[Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model].

OBJECTIVE: To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted. RESULTS: Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses. CONCLUSION: Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

Lipocalin-2: a role in hepatic gluconeogenesis via AMP-activated protein kinase (AMPK).

PURPOSE: Evidence is accumulating that lipocalin2 (LCN2) is implicated in insulin resistance and glucose homeostasis, but the underlying possible mechanisms remain unclear. This study is to investigate the possible linkage between LCN2 and AMP-activated protein kinase (AMPK) or forkhead transcription factor O1 (FoxO1), which influences insulin sensitivity and gluconeogenesis in liver. METHODS: LCN2 knockout (LCN2KO) mice and wild-type littermates were used to evaluate the effect of LCN2 on insulin sensitivity and hepatic gluconeogenesis through pyruvate tolerance test (PTT), glucose tolerance test (ipGTT), insulin tolerance test (ITT), and hyperinsulinemic-euglycemic clamps, respectively. LCN2KO mice and WT mice in vivo, and in vitro HepG2 cells were co-transfected with adenoviral FoxO1-siRNA (Ad-FoxO1-siRNA) or adenovirus expressing constitutively active form of AMPK (Ad-CA-AMPK), or dominant negative adenovirus AMPK (Ad-DN-AMPK), the relative mRNA and protein levels of two key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P) were measured. RESULTS: Improved insulin sensitivity and inhibited gluconeogenesis in the LCN2KO mice were confirmed by pyruvate tolerance tests and hyperinsulinemic-euglycemic clamps. Nuclear FoxO1 and its downstream genes PEECK and G6P were decreased in the livers of the LCN2KO mice, and AMPK activity was stimulated and directly phosphorylated FoxO1. In vitro, AMPK activity was inhibited in HepG2 cells overexpressing LCN2 leading to a decrease in phosphorylated FoxO1 and an increase in nuclear FoxO1. CONCLUSION: The present study demonstrates that LCN2 regulates insulin sensitivity and glucose metabolism through inhibiting AMPK activity, and regulating FoxO1 and its downstream genes PEPCK/G6P, which regulate hepatic gluconeogenesis.

Clinical and radiological characteristics of COVID-19: a multicentre, retrospective, observational study.

BACKGROUND: Multicentre cohort investigations of patients with coronavirus disease 2019 (COVID-19) have been limited. We investigated the clinical and chest computed tomography characteristics of patients with COVID-19 at the peak of the epidemic from multiple centres in China. METHODS: We retrospectively analysed the epidemiologic, clinical, laboratory, and radiological characteristics of 189 patients with confirmed COVID-19 who were admitted to seven hospitals in four Chinese provinces from 18 January 2020 to 3 February 2020. RESULTS: The mean patient age was 44 years and 52.9% were men; 186/189 had ≥1 co-existing medical condition. Fever, cough, fatigue, myalgia, diarrhoea, and headache were common symptoms at onset; hypertension was the most common co-morbidity. Common clinical signs included dyspnoea, hypoxia, leukopenia, lymphocytopenia, and neutropenia; most lesions exhibited subpleural distribution. The most common radiological manifestation was mixed ground-glass opacity with consolidation (mGGO-C); most patients had grid-like shadows and some showed paving stones. Patients with hypertension, dyspnoea, or hypoxia exhibited more severe lobe involvement and diffusely distributed lesions. Patients in severely affected areas exhibited higher body temperature; more fatigue and dyspnoea; and more manifestations of multiple lesions, lobe involvement, and mGGO-C. During the Wuhan lockdown period, cough, nausea, and dyspnoea were alleviated in patients with newly confirmed COVID-19; lobe involvement was also improved. CONCLUSIONS: Among patients with COVID-19 hospitalised at the peak of the epidemic in China, fever, cough, and dyspnoea were the main symptoms at initial diagnosis, accompanied by lymphocytopenia and hypoxaemia. Patients with severe disease showed more severe lobe involvement and diffuse pulmonary lesion distribution.

Research Progress on Pathological Fibrosis of Sinoatrial Node.

