[Comparison of diagnostic criteria for acute kidney injury in critically ill children].

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ2=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.

Cigarette Smoke Extract and Lipopolysaccharide Induce Pyroptosis in Pulmonary Microvascular Endothelial Cells of Rats.

We studied the effect of cigarette smoke extract (CSE), LPS, or their combination on the activity and pyroptosis of pulmonary microvascular endothelial cells (PMVEC) in rats. PMVEC were cultured without treatment, with CSE in different concentrations (1-25%), with 20 ng/ml LPS, or with 20% CSE+20 ng/ml LPS. Cell viability was determined using the CCK8 kit, apoptosis was evaluated by flow cytometry, and cell morphology was evaluated using light microscopy. The content of IL-1ß and IL-18 was measured by ELISA. CSE decreased cell viability in a dose-dependent manner. The morphology of cells in the CSE+LPS group showed the most significant cytomorphological changes and the highest pyroptosis rate. Flow cytometry showed that the apoptosis rates in the CSE and LPS groups were higher than in the control group, but the highest rate of apoptosis was revealed in the CSE+LPS group (p<0.01). The levels of IL-18 and IL-1ß in the cell supernatant of the CSE, LPS, and CSE+LPS groups were significantly (p<0.01) increased in comparison with the control. These levels in the CSE+LPS group were higher (p<0.01) than in other groups. There were no differences between the CSE and LPS groups. Thus, the effect of CSE on cell viability is dose-dependent. Combined treatment with CSE+LPS can induce cell pyroptosis and increase the levels of inflammatory cytokines in PMVEC. These observations demonstrated that pyroptosis caused by CSE and LPS can play an important role in pulmonary vascular remodeling.

Observation of a Strongly Isospin-Mixed Doublet in

ß decay of proton-rich nuclei plays an important role in exploring isospin mixing. The ß decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through ß-delayed two-proton emission (ß2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P ß decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in ß-decay experiments.

Probing

The isomer depletion of ^{93m}Mo was recently reported [Chiara et al., Nature (London) 554, 216 (2018)NATUAS0028-083610.1038/nature25483] as the first direct observation of nuclear excitation by electron capture (NEEC). However, the measured excitation probability of 1.0(3)% is far beyond the theoretical expectation. In order to understand the inconsistency between theory and experiment, we produce the ^{93m}Mo nuclei using the ^{12}C(^{86}Kr,5n) reaction at a beam energy of 559 MeV and transport the reaction residues to a detection station far away from the target area employing a secondary beam line. The isomer depletion is expected to occur during the slowdown process of the ions in the stopping material. In such a low γ-ray background environment, the signature of isomer depletion is not observed, and an upper limit of 2×10^{-5} is estimated for the excitation probability. This is consistent with the theoretical expectation. Our findings shed doubt on the previously reported NEEC phenomenon and highlight the necessity and feasibility of further experimental investigations for reexamining the isomer depletion under low γ-ray background.

Circulating myeloid-derived suppressors cells correlate with clinicopathological characteristics and outcomes undergoing neoadjuvant chemoimmunotherapy in non-small cell lung cancer

PurposeMyeloid-derived suppressors cells (MDSCs) are heterogeneous immunosuppressive cells, closely related to the development, efficacy and prognosis in various tumors. The relationship between clinicopathological characteristics, efficacy of neoadjuvant chemoimmunotherapy (NCIO) and circulating MDSCs in patients with non-small cell lung cancer (NSCLC) was investigated in this study.MethodsThis study analyzed the clinical data of patients diagnosed at Department of Thoracic Surgery, Beijing Chest Hospital from November 2020 to August 2021. MDSCs and T cells subgroups were measured in fresh peripheral blood mononuclear cells(PBMCs) at baseline. Flow cytometry was used to detect MDSCs and T cells subgroups.ResultsA total of 78 patients with NSCLC and 20 patients with benign nodule underwent direct surgery. 23 patients with NSCLC scheduled to accept NCIO before surgery. NSCLC had elevated levels of total MDSCs, PMN-MDSCs and M-MDSCs compared to patients with benign nodule. MDSCs subgroups were correlated to the pTNM stage in NSCLC patients. The frequency of total MDSCs were moderately positively correlated with regulatory T cells (Tregs)(r = 0.3597, P < 0.01) and negatively correlated with CD4 + T cells(r = 0.2714, P < 0.05). The baseline levels of total MDSCs, PMN-MDSCs and Tregs in pCR patients were significantly decreased than those of non-pCR patients (P < 0.05).ConclusionCirculating MDSCs were increased in NSCLC patients. MDSC subgroups were related to pTNM stage in NSCLC patients. Total MDSCs were positively correlated with Tregs levels and negatively correlated with CD4 + T cells in peripheral blood. The level of MDSCs and Tregs in peripheral blood may have potential value in predicting pathological response in NSCLC.

