Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Clinical value of Cyclin D1 and P21 in the differential diagnosis of papillary thyroid carcinoma.

BACKGROUND: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. METHODS: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. RESULTS: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. CONCLUSIONS: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.

Piperonyl-Tethered Rhodanine Derivatives Potently Inhibit Chitinolytic Enzymes of Ostrinia furnacalis.

Insect pest chitinases are potential target for developing new insect growth regulators. Piperine was found first to inhibit the insect chitinase (OfChi-h) from Ostrinia furnacalis (Asian corn borer) in this work, except for previously reported OfChtI. Novel piperonyl-tethered rhodanine derivatives 7a-j were rationally designed with piperine as lead and synthesized by introducing a unique rhodanine moiety into the piperine scaffold based on the similar binding cavity of OfChtI and OfChi-h. Compared to piperine, compounds 7a-j showed approximately 100- to 400-fold or 110- to 210-fold higher inhibitory capacity against two chitinases, respectively. Molecular mechanism studies indicated that π interactions are crucial for improving inhibitory activity against two chitinases due to the introduction of the conjugated rhodanine ring. Moreover, compounds 7a-c could dramatically inhibit the growth and development of O. furnacalis larvae by in vivo activity evaluation. This study provides novel piperonyl-tethered rhodanine derivatives inhibiting dual chitinases as insect growth regulator candidates.

Analysis of biolo artificial neural network in prediction of aerobic exercise index based on algorithm / Análise de rede neural artificial na predição do índice de exercício aeróbio baseada em algorítimo / Análisis de red neuronal artificial en la predicción del índice de ejercicio aeróbico

ABSTRACT Objective: To study the relationship between aerobic activity and cardiac autonomic nerve activity by artificial neural network algorithm and biological image fusion; because of the artificial neural network model (ANN) problems, biological image processing technology is introduced based on ANN. Methods: An Ann under biological image intelligence algorithm is proposed, a classifier suitable for electrocardiograph (ECG) screening is designed, and an ECG signal screening system is successfully established. Moreover, the data set of normal recovered ECG signals of the subjects during the experimental period is constructed, and a classifier is used to extract the characteristic data of a normal ECG signal during the experimental period. Results: The changes in resting heart rate and other physical health indicators are analyzed by combining resting physiological indicators, namely heart rate, body weight, body mass index and body fat rate. The results show that the self-designed classifier can efficiently process the ECG images, and long-term regular activities can improve the physical conditions of most people. Most subjects' body weight and body fat rate decrease with the extension of experiment time, and the resting heart rate decreases relatively. Conclusions: Certain indicators can be used to predict a person's dynamic physical health, which indicates that the experimental research of index prediction in this research has a good effect, which not only extends the application of artificial neural network but also lays a foundation for the research and implementation of ECG intelligent testing wearable devices. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Objetivo: Com o objetivo de estudar a relação entre atividade aeróbia e atividade nervosa autonômica cardíaca por algoritmo de rede neural artificial e fusão biológica de imagens, tendo em vista os problemas existentes no modelo de rede neural artificial (RNA), é introduzida a tecnologia de processamento biológico de imagens com base em ANN. Métodos: um algoritmo de inteligência biológica de imagem Ann é proposto, um classificador adequado para triagem eletrocardiográfica (ECG) é projetado e um sistema de triagem de sinal de ECG é estabelecido com sucesso. Além disso, o conjunto de dados de sinais de ECG normais recuperados dos sujeitos durante o período experimental é construído e um classificador é usado para extrair os dados característicos de um sinal de ECG normal durante o período experimental. Resultados: As alterações na frequência cardíaca em repouso e outros indicadores de saúde física são analisadas pela combinação de indicadores fisiológicos de repouso, a saber, frequência cardíaca, peso corporal, índice de massa corporal e índice de gordura corporal. Os resultados mostram que o classificador autodesenhado pode processar com eficiência as imagens de ECG, e as atividades regulares de longo prazo podem melhorar as condições físicas da maioria das pessoas. O peso corporal e a taxa de gordura corporal da maioria dos indivíduos diminuem com a extensão do tempo do experimento, e a freqüência cardíaca em repouso diminui relativamente. Conclusões: Certos indicadores podem ser usados para prever a saúde física dinâmica de uma pessoa, o que indica que a pesquisa experimental de predição de índice nesta pesquisa tem um bom efeito, que não apenas estende a aplicação da rede neural artificial, mas também estabelece uma base para a pesquisa e implementação de dispositivos vestíveis de teste inteligente de ECG. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.