ABSTRACT: Human heart rhythm is mainly regulated and controlled by the sinoatrial node. Fibrosis plays an important regulating role in adjusting the structural and functional integrity of the sinoatrial node pacemaker complex. In physiological state, the fibrosis degree of sinoatrial node is negatively correlated with heart rate, positively correlated with age and heart size, and can maintain a relatively stable heart rate. Pathological fibrosis of sinoatrial node can induce various types of arrhythmias which can result in sudden death. Determination of the mechanisms related to sinoatrial node pathological fibrosis could provide a target for clinical treatment of sinoatrial node fibrosis and diagnosis basis for forensic pathologists. This paper reviews the main mechanism of sinoatrial node pathological fibrosis, including abnormal activation of cardiac fibroblast cells in sinoatrial node, hyperplasia of epicardial adipose tissue, calcium clock disorder, artery stenosis, etc., introduces the test methods, diagnostic criteria as well as its role in sudden cardiac death and discusses the potential application, to provide reference for relevant research and application.

[Comparison on efficacy and safety of different bridging anticoagulation therapies in patients undergoing mechanical heart valve replacement surgery].

Objective: To evaluate the efficacy and safety of different bridging anticoagulant therapies in patients undergoing mechanical heart valve replacement (MHVR) surgery. Methods: Consecutive patients undergoing MHVR surgery from January 2018 to December 2018 in First Hospital of Lanzhou University were prospectively enrolled in this study. Patients were divided into unfractionated heparin (UFH) group and low molecular weight heparin (LMWH) group according to the postoperative bridging anticoagulation methods. Preoperative clinical data and postoperative related time and cost parameters, including drainage time, duration of stay in intensive care unit (ICU), postoperative time (interval from end of operation to discharge) and INR stabilization time (interval from start of bridge anticoagulation to INR value reaching the standard for 2 consecutive days) of all enrolled patients were collected, and all patients were followed up for 4 weeks and thromboembolic or bleeding events were analyzed. Multivariate logistic regression was used to determine the independent prognostic factors of thromboembolic or bleeding events after MHVR receiving various bridging anticoagulant therapies. Results: A total of 217 patients were included in the study, including 120 patients in the UFH group and 97 patients in the LMWH group. Stroke occurred in two patients in the UFH group, while no stroke event occurred in the LMWH group. The incidence of bleeding events was significantly higher (9.28%(9/97) vs. 1.67%(2/120), P=0.02), while the drainage time, duration of stay in ICU, postoperative time, INR stabilization time were all significantly shorter in LMWH group than in UFH group (all P<0.05). Multivariate logistic regression analysis showed that bridging anticoagulation therapies (OR=0.18, 95%CI 0.04-0.86, P=0.03), fibrinogen level (OR=1.99, 95%CI 1.16-3.41, P=0.01) and creatinine level (OR=1.05, 95%CI 1.01-1.08, P=0.04) were independent prognostic factors for bleeding events. Conclusion: LMWH use is associated with increased risk of bleeding events, but can significantly reduce the drainage time, duration of stay in ICU, postoperative time, INR stabilization time in patients post MHVR surgery.

Retention Time and Ion Abundance Ratio of 8 Common Drugs （Poisons） by LC-MS/MS Qualitative Analysis.

