Ruthenium/η5-Phenoxo-Catalyzed Amination of Phenols with Amines.

Ruthenium(II) complexes are known to form η6-arene complexes with benzene-containing compounds through π-coordination, a property extensively utilized to initiate reactions not typically observed with free arenes. A prime example is nucleophilic aromatic substitution, where ruthenium-complexed aryl halides undergo nucleophilic attack, allowing the direct synthesis of diverse aromatic compounds by displacing halides with nucleophiles. However, this activation relies on the electron-withdrawing effect of the Ru(II) species, as well as is hindered by the resistance of η6-arenes to arene exchange. In the previous pursuit of catalysis, the emphasis of ligand design has centered on promoting arene exchange. In this study, we extended the ruthenium activation strategy to umpolung substitution reactions of phenols. The amination proceeds through a direct condensation between phenols and amines, with a key intermediate identified as [bis(η5-phenoxo)Ru], which is in situ generated from a commercially available ruthenium catalyst. In comparison with the well-studied cyclopentadienyl (Cp) type ligands, we demonstrated that an η5-phenoxo motif, as a superior alternative to Cp, contributes to the amination of phenols in two crucial ways: its less electron-donating nature enhances the withdrawing effect of the ruthenium unit, facilitating substitution on the phenol complex; its distinctive behavior in arene exchange allows for conducting the amination with a catalytic amount of metal. Additionally, hydrogen bonding, wherein the phenoxo serves as the acceptor, was found to be important for the substitution. The versatility of this ruthenium-catalyzed amination was validated by performing reactions with a diverse array of phenols exhibiting various electronic properties, in combination with a wide range of primary amines. This work exemplifies the expansion of the scope of π-coordination activation in catalysis through innovative ligand development.

Alternative splicing of histone demethylase Kdm6bb mediates temperature-induced sex reversal in the Nile tilapia.

Sex determination in many fish species is remarkably plastic and temperature sensitive. Nile tilapia display a genetic sex-determination system (XX/XY). However, high-temperature treatment during critical thermosensitive periods can induce XX females into XXm pseudo-males, and this phenomenon is termed temperature-induced sex reversal (TISR). To investigate the molecular mechanism of TISR in Nile tilapia, we performed Iso-seq analysis and found a dramatic effect of high temperature on gene alternative splicing (AS). Kdm6bb histone demethylase showed a novel AS at intron 5 that generates Kdm6bb_tv1 transcripts without intron 5 and Kdm6bb_tv2 with intron 5. Kdm6bb_tv1 encodes a full-length protein while Kdm6bb_tv2 encodes a truncated protein. Expression analysis revealed that intron 5 splicing of Kdm6bb is male and gonad biased at larval stage, and only gonad biased at adult stage. High-temperature treatment induced intron 5 splicing in the gonads of XX and XY fish, resulting in increased Kdm6bb_tv1 expression. To directly test the role of Kdm6bb_tv1 in Nile tilapia TISR, we knocked out expression of Kdm6bb_tv1. However, Kdm6bb_tv1-/- homozygous mutants showed embryonic lethality. Overexpression of Kdm6bb_tv1, but not Kdm6bb_tv2, induced sex reversal of XX females into pseudo-males. Overexpression of Kdm6bb_tv1, as with high-temperature treatment, modified the promotor region of Gsdf and Dmrt1 by demethylating the trimethylated lysine 27 of histone 3 (H3K27me3), thereby increasing expression. Collectively, these studies demonstrate that AS of Kdm6bb intron 5 increases the expression of Kdm6bb_tv1, which acts as a direct link between high temperature and activation of Gsdf and Dmrt1 expression, leading to male sex determination.

Genome Size Variation and Evolution Driven by Transposable Elements in the Genus Oryza.

