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Probiotics effectively prevent and improve metabolic diseases such as diabetes by regulating the intestinal microenvironment and gut microbiota. However, the effects of probiotics in gestational diabetes mellitus are not clear. Here, we showed that probiotic supplements significantly improved fasting blood glucose in a gestational diabetes mellitus rat model. To further understand the mechanisms of probiotics in gestational diabetes mellitus, the gut microbiota were analyzed via 16S rRNA sequencing. We found that compared with the normal pregnant group, the gestational diabetes mellitus rats had decreased diversity of gut microbiota. Moreover, probiotic supplementation restored the diversity of the gut microbiota in gestational diabetes mellitus rats, and the gut microbiota structure tended to be similar to that of normal pregnant rats. In particular, compared with gestational diabetes mellitus rats, the abundance of Firmicutes and Actinobacteria was higher after probiotic supplementation. Furthermore, activating carbohydrate metabolism and membrane transport pathways may be involved in the potential mechanisms by which probiotic supplements alleviate gestational diabetes mellitus. Overall, our results suggested that probiotic supplementation might be a novel approach to restore the gut microbiota of gestational diabetes mellitus rats and provided an experimental evidence for the use of probiotic supplements to treat gestational diabetes mellitus.

AimLimited investigations on metabolic responses to exercise training in female adolescent volleyball athletes exist. The aim of this study was to obtain serum and urine metabolite markers in female adolescent volleyball athletes within 2-week strength-endurance training using a metabolomics approach coupled with biochemical analysis, which would be potential biomarkers for evaluating the physiological state of athletes.MethodsTwelve female adolescent volleyball athletes were recruited for 2-week strength-endurance training. Differential serum and urine metabolic profiles between the pre- and post-training group were obtained on gas chromatography coupled to mass spectrometry (GC-MS) and data subsequently underwent orthogonal partial least-squares analysis (OPLS).ResultsStrength-endurance training exerted a significant influence on the athletes' serum and urine metabolic profiles. The changed metabolites were primarily involved in energy metabolism, lipid metabolism and amino acids metabolism. Results support the hypothesis that female athletes displayed an increased propensity to oxidize lipids as the major energy source. Exposure to strength-endurance training also led to a significant increase in cortisol, but a decrease in testosterone, indicating disordered hormone adjustment. Exercise-induced oxidative stress occurred, as was evidenced by the decrease in reduced glutathione, and increases in blood malondialdehyde and oxidized glutathione. Since the muscle damage markers creatine kinase and lactate dehydrogenase did not show significant changes, the training might not cause cell membrane damage and the athletes did not cross the adaptive injury level.ConclusionBy measurement of endogenous metabolites, the metabolomics study has the potential to reveal the global physiological changes in response to exercise training.

An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs (n = 8, 11 weeks old) and normotensive Wistar rats (n = 8, age-matched) using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of cis-11,14-eicosadienoic acid, cis-13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of γ-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase (p < 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP (p < 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs (p < 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.

Per- and polyfluoroalkyl substances (PFAS) have been found to be associated with gestational diabetes mellitus (GDM) development, a maternal health disorder in pregnancy with negative effects that can extend beyond pregnancy. Studies that report on this association are difficult to summarize due to weak associations and wide confidence intervals. One way to advance this field is to sharpen the biologic theory on a causal pathway behind this association, and to measure it directly by way of molecular biomarkers. The aim of this review is to summarize the literature that supports a novel pathway between PFAS exposure and GDM development. Epidemiological studies demonstrate a clear association of biomarkers of thyroid hormones and glucose metabolism with GDM development. We report biologic plausibility and epidemiologic evidence that PFAS dysregulation of maternal thyroid hormones and thyrotropin (TSH) may disrupt glucose homeostasis, increasing the risk of GDM. Overall, epidemiological studies demonstrate that PFAS were positively associated with TSH and negatively with triiodothyronine (T3) and thyroxine (T4). PFAS were generally positively associated with glucose and insulin levels in pregnancy. We propose dysregulation of thyroid function and glucose metabolism may be a critical and missing component in the accurate estimation of PFAS on the risk of GDM. Supplementary Information The online version contains supplementary material available at 10.1186/s12940-021-00740-z.

Background The study was performed to assess the diagnostic capability of ECG on the cardiogenic shock (CS) in acute myocarditis. A new score was derived from the combination of the ECG parameters and the diagnostic value was also evaluated. Methods Total 103 consecutive patients with acute myocarditis admitted in Nanjing Drum Hospital were enrolled in the current study. The cohort was divided into fulminant myocarditis group (FM, n = 20) and non fulminant myocarditis group (NFM, n = 83). The demographic features, results of electrocardiography (ECG) and ultracardiography were compared. Logistic regression analysis was conducted to identify the relevant factors in ECG parameters. We created a new variable called “ECG score” by certain combination of ECG parameters. The diagnostic capability of ECG score for CS was compared with the existing diagnostic indices using regression model and receiver-operating characteristics (ROC) analysis. Results There were several changes on ECG significantly different between the two groups. Multivariate regression analysis demonstrated PR + QRS interval (P = 0.008), ventricular arrhythmia (P = 0.001) and pathological Q wave (P = 0.003) were the independent relevant factors of CS. The derived variable “ECG score” was identified as a significant relevant factor of CS by multivariate regression model. ROC analysis showed PR + QRS interval, ventricular arrhythmia and pathological Q wave all had equivalent diagnostic capability to left ventricular ejection fraction (LVEF) and shock index (SI). ECG score was equivalent to LVEF but superior to SI in diagnosing CS Conclusions ECG was valuable in diagnosing CS due to acute myocarditis. The ECG score was superior to the traditional diagnostic indices and could be used for an rapid recognition of CS.

Background. The relationship between fasting blood glucose (FBG) and microvascular obstruction (MVO) after primary percutaneous coronary intervention (PCI) remains unclear in nondiabetic patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to determine the predictive value of FBG in MVO in nondiabetic STEMI patients. Methods. A total of 108 nondiabetic STEMI patients undergoing primary PCI were enrolled in this study. The patients were classified into either the MVO group or non-MVO group based on cardiac magnetic resonance imaging (CMR). Results. FBG in the MVO group was higher than in the non-MVO group. Univariate analysis showed that FBG, peak high-sensitive troponin T (TnT), pre-PCI thrombolysis in myocardial infarction (pre-PCI TIMI) flow, left ventricular ejection fraction (LVEF), infarction size, left ventricular end-diastolic diameter (LVEDd), left ventricular end-diastolic volume (LVEDV), and global longitudinal strain (GLS) were likely predictive factors of MVO. After adjustment for other parameters, FBG, peak TnT, LVEF, and LVEDV remained independent predictors for MVO. Conclusion. FBG was independently associated with MVO in nondiabetic STEMI patients.

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.

