Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Quantitative cardiac MRI parameters for assessment of myocarditis in children and adolescents: a systematic review and meta-analysis.

AIM: To evaluate the role of quantitative cardiac magnetic resonance imaging (CMRI) parameters in myocarditis, including acute and chronic myocarditis (AM and CM), for children and adolescents. MATERIALS AND METHODS: PRISMA principles were followed. PubMed, EMBASE, Web of Science, Cochrane Library, and grey literature were searched. The Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist were utilised for quality assessment. Quantitative CMRI parameters were extracted and a meta-analysis was performed in comparison with healthy controls. The overall effect size was measured as the weighted mean difference (WMD). RESULTS: Ten quantitative CMRI parameters of seven studies were analysed. Compared with the control group, the myocarditis group reported longer native T1 relaxation time (WMD=54.00, 95% confidence interval [CI]: 33.21,74.79, p<0.001), longer T2 relaxation time (WMD=2.13, 95% CI: 0.98, 3.28, p<0.001), increased extracellular volume (ECV; WMD=3.13, 95% CI: 1.34,4.91, p=0.001), elevated early gadolinium enhancement (EGE) ratio (WMD=1.47, 95% CI: 0.65,2.28, p<0.001), and increased T2-weighted ratio (WMD=0.43, 95% CI: 0.21,0.64, p<0.001). The AM group had longer native T1 relaxation times (WMD=72.02, 95% CI: 32.78,111.27, p<0.001), increased T2-weighted ratios (WMD=0.52, 95% CI: 0.21,0.84 p=0.001), and impaired left ventricular ejection fractions (LVEF; WMD=-5.84, 95% CI: -9.69, -1.99, p=0.003). Impaired LVEF (WMD=-2.24, 95% CI: -3.32, -1.17, p<0.001) was observed in the CM group. CONCLUSION: Statistical differences can be observed in some CMRI parameters between patients with myocarditis and healthy controls; however, apart from native T1 mapping, there were no large differences in other parameters between two groups, which may reveal the limited benefit of CMRI in assessing myocarditis in children and adolescents.

[Impact of different types of heart failure on long-term renal prognosis in patients with renal insufficiency and heart failure].

Objective: To investigate the effects of different types of heart failure on long-term renal prognosis in patients with renal insufficiency and heart failure. Methods: The patients with renal insufficiency [baseline estimated glomerular filtration rate < 60 ml·min-1·(1.73 m2)-1] and heart failure followed-up for more than 2 years and hospitalized in Beijing Anzhen Hospital, Capital Medical University from January 1, 2018 to June 30, 2019 were enrolled in this retrospective cohort study. The patients were divided into three groups based on the baseline left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction (HFrEF, LVEF < 40%) group, heart failure with mildly reduced ejection fraction (HFmrEF, 40% ≤ LVEF < 50%) group, and heart failure with preserved ejection fraction (HFpEF, LVEF ≥ 50%) group. Clinical data were collected and endpoint events (adverse renal outcome: the composite outcome of all-cause death or worsening renal function) were recorded through the electronic medical record system. Kaplan-Meier survival curve was used to analyze the incidence of endpoint events of different heart failure subgroups. Cox regression model was performed to analyze the risk factors of endpoint events. Results: A total of 228 patients with renal insufficiency complicated with heart failure were included, with age of (68.14±14.21) years old and 138 males (60.5%). There were 85 patients (37.3%) in the HFrEF group, 40 patients (17.5%) in the HFmrEF group, and 103 patients (45.2%) in the HFpEF group. There were statistically significant differences in age, proportion of age > 65 years old, sex distribution, systolic blood pressure, pulmonary artery pressure, serum sodium, serum calcium, hemoglobin, serum cholesterol, low-density lipoprotein cholesterol, serum uric acid, troponin I, hypersensitive C-reactive protein, LVEF, ventricular septal thickness, left ventricular end-diastolic diameter, B-type natriuretic peptide, estimated glomerular filtration rate, and proportions of using beta blockers, using spirolactone, myocardial infarction, hypertension, cardiomyopathy and atrial fibrillation (all P < 0.05). During the median follow-up of 36.0 (28.0, 46.0) months, 73 patients (32.0%) had adverse renal outcomes. The total incidences of adverse renal outcomes were 32.9% (28/85) in the HFrEF group, 35.0% (14/40) in the HFmrEF group, and 30.1% (31/103) in the HFpEF group. Kaplan-Meier survival curve showed that there was no significant difference in the incidence of endpoint events among the three groups (log-rank test χ2=0.17, P=0.680). Multivariate Cox regression analysis showed that HFpEF (HFrEF as reference, HR=2.430, 95% CI 1.055-5.596, P=0.037) was an independent influencing factor of endpoint events. Conclusions: The long-term renal prognosis of patients with renal insufficiency and heart failure is poor. Compared with HFrEF, HFpEF is an independent risk factor of poor long-term renal prognosis in renal insufficiency patients with heart failure.