Genome size variation and evolutionary forces behind have been long pursued in flowering plants. The genus Oryza, consisting of approximately 25 wild species and two cultivated rice, harbors eleven extant genome types, six of which are diploid (AA, BB, CC, EE, FF, and GG) and five of which are tetraploid (BBCC, CCDD, HHJJ, HHKK, and KKLL). To obtain the most comprehensive knowledge of genome size variation in the genus Oryza, we performed flow cytometry experiments and estimated genome sizes of 166 accessions belonging to 16 non-AA genome Oryza species. k-mer analyses were followed to verify the experimental results of the two accessions for each species. Our results showed that genome sizes largely varied fourfold in the genus Oryza, ranging from 279 Mb in Oryza brachyantha (FF) to 1,203 Mb in Oryza ridleyi (HHJJ). There was a 2-fold variation (ranging from 570 to 1,203 Mb) in genome size among the tetraploid species, while the diploid species had 3-fold variation, ranging from 279 Mb in Oryza brachyantha (FF) to 905 Mb in Oryza australiensis (EE). The genome sizes of the tetraploid species were not always two times larger than those of the diploid species, and some diploid species even had larger genome sizes than those of tetraploids. Nevertheless, we found that genome sizes of newly formed allotetraploids (BBCC-) were almost equal to totaling genome sizes of their parental progenitors. Our results showed that the species belonging to the same genome types had similar genome sizes, while genome sizes exhibited a gradually decreased trend during the evolutionary process in the clade with AA, BB, CC, and EE genome types. Comparative genomic analyses further showed that the species with different rice genome types may had experienced dissimilar amplification histories of retrotransposons, resulting in remarkably different genome sizes. On the other hand, the closely related rice species may have experienced similar amplification history. We observed that the contents of transposable elements, long terminal repeats (LTR) retrotransposons, and particularly LTR/Gypsy retrotransposons varied largely but were significantly correlated with genome sizes. Therefore, this study demonstrated that LTR retrotransposons act as an active driver of genome size variation in the genus Oryza.

Diuretic Resistance Prediction and Risk Factor Analysis of Patients with Heart Failure During Hospitalization.

Objectives: This study performed a prediction and risk factor analysis of diuretic resistance (DR) in patients with decompensated heart failure during hospitalization. Methods: The data of patients with decompensated heart failure treated in 2010-2018 with DR (n = 3,383) or without DR (n = 15,444) were retrospectively collected from Chinese PLA General Hospital medical records. Statistical analysis of baseline was performed on two groups of people, and the risk factor of DR was analyzed through logic regression. Six machine learning models were built accordingly, and the adjustment of model super parameters was performed by using Bayesian optimization method. Finally, the optimal algorithm was selected according to prediction efficiency. Results: The preliminary analysis of variance showed significant differences in the incidence of DR among patients with lung infection, hyperlipidemia, type 2 diabetes, and kidney disease. There were significant differences in estimated glomerular filtration rate (eGFR) (P < 0.001). In addition, some physical indicators like BMI were different, the laboratory results like mean red blood cell volume or C-reactive protein assay were also significantly different. The optimal classification model indicated that the best cutoff points for risk factors were vein carbon dioxide, 21 mmol/L and 29 mmol/L; total protein, 64 g/L; pro-brain natriuretic peptide (pro-BNP), 7,600 pg/mL; eGFR, 50 mL/(min ∙ 1.73 m2); serum albumin, 33 g/L; hematocrit, 0.32% and 0.56%; red blood cell volume distribution width, 13; and age, 59 years. The optimal area under the curve was 0.9512. The ranked features derived from the model were age, abnormal sodium level, pro-BNP level, serum albumin level, D-dimer level, direct bilirubin level, and eGFR. Conclusions: The DR risk prediction model based on a gradient boosting decision tree created here identified its important risk factors. The model made very accurate predictions using simple indicators and simultaneously calculated cutoff values to help doctors predict the occurrence of DR.

Genome-Wide Analysis of CCT Transcript Factors to Identify Genes Contributing to Photoperiodic Flowering in Oryza rufipogon.