RESUMEN Objetivo: Para estudiar la relación entre la actividad aeróbica y la actividad del nervio autónomo cardíaco mediante el algoritmo de red neuronal artificial y la fusión de imágenes biológicas, ante los problemas existentes en el modelo de red neuronal artificial (ANN), se introduce la tecnología de procesamiento de imágenes biológicas basada en ANA. Métodos: Se propone un algoritmo de inteligencia de imagen biológica de Ann, se diseña un clasificador adecuado para el cribado electrocardiógrafo (ECG) y se establece con éxito un sistema de cribado de señales de ECG. Además, se construye el conjunto de datos de las señales de ECG recuperadas normales de los sujetos durante el período experimental, y se utiliza un clasificador para extraer los datos característicos de una señal de ECG normal durante el período experimental. Resultados: Los cambios en la frecuencia cardíaca en reposo y otros indicadores de salud física se analizan combinando indicadores fisiológicos en reposo, a saber, frecuencia cardíaca, peso corporal, índice de masa corporal y tasa de grasa corporal. Los resultados muestran que el clasificador de diseño propio puede procesar de manera eficiente las imágenes de ECG, y las actividades regulares a largo plazo pueden mejorar las condiciones físicas de la mayoría de las personas. El peso corporal y la tasa de grasa corporal de la mayoría de los sujetos disminuyen con la extensión del tiempo del experimento, y la frecuencia cardíaca en reposo disminuye relativamente. Conclusiones: Ciertos indicadores pueden usarse para predecir la salud física dinámica de una persona, lo que indica que la investigación experimental de predicción de índices en esta investigación tiene un buen efecto, lo que no solo extiende la aplicación de la red neuronal artificial sino que también sienta las bases para la investigación. e implementación de dispositivos portátiles de prueba inteligente de ECG. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.

Integrating Sugar Metabolism With Transport: Elevation of Endogenous Cell Wall Invertase Activity Up-Regulates SlHT2 and SlSWEET12c Expression for Early Fruit Development in Tomato.

Early fruit development is critical for determining crop yield. Cell wall invertase (CWIN) and sugar transporters both play important roles in carbon allocation and plant development. However, there is little information about the relationship between CWIN and those functionally related sugar transporters during fruit development. By using transgenic tomato with an elevated CWIN activity, we investigated how an increase in CWIN activity may regulate the expression of sugar transporter genes during fruit development. Our analyses indicate that CWIN activity may be under tight regulation by multiple regulators, including two invertase inhibitors (INVINHs) and one defective CWIN (deCWIN) in tomato ovaries prior to anthesis. Among the sugar transporters, expression of SlSWEET12c for sucrose efflux and SlHT2 for hexose uptake was enhanced by the elevated CWIN activity at 10 and 15 days after anthesis of tomato fruit development, respectively. The findings show that some specific sugars will eventually be exported transporters (SWEETs) and hexose transporters (HTs) respond to elevate CWIN activity probably to promote rapid fruit expansion when sucrose efflux from phloem and hexose uptake by parenchyma cell are in high demand. The analyses provide new leads for improving crop yield by manipulating CWIN-responsive sugar transporters, together with CWIN itself, to enhance fruit development and sugar accumulation.

Screening active components from Rubus amabilis for pancreatic ß-cells protection.

CONTEXT: Rubus species (Rosaceae) have been used in folk medicine to treat diabetes due to their hypoglycaemic activity. OBJECTIVE: To screen the active components that act as hypoglycaemic agents in Rubus amabilis Focke and the underlying mechanisms. MATERIALS AND METHODS: Aqueous stem extract of R. amabilis was incubated with MIN6 ß-cells, PBS was used as the blank control. Then the cells were washed, cell membrane-bound components were dissociated and identified by UPLC/MS. Total procyanidins (PCs) in R. amabilis was enriched and the cytotoxicity and anti-proliferation on ß-cell were evaluated by MTT assay. PCs at 25, 50, and 75 µg/mL was applied for 24 h to determine its effects on palmitate (PA)-induced apoptosis and GSIS. Western blotting was employed to detect the protein expression of PI3K/Akt/FoxO1 signalling. The antioxidant indices were also measured. RESULTS: ß-Cell membrane-bound components were identified as three procyanidin B dimers and a C trimer. PCs showed no significant cytotoxicity up to a concentrations of 100 µg/mL. PCs treatment reversed the elevated apoptosis rate and impaired GSIS induced by PA. PCs markedly decreased the intracellular ROS and MDA production and increased the SOD activity. Moreover, PCs promoted the phosphorylation of Akt and FoxO1, and regulated Pdx-1 and Bax expression in MIN6 cells. Discussion and conclusion: The active components that act as hypoglycaemic agents in R. amabilis are procyanidins, which protected MIN6 cells against PA-induced apoptosis by activating PI3K/Akt/FoxO1 signalling. These results indicate that ß-cell extraction, combined with UPLC/MS, is a valid method for screening antidiabetic components from herbal medicines.

