[The prognostic value of free triiodothyronine/free thyroxine ratio in patients hospitalized with heart failure].

Objective: To investigate the effect of free triiodothyronine/free thyroxine (FT3/FT4) ratio on the prognosis of patients with heart failure (HF). Methods: A total of 3 527 patients hospitalized in the Heart Failure Center of Fuwai Hospital from March 2009 to June 2018 were analyzed in our study. Patients were divided into two groups according to median of FT3/FT4 ratio: low FT3/FT4 group (n=1 764, FT3/FT4<2.15) and high FT3/FT4 group (n=1 763, FT3/FT4≥2.15). The primary endpoint was defined as a composite endpoint of all-cause death or heart transplantation or implantation of a left ventricular assist device. The baseline characteristics of patients with different FT3/FT4 ratio groups were compared, and a multivariate Cox proportional hazard regression model was used to analyze the relationship between FT3/FT4 ratio and the prognosis of hospitalized patients with HF. Results: The age of the total population was (56.8±16.0) years, and 2 544 cases (72.1%) were males. The median follow-up time was 2.79 (1.00, 5.03) years, and a total of 1 542 end-point events were recorded at the final follow-up. The mean ages of patients in the low FT3/FT4 group and high FT3/FT4 group were (58.8±16.5) and (54.8±15.2) years (P<0.001), respectively; and the cumulative survival rates were 38.4% and 61.9%, respectively (P<0.001). FT3 (HR=0.72, 95%CI: 0.63-0.84, P<0.001), FT3/FT4 (HR=0.76, 95%CI: 0.65-0.87, P<0.001) was associated with all-cause death, heart transplantation, or LVAD implantation in patients with heart failure. HR values (95%CI) of FT3/FT4 ratio predicting the risk of composite endpoint in the subgroup of left ventricular ejection fraction (LVEF)<40%, 40% to 49%, and≥50% were 0.91 (0.77-1.08), 0.83 (0.50-1.39), and 0.65 (0.50-0.85), respectively (P interaction=0.045). Conclusions: Low FT3 and low FT3/FT4 are important correlative factors for poor prognosis in hospitalized HF patients, especially in patients with LVEF≥50%.

[Clinical features and prognosis of patients hospitalized with heart failure and low T3 syndrome].

Objective: To investigate the association between triiodothyronine (T3) and inflammatory factors, and its potential effect on long-term outcomes in hospitalized patients with heart failure (HF). Methods: A total of 2 475 patients with HF admitted in Heart Failure Care Unit were consecutively enrolled in this retrospective cohort study from December 2006 to June 2018. Patients were divided into low T3 syndrome group (n=610, 24.6%) and normal thyroid function group (n=1 865, 75.4%). The median follow-up time was 2.9 (1.0, 5.0) years. A total of 1 048 all-cause deaths were recorded at the final follow-up. The effects of free T3 (FT3) and high-sensitivity C-reactive protein (hsCRP) on the risk of all-cause death were evaluated by Cox regression analysis and Kaplan-Meier analysis. Results: The age of the total population was 19-95 (57±16) years, 1 823 cases (73.7%) were male. Compared to those with normal thyroid function, albumin [(36.5±5.4) vs. (40.7±4.7) g/L], hemoglobin [(129.4±25.1) vs. (140.6±20.6) g/L], total cholesterol [3.6 (3.0, 4.4) vs. 4.2 (3.5, 4.9) mmol/L] (all P<0.001) were lower, Whereas age [(60.5±16.0) vs. (55.2±15.4) years], creatinine [105.0 (83.6, 137.0) vs. 87.8 (75.6, 106.3) mmol/L], log N-terminal B-type natriuretic peptide [(8.2±1.3) vs. (7.2±1.4) ng/L] were higher in LT3S patients (all P<0.001). In Kaplan-Meier survival analysis, patients with lower FT3 and higher hsCRP had significantly lower cumulative survival (P<0.001), lower FT3 combined with higher hsCRP subgroup had the highest risk of all-cause death (Ptrend<0.001). In multivariate Cox regression analysis, LT3S was an independent predictor of all-cause mortality (HR=1.40, 95%CI 1.16-1.69, P<0.001). Conclusion: LT3S is an independent predictor of poor prognosis in patients with heart failure. FT3 combined with hsCRP improve the predictive value of all-cause death in hospitalized patients with heart failure.