Photoperiod sensitivity is a dominant determinant for the phase transition in cereal crops. CCT (CONSTANS, CO-like, and TOC1) transcription factors (TFs) are involved in many physiological functions including the regulation of the photoperiodic flowering. However, the functional roles of CCT TFs have not been elucidated in the wild progenitors of crops. In this study, we identified 41 CCT TFs, including 19 CMF, 17 COL, and five PRR TFs in Oryza rufipogon, the presumed wild ancestor of Asian cultivated rice. There are thirty-eight orthologous CCT genes in Oryza sativa, of which ten pairs of duplicated CCT TFs are shared with O. rufipogon. We investigated daily expression patterns, showing that 36 OrCCT genes exhibited circadian rhythmic expression. A total of thirteen OrCCT genes were identified as putative flowering suppressors in O. rufipogon based on rhythmic and developmental expression patterns and transgenic phenotypes. We propose that OrCCT08, OrCCT24, and OrCCT26 are the strong functional alleles of rice DTH2, Ghd7, and OsPRR37, respectively. The SD treatment at 80 DAG stimulated flowering of the LD-grown O. rufipogon plants. Our results further showed that the nine OrCCT genes were significantly downregulated under the treatment. Our findings would provide valuable information for the construction of photoperiodic flowering regulatory network and functional characterization of the CCT TFs in both O. rufipogon and O. sativa.

CD147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression.

Major gaps in understanding the molecular mechanisms of colorectal cancer (CRC) progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders. Trefoil factor 3 (TFF3) has been reported to be involved in CRC progression and intestinal mucosal repair; however, how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood. Here, we found that the upregulated TFF3 in CRC predicted a worse overall survival rate. TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis. CD147, a membrane protein, was identified as a binding partner for TFF3. Via binding to CD147, TFF3 enhanced CD147-CD44s interaction, resulting in signal transducer and activator of transcription 3 (STAT3) activation and prostaglandin G/H synthase 2 (PTGS2) expression, which were indispensable for TFF3-induced migration, proliferation, and invasion. PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype (PTGER4) and contributed to TFF3-stimulated CRC progression. Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression. The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor. Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice. Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression, which widens and deepens the understanding of the molecular function of trefoil factors.

Incidence, predictors, and prognosis of thrombocytopenia among patients undergoing intra-aortic balloon pumping in the intensive care unit: a propensity score analysis.

OBJECTIVE: To explore the incidence, predictors, and prognosis of intra-aortic balloon pumping (IABP)-related thrombocytopenia in critically ill patients. METHODS: This multi-center study used the eICU Collaborative Research Database V1.2, comprising data on > 130,000 patients from multiple intensive care units (ICUs) in America between 2014 and 2015. A total of 710 patients undergoing IABP were included. Thrombocytopenia was defined as a drop in platelet count > 50% from baseline. From the cohort, 167 patients who developed thrombocytopenia were matched 1:1 with 167 patients who did not, after propensity score (PS) matching. The associations between IABP-related thrombocytopenia and clinical outcomes were examined by multivariable logistic regression. RESULTS: Among 710 patients undergoing IABP, 249 patients (35.07%) developed thrombocytopenia. The APACHE IVa score was a predictor of thrombocytopenia [adjusted odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.02-1.15]. After 1:1 PS matching, in-hospital mortality (adjusted OR = 0.76, 95% CI: 0.37-1.56) and in-ICU mortality (adjusted OR = 0.74, 95% CI: 0.34-1.63) were similar between the thrombocytopenia and non-thrombocytopenia groups. However, major bleeding occurred more frequently in the thrombocytopenia group (adjusted OR = 2.54, 95% CI: 1.54-4.17). In-hospital length of stay (LOS) and in-ICU LOS were significantly longer in patients who developed thrombocytopenia than in those who did not (9.71vs. 7.36, P < 0.001; 5.13 vs. 2.83, P < 0.001). CONCLUSIONS: Among patients undergoing IABP in the ICUs, thrombocytopenia was not associated with a difference in in-hospital mortality or in-ICU mortality; however, thrombocytopenia was significantly associated with a greater risk of major bleeding and increased in-ICU and in-hospital LOS.

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma.

