Complete remission of combined pulmonary large cell neuroendocrine carcinoma: a case report.

Pulmonary large cell neuroendocrine carcinoma (LCNEC), which accounts for approximately 1% of all lung cancers, is a rare and highly aggressive malignancy with a poor prognosis. Therefore, it is important to devise an effective treatment strategy. In the treatment of locally advanced complex LCNEC, it is unique to first administer radiotherapy combined with albumin-bound paclitaxel plus carboplatin, followed by durvalumab for immune maintenance treatment after concurrent radiotherapy and chemotherapy to achieve complete remission. We report a 54-year-old man who smoked and who felt chest tightness for 2 weeks and was diagnosed as having combined pulmonary LCNEC. For patients with locally advanced pulmonary LCNEC, chemoradiotherapy increases overall survival. After surgical resection and chemoradiotherapy, our patient achieved complete remission. Durvalumab was then started to consolidate the treatment. After six courses of immune maintenance therapy, the patient developed grade 2 immune-related pneumonitis and took prednisone orally until the symptoms resolved, and then reached complete remission again. The patient achieved complete remission, which was a challenge with this rare carcinoma, through albumin-bound paclitaxel plus platinum-based chemotherapy combined with radiotherapy and durvalumab for immune maintenance therapy. This approach may provide a treatment option for locally advanced combined pulmonary LCNEC.

Effectiveness of early treatment of lopinavir-ritonavir in patients with severe COVID-19: a case series.

AIM: The inconsistent effects of lopinavir-ritonavir (LPV/r) on COVID-19 seem to be caused by the therapeutic window. In the present study, we aim to present the effects of early LPV/r treatment on patients with severe COVID-19. METHODS: The demographics, characteristics, treatments, SARS-CoV-2 test results and outcomes of 19 patients with severe COVID-19 treated with LPV/r within 12 days of onset of symptoms were retrospectively assessed. RESULTS: Within 3 days of admission, three (15.79%) patients received noninvasive ventilation, and 16 (84.21%) patients received high-flow oxygen support. The median duration between the onset of symptoms and initiating LPV/r therapy was 9 (range 2-12) days. The median course of LPV/r treatment was 11 (range 7-17) days. One of the 19 patients (5.26%) died. Of the 18 patients discharged, the median hospital stay was 17 (range 11-45) days. At day 6 after LPV/r therapy was initiated, 68.42% of patients were virologically cured, increasing to 84.22% at day 12. CONCLUSION: In this cohort of patients with severe COVID-19 who were treated with LPV/r within 12 days of the onset of symptoms, clinical improvement was observed in 18/19 patients (94.74%). Randomised controlled trials are urgently needed to further evaluate this strategy.

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis.

Metformin was proposed to be a candidate for host-directed therapy for COVID-19. However, its efficacy remains to be validated. In this study, we compared the outcome of metformin users and nonusers in hospitalized COVID-19 patients with diabetes. Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China, from January 27, 2020 to March 24, 2020, were grouped into metformin and no-metformin groups according to the diabetic medications used. The demographics, characteristics, laboratory parameters, treatments, and clinical outcome in these patients were retrospectively assessed. A total of 283 patients (104 in the metformin and 179 in the no-metformin group) were included in this study. There were no significant differences between the two groups in gender, age, underlying diseases, clinical severity, and oxygen-support category at admission. The fasting blood glucose level of the metformin group was higher than that of the no-metformin group at admission and was under effective control in both groups after admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. The length of hospital stay did not differ between the two groups (21.0 days for metformin versus 19.5 days for no metformin, P = 0.74). However, in-hospital mortality was significantly lower in the metformin group (3/104 (2.9%) versus 22/179 (12.3%), P = 0.01). Antidiabetic treatment with metformin was associated with decreased mortality compared with diabetics not receiving metformin. This retrospective analysis suggests that metformin may offer benefits in patients with COVID-19 and that further study is indicated.

