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Right ventricular (RV) failure determines the prognosis in pulmonary arterial hypertension (PAH), but the underlying mechanism is still unclear. Growing evidence has shown that microRNAs participate in RV remodeling. This study is undertaken to explore the role of miR-335-5p in regulating RV remodeling induced by PAH. Two PAH models were used in the study, including the monocrotaline rat model and hypoxia/su5416 mouse model. miRNA sequencing and RT-qPCR validation identified that miR-335-5p was elevated in the RV of PAH rats. In vitro, miR-335-5p expression was increased after angiotensin II treatment, and miR-335-5p inhibition relieved angiotensin II-induced cardiomyocyte hypertrophy. The luciferase reporter assay showed that calumenin was a target gene for miR-335-5p. Pretreatment with miR-335-5p inhibitors could rescue calumenin downregulation induced by angiotensin II in H9C2 cells. Moreover, intracellular Ca2+ concentration and apoptosis were increased after angiotensin II treatment, and miR-335-5p inhibition decreased intracellular Ca2+ accumulation and apoptosis. Finally, in vivo miR-335-5p downregulation (antagomir miR-335-5p) attenuated RV remodeling and rescued calumenin downregulation under conditions of hypoxia/su5416 exposure. Our work highlights the role of miR-335-5p and calumenin in RV remodeling and may lead to the development of novel therapeutic strategies for right heart failure. [ABSTRACT FROM AUTHOR]

The CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays an extremely important role of the programed death receptor ligand-1 (PD-L1) protein. Our study is aimed at investigating the expression of CMTM6 and PD-L1 proteins in triple-negative breast cancer and their correlation with the clinical pathological data of patients. We selected 89 cases of triple-negative breast cancer and 62 cases of normal breast tissue specimens. Immunohistochemical methods were used to detect the expression levels of CMTM6 and PD-L1 and to carefully study differences in their expression. The expression of CMTM6 and PD-L1 in TNBC was higher than that in normal breast tissue, and the expression of the two was positively correlated (p < 0.05). In TNBC, CMTM6 expression is positively correlated with tumor size, lymph node metastasis, Ki67 proliferation index, and TNM stage (p < 0.05). PD-L1 expression is positively correlated with tumor size, lymph node metastasis, Ki67 proliferation index, TNM stage, and vascular infiltration (p < 0.05). Kaplan-Meier analysis showed that the positive expression of CMTM6 and PD-L1 had no correlation with the survival rate of patients (p > 0.05). According to KM-plotter, we found that a higher CMTM6 expression was positively related with relapse-free survival rate of patients (p < 0.05). A higher PD-L1 expression was positively correlated with relapse-free, overall, and distant metastasis survival rate of patients (p < 0.05). In timer database, we found a positive correlation between the expression of CMTM6 and PD-L1 in triple-negative breast cancer. Both CMTM6 and PD-L1 are highly expressed in TNBC, and their expressions are positively related. In the future, the two gene might become targets for the treatment of TNBC, providing a basis of clinical treatment of TNBC. [ABSTRACT FROM AUTHOR]

A calculation method of the bearing capacity of single squeezed branch pile is established based on the load transfer method. In the method, the hyperbolic model is used to describe the nonlinear load-displacement relationship of pile-soil interaction at the pile tip, the pile skin, and the squeezed branch, and the theoretical expression of six load transfer coefficients of squeezed branch pile is given. The correctness of the method is proved by a small-scale model test in homogeneous soil and a large-scale model test in stratified soil. The results show that the calculation based on the load transfer method is applicable to predict the ultimate load in engineering application. [ABSTRACT FROM AUTHOR]

Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin), is a small molecule glycoprotein associated with cell secretions. The purpose of our research is to clarify the clinicopathological and prognostic significance of SPARC expression in breast cancer. In this study, we performed a meta-analysis and bioinformatics analysis using the PubMed, Web of Science, Wanfang Data, and CNKI databases. The meta-analysis showed that SPARC expression was elevated in breast cancer tissue, compared with normal tissue, while SPARC expression in tumor stromal cells was higher than that of tumor cells. The expression of SPARC was positively correlated with histological grade and TNM staging. The Kaplan-Meier plotter showed that low SPARC expression was negatively correlated with the overall, postprogression, and distant metastasis survival rates of patients. According to Oncomine database, SPARC expression was upregulated in breast cancer than normal tissues. In TCGA database, univariate analysis showed that lymph node metastasis, distant metastasis, and TNM staging were negatively correlated with patient prognosis in breast cancers. Cox multivariate analysis showed that age, lymph node metastasis, distant metastasis, and TNM staging were important factors affecting the survival time of breast cancer patients. SPARC expression can be employed as a good indicator of prognosis of breast cancer patients, which will provide new methods and ideas of preventive treatment. [ABSTRACT FROM AUTHOR]

