Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

The Predictive Value of CA-125 and Hb for Ocular Metastasis in Hepatocellular Carcinoma Patients.

Objective: To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers. Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student's t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM. Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L. Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125+Hb has potentially greater utility in diagnosing hepatocellular carcinoma.

Risk Factors and Their Diagnostic Values for Ocular Metastases in Gastric Adenocarcinoma.

OBJECTIVE: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. METHODS: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. RESULTS: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001). CONCLUSION: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.

[Possible pharmaceutical effect and active components in different parts of Eucommia ulmoides based on network pharmacology].

The difference in pharmacological activities and active components between leaves, barks and flowers of Eucommia ulmoides(EU) are still unclear. However, clarifying the differences in pharmacological effects of different parts of EU is of great significance for the development of EU products, and their corresponding active components provide basis for quality control of different parts of EU. Based on the chemical compositions of different parts of EU, integrated strategy of target prediction and target analysis of the compounds was used to investigate the difference in the pharmacological effects of leaves, barks and followers. The "component-target-function" association network was constructed to mine the specific material basis corresponding to specific efficacy of different parts of EU. In this study, the author found that EU may have the activities of anti-oxidation, neuromodulation, blood pressure regulation, myo-cardial expansion, and anti-apoptosis according to target prediction and function analysis. However, the effects of different parts of EU were different. Leaves were involved in the process of bone development such as osteoblast differentiation and bone mineralization in a specific way. In addition, the leaves may affect the process of bone development by regulating the metabolism of vitamin D and affecting the absorption of calcium. Leaves may also specifically act on estrogen and estradiol response processes where estrogen receptors were involved. Regarding its protective function for the liver, leaves may play a role by regulating vitamin A-related pathways. As compared with leaves, the specific pharmacological effects of barks may be related to the development of the urinary system. Flowers specifically participate in functions related to pain sensation, glutamate signaling pathway, and excitatory postsynaptic potential. Based on the hie-rarchical network of "component-target-pathway", we further found that specific activities of different parts of EU were inseparable from its specific chemical compositions. Phenylpropanoids, terpenoids and rings, iridoids, flavonoids and other components which are specific in leaves can target the specific effects of leaves, while the flavonoids in barks and the quinones in flowers may be the material basis for their respective specific effects. The prediction of the activities of different parts of EU provides a new basis for the focuses and differences in subsequent Eucommia product development. At the same time, the material basis research based on differential efficacy also provides a basis for the quality control of Eucommia differentiated products.

[Research advances in chemical constituents and pharmacological activities of different parts of Eucommia ulmoides].

To date, 205 compounds have been identified from different medicinal parts of Eucommia ulmoides, including lignans, iridoid terpenoids, phenols, flavonoids, terpenoids and steroids, polysaccharides and others. Their pharmacological effects include blood pressure-lowering, blood sugar-lowering, blood lipids-regulating, prevention of osteoporosis, anti-inflammation, liver protection, anti-cancer and so on. Their efficacy and mechanism from different parts are slightly different. In this paper, the chemical composition, pharmacological action and mechanism of different parts of E. ulmoides were systematically summarized, as well as its quality control and processing research, to provide theoretical basis for further rational development and utilization of E. ulmoides.

The prognosis and effects of local treatment strategies for orbital embryonal rhabdomyosarcoma: a population-based study.