[Association between serum potassium levels and all-cause mortality in patients with acute heart failure].

Objective: To investigate the relationship between different serum potassium levels at admission and discharge and all-cause mortality in patients with acute heart failure (HF). Methods: A total of 2 621 patients with acute HF who were hospitalized in the Heart Failure Center of Fuwai Hospital from October 2008 to October 2017 were analyzed. Patients were divided into three groups according to the different serum potassium levels at admission: hypokalemia with serum potassium<3.5 mmol/L (n=329), normokalemia with 3.5-5.5 mmol/L (n=2 270), and hyperkalemia with serum potassium>5.5 mmol/L (n=22). Clinical data such as patient history, comorbidities, clinical examination and drug use were collected, and systematic outpatient review or telephone follow-up was performed after patients were discharged from the hospital until January 2020. The primary outcome was all-cause death at 90 days, 2 years, and 5 years of follow-up. We compared the clinical characteristics of patients with different serum potassium levels at admission and discharge, and used a multivariate Cox proportional hazards regression model to analyze the association between serum potassium levels at admission and discharge and all-cause mortality. Results: The age of all patients was (58.0±15.3) years old, and 1 877 patients (71.6%) were male. There were 329 (12.6%) and 22 (0.8%) patients with hypokalemia and hyperkalemia at admission, and 38 (1.4%) and 18 (0.7%) at discharge, respectively. The serum potassium levels of all patients were (4.01±0.50) and (4.25±0.44) mmol/L at admission and discharge, respectively. The follow-up time[M(Q1,Q3)] of this study was 2.63(1.00,4.42)years, and a total of 1 076 all-cause deaths were recorded at the last follow-up. Compared with patients with normokalemia at discharge, discharged patients with hypokalemia and hyperkalemia were followed up for 90 days (90.3% vs 76.3% vs 38.9%), 2 years (73.8% vs 60.5% vs 33.3%) and 5 years (63.4% vs 44.7% vs 22.2%), respectively, and the difference of which in cumulative survival rates were statistically significant (all P values<0.001). The multivariate-adjusted Cox regression analysis showed that hypokalemia (HR=0.979, 95%CI: 0.812-1.179, P=0.820) and hyperkalemia (HR=1.368, 95%CI: 0.805-2.325, P=0.247) at admission were not associated with all-cause mortality risk, however, hypokalemia (HR=1.668, 95%CI: 1.081-2.574, P=0.021) and hyperkalemia (HR=3.787, 95%CI: 2.264-6.336, P<0.001) at discharge were associated with increased all-cause mortality risk. Conclusions: Both hypokalemia and hyperkalemia at discharge in hospitalized patients with acute HF were associated with increased short-and long-term all-cause mortality, and serum potassium levels should be closely monitored.

[The influence of meteorological factors on SARS-CoV-2 transmission: evidence from laboratory and epidemiological studies].

SARS-CoV-2 has infected more than 600 million people worldwide and caused more than 6 million deaths. The emerging novel variants have made the epidemic rebound in many places. Meteorological factors can affect the epidemic spread by changing virus activity, transmission dynamic parameters and host susceptibility. This paper systematically analyzed the currently available laboratory and epidemiological studies on the association between the meteorological factors and COVID-19 incidence, in order to provide scientific evidence for future epidemic control and prevention, as well as developing early warning system.

[Associations between adverse childhood experiences and adulthood substance use among lesbians].