The brainstem, the core of the central nervous system, plays a vital role in controlling arterial blood pressure and its elevation of hypertension subtypes, especially essential hypertension. Integrative metabolic and proteomic profiling was performed on the brainstem samples of 11 week old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar rats, using hydrophilic interaction liquid chromatography quadrupole/time-of-flight mass spectrometry (HILIC-Q/TOFMS) (PeptideAtlas: PASS01621) and nano-liquid chromatography-high-resolution-MS (nano-LC-high-resolution) combined with quantitative tandem mass tags (ProteomeXchange: PXD021210). The results showed a potentially significant measure of metabolic disorders in the brainstem of SHRs, including purine and pyrimidine metabolism and carnitine and acylcarnitine deficiency. By integrating the differential metabolites (VIP > 1 and p 1.2-fold and p < 0.05), the results revealed aberrant insulin signaling in the brainstem of SHRs, including reduced carnitine and acetylcarnitine; increased arginine; and increased flotillin-1 (FLOT1), hemoglobin subunit alpha-1/2, and hemoglobin subunit beta-2 proteins verified by the parallel reaction monitoring analysis (PeptideAtlas: PASS01622). The aberrant insulin signaling pathway in the brainstem of SHRs might help explain the correlation between essential hypertension and insulin resistance. These findings on the brainstem of SHRs could provide new insights into the dysregulation of the central nervous system in hypertension, especially as it relates to metabolite and protein levels.

Objective We aim to assess the left ventricular strain in patients with ventricular aneurysm(VA) after myocardial infarction(MI) using cardiac magnetic resonance-feature tracking (CMR-FT) and to evaluate its value for long term prognosis of patients.Methods Sixty-five patients who underwent CMR with VA after MI from January 2018 to December 2019 in Drum Tower Hospital Affiliated Hospital of Nanjing University School of Medicine were selected for the study. They were divided into two groups based on New York Heart Association (NYHA): 25 cases of NYHA I as group A and 40 cases of NYHA II-IV as group B. CMR was performed in both groups to quantify the parameters of overall and segmental left ventricular myocardial strain in patients with aneurysm. 37 of whom underwent a second CMR 3-12 months after cardiac infarction to investigate the effects of aneurysm on patients' left ventricular strain and left ventricular cardiac function.Results Patients from group B have larger VA basilar transverse diameter and significant more impaired LV Global longitudinal strain(GLS)、Global circumferential strain(GCS)、Global radial strain(GRS) (-12.34±7.31 vs. -7.68±6.11;p=0.0072, -21.31±13.49 vs. -14.93±10.44;p=0.0361, 37.13±27.87 vs. 22.00±20.05;p=0.0135) without change in infarct size. GLS, GCS, GRS were significant indicators of NYHA classification after AMI by multivariate regression analysis.Conclusions Myocardial strain assessed by CMR-FT may be an independent predictor of NYHA of patients with aneurysm after MI and could be used for identifying high-risk patients with VA.

Facing the increasingly severe environmental problems, the development of a green and sustainable low-carbon economy has become an international trend. In China, the core issue of low-carbon economic development is effectively resolving the contradiction between the exploitation and utilization of fossil energy and greenhouse gas emissions (mainly carbon emissions). Based on the SAM matrix, we established a static Computable General Equilibrium (CGE) model to simulate the impact of carbon tax policies on energy consumption, carbon emissions, and macroeconomics variables under 10, 20, and 30% emission reductions. Meanwhile, we analyze the impact of different carbon tax recycling mechanisms under the principle of tax neutrality. We find that the carbon tax effectively reduces carbon emissions, but it will negatively impact economic development and social welfare. A reasonable carbon tax recycling system based on the principle of tax neutrality can reduce the negative impact of carbon tax implementation. Among the four simulated scenarios of carbon tax cycle, the scenario of reducing residents’ personal income tax is most conducive to realizing the “double dividend” of carbon tax.

Background: The ischemia/reperfusion (I/R) process in patients with ST-segment elevation myocardial infarction (STEMI) triggers an immune response, resulting in myocyte death. Krüppel-Like Factor 2 (KLF2), which is highly expressed in endothelial cells (ECs) under laminar flow, exerts anti-inflammatory effects. In this study, we explored the role of small extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in the immunomodulation and its implications in myocardial I/R injury. Methods and Results: The small EVs were isolated from KLF2-overexpressing ECs' supernatant using gradient centrifugation. Mice were subjected to 45 min of ischemia followed by reperfusion, and KLF2-EVs were administrated through intravenous injection. KLF2-EVs ameliorated I/R injury and alleviated inflammation level in the serum and heart. We employed the macrophage depletion model and splenectomy and showed that Ly6Chigh monocyte recruitment from bone marrow was the main target of KLF2-EVs. miRNA-sequencing of KLF2-EVs and bioinformatics analysis implicated miRNA-24-3p (miR-24-3p) as a potent candidate mediator of monocyte recruitment and CCR2 as a downstream target. miR-24-3p mimic inhibited the migration of Ly6Chigh monocytes, and miR-24-3p antagomir reversed the effect of KLF2-EVs in myocardial I/R. Conclusion: Our data demonstrated that KLF2-EVs attenuated myocardial I/R injury in mice via shuttling miR-24-3p that restrained the Ly6Chigh monocyte recruitment. Thus, KLF2-EVs could be a potential therapeutic agent for myocardial I/R injury.

African swine fever (ASF) is an acute and highly contagious disease that causes severe economic losses to the swine industry. ASF is caused by infection of African swine fever virus (ASFV) in domestic pigs, leading to almost 100% mortality. However, no effective vaccines and pharmacologic treatment against ASF are available. ASF poses a severe threat to the swine industry and the economy. Here we summarize potential virus-host cell interaction mechanisms involving the suppression of innate and adaptive immune responses to ASFV entry and infection. These mechanisms include modulation of apoptosis, inhibition of inflammatory responses, reduction of IFN production, inhibition of autophagy, and suppression of MHC-I expression. Insights into immunoevasion strategies by ASFV may shed light on the development of vaccines, as well as preventive and therapeutic drugs.

Background To investigate the feasibility and indications of video-assisted thoracic surgery (VATS) in thymoma resection. Methods The clinical data of 103 patients undergoing thymoma resection via different approaches [including conventional lateral thoracotomy approach (LTA) in 41 cases, median sternotomy approach (MSA) in 40 cases, and right-sided VATS in 22 cases] were analyzed. Among them, 59, 13, 25, and 6 patients were in Masaoka stage I, II, III, and IV, respectively. Myasthenia gravis (MG) was also found in 54 cases. The patients were followed up for postoperative survival and the improvement in MG. The prognostic indicators of patients undergoing thymoma resection via different surgical approaches (i.e., LTA, MSA, and VATS) were statistically analyzed. Results Eight of 103 patients died. Six patients underwent unilateral sacral nerve resection, among whom 4 patients developed respiratory dysfunction, and 3 died. Two patients died of MG after surgery, 1 patient died of tumor recurrence and metastasis, 1 patient died of heart disease, and the cause of death was unknown in the remaining patient. The drainage time was shorter in VATS group than in open groups, along with smaller tumor size. The VATS group also had shorter hospital stay in the whole series and the subgroup without accompanying MG. The improvement in MG showed no significant difference among the three surgical groups. Both 5- and 10-year survival rates were 91% in the entire cohort. Conclusions VATS is like a conventional surgeries for improving MG in thymoma patients with accompanying MG. VATS resection can still be considered for thymoma that only invades the mediastinal pleura. For thymomas that have intact capsules and have not invaded mediastinal pleura, MSA surgery shall be performed to ensure patient safety if the anteroposterior diameters of the tumors are large and the masses have produced severe compression of the innominate vein, even if the tumors are still in the Masaoka stage II. For thymomas with large left-to-right diameters and with most parts of the tumors located in the left thoracic cavity, a left-sided approach (either VATS or an open approach) may be used in the absence of MG; if MG accompanies the condition, an MT approach or a bilateral VATS may be considered. In patients with unilateral pericardial phrenic nerve and/or local pericardial involvement, right-sided VATS thymectomy may be considered for thymomas located at the right side and bilateral VATS surgery can be performed for tumors located at the left side. In summary, VATS is feasible for the treatment of thymoma complicated by MG. VATS can be performed in patients with Masaoka stage I, II and (a certain portion of) III thymoma; for some patients with Masaoka stage II thymoma, especially those with compression of the innominate vein, the use of VATS should be cautious.