INTRODUCTION: Orbital embryonal rhabdomyosarcoma is a rare childhood malignancy with a good prognosis, but the optimal treatment remains unclear. Using a population-based cancer registry, we assessed the prognoses and survival outcomes of patients with orbital embryonal rhabdomyosarcoma according to the local treatment strategy. PATIENTS AND METHODS: Patients diagnosed with orbital embryonal rhabdomyosarcoma between 1988 and 2012 as part of the Surveillance Epidemiology and End Results program were included. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors associated with cause-specific survival (CSS) and overall survival (OS). RESULTS: In total, 102 patients were included; their median age was 6 years, 78.4% were white, and 56.9% were male. The median tumor size was 30 mm. Of 20 patients with an available histologic grade, the tumors of 90% were poorly differentiated/undifferentiated. Of 92 patients with available surgical and radiotherapy (RT) statuses, 50 (54.3%), 36 (39.1%), and 6 (6.5%) received surgery and RT, primary RT, and primary surgery, respectively. Ninety-five patients (93.1%) received chemotherapy. The 5- and 10-year CSSs of the entire cohort were 94.3% and 92.2%, respectively. The 5- and 10-year OSs were 93.3% and 91.3%, respectively. In 95 patients who were followed up for at least 12 months, there were no significant prognostic factors related to CSS and OS. Furthermore, the local treatment strategy did not significantly affect CSS (P=0.29) or OS (P=0.468). CONCLUSION: There is no local treatment of choice for orbital embryonal rhabdomyosarcoma in terms of survival. However, RT is a reasonable alternative treatment to surgery.

Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: A population-based analysis.

OBJECTIVE: To investigate the demographic features, clinicopathological characteristics and treatment outcomes of patients with nasopharyngeal carcinoma (NPC) according to age at diagnosis. METHODS: We assessed demographic and clinicopathological variables extracted from the Surveillance, Epidemiology, and End Results database (2004-2014). The Cox proportional hazards regression model was used to perform univariate and multivariate analyses of NPC-related mortality (cause-specific survival). RESULTS: A total of 3880 patients were analyzed. Median age was 55-years-old; 108 (2.8%), 508 (13.1%), 1876 (48.4%), 1240 (32.0%), and 148 (3.8%) patients were aged 1-19, 20-39, 40-59, 60-79, and 80-99-years-old, respectively. Younger patients tended to be black and present with poorly/undifferentiated disease and advanced tumor and nodal category compared to older patients. Younger patients were more likely to receive chemotherapy than older patients. In multivariate analyses, age at diagnosis was an independent prognostic factor for cause-specific survival. Increasing age at diagnosis was associated with a significantly higher risk of NPC-related mortality. Compared to patients aged 1-19-years-old, the hazard ratios for patients aged 20-39, 40-59, 60-79, and 80-99-years-old were 2.030 (95% confidence interval 1.004-4.104), 2.871 (1.474-5.590), 4.443 (2.273-8.683), and 12.024 (5.855-24.695), respectively. With the exception of black patients (P=0.100), older age was associated with poor survival in all demographic and clinical subgroups. CONCLUSION: Although younger patients tended to have advanced disease at diagnosis, older age at diagnosis was associated with a higher risk of NPC-related mortality.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Clinicopathological features of small cell carcinoma of the uterine cervix in the surveillance, epidemiology, and end results database.

To investigate the clinicopathological characteristics and survival of small cell carcinoma of the cervix using Surveillance, Epidemiology, and End Results database. Patients with a diagnosis of small cell carcinoma of the cervix were included between 1988 and 2012. Kaplan-Meier method and Cox regression models were used. A total of 487 patients were included. Of the patients with known International Federation of Gynecology and Obstetrics stage and tumor grade, the stage IV disease was diagnosed in 37.9% patients, and 98.5% patients had poorly or undifferentiated histology. The 5-year cause specific survival and overall survival were 33.0% and 29.4%, respectively. In multivariate analysis, increasing age, advanced stage, and treatment by primary radiotherapy were associated with worse survival outcomes. Small cell carcinoma of the cervix is a rare disease with aggressive characteristics and prone to metastasize and is dismal in prognosis. Reduced survival was associated with increasing age, advanced stage, and treatment by primary radiotherapy.

Patterns of distant metastasis in Chinese women according to breast cancer subtypes.

To access possible relationships between breast cancer subtypes (BCS) and patterns of distant metastasis in advanced breast cancer. Breast cancer patients with distant metastasis at two academic centers from 2000-2015 were retrospectively reviewed. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) - (i.e., estrogen receptor [ER] + and/or progesterone receptor [PR] +, HER2-); HR+/HER2+ (ER+ and/or PR+, HER2+), HR-/HER2+ (ER- and PR-, and HER2+); and HR-/HER2- (ER- and PR-, and HER2-). A total of 679 patients were identified. The distribution of the BCS was 39.9% (271/679), 23.7% (161/679), 16.8% (114/679), and 19.6% (133/679) in HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-, respectively. Patients with HR+/HER2+ and HR-/HER2+ subtypes were prone to abdominal and pelvic metastasis, those with HR+/HER2- and HR+/HER2+ subtypes were prone to bone metastasis, while patients with the HR-/HER2- subtype were prone to lung/mediastinal and brain metastases. In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS. There are different patterns of distant metastasis associated with different BCS. There should be a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.

