[Safety and efficacy of ultrafiltration on heart failure patients with reduced ejection fraction and diuretic resistance: results from a single-center randomized controlled trial].

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.

[Feasibility and safety of new simplified left bundle branch area pacing via nine-partition method].

Objective: To investigate the efficacy and safety of left bundle branch area pacing (LBBaP) with the new simplified approach (nine-partition method). Methods: A total of 118 patients with clinical indications and received pacemaker implantation from December 1, 2018 to December 31, 2019 in Beijing Anzhen Hospital were enrolled. LBBaP was performed with the nine-partition method (in the right anterior oblique 30° position, the ventriculogram was divided into nine partitions and the initial implant sites were located in the lower base 1/3 partitions). In X-ray image, the 3830 lead is located in the left bundle branch area, the unipolar pacing QRS wave is in the form of right bundle branch block, and the peak time from stimulation to left ventricular activation<90 ms is defined as successful operation. The clinical characters, such as the methods of venipuncture, electrode parameters, operation duration, fluoroscopy duration, the peak time from stimulation to left ventricular, pacemaker types, surgical success rate, complications, and immediate postoperative ECG parameters were collected. The patients were followed up after the operation, and the electrode parameters and postoperative complications were recorded. Results: This study is a retrospective study. There were 62 (52.5%) male patients in this cohort, the average age was (65.9±13.4) years old,and there were 49(41.5%) sick sinus syndrome, 6(5.1%) abnormal sinus node and atrioventricular node simultaneously, 63(53.4%) atrioventricular block, 26(22.0%) atrial fibrillation, 20(16.9%) cardiomyopathy; the baseline duration of QRS was (109.21±39.03) ms. Successful LBBaP was achieved in 109 patients with"nine-partition method"and the success rate was 92.4%; 104 patients (95.5%) were axillary vein puncture, 5 (4.6%) were subclavian vein puncture; the operation duration was (80.3±23.0) min, the fluoroscopy duration was (12.29±5.13) min; the QRS duration after LBBaP was (116.36±18.11) ms. The threshold of the left bundle branch (LBB) lead was (0.92±0.63) V, the R wave amplitude was (10.60±5.04) mV and the impedance was (798.71±194.90) Ω. In 1 V pacing, the peak time from stimulation to left ventricular activation was (67.91±12.15) ms, and in 5 V pacing was (67.52±12.45) ms; 1 case (0.9%) with a single-chamber pacemaker implanted, 106 cases (97.3%) with dual-chamber pacemaker and 2 cases (1.8%) with three-chamber pacemakers. There were no hematomas, pneumothorax, hemothorax, electrode dislocation, infection, and capsular hemorrhage and other serious surgery-related complications during the operation. A total of 97 patients (89.0%) were followed up for (6.21±2.90) months. The electrode parameters of all patients were stable and no complications observed. Conclusions: The LBBaP with nine-partition method is a simple, safe and effective physiological pacing approach. However, its long-term effect still needs to be further verified.

[Hypoxia and inflammation are risk factors for acute myocardial injury in patients with coronavirus disease 2019].

OBJECTIVE: To investigate the risk factors for acute myocardial injury in coronavirus disease 2019 (COVID-19) patients. METHODS: This is a retrospective analysis of a COVID-19 cohort, in which 149 confirmed COVID-19 patients enrolled were divided into the group of myocardial injury (19 cases) and the group of non-myocardial injury (130 cases). Myocardial injury was defined according to Fourth universal definition of myocardial infarction released by European Society of Cardiology (ESC) in 2018, that cardiac troponin (cTn) was above 99th percentile of the reference level. Clinical information and results of laboratory tests of the eligible patients were collected. Factors associated with myocardial injury in COVID-19 patients were evaluated. RESULTS: Compared with the group of non-injury, the patients in the group of injury were older and had a larger proportion of severe or critical cases (P < 0.05), higher respiratory rate and lower percutaneous oxygen saturation (SpO2) without oxygen therapy on admission (P < 0.05). All inflammatory indexes except for tumor necrosis factor α (TNF-α) showed significant elevation in the patients of the group of injury (P < 0.05). Analyzed by Spearman correlation test, we showed that the levels of circulatory cTnI were in positive correlation with the levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, receptor of interleukin-2 (IL-2R), interleukin-6 (IL-6) and interleukin-8 (IL-8) (ρ > 0, P < 0.05). Lower SpO2 without oxygen therapy on admission (OR: 0.860, 95%CI: 0.779-0.949, P=0.003) and higher plasma IL-6 levels (OR: 1.068, 95%CI: 1.019-1.120, P=0.006) were independent risk factors for acute myocardial injury in the patients with COVID-19 by multivariate Logistic regression analyses. CONCLUSION: Hypoxic state and inflammation may play a key role in the pathogenesis of acute myocardial injury in COVID-19 patients.