Objective To investigate the expression level and potential mechanism of hypoxia‐inducible factor 1 alpha (HIF‐1α) in patients with myelodysplastic syndromes (MDS). Methods Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF‐1α in paraffin‐embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF‐1α and clinical parameters were examined. To further investigate the significance of HIF‐1α expression in MDS patients, the researchers not only extracted the data about HIF‐1α expression from MDS‐related microarrays but also analyzed the correlation between the level of HIF‐1α expression and MDS. The microRNA (miRNA) targeting HIF‐1α was predicted and verified with a dual luciferase experiment. Results Immunohistochemistry revealed that the positive expression rate of HIF‐1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P, The up‐regulated expression of hypoxia‐inducible factor 1 alpha was examined in the myeloid tissues of myelodysplastic syndromes (MDS) patients. In terms of immunohistochemistry staining intensity, the MDS cohort (Figures B&D) displayed more intense staining than the controls (Figures A&C).

Objective The objective of current study was to investigate the lactation performance and rumen fermentation characteristics of dairy cows fed a diet with alfalfa hay replaced by corn stover but supplemented with molasses. Methods Sixteen Holstein cows in mid-lactation were randomly assigned to 1 of 2 dietary treatments: i) alfalfa based diet (AH), and ii) corn stover based diet supplemented with molasses (CSM). The experiment was conducted according to a 2×2 crossover design with 22-d each period, consisting of 17 d for adaptation and 5 d for data and samples collection. Results Dry matter intake and milk yield were higher for cows fed AH than CSM (p0.10). Total rumen volatile fatty acid concentration tended to be higher (p = 0.06) for cows fed AH than CSM-fed cows. Molar proportion of acetate was lower (p = 0.04), but valerate was higher (p = 0.02) in cows fed AH than CSM-fed cows. Rumen concentration of propionate, and isobutyrate, and ratio of acetate to propionate tended to be different (p0.10). Conclusion In comparison with AH diet, CSM diet could be fed to dairy cows without negative effect on feed efficiency, ruminal fermentation, but economically beneficial, indicating that CSM could be an alternative choice for dairy farms instead of AH to feed mid-lactation dairy cows.

BACKGROUND/AIM Salivary adenoid cystic carcinoma (SACC) is the most common malignancy of the salivary gland with a poor prognosis and survival. The present study aimed to investigate the role of histone methyltransferase WHSC1 in SACC. MATERIALS AND METHODS Human SACC specimens were evaluated for WHSC1 expression by RT-PCR and immunohistochemistry. The effects of WHSC1 knockdown on SACC cells proliferation, cell cycle, clone and tumorsphere formation, and apoptosis as well as on the expression of related genes were examined. A xenograft mouse model of SACC was used to evaluate the in vivo effects of WHSC1 knockdown on SACC tumorigenesis. RESULTS WHSC1 expression was up-regulated in human SACC tissues (p

Aerogels with multiple advantages have been developed for various requirements, but aerogels tend to be fragile and easy to break when bent or compressed. Herein, high-aspect-ratio cotton-derived n...

The gestational weight gain (GWG) range of Chinese women with gestational diabetes mellitus (GDM) still remains unclear. Our objective was to identify the ranges of GWG in Chinese women with GDM, and to investigate the associations between pre-pregnancy body mass index (BMI), GWG and maternal-infant adverse outcomes. GDM Women delivering singleton from 2013 to 2018 in a tertiary public hospital were collected. Logistic regression analysis was used to assess the joint effects of pre-pregnancy BMI and GWG on maternal-infant adverse outcomes. Finally, 14,578 women were collected. The ranges of GWG of Chinese women with GDM in the underweight, normal weight, overweight and obese groups were 5.95-21.95kg, 4.23-21.83kg, 0.88-21.12kg and-1.76-19.95kg, respectively. The risks of large for gestational age (LGA), macrosomia and cesarean delivery were significantly increased with the increase of pre-pregnancy BMI. Furthermore, the risks of LGA, macrosomia and cesarean delivery were significantly higher in normal weight group with GWG higher than the National Academy of Medicine’s (NAM) recommendation. Similarly, in overweight group with GWG higher than NAM recommendation, the risks of LGA were significantly higher, while, the risks of macrosomia were significantly lower. In conclusion, the ranges of GWG in GDM women were different with NAM recommendation.

Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The results demonstrate that the elevating ROS can up-regulate the expression of DR5, resulting in apoptosis via mitochondrial pathway. Although the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway served an important role in protecting gastric cancer cells against the injury of ROS, it can’t reverse LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d induced apoptosis via DR5-mediated mitochondrial apoptotic pathway in gastric cancer cells. LCT-3d could be a novel lead compound for development of anti-cancer activity in gastric cancer.

The present study aimed to investigate the role of partner of NOB1 homolog (PNO1) in esophageal cancer (EC). The expression levels of PNO1 in EC were primarily analyzed using data obtained from databases. PNO1 expression was also knocked down in EC cells (Eca‑109 and TE1) to determine the biological effects of PNO1 on tumorigenesis in vitro and in vivo. In addition, possible downstream targets of PNO1 in EC were identified. The expression levels of PNO1 were upregulated in the tumor tissues compared with that noted in normal tissues. Moreover, the knockdown (KD) of PNO1 suppressed cell proliferation, migration and invasion, and promoted cell apoptosis (P < 0.05). Furthermore, the protein expression levels of AKT1, Twist, Myc, mTOR, matrix metalloproteinase 2 (MMP2), nuclear factor (NF)‑κB p65 and β‑catenin 1 (CTNNB1) were downregulated following the KD of PNO1 in Eca‑109 cells (P < 0.05). In addition, the overexpression of CTNNB1 reversed the effects of PNO1 KD in Eca‑109 cells (P < 0.05). In conclusion, the findings of the present study suggest that PNO1 promotes EC progression by regulating AKT1, Twist, Myc, mTOR, MMP2, NF‑κB p65 and CTNNB1 expression.