Objective. Leucine-rich α2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI). Methods. This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI. Results. All participants were divided into PSCI group (n = 64) and NC group (n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups (p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients (p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1 μg/ml. Conclusions. Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI. [ABSTRACT FROM AUTHOR]

As one of the possible signals for the whereabouts of the critical point on the QCD phase diagram, recently, the multiplicity fluctuations in heavy-ion collisions have aroused much attention. It is a crucial observation of the Beam Energy Scan program of the Relativistic Heavy Ion Collider. In this work, we investigate the centrality dependence of the multiplicity fluctuations regarding the recent measurements from STAR Collaboration. By employing a hydrodynamical approach, the present study is dedicated to the noncritical aspects of the phenomenon. To be specific, in addition to the thermal fluctuations, finite volume corrections, and resonance decay at the freeze-out surface, the model is focused on the properties of the hydrodynamic expansion of the system and the event-by-event initial fluctuations. It is understood that the real signal of the critical point can only be obtained after appropriately subtracting the background; the latter is investigated in the present work. Besides the experimental data, our results are also compared to those of the hadronic resonance gas, as well as the transport models. [ABSTRACT FROM AUTHOR]

Background. Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. Methods. We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. Results. AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. Conclusions. AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC. [ABSTRACT FROM AUTHOR]

The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms. [ABSTRACT FROM AUTHOR]

[BMIM]OH was used in mobile and stationary phase of thin layer chromatography (TLC) to analyze berberine hydrochloride and tetrahydropalmatine for the first time. Supported imidazole ionic liquid with hydroxide ion on silica gel (SiO2·Im+·OH−) was synthesized through simple procedure and characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, and scanning electron microscope (SEM). Moreover, on the plates prepared by SiO2·Im+·OH−, the contents of the above alkaloids in the Chinese patent medicine (CPM) of “Stomacheasy” capsule were successfully determined by TLC scanner. The key conditions and chromatographic behaviors were also investigated in detail. According to similar ways, ionic liquids (ILs) also can be used in other planar chromatographies in two modes. This study is expected to be helpful in expanding the application of IL and its bonded silica gel in TLC separation field. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with intestinal flora dysbiosis in a rat model. We compared the changes in the intestinal flora of letrozole-induced rats fed with HFD or normal chow, to explore the effects of HFD and letrozole independently and synergistically on the intestinal flora. Methods. Five-week-old female Sprague Dawley (SD) rats were divided into four groups: control (C) group fed with regular diet; L1 group administered with letrozole and fed with regular diet; L2 group received letrozole and fed with HFD; and HFD group fed with HFD. At the end of the experiment, ovarian morphology, hormones, metabolism, oxidative stress, and inflammatory status of all rats were studied. 16S rDNA high-throughput sequencing was used to profile microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. Results. Compared to the C group, the increased plasma fasting insulin and glucose, HOMA-IR, triglyceride, testosterone, and malondialdehyde were significantly higher in the L2 group, while high-density lipoprotein cholesterol was significantly lower in the L1 group and L2 group. The indices of Chao1 and the Abundance-based Coverage Estimator (ACE) (α-diversity) in the L2 and HFD groups were significantly lower than that in the C group. Bray–Curtis dissimilarity based principal coordinate analysis (PCoA) plots and analysis of similarities (ANOSIM) test showed obvious separations between the L2 group and C group, between the HFD group and C group, and between the L2 and HFD groups. At the phylum level, Firmicutes and ratio of Firmicutes and Bacteroidetes (F/B ratio) were increased in the L2 group; Bacteroidetes was decreased in the L2 and HFD groups. No significant differences in bacterial abundance between the C group and L1 group were observed at the phylum level. Based on linear discriminant analysis (LDA) effect size (LEfSe) analysis, the bacterial genera (the relative abundance > 0.1%, LDA > 3, p < 0.05) were selected as candidate bacterial signatures. They showed that the abundance of Vibrio was significantly increased in the L1 group; Bacteroides and Phascolarctobacterium were enriched in the HFD group, and Bacteroides, Phascolarctobacterium, Blautia, Parabacteroides, Akkermansia [Ruminococcus]_torques_group, and Anaerotruncus were enriched in the L2 group. Conclusion. The effect of letrozole on intestinal flora was not significant as HFD. HFD could destroy the balance of intestinal flora and aggravate the intestinal flora dysbiosis in PCOS. Letrozole-induced rats fed with HFD have many characteristics like human PCOS, including some metabolic disorders and intestinal flora dysbiosis. The dysbiosis was characterized by an increased Firmicutes/Bacteroidetes ratio, an expansion of Firmicutes, a contraction of Bacteroidetes, and the decreased microbial richness. Beta-diversity also showed significant differences in intestinal microflora, compared with control rats. [ABSTRACT FROM AUTHOR]