Expression and significance of CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56, Syn and CgA in biopsy specimen of squamous cell carcinoma, adenocarcinoma and small cell lung carcinoma / Expresión y significado de CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56 Syn y CgA en muestras de biopsia de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas de pulmón

Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %,and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P<0.05), The incidences of a positive P40 expression were 100 % in squamous cell carcinoma, with specificity of 98.81 %.CK7, TTF-1 and NapsinA expression were more frequent in adenocarcinoma, with sensitivity and specificity of 85.09 % and 78.69 %, 79.82 % and 93.44 %, 56.14 % and 95.08 %, and compared with squamous cell carcinoma and small cell carcinoma difference was statistically significant (P<0.05). TTF-1, Syn, CgA and CD56 expression were more frequent in adenocarcinoma, with sensitivity and specificity of 86.33 % and 93.44 %, 89.21 % and 98.36 %, 74.10 % and 100 %, 96.40 % and 96.72 %. The combined detection of CK5/6, P63 and P40 were more useful and specific in differentiating squamous cell carcinoma. CK7, TTF-1 and NapsinA were more useful and specific in differentiating lung adenocarcinoma. The impaired CD56, TTF-1, Syn and CgA reflects the progression of small cell lung cancer.

Se midieron tumores y utilizaron nueve biomarcadores potenciales y se analizó la información para diagnosticar la enfermedad. A todos los pacientes se les realizó citología en líquido con broncoscopía de fibra y examen histopatológico para detectar de manera confiable el cáncer pulmonar. Se obtuvieron muestras de 314 pacientes chinos con cáncer de pulmón y CK5 / 6, P63, P40, CK7, TTF-1, Napsina A, CD56, Syn y CgA se midieron a través de histoquímica SP y analizaron la correlación de la expresión de estos marcadores con características patológicas y clínicas de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas en el cáncer de pulmón. El carcinoma de células escamosas, el adenocarcinoma y el carcinoma de células pequeñas fueron 61 casos, 114 casos y 139 casos, respectivamente, la expresión de CK5 / 6 y P63 fueron más frecuentes en el carcinoma de células escamosas, con una sensibilidad y especificidad del 77,05 % y 96,44 %, 83,61 % y 88,93 %, y en comparación con el adenocarcinoma y el carcinoma de células pequeñas, la diferencia fue estadísticamente significativa (P <0,05). La incidencia de ap la expresión positiva P40 fue del 100 % en el carcinoma de células escamosas, con una especificidad del 98,81 %. La expresión de CK7, TTF-1 y NapsinA fueron más frecuentes en el adenocarcinoma, con una sensibilidad y especificidad del 85,09 % y 78,69 %, 79,82 % y 93,44 %, 56,14 % y 95,08 %, y en comparación con el carcinoma de células escamosas y la diferencia de carcinoma de células pequeñas fue estadísticamente significativa (P <0,05) .TTF-1, Syn, CgA y la expresión de CD56 fueron más frecuentes en adenocarcinoma, con sensibilidad y especificidad de 86.33 % y 93.44 %, 89.21 % y 98.36 %, 74.10 % y 100 %, 96.40 % y 96.72 %. La detección combinada de CK5 / 6, P63 y P40 fue más útil y específica en la diferenciación del carcinoma de células escamosas. CK7, TTF-1 y NapsinA fueron más útiles y específicos para diferenciar el adenocarcinoma de pulmón. El deterioro de CD56, TTF-1, Syn y CgA refleja la progresión del cáncer de pulmón de células pequeñas.

Comparative efficacy and safety of sunitinib vs sorafenib in renal cell carcinoma: A systematic review and meta-analysis.

To evaluate the safety and efficiency of sunitinib and sorafenib in the treatment of renal cell carcinoma (RCC).Databases were searched up till February 28, 2018. Two reviewers independently assessed trials for eligibility, quality, and extracted relevant data. Results are expressed as risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI). Six studies including 3112 patients were accessed. Sorafenib group exhibited higher median progression-free survival (mPFS) compared to sunitinib group (MD, -1.30; 95% CI, -2.56 to -0.03), especially in the first-line treatment (MD, -1.33; 95% CI, -2.61 to -0.04). However, sunitinib significantly reduced the risk of progression-free survival (PFS) compared to sorafenib (HR, 0.71; 95% CI, 0.6-0.82). Sunitinib also significantly reduced risk of overall survival (OS) compared to sorafenib (HR, 0.79; 95% CI, 0.65-0.92), while median OS was similar in both groups (MD, -0.48; 95% CI, -3.40-2.43). With regards to safety, the risk of rash (RR, 0.31, 95% CI, 0.12-0.79) was greater in sunitinib than sorafenib group, while the risk of decreased appetite (RR 2.10, 95% CI: 1.33-3.30) and dehydration (RR 2.73, 95% CI: 1.14-6.56) was smaller in contrast.Based on risk of PFS and OS, sunitinib was a better treatment option for RCC treatment while patients faced with severe skin reaction. And for those Asian patients classified under MSKCC moderate risk, whether in first or second-line treatment, had difficulty in feeding, sorafenib is a better choice for prolong mPFS.

