened, including MMP9, TNF, IL1ß, and IL6. The enrichment analysis results showed that the treatment of GN with PS was mainly involved in the TGF-ß1 signaling pathway, MAPK signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K Akt signaling pathway. Validation experiment results showed that PS could reduce the content of urinary protein and UA and deregulate the expression of TGF-ß1, TNF-α, and IL-1ß in the treatment of GN. The molecular mechanism of PS in the treatment of GN indicated the synergistic features of multicomponent, multitarget, and multipathway of traditional Chinese medicine, which provided an essential scientific basis for further elucidating the mechanism of PS in the treatment of GN.

Prevalence and associated factors of hyperuricemia among urban adults aged 35-79 years in southwestern China: a community-based cross-sectional study.

Hyperuricemia is prevalent throughout the world. However, a well-designed large-scale epidemiological investigation of hyperuricemia in southwestern China is lacking. A regional representative sample of 10,141 participants were included using multistage, stratified sampling in Chengdu and Chongqing from September 2013 to March 2014. Hyperuricemia was defined as the self-reported of the doctor's diagnosis of hyperuricemia, or serum uric acid > 420 µmol/L in men or serum uric acid > 360 µmol/L in women. The overall age- and sex-standardized prevalence of hyperuricemia among adults aged 35-79 years was 13.5%. Compared with women, the prevalence of hyperuricemia in men was higher (17.3% versus 10.0%). Hypertension, hyperlipidemia, overweight or obesity, central obesity were associated with an increased risk for hyperuricemia both in men and in women. Married men and women were not susceptible to hyperuricemia. Current cigarette smoking was an associated risk factor of hyperuricemia only in women. Hyperuricemia has become a major health problem among urban adults aged 35-79 years in southwestern China, and special attention should be paid to men. Comorbidities associated with hyperuricemia and causality worth further investigation.

Prevalence and Associated Factors of Diabetes Mellitus in a Very Elderly Chinese Population: A Cross-sectional Study.

OBJECTIVES: This paper aimed to investigate the prevalence of diabetes mellitus (DM) and explore the associated risk factors in a very elderly southwest Chinese population. METHODS: From September 2015 to June 2016, a cross-sectional survey was conducted to obtain a representative sample of 1,326 participants over 80 years old living in Chengdu. The presence of DM was based on fasting plasma glucose (FPG) and 2-h plasma glucose (2-hPG) levels during an oral glucose tolerance test (OGTT). A logistic regression model was used to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) of the potential associated factors. RESULTS: The participants' mean age was 83.5 ± 3.1 years. The overall prevalence of DM was 27.4%. The prevalence was higher in males (30.2%) than females (24.7%) ( P = 0.02). The prevalence of DM increased with body mass index (BMI) and decreased with aging. The multivariate analysis suggested that male sex ( OR = 1.433; 95% CI, 1.116-1.843), hypertension ( OR = 1.439; 95% CI, 1.079-1.936), overweight or obesity ( OR = 1.371; 95% CI, 1.023-1.834), high heart rate (≥ 75 beats/min; OR = 1.362; 95% CI, 1.063-1.746), and abdominal obesity ( OR = 1.615; 95% CI, 1.216-2.149) were all significantly positively correlated with DM. However, age was negatively correlated with DM ( OR = 0.952; 95% CI, 0.916-0.989). CONCLUSIONS: The prevalence of DM and newly diagnosed DM in a very elderly southwest Chinese population was high. OGTT screening should be performed regularly in people aged ≥ 80 years to ensure timely diagnosis of DM.

Radiomic Features at Contrast-enhanced CT Predict Recurrence in Early Stage Hepatocellular Carcinoma: A Multi-Institutional Study.