BACKGROUND: Mounting evidence suggests that solid tumors display the features of collective invasion, however, the molecular mechanisms are far from clear. This study aims to verify the role and the underlying mechanisms of CD147 in collective invasion in hepatocellular carcinoma. METHODS: Immunostaining was used to analyze human hepatocellular carcinoma specimens and three-dimensional cultures. Three-dimensional invasion model was established to mimic in vivo invasion. RNA-sequencing was used to identify downstream effectors. RESULTS: Human hepatocellular carcinoma underwent collective invasion and CD147 was observed to be upregulated at the invasive front of tumor cell groups. CD147 was demonstrated to promote collective invasion using the modified three-dimensional invasion model, which recapitulated the main features of collective invasion. Through transcriptome analysis and enzyme activity assay, we found that CD147 enhanced cathepsin B expression and activity. Upregulated cathepsin B in hepatocellular carcinoma cells facilitated migration and invasion, which mediated CD147-induced invasive phenotype in hepatocellular carcinoma. In terms of mechanism, we found that CD147 promoted cathepsin B transcription by activating ß-catenin signaling as a result of reduced GSK-3ß expression. Furthermore, we found that elevated expression of CD147 as well as cathepsin B were correlated with poor prognosis in patients with hepatocellular carcinoma. CONCLUSIONS: CD147 promotes hepatocellular carcinoma cells collective invasion via upregulating cathepsin B expression and targeting CD147 would be valuable for the development of novel therapeutic modalities against invasion and metastasis of cancer.

Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone.

To find novel human carbonic anhydrase (hCA) inhibitors, we synthesized thirteen compounds by combining thiazolidinone with benzenesulfonamide. The result of the X-ray single-crystal diffraction experiment confirmed the configuration of this class of compounds. The enzyme inhibition assays against hCA II and IX showed desirable potency profiles, as effective as the positive controls. The docking studies revealed that compounds (2) and (7) efficiently bound in the active site cavity of hCA IX by forming sufficient interactions with active site residues. The fragment of thiazolidinone played an important role in the binding of the molecules to the active site.

Hypo-phosphorylated CD147 promotes migration and invasion of hepatocellular carcinoma cells and predicts a poor prognosis.

PURPOSE: CD147 is a tumor-associated antigen that plays a key regulatory role in tumor invasion and distant metastasis. However, the exact role of CD147 phosphorylation, which is deregulated during cancer progression, is unknown. Here, the effects of CD147 phosphorylation on the malignant behavior of hepatocellular carcinoma (HCC) cells and its possible underlying mechanisms are explored. METHODS: An in situ Duolink-proximity ligation assay (PLA) was used to detect CD147 phosphorylation. Tandem mass spectrometry was employed to identify the phosphorylation sites of CD147. The effects of CD147 phosphorylation on the malignant behavior of HCC cells were evaluated using scratch wound healing assays, transwell invasion assays and cell cycle assays. The genes regulated by CD147 phosphorylation were detected by RNA sequencing. RESULTS: We identified phosphorylated serine-246 in the C terminus of CD147 in primary HCC tissues, whereas serine to alanine substitution mutation analysis suggested that CD147 is phosphorylated mainly at serine-252 in HCC-derived Huh-7 cells. Recovery expression of S246A/S252A mutants in CD147 knockout cells revealed significantly increased migration and invasion capacities compared to wildtype CD147 expressing cells. Cyclophilin A (CyPA) treatment decreased the phosphorylation level of CD147, whereas NIMA-related kinase 6 (NEK6) increased the CD147 phosphorylation level. Moreover, the CD147 phosphorylation level was found to be dramatically decreased in HCC tissues in patients with distant metastases, and a low phosphorylation level of CD147 was found to be associated with a high serum AFP level, recurrence and a poor overall survival. CONCLUSIONS: From our data we conclude that hypo-phosphorylated CD147 promotes the migration and invasion of HCC cells and correlates with an unfavorable prognosis in HCC patients, indicating that targeting the aberrantly hypo-phosphorylated form of CD147 may be instrumental for the development of novel therapeutic modalities directed against HCC metastasis.