The characteristics of enhanced biological phosphorus removal (EBPR) process under the combined actions of intracellular and extracellular polyphosphate (polyP) were investigated with the 31P Nuclear Magnetic Resonance (NMR) and the fractionation extracting the loosely-bound and tightly-bound extracellular polymer substances (i.e., LB-EPS and TB-EPS) and bacterial cells in EBPR sludge. The hydrolysis/synthesis of extracellular and intracellular polyP was a key step of the phosphate migration and transformation in EBPR sludge. The orthophosphate (orthoP) produced from the intracellular and extracellular polyP anaerobic-hydrolysis was partially accumulated in the bacterial cells and TB-EPS, and then the accumulated orthoP was main composition for these polyP aerobic-synthesis. Importantly, the anaerobic-hydrolysis enhancement of intracellular and extracellular ployP could promote EBPR sludge to absorb volatile fatty acids (VFAs) followed by being transformed into intracellular poly-hydroxy-alkanoates (PHAs). The mechanism for VFAs passing through the LB-EPS and TB-EPS should be an anion-exchange action between orthoP and VFAs. The orthoP accumulation in the TB-EPS kept an orthoP concentration gradient among the TB-EPS, LB-EPS and bulk solution, driving orthoP and VFAs migrations. The orthoP accumulation in the bacterial cells could keep an orthoP concentration difference between the cell-membrane two sides of phosphorus accumulating organisms (PAOs) to promote VFAs passing through the cell membrane considered as an anion exchange membrane. The intracellular PHAs continuously hydrolyzed accompanied with the average chain-length increases of the extracellular and intracellular polyP during the whole aerobic stage. Additionally, the energy of the extracellular polyP synthesized in situ should came from the intracellular PHAs hydrolysis.

Melatonin (MT) is an indoleamine hormone that can counteract ischemia‑induced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)‑induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)‑κB signaling pathway in this process. A rat model of HS‑induced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑6 and IL‑1β were measured every 6 h, and the 24‑h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NF‑κB p65 and NF‑κB inhibitor α (IκBα) were analyzed by reverse transcription‑quantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNF‑α, IFN‑γ, IL‑6 and IL‑1β gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNF‑α, IFN‑γ, IL‑6 and IL‑1β were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NF‑κB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NF‑κB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HS‑induced hepatic ischemic injury in rats via the inhibition of NF‑κB activation and IκBα phosphorylation.

Triple-negative breast cancer (TNBC) is well-known for its metastatic aggressiveness and poor survival prognosis, accounting for nearly a quarter of cases in breast cancer. We performed intra- and extra-cellular profiling of 40 amino acids and derivatives on three cell lines and their culture media, including TNBC, non-TNBC and normal breast epithelial cells, using HILIC-MS/MS. Characteristic metabolic alteration of amino acids and derivatives was observed in TNBC cells, compared to non-TNBC cells, especially in correlated intra- and extra-cellular metabolic pathways. Intra-cellularly, quantified glutamic acid, β-alanine, aspartic acid, glutathione, N-acetyl-serine and N-acetyl-methionine were most significantly increased (2-fold, p0.01 and VIP1) in TNBC cells. Extra-cellularly, significantly increased uptake of glutamine, serine, β-alanine, and lysine and elevated excretion of glutamic acid and l-cysteine-glutathione (p0.01 and VIP1) were observed by TNBC cells from or to their cell culture media. This study depicted a novel dynamic portrayal of metabolic dysregulation between TNBC and non-TNBC cells, correlated in both intra- and extra-cellular amino acid profiles. Quantification of these distinctive metabolites of TNBC cells might offer advanced understanding and new treatment targets for TNBC.

In addition to the altered amino acids in many cancer cells for their uncontrolled growth, targeted metabolomics in cell culture media could display a dynamic interaction between cancer cells and their micro-environments. Methodology for cell culture medium samples is different from that of cell lysates on sampling points, calculation and statistical analysis. Targeted profiling method of 40 amino acid and derivatives was validated and performed on cell culture medium samples from cell lines of HCC 1806 (breast cancer cell) and MCF-10A (normal breast epithelial cell). Different from the common up-regulation of amino acids in cancer cell lysates, significantly increased uptake (2.5-fold, VIP1 and p 0.001) of branched amino acids was observed in the cell culture media from the breast cancer cells while acetylmethionine, cysteine-glutathione, glutathione, cysteine and glutamic acid were excreted significantly more by the cancer cells to their media. The characteristic metabolic changes of amino acid and derivatives in the cell culture media provide a dynamic portrayal for the interaction of the breast cancer cells, normal breast cells with their micro-environments, which helps to understand the underlying proliferation mechanism of breast cancer cells.

Background A transthoracic impedance (TTI) signal is an important indicator of the quality of chest compressions (CCs) during cardiopulmonary resuscitation (CPR). We proposed an automatic detection algorithm including the wavelet decomposition, fuzzy c-means (FCM) clustering, and deep belief network (DBN) to identify the compression and ventilation waveforms for evaluating the quality of CPR. Methods TTI signals were collected from a cardiac arrest model that electrically induced cardiac arrest in pigs. All signals were denoised using the wavelet and morphology method. The potential compression and ventilation waveforms were marked using an algorithm with a multi-resolution window. The compressions and ventilations in these waveforms were identified and classified using the FCM clustering and DBN methods. Results Using the FCM clustering method, the positive predictive values (PPVs) for compressions and ventilations were 99.7% and 95.7%, respectively. The sensitivities of recognition were 99.8% for compressions and 95.1% for ventilations. The DBN approach exhibited similar PPV and sensitivity results to the FCM clustering method. The time cost was satisfactory using either of these techniques. Conclusions Our findings suggest that FCM clustering and DBN can be utilized to effectively and accurately evaluate CPR quality, and provide information for improving the success rate of CPR. Our real-time algorithms using FCM clustering and DBN eliminated most distortions and noises effectively, and correctly identified the compression and ventilation waveforms with a low time cost.

Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High‐mobility group box‐1 (HMGB‐1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB‐1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB‐1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4‐phenylbutyrate (4‐PBA). Mineral deposition was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT‐PCR. Expression and location of HMGB‐1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB‐1 expression, ERS and vascular calcification. However, inhibition of HMGB‐1 with Gly or inhibition of ERS with 4‐PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB‐1 attenuated advanced glycation end products (AGEs)‐induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB‐1 in VSMCs, which was reversed by 4‐PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB‐1 and AGEs. However, inhibition of ERS with 4‐PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB‐1. Thus, diabetes induced translocation and secretion of HMGB‐1 via ERS, which resulted in calcification in diabetic mice and in AGEs‐treated VSMCs.

The controversy of adjuvant radiotherapy of meningiomas is at least partially due to the insufficient understanding on meningioma cells' response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in meningiomas has yet to be confirmed. Therefore, the malignant meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors, and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression, and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee's radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for malignant meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.