In this article, a novel ultra‐wideband four‐way power divider based on spoof surface plasmon polaritons (SSPPs) is proposed. The study of the transition structure indicates that the wave supported by unilateral SSPPs possesses the similar dispersion relation to the ones restricted by bilateral SSPPs and effective transmission of electromagnetic wave can be realized in this structure. Owning to these features, waves propagating along the bilateral SSPPs can be equally divided into two unilateral SSPPs and the power divider can be realized by loading this structure, which solves the problem of power distribution in multi‐way or even arbitrary ways. With the help of HFSS, the microstrip‐fed power divider is simulated and results show that it performs well. In order to verify the simulation effect, a object is fabricated and the measured results are in good agreement with simulation results. This power divider has the advantages of ultra‐wideband, low insertion loss and arbitrary‐way of power distribution, which opens up a new avenue for the application of SSPPs in power divider and has a great application prospects in photonics integrated circuits. [ABSTRACT FROM AUTHOR]

In spacecraft networks, the time-varying topology, intermittent connectivity, and unreliable links make management of the network challenging. Previous works mainly focus on information propagation or routing. However, with a large number of nodes in the future spacecraft networks, it is very crucial regarding how to make efficient network topology controls. In this article, we investigate the topology control problem in spacecraft networks where the time-varying topology can be predicted. We first develop a model that formalizes the time-varying spacecraft network topologies as a directed space–time graph. Compared with most existing static graph models, this model includes both temporal and spatial topology information. To capture the characteristics of practical network, links in our space–time graph model are weighted by cost, efficiency, and unreliability. The purpose of our topology control is to construct a sparse (low total cost) structure from the original topology such that (1) the topology is still connected over space–time graph; (2) the cost efficiency ratio of the topology is minimized; and (3) the unreliability parameter is lower than the required bound. We prove that such an optimization problem is NP-hard. Then, we provide five heuristic algorithms, which can significantly maintain low topology cost efficiency ratio while achieving high reliable connectivity. Finally, simulations have been conducted on random space networks and hybrid low earth orbit/geostationary earth orbit satellite-based sensor network. Simulation results demonstrate the efficiency of our model and topology control algorithms. [ABSTRACT FROM AUTHOR]

In this paper, geometrically nonlinear analysis of functionally graded curved beams with variable curvatures based on Timoshenko beam theory is presented. Considering the axial extension and the transversal shear deformation, geometrically nonlinear governing equations for the FGM curved beams with variable curvatures subjected to thermal and mechanical loads are formulated. Material properties of the curved beams are assumed to vary arbitrarily in the thickness direction and be independent on the temperature change. By using the numerical shooting method to solve the coupled ordinary differential equations, the nonlinear response of static thermal bending of a FGM semielliptic beams subjected to transversely nonuniform temperature rise is obtained numerically. The effects of material gradient, shear deformation, and temperature rise on the response of the curved beam are discussed in detail. Nonlinear bending of a closed FGM elliptic structure subjected to two pinching concentrated loads is also analyzed. This paper presents some equilibrium paths and configurations of the elliptic curved beam for different pinching concentrated loads. [ABSTRACT FROM AUTHOR]