ABSTRACT: Objective To investigate the maximum allowable deviations of retention time and ion abundance ratio of the 8 common drugs （poisons） from 3 categories, poisons （methamphetamine, morphine, ketamine）, benzodiazepines （estazolam, midazolam, diazepam, clonazepam） and barbiturates （phenobarbital） in blood, by liquid chromatography-tandem mass spectrometry （LC-MS/MS） in forensic toxicology analysis. Methods The deviations of retention time and ion abundance ratio at 7 low mass concentrations, limit of detection （LOD）, 2LOD, limit of quantitation （LOQ）, 1.5LOQ, 2LOQ, 4LOQ and 6LOQ, were tested by LC-MS/MS after liquid-liquid extraction under the conditions of two chromatographic columns and three chromatographs. Results The deviation of absolute retention time of 98.11% of 8 drugs （poisons） in the blood samples was within the range of ±0.05 min, and that of the relative retention time of 96.21% was within the range of ±0.4%. The maximum deviation of the ion abundance ratio was highly correlated with the mass concentration. When the mass concentration of drugs （poisons） was LOQ or above, more than 95% of the absolute deviation and relative deviation of the ion abundance ratio were in the range of ±25% and ±40%, respectively; when the mass concentration was below LOQ, the range could be expanded to ±35% and ±50%, respectively. Conclusion It is recommended for the determination range of the absolute retention time deviation of 8 common drugs （poisons） to be ±0.1 min and that of the relative retention time deviation to be ±1.0%. The determination range of absolute deviation of the ion abundance ratio should be ±25% when the mass concentration is LOQ or above, and the relative deviation should be ±40%. When the mass concentration is below LOQ, the deviation determination range can be expanded to ±35% and ±50%, respectively.

Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs （Poisons.

ABSTRACT: Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs （poisons） in blood by gas chromatography-mass spectrometry （GC-MS） method. Methods Four common drugs （poisons） （dichlorvos, phorate, diazepam and estazolam） were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs （poisons） in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 µg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection （LOD）, 2LOD, limit of quantitation （LOQ） and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs （poisons） and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant （P>0.05）. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration （concentration less than 2LOQ） or low signal to noise ratio （3-15）, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs （poisons） in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.

Identification of a glutathione S-transferase gene of Physarum polycephalum as a biomarker for nanosized TiO2 exposure under dark conditions.

In this study, a glutathione S-transferase gene (gst) from sensitive Physarum polycephalum was selected for its ability to detect nanosized TiO2 (nTiO2 ) exposure under dark conditions. The concentration of nTiO2 (25, 40 and 60 nm) for subsequent assays was first determined (5-18 mg ml-1 ) and total GST enzyme activity of P. polycephalum was confirmed to be increased 6-44 fold in groups treated with nTiO2 . Second, an RNA-seq study was performed to identify candidate gst genes before isolation of an optimum gst gene of P. polycephalum (Ppgst), which encoded 223 amino acids. Third, the transcriptional level of the Ppgst gene was further confirmed to be positively correlated with nTiO2 exposure within the concentration range of (5-15 mg ml-1 ) by qPCR. In conclusion, these results indicated that the transcriptional level of Ppgst can reflect nTiO2 exposure, suggesting that it may be employed as a new biomarker for nTiO2 pollution under dark conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study identifies a new gst gene for indicating nanosized TiO2 under dark conditions and provides a new option for detection of nanosized TiO2 pollution under dark conditions.

Retention Time of Four Common Poisons （Drugs） by GC-MS Qualitative Analysis.

OBJECTIVES: To investigate the maximum allowable deviation of retention time （RT） or relative retention time （RRT） between the common poisons （drugs） and standard solvent by gas chromatography-mass spectrometry （GC-MS）. METHODS: After pretreatment with liquid-liquid extraction, four common poisons （drugs）-dichlorvos, phorate, diazepam and estazolam-were detected by full scan mode GC-MS. RT and RRT were analyzed according to combined uncertainty and expanded uncertainty. RESULTS: The expanded uncertainty of RT and RRT were 6.0×10-4-14.1×10-3 and 2.5×10-6-5.9×10-5 （k=3）, respectively. The RT of poisons （drugs） was relatively stable in blood samples with different mass concentrations. Among dichlorvos, phorate, diazepam and estazolam, the absolute deviation and relative deviation of RT were ≤0.03 min and ≤0.4%, respectively, and those of RRT were ≤0.003 min and ≤0.3%, respectively. CONCLUSIONS: The maximum allowable deviations of RT and RRT for common poisons （drugs） in blood samples are recommended to be ±0.05 min and ±0.5%.

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.

BACKGROUND: MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated. METHODS: In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice. RESULTS: MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial-mesenchymal transition (EMT)-associated proteins. TGF-ß1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-ß1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1. CONCLUSIONS: miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.