Objective: To investigate the associations between adverse childhood experiences (ACE) and substance use behaviors among lesbians to provide a scientific basis for high-risk population identification and formulation of targeted intervention measures. Methods: Lesbians who participated in routine AIDS voluntary counseling, testing services, activities, and peer recommendations were recruited from July to December 2018, with the help of LesPark in Beijing. Convenient sampling method was used. Demographic characteristics, ACE, and substance use behaviors of subjects were investigated using an online platform powered by www.wjx.cn. Subsequently, the associations between ACE and adulthood substance use behaviors were evaluated using the logistic regression model. The SPSS 22.0 was used for statistical analysis. Results: A total of 294 lesbians were recruited in the study, 81.3% (239/294) of them were lesbians, and 18.7% (55/294) were bisexuals. Besides, 55.8% (164/294) of subjects reported they had had ACE, with proportions of lesbians experiencing abuse, neglect, and family dysfunction as 33.3% (98/294), 24.5% (72/294), and 32.7% (96/294), respectively. 55.1% (162/294) of the lesbians reported they had smoked in the past 30 days, 11.2% (33/294) reported having drug-use behavior in the past three months, and 22.8% (67/294) claimed drinking alcohol weekly. Multivariate logistic regression analysis showed that lesbians with ACE were at high risks to smoke (OR=1.87, 95%CI: 1.13-3.08), drink (OR=2.13, 95%CI: 1.18-3.84), and use drugs (OR=3.33, 95%CI: 1.29-8.61) in adulthood. Moreover, lesbians with childhood family dysfunction were at higher risk of smoking cigarettes (OR=2.60, 95%CI: 1.46-4.62) and drinking alcohol (OR=2.65, 95%CI: 1.44-4.87). At the same time, those with abuse experience were at higher risk of drug use (OR=3.17, 95%CI: 1.26-7.96). Conclusions: Substance use behaviors, including cigarette smoking, drinking alcohol, and drugs use, were common among lesbians. Positive associations were found between ACE and adulthood substance use behaviors.

[Ultrasound-guided stellate ganglion block improves sleep quality in elderly patients early after thoracoscopic surgery for lung cancer: a randomized controlled study].

OBJECTIVE: To investigate the effects of ultrasound-guided stellate ganglion block (SGB) on sleep quality in elderly patients with lung cancer early after thoracoscopic surgery. METHODS: A total of 86 patients with lung cancer (ASA class I-III, aged 60-80 years) undergoing elective thoracoscopic surgery were randomized into stellate ganglion block (SGB) group (n=43) and control group (n=43) to receive ultrasound-guided right SGB with 7 mL of 0.5% ropivacaine at the C6-7 level and injection of 7 mL saline at the same site 30 min before anesthesia induction, respectively. On the day before surgery and the first two days after the surgery, sleep duration, sleep efficiency index (SEI) and N3 sleep stage of the patients were monitored using a BIS-Vista monitor, and Athens Insomnia Scale (AIS) scores were recorded. The plasma levels of norepinephrine and cortisol of the patients were measured before SGB (T1), at 5 min after extubation (T2) and at 6:00 on the first morning after the surgery (T4). Urine levels of 6-hydroxysulfate melatonin (6-HMS) were measured at 6:00 in the morning for 3 consecutive days starting on the day of surgery (T3, T4 and T5, respectively). VAS score, incidences of postoperative delirium and depression, sufentanil consumption after surgery, and discharge time of the patients were recorded. RESULTS: Thirty-six patients in SGB group and 35 in the control group were analyzed. In both groups, most of the patients had insomnia after surgery, but compared with those in the control group, the patients in SGB group had significantly longer sleep duration (P < 0.05) with a higher sleep efficiency index (P < 0.05) and a longer sleep time in N3 stage (P < 0.05) on the first two nights after surgery. The mean postoperative AIS score and incidence of insomnia were significantly lower in SGB group than in the control group (P < 0.05). Compared with the control group, SGB group showed significantly lower plasma levels of norepinephrine and cortisol at T2 and T4 (P < 0.05), a higher urine level of 6-HMS at T5 (P < 0.05), and a shorter discharge time after the surgery (P < 0.05). The VAS scores, postoperative incidences of delirium and depression, or postoperative sufentanil consumption did not differ significantly between the two groups. CONCLUSION: Ultrasound-guided SGB improves objective and subjective sleep quality in elderly patients early after thoracoscopic surgery for lung cancer to alleviate stress responses and sleep disorders, reduce postoperative hospital stay, and accelerate postoperative recovery of the patients.

[The Ophthalmology-centered medical industry in Suzhou in the Ming and the Qing Dynasties - from the Painting Album of Cityscapes and Business].

The Painting Album of Cityscapes and Business was finished in the early Qing Dynasty with realism. This painting album described the prosperity in business and everyday life in Suzhou during the late Ming and the early Qing Dynasties. They were drawn and painted retrospectively, ie, the content of the pictures was based on existing paintings handed down. In the painting album, more than ten medical-related elements were specifically depicted, such as traditional Chinese medicine clinics and pharmacies and seven ophthalmology-related elements including one clinic specialized in ophthalmology, two spectacle shops, two people wearing eyeglasses and three blind people. Up to now, no specialized ophthalmology clinics and spectacle shops have been found in earlier literature and paintings. It can be speculated that the Painting Album of Cityscapes and Business is the earliest album of paintings depicting clinics specialized in ophthalmology and spectacle shops in China. This painting album provides important information for the study of the medical industry in Suzhou in the late Ming and the early Qing Dynasties, particularly, in terms of ophthalmology-related diagnosis and treatment.