BackgroundThe comparative performances of transcatheter aortic-valve replacement (TAVR) with balloon-expandable valves (BEV) and self-expanding valves (SEV) in severe aortic stenosis remain unclear.PurposeTo compare the early (30-day) and midterm (1-year) mortality and cardiovascular outcomes of BEV with SEV.Data SourcesPubMed, EMBASE, and the Cochrane Library from inception until February 13, 2020.Study Selection3 randomized controlled trials (RCTs) and 12 propensity-score matched (PSM) studies, with 37,958 patients.Data Extraction2 reviewers independently extracted study data and rated study quality. Data Synthesis: Compared with SEV, BEV was associated with significantly lower mortality at 30 days (OR 0.77, 95% CI 0.71–0.83, P<0.00001, I2=0) and a trend toward lower mortality at 1 year (OR 0.88, 95% CI 0.78–1.00, P=0.05, I2=15.8%), mainly driven from PSM studies, but regardless of valve generations and SEV types. 30-day and 1-year cardiovascular mortality, 30-day incidences of moderate to severe paravavular leak, procedural contrast agent volume and procedure time were lower, but transvalvular pressure gradient was higher in BEV than SEV. 30-day incidences of permanent pacemaker implantation (PPI), acute kidney injury, stroke, major bleeding, major vascular complications and rehospitalization were not statistically different between BEV and SEV. Early-generation SEV was associated with a higher 30-day PPI risk than corresponding BEV comparators. PPI risk was lower in ACURATE neo but higher in Evolut R SEV, both compared with SAPIEN 3 BEV.LimitationsStudy-level but not patient-level data; residual confounders in PSM studies; study designs and patient characteristics were heterogeneous.ConclusionsCompared with SEV, BEV might be associated with lower early and midterm mortality. Results from adequately powered RCTs with long-term follow-up are critically needed to confirm these findings.RegistrationPROSPERO (CRD42020172889).Funding SourceNational Natural Science Foundation of China (NO. 81600312).

The mechanism(s) through which mammalian kinase MELK promotes tumorigenesis is not understood. We find that theC. elegansorthologue of MELK, PIG-1, promotes apoptosis by partitioning an anti-apoptotic factor. TheC. elegansNSM neuroblast divides to produce a larger cell that differentiates into a neuron and a smaller cell that dies. We find that in this context, PIG-1 is required for partitioning of CES-1 Snail, a transcriptional repressor of the pro-apoptotic geneegl-1BH3-only.pig-1MELK is controlled by both aces-1Snail- andpar-4LKB1-dependent pathway, and may act through phosphorylation and cortical enrichment of nonmuscle myosin II prior to neuroblast division. We propose thatpig-1MELK-induced local contractility of the actomyosin network plays a conserved role in the acquisition of the apoptotic fate. Our work also uncovers an auto-regulatory loop through whichces-1Snail controls its own activity through the formation of a gradient of CES-1 Snail protein.Significance StatementApoptosis is critical for the elimination of ‘unwanted’ cells. What distinguishes wanted from unwanted cells in developing animals is poorly understood. We report that in theC. elegansNSM neuroblast lineage, the level of CES-1, a Snail-family member and transcriptional repressor of the pro-apoptotic geneegl-1, contributes to this process. In addition, we demonstrate thatC. elegansPIG-1, the orthologue of mammalian proto-oncoprotein MELK, plays a critical role in controlling CES-1Snaillevels. Specifically, during NSM neuroblast division, PIG-1MELKcontrols partitioning of CES-1Snailinto one but not the other daughter cell thereby promoting the making of one wanted and one unwanted cell. Furthermore, we present evidence that PIG-1MELKacts prior to NSM neuroblast division by locally activating the actomyosin network.

Soluble Nogo66 receptor-Fc protein (sNgR-Fc) enhances axonal regeneration following central nervous system injury. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of sNgR-Fc on the proliferation and differentiation of neural progenitor cells. The photothrombotic cortical injury model of ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats. The rats with photothrombotic cortical injury were randomized to receive infusion of 400 μg/kg sNgR-Fc (sNgR-Fc group) or an equal volume of phosphate-buffered saline (photothrombotic cortical injury group) into the lateral ventricle for 3 days. The effects of sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using BrdU staining. Neurological function was evaluated with the Morris water maze test. To further examine the effects of sNgR-Fc treatment on neural progenitor cells, photothrombotic cortical injury was produced in another group of rats that received transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats. The animals were then given an infusion of phosphate-buffered saline (neural progenitor cells group) or sNgR-Fc (sNgR-Fc + neural progenitor cells group) into the lateral ventricle for 3 days. sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo, compared with phosphate-buffered saline, and it also induced the differentiation of neural progenitor cells into neurons. Compared with the photothrombotic cortical injury group, escape latency in the Morris water maze and neurological severity score were greatly reduced, and distance traveled in the target quadrant was considerably increased in the sNgR-Fc group, indicating a substantial improvement in neurological function. Furthermore, compared with phosphate-buffered saline infusion, sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells. Our findings show that sNgR-Fc regulates neural progenitor cell proliferation, migration and differentiation. Therefore, sNgR-Fc is a potential novel therapy for stroke and neurodegenerative diseases, The protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong (approval No. 4560-17) in November, 2015.

The goal of this study was to compare in-hospital and long-term events between bailout rotational atherectomy (RA) and planned RA. In this retrospective study, All patients who underwent percutaneous coronary intervention (PCI) using RA at Nanjing Drum Tower Hospital from November 2011 to December 2018 were enrolled in this study. Planned RA was defined as RA performed immediately before balloon pre-dilation, while bailout RA was defined as RA after failure to expand the balloon or perform any other procedure. In-hospital and long-term major adverse cardiac events (MACE, defined as cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR) and stroke) were compared between the two groups. After statistical analysis, a total of 211 patients underwent PCI with RA during the study period: 153 in the planned RA group, and 58 in the bailout group. The incidence of coronary dissection was significantly higher in the bailout RA group than in the planned RA group (22.4% vs. 6.5%, P = 0.001). However, no significant difference in in-hospital MACE was found between the two groups (12.1% vs. 13.7%, P = 0.752). There was no difference in all-cause mortality (9.1% vs. 12.5%, P = 0.504) or long-term MACE (13.8% vs. 17.1%, P = 0.560) between the groups. Bailout RA was associated with a significantly longer procedural time (139.86 ± 56.24 min vs. 105.56 ± 36.71 min, P < 0.001) than planned RA. Therefore, compared with bailout RA, planned RA is associated with shorter procedural time and reduced incidence of coronary dissection, with no difference in MACE or mortality.

Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase of reductase protein following statin treatment may attenuate the effect and increase the side effects. Here we present a previously unexplored strategy to alleviate statin-induced reductase accumulation by inducing its degradation. Inspired by the observations that cholesterol intermediates trigger reductase degradation, we identify a potent degrader, namely Cmpd 81, through structure–activity relationship analysis of sterol analogs. Cmpd 81 stimulates ubiquitination and degradation of reductase in an Insig-dependent manner, thus dramatically reducing protein accumulation induced by various statins. Cmpd 81 can act alone or synergistically with statin to lower cholesterol and reduce atherosclerotic plaques in mice. Collectively, our work suggests that inducing reductase degradation by Cmpd 81 or similar chemicals alone or in combination with statin therapy can be a promising strategy for treating cardiovascular disease., Accumulated HMG-CoA reductase (HMGCR) limits the cholesterol-lowering effect of statins via a feedback loop. Here the authors developed a compound that degrades HMGCR, thus decreasing cholesterol levels and reducing atherosclerotic plaques.

