Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study.

BACKGROUND: Clinical studies have reported that patients with gastroesophageal reflux disease (GERD) have a higher prevalence of hypertension. AIM: To performed a bidirectional Mendelian randomization (MR) analysis to investigate the causal link between GERD and essential hypertension. METHODS: Eligible single nucleotide polymorphisms (SNPs) were selected, and weighted median, inverse variance weighted (IVW) as well as MR egger (MR-Egger) regression were used to examine the potential causal association between GERD and hypertension. The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs. The MR-Egger intercept test, Cochran's Q test and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of single instrumental variable. RESULTS: IVW analysis exhibited an increased risk of hypertension (OR = 1.46, 95%CI: 1.33-1.59, P = 2.14E-16) in GERD patients. And the same result was obtained in replication practice (OR = 1.002, 95%CI: 1.0008-1.003, P = 0.000498). Meanwhile, the IVW analysis showed an increased risk of systolic blood pressure (ß = 0.78, 95%CI: 0.11-1.44, P = 0.021) and hypertensive heart disease (OR = 1.68, 95%CI: 1.36-2.08, P = 0.0000016) in GERD patients. Moreover, we found an decreased risk of Barrett's esophagus (OR = 0.91, 95%CI: 0.83-0.99, P = 0.043) in essential hypertension patients. CONCLUSION: We found that GERD would increase the risk of essential hypertension, which provided a novel prevent and therapeutic perspectives of essential hypertension.

Mitochondrial energy metabolism is downregulated in repeated implantation failure patients related to alteration of PGC-1α acetylation level.

Herein we aimed at exploring mitochondrial energy metabolism status in patients with repeated implantation failure (RIF) and whether key regulatory factor PGC-1α of energy metabolism is involved in the decidualization of endometrial stromal cells. Mitochondrial oxidative phosphorylation level and ATP synthesis were compared in primary endometrial stromal cells from RIF and control group. At the same time, as one of key transcription regulators of mitochondrial energy metabolism, the expression level and acetylation level of PGC-1α were compared with two groups. Then, we downregulated the acetylation levels of PGC-1α, and the expression of decidual markers (PRL and IGFBP1) was observed further. Mitochondrial energy metabolism, showing by mitochondrial oxidative phosphorylation level and ATP synthesis, was decreased in the endometrial stromal cells of the RIF group (RIF-hEnSCs). Meanwhile, PGC-1α acetylation levels were significantly higher in RIF-hEnSCs. When we reduced the acetylation levels of PGC-1α in RIF-hEnSCs, the basal O2 consumption rate and maximal respiration were increased, and also the PRL and IGFBP1. Overall, our data indicated that the endometrial stromal cells of the RIF patients had low level of mitochondrial energy metabolism. Reducing acetylation level of key energy metabolism regulator PGC-1α can increase the decidualization level of RIF-hEnSCs. These findings may inspire new ideas about the treatment of RIF.

Trehalose hydrolysis and transport-related genes promote Bombyx mori nucleopolyhedrovirus proliferation through the phosphoinositide 3-kinase-Akt signalling pathway in BmN cell.

The reprogramming of host physiology has been considered an essential process for baculovirus propagation. Trehalose, the main sugar in insect blood, plays a crucial role as an instant energy source. Although the trehalose level is modulated following infection with Bombyx mori nucleopolyhedrovirus (BmNPV), the mechanism of trehalose metabolism in response to BmNPV infection is still unclear. In this study, we demonstrated that the trehalose level tended to be lower in BmNPV-infected hemolymph and higher in the midgut. The omics analysis revealed that two trehalose transporters, BmTret1-1 and BmTret1-2, and trehalase, BmTRE1 and BmTRE2, were differentially expressed in the midgut after BmNPV infection. BmTret1-1 and BmTret1-2 had the ability to transport trehalose into the cell and promoted cellular absorption of trehalose. Furthermore, the functions of BmTret1-1, BmTret1-2, BmTRE1 and BmTRE2 in BmNPV infection were analyzed. These genes were upregulated in the midgut after BmNPV infection. Virus amplification analysis revealed that these genes could promote BmNPV proliferation in BmN cells. In addition, these genes could promote the expression of BmPI3K, BmPDK1 and BmAkt and inhibit the expression of BmFoxO in the phosphoinositide 3-kinase (PI3K)-Akt signalling pathway. Similarly, the increased trehalose level in BmN cells could promote the expression of BmPI3K, BmPDK1 and BmAkt and inhibit the expression of BmFoxO. Taken together, BmNPV infection promote the expression of trehalose hydrolysis and transport-related genes. These changes affect the PI3K-Akt signalling pathway to facilitate BmNPV proliferation. These findings help clarify the relationship between trehalose metabolism and BmNPV infection.