Impacts of international food and feed trade on nitrogen balances and nitrogen use efficiencies of food systems.

International trade of agricultural products has greatly increased over time, but its impacts on sustainable development are debated. It may contribute to food security in importing countries, increases the dependency between countries, and has been implicated in displacement of environmental pollution and resource depletion. There is also discussion about the relationships between trade and nitrogen (N) balances and N use efficiencies (NUE). We explored relationships between changes in the trade of food and feed and in N balances and NUE of the food supply systems through simulation modeling and an analysis of empirical data of 115 countries (representing 91% of global population) for the period 1961-2011. In the empirical analysis, 64 main importing countries and 14 main exporting countries, were distinguished. Importing countries had on average a higher population density than exporting countries but rather similar protein intake and GDP per capita. The empirical analysis indicate that main importing countries had on average higher N fertilizer inputs to their food supply systems, and also higher N surpluses and higher NUE than main exporting countries. The overall mean NUE of the food supply system of main importing countries decreased with increasing import, but the relationships between import and NUE were diverse when these countries were grouped according to population density and GDP per capita. We compared N balances and partial N balances, and three methodologies commonly used for estimating NUE. We observed that NUE2 provides an unbiased estimate for both importing and exporting countries. Our study contributes to the understanding of the diverse relationships between international trade, N balances and NUE of food systems.

Experimental study on fire characteristics in cable compartment of utility tunnel with natural ventilation.

The fire characteristics under natural ventilation in the cable compartment of the utility tunnel are studied. A series of small-scale fire experimental tests are conducted to obtain the maximum temperature below the ceiling of different ignition vertical heights and cable types. In this paper, the ceiling temperature decay and heat release rate (HRR) are studied in the cable compartment of utility tunnel. Through experimental tests, the fire characteristics of placing the fire source on the near wall side 3.0 m away from the shaft of the utility tunnel cable compartment are studied. The results showed that under the action of natural ventilation, with the decrease of fuel quantity, the mass loss of cable decreases, and the maximum temperature below the ceiling of the cable compartment in the utility tunnel decreases. ZRYJV cables burn more sufficient combustion than RVVR cables. A new empirical association for total HRR is proposed. Those experimental test results are used as validation data for the newly proposed empirical correlation of total HRR. This paper hopes to provide some basic fire safety references for the utility tunnel planning of the urban underground cable compartment.

Risk factors for progression of Urolith Associated with Obstructive Urosepsis to severe sepsis or septic shock.

INTRODUCTION: To analyze the risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock, we had done the retrospective cross-sectional study, which would facilitate the early identification of high-risk patients. MATERIALS AND METHODS: Datas were retrospectively reviewed from 160 patients, suffering from obstructive urosepsis associated with urolith between December 2013 and December 2019. There were 49 patients complicating by severe sepsis (severe sepsis group), 12 patients complicating by septic shock (septic shock group), and 99 patients without progressing to severe sepsis or septic shock (sepsis group). The data covered age, gender, BMI (body mass index), time interval from ED (emergency department) to admission, WBC count (white blood cell count), NLR (neutrophil/lymphocyte ratio), HGB (hemoglobin), etc. Datas were analyzed by univariate analyses and multivariate logistic regression analysis. The corresponding nomogram prediction model was drawn according to the regression coefficients. RESULTS: Univariate analysis showed that the differences of age, the time interval from ED to admission, history of diabetes mellitus, history of CKI (chronic kidney disease), NLR, HGB, platelet count, TBil (total bilirubin), SCr (serum creatinine), ALB (albumin), PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio), PCT (procalcitonin), and positive rate of pathogens in blood culture were statistically significant (P < 0.05). Multivariatelogistic regression analysis showed that age, SCr, and history of CKI were independent risk factors for progression to severe sepsis, or septic shock (P < 0.05). CONCLUSIONS: Aged ≥ 65 years, SCr ≥ 248 mol/L, and history of CKI were independent risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock. We need to pay more attention to these aspects, when coming across the patients with urolithic sepsis.

