Choline suppresses hepatocellular carcinoma progression by attenuating AMPK/mTOR-mediated autophagy via choline transporter SLC5A7 activation.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/ß-catenin signaling.

Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the ß-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating ß-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.

Reinvestigation of 2-acetylthiazole formation pathways in the Maillard reaction.

2-Acetylthiazole possesses a nutty, cereal-like and popcorn-like aroma and a low odor threshold, and this compound has been identified in some processed foods, while the formation pathway of 2-acetylthiazole has not been clearly elucidated. Here, a model reaction of d-glucose and l-cysteine was constructed to investigate the formation pathway of 2-acetylthiazole. l-Cysteine, d-glucose and the corresponding intermediates, namely, dicarbonyl compounds (DCs), were involved in the formation of 2-acetylthiazole and detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), high-performance ion chromatography (HPIC) and HPLC, respectively. The carbon module labeling (CAMOLA) technique revealed that the C-4 and C-5 of 2-acetylthiazole were derived from the carbons of glucose. The potential of glyoxal, which is degraded by glucose, to form 2-acetylthiazole was revealed for the first time. A novel route to form 2-acetylthiazole by the reaction of glyoxal and methylglyoxal produced by d-glucose with H2S and NH3 produced by l-cysteine was proposed.

Genome-wide selective sweep analysis of the high-altitude adaptability of yaks by using the copy number variant.

The domestic yak (Bos grunniens) from the Qinghai-Tibet Plateau is an important animal model in high-altitude adaptation studies. Here, we performed the genome-wide selective sweep analysis to identify the candidate copy number variation (CNV) for the high-altitude adaptation of yaks. A total of 531 autosomal CNVs were determined from 29 yak genome-wide resequencing data (15 high- and 14 low-altitude distributions) by using a CNV caller with a CNV identification interval > 5 kb, CNV silhouette score > 0.7, and minimum allele frequency > 0.05. Most high-frequency CNVs were located at the exonic (44.63%) and intergenic (46.52%) regions. In accordance with the results of the selective sweep analysis, 7 candidate CNVs were identified from the interaction of the top 20 CNVs with highest divergence from the F ST and V ST between the low (LA) and high (HA) altitudes. Five genes (i.e., GRIK4, IFNLR1, LOC102275985, GRHL3, and LOC102275713) were also annotated from the seven candidate CNVs and their upstream and downstream ranges at 300 kb. GRIK4, IFNLR1, and LOC102275985 were enriched in five known signal pathways, namely, glutamatergic synapse, JAK-STAT signaling pathway, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and olfactory transduction. These pathways are involved in the environmental adaptability and various physiological functions of animals, especially the physiological regulation under a hypoxic environment. The results of this study advanced the understanding of CNV as an important genomic structure variant type that contributes to HA adaptation and helped further explain the molecular mechanisms underlying the altitude adaptability of yaks.

Genome-wide selection signatures analysis of litter size in Dazu black goats using single-nucleotide polymorphism.

Litter size is considered to be the most important index for estimating domestic animal productivity. The number of indigenous goats in China with higher litter sizes than those of commercial breeds in other countries may be helpful for accelerating genetic improvements in goat breeding. We performed a genome-wide selective sweep analysis of 31 Dazu black goats with extreme standard deviation in litter size within the third fetus to identify significant genomic regions and candidate genes through different analyses. The analysis identified a total of 33,917,703 variants, including 32,262,179 SNPs and 1,655,524 indels. In addition, two novel candidate genes (LRP1B and GLRB), which are related to litter size, were obtained with π, Tajima's D, πA/πB, and F ST at the individual level with a 95% threshold for each parameter. These two genes were annotated in five GO terms (localization, binding, macromolecular complex, membrane part, and membrane) and two pathways (long-term depression and neuroactive ligand-receptor interaction pathway). Regarding the result of linkage disequilibrium (LD) analysis, in LRP1B and GRID2, the high-yield Dazu black goats exhibit significantly different LD patterns from low-yield goats. Litter size variability has low heritability and is related to multiple complex factors found in domestic animals. Obtaining a clear explanation and significant signal by genome-wide selective sweep analysis with a small sample size is difficult. However, we investigated some candidate genes, particularly LRP1B and GLRB, which may provide useful information for further research.