11 páginas, 6 figuras, 2 tablas. Accesible en PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295914/, A small number of high-burden countries account for the majority of tuberculosis cases worldwide. Detailed data are lacking from these regions. To explore the evolutionary history of Mycobacterium tuberculosis in China-the country with the third highest tuberculosis burden-we analysed a countrywide collection of 4,578 isolates. Little genetic diversity was detected, with 99.4% of the bacterial population belonging to lineage 2 and three sublineages of lineage 4. The deeply rooted phylogenetic positions and geographic restriction of these four genotypes indicate that their populations expanded in situ following a small number of introductions to China. Coalescent analyses suggest that these bacterial subpopulations emerged in China around 1,000 years ago, and expanded in parallel from the twelfth century onwards, and that the whole population peaked in the late eighteenth century. More recently, sublineage L2.3, which is indigenous to China and exhibited relatively high transmissibility and extensive global dissemination, came to dominate the population dynamics of M. tuberculosis in China. Our results indicate that historical expansion of four M. tuberculosis strains shaped the current tuberculosis epidemic in China, and highlight the long-term genetic continuity of the indigenous M. tuberculosis population., This work was supported by the Natural Science Foundation of China (91631301 and 81661128043 to Q.G. and 81701975 to Q.L.). C.S.P. was supported by the National Institutes of Health (grant 1R01AI113287-01A1). S.G. was supported by the Swiss National Science Foundation (grants IZRJZ3_164171, 310030_166687, IZLSZ3_170834 and CRSII5_177163). This work was also supported by MINECO research grant SAF2016-77346-R (to I.C.), the European Research Council (638553-TB-ACCELERATE to I.C.), the National Science and Technology Major Project of China (2017ZX10201302 to Q.G., 2018ZX10103001 to Y.Z.), the Sanming Project of Medicine in Shenzhen (SZSM201611030 to Q.G.), JSGG20170413142559220 (to Q.G.), and National Basic Research programme of China (2014CB744403 to Y.Z.).

Background/Aims: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). Methods: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. Results: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR-30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. Significant pathways including the Mucin type O-glycan biosynthesis pathway, cell cycle pathway and cysteine and methionine metabolism pathway (all P< 0.05) revealed potential roles of the target genes of miR-30d-5p in the oncogenesis of NSCLC. Results from in vitro experiments indicated that miR-30d-5p could attenuate proliferation and viability of NSCLC cells. Among the 12 identified hub genes, nine genes including E2F3, CCNE2, SKP2, CDK6, TFDP1, LDHA, GOT2, DNMT3B and ST6GALNAC1 were validated by Pearson’s correlation test and the human protein atlas (HPA) database as targets of miR-30d-5p with higher probability. Specifically, dual luciferase reporter assay confirmed that CCNE2 was directly targeted by miR-30d-5p. Conclusion: In summary, miR-30d-5p expression is decreased in NSCLC, and it might play the role as tumor suppressor in NSCLC by regulating target genes.

Lu Yang,1,* Ming Xu,2,* Chuan-Bao Cui,1 Peng-Hai Wei,1 Shu-Zhi Wu,1 Zuo-Jie Cen,1 Xing-Xing Meng,1 Qiong-Guang Huang,1 Zhi-Chun Xie1 1Department of Epidemiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Human Anatomy and Histology and Embryology, Qilu Medical University, Zibo 255213, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Materials and methods: Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis.Results: ROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442–0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399–0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair. Conclusion: The present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis. Keywords: HBV, hepatocellular carcinoma, diagnosis, prognosis, ERCC

Purpose Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are important vision-threatening diseases worldwide. For effective treatment, the risk factors for the diseases merit investigation. This study aimed to compare the risk factors for nAMD vs. PCV in Chinese patients. Methods A total of 946 participants were recruited in this case-control study, including 281 patients with nAMD, 306 patients with PCV, and 359 controls. All participants underwent comprehensive ophthalmic examinations. Information on risk factors were collected by questionnaire. Multivariate logistic regression analyses were performed to investigate the difference in risk factors between nAMD and PCV. In a subgroup of subjects, serum lipid data were obtained and analyzed. Results Risk factors for nAMD included older age (OR 1.03, P = 0.001), male gender (OR 1.55, P = 0.020), asthma (OR 2.50, P = 0.028), smoking (OR 1.92, P = 0.001), and family history (OR 6.82, P = 0.001), while smoking (OR 1.67, P = 0.013) was the only risk factor for PCV. Compared to patients with PCV, patients with nAMD were more likely to be older and suffer from hyperlipidemia, coronary artery disease, rheumatism, and tumor. Interestingly, higher levels of high-density lipoprotein were positively associated with PCV in the subgroup analysis (OR 7.74, P = 0.011). Besides, results were quite different between the combination of patients with nAMD and PCV and patients with nAMD or PCV alone. Conclusions The risk factors for nAMD and PCV is varying with the exception of smoking. Our findings suggest that different strategies might be applied in the clinical management and scientific research on nAMD and PCV.

BACKGROUND Liver cancer is considered one of the main causes of cancer related deaths across the globe. Moreover, the incidence of liver cancer in developed countries is likely to increase in future. The increase in the incidence of liver cancer, the limited availability of standard treatments, and the side effects of the existing drugs demands exploration and identification of new targets and treatment strategies for liver cancer. In this context, the present study investigated the potential of miR-21 as the therapeutic target for the management of liver cancer. MATERIAL AND METHODS Total RNA was extracted by RNA isolation kit (RNeasy) as per the manufacturer's instructions. The cDNA synthesis was carried out with the help of RevertAid cDNA synthesis kit (Fermentas). Expression analysis was performed by quantitative RT-PCR. Cell proliferation was examined by CellTiter 96 aqueous one cell proliferation assay kit (Promega) as per manufacturer's guidelines. Apoptosis was detected by DAPI and Annexin V/PI staining. Cell migration was assessed by wound healing assay. MicroRNA-383 target was delimited by TargetScan software. Protein expression analysis was evaluated by western blotting. RESULTS Our results revealed that miR-21 was significantly upregulated in liver cancer cells. However, downregulation of miR-21 inhibited cancer cell proliferation, promoted apoptosis, inhibited cell migration, and triggered cell cycle arrest in KYN-2 liver cancer cells. Additionally, in silico analysis revealed PTEN to be the downstream target of miR-21, which was further confirmed by expression analysis through western blotting. CONCLUSIONS Our results reveal that miR-21 might prove to be an important target for the management of liver cancer.

Background: High platelet reactivity (HPR) during clopidogrel treatment predicts postpercutaneous coronary intervention (PCI) ischemic events strongly and independently. Tongxinluo capsules (TCs) are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome (ACS) patients with HPR. Methods: This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2Y12reaction units (PRUs) between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. Results: Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction (15.8% vs. 24.8%, P = 0.013), especially among patients with one cytochrome P450 2C19 loss of function (LOF) allele (χ2 = 2.931, P = 0.047). The TC group also had a lower prevalence of HPR (33.3% vs. 54.2%, t = 5.284, P = 0.022) and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein (hsCRP), but the composite prevalence of ischemic events did not differ significantly (χ2 = 1.587, P = 0.208). Conclusions: In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.