Circulating myeloid-derived suppressors cells correlate with clinicopathological characteristics and outcomes undergoing neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

PURPOSE: Myeloid-derived suppressors cells (MDSCs) are heterogeneous immunosuppressive cells, closely related to the development, efficacy and prognosis in various tumors. The relationship between clinicopathological characteristics, efficacy of neoadjuvant chemoimmunotherapy (NCIO) and circulating MDSCs in patients with non-small cell lung cancer (NSCLC) was investigated in this study. METHODS: This study analyzed the clinical data of patients diagnosed at Department of Thoracic Surgery, Beijing Chest Hospital from November 2020 to August 2021. MDSCs and T cells subgroups were measured in fresh peripheral blood mononuclear cells(PBMCs) at baseline. Flow cytometry was used to detect MDSCs and T cells subgroups. RESULTS: A total of 78 patients with NSCLC and 20 patients with benign nodule underwent direct surgery. 23 patients with NSCLC scheduled to accept NCIO before surgery. NSCLC had elevated levels of total MDSCs, PMN-MDSCs and M-MDSCs compared to patients with benign nodule. MDSCs subgroups were correlated to the pTNM stage in NSCLC patients. The frequency of total MDSCs were moderately positively correlated with regulatory T cells (Tregs)(r = 0.3597, P < 0.01) and negatively correlated with CD4 + T cells(r = 0.2714, P < 0.05). The baseline levels of total MDSCs, PMN-MDSCs and Tregs in pCR patients were significantly decreased than those of non-pCR patients (P < 0.05). CONCLUSION: Circulating MDSCs were increased in NSCLC patients. MDSC subgroups were related to pTNM stage in NSCLC patients. Total MDSCs were positively correlated with Tregs levels and negatively correlated with CD4 + T cells in peripheral blood. The level of MDSCs and Tregs in peripheral blood may have potential value in predicting pathological response in NSCLC.

Immune cells in the small intestinal mucosa of newborn yaks.

BACKGROUND: This study aimed to characterise and evaluate the main markers of T lymphocytes, B lymphocytes, immunoglobulin (Ig) A and IgG plasmocytes, macrophages, and dendritic cells of the intestinal mucosa of newborn yaks. MATERIALS AND METHODS: Ten newborn yaks (2-4 weeks old) were chosen. Immunohistochemistry and real-time quantitative polymerase chain reaction were used to analyse the immune cell distribution and specific markers at the mRNA expression level in the duodenum, jejunum, and ileum. RESULTS: The results showed in the epithelium, CD3e-positive T lymphocyte levels were higher than other immune cell levels (p < 0.05). Additionally, in the lamina propria, the number of cells positive for CD3e, CD68, and signal inhibitory regulatory protein alpha (SIRPa) were higher in the villi, while CD79a, IgA and IgG cells were more common at the base of the crypt. Moreover, both in the epithelium and lamina propria, the number of CD3e, CD68 and SIRPa were decreased from the duodenum to the ileum (p < 0.05), additionally the number of CD79a, IgA and IgG positive cells were increased from the duodenum to the ileum of newborn yaks (p < 0.05). Furthermore, the mRNA expression levels of CD3e, CD68, and SIRPa increased from the duodenum to the ileum (p < 0.05), while the mRNA expression levels of CD79a, IgA and IgG decreased from the duodenum to the ileum. CONCLUSIONS: Immunohistochemical characterisation and expression levels of immune factors in the small intestinal mucosa of newborn yaks suggest that the intestinal mucosa is an important part of the natural barrier and provides useful references for immunity functions of newborn yak intestinal mucosa.

[Prospective cohort study of relationship of triglyceride, fasting blood-glucose and triglyceride glucose product index with risk of hypertension].