Loss of MED12 Induces Tumor Dormancy in Human Epithelial Ovarian Cancer via Downregulation of EGFR.

A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecologic malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells in vitro and in vivo, and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation. Additionally, MED12 bound to the promoter of EGFR, and correlation studies showed that MED12 expression positively correlated with EGFR expression in EOC patient samples. Clinical data demonstrated that chemotherapy-resistant patients expressed lower levels of MED12 compared with responsive patients. Overall, our data show that MED12 plays an important role in regulating dormancy of EOC through regulation of EGFR.Significance: MED12 is identified as a novel, important regulator of tumor dormancy in human ovarian cancer. Cancer Res; 78(13); 3532-43. ©2018 AACR.

Prenatal choline supplementation attenuates spatial learning deficits of offspring rats exposed to low-protein diet during fetal period.

Prenatal intake of choline has been reported to lead to enhanced cognitive function in offspring, but little is known about the effects on spatial learning deficits. The present study examined the effects of prenatal choline supplementation on developmental low-protein exposure and its potential mechanisms. Pregnant female rats were fed either a normal or low-protein diet containing sufficient choline (1.1g/kg choline chloride) or supplemented choline (5.0g/kg choline chloride) until delivery. The Barnes maze test was performed at postnatal days 31-37. Choline and its metabolites, the synaptic structural parameters of the CA1 region in the brain of the newborn rat, were measured. The Barnes maze test demonstrated that prenatal low-protein pups had significantly greater error scale values, hole deviation scores, strategy scores and spatial search strategy and had lesser random search strategy values than normal protein pups (all P<.05). These alterations were significantly reversed by choline supplementation. Choline supplementation increased the brain levels of choline, betaine, phosphatidylethanolamine and phosphatidylcholine of newborns by 51.35% (P<.05), 33.33% (P<.001), 28.68% (P<.01) and 23.58% (P<.05), respectively, compared with the LPD group. Prenatal choline supplementation reversed the increased width of the synaptic cleft (P<.05) and decreased the curvature of the synaptic interface (P<.05) induced by a low-protein diet. Prenatal choline supplementation could attenuate the spatial learning deficits caused by prenatal protein malnutrition by increasing brain choline, betaine and phospholipids and by influencing the hippocampus structure.

Renal insufficiency and mortality in coronary artery disease with reduced ejection fraction.

BACKGROUND: Despite strong evidence linking decreased estimated glomerular filtration rate (eGFR) to worse cardiovascular outcome, the impact of eGFR on mortality in coronary artery disease (CAD) patients with different left ventricular ejection fraction (EF) is not well defined. METHODS: A retrospective cohort study. From Jul. 2008 to Jan. 2012, consecutive patients with CAD of West China Hospital were enrolled and were grouped into 3 eGFR categories: ≥90, 60-90, and <60mL/min/1.73m(2). Patients with EF≥50% or <50% were defined as preserved EF or reduced EF, respectively. The endpoints were all-cause mortality and cardiac mortality. RESULTS: There are 2161 patients according to the inclusion criteria and follow-up requirement. The mean follow-up time was 30.97±11.70months. Cumulative survival curves showed that in patients with reduced EF, renal insufficiency significantly increases all-cause mortality and cardiovascular mortality in a graded fashion (mortality rate, moderate or severe vs. normal: 29.3% vs. 5.4%, p<0.001; cardiac mortality rate, moderate or severe vs. normal: 18.2% vs. 4.5%, p=0.001, respectively). Cox regression analysis showed that in CAD patients with reduced EF, moderate to severe renal insufficiency increased all-cause mortality by 6.10-fold (HR 6.10, 95% CI 2.50 to 14.87) and cardiac mortality by 4.10-fold (HR 4.10, 95% CI 1.51 to 11.13). Use of beta-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and statins was associated with decreased risk of mortality, but the use was lower in renal insufficiency patients, especially in combination of reduced EF. CONCLUSION: This study has found that the effect of renal function on prognosis in patients with CAD is closely related to cardiac function. In patients with reduced EF, renal insufficiency accompanies the higher risks of all-cause mortality and cardiovascular mortality. A higher number of treatments from beta-blocker, ACEIs or ARBs, and statin therapy were associated with decreased risk of mortality, even in the combination of renal insufficiency or declining cardiac function.