Background Early stage hepatocellular carcinoma (HCC) is the ideal candidate for resection in patients with preserved liver function; however, cancer will recur in half of these patients and no reliable prognostic tool has been established. Purpose To investigate the effectiveness of radiomic features in predicting tumor recurrence after resection of early stage HCC. Materials and Methods In total, 295 patients (median age, 58 years; interquartile range, 50-65 years; 221 men) who underwent contrast material-enhanced CT and curative resection for early stage HCC that met the Milan criteria between February 2009 and December 2016 were retrospectively recruited from three independent institutions. Follow-up consisted of serum α-fetoprotein level, liver function tests, and dynamic imaging examinations every 3 months during the first 2 years and then every 6 months thereafter. In the development cohort of 177 patients from institution 1, recurrence-related radiomic features were computationally extracted from the tumor and its periphery and a radiomics signature was built with least absolute shrinkage and selection operator regression. Two models, one integrating preoperative and one integrating pre- and postoperative variables, were created by using multivariable Cox regression analysis. An independent external cohort of 118 patients from institutions 2 and 3 was used to validate the proposed models. Results The preoperative model integrated radiomics signature with serum α-fetoprotein level and tumor number; the postoperative model incorporated microvascular invasion and satellite nodules into the above-mentioned predictors. In both study cohorts, two radiomics-based models provided better predictive performance (concordance index ≥0.77, P < .05 for all), lower prediction error (integrated Brier score ≤0.14), and larger net benefits, as determined by means of decision curve analysis, than rival models without radiomics and widely adopted staging systems. The radiomics-based models gave three risk strata with high, intermediate, or low risk of recurrence and distinct profiles of recurrent tumor number. Conclusion The proposed radiomics models with pre- and postresection features helped predict tumor recurrence for early stage hepatocellular carcinoma. © RSNA, 2020 Online supplemental material is available for this article.

High prevalence of obesity-related hypertension among adults aged 40 to 79 years in Southwest China.

This study aimed to assess the prevalence and related factors of obesity-related hypertension among adults aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a multi-stage, stratified sampling method was conducted on 10,589 people aged 40 to 79 years and living in Chengdu and Chongqing investigated by using a questionnaire and performing physical and biochemical measurements. The prevalence of obesity-related hypertension and hypertension overall (systolic ≥130 mmHg and/or diastolic ≥80 mmHg or treated hypertension) was 22.8% and 57.4%, respectively, among all participants. For obesity-related hypertension, the prevalence was higher in women than in men (24.7% versus 19.4%, p < 0.001). For people in the age ranges of 40-49, 50-59, 60-69, and ≥70, the prevalence of obesity-related hypertension were 11.8%, 22.6%, 30.7%, and 36.6%, respectively. Participants with obesity-related hypertension as opposed to those with non-obesity-related hypertension had a higher prevalence of hypertriglyceridemia, high low-density lipoprotein cholesterolemia, diabetes, and hyperuricemia (all p < 0.05). Multivariate logistic regression analysis showed that age, female gender, current smoking, hypertriglyceridemia, diabetes and family history of hypertension were all positively correlated with obesity-related hypertension, whereas higher education level and having spouse were negatively correlated with obesity-related hypertension. The prevalence of obesity-related hypertension was high among adults aged 40 to 79 years in Southwest China. Cardiometabolic abnormalities among participants with obesity-related hypertension were more serious and frequently present than in those with non-obesity-related hypertension. Aggressive and holistic strategies aiming at the prevention and treatment of obesity-related hypertension are needed.

Machine-learning analysis of contrast-enhanced CT radiomics predicts recurrence of hepatocellular carcinoma after resection: A multi-institutional study.

BACKGROUND: Current guidelines recommend surgical resection as the first-line option for patients with solitary hepatocellular carcinoma (HCC); unfortunately, postoperative recurrence rate remains high and there is no reliable prediction tool. We explored the potential of radiomics coupled with machine-learning algorithms to improve the predictive accuracy for HCC recurrence. METHODS: A total of 470 patients who underwent contrast-enhanced CT and curative resection for solitary HCC were recruited from 3 independent institutions. In the training phase of 210 patients from Institution 1, a radiomics-derived signature was generated based on 3384 engineered features extracted from primary tumor and its periphery using aggregated machine-learning framework. We employed Cox modeling to build predictive models. The models were then validated using an internal dataset of 107 patients and an external dataset of 153 patients from Institution 2 and 3. FINDINGS: Using the machine-learning framework, we identified a three-feature signature that demonstrated favorable prediction of HCC recurrence across all datasets, with C-index of 0.633-0.699. Serum alpha-fetoprotein, albumin-bilirubin grade, liver cirrhosis, tumor margin, and radiomics signature were selected for preoperative model; postoperative model incorporated satellite nodules into above-mentioned predictors. The two models showed superior prognostic performance, with C-index of 0.733-0.801 and integrated Brier score of 0.147-0.165, compared with rival models without radiomics and widely used staging systems (all P < 0.05); they also gave three risk strata for recurrence with distinct recurrence patterns. INTERPRETATION: When integrated with clinical data sources, our three-feature radiomics signature promises to accurately predict individual recurrence risk that may facilitate personalized HCC management.