In recent researches, high expression of nesfatin-1/nucleobindin-2 (NUCB2) is linked to poor prognosis in prostate and colon cancer due to the enhancement in proliferation, migration, and invasion. However, the role of nesfatin-1 in bladder cancer is not clear. In this study, we examined the expression of NUCB2 in bladder cancer using immunohistochemistry and observed that its high expression was associated with recurrence and metastasis. In addition, the transwell assay and wound healing assay showed that cell migration and invasion were decreased with NUCB2 knockdown in T24 and 5637 cells. In vivo, tumor growth and metastasis were inhibited with shRNA treatment in T24 cells. Those results showed that NUCB2 played an important role in bladder cancer and could be considered a potent prognostic factor in bladder cancer. [ABSTRACT FROM AUTHOR]

For space robots, it is difficult to track continuous time-varying manifolds on SE(3) by using traditional closed-loop control strategies, which are designed to track the position and the attitude separately. Therefore, the dynamics model should be rebuilt, and the corresponding control strategy should be redesigned. Firstly, the dynamics equations for a space robot in the joint space and workspace are established separately in the framework of Lie group SE(3) and screw theory based on the Lagrange principle. Secondly, based on the proposed feedback form, a PD (proportional derivative) control law of output force on the end-effector is designed, and a closed-loop continuous tracking control strategy is proposed using the force Jacobian matrix and the kinematic model. The simulation results show that the control scheme has good performance when the system state changes gently. Furthermore, a robust sliding mode tracking control scheme is designed. The simulation results show that the proposed robust control law has better accuracy than the PD control law because the system state changes wildly. Finally, a robust fuzzy sliding mode tracking control scheme is designed to deal with the chattering phenomenon. The simulation results show that the proposed robust fuzzy control law can eliminate the chattering well and decrease the joint control torque significantly. The robustness of the proposed robust fuzzy control law is also verified by numerical simulation. [ABSTRACT FROM AUTHOR]

The blasting quality and the rock volume blasted directly affect the cost of mines. A small charge-forward blast crater experiment was conducted to study the relationships between the rock volume blasted, the explosive unit consumption, the bulk yield, and the depth ratio. The results showed that the rational resistant line or explosive charge depth should be 0.86 times the optimal resistant line. Based on theoretical analysis of the large spacing of the holes and the small resistance line, the uniform design method was used to conduct the lateral blasting crater tests. The relationship equations among the blasting parameters, the blasting volume, and the bulk yield were obtained by regression analysis. The results illustrated that the rock volume blasted was negatively correlated with the bulk yield. The contribution rates of the resistance lines and the spacing of the holes to the blasting volume regression were 32.4% and 13.9%, respectively, and to the bulk yield regression were 65.0% and 0.256%. The impact of the resistance line on the blasting volume and the bulk yield was more significant than that of the spacing of the holes. The blasting effect of the rectangular blast hole arrangement was better than that of the square pattern. The blasting technology of large hole spacing and a small resistance line could achieve a better blasting effect while ensuring a higher rock volume blasted. The economical and reasonable blasting parameters were determined as the hole spacing of a=8.5 m and the resistance line width of W=5.5 m, with the rock volume blasted of 413.1 m3 and the bulk rate of 0.218%. This method provides an effective method for optimization of the blasting parameters and has important guiding significance for efficient and economical mining. [ABSTRACT FROM AUTHOR]