[Confirming Indicators of Qualitative Results by Chromatography-mass Spectrometry in Biological Samples].

Because of the exist of complex matrix, the confirming indicators of qualitative results for toxic substances in biological samples by chromatography-mass spectrometry are different from that in non-biological samples. Even in biological samples, the confirming indicators are different in various application areas. This paper reviews the similarities and differences of confirming indicators for the analyte in biological samples by chromatography-mass spectrometry in the field of forensic toxicological analysis and other application areas. These confirming indicators include retention time （RT）, relative retention time （RRT）, signal to noise （S/N）, characteristic ions, relative abundance of characteristic ions, parent ion-daughter ion pair and abundance ratio of ion pair, etc.

Self-frequency-doubled BaTeMo2O9 Raman laser emitting at 589 nm.

In this paper, the spontaneous Raman spectra and second harmonic generation (SHG) properties at 589 nm of a novel Raman crystal BaTeMo(2)O(9) (BTM) were investigated. The BTM crystal was cut along the type-II SHG phase-matching direction for the first-order Raman shift at 1178 nm to realize the SRS and SHG simultaneously. Pumped by a nanosecond 1064 nm laser source, a self-frequency-doubled BTM Raman laser operating at 589 nm has been demonstrated for the first time. At the pump pulse energy of 48 mJ, the maximum yellow laser output pulse energy of 5.6 mJ was obtained with an optical-to-optical conversion efficiency of 11.7%. Our results show that BTM crystal is one of the promising candidate Raman materials to generate yellow laser radiation.

Passively Q-switched Nd:Sc0.2Y0.8SiO5 dual-wavelength laser with the orthogonally polarized output.

We have demonstrated a laser-diode pumped continuous-wave (CW) and passively Q-switched laser with a Nd:Sc(0.2)Y(0.8)SiO(5) (Nd:SYSO) crystal for the first time. In the CW operation, the laser was found to oscillate in tri-wavelength regime at 1074.8 nm, 1076.6 nm and 1078.2 nm, respectively. The maximum CW output power of 1.96 W was obtained, giving an optical-to-optical conversion efficiency of 35% and a slope efficiency of 39%. Using either Cr(4+):YAG or V(3+):YAG crystal as saturable absorber, stable passively Q-switched laser was obtained at dual-wavelength of 1074.8 nm and 1078.2 nm with orthogonal-polarization. The maximum average output power, pulse repetition rate, and shortest pulse width were 1.03 W, 50 kHz, and 24 ns, respectively. The passively Q-switched dual-wavelength laser could be potentially used as a source for generation of terahertz radiation.

Galectin-1-induced down-regulation of T lymphocyte activation protects (NZB x NZW) F1 mice from lupus-like disease.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a hyperactive immune system, including activation of autoreactive T and B cells. These studies demonstrate that administration of recombinant galectin-1, a ß-galactose binding protein, to SLE-prone (NZB × NZW) F1 mice reduced lymphocyte activation, inhibited serum anti-double-stranded DNA(dsDNA) IgG antibody production, decreased the incidence of proteinuria, and increased survival rate. In addition, recombinant galectin-1'-treated mice had a higher frequency of Foxp3 expression, which suggested an increase in the percentage of peripheral regulatory T cells. Consistent with the finding that there were fewer activated T lymphocytes, ex vivo T cells from mice treated with recombinant galectin-1 exhibited less proliferation in response to TCR stimulation. Furthermore, these cells were less efficient at lipid raft clustering in response to TCR/CD28 engagement, consistent with published reports that galectin-1 can reorganize the synaptic contact to interfere with TCR signaling and activation to prevent T cell activation. Aged galectin-1-deficient mice had higher serum levels of antibodies against dsDNA, elucidating a role for endogenous galectin-1 in decreasing susceptibility to autoimmunity. Together, the findings highlight galectin-1 as a novel potential therapeutic immune modulator for treatment of lupus-like disease.

High sensitivity and large field enhancement of symmetry broken Au nanorings: effect of multipolar plasmon resonance and propagation.