Sonographic findings of immunoglobulin G4-related sialadenitis and differences from Sjögren's syndrome.

OBJECTIVE: To evaluate ultrasonic features of the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and to explore the differences between IgG4-RS and Sjögren's syndrome (SS). METHOD: We conducted the study in 150 patients with IgG4-RS and 100 patients with SS. Ultrasonographic variables of the static images of major salivary glands were analysed. An experienced radiologist scored the confidence rating regarding the presence of the characteristic imaging findings using a five-grade rating system. Ultrasonography scores between IgG4-RS and SS were compared. RESULTS: The major salivary glands were significantly larger in patients with IgG4-RS than in the SS group. The main features of ultrasonography of the salivary glands in IgG4-RS were various hypoechoic lesions and increased colour Doppler signalling. In contrast, the major salivary glands in SS exhibited hyperechoic lines and/or spots and obscuration of the gland configuration. The scores of the summarized sonographic characteristics also showed statistically significant differences between the IgG4-RS and SS groups. CONCLUSION: This study revealed different ultrasonic features of the major salivary glands in patients with IgG4-RS and SS. The scored sonographic features were helpful in differentiating IgG4-RS from SS. Consequently, we suggest that ultrasonography of major salivary glands could be a useful imaging procedure in the evaluation of patients suspected of having IgG4-RS.

Correlation of hypertension and F2RL3 gene methylation with Prognosis of coronary heart disease.

The aim of this work was to investigate the correlation between methylation of F2RL3 gene and coronary heart disease (CHD) with or without hypertension, secondary cardiovascular events and mortality. Sixty patients with CHD who underwent a cardiovascular rehabilitation program were recruited. Group A included 30 patients with hypertension and CHD, and group B included 30 patients with non-hypertensive CHD, followed-up for more than 8 years. F2RL3 gene methylation was characterized by Sequenom matrix assisted laser desorption ionization time flight mass spectrometry. The correlation between methylation of the F2RL3 gene, hypertension and secondary cardiovascular events and all-cause mortality was analyzed by multivariate Cox, regression models that estimated confounders to control risk ratios. The results showed that during the follow-up, 3 patients in Group A developed non-fatal stroke, 2 patients died of cardiovascular disease, 1 patient died of other causes, and 4 patients in Group B developed non-fatal myocardial infarction. After adjusting for known prognostic factors, Cox model analysis showed that methylation of F2RL3 gene was closely related to hypertension and mortality. After F2RL3 included in the regression model, the correlation between hypertension and all prognostic outcomes increased. In conclusion, the methylation of F2RL3 can affect the prognosis of different types of acute coronary syndrome and is closely related to mortality.

Frequency Comparison of Two (40)Ca(+) Optical Clocks with an Uncertainty at the 10(-17) Level.

Based upon an over-one-month frequency comparison of two (40)Ca(+) optical clocks, the frequency difference between the two clocks is measured to be 3.2×10(-17) with a measurement uncertainty of 5.5×10(-17), considering both the statistic (1.9×10(-17)) and the systematic (5.1×10(-17)) uncertainties. This is the first performance of a (40)Ca(+) clock better than that of Cs fountains. A fractional stability of 7×10(-17) in 20,000 s of averaging time is achieved. The evaluation of the two clocks shows that the shift caused by the micromotion in one of the two clocks limits the uncertainty of the comparison. By carefully compensating the micromotion, the absolute frequency of the clock transition is measured to be 411 042 129 776 401.7(1.1) Hz.