Identification of mite-specific eosinophils in the colon of patients with ulcerative colitis.

The pathogenesis of ulcerative colitis (UC) is unclear. House dust mite (HDM) is associated with immune inflammation in the body. This study is designed to identify the association between HDM and UC clinical symptoms. UC patients (n = 86) and non-UC control (NC) subjects (n = 64) were recruited. Colon lavage fluids (CLF) were collected from HDM skin prick test positive patients during colonoscopy, and analyzed by immunological approaches. HDM was detected in fecal samples, which was positively correlated with UC clinical symptoms. HDM-specific eosinophils and Th2 cells were detected in CLF, which could be specifically activated by exposing to HDM in the culture. Direct exposure to HDM induced eosinophil activation in the colon of UC patients. UC patients displayed elevated levels of Th2 cytokines in the serum. UC clinical symptom scores were positively correlated with serum levels of Th2 cytokines. HDM was detected in UC patients' stools, which was positively correlated with UC clinical symptoms. Direct exposure to HDM could trigger eosinophilic activation of the colon.

Effects of Low Luteinizing Hormone During Ovarian Stimulation on Endometrial Gene Expression and Function - Transcriptome Analysis During the Implantation Window.

This study explored the impact of low luteinizing hormone (LH) levels during ovarian stimulation on endometrial function. Based on previous studies by us and others, we divided the patients into low (< 4 IU/L), medium (4-10 IU/L), and high (> 10 IU/L) LH groups. The study utilized a comparison control group design with three groups of 10 patients. Gene set enrichment analysis (GSEA) was applied for functional annotation. By analyzing the exon differentially expressed genes in the endometrium of these three patient groups during the embryo implantation window, we found that when compared to the medium LH group, low LH downregulated endometrial cell metabolism, including mitochondrial-nicotinamide adenine dinucleotide (Normalized Enrichment Scores, NES = - 1.53) and glycolytic metabolism (NES = - 1.22), immune regulation, and autophagy (NES = - 1.58). Transcription factors were the main regulators of cell function. We found that MCM2 was probably involved in regulating the endometrial function induced by low LH. MCM2 target genes were enriched in low LH group, NES = - 1.54. Low LH, but not high LH, altered the endometrial receptivity assay gene expression in comparison to the medium LH. Our results indicated that low LH impacted the endometrial cell function, with a greater effect than high LH. This research provides timely and necessary data on the involvement of LH in important endometrial cellular processes and these data support further clinical development of endometrial receptivity.

CD38+ B cells affect immunotherapy for allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases, but the therapeutic effects of AIT need to be improved. CD38+ B cells are an immune cell fraction involved in the pathogenesis of allergic diseases as well as in immune regulation. OBJECTIVE: We sought to elucidate the role of antigen-specific CD38+ B cells in AIT. METHODS: An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38+ B cells in AIT. RESULTS: A fraction of antigen-specific CD38+ B cell was detected in AR patients. CD38+ B-cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38+ B-cell frequency and regulatory T-cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38+ B cells to produce IL-6, that converted Treg cells to TH17 cells. Coadministration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT. CONCLUSIONS: Antigen-specific CD38+ B cells compromise AIT effects by producing IL-6 to convert regulatory T cells to TH17 cells. Inhibition of CD38+ B cells promotes the effects of AIT.

LncRNA ELF3-AS1 Promotes Non-Small Cell Lung Cancer Cell Invasion and Migration by Downregulating miR-212.