The multipolar plasmon resonance and propagation of Au nanorings with symmetry broken were analyzed by using DDA and FDTD methods. Based on the multipolar plasmon resonance and propagation, we proposed ring-nanosensors with high sensitivities and optical ringnanoantennas with large local field enhancements. We revealed that the refractive index sensitivities of split nanorings are about 100% larger than those of perfect nanorings with same size; the local field intensity enhancement of split nanoring with three gaps has increased by 37% than that of dipole antennas.

Effect of carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide.

This experiment was conducted to study the effects of orally administered carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide (LPS). Eighty 28-day-old (1.28 ± 0.15 kg) ROSS 308 broilers were assigned to a 2 × 2 factorial arrangement of treatments (20 pens of 1 chick/trt). Factors were carvacrol essential oil (orally administered or non-orally administered) and LPS (challenged or non-challenged). Individually housed broilers were randomly assigned (n = 20 broilers per treatment: 10 males and 10 females) to four treatments: (1) basic diet (CTR), (2) basic diet + carvacrol (CAR), (3) basic diet + LPS-challenge (LPS), (4) basic diet + carvacrol + LPS-challenge (CAR+LPS). All were fed with the same diet. The experimental period was for 15 d, after which injecting LPS significantly up-regulated the gene expression levels of TNF-α (P < 0.05), IL-1ß (P < 0.05), IL-6 (P < 0.05), IL-8 (P < 0.05), TLR2 (P < 0.05), TLR4 (P < 0.05), NF-κB p65 (P < 0.05), AVBD-9 (P < 0.05), and SIgA(P < 0.05) compared with the CTR group; the broilers were challenged by LPS after oral administration of carvacrol, they had significant lower on the gene expression levels of TNF-α (P < 0.05), IL-1ß (P < 0.05), IL-6 (P < 0.05), TLR4 (P < 0.05), NF-κB p65 (P < 0.05), and AVBD-9 (P < 0.05) than the LPS group. In conclusion, the broilers orally administrated carvacrol essential oils inhibited the secretion of inflammatory cytokines caused by LPS, affected the pathway of TLRs/NF-κB, and showed an anti-inflammatory function.

MiR-490-3p inhibited the proliferation and metastasis of esophageal squamous cell carcinoma by targeting HMGA2.

OBJECTIVE: To identify the potential role of miR-490-3p in the development of esophageal squamous cell carcinoma (ESCC), and to explore the possible underlying mechanism. PATIENTS AND METHODS: Human ESCC tissues and cancer-adjacent normal tissues were collected. The mRNA expression level of miR-490-3p was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). On-line target gene prediction software was applied to screen high-mobility group AT-hook 2 (HMGA2). Subsequently, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), qRT-PCR, Western blotting, transwell and scratch-wound assays were conducted to analyze the effect of miR-490-3p on the biological function of the ESCC cell line (EC-109). RESULTS: In our study, the mRNA expression level of miR-490-3p was remarkably reduced in ESCC tissues and cells. Molecular mechanism analysis confirmed that miR-490-3p could act on the 3'-UTR of HMGA2 and regulate its expression. Subsequent functional experiments indicated that decreased expression of HMGA2 resulting from the up-regulation of miR-490-3p could inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of ESCC cells. CONCLUSIONS: We discovered the inhibitory effect of miR-490-3p on ESCC by targeting HMGA2, and revealed that miR-490-3p could be a potential therapeutic target for ESCC.

GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury via upregulating LAS1 expression.