Cervical carcinoma is one of the serious pernicious cancers that influence women's health. Invasion and metastasis are the chief reason of poor prognosis of cervical carcinoma. Hypoxia-inducible factor-1α (HIF-1α) is a significant regulatory factor of intracellular oxygen supersession, and its expression or increased activity is closely related to the arise and expansion of various human tumors. However, the relationship between HIF-1α (hypoxia-inducible factor 1) and Hippo pathway target gene Yes-related protein (YAP) and transcriptional coactivator (TAZ) in cervical carcinoma remains unclear. Here, we studied the clinical correlation of HIF-1α and YAP/TAZ expression in normal tissues, cervical intraepithelial neoplasia (CIN), and cervical squamous cell carcinoma (CSCC). In order to analyze the role of HIF-1α in CCSC in vitro, SiHa cells with high expression of HIF-1α and C33a cells with low expression of HIF-1α were screened by detection. After transfection with lentivirus, HIF-1α levels were downregulated in SiHa cells and upregulated in C33a Cells, respectively. Then, the expression of HIF-1α in transfected cervical cancer cells Siha and C33a was detected by qRT-PCR and Western blot, and the expression of YAP/TAZ was detected in cervical squamous cell carcinoma cells after HIF-1α expression was altered. To explore HIF-1α role in cell proliferation, invasion, and metastasis, we examined the changes of cell function in cervical cancer cells with HIF-1α overexpression and inhibition by MTT assay, wound healing assay, Transwell test, and other cell function tests. At the same time, HIF-1α overexpression and HIF-1α inhibition cervical cancer cells were transplanted into nude mice, and tumors were isolated from the nude mice, and tumor volume and weight were observed. In conclusion, HIF-1α significantly promotes the proliferation, invasion, and migration of cervical carcinoma cells by upregulating YAP/TAZ. In addition, YAP/TAZ, the target gene of Hippo pathway, plays an important role in CCSC cells, pointing out that HIF-1α is provided with treatment potential for the treatment of CCSC. [ABSTRACT FROM AUTHOR]

What is known and objective: Administration of corticosteroids to immune checkpoint inhibitors (ICI)–treated patients has raised concerns due to doubts about ICIs' efficacy under those conditions. Hence, we reviewed studies comparing overall and progression‐free survival (OS and PFS) outcomes in patients with non–small‐cell lung carcinoma (NSCLC) treated with ICI and either with or without corticosteroids for any reason. Methods: We searched the PubMed Central, Cochrane library, EMBASE and MEDLINE databases from inception until February 2021 for relevant publications. We used the Newcastle‐Ottawa scale to assess the quality of the identified studies. We used the published data to carry out a meta‐analysis with a random‐effects model and report pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We included data from 14 studies with 5461 participants in the meta‐analysis. Most studies were retrospective in nature and of low quality, and most of them were conducted in the USA and in European countries. Nivolumab is the most common ICI used in the included studies followed by pembrolizumab. We found that patients using corticosteroids had reduced OSs (pooled HR, 1.82; 95% CI, 1.51–2.18) and PFSs (pooled HR, 1.69; 95% CI, 1.41–2.04) than the patients not using corticosteroids. We identified significant heterogeneity and publication bias for both the outcomes. However, the sensitivity analysis revealed that the estimates were robust to the individual study effects. What is new and conclusion: Our findings suggest that corticosteroids significantly reduce the OS and PFS of patients with NSCLC under ICI therapy. Hence, clinicians and oncologists should consider this information when prescribing corticosteroids for this target population. [ABSTRACT FROM AUTHOR]

This study investigated potential imaging biomarkers for predicting the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). A total of 59 PD patients and 50 healthy control subjects underwent high-resolution 3-dimensional T1-weighted brain magnetic resonance imaging. Bilateral STN volumes were compared between the 2 groups, and a correlation analysis was performed to assess the relationship between bilateral STN volumes or intracranial volume (ICV) and pre- or postoperative clinical scale scores. The results showed that the left STN volume differed significantly between PD patients and controls. In patients, the left STN volume was negatively correlated with pre- and postoperative quality of life scores and positively correlated with Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment scores; ICV was also positively correlated with the MMSE score. These findings indicate that changes in the left STN volume are a useful biomarker for evaluating the clinical outcome of PD patients following DBS. [ABSTRACT FROM AUTHOR]

Objective. Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI. Methods. All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination. Results. A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant (p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant (p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly (p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score (r = − 0.327 , p < 0.05). Conclusion. The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI. [ABSTRACT FROM AUTHOR]

Objective. Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI. Methods. In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population. Results. A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups (p > 0.05). Compared with the NC group, the SCI group had a higher serum CCL21 level (p < 0.001) and a lower MoCA score (p < 0.001). Serum CCL21 level in SCI was negatively correlated with MoCA score (p = 0.023). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI. Conclusions. MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI. [ABSTRACT FROM AUTHOR]

Objective. Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI. Methods. All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination. Results. A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant (p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant (p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly (p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score (r = − 0.327 , p < 0.05). Conclusion. The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI. [ABSTRACT FROM AUTHOR]