[Relationship between angiopoietin-2 and vascular endothelial factor and vasodilation function in hypertensive patients].

Objective: To analyze the relationship between angiopoietin 2 (Ang2) and vascular endothelial factor and vasodilation function in hypertensive patients. Methods: Patients with new onset grade 1~2 hypertension (n=40) and healthy control group (n=25) wereenrolledprospectively. Serum Ang2 and nitric oxide (NO), nitric oxide synthase (eNOS), endothelin-1 (ET-1) were measured in both groups. Flow-mediated vasodilation (FMD) were measured in hypertensive patients. The above indicators were reviewed in hypertensive patients after antihypertensive treatment until blood pressure<140/90 mmHg. Results: Compared with the control group, serum Ang2 (P=0.049) and ET-1 (P<0.001) were significantly higher. Serum NO (P<0.001) and eNOS (P<0.001) was significantly lower in the hypertensive group. Compared with baseline, serum Ang2 (P=0.049) and ET-1 (P<0.001) were decreased significantly, meanwhile serum NO (P<0.001) and eNOS (P<0.001) were significantly increased. Serum Ang2 after antihypertensive treatment was not significantly different from that of the control group, but no statistical difference was observed in FMD after antihypertensive therapy. Correlation analysis found that serum Ang2 was positively correlated with mean arterial pressure (R=0.432, P<0.001), and negative correlated with serum NO(R=-0.374, P=0.001) and FMD (R=-0.368 0, P=0.002). Multiple linear regression found that serum Ang2 was independently associated with body mass index, mean arterial pressure, and serum NO. Conclusion: Serum Ang 2 can reflect the degree of endothelial and vasodilation impairment in hypertensive patients. Antihypertensive therapy can improve endothelial function, but whether it can restore damaged vasodilation function needs further verification.

[The efficacy and safety of ultrafiltration for patients with heart failure: results from a single-center randomized controlled study].

Objective: To evaluate the efficacy and safety of ultrafiltration in patients with heart failure. Methods: One hundred and thirty four cases of patients with heart failure, who hospitalized in our hospital from June 2010 to June 2016 were enrolled in this study. Random serial number was generated using SPSS 22.0 software, patients were then randomly divided into control group and ultrafiltration group with the proportion of 1∶1 (67 cases in each group). Patients in the control group received standard therapy. Patients in the ultrafiltration group received ultrafiltration therapy for 8 hours. Curative effect was evaluated after 8 hours treatment in the control group and after 12 hours in the ultrafiltration group. Following parameters were compared between the two groups: body weight, dyspnea score and 6 minutes walking distance as well as blood pressure, heart rate, Na(+) , K(+) , Cl(-), pH, HCO(3)(-), Hb, PLT, Cr, BUN levels. Results: (1)Two patients died during run-in process and eventually 132 cases were chosen for final analysis (65 cases in control group and 67 cases in the ultrafiltration group). Gender, age, type of heart failure, dyspnea score, body weight at baseline were similar between the two groups. (2)Post therapy, patients' body weight decreased obviously, while dyspnea score and 6 minutes walking distance increased significantly in the ultrafiltration group compared to baseline(all P<0.05), and the improvement was significantly greater compared to control group(all P<0.05). (3)The safety index comparison of two groups: blood pressure, heart rate, Na(+) , K(+) , Cl(-), pH, HCO(3)(-), Hb, PLT, Cr, and BUN were similar between the two groups at baseline and post therapy. Conclusion: Ultrafiltration therapy is safe and effective to treat patients with heart failure.