Clinical, Laboratory and Imaging Features of High Altitude Pulmonary Edema in Tibetan Plateau.

Objective To analyze characteristics of high altitude pulmonary edema (HAPE) in Chinese patients.Methods We performed a retrospective study of 98 patients with HAPE. We reviewed the medical records and summarized the clinical, laboratory and imaging characteristics of these cases, and compared the results on admission with those determined before discharge.Results Forty-eight (49.0%) patients developed HAPE at the altitude of 2800 m to 3000 m. Ninty-five (96.9%) patients were man. Moist rales were audible from the both lungs, and moist rales over the right lung were clearer than those over the left lung in fourteen patients. The white blood cells [(12.83±5.55) versus (8.95±3.23) ×10 9/L, P=0.001)] as well as neutrophil counts [(11.34±3.81) versus (7.49±2.83)×10 9/L, P=0.001)] were higher, whereas the counts of other subsets of white blood cells were lower on admission than those after recovery (all P<0.05). Serum levels of alkaline phosphatase (115.8±37.6 versus 85.7±32.4 mmol/L, P=0.020), cholinesterase (7226.2±1631.8 versus 6285.3±1693.3 mmol/L, P=0.040), creatinine (85.2±17.1 versus75.1±12.8 mmol/L, P=0.021), uric acid (401.9±114.2 versus 326.0±154.3 mmol/L, P=0.041), and uric glucose (7.20±1.10 versus 5.51±1.11 mmol/L, P=0.001) were higher, but carbondioxide combining power (CO2CP, 26.7±4.4 versus 28.9±4.5 mmol/L, P=0.042) and serous calcium (2.32±0.13 versus 2.41±0.10 mmol/L, P=0.006) were lower on admission. Arterial blood gas results showed hypoxemia and respiratory alkalosis on admission. Conclusions In the present research, men were more susceptible to HAPE than women, and in the process of HAPE, the lesions of the right lung were more serious than those of the left lung. Some indicators of routine blood test and blood biochemistry of HAPE patients changed.

Aberrant Expression of miR-362 Promotes Lung Cancer Metastasis through Downregulation of Sema3A.

miR-362 is a recently discovered member of the microRNA family, and it modulates a variety of physical activities and plays an important role in the occurrence and development of many tumors. However, the biological functions of hsa-miR-362-5p in non-small-cell lung carcinoma (NSCLC) are unknown. Transwell assay and colony formation were used to determine the migration, invasion, and proliferation of NSCLC cells in vitro. A subcutaneous tumor model in nude mice was established to detect NSCLC tumor growth in vivo. The direct binding of miR-362 to the 3'UTR of Semaphorin 3A (Sema3A) was confirmed by luciferase reporter assay. In this study, we found that the level of miR-362 was higher in NSCLC tissues than in adjacent normal tissues and that the level of miR-362 expression was also elevated in five NSCLC cell lines (A549, 95-D, H1299, H292, and H460) relative to a human normal lung epithelial cell line (BEAS2B). Furthermore, miR-362 promoted NSCLC cell invasion, migration, and colony formation in vitro and tumor formation in vivo. Next, we identified the miR-362 target gene Sema3A, which is significantly correlated with metastasis. Sema3A expression was increased in normal tissues relative to NSCLC tissues. This result is consistent with the fact that miR-362 expression is negatively correlated with Sema3A expression in clinical tissue samples and indicated that miR-362 can regulate Sema3A expression in NSCLC cells and consequently affect NSCLC invasion, migration, and colony formation. Taken together, these findings on the newly identified miR-362/Sema3A axis elucidate the molecular mechanism of NSCLC invasion and migration and could lead to a potential therapeutic target in NSCLC treatment.