Morphologic heterogeneity and markers of renal cell carcinoma with t(6; 11)(p21; q12): a case report and literature review.

OBJECTIVE: Renal cell carcinoma (RCC) with t(6; 11)(p21; q12) case report and review to explore its pathology morphologic heterogeneity and diagnostic criteria. METHODS: A female patient is 46 years old, who was admitted to hospital due to tumor of kidney. The gross and histological morphology of tumor were observed. Fluorescence in situ hybridization and immunohistochemistry were used to analyze the molecular markers, and the related literatures were reviewed. RESULTS: Grossly, the tumor was a 6 cm×5.5 cm×4.5 cm mass locating at the lower lobe of the right kidney. The tumor was poorly circumscribed, gray to tan cut surface with focal hemorrhage and cystic change. Histologically, the tumor was predominantly composed of alveolar architecture of polygonal tumor cells with well-defined cell borders, separated by thin capillaries. The tumor cells were positive for TFEB, Cathepsin-K, HMB45, Melan-A, E-cadherin and Vimentin. Gene rearrangement of TFEB was found. These markers showed that the tumor is a RCC with t(6; 11)(p21; q12). CONCLUSION: The morphology of RCC with t(6; 11)(p21; q12) is not entirely distinctive. Differential diagnosis of RCC with t(6; 11)(p21; q12), high-grade clear cell RCC and papillary RCC was necessary. For cases morphologically suspicious for t(6; 11)(p21; q12) RCC, FISH and IHC may be helpful for pathological diagnosis.

Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis.

Aberrant activation of Wnt/ß-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of ß-catenin and cyclin D1 genes in Wnt/ß-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer.

High admission glucose levels increase Fas apoptosis and mortality in patients with acute ST-elevation myocardial infarction: a prospective cohort study.

BACKGROUND: The presence of diabetes and plasma glucose concentration on admission are associated with adverse outcomes after an acute myocardial infarction (AMI), as high glucose can induce vascular endothelial cell apoptosis. This study explored the relative associations among admission plasma glucose level, soluble Fas (sFas) concentration, and long-term survival in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: This prospective cohort study include 83 patients with acute STEMI. Based on their admission plasma glucose levels (7.8 and 11.1 mmol/L as the limits for low and high levels, respectively), patients were allocated into one of three groups: normal glucose (n = 33), median glucose (n = 24), and high glucose (n = 26). The admission plasma level of sFas was measured with a sandwich enzyme-linked immunosorbent assay (ELISA). Patients were followed up for an average of 89 ± 20 months for all causes of death and cardiovascular death. RESULTS: sFas levels were significantly higher in the high glucose group compared to the normal glucose group (5.87 ± 1.70 mmol/L vs. 3.07 ± 0.93 mmol/L, respectively, P < 0.05). The sFas level was positively associated with the admission plasma glucose level. The correlation coefficient (R) was 0.747, and R2 was 0.559. Mortality was significantly higher in the high glucose group compared to the normal glucose group (19.2% vs. 3.0%, respectively, P < 0.05). CONCLUSIONS: In patients with acute STEMI, plasma glucose level was high on admission, and sFas apoptosis levels were increased. Long-term follow-up revealed that a high admission plasma glucose level was associated with higher mortality compared to a normal admission glucose level.

[Effects of weizhong (BL 40) area scraping on blood perfusion level of the skin microcirculation of qihaishu (BL 24) region at the ipsilateral back of the volunteer's body].