Critical behavior in tetragonal antiperovskite GeNFe3 with a frustrated ferromagnetic state.

Tetragonal GeNFe3 has a second-order ferromagnetic (FM) to paramagnetic transition at 76 K. Our integrated investigations indicate that the ground FM state is frustrated and the tetragonal symmetry is retained below 550 K based on the results of variable temperature X-ray diffraction. Critical behavior was analyzed by a systematic bulk magnetization study. The estimated critical exponents by three different methods (modified Arrott plot, the Kouvel-Fisher method, and critical isotherm analysis) conformably suggest that long-range magnetic coupling described by mean-field (MF) theoretical model is dominant in GeNFe3. The experimental M-T-H data collapse into two independent branches according to the scaling equations m = f±(h) with the renormalized magnetization m = ε-ßM(H, ε) and the magnetic field h = Hε-(ß+γ). The exchange distance is estimated as J(r) ∼ r-4.8 on the basis of the ß and γ values, which lies between the long-range MF model (r-4.5) and the short-range 3D Heisenberg (3DH) model (r-5). Our results indicate that the competition between local magnetic moments of iron 3d electronic state and itinerant covalent interactions of N-Fe bonds should be responsible for critical behavior in this system.

IL-6 secreted by cancer-associated fibroblasts induces tamoxifen resistance in luminal breast cancer.

Cancer-associated fibroblasts (CAFs) have been implicated in the development of resistance to anticancer drugs; however, the role and mechanism underlying CAFs in luminal breast cancer (BrCA) tamoxifen resistance are unclear. We found that stromal fibroblasts isolated from the central or peripheral area of BrCA have similar CAF phenotype and activity. In vitro and in vivo experiments showed that CAFs derived from clinical-luminal BrCAs induce tamoxifen resistance through decreasing estrogen receptor-α (ER-α) level when cultured with luminal BrCA cell lines MCF7 and T47D. CAFs promoted tamoxifen resistance through interleukin-6 (IL-6) secretion, which activates Janus kinase/signal transducers and activators of transcription (JAK/STAT3) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways in tumor cells, followed by induction of epithelial-mesenchymal transition and upregulation of E3 ubiquitin ligase anaphase-promoting complex 10 activity, which targeted ER-α degradation through the ubiquitin-proteasome pathway. Inhibition of proteasome activity, IL-6 activity or either the JAK/STAT3 or PI3K/AKT pathways markedly reduced CAF-induced tamoxifen resistance. In xenograft experiments of CAFs mixed with MCF7 cells, CAF-specific IL-6 knockdown inhibited tumorigenesis and restored tamoxifen sensitivity. These findings indicate that CAFs mediate tamoxifen resistance through IL-6-induced degradation of ER-α in luminal BrCAs.Oncogene advance online publication, 9 June 2014; doi:10.1038/onc.2014.158.

MicroRNA-449a inhibits cell growth in lung cancer and regulates long noncoding RNA nuclear enriched abundant transcript 1.

OBJECTIVE: Lung cancer has become the primary cause of cancer-related death now. New therapies targeting the molecular regulatory machinery were required imperatively. MicroRNAs and long noncoding RNAs can respectively or cooperatively function as oncogenes or tumor suppressor genes in human cancers. The present study identified that miR-449a was down-regulated in tissue of human lung cancer. In this study, we aimed to investigate the function of miR-449a in NL9980 and L9981 lung carcinoma cells lines and the relationship with lncRNA nuclear enriched abundant transcript 1 (NEAT1). MATERIALS AND METHODS: miR-449a was profiled in several lung carcinoma cell lines by quantitative reverse transcription-polymerase chain reaction RT-PCR. We analyzed the effects of miR-449a overexpression on proliferation, apoptosis and cell cycle in L9981 cells. The regulatory relationship between miR-449a and NEAT1 was predicted in silico and further studied by miR-449a inhibitor and mimics assay. RESULTS: miR-449a was expressed in four cell lines, which we selected, however miR-449a was in high level in NL9980 and in low level in L9981 (P < 0.05). When the miR-449a was the overexpression in L9981 cells, the cell growth was suppressed, and the apoptosis cells were promoted compared with the control group (P < 0.05). The G1/G0 became longer and S, G2/M became shorter (P < 0.05) by miR-449a overexpression. Further study of the interaction between miR-449a and NEAT1 show that NEAT1 was up-regulated when cells were transfected with miR-449a inhibitor, and NEAT1 was down-regulated when cells transfected with miR-449a mimics. CONCLUSIONS: Our data indicate that miR-449a may function as a suppressor of lung cancer, and affects the expression of NEAT1 in lung cancer cells.