LncRNA ELF3-AS1 has been characterized as an oncogenic lncRNA in bladder cancer and oral cancer, whereas its role in non-small cell lung cancer (NSCLC) is unknown. In this study, the authors observed that ELF3-AS1 was upregulated in NSCLC tissues in comparison with that in paired nontumor tissues collected from 68 NSCLC patients. High expression levels of ELF3-AS1 predicted the poor survival of NSCLC patients. Expression levels of miR-212 were inversely and significantly correlated with the expression levels of ELF3-AS1 across NSCLC tissue samples. In NSCLC cells, overexpression of ELF3-AS1 led to downregulated miR-212 and increased methylation of miR-212 gene. In addition, overexpression of ELF3-AS1 inhibited the role of miR-212 in suppressing cancer cell invasion and migration. Therefore, ELF3-AS1 is upregulated in NSCLC and promotes cancer cell invasion and migration by downregulating miR-212 through methylation.

Value of Traditional Chinese Medicine syndrome differentiation in predicting the survival time of patients with advanced cancer.

OBJECTIVE: To prospectively study the accuracy of the palliative prognostic index (PPI) survival prediction model combined with Traditional Chinese Medicine (TCM) syndrome differentiation. METHODS: The PPI survival prediction model was used to predict survival time. Patients' real survival time was recorded. The survival time was calculated using the Kaplan-Meier method, and the logrank method was used to test the difference. RESULTS: The average PPI survival prediction score of 227 patients was 5.83 (95% CI: 5.29-6.37). There was a significant difference in the real-life period between the different PPI groups (P < 0.05). PPI group I (predicted survival of > 6 weeks) showed the highest predictive sensitivity and PPI group II (predicted survival of 3-6 weeks) showed the highest predictive specificity. According to TCM syndrome differentiation, 82 cases (36% ) were diagnosed with liver and kidney Yin deficiency (type IV). The actual survival time of type IV patients was significantly shorter than that of other types of patients (mean: 21.85 vs 28.70, P = 0.007). In group I, the median survival time of type IV patients and other types was 25 and 34 d, respectively (P < 0.001). The sensitivity and specificity of PPI prediction were improved in group II by TCM syndrome differentiation. For patients in group III whose predicted survival time was < 3 weeks, the specificity of PPI survival prediction was higher in type IV patients. CONCLUSION: This study shows that the PPI predictive tool for survival rate has important value. TCM syndrome differentiation and typing has certain significance for further classification and survival prediction.

Novel dual-mode antitumor chlorin-based derivatives as potent photosensitizers and histone deacetylase inhibitors for photodynamic therapy and chemotherapy.

The combination of photodynamic therapy (PDT) and chemotherapy is a prospective strategy to improve antitumor efficacy. Herein, a series of novel cytotoxic chlorin-based derivatives as dual photosensitizers (PSs) and histone deacetylase inhibitors (HDACIs) were synthesized and investigated for biological activity. Among them, compound 15e showed definite HDAC2 and 10 inhibitory activities by up-regulating expression of acetyl-H4 and highest phototoxicity and dark-toxicity, which was more phototoxic than Talaporfin as a PS while with stronger dark-toxicity compared to vorinostat (SAHA) as a HDACI. The biological assays demonstrated that 15e was liable to enter A549 cells and localized in mitochondria, lysosomes, golgi and endoplasmic reticulum (ER) etc. multiple organelles, resulting in higher cell apoptosis rate and ROS production compared to Talaporfin. Moreover, it could induce tumor cell autophagy as a dual PS and HDACI. All results suggested that compound 15e could be applied as a potential dual cytotoxic drug for PDT and chemotherapy.

Chemotherapy and targeted therapy near the end of life affects aggressiveness of palliative care.