OBJECTIVE: To observe the effect of Guasha (scraping) of Weizhong (BL 40) on the cutaneous blood perfusion of Qihaishu (BL 24) region of the Bladder Meridian on the back. METHODS: Ten healthy volunteer subjects were recuited in the present study. Weizhong (BL 40, at the politeal fossa) area was repeatedly scraped till regional flush using a cornu bubali scraping plate for 5 min after applying scraping oil to the regional skin. Then blood perfusion levels of the skin microcirculation around Weizhong (BL 40) and Qihaishu (BL 24) regions on the ipsilateral back were detected using a Laser Doppler flowmetry (PeriScan PIM II). RESULTS: Following scraping Weizhong (BL 40) region, the cutaneous blood perfusion levels in the stimulated region were increased significantly at the time-points of 0, 15, 60 and 90 min after scraping (P < 0.001, P < 0.01), while those of Qihaishu (BL 24) area at the lumbar part also showed a remarkable increase 15, 60 and 90 min after scraping compared with the basic value (P < 0.05). A positive correlation was found between BL 40 and BL 24 areas in the cutaneous blood perfusion levels after scraping BL 40 (P < 0.05). CONCLUSION: Scraping stimulation of Weizhong (BL 40) can improve the cutaneous microcirculation of the stimulated BL 40 and Qihaishu (BL 24) regions in healthy volunteers, suggesting a close connection between BL 40 and the back described in Chinese medicine.

Effects of breviscapine on pulmonary inflammatory response and lung injury in children undergoing open heart surgery.

This study examined the effects of breviscapine (1) on pulmonary inflammatory response and lung function in pediatric patients undergoing open heart surgery. Forty-five children (ASA II or III, aged 2-72 months) were randomly assigned to control group (saline, Group C), low dose 1 group (0.5 mg/kg, Group Bre0.5), and high dose 1 group (1.0 mg/kg, Group Bre1.0), 15 cases each group. Plasma concentrations of procalcitonin (PCT) and neutrophil elastase (NE) were measured and compared at different time points. Plasma concentrations of PCT and NE were increased after cardiopulmonary bypass (CPB) induction, and the concentrations were lower in 1-treated groups. The present results indicated that continuous infusion of 1 before the CPB suppressed the production of PCT and NE attenuated systemic inflammatory response, which could result in lung protective effect in children undergoing open heart surgery.

[A study of association rules in three-dimensional property-taste-effect data of Chinese herbal medicines based on Apriori algorithm].

The theory of four properties (Qi) and five tastes (Wei) is the core of the property theory of Chinese materia medica. It is known that Qi and Wei are associated with the pharmacological effects (Xiao) of herbs. This study took records of all 365 Chinese herbs in Shennong's Classic of Materia Medica (Shennong Ben Cao Jing) as the data resource and established a three-dimensional data cube, in the purpose of finding out and analyzing the frequent patterns and valued association rules of Qi, Wei and Xiao based on Apriori algorithm. The results of this study may give rise to innovative ideas and methods in research of traditional Chinese materia medica.

Attenuation of tumor necrosis factor-alpha elevation and improved heart function by postconditioning for 60 seconds in patients with acute myocardial infarction.

BACKGROUND: Postconditioning has been shown to reduce infarct size, ischemic/reperfusion injury and myocardial injury in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). This study tested the hypothesis that postconditioning attenuates the elevation of tumor necrosis factor-alpha (TNF-alpha) and improves heart function in patients with AMI after PCI. METHODS: A total of 75 patients were randomly assigned to 1 of 3 groups: the routine group (n = 26), in which no intervention was given at the onset of reperfusion; and the Postcon-30s (n = 25) or Postcon-60 s (n = 24) groups, in which 3 cycles of 30- or 60-second balloon deflation and inflation were repetitively performed. TNF-alpha serum concentration was measured by ELISA. Global and regional left ventricular systolic function was determined by echocardiography at 1 year. Thirty-four normal controls (NC) were enrolled in the study. RESULTS: The TNF-alpha concentration in patients with AMI was significantly elevated at baseline compared to controls (P < 0.01). Concentration levels increased in the routine and Postcon-30s, but not in Postcon-60s group at 7 days (P < 0.05). As for linear associations among the three groups, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were ranked as follows: Postcon-60s > Postcon-30s > routine (P values all < 0.05, 65% vs. 57% vs. 52% and 1.10 vs. 1.27 vs. 1.53) after 1 year. More importantly, there was a significant relevance between the soluble TNF-alpha serum concentration at 7 days and LVEF or WMSI after 1 year (P values all < 0.0001). CONCLUSIONS: Postconditioning, in particular Postcon-60s was associated with long-term cardioprotective effects for inhibition of the inflammatory response and reperfusion injury. The soluble TNF-alpha serum concentration provided powerful prognostic information of global and regional left ventricular systolic function in patients with AMI.