[Clinical characteristics of hypertrophic cardiomyopathy and restricted cardiomyopathy patients complicating with intracardiac thrombosis].

Objective: To investigate the clinical characteristics of patients with hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) complicating with intracardiac thrombosis. Methods: This is a retrospective observational study. Consecutive patients diagnosed with HCM or RCM and complicated with intracardiac thrombosis (including left and right atrium or ventricular thrombosis), who were admitted to the Heart Failure Care Unit of Fuwai Hospital, Chinese Academy of Medical Sciences, from September 2008 to September 2018, were enrolled in this study. Patients with myocardial infarction were excluded. The general clinical data of the enrolled patients, including demographic data, major complications, laboratory indicators, echocardiographic indicators, drug application and distribution of intracardiac thrombosis, were collected from electronic medical record system and analyzed. Results: A total of 98 patients were enrolled in this study, including 52 patients (53.1%) with HCM and 46 patients (46.9%) with RCM. The most common comorbidity was atrial fibrillation/flutter: 40 patients (76.9%) in HCM group and 36 patients (78.3%) in RCM group. Majority of patients received oral anticoagulants treatment: 43 patients (82.7%) in HCM group and 35 patients (76.1%) in RCM group. Intracardiac thrombosis was mainly located in the left atrium in both HCM group (39 cases (75.0%)) and RCM group (32 cases (69.6%)). Thrombosis was found in ≥ 2 chambers in 7 patients (7.1%). Rate of left atrial thrombosis was the highest (81.6% (62/76)) in HCM and RCM patients complicating with atrial fibrillation/flutter. Intra-aneurysmal thrombosis occurred in 4 out of 5 patients complicated with apical left ventricular aneurysm. The rate of left ventricular thrombosis in patients with left ventricular ejection fraction≥50% was 7.4% (4/54), which was significantly lower than that in patients with left ventricular ejection fraction<50% (34.5%(10/29)) (P<0.01). Conclusion: There are certain distribution characteristics of HCM and RCM patients with intracardiac thrombosis, and the left atrium is the most common site of thrombosis, more attention should be paid in HCM and RCM patients on the diagnosis and treatment of intracardiac thrombosis.

A novel therapy, using Ghrelin with pegylated G-CSF, inhibits brain hemorrhage from ionizing radiation or combined radiation injury.

Medical treatment becomes challenging when complicated injuries arise from secondary reactive metabolic and inflammatory products induced by initial acute ionizing radiation injury (RI) or when combined with subsequent trauma insult(s) (CI). With such detrimental effects on many organs, CI exacerbates the severity of primary injuries and decreases survival. Previously, in a novel study, we reported that ghrelin therapy significantly improved survival after CI. This study aimed to investigate whether brain hemorrhage induced by RI and CI could be inhibited by ghrelin therapy with pegylated G-CSF (i.e., Neulasta®, an FDA-approved drug). B6D2F1 female mice were exposed to 9.5 Gy 60Co-γ-radiation followed by 15% total-skin surface wound. Several endpoints were measured at several days. Brain hemorrhage and platelet depletion were observed in RI and CI mice. Brain hemorrhage severity was significantly higher in CI mice than in RI mice. Ghrelin therapy with pegylated G-CSF reduced the severity in brains of both RI and CI mice. RI and CI did not alter PARP and NF-κB but did significantly reduce PGC-1α and ghrelin receptors; the therapy, however, was able to partially recover ghrelin receptors. RI and CI significantly increased IL-6, KC, Eotaxin, G-CSF, MIP-2, MCP-1, MIP-1α, but significantly decreased IL-2, IL-9, IL-10, MIG, IFN-γ, and PDGF-bb; the therapy inhibited these changes. RI and CI significantly reduced platelet numbers, cellular ATP levels, NRF1/2, and AKT phosphorylation. The therapy significantly mitigated these CI-induced changes and reduced p53-mdm2 mediated caspase-3 activation. Our data are the first to support the view that Ghrelin therapy with pegylated G-CSF is potentially a novel therapy for treating brain hemorrhage after RI and CI.