Objective. Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI. Methods. In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population. Results. A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups (p > 0.05). Compared with the NC group, the SCI group had a higher serum CCL21 level (p < 0.001) and a lower MoCA score (p < 0.001). Serum CCL21 level in SCI was negatively correlated with MoCA score (p = 0.023). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI. Conclusions. MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI. [ABSTRACT FROM AUTHOR]

Objective. To investigate the relationships between sex hormone-binding globulin (SHBG) and comprehensive metabolic parameters including biometric, glycemic, lipid, liver, and renal functions of women with polycystic ovary syndrome (PCOS). Study Design and Methods. A total of 1000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in a randomized controlled trial. SHBG and comprehensive metabolic parameters were measured at the baseline visit. Metabolic parameters included biometric parameters, glucose and lipid panels, and liver and renal function parameters. An independent t-test and linear regression were performed to investigate the associations between SHBG and metabolic parameters. Logistic regression was used to detect the relationship between SHBG and the presence of metabolic syndrome. Results. In comparative analyses, PCOS women with lower SHBG levels had higher body mass index, waist circumference, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, systolic and diastolic blood pressure, triglycerides, apolipoprotein B (APOB), low-density lipoprotein (LDL), aspartate transferase (AST), alanine transferase (ALT), and blood urea nitrogen (BUN), but lower high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). In linear regression, SHBG was inversely associated with waist circumference, systolic blood pressure, triglyceride, LDL, APOB, ALT, AST, and BUN but positively associated with HDL and APOA1 after adjusting the BMI. In logistic regression, SHBG is a protective predictor for metabolic syndrome (odds ratio = 0.96; 95% confidence interval: 0.95–0.97). The area under the receiver-operator characteristic curve is 0.732 with a 95% confidence interval of 0.695–0.770. SHBG <26.75 mmol/L is the cutoff point with the best Youden index, which has a sensitivity of 0.656 and specificity of 0.698. Conclusions. Lower SHBG was associated with worsening biometric, lipid, liver, and renal functions but not glycemic parameters among women with PCOS. SHBG can be used as a tool to screen metabolic syndrome. This trial is registered with NCT01573858 and ChiCTR-TRC-12002081. [ABSTRACT FROM AUTHOR]

Objective. To investigate the relationships between sex hormone-binding globulin (SHBG) and comprehensive metabolic parameters including biometric, glycemic, lipid, liver, and renal functions of women with polycystic ovary syndrome (PCOS). Study Design and Methods. A total of 1000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in a randomized controlled trial. SHBG and comprehensive metabolic parameters were measured at the baseline visit. Metabolic parameters included biometric parameters, glucose and lipid panels, and liver and renal function parameters. An independent t-test and linear regression were performed to investigate the associations between SHBG and metabolic parameters. Logistic regression was used to detect the relationship between SHBG and the presence of metabolic syndrome. Results. In comparative analyses, PCOS women with lower SHBG levels had higher body mass index, waist circumference, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, systolic and diastolic blood pressure, triglycerides, apolipoprotein B (APOB), low-density lipoprotein (LDL), aspartate transferase (AST), alanine transferase (ALT), and blood urea nitrogen (BUN), but lower high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). In linear regression, SHBG was inversely associated with waist circumference, systolic blood pressure, triglyceride, LDL, APOB, ALT, AST, and BUN but positively associated with HDL and APOA1 after adjusting the BMI. In logistic regression, SHBG is a protective predictor for metabolic syndrome (odds ratio = 0.96; 95% confidence interval: 0.95–0.97). The area under the receiver-operator characteristic curve is 0.732 with a 95% confidence interval of 0.695–0.770. SHBG <26.75 mmol/L is the cutoff point with the best Youden index, which has a sensitivity of 0.656 and specificity of 0.698. Conclusions. Lower SHBG was associated with worsening biometric, lipid, liver, and renal functions but not glycemic parameters among women with PCOS. SHBG can be used as a tool to screen metabolic syndrome. This trial is registered with NCT01573858 and ChiCTR-TRC-12002081. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of electroacupuncture (EA) at “Zusanli” (ST36) and “Shangjuxu”(ST37) on reducing inflammatory reaction and improving intestinal dysfunction in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi. Methods. A total of 71 patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi were randomly assigned to control group (n=36) and treatment group (n=35). Patients in control group were given conventional therapies including fluid resuscitation, anti-infection, vasoactive agents, mechanical ventilation, supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in treatment group underwent 20 minutes of EA at ST36-ST37 twice a day for five days. At baseline, day 1, day 3, and day 7 after treatment, the plasma levels of procalcitonin (PCT), tumor necrosis factor-α (TNF-α), intestinal fatty acid-binding proteins (I-FABP), D-lactate, citrulline, and TCM quantitative score of intestinal dysfunction were measured and recorded, respectively. And days on mechanical ventilation (MV), length of stay in intensive care unit (ICU), and 28d mortality were recorded. Results. During treatment, the plasma levels of PCT, TNF-α, I-FABP, D-lactate, and TCM quantitative score of intestinal dysfunction were declining in both groups, while the treatment group showed a significant decline (P<0.05). Plasma levels of citrulline were increasing in both groups, while the treatment group showed a significant increase (P<0.05). However, there were no significant differences in the days on MV, length of stay in ICU, and 28d mortality between two groups (P>0.05). Conclusions. EA at ST36-ST37 can reduce inflammatory reaction and has protective effects on intestinal function in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi. Trial Registration. This trial was registered at http://www.chictr.org.cn/(ChiCTR-IOR-17010910). [ABSTRACT FROM AUTHOR]