Effects of warm acupuncture on breast cancer-related chronic lymphedema: a randomized controlled trial.

BACKGROUND: Effective treatment for breast cancer-related chronic lymphedema (bcrl) remains a clinical challenge. Acupuncture and moxibustion treatments have been shown to be beneficial and safe for treating bcrl. In the present randomized controlled trial, we compared the effectiveness of combined acupuncture and moxibustion ("warm acupuncture") with that of diosmin in bcrl. METHODS: Breast cancer patients who met the inclusion and exclusion criteria (n = 30) were randomized to experimental and control groups (15 per group). On alternate days, patients in the experimental group received 30 minutes of acupuncture at 6 acupoints, with 3 of the needles each being topped by a 3-cm moxa stick. The control treatment was diosmin 900 mg 3 times daily. The control and experimental treatments were administered for 30 days. Outcome measures included arm circumferences (index of effectiveness), range of motion [rom (shoulder joint function)], quality of life, clinical safety, and adverse events. RESULTS: Measured by the index of effectiveness, bcrl improved by 51.46% in the experimental group and by 26.27% in the control group (p < 0.00001). Effects were greatest at 10 cm above the elbow and at the wrist, where the warm needling was provided. Impairments in shoulder joint rom were minimal at baseline in both treatment groups. However, the roms of rear protraction, abduction, intorsion, and extorsion in the experimental group improved significantly; they did not change in the control group. Self-reported quality of life was significantly better with warm acupuncture than with diosmin. No adverse effects were reported during the treatment period, and laboratory examinations for clinical safety fell within the normal ranges. CONCLUSIONS: Compared with diosmin, warm acupuncture treatment can effectively reduce the degree of bcrl at the specific acupoints treated and can promote quality of life. Warm acupuncture showed good clinical safety, without any adverse effects on blood or the cardiovascular system.

Population genetic structure of Myzus persicae nicotianae (Hemiptera: Aphididae) in China by microsatellite analysis.

The tobacco aphid, Myzus persicae nicotianae (Hemiptera: Aphididae), is an important agricultural pest that feeds on host plants and transmits plant viruses in China. To effectively control this pest, we investigated the genetic variation and genetic structure of 54 populations of tobacco aphids collected in China, using five microsatellite loci. An average of 7 alleles with effective number ranging from 1.5 to 6.6 was detected using these five loci, and the average polymorphic information content (PIC) was 0.652, suggesting that the five selected microsatellite loci were polymorphic and suitable for the study of population genetics. The expected heterozygosities in the populations studied ranged from 0.128 and 0.653, with an average value of 0.464. However, the observed heterozygosities ranged from 0.250 and 0.942 (average = 0.735), revealing a high genetic variability and heterozygosity excess in the Chinese tobacco aphid populations. The global fixation index (F(ST)) and mean gene flow (N(m)) were 0.34 (P < 0.0001) and 0.50, respectively, suggesting the high genetic differentiation among Chinese populations. The 54 populations of tobacco aphids were classified into two groups. The populations did not cluster geographically, as populations from the same provinces were usually present in different clusters. This was also confirmed by the Mantel test, which showed no significant correlation between the genetic distance and geographical distance or altitude. Long distance migration might be responsible for the lack of distance-related isolation.

Establish and verify TSH reference intervals using optimized statistical method by analyzing laboratory-stored data.