Increasing evidence has demonstrated that microRNA (miR)-449a expression is reduced in various types of tumors and that it serves as a tumor suppressor. However, the molecular mechanism of miR-449a in hepatocellular carcinoma (HCC) has not been thoroughly elucidated and is disputed. Therefore, the aim of the present work was to systematically review the current literature and to utilize the public Gene Expression Omnibus database to determine the role of miR-449a and its significance in HCC. A total of eight original papers and seven microarrays were included in the present study. Based on the evidence, miR-449a was reduced in HCC. miR-449a is likely involved in various signaling pathways and is targeted to multiple mRNA as part of its function in HCC. In addition, a preliminary bioinformatic analysis was conducted for miR-449a to investigate the novel potential pathways that miR-449a may participate in regarding HCC.

Background: Very few data have been reported for ST-segment elevation myocardial infarction (STEMI) caused by unprotected left main coronary artery (ULMCA) occlusion, and very little is known about the results of this subgroup of patients who underwent primary percutaneous coronary intervention (PCI). The aim of this study was to determine the clinical features and outcomes of patients with STEMI who underwent primary PCI for acute ULMCA occlusion. Methods: From January 2000 to February 2014, 372 patients with STEMI caused by ULMCA acute occlusion (ULMCA-STEMI) who underwent primary PCI at one of two centers were enrolled. The 230 patients with non-ST-segment elevation MI (NSTEMI) caused by ULMCA lesion (ULMCA-NSTEMI) who underwent emergency PCI were designated the control group. The main indexes were the major adverse cardiac events (MACEs) in-hospital, at 1 month, and at 1 year. Results: Compared to the NSTEMI patients, the patients with STEMI had significantly higher rates of Killip class≥III (21.2% vs. 3.5%, χ2 = 36.253, P < 0.001) and cardiac arrest (8.3% vs. 3.5%, χ2 = 5.529, P = 0.019). For both groups, the proportions of one-year cardiac death in the patients with a post-procedure thrombolysis in myocardial infarction (TIMI) flow grade 0.05) and TVR (all P > 0.05) in the intervals of 0–1 month as well as 1 month to 1 year. The results of Cox regression analysis showed that the differences in the independent predictors for MACE included the variables of Killip class ≥ III and intra-aortic balloon pump support for the STEMI patients and the variables of previous MI, ULMCA distal bifurcation, and 2-stent for distal ULMCA lesions for the NSTEMI patients. Conclusions: Compared to the NSTEMI patients, the patients with STEMI and ULMCA lesions still remain at a much higher risk for adverse events at 1 year, especially on 1 month. If a successful PCI procedure is performed, the 1-year outcomes in those patients might improve.

Background Currently, some studies have demonstrated that miR-34a could serve as a suppressor of several cancers including hepatocellular carcinoma (HCC). Previously, we discovered that miR-34a was downregulated in HCC and involved in the tumorigenesis and progression of HCC; however, the mechanism remains unclear. The purpose of this study was to estimate the expression of miR-34a in HCC by applying the microarray profiles and analyzing the predicted targets of miR-34a and their related biological pathways of HCC. Methods Gene expression omnibus (GEO) datasets were conducted to identify the difference of miR-34a expression between HCC and corresponding normal tissues and to explore its relationship with HCC clinicopathologic features. The natural language processing (NLP), gene ontology (GO), pathway and network analyses were performed to analyze the genes associated with the carcinogenesis and progression of HCC and the targets of miR-34a predicted in silico. In addition, the integrative analysis was performed to explore the targets of miR-34a which were also relevant to HCC. Results The analysis of GEO datasets demonstrated that miR-34a was downregulated in HCC tissues, and no heterogeneity was observed (Std. Mean Difference(SMD) = 0.63, 95% confidence intervals(95%CI):[0.38, 0.88], P

High mobility group box-1 (HMGB-1), a typical damage-associated molecular pattern protein released from various cells, was first identified in 1973. It is usually stored in the nuclei of cells. Several modifications of HMGB-1 promote its translocation to the cytosol, and it is actively or passively released from cells. When outside of the cells, HMGB-1is crucial in inflammation. It exerts its biological functions via interaction with its receptors, including receptor for advanced glycation end products (RAGE) and Toll-like receptor 4(TLR4). A large number of studies showed a close link between inflammation and thrombosis. This review demonstrated the increased expression of HMGB-1 in thrombosis-related diseases, including coronary artery disease, stroke, peripheral arterial disease, disseminated intravascular coagulation, and venous thrombosis. Besides, it summarized the current understanding of the emerging link between HMGB-1 and thrombosis from three aspects: platelet, NETs, and coagulation and fibrinolysis factors. Finally, it explored the possible therapeutic strategies targeting HMGB-1 for treating thrombosis-related diseases.

Background: The prevalence, presentation, management, and prognosis of coronary heart disease differ according to sex. Greater understanding on the differences between men and women with acute aortic dissection (AAD) is needed. We aimed to investigate whether sex disparities are found in patients with AAD, and to study sex differences in complications, mortality in-hospital, and long-term. Methods: We included 884 patients enrolled in our institute between June 2002 and May 2016. Considering psychosocial factors, treatments, and the outcomes in men versus those in women with AAD, we explored the association of sex with psychosocial characteristics and mortality risk. For categorical variables, significant differences between groups were assessed with the Chi-square test or Fisher’s exact test, and continuous parameters were assessed with Student’s t-test. Univariate and stratified survival statistics were computed using Kaplan-Meier analysis. Results: A total of 884 patients (76.1% male, mean age 51.4±11.8 years) were included in this study. There were fewer current smokers in female compared with male (17.5% vs. 67.2%, χ2 = 160.06, P< 0.05). The percentage of men who reported regular alcohol consumption was significantly higher than that in women (40.6% vs. 3.8%, χ2 = 100.18, P< 0.05). About 6.2% (55 of 884) of patients with AAD died before vascular or endovascular surgery was performed, 34.4% (304 of 884) of patients underwent surgical procedures, and 52.7% (466 of 884) and 12.8% (113 of 884) of patients received endovascular treatment and medication. Postoperative mortality similar (6.0% vs. 5.6%, respectively, χ2 = 0.03, P = 0.91) between men and women. Follow-up was completed in 653 of 829 patients (78.8%). Adjustment for age, history of coronary disease, hypertension, smoking and drinking, Type A and use of beta-blocker, angiotensin II receptor blockers, angiotensin converting enzyme (ACE) inhibitor, calcium-channel blockers and statins by multivariate logistic regression analysis suggested that age (odds ratios [ORs], 1.04; 95% confidence interval [CI], 1.01–1.07; P< 0.05), using of calcium-channel blockers (OR, 0.37; 95% CI, 0.18- 0.74; P< 0.05), at discharge were independent predictors of late mortality, ACE inhibitors (OR, 1.91; 95% CI, 1.03–3.54; P = 0.04) was independent risk factor of late mortality. Conclusions: In Chinese with AAD, sex is not independently associated with long-term clinical outcomes. Age, the intake of calcium-channel blockers at discharge might help to improve long-term outcomes. Key words: Aortic Dissection; Prognosis; Sex

Characterized by the high concentration suspended solids (SS), chemical oxygen demand (COD), biological oxygen demand (BOD), ammonium nitrogen and total phosphorus (TP), a solid–liquid separation as a pretreatment is mandatory for swine wastewater before biological treatment. In this study, batch tests of electrocoagulation were investigated under different structural parameters (anode material, inter-electrode distance) and operational parameters (current density, stirring speed, initial pH and reaction time). The results showed that the optimal conditions were the Fe anode, inter-electrode distance of 2.0 cm, current density of 30 mA/cm2, no stirring, initial pH of 6.3 without control and reaction time of 35 min in this study. By comparing with chemical coagulation, satisfactory performance was achieved under optimal electrocoagulation: supernatant recovery of 60%, SS, TP, COD and BOD removal efficiencies of 98.5%, 99.5%, 50.6% and 10%. In addition, fluorescent substances formation was observed under electrocoagulation and thus increased the BOD/COD ratio from 0.36 to 0.66. The enhanced biodegradability would facilitate the subsequent biological removal and the overall swine wastewater treatment. Conclusively, the iron electrocoagulation technology is a promising process for high-strength swine wastewater pretreatment.