BACKGROUND: The purpose of this study was to explore the difference in quality indicators for chemotherapy or targeted therapy for patients with cancer in their last month of life. METHODS: A total of 585 patients who had received targeted therapy or palliative chemotherapy (PCT) from April 2007 to December 2018 at the Department of Integrated Therapy of Fudan University Shanghai Cancer Center were included in this retrospective study. The patients' social demographic and clinical data were collected, and variables judged to be independent predictors of PCT or targeted therapy were selected for univariate and multivariate analyses of differences. RESULTS: Treatment with PCT was independently associated with age (P<0.001) and performance status (PS) (P<0.001). Treatment with targeted therapy was independently associated with PS (P<0.001). Patients who received continued chemotherapy or cardiopulmonary resuscitation (CPR) within the last month of life were subjected to more intensive treatment in comparison with those who did not know when they were admitted to the intensive care unit (ICU) in the last month of life (P<0.001). Subgroup analysis showed that lung cancer was independently associated with targeted therapy (P<0.001), and admission to the ICU was independently associated with PCT (P<0.001). CONCLUSIONS: In the last month of life, approximately 14.9% of patients with cancer received PCT, which conformed to international recommendations. Lower CPR rates and admission to the ICU were positively correlated with targeted therapy versus those who received chemotherapy at the end of life (EOL).

Effect of luteinizing hormone concentration on transcriptome and subcellular organelle phenotype of ovarian granulosa cells.

RESEARCH QUESTION: Granulosa cells (GCs) surrounding oocytes are crucial for follicular growth, oocyte development, ovulation, and luteinization under the dynamic co-stimulation of follicle stimulating hormone (FSH) and luteinizing hormone (LH). This study aimed to investigate the effect of LH levels on GCs in preovulatory follicles under gonadotropin releasing hormone antagonist-based ovarian stimulation. In vitro experiments were also conducted to study the direct effect of LH on GCs. METHODS: Twelve infertile women were divided into low (L), medium (M), and high (H) LH groups according to their serum LH levels during ovarian stimulation. RNA-sequencing (RNA-seq) was conducted to examine the transcriptome profiles of GCs obtained from the above patients during the oocyte retrieval. The activity of mitochondrial dehydrogenase was measured under the stimulation of recombinant LH (rLH) concentration gradient combined with recombinant FSH. The ultrastructures of subcellular organelles were observed. RESULTS: Bioinformatic analyses showed that compared with the M group, molecule and pathway changes in the L group and in the H group were similar. In cultured GCs, both insufficient and excessive rLH impaired the activity of mitochondrial dehydrogenase. With the medium rLH concentration, numerous cell connections and abundant mitochondria and liposomes were observed. Compared with the medium concentration, GCs showed smaller and rounder mitochondria, more autophagosomes, and massive organelles damages with excessive rLH, and swollen, circular, or forked mitochondria were observed with inadequate rLH. CONCLUSIONS: RNA-seq provided a novel spectrum of transcriptome characteristics of GCs potentially affected by serum LH levels during ovarian stimulation. In vitro, rLH could directly affect GCs at the subcellular level.

Long Noncoding RNA SNHG10 Sponges miR-543 to Upregulate Tumor Suppressive SIRT1 in Nonsmall Cell Lung Cancer.

Background: Long noncoding RNA SNHG10 has been reported to promote the development of liver cancer. While by analyzing The Cancer Genome Atlas (TCGA) dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC). This study aimed to investigate the roles of SNHG10 in NSCLC. Materials and Methods: This study included 60 pairs of NSCLC and nontumor tissue samples collected from 60 NSCLC patients (males and females, 39-66 years, 50.9 ± 5.5 years). Gene expression was detected by quantitative polymerase chain reaction and western blot. Overexpression experiments were used to analyze gene interactions. Effects of cell transfections on cell proliferation were analyzed by performing CCK-8 cell proliferation assays. Results: We confirmed the downregulation of SNHG10 in NSCLC. In addition, low expression level of SNHG10 predicted the poor survival of NSCLC patients. SNHG10 can directly interact with miR-543, while overexpression of miR-543 failed to downregulate SNHG10. However, SNHG10 overexpression led to upregulation of sirtuin 1 (SIRT1), a downstream target of miR-543. Cell proliferation assay showed that SNHG10 and SIRT1 overexpression led to the decreased proliferation rate of NSCLC cells. In contrast, miR-543 over-expression played an opposite role and reduced the effects of SNHG10 and SIRT1 overexpression. Conclusions: In conclusion, SNHG10 sponges miR-543 to upregulate tumor suppressive SIRT1 in NSCLC to suppress cell proliferation.