Solvent retention capacity (SRC) test is an effective method for quality evaluation of soft wheat. Ningmai 9 is a founder in soft wheat breeding. The SRC and genotype of Ningmai 9 and its 117 derivatives were tested. Association mapping was employed to identify the quantitative trait loci (QTL) associated with SRCs. Ningmai 9 had the allele frequency of 75.60% and 67.81% to its first- and second-generation derivatives, respectively, indicating higher contribution than theoretical expectation. Neighbor-joining cluster based on the genotyping data showed that Ningmai 9 and most of its first-generation derivatives were clustered together, whereas its second-generation derivatives were found in another group. The variation coefficients of SRCs in the derivatives ranged from 5.35% to 8.63%. A total of 29 markers on 13 chromosomes of the genome were associated with the SRCs. There were 6 markers associated with more than one SRC or detected in two years. The results suggested that QTL controlling SRCs in Ningmai 9 might be different from other varieties. Markers Xgwm44, Xbarc126, Xwmc790, and Xgwm232 associated with SRCs in Ningmai 9 might be used for quality improvement in soft wheat breeding. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH) treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS) (not acute kidney injury, AKI) with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n = 24) and a non-ECVVH group (n= 27). Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, extravascular lung water index (EVLWI), and E-selectin level were not significantly different between groups (all p > 0.05). Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVHgroup (all p < 0.05) at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU) were shorter in ECVVH group (all p < 0.05), but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI), treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU. [ABSTRACT FROM AUTHOR]

Profibrogenesis cytokine, transforming growth factor- (TGF-) β1, induces hepatic progenitors experiencing epithelial to mesenchymal transition (EMT) to matrix synthesis cells, even tumor initiating cells. Our previous data found that epidermal growth factor (EGF) blocks and reverses TGF-β1-induced transition. The aim of this study is to determine the characteristic changes of hepatic progenitors after TGF-β1-induced transition and EGF-induced reversion. Hepatic oval cells, rat hepatic progenitors, were isolated from rats fed a choline-deficient diet supplemented with ethionine. TGF-β1-containing medium was used for inducing EMT, while EGF-containing medium was used for reversing EMT. During TGF-β1-induced transition and EGF-induced reversion, hepatic oval cells sustained their progenitor cell marker expression, including α-fetoprotein, albumin, and cytokeratin-19. The proliferation ability and differentiation potential of these cells were suppressed by TGF-β1, while EGF resumed these capacities to the level similar to the control cells. RNA microarray analysis showed that most of the genes with significant changes after TGF-β1 incubation were recovered by EGF. Signal pathway analysis revealed that TGF-β1 impaired the pathways of cell cycle and cytochrome P450 detoxification, and EGF reverted TGF-β1 effects through activating MAPK and PI3K-Akt pathway. EGF reverses the characteristics impaired by TGF-β1 in hepatic oval cells, serving as a protective cytokine to hepatic progenitors. [ABSTRACT FROM AUTHOR]