Efficient Expression and Purification of Recombinant Human Enteropeptidase Light Chain in Esherichia coli

Human enterokinase (synonym: enteropeptidase, EC 3.4.21.9) light chain (hEKL) gene was designed and artificially synthesized with built-in codon blas towards Escherichia coli codon preference. The synthetic hEKL gene was cloned into prokaryotic expression vector pMAL-s and transferred into the expression strain E. coli BL21 (DE3). Recombinant hEKL protein with a maltose binding protein (MBP) tag was expressed at high levels in soluble form, which yielded about 42% of the total cellular protein. The target protein was then purified to the homogeneity (> 95%) by affinity chromatography. The peptide substrate GST-Melittin with enterokinase recognition site was completely cleaved by the purified MBP-hEKL at the molar ratio of 1:5000 (enzyme:substrate). Tricine SDS-PAGE analysis showed that the activity of MBP-hEKL was approximately seven times that of bovine enterokinase catalytic subunit (EKMaxTM, Invitrogen). From 1 L flask culture, 206 mg pure active MBP-hEKL was with specific activity of 1.4×104 U/mg.

[Analysis of risk factors of cardiogenic shock secondary to acute myocardial infarction].

OBJECTIVE: To explore risk factors for cardiogenic shock (CS) secondary to acute myocardial infarction (AMI) patients arising from comorbidities so as to identify high risk patients earlier. METHODS: A retrospective study was conducted on 5523 patients who were hospitalized with AMI in PLA General Hospital from January 1993 to December 2009. The patients were divided into two groups based on presence or absence of CS. Logistic regression analysis was used from comorbidities to evaluate the independent risk factors for CS. RESULTS: Among 5523 hospitalized AMI patients, 197 (3.57%) developed CS. The 30-day in hospital mortality rate of CS group was significantly higher than that of non-CS group [55.33% (109/197) vs. 7.49% (399/5326), P<0.001]. On the basis of logistic regression analysis, advanced age [odds ratio (OR)=1.03, 95% confidence interval (95%CI) 1.02 - 1.05, P<0.001], previous attack of myocardial infarction (OR=1.57, 95%CI 1.13 - 2.19, P=0.007), history of stroke (OR=1.98, 95%CI 1.20 - 3.27, P=0.008), chronic renal failure (OR=1.76, 95%CI 1.23 - 2.51, P=0.002) and pneumonia (OR=1.72, 95%CI 1.17 - 2.52, P=0.006) were independent risk factors for CS. Using receiver operator characteristic curve (ROC curve) analysis, the model was shown a good quality to judge the outcome of CS patients as the area under curve equals 0.81 (95%CI 0.75 - 0.85, P<0.001). CONCLUSIONS: Advanced age and comorbidities including previous myocardial infarction, previous stroke, chronic renal failure and pneumonia were independent risk factors for CS.

Mutational analysis of KCNJ11 in Chinese elderly essential hypertensive patients.

OBJECTIVE: To compare the distribution of KCNJ11 polymorphisms between elderly Chinese population with and without hypertension. METHODS: We examined the mutation of KCNJ11 gene by directly sequencing. Data for the present study were obtained from 250 hypertensive subjects (60 to 83 years old) as well as 250 normotensive subjects (60 to 86 years old). RESULTS: We found nine different mutations in KCNJ11, including six novel mutations (I131M, L147I, L147V, L147L, Q235H, G245C). None of the novel mutations were found in the normotensive subjects, and all the residues were conserved in other species. These sequence variants in Chinese population indicate the diversity of the human library and the complexity of hypertension. CONCLUSIONS: The consistent finding of our present study provided a basis for the development of new strategies to diagnosis and treat hypertension in the elderly.

Secular trends in the etiology and comorbidity of hospitalized patients with congestive heart failure: A single-center retrospective study.