Acoustic Radiation Force Impulse Imaging With Virtual Touch Tissue Quantification Enables Characterization of Mild Hypoxic-Ischemic Brain Damage in Neonatal Rats.

OBJECTIVES: The aim of this study was to investigate whether the measurement of brain tissue stiffness using acoustic radiation force impulse (ARFI) elastography with virtual touch tissue quantification can improve the early detection of neonatal hypoxic-ischemic brain damage in rats. METHODS: Seven-day-old Sprague-Dawley rats were randomly assigned to 3 groups: the mild asphyxia (n = 30), moderate asphyxia (n = 30), and sham control (n = 10) groups. Rats in the mild and moderate asphyxia groups were exposed to 8% oxygen (hypoxia) for 30 and 60 minutes, respectively, at 1 hour after ligation of the right common carotid artery. An ultrasound diagnostic instrument was used to obtain 2-dimensional ultrasound images, and ARFI with virtual touch tissue quantification was used to measure shear wave velocity preoperatively and at 12, 24, 48, and 72 hours postoperatively. Hematoxylin-eosin staining was used to evaluate brain damage. RESULTS: Two-dimensional ultrasound imaging detected swelling and increased echogenicity at 48 to 72 hours in the mild asphyxia group and at 24 to 72 hours in the moderate asphyxia group. The shear wave velocity substantially increased from 0.65 ± 0.04 m/s preoperatively to 0.78 ± 0.07 m/s at 72 hours in the moderate asphyxia group and from 0.64 ± 0.04 m/s preoperatively to 0.70 ± 0.03 m/s at 72 hours in the mild asphyxia group. The changes in the shear wave velocity coincided with the histopathologic changes in the brain, which included neuronal demyelination, hyperplasia, and necrosis; edema around vascular structures; and hemorrhage in the ependymal and periventricular areas. CONCLUSION: Shear wave velocity data obtained with the virtual touch tissue quantification technique may be used for early diagnosis of neonatal hypoxic-ischemic brain damage.

Palliative Chemotherapy Near the End of Life in Oncology Patients.

BACKGROUND: Although palliative chemotherapy during end-of-life (EOL) care is used to relieve symptoms in patients with metastatic cancer, chemotherapy may lead to more aggressive EOL care. We evaluated the use of and variables associated with chemotherapy at EOL. METHODS: This study included data from patients who died from advanced cancer and underwent palliative chemotherapy between April 2007 and May 2017 at the Department of Palliative Care of Fudan University, Shanghai Cancer Center. Data were collected from hospital medical records. Univariate and multivariate analyses were conducted to identify the variables that independently predicted the use of palliative chemotherapy. RESULTS: Among the 542 patients in the study, 85 (15.7%) underwent palliative chemotherapy during the last month and 28 (5.2%) underwent it during the last 2 weeks of life. Age <59 years (odds ratio [OR] = 1.82, 95% confidence interval [CI]: 1.51-2.61), performance status <3 (OR = 3.73, 95% CI: 1.46-4.67), and cardiopulmonary resuscitation (OR = 3.88, 95% CI: 3.01-5.34) were independently associated with the use of chemotherapy. The use of palliative chemotherapy during the last year of life differed significantly by patient age ( P < .001). CONCLUSION: The observed chemotherapy rates of 15.7% during the last month of life and 5.2% during the last 2 weeks of life are in line with international recommendations. This study showed that palliative chemotherapy is associated with more aggressive EOL care and indicates that younger patients and those with lower performance status are more likely to receive palliative chemotherapy. Significant variations in EOL treatment strategies among different age groups during the last year of life were also identified.

Use of Palliative Chemo- and Radiotherapy at the End of Life in Patients With Cancer: A Retrospective Cohort Study.

