Upregulated CANT1 is correlated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: CANT1, as calcium-activated protein nucleotidase 1, is a kind of phosphatase. It is overexpressed in some tumors and related to poor prognosis, but few studies explore its function and carcinogenic mechanism in hepatocellular carcinoma (HCC). METHODS: The expression of CANT1 mRNA and protein was analyzed by the Cancer Genome Atlas (TCGA) database and immunohistochemistry(IHC) staining. The relationship between CANT1 expression and clinicopathology was evaluated by various public databases. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of CANT1 by the area under curve (AUC). Univariate, multivariate Cox regression and Kaplan-Meier curves were applied to evaluate the predictive value of CANT1 on the prognosis of HCC. Methsurv was used to analyze gene changes and DNA methylation, and its impact on prognosis. The enrichment analysis of DEGs associated with CANT1 revealed the biological process of CANT1 based on Gene Set Enrichment Analysis (GSEA). The relationship between immune cell infiltration level and CANT1 expression in HCC was investigated using the single-sample GSEA (ssGSEA) method and the Tumor Immune Estimation Resource (TIMER) database. Finally, the association between CANT1 and immune checkpoints and drug sensitivity was also analyzed. RESULTS: CANT1 was highly expressed in 22 cancers, including HCC, and CANT1 overexpression in HCC was confirmed by IHC. The expression of CANT1 was correlated with clinical features, such as histologic grade. Highly expressed CANT1 caused poor overall survival (OS) of HCC patients. Univariate and multivariate regression analysis suggested that CANT1 was an independent prognostic marker. Of the 31 DNA methylation at CpG sites, three CpG sites were associated with the prognosis of HCC. GSEA indicated that CANT1 was mainly involved in the cell cycle, DNA replication, and etc. Moreover, CANT1 expression was correlated with immune cell infiltration and independently associated with the prognosis of HCC patients. Finally, CANT1 expression was correlated with most immune checkpoints and drug sensitivity. CONCLUSION: CANT1 may be a latent oncogene of HCC, and associated with immune cells and immune checkpoints, which may assist in HCC treatment.

The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma.

BACKGROUND: RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. METHOD: The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan-Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis（DCA）analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. RESULT: The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. CONCLUSION: We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.

Association Between Pre-Radiofrequency Catheter Ablation Serum Lipid Levels and Recurrence of Atrial Fibrillation in 412 Patients in Beijing, China: A Single-Center Study.

BACKGROUND This study from a single center in Beijing, China, included 412 patients with atrial fibrillation (AF) who underwent radiofrequency catheter ablation. We aimed to determine whether pre-ablation serum lipid levels were related to recurrence of atrial fibrillation (RAF). MATERIAL AND METHODS A total of 412 patients with AF who underwent radiofrequency catheter ablation were enrolled in the study. Fasting levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), were measured at baseline before ablation, and patients were classified according to lipid level quartiles (Q1-Q4). RAF was affirmed via 24-h electrocardiography or 12-lead electrocardiography. RESULTS A total of 82 (19.90%) patients experienced RAF. After adjusting for other relevant factors and sex, univariate logistic regression analysis revealed LDL-C (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.93-1.47) and TC (HR, 1.17; 95% CI, 0.96-1.42) levels were not significantly related to RAF. Multivariate logistic regression analysis revealed that, compared with the highest quartile (Q4), female patients with lower quartiles of TC had higher RAF, especially Q3 (HR, 16.24; 95% CI, 1.14-231.56). LDL-C levels were higher in Q1 than in Q4 but lower in Q2 and Q3 than in Q4 (Q1: HR, 1.34; 95% CI, 0.08-18.89; Q2: HR, 0.09, 95% CI, 0.06-1.52; Q3: HR, 0.02, 95% CI, 0.14-0.57). CONCLUSIONS This study showed RAF in almost 20% of treated patients and RAF was significantly related to pre-ablation serum levels of LDL-C and TC in women.

Cholesterol Metabolic Markers for Differential Evaluation of Patients with Hyperlipidemia and Familial Hypercholesterolemia.