Knockdown of annexin VII enhances nasopharyngeal carcinoma cell radiosensitivity in vivo and in vitro.

BACKGROUND: Radioresistance leads to treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, enhancing the radiosensitivity of NPC cells would likely increase the effectiveness of radiotherapy. Annexin VII (Annexin A7, ANXA7) might be a tumor promoter in NPC but its functions in radiosensitivity remain unclear. METHODS: NPC cell lines CNE2-shANXA7 and CNE2-pLKO.1 were generated and CNE2-shANXA7 nude mice xenograft tumor models were established. The main effects and molecular mechanisms of ANXA7 knockdown in NPC radiosensitivity were studied in vitro and in vivo by analyzing cell viability, clonogenicity, apoptosis, cell cycle distribution, tumor radioresponse and immunohistochemistry assay. RESULTS: ANXA7 knockdown revealed potentially enhanced NPC cell radiosensitivity via apoptosis and increased the cell number at the G2/M phase. In the xenograft model, NPC cells with ANXA7 knockdown were dramatically sensitive to irradiation and tumor growth was significantly suppressed. Compared to CNE2-pLKO.1 xenografts, CNE2-shANXA7 showed more γ-H2AX foci and less phospho-DNA PKcs. CONCLUSIONS: ANXA7 knockdown increased the radiosensitivity of NPC by enhancing apoptosis, modulating the cell cycle distribution into more radiosensitive phases, promoting DNA damage, and inhibiting repair. We showed that decreased ANXA7 levels enhanced radiosensitivity and provided insights into the therapeutic targets for NPC radiotherapy.

Effect of Resourcefulness Training on Symptoms Distress of Patients with Nasopharyngeal Carcinoma.

BACKGROUND Symptom distress is very common in patients with nasopharyngeal carcinoma (NPC) during radiotherapy, seriously affecting their quality of life and impeding the process of rehabilitation. Resourcefulness training can enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation. However, the effects of resourcefulness training on local complications and benefit-finding in NPC patients during radiotherapy remains poorly understood. MATERIAL AND METHODS Questionnaires and resourcefulness training intervention were used in this study. The relationships among resourcefulness, benefit-finding, and symptom distress of 304 NPC patients were analyzed and the effects of resourcefulness training on NPC patients (N=80) were evaluated during radiotherapy. RESULTS Among the 304 NPC patients, age, educational level, occupation, family monthly income, method of payment of medical expenses, and histological types were significant factors influencing resourcefulness and benefit-finding. The patients' resourcefulness was positively correlated to their benefit-finding; and their distress was negatively correlated to their resourcefulness. After resourcefulness training for 2 months, average scores of the resourcefulness and benefit-finding were significantly increased in the intervention group (N=40) compared to those in the control group (N=40). Average scores of symptom distress were significantly reduced in the 2 groups, but they were reduced more significantly in the intervention group than in the control group. CONCLUSIONS The patients' benefit-finding and symptom distress were correlated with their resourcefulness. Resourcefulness training could enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation in NPC patients during radiotherapy.

Transcriptomic and metabolomics responses to elevated cell wall invertase activity during tomato fruit set.

Fruit set is a developmental transition from ovaries to fruitlets that determines yield potential. Cell wall invertase (CWIN) is essential for fruit and seed set, but the underlying molecular basis remains elusive. We addressed this issue by using CWIN-elevated transgenic tomato, focusing on ovaries and fruitlets at 2 d before and after anthesis, respectively. RNAseq analyses revealed that ovaries and fruitlets exhibited remarkable differences in their transcriptomic responses to elevated CWIN activity. Ovaries 2 d before anthesis were far more responsive to elevated CWIN activity compared with the fruitlets. We identified several previously unknown pathways that were up-regulated by elevated CWIN activity during fruit set. The most notable of these were expression of genes for defence, ethylene synthesis and the cell cycle along with a large number of cell wall-related genes. By contrast, expression of photosynthetic, protein degradation and some receptor-like kinase genes were generally decreased as compared with the wild type ovaries. GC-MS analyses revealed that 22 out of 24 amino acids exhibited reduced levels in the RNAi ovaries as compared with that in the wild type, probably owing to a down-regulated expression of protein degradation genes. Overall, the data indicate that (i) ovaries are much more sensitive to metabolic intervention than fruitlets; (ii) high CWIN activity could promote fruit set by improving resistance against pathogens and altering cell cycle and cell wall synthesis.