Multiple functions of miR-8-3p in the development and metamorphosis of the red flour beetle, Tribolium castaneum.

The microRNA miR-8-3p is conserved among insects and closely involved in development and immunity, but its functions in vivo are unexplored in the red flour beetle, Tribolium castaneum. Here, we show that miR-8-3p was highly expressed in late larva and early adult stages, as determined by quantitative real-time PCR. It was enriched in the fat body and cuticle in late larval tissues and abundant in the head and cuticle in early adult tissues, indicating this microRNA plays important roles during T. castaneum development. Specific inhibition of miR-8-3p in late larvae led to metamorphosis defects in the development of wings, eyes, legs and embryo. Moreover, a series of genes related to organism development were identified as miR-8-3p targets by computational prediction and microRNA-messenger RNA interaction validation, including Wingless, Eyg, Fpps and Sema-1a. These genes were critical for the regulation of the larva-to-adult transition. Eyg, as a functional target of miR-8-3p, participates in eye development, which was further confirmed by luciferase assay and loss-of-function analyses. In brief, miR-8-3p is broadly involved in the development of wings, eyes and legs through its target genes and has extensive regulatory roles during T. castaneum development.

Curcumin attenuates IR-induced myocardial injury by activating SIRT3.

OBJECTIVE: Ischemia-reperfusion (IR) injury remains an unresolved and complicated situation in clinical practice. In this study, H9c2 cardiomyocytes were subjected to curcumin (Cur) treatment in the absence or presence of the silent information regulator 3 (SIRT3) inhibitor 3-TYP and were then subjected to IR. MATERIALS AND METHODS: H9c2 cells and male Sprague-Dawley (SD) rats were cultured. MTT assay was performed to assess H9c2 cell viability. Cellular apoptosis was analyzed by TUNEL assay. The expressions of Bcl-2, Bax, SIRT3, and AcSOD2 were measured by Western-blotting. The activities of SOD, GSH-Px, and MDA were determined using commercially available kits. The myocardial infarct size was evaluated using TTC staining. RESULTS: Cur significantly increased H9c2 cell viability, decreased the cell apoptotic index, and altered several biochemical parameters, including upregulation of the anti-apoptotic protein Bcl-2, downregulation of the proapoptotic protein Bax and AcSOD2, activation of SIRT3, increase in SOD and GSH-Px activity, and decrease in MDA content. In isolated rat hearts, Cur significantly improved cardiac function, decreased infarct size, and lowered lactate dehydrogenase levels. These protective effects induced by Cur were reversed by treatment with the SIRT3 inhibitor 3-TYP. CONCLUSIONS: These results demonstrate that Cur protects cardiomyocytes and that rat hearts were exposed to IRI by activating SIRT3.

Both JrWRKY2 and JrWRKY7 of Juglans regia mediate responses to abiotic stresses and abscisic acid through formation of homodimers and interaction.

WRKY transcription factors belong to a large protein family that is involved in diverse developmental processes and abiotic stress responses. Currently, there is little understanding of the role of WRKY transcription factors in regulatory mechanisms in plants, especially in the protein-protein interactions that are essential for biological regulatory functions and networks. In the present study, yeast one-hybrid, yeast two-hybrid, transient expression and quantitative RT-PCR were applied to investigate the potential characteristics of two WRKY proteins from Juglans regia, JrWRKY2 (GenBank Accession No. KU057089) and JrWRKY7 (GenBank Accession No. KP784651). JrWRKY2 and JrWRKY7 can form homodimers and interact with each other. JrWRKY2 and JrWRKY7 can bind to W-box motifs. Similarly high levels of transcription were found for JrWRKY2 and JrWRKY7 under NaCl and polyethylene glycol (PEG) stresses, as well as at different developmental stages, e.g., the pistil or terminal leaf. JrWRKY2 and JrWRKY7 were transiently overexpressed in an independent manner in the terminal leaf. Analyses of superoxide dismutase (SOD) and peroxidase (POD) activities, proline and malondialdehyde (MDA) contents, and electrolyte leakage rate showed that JrWRKY2 and JrWRKY7 overexpression improved plant tolerance to NaCl, PEG, abscisic acid, and cold stress. Additionally, JrWRKY2 and JrWRKY7 overexpression elevated transcription of SOD, POD, glutathione peroxidase (GPX), catalase (CAT), ascorbate peroxidase (APX), and MYB genes, but downregulated the expression of NAC. Overall, the results demonstrate that JrWRKY2 and JrWRKY7 are dimeric proteins that can form functional homodimers and interact with each other and that they are involved in abiotic stress responses.