The cholesterol metabolism in humans can be indirectly reflected by measuring cholesterol metabolism marker levels. We aimed to investigate the association of cholesterol homeostasis markers on standard lipid profiling components in familial hypercholesteremia and hyperlipidemia patients. A total of 69 hyperlipidemia patients, 25 familial hypercholesteremia (FHC) patients, and 64 healthy controls were enrolled in this study. We performed routine testing of blood lipid water. Gas chromatography was used to determine the changes in the concentration of cholesterol synthesis (squalene, desmosterol, and lathosterol) and absorption markers (campesterol, sitosterol, and stigmasterol) in the blood. Baseline hyperlipidemia patients displayed significantly higher total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in comparison to the control group, which was reflected in the increased levels of squalene, desmosterol, campesterol, and sitosterol observed (P < 0.05) in the hyperlipidemia patients. The desmosterol, lathosterol, campesterol, stigmasterol, and sitosterol were statistically different in the FHC group than the hyperlipidemic group (P < 0.05). The proportions of squalene/cholesterol, lathosterol/cholesterol, stigmasterol/cholesterol, and sitosterol/cholesterol in the FHC group were lower than those in the hyperlipidemic group; only desmosterol/cholesterol was higher than that in the hyperlipidemic group. Correlation studies between lipid metabolic factors showed that the proportion of moderate and strong correlations was much higher in the FHC group than in the other two groups (76.92% vs. 32.50% and 31.25%). Logistic regression analysis showed that the concentrations of glucose, LDL-C, lactosterol, and sitosterol were all independent risk factors for developing hyperlipidemia. This result was further confirmed by the ROC curve. These results indicated that the study of cholesterol synthesis and decomposition markers can serve as a reference index for related diseases caused by changes in its concentration.

Impact of Low-density Lipoprotein Cholesterol Levels on Outcomes in Nonvalvular Atrial Fibrillation: Results from the China Atrial Fibrillation Registry Study.

BACKGROUND Low-density lipoprotein cholesterol (LDL-C) reduction improves cardiovascular outcomes. This study investigates the relationship between lipid levels and outcomes in patients with nonvalvular atrial fibrillation by LDL-C quarters. MATERIAL AND METHODS Patients with atrial fibrillation were enrolled from 31 typical hospitals in China. Of 19 515 patients, 6775 with nonvalvular atrial fibrillation (NVAF) were followed for 5 years or until an event occurred. RESULTS Hyperlipidemia was not an independent risk factor for stroke/thromboembolism and cardiovascular mortality among patients with NVAF (hazard ratio 0.82, 95% CI 0.7-0.96, P=0.82). When patients were divided into quartiles according to LDL-C levels at the time of enrollment (Q1, <1.95; Q2, 1.95-2.51; Q3, 2.52-3.09; and Q4, >3.09 mmol/L), as LDL-C increased, events tapered off according to Kaplan-Meier curves for patients who were without oral anticoagulants and off statins (non-OAC; log-rank=8.3494, P=0.0393) and for those with oral anticoagulants (OAC; log-rank=6.7668 P=0.0797). This relationship was stronger for patients who were without OAC treatment and off statins than for those with OAC treatment. The relationship was not significant in patients with or without OAC and on statins (log-rank=2.5080, P=0.4738). This relationship also existed in patients with CHA2DS2-VASc scores <2 (log-rank=5.893, P=0.1167). For those with CHA2DS2-VASc scores ≥2 (log-rank=6.6163, P=0.0852), the relationship was stronger. CONCLUSIONS In patients with NVAF using standard or no lipid-lowering medication, low plasma LDL-C levels were related to an increased risk of stroke/thromboembolism and cardiovascular mortality.

Gas Chromatography and Flame-Ionization Detection of Non-Cholesterol Sterols as Indicators of Cholesterol Absorption and Synthesis in 158 Chinese Individuals with Normolipidemia, Hyperlipidemia, and Familial Hypercholesterolemia.

BACKGROUND There are limited studies on the effects of cholesterol homeostasis in populations at high risk for cardiovascular disease. We aimed to use gas chromatography and flame-ionization detection (GC-FID) of non-cholesterol sterols as indicators of cholesterol absorption and synthesis. Sterol indicators of cholesterol absorption included campesterol, stigmasterol, and sitosterol. Sterol indicators of cholesterol synthesis included squalene, 7-lathosterol, and desmosterol. MATERIAL AND METHODS A total of 158 participants were enrolled in 3 groups: healthy control (n=64), hyperlipidemia (n=69), and familial hypercholesterolemia (FH, n=25). Age, sex, blood pressure, blood glucose, and lipoprotein were collected, and cholesterol absorption and synthesis markers were determined by GC-FID. RESULTS All 6 cholesterol concentration indicators, except squalene, were significantly different among the 3 groups (all P<0.05); whereas in the ratio to cholesterol (%, sterols/cholesterol), only desmosterol and lathosterol were significantly different (P<0.05). Multifactorial regression analysis showed that triglycerides, total cholesterol, and desmosterol were independent risk factors affecting the development of hyperlipidemia (P<0.05). The efficacy of the ROC curve for the diagnosis of dyslipidemia was also higher for all 3 indices (Model 1, AUC=0.960). Model 1 was superior to Model 2 for the 6 indicators of cholesterol. For the FH and dyslipidemia groups, the 6-indicator model (Model 3) was shown to have a good diagnostic value (AUC=1.000). CONCLUSIONS The 6 sterol indicators of cholesterol absorption and synthesis had a dynamic course in all study participants. Desmosterol was an indicator of dyslipidemia. The combined use of the 6 sterol indicators differentiated between healthy individuals and patients with dyslipidemia and FH.