BACKGROUND: Administration of chemotherapy and radiotherapy near the end of life is a frequently discussed issue nowadays. We have evaluated the factors associated with the use of chemotherapy and radiotherapy at the end of life among terminally ill patients in China. METHODS: This study included the data from patients who had died from advanced cancer who underwent palliative chemotherapy and radiotherapy between January 2007 and December 2013 at the Department of Palliative Care of Fudan University, Shanghai Cancer Center. Data were collected from hospital medical records. Univariate and multivariate analyses were conducted to identify the factors independently associated with the use of chemo- and radiotherapy. RESULTS: Among the 410 patients included (median age, 68 years; range, 18-93; 53% males), 47 (11.5%) underwent palliative chemotherapy and 28 (6.8%) underwent radiotherapy in the last 30 days. Age <65 years (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.06-2.88), performance status <3 (OR: 3.95; 95% CI: 1.56-5.07), and cardiopulmonary resuscitation (OR: 4.09, 95% CI: 2.66-5.34) were independently associated with the use of chemotherapy. Performance status <3 (OR: 4.06, 95% CI: 2.17-5.83) and cardiopulmonary resuscitation (OR: 5.28, 95% CI: 3.77-7.21) were independently associated with the use of radiotherapy. CONCLUSION: The findings indicate that younger patients with a lower performance status who do not have complications are more likely to opt for chemo- or radiotherapy. Further, the use of palliative chemo- and radiotherapy should be considered carefully in terminally ill patients with cancer, as they seem to indicate a higher risk of cardiovascular complications requiring resuscitation.

Cultural and ethical considerations for cardiopulmonary resuscitation in chinese patients with cancer at the end of life.

End-of-life (EOL) decision making is based on the values and wishes of terminally ill patients. However, little is known on the extent to which cultural factors affect personal attitudes toward life-sustaining treatments (LSTs) such as cardiopulmonary resuscitation (CPR) in China. This study evaluated the cultural and ethical considerations during EOL decisions and assessed the factors that affect pursuing LSTs in China. We used a case-control study design and compared their baseline characteristics with the provided EOL care and treatments. The CPR treatment among patients with cancer at EOL was affected by Chinese family traditions and Western influences. Our results reflect the need to improve EOL care and treatment in China.

Clinical manifestations and imaging characteristics of gliomatosis cerebri with pathological confirmation.

OBJECTIVE: To explore the clinical manifestations and imaging characteristics of gliomatosis cerebri to raise the awareness and improve its diagnostic accuracy for patients. MATERIALS AND METHODS: Clinical data, imaging characteristics and pathological examination of 12 patients with GC from Jan., 2008 to Jan., 2012 were analyzed retrospectively. RESULTS: Patients with GC were clinically manifested with headache, vomiting, repeated seizures, fatigue and unstable walking, most of whom had more than 2 lesions involving in parietal lobe, followed by temporal lobe, frontal lobe, periventricular white matter and corpus callosum. Magnetic resonance imaging (MRI) showed diffuse distribution, T1-weighted images (T1WI) with equal and low signals and T2-weighted images (T2WI) with bilateral symmetrical high diffuse signals. There was no reinforcement by enhancement scanning and signals were different in diffusion-weighted images (DWI). The higher the tumor staging, the stronger the signals. Pathological examination showed neuroastrocytoma in which tumor tissues were manifested by infiltrative growth in blood vessels and around neurons. CONCLUSIONS: In clinical diagnosis of GC, much attention should be paid to the diffuse distribution of imaging characteristics, incomplete matching between clinical and imaging characteristics and confirmation by combining with histopathological examination.

[Relation of apoptosis of K562 cells induced by naringenin in vitro to enzyme activity changes of caspase-3 and caspase-8 and expression of FAS/FASL proteins].