OBJECTIVE: To establish reference intervals using an optimized statistical method by collecting available laboratory data of thyroid stimulating hormone (TSH), and then to verify with the laboratory-present reference intervals. METHODS: TSH RIs of the total population and different races, genders, age, source of sample are established through improved Hoffmann and Katayev's method with TSH test results data from Jan 2010 to April 2012 were collected, and finally conduct comparative verification with the laboratory present RIs. RESULTS: According to the improved method, we get various RIs of different sample populations. On comparing with the laboratory current RI (0.270-4.200 mIU/L) most reference change values (RCV) were within acceptable limits. Only lower limit of Han male, Uygur male and out-patient male populations outwith acceptable limits. On excluding the different values, finally, the new RI by the optimized statistical method is 0.233-4.979 mIU/L. Because the new RI expanded the current RI and was not different from the current RI, it was indicated that new RI could be used to verify the laboratory current RIs and seen as the current RI's confidence interval (CI). INFERENCE: TSH RIs established by optimized Hoffmann's and Katayev's methods is viable and can be used to verify RIs provided by manufacturers or other laboratories.

KL-6 regulated the expression of HGF, collagen and myofibroblast differentiation.

OBJECTIVES: KL-6 is a pulmonary epithelial-derived mucin which is secreted mainly by type II alveolar epithelial cells. The level of KL-6 in serum is closely correlated to the clinical activity of various interstitial lung diseases (ILD) and acts as a prognostic factor for ILD patients. Previous studies have showed that KL-6 promoted chemotaxis, proliferation and inhibited the apoptosis of human lung fibroblasts. However, the underlying mechanism remains unknown. In this study, we investigated the function of KL-6 on the expression of hepatocyte growth factor (HGF), transforming growth factor-ß1 (TGF-ß1), collagen and α-smooth muscle actin(α-SMA) in human embryonic lung fibroblasts cell line MRC-5. METHODS: Human embryonic lung fibroblasts were cultured in Eagle's minimum essential medium. The cells plated in 6-well plates was cultured in serum-free medium at 37°C in 5% CO2 and challenged with recombinant KL-6 at a final concentration of 0, 10, 20, 40 ng/mL. Five micrograms of total RNA template were transcripted to cDNA by using AMV (Avian Myeloblastosis Virus) reverse transcriptase and random 9 mers as the first-strand primer. Synthesized cDNA was used in PCR experiments. The expression of TGF-ß1 and HGF in cell culture supernatants was measured using ELISA kit. Cells incubated with KL-6 for 72h were collected for flow-cytometry analysis. The analysis was done using a Beckman counter device. RESULTS: It was found that KL-6 up-regulated the expression of collagen type I and III in a dose-dependent manner. However, the addition of KL-6 significantly inhibited the production of HGF. As regard to the biological function, KL-6 induced myofibroblast differentiation confirmed by the elevated expression of a-SMA. CONCLUSIONS: KL-6 is one of the key molecules involved in epithelial-mesenchymal interactions and might contribute to the fibrosis in ILD.

Fabrication of porous beta-tricalcium phosphate with microchannel and customized geometry based on gel-casting and rapid prototyping.

The tissue engineering scaffolds with three-dimensional porous structure are regarded to be beneficial to facilitate a sufficient supply of nutrients and enable cell ingrowth in bone reconstruction. However, the pores in scaffolds tend to be blocked by the cell ingrowth and result in a restraint of nutrient supply in the further side of the scaffold. An indirect approach of combining the rapid prototyping and gel-casting technique is introduced in this study to fabricate beta-tricalcium phosphate (beta-TCP) scaffolds which not only have interconnected porous structure, but also have a microchannel network inside. The scaffold was designed with customized geometry that matches the defect area, and a double-scale (micropores-microchannel) porous structure inside that is beneficial for cell ingrowth. The scaffolds fabricated have an open, uniform, and interconnected porous architecture with a pore size of 200-400 microm, and posses an internal channel network with a diameter of 600 microm. The porosity was controllable. The compressive yield strength was 4.5 MPa with a porosity of 70 per cent. X-ray diffraction analysis shows that these fabrication processes do not change the crystal structure and chemical composition of beta-TCP. With this technique, it was also possible to fabricate porous scaffolds with desired pore size, porosity, and microchannel, as well as customized geometries by other bioceramics.

Reduced miR-363-3p expression in non-small cell lung cancer is associated with gemcitabine resistance via targeting of CUL4A.