Noncoding RNA small nucleolar RNA host gene 1 promote cell proliferation in nonsmall cell lung cancer.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidence shows that noncoding RNAs (ncRNAs) are widely involved in the development and progression of NSCLC. ncRNA small nucleolar RNA host gene 1 (SNHG1) has not been studied in cancer, especially its role in lung cancer remains unknown. Our studies were designed to investigate the expression and biological significance of SNHG1 in lung cancer. SNHG1 may be a novel ncRNA in early diagnosis in lung cancer. METHODS: Noncoding RNA SNHG1 expression in 7 lung cancer cell lines was measured by quantitative real-time polymerase chain reaction. RNA interference approaches were used to find the biological functions of SNHG1. The effect of SNHG1 on proliferation was evaluated by cell count and crystal violet stains. RESULTS: Noncoding RNA SNHG1 expression was significantly upregulated in lung cancer cells when compared with normal bronchial epithelial cells. In addition, in vitro assays our results indicated that knockdown of SNHG1 inhibited cell proliferation. CONCLUSIONS: Our data indicated that ncRNA SNHG1 is significantly upregulated in NSCLC cell lines and may represent a new biomarker and a potential therapeutic target for NSCLC intervention.

Rippling muscle disease: evidence for phenotypic and genetic heterogeneity.

We describe the clinical features of a family with rippling muscle disease. Muscle stiffness and myalgia were the most prominent symptoms. Muscle rippling, although distinctive, was present in only 6 of the 11 affected family members, whereas persistent muscle contraction to muscle percussion was present in all affected adults. Although this persistent contraction resembled percussion myotonia, it was electrically silent and is therefore more aptly called "percussion contracture." We also observed two clinical features not emphasized in previously reported kindreds: mild but asymptomatic weakness of face or proximal muscles was present in 5 of 11 affected members, and 5 individuals also complained of toe walking after a prolonged period of inactivity, reflecting the disproportionate involvement of the calf muscles. The pedigree suggested autosomal dominant inheritance. Our linkage analysis excluded the region on chromosome 1q identified in a previous linkage study.

Effects of hypoxia/reoxygenation on angiogenic factors and their tyrosine kinase receptors in the rat myocardium.

The process of angiogenesis is initiated primarily as a consequence of hypoxic stimulation at the cellular and molecular level. Although several angiogenic growth factors have been identified, at present a detailed understanding of the interplay among inducing stimuli, growth factors, and their respective molecular targets remains to be evaluated. Here we report the effects of progressively increasing durations of moderate hypoxia on the protein expression profiles and tissue distribution patterns of the vascular endothelial growth factor system and the angiopoietin/Tie system in the adult rat myocardium. The relative temporal trends of expression of the various components of these two systems, as well as apparent relationships between Flk-1 and angiopoietin-2 and between Flt-1 and Tie-1, suggest a probable sequence of involvement during myocardial angiogenesis, as proposed in our model. Such relationships may potentially be utilized in formulating strategies for sequential gene therapy to achieve clinically relevant myocardial angiogenesis.

[Computer-assisted acquisition and analysis of high-resolution spectrum].

Based on the unique characteristic of spectral line center in the whole spectrum and noise threshold, a computer approach and program for the determination of spectral line position and relative intensity automatically are presented in this paper. Exploring this approach and computer program, we pre-analyzed the partially overlapped 16 line TuFIR experiment spectra of CHF3. The results of line positions and intensities for these TuFIR spectra are in excellent agreement with the results by least-square fit with heavily manual inference. The accuracy and efficiency of this method and program will ensure their wide application in complex high-resolution molecular spectrum.

Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22.

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. The clinical symptoms include cerebellar dysfunction and associated signs from dysfunction in other parts of the nervous system. So far, five spinocerebellar ataxia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7. Loci for SCA4 and SCA5 have been mapped. However, approximately one-third of SCAs have remained unassigned. We have identified a Mexican American pedigree that segregates a new form of ataxia clinically characterized by gait and limb ataxia, dysarthria, and nystagmus. Two individuals have seizures. After excluding all known genetic loci for linkage, we performed a genomewide search and identified linkage to a 15-cM region on chromosome 22q13. A maximum LOD score of 4.3 (recombination fraction 0) was obtained for D22S928 and D22S1161. This distinct form of ataxia has been designated "SCA10." Anticipation was observed in the available parent-child pairs, suggesting that trinucleotide-repeat expansion may be the mutagenic mechanism.

Clinical and genetic analysis of a distinct autosomal dominant spinocerebellar ataxia.

OBJECTIVE: To characterize a distinct form of spinocerebellar ataxia (SCA) clinically and genetically. BACKGROUND: The SCAs are a genetically heterogeneous group of neurodegenerative disorders affecting the cerebellum and its connections. The mutations for SCA1, 2, 3, 6, and 7 have been identified and shown to be due to expansion of a CAG repeat in the coding region of these genes. Two additional SCA loci on chromosomes 16 and 11 have been designated SCA4 and SCA5. However, up to 20% of individuals with autosomal dominant forms of ataxias cannot be assigned any of these genotypes, implying the presence of other unidentified genes that may be involved in the development of ataxia. METHODS: We ascertained and clinically characterized a six-generation pedigree segregating an autosomal dominant trait for SCA. We performed direct mutation analysis and linkage analysis for all known SCA loci. RESULTS: The mutation analysis excludes SCA1, 2, 3, 6, and 7, and genetic linkage analysis excludes SCA4 and SCA5 (multipoint location scores < -2 across the candidate region). Clinical analysis of individuals in this family shows that all affected members have dysarthria, gait and limb ataxia, and nystagmus. No individuals have major brainstem or long-tract findings. Analysis of age at disease onset through multiple generations suggests anticipation. CONCLUSION: This pedigree represents a genetically distinct form of SCA with a phenotype characterized by predominantly cerebellar symptoms and signs.

[Treatment of soil-transmitted helminth infections by anthelmintics in current use].

The efficacy of broad-spectrum anthelmintics in current use was studied in Hengshan County, Hunan Province. The vermicides under study include albendazole (400mg, single dose), mebendazole composite (mebendazole 100 mg and levamisole 25mg bid x 3d), oxantel pyrantel pamoate composite (pyrantel pamoate 150 mg and oxantel pamoate 150 mg bid x 2d), and pyrantel pamoate composite (base 10 mg/kg, single dose). Therapeutic effect assessed 2 weeks after medication revealed Ascaris egg negative rates or cure rates (CR) of 97.5-100% for the former 3 regimens, and 80.9% for the latter one; while CR for hookworm infection were 95.4%, 78.6-100%, 96.7% and 83.3%, respectively. A follow-up survey pursued 4 weeks post treatment showed no significant difference in CR for the above regimens. Judging from CR in Trichuris trichiura infection, pyrantel pamoate composite was recommended as the drug of choice (89.3%), which was followed by mebendazole composite (64.6-83.8%) and albendazole (28.2-42.6%), whereas pyrantel pamoate was inefficacious. Obvious egg reduction rates were evidenced post application of the above drugs in trichuriasis treatment except pyrantel pamoate at single dose.

[Studies on the T4+2H4+ cell of peripheral blood lymphocyte in systemic lupus erythematosus].

The cell surface phenotype of peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE) was studied with the anti-T4+, T8+ and T4+2H4+ monoclonal antibodies by flow cytometry. 13 patients with active SLE had a markedly low percentage of T4+2H4+ cells but had normal percentage of T8+ cells. Our results reveal that the influence of T cell to B cell is not only because of the quantity of T cells, also because of the function of T cells. The abnormality of T4+2H4+ cells may be important in the pathogenesis of SLE.