Tomato ovary-to-fruit transition is characterized by a spatial shift of mRNAs for cell wall invertase and its inhibitor with the encoded proteins localized to sieve elements.

Central to understanding fruit development is to elucidate the processes mediating a successful transition from pre-pollination ovaries to newly set fruit, a key step in establishing fruit yield potential. In tomato, cell wall invertase (CWIN) LIN5 and its inhibitor INH1 are essential for fruit growth. However, the molecular and cellular basis by which they exert their roles in ovary-to-fruit transition remains unknown. To address this issue, we conducted a study focusing on ovaries and fruitlets at 2 days before and 2 days after anthesis, respectively. In situ hybridization analyses revealed that LIN5 and INH1 exhibited a dispersed expression in ovaries compared with their phloem-specific expression in fruitlets. Remarkably, LIN5 and INH1 proteins were immunologically co-localized to cell walls of sieve elements (SEs) in ovaries immediately prior to anthesis and in young fruitlets, but were undetectable in provascular bundles of younger ovaries. A burst in CWIN activity occurred during ovary-to-fruit transition. Interestingly, the ovaries, but not the fruitlets, exhibited high expression of a defective invertase, SldeCWIN1, an ortholog of which is known to enhance inhibition of INH on CWIN activity in tobacco. Imaging of a fluorescent symplasmic tracer indicated an apoplasmic phloem unloading pathway operated in ovaries, contrary to the previously observed symplasmic unloading pathway in fruit pericarp. These new data indicate that (1) a phloem-specific patterning of the CWIN and INH mRNAs is induced during ovary-to-fruit transition, and (2) LIN5 protein functions specifically in walls of SEs and increases its activity during ovary-to-fruit transition, probably to facilitate phloem unloading and to generate a glucose signal positively regulating cell division, hence fruit set.

Reduced endoplasmic reticulum stress might alter the course of heart failure via caspase-12 and JNK pathways.

BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in mediating ischemic heart cell death. The aim of this study was to investigate whether manipulation of a key factor of the ER stress pathway, eukaryotic translation initiation factor 2 subunit α (eIF2α), can change the natural history of heart failure (HF). METHODS: HF was induced using coronary artery ligation in adult rats and a selective eIF2α dephosphorylation inhibitor, salubrinal (Sal), was used. Thirty minutes after ligation, rats were randomly assigned to 3 groups: myocardial infarction (MI) plus placebo injections (dimethyl sulfoxide; n = 12), MI plus Sal injection (Sal; n = 12), and MI (HF; n = 12). Hemodynamic parameters were examined. Hearts were harvested for apoptosis assessment after 8 weeks of Sal treatment by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labelling and flow cytometric analysis. Hearts were harvested to determine ER chaperones by Western analysis, real-time polymerase chain reaction and immunohistochemical analysis. RESULTS: Cardiac function was significantly improved in Sal-treated rats. Apoptosis was reduced by Sal treatment. Glucose-regulated protein-78 and -94 were increased in HF but normalized by Sal treatment. HF caused a significant increase in eIF2α phosphorylation, which was further increased by Sal treatment, and caspase-12 and phospho-c-JUN NH2-terminal kinase were markedly increased in rats with HF alone but significantly reduced by Sal treatment. CONCLUSIONS: Our results suggest that reduction of ER stress and myocardial apoptosis through inhibition of eIF2α dephosphorylation might alter the natural history of HF, which might provide a new approach for its treatment.

[Analyses of super-response to cardiac resynchronization therapy in patients with congestive heart failure: a multiple center trial].

OBJECTIVE: To evaluate the incidence of super-response and the potential predictors related to super-response after cardiac resynchronization therapy (CRT) in patients with congestive heart failure. METHODS: 190 patients [145 men and 45 women;age: (60.48 ± 11.91) years] underwent CRT between March 2001 and March 2012 were enrolled in this multi-center trial, of which, 54 patients with ischemic cardiomyopathy and 136 patients with non-ischemic cardiomyopathy. These patients were followed up from 6 months to 11 years (mean 58 months) post CRT. RESULTS: Ten patients died within 6 months post CRT, the others were followed up for more than 6 months. At 6-month follow-up, 51 patients were identified as CRT super-responders (28.33%), 75 patients were CRT responders (41.67%) and 29 patients were CRT non-responders (16.11%), and 25 patients were CRT negative responders (13.89%). Super-response occurred more frequently in non-ischemic cardiomyopathy patients, while non-response most commonly occurred in ischemic cardiomyopathy patients (P < 0.05); patients in the negative response group had higher serum creatinine level than other groups (P < 0.05) , and patients in the non-response group and negative response group had higher pulmonary artery pressure than patients in the super-response group (P < 0.05); the average QRS duration was ≥ 160 ms before CRT, and the mean decrease was around 30 ms after CRT in the super-response group while the average QRS duration was 139 ms before CRT, and the mean reduction was around 8 ms after CRT in the negative response group (P < 0.05). LV lead position in the super-response group was usually in the middle and base of the heart, while in the negative response group it was more commonly located in the apex of the heart (P < 0.01) . CONCLUSIONS: LV lead located at the middle and pre-CRT ORS duration ≥ 160 ms are associated with super-response post CRT procedure in this patient cohort.