OBJECTIVE: This study aims at investigating whether GAS5 (grow arrest-specific 5) could promote cardiomyocyte apoptosis by upregulating LAS1 expression, thereby participating in the development of myocardial ischemia-reperfusion injury. MATERIALS AND METHODS: The expression level of GAS5 in H9c2 cells after hypoxia/reoxygenation (H/R) treatment was detected by quantitative Real time-polymerase chain reaction (qRT-PCR). Myocardial injury markers in H9c2 cells were evaluated using relative commercial kits, including activities of LDH (lactate dehydrogenase), MDA (malondialdehyde), SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The protein expressions of apoptosis-related genes and p38/MAPK pathway-related genes were detected by Western blot. The regulatory effects of GAS5 on the p38/MAPK pathway were assessed after treatment with p38/MAPK pathway inhibitor in H9c2 cells. RESULTS: QRT-PCR results showed that the expression levels of GAS5 and LAS1 in H/R-treated H9c2 cells were remarkably upregulated compared to those of controls. GAS5 overexpression increased activities of LDH, MDA, SOD and GSH-PX in H/R-treated H9c2 cells. Meanwhile, GAS5 overexpression reduced cell proliferation and apoptosis of H/R-treated cells. Western blot results suggested that the pro-apoptosis genes Bax and cytochrome C were upregulated, whereas the anti-apoptosis gene Bcl-2 was downregulated after GAS5 overexpression. The overexpression of LAS1 in H9c2 cells obtained the same results as GAS5 overexpression. Furthermore, the expressions of p-p38 and p-ERK were upregulated by GAS5 overexpression. SB203580, the p38/MAPK pathway inhibitor, could reverse the inhibited proliferation and increase apoptosis induced by overexpression of GAS5. CONCLUSIONS: GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury by upregulating LAS1 expression via p38/MAPK pathway. GAS5 may be a potential therapeutic target for myocardial ischemia-reperfusion injury.

Lonidamine as a modulator of alkylating agent activity in vitro and in vivo.

We are searching for relatively nontoxic compounds that can positively modulate the efficacy of antitumor alkylating agents. Lonidamine inhibits cellular energy metabolism and could potentially increase damage by alkylating agents if cellular defenses are energy requiring. Exposure of cells to lonidamine (500 microM) for 2 h under hypoxic conditions followed by 1-h exposures to lonidamine plus alkylating agents under normally oxygenated conditions in vitro significantly increased the cell kill achieved by cis-diamminedichloroplatinum(II) (CDDP) approximately 5-fold and by D-tetraplatin approximately 10-fold at 90% inhibitory concentration in MCF-7/CDDP (CDDP-resistant) cells. Carboplatin cytotoxicity, however, was little changed. In the MCF-7 parent cell line, treatment with lonidamine increased CDDP cytotoxicity by approximately 10-fold, D-tetraplatin by approximately 10-fold, and carboplatin by approximately 8-fold at the 90% inhibitory concentration. For L-phenylalanine mustard (melphalan), N,N',N"-triethylenethiophosphoramide (thiotepa), and N,N'-bis(2-chloroethyl)-N-nitrosourea, little resistance was evident in the MCF-7/CDDP lines compared with the parent line. Treatment with lonidamine increased the cytotoxicity of each drug by 1.5- to 3-fold in both cell lines. When exposure to lonidamine was extended to 24 h before and 12 h after drug exposure in MCF-7 normally oxygenated cultures, CDDP (250 microM) cytotoxicity was increased by approximately 100-fold, but melphalan cytotoxicity was increased only 2- to 3-fold over the concentration range tested. In the FSaIIC murine fibrosarcoma tumor system, five i.p. injections of 50 mg/kg of lonidamine over 36 h increased the tumor cell kill by CDDP and carboplatin approximately 2- to 3-fold over the dose range tested when the platinum complexes were given i.p. immediately after the third lonidamine injection. When cyclophosphamide and thiotepa were given in the same schedule, 10-fold increases in tumor cell killing were evident on tumor excision assay over the dosage ranges. The increase in bone marrow toxicity caused by lonidamine in addition to the alkylating agents was less than for tumor cells. Finally, in the EMT6 murine mammary carcinoma, use of lonidamine at 500 mg/kg twice daily along with CDDP, carboplatin, thiotepa, and cyclophosphamide significantly increased tumor growth delays by approximately 1.6- to 3.0-fold. The results suggest that lonidamine can positively modulate antitumor alkylating agent cytotoxicity and may be a clinically useful adjunctive therapy with these drugs.

Diet and cancer of the colon and rectum: a case-control study in China.

A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.