Unconjugated Bilirubin Is a Novel Prognostic Biomarker for Nasopharyngeal Carcinoma and Inhibits Its Metastasis via Antioxidation Activity.

Distant metastasis is the most common cause of treatment failure and mortality in nasopharyngeal carcinoma (NPC) patients. Thus, it is important to understand the mechanism of NPC metastasis and identify reliable prognostic factors. In this study, we investigated the prognostic value of unconjugated bilirubin (UCB), which was previously considered a byproduct of heme catabolism, in NPC patients and examined the effects of UCB on NPC metastasis. The receiver operating characteristic analysis-generated UCB cutoff point for DMFS was 9.7 µmol/L. We found that higher UCB levels were significantly associated with favorable distant metastasis-free survival (DMFS, 93.3% vs. 84.2%, P < 0.001) in NPC patients and was an independent predictor for DMFS (HR, 0.416; 95% confidence interval, 0.280-0.618; P < 0.001). We next found that UCB treatment impaired the invasion capability of NPC cells and potently inhibited lung metastasis of NPC cells in nude mice. Further investigation showed that UCB inhibited reactive oxygen species production, which is involved in the repression of ERK1/2 activation and matrix metalloproteinase-2 (MMP-2) expression. Moreover, lower levels of ERK1/2 phosphorylation and MMP-2 expression were observed in the NPC lung metastases of nude mice administered UCB. Taken together, our results indicate that UCB is a significantly favorable factor for DMFS in NPC patients and may play an important role in NPC chemoprevention.

Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma.

BACKGROUND: We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I. RESULTS: The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis. CONCLUSION: Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.

Obstetrical disease spectrum in China: an epidemiological study of 111,767 cases in 2011.

BACKGROUND: No national research on maternal and fetal complications and outcomes has been carried out in the mainland of China in recent years. This study was to provide a scientific basis for better control of obstetrical and neonatal diseases and better allocation of medical resources by analyzing the epidemiological characteristics of obstetrical diseases in the mainland of China. METHODS: Hospitalized obstetrical cases from 19 tertiary and 20 secondary hospitals in 14 provinces (nationally representative) during the period January 1, 2011 to December 31, 2011 were randomly selected. The general condition, pregnancy complications, and perinatal outcomes of the patients were studied. RESULTS: The top five medical and surgical complications of pregnant women in the mainland of China were anemia (6.34%), uterine fibroids (2.69%), thyroid disease (1.11%), thrombocytopenia (0.59%), and heart disease (0.59%). The incidences of premature rupture of membranes (PROM), preterm birth, prolonged pregnancy, hypertensive disorders complicating pregnancy (HDCP), multiple pregnancy, intrahepatic cholestasis of pregnancy (ICP), placenta previa, placental abruption, postpartum hemorrhage, and amniotic fluid embolism were 15.27%, 7.04%, 6.71%, 5.35%, 1.57%, 1.22%, 1.14%, 0.54%, 3.26% and 0.06%, respectively. The incidences of anemia and prolonged pregnancy were significantly lower in tertiary than secondary hospitals (P < 0.001), whereas the incidence of uterine fibroids, thyroid diseases, thrombocytopenia, heart disease, PROM, preterm birth, HDCP, multiple pregnancy, ICP, placenta previa, and placental abruption were significantly higher in tertiary than secondary hospitals (P < 0.001). The cesarean section (CS) rate was 54.77%. The newborn sex ratio was 119:100, and 1.03% of the neonates were malformed. The percentages of low birth weight and fetal macrosomia in full-term babies were 2.10% and 7.09%, respectively. CONCLUSIONS: The incidence of some obstetrical diseases is still high in the mainland of China. The CS rate is much higher than World Health Organization recommendations, in which CS delivery by maternal request (CDMR) accounted for a large proportion. The government should propose solutions to reduce CS rate, especially the rate of CDMR. Most obstetrical complications have higher incidence in tertiary hospitals compared with secondary hospitals. It is important to manage the health of pregnant women systematically, especially those with high-risk factors.

Relation between admission serum potassium levels and long-term mortality in acute coronary syndrome.