Laparoscopic circular stapled gastrointestinal anastomosis using novel device of sealed cap access after total laparoscopic gastrectomy / 中华胃肠外科杂志

Intracorporeal classic gastrointestinal anastomosis using circular stapler in totally laparoscopic gastrectomy (TLG) for gastric cancer requires intracorporeal anvil placement and suitable access for introduction of the circular stapler to the abdominal cavity without gas leak. The novel techniques for anvil placement have been updated, but there is no progress for proper access for circular stapler. In the study, intracorporeal circular-stapled gastrointestinal anastomosis were successfully accomplished using a novel device of sealed cap access with a central hole (WLB-60/70-60/100, Wuhan Widerep Medical Instrument Co.,Ltd, China) customized to the incision protection retractor for the simple and accessible introduction of the circular stapler and anvil under the optimal maintenance of pneumoperitoneum pressure in TLG. In these 3 cases, there was no gas leakage and the pneumoperitoneum was well maintained when performing the gastrointestinal anastomosis, and there was no transition to laparotomy or other anastomosis techniques. The result suggests that the sealed cap access could be a novel choice for introduction of the circular stapler to the abdominal cavity in order to obtain laparoscopic circular-stapled gastroin-testinal anastomosis in TLG.

Association Between Blood Lipid Profiles and Atrial Fibrillation: A Case-Control Study.

BACKGROUND Dyslipidemia is the most frequent comorbidity in patients with cardiovascular disease. However, studies examining the relationship between blood lipid profiles and AF have produced inconsistent results. MATERIAL AND METHODS A total of 651 patients were enrolled into 3 groups: Healthy controls (n=64), Paroxysmal AF (PAF; n=270), and Continuous AF (CAF; n=317). All enrolled patients underwent routine baseline 12-lead electrocardiography (ECG) and 24-h dynamic ECG along with blood testing, which included the following: complete metabolic panel, hepatic function, renal function, circulating thyroxine, fasting high-density lipoprotein cholesterol (HDL -C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC). RESULTS Patients with AF had significantly higher levels of triglycerides (TG), lower levels of LDL-C-c, and lower levels of HDL-C (p<0.05). TC (OR 0.979, p<0.9247) and TG (OR 0.945, p<0.6496) were negatively and linearly associated with PAF, while TG (OR 0.807, p=0.2042), LDL-C (OR 0.334, p=0.0036), and HDL-C (OR 0.136, p=0.0002) were negatively and linearly associated with CAF. CONCLUSIONS Compared to healthy controls, patients with AF had lower blood lipid levels, especially LDL-c and HDL-c levels. Hypolipoproteinemia may increase patient susceptibility to developing AF.

Imaging characteristics of pneumocystis pneumonia after renal transplantation.

Identification of Pneumocysis pneumonia (PCP) after renal transplantation has a great impact on early diagnosis and therapy, which could decrease its mortality. Due to a lack of characteristic clinical symptoms, imaging modalities became very important in the diagnosing PCP. Thirteen PCP patients after renal transplantation were reviewed. They underwent a series of chest radiographs and chest high-resolution CT scans. The common radiological presentations were bilateral diffuse symmetrical ground-glass and consolidation opacities, followed by pneumoceles or air-filled cysts or linear or reticular shadows. Ground-glass attenuations were showed clearly on HRCT in 13 patients, while only 6 on CXR. Pneumoceles or cysts (n = 8) were seen only on HRCT. Air-filled cysts or pneumoceles within bilateral diffuse symmetrical ground-glass and consolidation opacities may be the characteristic of this disease. If combined with clinical data, the diagnosis of PCP could be established.

Synthesis and bioactivity of substituted alpha-aminobenzylphosphonate / 药学学报

<p><b>AIM</b>To search for some substituted alpha-amino phosphonates as leading compounds with the vasodilator effects.</p><p><b>METHODS</b>Target compounds were prepared from benzyl aldehyde, piperazine and diethyl phosphite using alcohol as solvent via Mannich-type reaction. In isolated rat aorta and in isolated guinea pig ileum, the vasodilator effects of compounds were investigated and evaluated whether they activated muscarine receptor.</p><p><b>RESULTS</b>Seven compounds of substituted alpha-amino phosphonates have been synthesized and identified by IR, 1H NMR and elemental analysis. Three of them, compound 2a, 2b and 2c have vasodilator activity and do not activate M receptor.</p><p><b>CONCLUSION</b>Two (2b and 2c) of them were found to have the notable vasodilator effect, and the rates of relaxing are (67 +/- 21) % and (82 +/- 18)%, separately. But they did not activate M receptors on ileum.</p>