Hydrogen sulfide opens the KATP channel on rat atrial and ventricular myocytes.

OBJECTIVE: Hydrogen sulfide (H(2)S), an endogenous gaseous transmitter, was found to protect the heart from various forms of injury, but the underlying mechanism is not known. H(2)S can open the K(ATP) channel on vascular smooth muscle cells, and the objective of this study was to determine whether H(2)S can open the K(ATP) channel on myocardiocytes. METHODS: The whole-cell patch-clamp technique was used to record I(K,ATP) and action potentials of atrial and ventricular myocytes isolated from the hearts of male Wistar rats. Sodium hydrogen sulfide (NaHS) was used as a donor of H(2)S to observe the effect of exogenous H(2)S on I(K,ATP). DL-propargylglycine (PPG), an inhibitor of the synthesis of H(2)S, was used at a concentration of 200 microM to observe the effect of endogenous H(2)S on I(K,ATP). RESULTS: NaHS at concentrations (in microM) of 9.375, 18.75, 37.5, 75 and 150 increased I(K,ATP) by 12.8% (p > 0.05), 28.4% (p < 0.05), 38.8% (p < 0.01), 51.2% (p < 0.01) and 58.6% (p< 0.01) on ventricular myocytes, respectively, and by 6.8% (p > 0.05), 10.4% (p > 0.05), 18.9% (p < 0.01), 24.8% (p < 0.01) and 37.2% (p < 0.01) on atrial myocytes, respectively. The H(2)S-induced decrease in the duration of action potentials (APD(90)) of ventricular myocytes was concentration-dependent, although only NaHS at a concentration of 150 microM decreased the APD(90) significantly (15%, p < 0.05). The H(2)S-induced decrease in APD(90) on atrial myocytes was concentration dependent, but the statistical difference was not significant. Inhibition of I(K,ATP) by PPG was time dependent and the level of inhibition was: ventricular myocytes, 7% (p > 0.05), 10% (p < 0.05), 15.3% (p < 0.01), 24.0% (p < 0.01) and 28.9% (p < 0.01); atrial myocytes, 15.8% (p > 0.05), 21.3% (p > 0.05), 26.5% (p < 0.01), 34.0% (p < 0.01) and 43.2% (p < 0.01) measured at 5, 10, 15, 20 and 25 min, respectively. The increase in the APD(90), by PPG was time dependent for ventricular myocytes [increased by 12.8% (p < 0.05) at 25 min]. The same was true for atrial myocytes, although only the value at 25 min was significant (15%, p < 0.05). CONCLUSIONS: H(2)S decreased the APD(90),and both the endogenous and exogenous H(2)S-induced increase in I(K,ATP) on both atrial and ventricular myocytes was concentration dependent. These results may help to explain, at least in part, how H(2)S protects heart cells from various forms of injury.

[Effects of hydrogen sulfide on the K ATP current in isolated rat ventricular myocytes].