The article "Reduced miR-363-3p expression in non-small cell lung cancer is associated with gemcitabine resistance via targeting of CUL4A", W.-G. Bian, X.-N. Zhou, S. Song, H.-T. Chen, Y. Shen, P. Chen, published in Eur Rev Med Pharmacol Sci 2019; 23 (2): 649-659-DOI: 10.26355/eurrev_201901_16879-PMID: 30720173, has been retracted by the authors due to several inaccuracies in the research design. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16879.

LncRNA HCG11 suppresses laryngeal carcinoma cells progression via sponging miR-4469/APOM axis.

OBJECTIVE: Longnon-coding RNAs (lncRNAs) have been reported to participate in the regulatory mechanisms of various cancers. Therefore, the aim of this study was to investigate the functional role of lncRNA HLA complex group 11 (HCG11) in laryngeal carcinoma. MATERIALS AND METHODS: The laryngeal carcinoma cell lines SNU46, SNU899, AMC-HN-8, and normal human nasopharyngeal epithelial cells NP69 were purchased. The expression of HCG11, miR-4469, and apolipoprotein M (APOM) was detected by quantitative Real Time-PCR (qRT-PCR) in tissues and cells. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay and colony formation assays. The protein expression of Bax and Bcl-2 was detected by Western blot. Besides, the mechanism assays were conducted to observe the interaction between miR-449 and HCG11 or APOM. The apoptosis in each group was detected by TUNEL assay. RESULTS: In this research, low expression of HCG11 was discovered in laryngeal carcinoma tissues and cells. Overexpression of HCG11 retarded cell proliferation and enhanced cell apoptosis. Later, we found that APOM was also downregulated in laryngeal carcinoma tissues and cell lines, and inhibited laryngeal carcinoma progression. HCG11 positively regulated APOM at the post-transcriptional level. MiR-4469 was predicted to have the binding sites of HCG11 and APOM. Furthermore, it was demonstrated that HCG11 absorbed miR-4469 to upregulate APOM expression. Finally, it was indicated that the repression of APOM rescued the effects of HCG11 overexpression on cell proliferation and cell apoptosis. CONCLUSIONS: This study uncovered that HCG11 sponged miR-4469 to suppress laryngeal carcinoma progression by upregulating APOM expression.

Inhibition of p53/p21 by TWIST alleviates TNF-α induced nucleus pulposus cell senescence in vitro.

OBJECTIVE: This study aims to reveal the TWIST protein expression in the degenerated nucleus pulposus (NP), its effect on the TNF-α treated NP cells, and to explore its specific mechanism of anti-senescence. PATIENTS AND METHODS: NP tissues from spine fracture patients without intervertebral disc degeneration (IDD) and the IDD patients were collected to detect the TWIST1/2 protein expression by Western blot (WB). NP cells isolated from the healthy tissue was treated with TNF-α to induce senescence, and the TWIST1/2 protein expression was also analyzed. We transfected NP cells with the plasmid coding TWIST to upregulate its expression, which was also cultured in the TNF-α condition. Besides, the TNF-α pretreated NP cells were further stimulated with the recombinant human TWIST1/2 protein. The collagen II and senescent marker ß-galactosidase (ß-gal) were determined by immunofluorescence (IF); the MMP-13, TIMP-3, IL-10, IL-1ß mRNA expression level was detected by quantitative Real Time PCR; the cell proliferation was analyzed by CCK8 assay; the cell cycle was measured by flow cytometry. RESULTS: TWIST1/2 protein was decreased both in the degenerated NP tissue, and TNF-α treated NP cells. The overexpression of TWIST1/2 could prevent the p53, p21, ß-gal, MMP-13, and IL-1ß expression, moreover, it protected the collagen II, TIMP-3, and IL-10 expression in the TNF-α treated NP cells. Additionally, TWIST overexpression also promoted cell proliferation by ensuring the process of the cell cycle. Furthermore, the supplement of TWIST protein was functional to reverse these senescent phenotypes caused by TNF-α partly. CONCLUSIONS: TWIST alleviates the TNF-αinduced NP cells senescence via the inhibition of the p53/p21 pathway.