Serum potassium homeostasis play an important role in myocardial function, but the impact of serum potassium levels on long-term mortality has not been well evaluated. In the current study, we investigated patients with acute coronary syndrome (ACS) and analyzed the relationship between admission serum potassium levels and long-term mortality. Between July 2008 and September 2012, 2369 patients with ACS that was confirmed by coronary angiography were enrolled in this study and completed the follow-up. The serum potassium level was evaluated within first 24 h after admission. The primary outcome in this study was all-cause mortality. Patients were categorized into five groups to determine the relation between admission serum potassium levels and long-term mortality: < 3.5, 3.5 to < 4.0, 4.0 to < 4.5, 4.5 to < 5.0, and > 5 mEq/L. There was a U-shaped relationship between admission serum potassium levels and long-term mortality that persisted after multivariable adjustment. The mortality risk was lowest in the group of patients with potassium levels of 3.5 to < 4.0 mEq/L, whereas mortality was higher in patients with potassium levels > 4.5 [hazard ratio (HR) 1.62, 95 % confidence interval (CI) 0.90 to 2.93 and HR 1.55, 95 % CI 0.54 to 4.49, for patients with potassium levels of 4.5 to < 5.0 mEq/L and ≥ 5.0 mEq/L, respectively] or < 3.5 mEq/L (HR 2.14, 95 % CI 1.28 to 3.59). There was a U-shaped relationship between admission serum potassium levels and long-term mortality for ACS patients; in particular, among the examined patients, the lowest mortality was observed in those with admission serum potassium levels of between 3.5 and < 4.5 mEq/L compared with those who had higher or lower potassium levels.

Impact of renal dysfunction on mid-term outcome after transcatheter aortic valve implantation: a systematic review and meta-analysis.

BACKGROUND: There is conflicting evidence regarding the impact of preexisting renal dysfunction (RD) on mid-term outcomes after transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis (AS). METHODS AND RESULTS: Forty-seven articles representing 32,131 patients with AS undergoing a TAVI procedure were included in this systematic review and meta-analysis. Pooled analyses were performed with both univariate and multivariate models, using a fixed or random effects method when appropriate. Compared with patients with normal renal function, mid-term mortality was significantly higher in patients with preexisting RD, as defined by the author (univariate hazard ratio [HR]: 1.69; 95% confidence interval [CI]: 1.50-1.90; multivariate HR: 1.47; 95% CI: 1.17-1.84), baseline estimated glomerular filtration rate (eGFR) (univariate HR: 1.65; 95% CI: 1.47-1.86; multivariate HR: 1.46; 95% CI: 1.24-1.71), and serum creatinine (univariate HR: 1.69; 95% CI: 1.48-1.92; multivariate HR: 1.65; 95% CI: 1.36-1.99). Advanced stage of chronic kidney disease (CKD stage 3-5) was strongly related to bleeding (univariate HR in CKD stage 3: 1.30, 95% CI: 1.13-1.49; in CKD stage 4: 1.30, 95% CI: 1.04-1.62), acute kidney injure (AKI) (univariate HR in CKD stage 3: 1.28, 95% CI: 1.03-1.59; in CKD stage 4: 2.27, 95% CI: 1.74-2.96), stroke (univariate HR in CKD stage 4: 3.37, 95% CI: 1.52-7.46), and mid-term mortality (univariate HR in CKD stage 3: 1.57, 95% CI: 1.26-1.95; in CKD stage 4: 2.77, 95% CI: 2.06-3.72; in CKD stage 5: 2.64, 95% CI: 1.91-3.65) compared with CKD stage 1+2. Patients with CKD stage 4 had a higher incidence of AKI (univariate HR: 1.70, 95% CI: 1.34-2.16) and all-cause death (univariate HR: 1.60, 95% CI: 1.28-1.99) compared with those with CKD stage 3. A per unit decrease in serum creatinine was also associated with a higher mortality at mid-term follow-up (univariate HR: 1.24, 95% CI: 1.18-1.30; multivariate HR: 1.19, 95% CI: 1.08-1.30). CONCLUSIONS: Preexisting RD was associated with increased mid-term mortality after TAVI. Patients with CKD stage 4 had significantly higher incidences of peri-procedural complications and a poorer prognosis, a finding that should be factored into the clinical decision-making process regarding these patients.

Heparin is Not Inferior to Bivalirudin in Percutaneous Coronary Intervention-Focusing on the Effect of Glycoprotein IIb/IIIa Inhibitor Use: A Meta-Analysis.