OBJECTIVE: To investigate the effects of endogenous and exogenous hydrogen sulfide (H(2)S) on the K(ATP) current in isolated rat ventricular myocytes. METHODS: Ventricular myocytes were isolated from rat heart by modified Langendorff perfusion with collagenase. K(ATP) current of single rat ventricular myocytes was recorded by whole-cell patch-clamp technique. RESULTS: The density of K(ATP) current was significantly reduced by 200 micromol/L DL-propargylglycine (PPG, an irreversible inhibitor of the H(2)S) [(5.3258 +/- 0.7556) pA/pF vs. (3.7856 +/- 0.4312) pA/pF, P < 0.01] in a time-dependent way. The density of K(ATP) current could be significantly increased by NaHS (a H(2)S donor, 9.375, 18.75, 37.5, 75, 150 micromol/L) in a concentration-dependent manner [(6.6310 +/- 0.6092) pA/pF vs. (9.0949 +/- 1.0259) pA/pF at 150 micromol/L, P < 0.01]. CONCLUSION: Both endogenous and exogenous H(2)S could open K(ATP) channels and enhance the K(ATP) current in rat ventricular myocytes.

A 60-s postconditioning protocol by percutaneous coronary intervention inhibits myocardial apoptosis in patients with acute myocardial infarction.

Different postconditioning (Postcon) methods have been demonstrated to protect heart from ischemia/reperfusion injury. The relationship between Postcon by percutaneous coronary intervention (PCI) and apoptosis is not clear. Our objective was to test whether Postcon by PCI in patients with acute myocardial infarction (AMI) reduces myocardial apoptosis. Seventy-five patients were randomly assigned to one of three groups before stenting. The Routine group (n = 26) received no Postcon intervention prior to the onset of reperfusion; Postcon-30s (n = 25) and Postcon-60s groups (n = 24) underwent three cycles of 30- or 60-s balloon deflation and 30- or 60-s inflation. Additionally, 34 normal controls (NC) were enrolled in the study. Plasma concentrations of soluble Fas/APO-1 ([sFas]) and Fas ligand ([sFasL]) were determined at baseline and 7 days after PCI via ELISA. The [sFas] and [sFasL] in AMI patients were significantly elevated at baseline as compared with NC (P < 0.01), and showed an upward trend in the Routine group, a slightly upward trend in Postcon-30s, and a downward trend in Postcon-60s at 7 days. Comparison among the three groups showed significant differences (P < 0.05, 3.8 vs. 4.6 vs. 5.1 ng ml(-1)). The [sFasL] in Postcon-60s was significantly decreased at 7 days (P < 0.05, 3.9 vs. 3.1 ng ml(-1)) compared with baseline, but not Postcon-30s and Routine. More importantly, Postcon-60s group had the lowest [sFasL], followed by Postcon-30s, which had a lower value than Routine at 7 days (P < 0.05, 3.1 vs.3.7 vs. 4.2 ng ml(-1)). Our results suggest that Postcon-60s was visibly better than Postcon-30s, which in turn was better than Routine for inhibition of the effects of myocardial apoptosis and reduction of reperfusion injury in patients with acute myocardial infarction.

[Effects of ShenSongYangXin on action potential and some current channels in isolated rabbit pulmonary vein cardiomyocytes].

OBJECTIVE: To investigate the effects of ShenSongYangXin on action potential and some current channels in isolated rabbit pulmonary vein cardiomyocytes and to elucidate its possible mechanism of curing atrial fibrillation. METHODS: Action potentials as well as L-type calcium channel current (I(Ca-L)), transient outward potassium current (I(K1)) and inward rectifier potassium current (I(To)) were recorded using whole cell patch-clamp technique. RESULTS: ShenSongYangXin prolonged the action potential duration (APD) significantly, APD90 was enlarged from (187 +/- 49) ms to (286 +/- 76) ms at the concentration of 5 mg/ml and to (312 +/- 82) ms at the concentration of 10 mg/dl respectively (P < 0.05). It also depressed the current of I(Ca-L), I(K1) and Iro in a concentration-dependent manner. CONCLUSION: ShenSongYangXin can be used to treat atrial fibrillation through its actions on multiple current channels.

Cyclosporin A suppresses proliferation of endothelial progenitor cells: involvement of nitric oxide synthase inhibition.