[Effects of transcutaneous electrical acupoint stimulation on pain of patients in expansion process of skin soft tissue dilator on forehead by water injection].

Objective: To explore the effects of transcutaneous electrical acupoint stimulation (TEAS) on pain of patients in expansion process of skin soft tissue dilator on forehead by water injection. Methods: From June 2016 to June 2017, 100 patients in expansion process of skin soft tissue dilator on forehead by water injection meeting the inclusion criteria were admitted to Outpatient Department of Orthopedic Surgery of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. There were 43 men and 57 women among the patients, aged 27 to 55 years, and the prospective randomized controlled study was performed on them. The patients were divided into TEAS nursing group and routine nursing group according to the random number table, with 50 patients in each group. Patients in routine nursing group were performed with routine nursing in every water injection in outpatient department and 2 days later. On the basis of routine nursing, patients in TEAS nursing group were performed with TEAS treatment by responsible nurses in each water injection in outpatient department. The Shangxing, Diwei, and Hegu points were positioned accurately, and electrical stimulation was performed on the 3 points simultaneously by pulse acupuncture treatment instrument, with 30 minutes each time. Two days after every water injection of outpatient department, TEAS nursing was performed at home by patients and their family members under remote guidance of the responsible nurses, with 2 times each day and 30 minutes each time. Besides, follow-up was done by phone by the responsible nurses everyday. The nursing of patients in the 2 groups lasted the whole expansion process. After the expansion process, the overall pain degree and the most severe pain degree of patients during expansion process were scored by numerical rating scale, and the overall comfort degree and its dimensions of patients during expansion process were scored by the responsible nurses every day by simplified Comfort Status Scale. Data were processed with independent sample t test and chi-square test. Results: During expansion process, the overall pain score degree and the most severe pain degree score of patients in TEAS nursing group were (5.4±1.2) and (6.5±1.0) points, which were significantly lower than (6.1±1.3) and (7.5±1.4) points of patients in routine nursing group (t=-2.62, -4.00, P<0.05 or P<0.01). During expansion process, the physiological dimension, sociocultural dimension, psychological spirit dimension, environmental dimension, and total score of the overall comfort degree of patients in TEAS nursing group were (9.6±2.9), (20.1±2.8), (29.1±1.9), (22±3), and (80±6) points, significantly higher than (5.7±2.1), (16.8±2.8), (26.0±2.8), (21±4), and (69±8) points of patients in routine nursing group (t=8.03, 6.35, 7.60, 2.11, 10.64, P<0.05 or P<0.01). Conclusions: TEAS with appropriate intensity, frequency, and duration can alleviate the pain of patients during expansion process of skin soft tissue dilator on forehead by water injection and improve their comfort degree.

Reduced miR-363-3p expression in non-small cell lung cancer is associated with gemcitabine resistance via targeting of CUL4A.

OBJECTIVE: Accumulating evidence has suggested that aberrant expression of microRNAs (miRNAs) is associated with non-small cell lung cancer (NSCLC) proliferation, migration, invasion and chemotherapy resistance. Cullin4A (CUL4A) has been previously reported to desensitize NSCLC cells to chemotherapy treatment. However, whether miRNAs regulate CUL4A to promote chemotherapy resistance remains unknown. PATIENTS AND METHODS: Tissues were obtained from 40 NSCLC patients who received surgery at the Yancheng City No. 1 People's Hospital. Cell Counting Kit-8 (CCK-8) assays were applied for the detection of cell proliferation; mRNA and protein levels were determined by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot, respectively. The interaction between mRNA 3'UTR and miRNA was predicted by TargetScan and verified by Dual-Luciferase reporter assay. RESULTS: In the present study, miR-363-3p levels were revealed to be significantly decreased in tumor tissues obtained from NSCLC patients compared with adjacent normal tissues. The results of the CCK-8 assays showed that the overexpression of miR-363-3p may slightly inhibit the proliferation of A549 and H23 cells. Notably, the transfection with miR-363-3p antagonists reduced the sensitivity of A549 and H23 cells to gemcitabine treatment, whereas the overexpression of miR-363-3p markedly increased the sensitivity of A549 and H23 cells to gemcitabine treatment. Furthermore, CUL4A mRNA and protein levels were revealed to be decreased in A549 cells transfected with miR-363-3p mimics. The Dual-Luciferase reporter assay results further suggested that CUL4A represents a target gene of miR-363-3p. CONCLUSIONS: The results indicated that decreased miR-363-3p expression enhanced gemcitabine resistance in NSCLC cells via regulation of CUL4A.