Resveratrol ameliorates lipid accumulation in HepG2 cells, associated with down-regulation of lipin1 expression.

The pathogenesis of alcoholic fatty liver (AFL) disease is associated with the excessive accumulation of lipids in hepatocytes as well as oxidative stress. Resveratrol (RES), a dietary polyphenol found in red wine and grapes, has been shown to protect against AFL disease. However, the precise mechanisms that lead to this protective effect remain elusive. In this study, we used HepG2 cells to investigate the effects of RES on lipid metabolism and the mechanisms underlying these effects. HepG2 cells were cultured with oleic acid and alcohol for 48 h to induce excessive lipid accumulation. Oil red O staining showed that administration of oleic acid and alcohol induced more lipid accumulation than was observed in the control group, and that RES (15, 45, or 135 µmol/L) treatment reduced intracellular lipid droplets. RES treatment also significantly attenuated hepatic steatosis and lowered levels of intracellular triglycerides (TG). Western blot analysis showed that RES enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and down-regulated the expression of sterol regulatory element-binding protein 1c (SREBP-1c) and lipin1. However, compound C, an AMPK inhibitor, reversed these effects of RES. In conclusion, RES reduced lipid accumulation and protected HepG2 cells. This effect may be associated with the down-regulation of SREBP-1c and lipin1 expression, increased levels of phosphorylated AMPK and ACC, and the activation of AMPK-lipin1 signaling.

Effects of somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma motilin.

Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue damage and pancreatic stump complications. Because our earlier clinical work saw a major increase in delayed gastric emptying (DGE) with somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy (PPPD), this small-group study was designed to confirm or disprove that observation. From August 1997 to December 2000, a total of 23 post-PPPD patients were randomized to receive somatostatin prophylaxis [somatostain (+)] (n = 11) or not [somatostatin] (-) (n = 12). The incidence of DGE, scintographic solid-phase emptying results on day 14 postoperatively, and sequential fasting plasma motilin levels were compared, as motilin levels are related to both gastric motility and somatostatin levels. The somatostatin(+) group exhibited greatly increased patient complaints of DGE: 9 of 11 (82%) versus 3 of 12 (25%) in the somatostatin(-) group. Radiologic scintography showed somatostatin prophylaxis prolonged the half-time (T(1/2)) of solid-phase emptying: 144.5 +/- 51.4 minutes for somatostatin(+) versus 89.0 +/- 59.9 minutes for somatostatin(-) (p < 0.001). Comparing pre-PPPD and post-PPPD plasma motilin levels prior to somatostatin infusion, motilin decreased 80% in reaction to the surgery. For somatostatin(-) patients, motilin levels oscillated, or "rang," postoperatively, reaching a higher level on day 3, declined to a new record minimum on day 7, and by day 21 were 50% of the original and the slope of the recovery curve was increasing well. In somatostatin(+) patients the same ringing pattern was observed but decreased with motilin levels 30% to 70% lower than in the somatostatin(-) patients. By day 21 somatostatin(+) motilin levels were recovering but still only 20% original levels, and the slope of the recovery curve was not optimistic. On postoperative day 14 the plasma motilin levels (below approximately 6 bg/ml) correlated strongly with DGE for both groups. Despite the small sample size, the results indicated that (1) somatostatin prophylaxis significantly decreases fasting plasma motilin; (2) somatostatin prophylaxis produces lingering suppression of plasma motilin; (3) PPPD surgery itself significantly reduces fasting motilin levels with recovery to 50% normal at day 21; (4) the mechanism of somatostatin-induced DGE seems related to reduced fasting plasma motilin levels.