OBJECTIVE: To investigate the effects of the potent immunosuppressive agent cyclosporin A (CsA) on the proliferation of human endothelial progenitor cells (EPCs) and endothelial nitric oxide synthase (eNOS) expression in EPCs. METHODS AND RESULTS: The EPCs were obtained from cultured mononuclear cells, which were isolated from the peripheral blood of healthy adults, and stimulated with CsA (10 microg/mL) in the presence or absence of either vascular endothelial growth factor (VEGF; 50 ng/mL) or L-arginine (1 mM). To explore the effect of different concentrations of CsA alone on EPC proliferation, some cells were treated with CsA in a series of final concentrations ranging from 0 to 10 microg/mL. Cell proliferation and apoptosis were determined, respectively, by the Cell Counting Kit-8 assay and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of eNOS was assayed by reverse transcription-polymerase chain reaction analysis while nitric oxide (NO) generation was detected using the Griess method. The effects of CsA on EPC proliferation, apoptosis, and eNOS/NO production were dose dependent in the concentration ranging from 0.1 microg/mL to 10 microg/mL. Treatment with VEGF (50 ng/mL) significantly promoted EPC proliferation and eNOS/NO production, which were completely abrogated by pre-incubation with CsA (10 microg/mL). The supplement of L-arginine (1 mM) promoted NO production that enhanced EPC proliferation and attenuated the effect of CsA on EPC proliferation and apoptosis. CONCLUSION: CsA significantly inhibited proliferation, eNOS mRNA expression and NO production of human EPCs, in a dose-dependent manner.

[Serum autoantibodies against the cardiac beta(1)-adrenergic receptor in patients with chronic heart failure: clinical characteristics and response to carvedilol].

OBJECTIVE: To detect the serum autoantibodies against the cardiac beta(1)-adrenergic receptor and observe the clinical characteristics and response to carvedilol use in patients with chronic heart failure (CHF). METHODS: Cardiac function was examined by echocardiography and levels of autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 65 patients with CHF by means of enzyme linked immune assay. Carvedilol was added on ACEI, diuretics and digitalis regimen for a target dose of 50 mg/d. All patients were followed up for 6 months. RESULTS: Autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 30 patients (group 1) and not detected in the remaining 35 patients (group 2). The achieved target dose of carvedilol was significantly higher in group 1 than that in group 2 [(36.25 +/- 14.31) mg/d vs. (25.97 +/- 8.83) mg/d, P < 0.01]. Heart rate was significantly higher in group 1 compared to group 2 [(94.19 +/- 14.46) beats/min vs. (86.56 +/- 15.88) beats/min, P < 0.05] before treatment and heart rate and blood pressure of both groups decreased significantly (P < 0.01) and there was no significant difference between two group (P > 0.05) after 6 months treatment. LVEDD and LVESD were significantly larger while LVEF significantly lower in group 1 patients than those in group 2 patients (all P < 0.05) before treatment and LVEDD and LVESD decreased and LVEF increased significantly in both groups (all P < 0.01 vs. before treatment) and there was on significant difference in LVEDD, LVESD and LVEF between two groups (all P > 0.05) post 6 months treatment. Moreover, average titer of autoantibodies against the cardiac beta(1)-adrenergic receptors significantly decreased after 6 months treatment (1:119.35 vs. 1:72.21, P < 0.01). CONCLUSION: The detection of autoantibodies against the cardiac beta(1)-adrenergic receptors is related to severer cardiac dysfunction and autoantibodies title decrease was found with improved cardiac function after standard therapy (ACEI, digitalis, betablocker) in patients with CHF.

[Effects of reperfusion arrhythmia on myocardial apoptosis and left ventricular remodeling in patients with acute myocardial infarction].