Spectrum of ß-thalassemia mutations in Guizhou Province, PR China, including first observation of codon 121 (GAA>TAA) in Chinese population.

OBJECTIVES: Although the population prevalence and mutation spectrum of ß-thalassemia in most areas of south China have been characterized, the mutations have not been elucidated in Guizhou Province. The aim of this study was to investigate the spectrum of ß-thalassemia in this province. DESIGN AND METHODS: We detected and analyzed ß-globin gene mutations in 407 ß-thalassemia patients and carriers by PCR-based reverse dot blot (RBD) and direct sequencing methods. RESULTS: Twelve types of ß-globin gene mutations were detected. Among the 12 different mutations, six mutations are common, accounting for 97% of mutated alleles. The most prevalent mutation is codon 17 (A→T) with an allele frequency of 40.7%. In addition, codon 121 (GAA>TAA), a rare dominant mutation, was detected in a patient with ß-thalassemia intermedia for the first time in China. CONCLUSIONS: The results of this study will be useful in genetic counseling and prenatal diagnostic service of ß-thalassemia in Guizhou Province.

[RNAi-mediated knockdown of cyclooxygenase 2 inhibits the growth and migration of SaOS2 human osteosarcoma cells].

OBJECTIVE: To explore the effects of a knockdown of cyclooxygenase 2 upon the growth and migration of SaOS2 cells. METHODS: We employed lentivirus mediated-RNA interference technology to knockdown the endogenous expression of gene COX-2 in human osteosarcoma cells (SaOS2) and analyzed their phenotypical changes. The effects of COX-2 silencing on the proliferation, cell cycle and migration of SaOS2 cells were assessed by thiazolyl blue tetrazolium bromide, flow cytometry and migration assays respectively. COX-2, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) mRNA and protein expression were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: A decreased expression of COX-2 in human osteosarcoma cells significantly inhibited the growth and decreased the migration ability of SaOS2 cells. Furthermore, it also reduced VEGF, EGF and bFGF mRNA and protein expression. CONCLUSION: The COX-2 signaling pathway may provide a novel therapeutic target for the treatment of human osteosarcoma.

[Causes of non-response to cardiac resynchronization therapy in heart failure patients with permanent atrial fibrillation].

OBJECTIVE: To evaluate the long-term effects and analyze causes of non-response to cardiac resynchronization therapy (CRT) in heart failure (HF) patients with permanent atrial fibrillation (AF). METHODS: Thirty-three patients with HF and AF [29 men, mean age (61 ± 10) years, NYHA class III or IV, left ventricular ejection fraction (LVEF) ≤ 35%, QRS ≥ 120 ms in 31 cases] underwent bi-ventricular pacing (n = 26) or bi-ventricular pacing and atrioventricular node ablation (AVN-ablation, n = 7) were included in this study. Non-response was defined: the increase of left ventricular ejection fraction (LVEF) was less than 15%. Patients were followed-up for 4 years. RESULTS: Six patients died during follow up. Non-responder to CRT was observed in 6 out of 27 survived patients (22.22%). Six out of 7 patients underwent AVN-ablation were in responder group and 1 in non-responder group. Comparing with responder group, the baseline LVEF was significantly higher (37% vs. 32%, P = 0.003), and the history of HF was significantly longer (6.3 years vs. 4.1 years, P = 0.039), pulmonary artery pressure was significantly higher (53 vs. 32 mm Hg, P = 0.027), bi-ventricular pacing percentage (BIVP%) was significantly lower (75.86% vs. 91.73%, P = 0.007) in non-responder group. CONCLUSIONS: Higher LVEF, longer HF history, higher pulmonary artery pressure and lower BIVP% are factors linked with non-responses to CRT in this patient cohort. CRT plus AVN-ablation is associated with high response rate to CRT in this patient cohort.