Arg188His polymorphism in the XRCC2 gene and the risk of ovarian cancer: a meta-analysis.

Numerous studies have evaluated the association between the Arg188His polymorphism of the X-ray repair cross-complementing group 2 (XRCC2) gene and ovarian cancer risk. However, the specific association is still controversial. This meta-analysis was therefore designed to clarify these controversies. Relevant case-control studies were enrolled in the meta-analysis. Quality evaluation of the included studies was conducted by two physicians. Statistical analyses were carried out using the Stata 12.0 software for meta-analysis. Analyses of sensitivity and publication bias were also conducted. Overall, a significant association was found between the Arg188His polymorphism and ovarian cancer risk when all studies were pooled into the meta-analysis (Arg/Arg vs His/His: OR = 1.85, 95%CI = 1.15-3.00; Arg/Arg vs Arg/His: OR = 1.17, 95%CI = 1.03-1.32; dominant model: OR = 0.84, 95%CI = 0.74-0.95; recessive model: OR = 1.69, 95%CI = 1.05-2.70). This meta-analysis suggested that the XRCC2 Arg188His polymorphism was associated with the risk of ovarian cancer. Further large and well-designed studies are needed to confirm these conclusions.

The influence of cytidine deaminase -33delC polymorphism on treatment outcome with high-dose cytarabine in Chinese patients with relapsed acute myeloid leukaemia.

WHAT IS KNOWN AND OBJECTIVE: Identification of biomarkers that could predict high-dose cytarabine (Ara-C) efficacy and toxicity is a key issue in individualized therapy. The aim of our study was to evaluate the influence of cytidine deaminase (CDA) single nucleotide polymorphisms (SNPs) -451G>A (rs532545), 435C>T (rs1048977) and -33delC (rs3215400) on treatment outcome in patients with relapsed acute myeloid leukaemia (AML) after high-dose Ara-C chemotherapy. METHODS: In total, 173 patients with relapsed AML, treated with high-dose Ara-C chemotherapy, were genotyped for three polymorphisms in CDA gene using the allele-specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays. Binary logistic regression was used to evaluate the influence of selected polymorphisms on tumour response and occurrence of treatment-related toxicity. RESULTS AND DISCUSSION: The CC genotype at -33delC, a promoter polymorphism, increased the odds of overall response rate (odds ratio [OR] = 5·125; 95% confidence intervals (CI) = 2·446-10·74; P = 0·0008) and grade ≥3 infection toxicity incidence rate (OR = 3·572; 95% CI = 1·68-7·594; P = 0·003). In multivariable analysis, this polymorphism was a potential independent prognostic marker for the risk of overall response (P = 0·011), but not grade ≥3 infection toxicity incidence rate (P = 0·49). Two other polymorphisms, -451G>A and 435C>T, did not influence treatment outcome, including overall response rate, infection toxicity and nausea/vomiting, in patients with relapsed AML (P > 0·05). WHAT IS NEW AND CONCLUSION: The findings suggest that CDA -33delC variant might be a potential marker for predicting treatment outcome in Chinese patients with relapsed AML given high-dose cytarabine chemotherapy.

A novel cytotoxic T lymphocyte epitope analogue with enhanced activity derived from cyclooxygenase-2.

Cyclooxygenase-2 is a promising target for cancer immunotherapy. Here, we designed the analogues p321-9L and p321-1Y9L (YLIGETIKL) from cyclooxygenase-2-derived native peptide p321. Then, we tested the binding affinity and stability of the analogues and their ability to elicit specific immune response both in vitro (from PBMCs of HLA-A*02⁺ healthy donors) and in vivo (from HLA-A2.1/K(b) transgenic mice). Our results indicated that the activity of cytotoxic T lymphocytes induced by p321-9L and p321-1Y9L was more potent than that of p321. In conclusion, the epitope analogue, especially p321-1Y9L, may be a good candidate which could be used to the immunotherapy of patients with tumours expressing cyclooxygenase-2.