The objective of this study was to investigate the apoptosis-inducing effect and underlying mechanism of naringenin (NGEN) on K562 cells in vitro. The inhibition of NGEN on K562 cells was evaluated by means of MTT assay so as to observe the cytotoxicity of NGEN; The morphological changes of the cells treated by NGEN were observed by transmission electron microscope; cell apoptosis rate influenced by NGEN was assessed by flow cytometry; the enzyme activity changes of caspase-3 and caspase-8 in the process of NGEN-induced K562 apoptosis were detected by Caspase Colorimetric Assay Kit; immunohistochemistry technique was used to detect FAS, FASL protein expression in K562 cells. The results showed that the growth of cells was inhibited by NGEN in dose-and time-dependent manners (p<0.05); NGEN-induced K562 cells apoptosis and sub-G1 peak was observed; some typically early and final phase changes of cell apoptosis were revealed under transmission electron microscope; the enzyme activity of caspase-3 and caspase-8 and the expression of FAS remarkably increased, meanwhile the expression of FASL was down-regulated (p<0.05). It is concluded that NGEN exerts anti-cancer effect by inducing K562 cell apoptosis, and the regulation of the expression of FAS and FASL. The caspase-3 and caspase-8 co-pathway brings about one of the mechanisms.

Role of endothelin-1 receptor antagonists in vasoconstriction mediated by endothelin and other vasoconstrictors in human internal mammary artery.

BACKGROUND: The action of antagonists for endothelin type A (ET(A)) and type B (ET(B)) on the vasoconstriction mediated by various vasoconstrictors in the human bypass grafts have not been well-defined. We studied the role of antagonists for both ET(A) and ET(B) receptors in vasoconstriction mediated by endothelin-1 and other vasoconstrictors in the human internal mammary artery (IMA). METHODS: Isolated IMA rings (n = 192, taken from 49 patients) were studied in organ bath for the interaction between endothelin-1, angiotensin II, U46619, and potassium chloride and the antagonist for ET(A) (BQ-123) or ET(B) (BQ-788). RESULTS: Significant relaxations were observed by BQ-123 (agonist: endothelin-1, 84.9 +/- 7.9%; angiotensin II, 45.5 +/- 5.1%; and U46619, 30.7 +/- 5.7%) or BQ-788 (agonist: endothelin-1, 66.5 +/- 11.3%; angiotensin II, 38.9 +/- 4.2%; and U46619, 30.8 +/- 4.0%), but not to potassium chloride-induced precontraction. Incubation of IMA with BQ-123 or BQ-123 + BQ-788 significantly shifted the concentration-contraction curve to endothelin-1 rightward (p < 0.05 vs control) with effective concentration causing 50% of maximal response (EC50) (-7.59 +/- 0.04 or -7.81 +/- 0.05 vs -8.47 +/- 0.05 log M in the control, p < 0.001), whereas BQ-788 alone did not affect the contraction curve (p = 1.0 vs control). In contrast, none of the endothelin-1 inhibitors and the combination demonstrated significant depression effects on angiotensin II, U46619, or potassium chloride-induced contraction. CONCLUSIONS: The present study demonstrates the role of ET(A) and ET(B) antagonists in the endothelin-1-mediated contraction in the human IMA and indicates the dominant role of ET(A) receptors. Although these effects are specific to endothelin-1, cross-action between endothelin-1 and angiotensin II exists. These findings provide useful knowledge for the future development of the clinical antispastic protocol in coronary bypass surgery.

[Diagnostic value of 2-dimentional ultrasonography and color Doppler flow imaging in primary bone tumor].

OBJECTIVE: To explore the diagnostic value of 2-dimentional ultrasonography and color Doppler flow imaging (CDFI) in primary bone tumor. METHODS: The hemodynamic parameters such as systolic maximum velocity (Vmax), diastolic minimum velocity (Vmin), resistance index (RI), and pulsatility index (PI) of intratumoral folw in 93 patients with primary bone tumors proved by histopathology were studied using 2-dimentional ultrasonography and CDFI techniques. RESULTS: The bone destruction periosteum response and soft tissue mass were essentially revealed with 2-dimentional ultrasonography techniques. The intratumoral flow features were clearly shown by CDFI. The Vmax and Vmin in malignant bone tumor were significantly higher than those in benign one (P < 0.01). RI and PI in malignant bone tumor were lower than those in benign one (P < 0.01). CONCLUSION: Observing the features of bone tumor and hemodynamic parameters by 2-dimentional ultrasonography and CDFI has a great clinical value in diagnosing primary bone tumor and distinguishing the malignant and benign bone tumors.