Objective: To investigate the relationship of triglyceride (TG), fasting blood glucose (FPG) and triglyceride glucose product index (TyG) with the incidence of hypertension, and provide basic data for the prevention and treatment of hypertension in the population. Methods: A total of 23 581 individuals who met the research criteria in Jinchang cohort were selected as the research subjects, the Cox proportional hazard model was used to analyze the relationship of TG, FPG, and TyG with the risk of hypertension. A stratified analysis was conducted by sex. Results: After adjusting for confounding factors, compared with the normal TG group, the HR(95%CI) of the elevated TG margin group and the elevated group were 1.16 (1.01-1.34) and 1.49 (1.30-1.70), respectively in the total population. Among men, they were 1.13 (1.01-1.27) and 1.17 (1.06-1.30), and among women, they were 1.05 (0.88-1.26) and 1.06 (0.88-1.28). Compared with the normal FPG group, the HR (95%CI) of the FPG-impaired group were 1.29 (1.13-1.48) in the total population, 1.26 (1.08-1.48) in men and 1.59 (1.14-2.21) in women. Taking the lowest quartile array as a reference, the HR (95%CI) of the highest quartile array of TyG was 1.73 (1.45-2.07) in the total population, 1.32 (1.14-1.53) in men and 1.87 (1.37-2.54) in women. TG, FPG had a nonlinear dose-response relationship with the risk of hypertension, while TyG had a linear correlation with the risk of hypertension. Conclusions: Higher TG, FPG, and TyG levels are independent risk factors for the incidence of hypertension. People with higher TG, FPG and TyG are at high risk for hypertension, to which close attention should be paid in the prevention and treatment of hypertension.

[A nested case-control study on relationship of traditional and combined lipid metabolism indexes with incidence of diabetes].

Objective: To explore the relationship between lipid indicators and the incidence of diabetes, and to compare the diabetes prediction and identification power of traditional lipid combined lipid indicators, in order to explore the best alternative indicators for identifying and predicting diabetes. Methods: Based on the Jinchang cohort, a nested case-control study was conducted in 1 025 new cases of diabetes after excluding patients with malignant tumor and related endocrine, circulatory system disease, then an age (±2 years), gender matched 1∶1 control group of 1 025 cases was set to analyze the relationship between the incidence of diabetes and lipid parameters. Results: Among the traditional lipid parameters, the fourth quartile of TG, TC, and LDL-C indicated higher risks of developing diabetes, which was 14.00 times (95%CI: 9.73-20.15), 2.15 times (95%CI: 1.65-2.79) and 1.66 times (95%CI: 1.29-2.14) than that of the first quartile, respectively. The risk of developing diabetes indicated by the fourth quartile of HDL-C was 0.21 times than that indicated by the first quartile (95%CI: 0.15-0.28). In the combined lipid parameters, the fourth quartile of TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C indicated higher risks of developing diabetes, which was 14.86 times (95%CI: 10.35-21.34), 8.12 times (95%CI: 5.94-11.01), 5.85 times (95%CI:4.34-7.88) and 5.20 times (95%CI: 3.85-7.03) than that indicated by the first quartile, respectively. The areas under the ROC curve of TG, TC, HDL-C, LDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C were 0.76 (95%CI: 0.74-0.78), 0.59 (95%CI: 0.57-0.61), 0.67 (95%CI: 0.65-0.69), 0.57 (95%CI: 0.55-0.59), 0.77 (95%CI: 0.75-0.78), 0.73 (95%CI: 0.71-0.75), 0.69 (95%CI: 0.67-0.71) and 0.66 (95%CI: 0.64-0.68), respectively. The optimal diabetes predicting point cuts of TG, TC, HDL-C, LDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C were 1.40, 4.70, 1.28, 3.25, 1.17, 3.43, 2.46, and 3.58 mmol/L, respectively. Conclusions: Lipid metabolic disorder is a risk factor for diabetes. TG and TG/HDL-C are the good lipid metabolism indicators for the prediction of diabetic.

[Relationship of body mass index and blood pressure with diabetes: a nested case-control study].

Objective: To explore the relationship of body mass index and blood pressure with the incidence of diabetes in Jinchang cohort. Methods: We designed a nested case-control study, a total of 29 572 workers who had no history of diabetes in baseline survey in Jinchang cohort were selected as the study cohort from June 2011 to December 2013. After 2 year follow-up, 1 021 workers with first diagnosed diabetes were selected as the case group, after 1∶1 matching according to the same gender and age ±2 years among those without diabetes, circulatory system, or endocrine system diseases during the same follow-up period, 1 021 controls was selected and 2 042 subjects were finally included. We used multivariate conditional logistic regression model, additive interaction model and multiplicative interaction model to explore the relationship of body mass index and blood pressure with the incidence of diabetes. Results: After adjusting for factors such as occupation, alcohol use, family history of diabetes, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, low-HDL cholesterolemia and high-LDL cholesterolemia, multivariate conditional logistic regression analysis showed that the risk of diabetes increased with body mass index and blood pressure. Hypertension and overweight/obesity had a multiplicative interaction on the incidence of diabetes. The risks of diabetes in men and women with hypertension and overweight/obese were 2.04 times (95%CI: 1.54-2.69) and 3.88 times (95%CI: 2.55-5.91) higher than those in men and women with normal body weight and blood pressure, respectively. In the combination of BMI and blood pressure, obese individuals with SBP≥160 mmHg were 4.57 times (95%CI: 2.50-8.34) more likely to have diabetes than those with normal BMI and SBP, obese individuals with DBP≥90 mmHg were 3.40 times (95%CI: 2.19-5.28) more likely to have diabetes than those with normal BMI and DBP. Conclusions: Overweight/obesity and hypertension can increase the risk of diabetes. Health education about body weight and blood pressure controls should be strengthened to reduce the risk of diabetes.