Influence of miR-34a on myocardial apoptosis in rats with acute myocardial infarction through the ERK1/2 pathway.

OBJECTIVE: To study the influence of micro-ribonucleic acid (miR)-34a on myocardial apoptosis in rats with acute myocardial infarction (AMI) through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. MATERIALS AND METHODS: A total of 24 Sprague-Dawley (SD) rats were randomly divided into sham group (n=12) and model group (n=12). The heart was exposed in the sham group, while the AMI model was established in the model group. After sampling, the morphology of myocardial tissues was observed via hematoxylin-eosin (HE) staining, the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected via immunohistochemistry, and the protein expression levels of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) were detected via Western blotting. Moreover, the expression of miR-34a was detected via quantitative Polymerase Chain Reaction (qPCR), the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the myocardial injury indexes were detected using a fully-automatic biochemical analyzer. RESULTS: The morphology of myocardial tissues was normal with a complete structure in the sham group, while there was damage to myocardial tissues in different degrees in the model group. The immunohistochemical results revealed that the Bax expression was increased and the Bcl-2 expression was decreased in the model group compared with those in the sham group (p<0.05). The results of Western blotting showed that the protein expression levels of both ERK1/2 and p-ERK1/2 were significantly increased in the model group compared with those in the sham group (p<0.05). The qPCR results manifested that the expression of miR-34a in the model group markedly declined compared with that in the sham group (p<0.05). Besides, the TUNEL detection showed that the apoptosis rate in the model group was remarkably increased compared with that in the sham group (p<0.05), and the content of cardiac troponin T and creatine kinase isoenzyme in the model group was significantly higher than that in the sham group ((p<0.05). CONCLUSIONS: MiR-34a affects the apoptosis in AMI by regulating the ERK1/2 signaling pathway.

Reducing postsurgical exudate in breast cancer patients by using San Huang decoction to ameliorate inflammatory status: a prospective clinical trial.

Background: Reducing inflammatory factors in wound exudate is a promising treatment approach for healing wounds in postsurgical breast cancer patients. Traditional Chinese Medicine (tcm) treatments have been shown to be beneficial and safe for optimal regulation of oxidative stress during the postoperative period. In the present clinical trial, we evaluated the effectiveness of a promising Chinese herbal formula, San Huang decoction [shd (Radix astragali, Radix et rhizoma rhei, and Rhizoma curcuma longa, 3:1:1; supplemental Table 1)], on wound inflammatory response after mastectomy. Methods: The study randomized 30 patients with breast cancer who fulfilled the inclusion and exclusion criteria to either a treatment (n = 15) or a control group (n = 15). Patients in the treatment group received liquid shd, taken twice daily with or without food. Treatment was given for 1 day before surgery and for 7 days postoperatively. Participants in the control group received a placebo on the same schedule as the treatment group. Outcomes measured in every subject included clinical tcm and wound inflammation symptom scores, daily and total amounts of drainage fluid, and levels of inflammatory factors in the exudate [tumour necrosis factor α (tnf-α), interleukins 6 (il-6), 8 (il-8), and 2R (il-2R), human C-reactive protein (crp)] at 2 hours and on days 1, 3, and 7 postoperatively. Results: The total amount of drainage fluid over 7 days was significantly lower in the treatment group (572.20 ± 93.95 mL) than in the control group (700.40 ± 107.38 mL). The tcm symptom score was also lower in treatment group (day 7: 1.87 ± 0.83 vs. 4.80 ± 3.61, p = 0.049), as was the inflammatory symptom score (day 7: 0.67 ± 0.72 vs. 3.67 ± 2.50, p = 0.001). Levels of tnf-α, il-6, il-8, il-2R, and crp in drainage fluid were significantly lower with shd treatment. Conclusions: Perioperative treatment with shd effectively lessened postoperative exudate and ameliorated inflammatory symptoms in patients who underwent surgery for breast cancer.