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv.

Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

OBJECTIVES: Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. PARTICIPANTS AND METHODS: Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. RESULTS: Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. CONCLUSION: Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.

Design of a prognostic score model for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this analysis was to create a prognostic score model for newly diagnosed nasopharyngeal carcinoma (NPC) which has not been created before. METHODS: We retrospectively reviewed the medical records of 419 patients with newly diagnosed, nondisseminated, and biopsy proven NPC. RESULTS: Independent prognostic factors included age >45, stage III/IV, antienzyme rate of Epstein-Barr virus DNase-specific neutralizing antibody (AER) >58%, and absolute neutrophil count (ANC) >4.7 × 10(9) /L. Four prognostic groups based on prognostic score model were obtained: low-risk group (total score = 0-2); low-intermediate-risk group (total score = 3-4); high-intermediate-risk group (total score = 5-6); and high-risk group (total score = 7). CONCLUSION: Our proposed prognostic score model was a useful tool for improving the prognostic assessment of patients with NPC, stratifying patients into different risk groups that call for different treatments, and comparing clinical trials.

Subclassification of left ventricular hypertrophy based on dilation stratifies coronary artery disease patients with distinct risk.

BACKGROUND: A new 4-tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown. METHODS: All the 2297 patients with CAD included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated, and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort was divided into five groups according to LV geometry: (i) eccentric nondilated LVH (normal LVM/EDV((2/3)) and EDV/BSA) (n = 129); (ii) eccentric dilated LVH (normal LVM/EDV((2/3)) with increased EDV/BSA) (n = 222); (iii) concentric nondilated LVH (increased LVM/EDV((2/3)) with normal EDV/BSA) (n = 441); (iv) concentric dilated LVH (increased LVM/EDV((2/3)) and EDV/BSA) (n = 118); and (v) normal LV mass (n = 1387). RESULTS: Dilated LVH was associated with a higher event rates of all-cause death (eccentric 13·1% vs. 3·1%; concentric 13·6% vs. 8·4%) and composite events (eccentric: 17·6% vs. 5·4%; concentric: 18·6% vs. 12·7%) compared with nondilated LVH. While eccentric nondilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0·68, 95% confidential interval (CI) 0·25-1·85; composite events: RR 0·75, 95% CI 0·36-1·58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2·752 [95% CI 1·749-4·328], P < 0·001) and composite events (aHR 2·462 [95% CI 1·688-3·592], P < 0·001). CONCLUSION: In patients with CAD, dilated LVH and nondilated LVH provide distinct prognostic information. Eccentric nondilated LVH does not predict adverse outcomes.

Percutaneous coronary intervention compared with coronary artery bypass graft in coronary artery disease patients with chronic kidney disease: a systematic review and meta-analysis.

Previous reports of percutaneous coronary intervention versus coronary artery bypass graft outcomes in coronary artery disease patients with chronic kidney disease (CKD) were inconsistent. We evaluated the optimal revascularization strategy for CKD patients. We searched Pub Med, EMBASE, and the Cochrane Central Register of Controlled Trials and scanned the references of relevant articles and reviews. All studies that compared relevant clinical outcomes between percutaneous coronary intervention and coronary artery bypass graft in CKD patients were selected. We defined short-term and long-term all-cause mortality as primary outcome, and long-term incidences of myocardial infarction and revascularization as secondary outcomes. A total of 2235 citations were retrieved, and 31 studies involving 99,054 patients, with 55,383 receiving percutaneous coronary intervention and 43,671 receiving coronary artery bypass graft, were included. In subgroup analyses of dialysis patients receiving percutaneous coronary intervention with stents versus coronary artery bypass graft, CKD patients with multivessel coronary disease, and CKD patients receiving drug-eluting stent versus coronary artery bypass graft, the pooled outcomes revealed that percutaneous coronary intervention possessed lower short-term mortality, but higher late revascularization risk. No significant differences in long-term mortality were observed between the two strategies in these subgroup analyses. In conclusion, in some specific clinical circumstances, CKD patients receiving percutaneous coronary intervention possessed lower short-term all-cause mortality, but higher long-term revascularization risk, than coronary artery bypass graft; long-term all-cause mortality was not different between the two strategies.