Propofol inhibited gastric cancer proliferation via the hsa-miR-328-3p/STAT3 pathway

Purpose The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. Methods Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 μM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. Results Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3′-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. Conclusions To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation (AU)

[Expression of microRNA-296 in rabbit hypertrophic scars and its role to human fibroblasts].

Objective: To investigate the expression of microRNA-296 (miR-296) in rabbit hypertrophic scars and its role in human fibroblasts (HFbs). Methods: The experimental method was used. Twelve healthy adult New Zealand long-eared rabbits regardless gender were randomly divided into normal control group and scar group, with 6 rabbits in each group. The rabbit ear hypertrophic scar model was created in scar group according to the literature, and the rabbits in normal control group did not receive any treatment. On 60 days after setting up the models in scar group, hematoxylin-eosin staining was performed to observe the growth and arrangement of fibroblasts (Fbs) in the ear scars and skin tissue of rabbits in the two groups. The mRNA expressions of miR-296 and transforming growth factor-ß1 (TGF-ß1) in ear scars and skin tissue of rabbits in the two groups were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction, and the correlation of mRNA between miR-296 and TGF-ß1 was performed with Pearson regression analysis. Two batches of HFbs were used and transfected respectively with corresponding sequences, with the 1st batch being divided into TGF-ß1 wild type+miR-296 negative control group and TGF-ß1 wild type+miR-296 mimic group and the 2nd batch being divided into TGF-ß1 mutant type+miR-296 negative control group and TGF-ß1 mutant type+miR-296 mimic group. At 48 h after transfection, luciferase reporter gene detection kit was used to detect the luciferase and renal luciferase expression of TGF-ß1 in the cells of each group, with their ratio being used to reflect the gene expression level. Two batches of HFbs were used, and each batch of cells were divided into miR-296 negative control group and miR-296 mimic group, being transfected with the corresponding sequences. At 0 (immediately), 12, 24, 36, and 48 h after transfecting the first batch of cells, the cell proliferation was detected by thiazolyl blue method. At 24 h after transfecting the second batch of cells, the expression of TGF-ß1 and collagen type Ⅰ was detected by Western blotting. The number of samples in cell experiments was 3. Data were statistically analyzed with analysis of variance for factorial design, independent sample t test. Results: On 60 days after setting up the models in scar group, the Fbs of rabbit ear scar tissue in scar group proliferated and arranged disorderly, while the growth and arrangement of Fbs in rabbit ear skin tissue in normal control group were normal. The mRNA expression of miR-296 of rabbit scar tissue in scar group (0.65±0.11) was significantly lower than 1.19±0.12 of rabbit ear skin tissue in normal control group (t=5.175, P<0.01). The mRNA expression of TGF-ß1 of rabbit ear scar tissue in scar group (1.47±0.06) was significantly higher than 1.10±0.03 of rabbit ear skin tissue in normal control group (t=12.410, P<0.01). Pearson regression analysis showed that there was a negative correlation between the mRNA expression of miR-296 and TGF-ß1 in the ear scars and skin tissue of 12 rabbits (F=7.278, P<0.05). At 48 h after transfection, the gene expression of TGF-ß1 of cells in TGF-ß1 wild type+miR-296 mimic group was significantly lower than that in TGF-ß1 wild type+miR-296 negative control group (t=35.190, P<0.01), while the gene expression of TGF-ß1 of cells in the two TGF-ß1 mutant type groups were close (P>0.05). The HFbs proliferation ability in miR-296 mimic group was significantly lower than that in miR-296 negative control group at 12, 24, 36, and 48 h after transfection(t=3.275, 11.980, 10.460, 17.260, P<0.05 or P<0.01). At 24 h after transfection, the protein expressions of TGF-ß1 and type Ⅰ collagen of cells in miR-296 negative control group were significantly higher than those in miR-296 mimic group (t=3.758, 29.390, P<0.05 or P<0.01). Conclusions: The miR-296 expression in rabbit hypertrophic scars is down-regulated; miR-296 can inhibit the proliferation of HFbs and the expression of type Ⅰ collagen by down regulating the expression of TGF-ß1.