Identification of a novel CD8+ T cell epitope derived from cancer-testis antigen MAGE-4 in oesophageal carcinoma.

MAGE-4 is considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy, and it is overexpressed in oesophageal carcinoma (EC). To identify MAGE-4-derived HLA-A2 restricted epitopes, native peptides and their analogues were predicted with prediction programs. The native peptide, p286 (KVLEHVVRV), and its analogues, p286-1Y2L and p286-1Y2L9L, showed potent binding affinity and stability towards HLA-A*0201 molecule. Cytotoxic T lymphocytes (CTLs) induced by p286-1Y2L9L could release IFN-γ in ELISPOT assay. In cytotoxicity assay, p286-1Y2L9L showed the capability to induce specific CTLs which could lyse the target cancer cells from both PBMCs of healthy donors and HLA-A2.1/K(b) transgenic mice. Our results indicated that the peptide p286-1Y2L9L could serve as a novel candidate epitope to develop peptide vaccines against oesophageal carcinoma.

Carvedilol reduces myocardial no-reflow by decreasing endothelin-1 via activation of the ATP-sensitive K+ channel.

It has been verified that carvedilol can attenuate myocardial no-reflow. However, the effects of carvedilol on adenosine triphosphate-sensitive K(+) (K(ATP)) channel and endothelin-1 (ET-1) are unknown. Forty mini-swines were randomized into 5 study groups: 8 control, 8 carvedilol pretreatment, 8 glibenclamide (K(ATP) channel blocker)-treated, 8 carvedilol and glibenclamide-pre-treated and 8 sham-operated. An acute myocardial infarction(AMI) and reperfusion model was created with a three-hour occlusion of the left anterior descending coronary artery followed by one-hour reperfusion. Compared with the control group, carvedilol significantly decreased the area of no-reflow (myocardial contrast echocardiography: from 78.5+/-4.5% to 24.9+/-4.1%, pathological means: from 82.3+/-1.9% to 25.8+/-4.3% of ligation area, respectively; all p < 0.01) and reduced necrosis size from 98.5+/-1.3% to 74.4+/-4.7% of ligation area, p < 0.05). It also decreased plasma ET-1 and myocardial tissue ET-1. However, glibenclamide abrogated the protective effect of carvedilol. The beneficial effect of carvedilol on myocardial no-reflow could be due to its effect on ET-1 via the activation of the K(ATP) channel.

Intravenous nicorandil preserves endothelial junctions by decreasing endothelin-1 via activation of ATP-sensitive K+ channel.

BACKGROUND: It has been verified that nicorandil can attenuate myocardial no-reflow. However; the effects of nicorandil on endothelial junctions and Endothelin-1 (ET-1) are unknown. METHODS: 40 mini-swines randomized into 5 study groups: 8 in control, 8 nicorandil pretreatment, 8 in glibenclamide (KATP channel blocker)-treated, 8 in nicorandil and glibenclamide-pretreated and 8 in sham-operated. Acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by one-hour reperfusion. RESULTS: In control group, plasma ET-1 significantly increased, ET-1 or VE-cadherin level in the reflow and no-reflow myocardium was significantly higher or lower than that in normal myocardium. Compared with the control group, nicorandil significantly decreased plasma ET-1 and myocardial tissue ET-1, maintained VE-cadherin level. However, glibenclamide abrogated the protective effect of nicorandil. CONCLUSIONS: The beneficial effect of nicorandil on endothelial junctions could be due to its effect on ET-1 via the activation of KATp channel.

Accumulation of Mn(II) in Deinococcus radiodurans facilitates gamma-radiation resistance.

Deinococcus radiodurans is extremely resistant to ionizing radiation. How this bacterium can grow under chronic gamma radiation [50 grays (Gy) per hour] or recover from acute doses greater than 10 kGy is unknown. We show that D. radiodurans accumulates very high intracellular manganese and low iron levels compared with radiation-sensitive bacteria and that resistance exhibits a concentration-dependent response to manganous chloride [Mn(II)]. Among the most radiation-resistant bacterial groups reported, Deinococcus, Enterococcus, Lactobacillus, and cyanobacteria accumulate Mn(II). In contrast, Shewanella oneidensis and Pseudomonas putida have high iron but low intracellular manganese concentrations and are very sensitive. We propose that Mn(II) accumulation facilitates recovery from radiation injury.