Assessment of tumor promoting effects of amniotic and umbilical cord mesenchymal stem cells in vitro and in vivo.

PURPOSE: Human mesenchymal stem cells (hMSCs) have been applied in a variety of therapies recently. However, the role of MSCs in tumor progression remains largely elusive. Some studies demonstrated that MSCs can promote tumor growth, while others had opposite results. Therefore, the lack of evidence about the effect of MSCs on tumor cells impedes its further use. METHODS: In the current study, hMSCs from amniotic membrane (hAMSCs) and umbilical cord (hUCMSCs) were used to evaluate the effects of MSCs on tumor development in vitro and in vivo. Two different animal models based on subcutaneous xenograft bearing nude mice and a murine experimental metastatic model were established for in vivo study. Moreover, cytokines regulated by MSCs co-cultured with cancer cells SPC-A-1 were also analyzed by cytokine array. RESULTS: Our results indicated that hUCMSCs not only did not promote proliferation in cancer cells, but also inhibited migration. In addition, they inhibited tube formation in human umbilical vein endothelial cells (HUVECs). Although hAMSCs also showed inhibitory effects on cancer cell motility, the proliferation of cancer cells was indeed enhanced. The in vivo data revealed that hUCMSCs did not promote tumor progression in lung adenocarcinoma and gastric carcinoma xenografts. Nevertheless, hAMSCs could do. The results from murine experimental metastatic model also demonstrated that neither hUCMSCs nor hAMSCs significantly enhanced the lung metastasis. The data from cytokine array showed that 11 inflammatory factors, 8 growth factors and 11 chemokines were remarkably secreted and changed. CONCLUSIONS: In view of the data from in vitro and in vivo studies, the exploitation of hUCMSCs in new therapeutic strategies should be safe compared to hAMSCs under malignant conditions. Moreover, this is the first report to systematically elucidate the possible molecular mechanisms involved in UCMSC- and AMSC-affected tumor growth and metastasis.

MicroRNA-671-3p promotes proliferation and migration of glioma cells via targeting CKAP4.

BACKGROUND AND OBJECTIVE: Glioma is one of the most aggressive and malignant cancers originating from the human brain. Increasing evidence suggests that aberrant expression of microRNAs (miRNAs) frequently occurs in glioma and miRNAs are critical regulators of glioma. miR-671 has recently been revealed to be a novel miRNA that plays a vital role in human glioblastoma multiforme. However, the functional role and underlying mechanisms of miR-671-3p require further analysis. MATERIALS AND METHODS: Western blot and fluorescence quantitative PCR were used to assess the expression of cytoskeleton-associated protein 4 (CKAP4) and miR-671-3p, respectively. A Cell Counting Kit-8 (CCK-8) assay and a Boyden chamber assay were used to detect the proliferative and migratory abilities of glioma cells. A luciferase assay was used to determine the target gene of miR-671-3p. Apoptosis was analyzed by flow cytometry. RESULTS: Our results revealed that overexpression of miR-671-3p promoted cell proliferation and migration in vitro. Meanwhile, forced expression of miR-671-3p reduced apoptosis. In contrast, inhibition of miR-671-3p had the opposite effects. We also identified CKAP4 to be a direct target of miR-671-3p. The expression levels of CKAP4 were decreased in clinical samples and inversely correlated with miR-671-3p expression levels. Ectopic expression of CKAP4 reversed the promotive activity of miR-671-3p in the proliferation and migration and enhanced apoptosis. CONCLUSION: Our study demonstrates that miR-671-3p is a predominant positive regulator of glioma progression, thus providing new insights into the molecular mechanisms of glioma development. The findings suggest that the miR-6713p/CKAP4 axis may serve as a potential therapeutic target or biomarker in glioma.