Propofol inhibited gastric cancer proliferation via the hsa-miR-328-3p/STAT3 pathway.

PURPOSE: The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. METHODS: Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 µM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. RESULTS: Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3'-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. CONCLUSIONS: To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation.

Enhancement of cadmium accumulation in sweet sorghum as affected by nitrate.

The Cadmium (Cd)-polluted soils are is an increasing concern worldwide. Phytoextraction of Cd pollutants by high biomass plants, such as sweet sorghum, is considered an environmentally-friendly, cost-effective and sustainable strategy for remediating this problem. Nitrogen (N) is a macronutrient essential for plant growth, development and stress resistance. Nevertheless, how nitrate, as an important form of N, affects Cd uptake, translocation and accumulation in sweet sorghum is still unclear. In the present study, a series of nitrate levels (N1, 0.5 mm; N2, 2 mm; N3, 4 mm; N4, 8 mm and N5, 16 mm) with or without added 5 µm CdCl2 treatment in sweet sorghum was investigated hydroponically. The results indicate that Cd accumulation in the aboveground parts of sweet sorghum was enhanced by optimum nitrate supply, resulting from both increased dry weight and Cd concentration. Although root-to-shoot Cd translocation was not enhanced by increased nitrate, some Cd was transferred from cell walls to vacuoles in leaves. Intriguingly, expression levels of Cd uptake and transport genes, SbNramp1, SbNramp5 and SbHMA3, were not closely related to increased Cd as affected by nitrate supply. The expression of SbNRT1.1B in relation to nitrate transport showed an inverted 'U' shape with increasing nitrate levels under Cd stress, which was in agreement with trends in Cd concentration changes in aboveground tissues. Based on the aforementioned results, nitrate might regulate Cd uptake and accumulation through expression of SbNRT1.1B rather than SbNramp1, SbNramp5 or SbHMA3, the well-documented genes related to Cd uptake and transport in sweet sorghum.

Large Isospin Asymmetry in

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

CircTMBIM6 promotes osteoarthritis-induced chondrocyte extracellular matrix degradation via miR-27a/MMP13 axis.

OBJECTIVE: Osteoarthritis is a degenerative disease characterized by degeneration of articular cartilage, but the current mechanism is unclear. Circular RNA (circRNA) plays a significant role in a series of biological processes related to osteoarthritis, but its mechanism remains unclear. The purpose of this study was to investigate the role of the circTMBIM6/miR-27a/MMP13 axis in osteoarthritis. PATIENTS AND METHODS: The expression levels of circTMBIM6, miR-27a and MMP13 in cartilage of osteoarthritis patients and normal human cartilage were detected by reverse transcription polymerase chain reaction (RT-PCR). Osteoarthritis cell model was induced by IL-1ß and TNF-α, and the expression changes of circTMBIM6, miR-27a and MMP13 in the in vitro model were detected. In addition, the in vitro regulation of circTMBIM6 and miR-27a in osteoarthritis was verified by transfection of circTMBIM6 and miR-27a plasmids, and the regulation of miR-27a on MMP13 was also verified. The dimethylmethylene blue (DMMB) method was used to analyze the secretion and formation of soluble glycosaminoglycan sulfate (sGAG), and the effects of circTMBIM6 and miR-27a chondrocytes were evaluated. RESULTS: The expression levels of circTMBIM6 and MMP13 in cartilage tissue of patients with osteoarthritis were higher than that of normal group, while the expression level of miR-195 in cartilage tissue of patients with osteoarthritis was lower. After IL-1ß and TNF-α treatment, the expression of circTMBIM6 and MMP13 in chondrocytes increased, while the expression of miR-27a decreased. CircTMBIM6 overexpression reduced miR-27a expression but increased MMP13 expression. The circTMBIM6 gene knockout showed the opposite effect. CONCLUSIONS: CircTMBIM6 promotes osteoarthritis-induced chondrocyte extracellular matrix degradation via miR-27a/MMP13 axis.