Hai-wei Liang,* Zhi-hua Ye,* Shu-ya Yin, Wei-jia Mo, Han-lin Wang, Jin-che Zhao, Guo-mei Liang, Zhen-bo Feng, Gang Chen, Dian-zhong Luo Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China *These authors contributed equally to this work Background: Studies which focused on the character of miR-144-3p in hepatocellular carcinoma (HCC) are limited. This study aimed to explore the expression, clinical significance and the potential targets of miR-144-3p in HCC. Methods: The Cancer Genome Atlas (TCGA) and a cohort of 95 cases of HCC were applied to investigate aberrant miR-144-3p expression in HCC. A meta-analysis was performed to accumulate data on miR-144-3p expression in HCC based on TCGA, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Gene Expression Omnibus (GEO). Additionally, the potential regulatory mechanisms of miR-144-3p in HCC were explored by bioinformatics. Results: MiR-144-3p expression was downregulated distinctly in HCC compared to para-HCC tissue both in TCGA data (8.9139±1.5986 vs 10.7721±0.9156, P

PURPOSE A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type. PATIENTS AND METHODS Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81). Blood samples for detecting UGT1A1 were collected from each patient after various administration regimens. RESULTS Colorectal cancer patients with the UGT1A1*6 mutant genotype had a significantly higher risk of severe delayed diarrhea than that of wild-type individuals when administered a CPT-11 dose ≥130 mg/m2 (P=0.042); the same phenomenon was observed when the UGT1A1*6 and UGT1A1*28 mutant genotypes were considered together (P=0.028). However, in lung cancer patients administered a low dose of CPT-11, UGT1A1*6/*28 variants were not significantly associated with severe neutropenia or delayed diarrhea. Furthermore, adult patients with the UGT1A1*6 mutation were more likely to develop severe delayed diarrhea than did wild-type adults (P=0.013); however, the difference was not significant in elderly patients. No significant differences in tumor response were found among the different genotypes (P>0.05). CONCLUSION Thus, age and tumor type influence our ability to predict adverse reactions based on UGT1A1 gene polymorphisms in cancer patients. Further, UGT1A1 gene polymorphisms are not correlated with the efficacy of CPT-11-based regimens.

Ling Zhang,1,* Hai-Wei Wu,1,* Weien Yuan,2 Jia-Wei Zheng1 1Department of Oral-Maxillary Head and Neck, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republicof China *These authors contributed equally tothis work Objective: Hemangiomas are the most common benign vascular tumors of infancy. Although most infantile hemangiomas (IHs) have the ability to involute spontaneously after initial proliferation and resolve without consequence, intervention is required in a subset of IHs, which develop complications resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment for this subset of IHs is pharmacological intervention, and propranolol has become the new first-line treatment for complicated hemangiomas. Here, we evaluated the efficacy of propranolol on proliferation IH in a clinical cohort including 578 patients.Methods: We retrospectively reviewed a total of 578 IH patients who were treated with oral propranolol from January 2010 to December 2012. Responses to the propranolol treatment were graded as: excellent, good, poor, or no response. Based on the response to propranolol treatment (once daily at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily total dose of 2 mg/kg for patients older than 2 months), additional pharmacotherapies or surgery were used for IH patients for satisfactory clinical outcome.Results: Five hundred and sixty (96.9%) of 578 IH patients in our study responded to oral propranolol treatment, and the response rate was significantly different for different ages of patients (P

Palmar hyperhidrosis involves excessive sweating of the palms, with no known etiology. Endoscopic thoracic sympathectomy (ETS) is a safe and effective treatment for palmar hyperhidrosis, but compensatory hyperhidrosis is a common complication after ETS, leading to reduced patient satisfaction and postoperative quality of life. However, the appropriate level of the sympathetic chain to target with ETS to achieve maximum efficacy and reduce the risk of compensatory hyperhidrosis (CH) is controversial. In this systemic review, we investigated the appropriate level of sympathectomy for palmar hyperhidrosis. PRISMA guidelines were implemented to complete a systematic review. We performed a computerized systematic literature search using PubMed and EMBASE from January 1990 to July 2016. We chose the Cochrane Collaboration’s tool and the methodological index for non-randomized studies tool for examining study bias. A total of 4075 citations were identified, of which 91 were eligible for inclusion, including 68 observational studies and 23 comparative trials. In observational studies, sympathectomies showed similar efficacies for curing PH at different levels. However, T2-free groups (i.e., at levels T3, T4, or T3–T4 combined) could render a lower risk of Horner’s syndrome (0 vs. 1.21 ± 0.49%, p = 0.036) and CH (28.75 ± 7.25 vs. 57.46 ± 3.86, p = 0.002) compared with T2 involved. In comparative trials, there were 12 studies describing the comparison between T2-free ETS and T2 involved, and 9 of 12 (75%) showed T2-free ETS could reduce the incidence of CH. Overall, lowering the level and limiting the extent of sympathectomy could reduce the incidence of complications. Cumulative data from more than 13,000 patients suggest that ETS is a safe, effective, and reproducible procedure with a high degree of patient satisfaction. Currently available evidence suggests that T2-free ETS may reduce the incidence of compensatory hyperhidrosis without compromising success rates and safety.

BACKGROUND MiR-101-3p can promote apoptosis and inhibit proliferation, invasion, and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not fully understood. Therefore, a comprehensive analysis of the target genes, pathways, and networks of miR-101-3p in BC is necessary. MATERIAL AND METHODS The miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA) were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected MCF-7 cells and scramble control cells was downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO) and pathway and network analyses were constructed for the DEGs and predicted genes. RESULTS In the TCGA data, a low level of miR-101-2 expression might represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic (HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis (M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and the 7924 potential target genes from the prediction databases. These genes were related to transcription, metabolism, biosynthesis, and proliferation. The results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt, and chemokine signaling pathways. CONCLUSIONS MiR-101-1 and miR-101-2 may be prospective biomarkers for the prognosis and diagnosis of BC, respectively, and are associated with diverse clinical parameters. The target genes of miR-101-3p regulate the development and progression of BC. These results provide insight into the pathogenic mechanism and potential therapies for BC.