MiR-210 protects cardiomyocytes from OGD/R injury by inhibiting E2F3.

OBJECTIVE: To detect the change in miRNA-210 expression of cardiomyocytes under hypoxia/reoxygenation status. Also, the effect of miR-210 on the apoptosis of cardiomyocytes induced by oxygen-glucose deprivation/reperfusion (OGD/R) and its mechanism through establishing the OGD/R injury model of primary cardiomyocytes in this experiment were investigated. MATERIALS AND METHODS: The cell model of OGD/R injury was established. The cell apoptosis in each group was detected by methyl thiazolyl tetrazolium (MTT) assay and detection of Caspase-3 activity. The change in miR-210 expression in each group was detected by Real-time fluorescence quantitative polymerase chain reaction (PCR). The high-expression and low-expression miR-210 models were established through the transient transfection of miR-210 mimic and inhibitor to detect the relevant indexes of cell apoptosis. At the same time, changes in mRNA and protein expressions of E2F3 were detected by RT-PCR and Western blotting, respectively. The E2F3 overexpression vector was constructed, and the overexpression vector plasmid and miR-210 mimic were jointly transfected into the cells to detect the relevant indexes of cell apoptosis. RESULTS: After OGD/R treatment, the activity of Caspase-3 was increased, the survival of cardiomyocytes was significantly inhibited and the expression level of miR-210 was up-regulated in OGD/R injury. Transfection of miR-210 mimic for miR-210 overexpression could alleviate the OGD/R-induced cardiomyocyte injury, while the decrease of miR-210 expression could aggravate the apoptosis of cardiomyocytes. In addition, the high expression of miR-210 could inhibit the protein expression of E2F3, and co-transfection of E2F3 plasmid and miR-210 mimic could reverse the inhibiting effect of miR-210 on the apoptosis of cardiomyocytes. CONCLUSIONS: We confirmed that miR-210 can inhibit the OGD/R-induced apoptosis of cardiomyocytes, and miR-210, as an upstream factor, plays a protective role in cardiomyocytes through directly inhibiting the protein expression of its target gene E2F3.

In Vivo 7T MR Quantitative Susceptibility Mapping Reveals Opposite Susceptibility Contrast between Cortical and White Matter Lesions in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Magnetic susceptibility measured with quantitative susceptibility mapping has been proposed as a biomarker for demyelination and inflammation in patients with MS, but investigations have mostly been on white matter lesions. A detailed characterization of cortical lesions has not been performed. The purpose of this study was to evaluate magnetic susceptibility in both cortical and WM lesions in MS by using quantitative susceptibility mapping. MATERIALS AND METHODS: Fourteen patients with MS were scanned on a 7T MR imaging scanner with T1-, T2-, and T2*-weighted sequences. The T2*-weighted sequence was used to perform quantitative susceptibility mapping and generate tissue susceptibility maps. The susceptibility contrast of a lesion was quantified as the relative susceptibility between the lesion and its adjacent normal-appearing parenchyma. The susceptibility difference between cortical and WM lesions was assessed by using a t test. RESULTS: The mean relative susceptibility was significantly negative for cortical lesions (P < 10-7) but positive for WM lesions (P < 10-22). A similar pattern was also observed in the cortical (P = .054) and WM portions (P = .043) of mixed lesions. CONCLUSIONS: The negative susceptibility in cortical lesions suggests that iron loss dominates the susceptibility contrast in cortical lesions. The opposite susceptibility contrast between cortical and WM lesions may reflect both their structural (degree of myelination) and pathologic (degree of inflammation) differences, in which the latter may lead to a faster release of iron in cortical lesions.