OBJECTIVE: To assess the secular trends in the etiology and comorbidity of patients hospitalized with congestive heart failure (CHF). METHODS: Data of 7,319 patients (mean age 59.6 years, 62.1% male) with a primary discharge diagnosis of CHF, hospitalized from January 1, 1993 to December 31, 2007 at the Chinese People's Liberation Army (PLA) General Hospital were extracted and analyzed. These patients were divided into three groups according to hospitalization period: 1993-1997 (n = 1623), 1998-2002 (n = 2444), and 2003-2007 (n = 3252). The etiological characteristics and comorbidities were assessed. RESULTS: Over the study period, the proportion of patients with ischemic heart disease (IHD) increased from 37.2% during the period 1993-1997 to 46.8% during the period 2003-2007, while that with valvular heart disease (VHD) decreased from 35.2% during the period 1993-1997 to 16.6% during the period 2003-2007 (both P < 0.05). Atrial fibrillation (AF) was the most common comorbidity of heart failure (23.2%, 23.0% and 20.6%, respectively, in the three periods). Compared to that of the period of 1993-1997 with that of, the proportion of patients with myocardial infarction, pneumonia, renal function impairment and hepatic cirrhosis of the period of 2003-2007 increased significantly (P < 0.05) and the proportion of patients with chronic obstructive pulmonary disease and atrial fibrillation decreased significantly (P < 0.05). CONCLUSIONS: This study implies that IHD has became a more common etiology of CHF, while VHD has deceased as an etiology of CHF in Chinese patients during the last two decades.

Hyperpolarization activated cation current (I(f)) in cardiac myocytes from pulmonary vein sleeves in the canine with atrial fibrillation.

OBJECTIVE: To investigate the characteristics of ectopic automaticity and cation current (I(f)) of cardiac myocytes from pulmonary vein sleeves (PVs) in canines with atrial fibrillation. METHODS: The canines (8-10 years old) were subjected to long-term, rapid atrial pacing (RAP) for 10 weeks, which induced the atrial fibrillation model. Disassociation of PVs of canines yielded single cardiac myocytes from a Landengorff column. Action potential, I(f) and hyperpolarisation activated cyclic nucleotide-gated (HCN) currents were measured with the patch-clamp technique. RESULTS: Compared with the control group, cardiac myocytes from the RAP canine PVs had spontaneous diastolic depolarization, shorter action potential duration, and larger I(f) densities. In the group of RAP cells, the half maximal activation potential (V(1/2)) was found to be less negative (-105.5 ± 5.2 mV) compared to control cells (-87.3 ± 4.9 mV). Current densities of I(f) were increased significantly by ß-adrenergic receptor stimulation with isoproterenol and caused an acceleration of current activation. In contrast, I(f) currents in the RAP were reduced by carvedilol, a selective beta-adrenergic receptor. Another important finding is that HCN4-based channels may make a significant contribution to I(f) in PVs cells, but not HCN2. Meanwhile, HCN4 current significantly increases in canine PVs cardiac myocytes with RAP. CONCLUSIONS: The spontaneous action potential and larger I(f) current were observed in the PVs cardiac myocytes using RAP, which may contribute to more ectopic activity events to trigger and maintain atrial fibrillation.

[Fifteen-year evolving trends of etiology and prognosis in hospitalized patients with heart failure].