OBJECTIVE: To observe plasma soluble Fas/APO-1 concentration in patients with reperfusion arrhythmia immediately after coronary reperfusion in patients with acute myocardial infarction (AMI) and to investigate the impact of reperfusion arrhythmia on left ventricular (LV) remodeling in AMI patients. To observe the relationship between cardiomyocytes apoptosis with reperfusion arrhythmia in patients with acute myocardial infarction (AMI), and investigate the impact of reperfusion arrhythmia on left ventricular (LV) remodeling in patients with AMI. METHODS: One hundred and fifty-six patients with AMI who received reperfusion therapy were selected as subjects. Fifty-eight patients underwent reperfusion arrhythmia within 24 hour after coronary reperfusion treatment (RA group). Ninety-eight patients did not occurred reperfusion arrhythmia (Non-RA group). Strepavidin-biotin ELISA was used to determine the soluble Fas/APO-1 plasma concentration at baseline, 7 day (d) and 2 - 4 week (W). All patients were followed up with scheduled evaluations of LV function and morphology with left ventriculography for 1 year. RESULTS: 1. It was later that the coronary reperfusion occurred in patients of RA group than that of Non-RA group, and the left anterior descending was more frequent infarct related artery (60.3%) than of Non-RA group (36.9%, P < 0.05). 2. The Fas/APO-1 levels in patients of RA group higher than those of Non-RA group at baseline [(13.82 +/- 4.36) microg/L vs (8.19 +/- 3.56) microg/L, P < 0.01]. 3. The highest level of Fas/APO-1 was on 7 d after AMI and the plasma levels of Fas/APO-1 in 2 - 4 W were slightly lower than those in 7 d in the two groups [RA group: (10.91 +/- 3.65) microg/L vs (14.26 +/- 4.98) microg/L, P < 0.05; Non-RA group: (4.69 +/- 1.87) microg/L vs (12.19 +/- 3.25) microg/L, P < 0.01]. However, the Fas/APO-1 level of 2 - 4 W in RA group was slightly higher than the level in Non-RA group [(10.91 +/- 3.65) microg/L vs (4.69 +/- 1.87) microg/L, P < 0.01]. 4. There was on difference between two groups in left ventricular ejection fraction (LVEF) and the left ventricular end-diastolic dimension (LVEDD) one week after AMI [LVEF: (47.7 +/- 9.6)% vs (49.2 +/- 8.9)%, P > 0.05; LVEDD: (59.7 +/- 10.3) mm vs (57.4 +/- 12.4) mm, P > 0.05]. 5. In the Non-RA group, the LVEF significantly increased from 1 W phase to the 1-year phase [from (49.2 +/- 8.9)% to (59.5 +/- 9.2)%, P < 0.05], but unchanged in the 58 patients without reperfusion arrhythmia [from (47.7 +/- 9.6)% to (49.9 +/- 10.1)%, P > 0.05]. The LVEF of Non-RA group was slightly higher than that of RA group at 1 year [(59.5 +/- 9.2)% vs (49.9 +/- 10.1)%, P < 0.05]. The LVEDD had no significant difference between two groups, but there was downtrend in the Non-RA group at 1 year after AMI. CONCLUSION: Reperfusion arrhythmia was related with cardiomyocytes apoptosis in patients with AMI, and might influence left ventricular function and promote LV remodeling.

[Effect of serum autoantibodies against the M2 muscarinic acetylcholine receptors from patients with heart failure on L-Type Ca2+ channel activity in guinea pig cardiac myocytes].

OBJECTIVE: To investigate the effect of serum autoantibodies against the human M(2) muscarinic acetylcholine receptors (M(2)-receptors, Abs) from patients with congestive heart failure on L-Type Ca(2+) channel activity in guinea pig cardiac myocytes. METHOD: Using whole cell patch-clamp technique, we quantitatively measured the ionic intensity and density of L-Type Ca(2+) channel (I(Ca-L)). RESULTS: The M(2)-receptors agonist (carbachol) could decrease the I(Ca-L) peak intensity and density stimulated by isoprenaline from (2111.65 +/- 203.13) pA and (18.83 +/- 1.14) pA/pF to (1230.87 +/- 208.14) pA (P < 0.01) and (10.72 +/- 1.06) pA/pF (P < 0.01). The serum Abs could also decrease I(Ca-L) peak intensity and density [from (1995.21 +/- 195.13) pA and (18.13 +/- 1.03) pA/pF to (636.42 +/- 110.07) pA (P < 0.01) and (5.54 +/- 0.81) pA/pF, P < 0.01]. The M(2)-receptors antagonist, atropine was able to block these effects of carbachol and Abs. CONCLUSIONS: The circulating serum autoantibodies against the M(2)-receptors has similar effect as M(2)-receptors agonist on decreasing the isoprenaline stimulated I(Ca-L) in guinea pig cardiac myocytes and possess negative inotropic effect. These results further suggest that serum autoantibodies against the human M(2) muscarinic acetylcholine receptors may participate in the pathophysiological processes in patients with heart failure.