OBJECTIVE: To investigate the etiological and prognostic changes of hospitalized patients with chronic heart failure. METHODS: This retrospective study analyzed 7319 hospitalized patients (male 62.07%) with validated primary discharge diagnosis of chronic heart failure in Chinese PLA General Hospital in Beijing from January 1, 1993 to December 31, 2007. Etiological characteristics, comorbidities and 30-day hospitalized mortality in the following three periods: 1993 - 1997 (n = 1623), 1998 - 2002 (n = 2444), and 2003 - 2007 (n = 3252) were compared. RESULTS: (1) The patient age increased [(56.0 ± 17.5) years, (57.8 ± 17.6) years and (62.7 ± 15.5) years, P < 0.01] and hospital stay time decreased [(31.3 ± 17.4) days, (22.7 ± 14.1) days and (20.1 ± 15.2) days, P < 0.01] from 1993 to 2007. (2) The common causes of heart failure were coronary heart disease, hypertension, rheumatic valvular heart disease and diabetes mellitus. From 1993 - 1998 to 2003 - 2007, the proportion of patients with coronary heart disease, hypertension and diabetes mellitus rose from 37.2%, 23.3% and 12.3% to 46.8%, 46.7% and 21.1%, respectively (all P < 0.05). Meanwhile the proportion of patients with rheumatic valvular heart disease fell from 35.2% to 16.6% (P < 0.05). (3) The main etiologies and comorbidities were atrial fibrillation, myocardial infarction, pneumonia, chronic obstructive pulmonary disease and renal failure. From 1993 - 1998 to 2003 - 2007, atrial fibrillation was the most common cause of heart failure, and the rate of myocardial infarction, pneumonia and renal failure rose from 11.0%, 8.9% and 5.2% to 14.7%, 14.5% and 9.1%, respectively (all P < 0.05) and the rate of COPD fell from 12.9% to 8.4% (P < 0.05). (4) The 30-day hospitalized mortalities in the three periods were 7.0%, 4.5% and 5.1%, respectively, and the mortalities in the 1998 - 2002 and 2003 - 2007 periods were lower than those of in the 1993 - 1998 period (all P < 0.05). The mortality related to coronary heart disease decreased significantly from 1993 to 2007 (9.3%, 5.0% and 3.8% in the three periods, respectively, P < 0.05). CONCLUSIONS: It is demonstrated that the primary diseases causing heart failure were coronary heart disease, hypertension, diabetes mellitus and rheumatic valvular heart disease, and the former three diseases exhibited a upward trend and the later one exhibited a downward trend. Moreover, the proportion of comorbidities in patients with heart failure increased over the study period. The 30-day hospital mortality exhibited a downward trend and decreased significantly in patients with coronary heart disease or myocardial infarction.

Glycemic and blood pressure control in older patients with hypertension and diabetes: association with carotid atherosclerosis.

BACKGROUND: Numerous studies have confirmed the effectiveness of slowing the progression of atherosclerosis by blood pressure (Bp) control in patients with hypertension and several studies also showed the efficacy of intensive glycemic control in decreasing progression of carotid intima-media thickness (CIMT) in patients with type 1 and type 2 diabetes. However, few studies have compared the relative importance of glycemic vs. Bp control in patients with diabetes and hypertension. We aimed to investigate the association between Bp and glycemic control and subclinical carotid atherosclerosis in older patients with hypertension and type 2 diabetes. METHODS: In a cross-sectional study, B-mode high-resolution ultrasonography of the carotid artery was performed in 670 subjects (508 males and 162 females) aged 60 years or over who had self-reported hypertension and diabetes but no history of coronary heart disease or stroke. Subjects were categorized by their systolic blood pressure: tight control, < 130 mmHg; usual control, 130-139 mmHg; or uncontrolled, ≥ 140 mmHg, and by their hemoglobin A1c (HbA1c) level: tight control, < 6.5%; usual control, 6.5%-7.5%; or uncontrolled, ≥ 7.5%, respectively. RESULTS: The mean CIMT was 8.20 ± 0.11 mm, and carotid plaque was found in 52.5% (352/670) subjects. Overall, 62.1% of the subjects had subclinical carotid atherosclerosis, defined as having either carotid plaque or elevated CIMT (≥ 1.1 mm). The mean CIMT was significantly different between Bp control categories (7.60 ± 0.09 mm, 7.90 ± 0.08 mm, and 8.60 ± 0.12 mm, respectively, P = 0.03) but not between glycemic control categories (8.20 ± 0.10 mm, 8.1 ± 0.08 mm, and 8.40 ± 0.14 mm, respectively, P = 0.13) using ANCOVA analysis. Multivariable logistic regression adjusting for potential confounding factors showed that usual or uncontrolled Bp control were associated with having carotid plaque (OR = 1.08 and OR = 1.42, respectively), or elevated CIMT [Odd ratio (OR) = 1.17, 95% confidence interval (CI) 1.04-2.24, and OR = 1.54, 95% CI 1.36-2.96, respectively compared to tight Bp control; but did not show glycemic control as independent predictor of either having carotid plaque or elevated CIMT. CONCLUSIONS: In older patients with hypertension and diabetes, blood pressure control, but not glycemic control is associated with subclinical carotid atherosclerosis.