Profibrogenesis cytokine, transforming growth factor- (TGF-) β1, induces hepatic progenitors experiencing epithelial to mesenchymal transition (EMT) to matrix synthesis cells, even tumor initiating cells. Our previous data found that epidermal growth factor (EGF) blocks and reverses TGF-β1-induced transition. The aim of this study is to determine the characteristic changes of hepatic progenitors after TGF-β1-induced transition and EGF-induced reversion. Hepatic oval cells, rat hepatic progenitors, were isolated from rats fed a choline-deficient diet supplemented with ethionine. TGF-β1-containing medium was used for inducing EMT, while EGF-containing medium was used for reversing EMT. During TGF-β1-induced transition and EGF-induced reversion, hepatic oval cells sustained their progenitor cell marker expression, including α-fetoprotein, albumin, and cytokeratin-19. The proliferation ability and differentiation potential of these cells were suppressed by TGF-β1, while EGF resumed these capacities to the level similar to the control cells. RNA microarray analysis showed that most of the genes with significant changes after TGF-β1 incubation were recovered by EGF. Signal pathway analysis revealed that TGF-β1 impaired the pathways of cell cycle and cytochrome P450 detoxification, and EGF reverted TGF-β1 effects through activating MAPK and PI3K-Akt pathway. EGF reverses the characteristics impaired by TGF-β1 in hepatic oval cells, serving as a protective cytokine to hepatic progenitors. [ABSTRACT FROM AUTHOR]

The nonpeptide AVE0991 is an agonist of the angiotensin-(1-7) (Ang-(1-7)) Mas receptor and is expected to be a putative new drug for treatment of cardiovascular disease. However, the mechanisms involved in the antiproliferative effects of AVE0991 are not fully understood. We saw that the compound attenuated proliferation in an angiotensin II-induced rat vascular smooth muscle cells (VSMC) proliferation model.Moreover, treatment with AVE0991 (10-5 mol/L or 10-7 mol/L) significantly attenuated reactive oxygen species (ROS) production, phosphorylation of p38 MAPK, and dose-dependently (10-8 to 10-5 mol/L) inhibited Ang II-induced VSMC proliferation. Meanwhile, heme oxygenase-1 (HO-1) expression increased in the AVE0991 + Ang II group (10-5 mol/L or 10-6 mol/L).However, the beneficial effects of AVE0991 were completely abolished when the VSMC were pretreated with A-779 (10-6 mol/L). Furthermore, treatment with the HO-1 inhibitor ZnPPIX attenuated the inhibitory effect of AVE0991 on Ang II-induced p38MAPK phosphorylation. These results suggest that AVE0991 attenuates Ang II-induced VSMC proliferation in a dose-dependent fashion and that this effect is associated with the Mas/HO-1/p38 MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

The nonpeptide AVE0991 is an agonist of the angiotensin-(1-7) (Ang-(1-7)) Mas receptor and is expected to be a putative new drug for treatment of cardiovascular disease. However, the mechanisms involved in the antiproliferative effects of AVE0991 are not fully understood. We saw that the compound attenuated proliferation in an angiotensin II-induced rat vascular smooth muscle cells (VSMC) proliferation model.Moreover, treatment with AVE0991 (10-5 mol/L or 10-7 mol/L) significantly attenuated reactive oxygen species (ROS) production, phosphorylation of p38 MAPK, and dose-dependently (10-8 to 10-5 mol/L) inhibited Ang II-induced VSMC proliferation. Meanwhile, heme oxygenase-1 (HO-1) expression increased in the AVE0991 + Ang II group (10-5 mol/L or 10-6 mol/L).However, the beneficial effects of AVE0991 were completely abolished when the VSMC were pretreated with A-779 (10-6 mol/L). Furthermore, treatment with the HO-1 inhibitor ZnPPIX attenuated the inhibitory effect of AVE0991 on Ang II-induced p38MAPK phosphorylation. These results suggest that AVE0991 attenuates Ang II-induced VSMC proliferation in a dose-dependent fashion and that this effect is associated with the Mas/HO-1/p38 MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Cutaneous CD30+ lymphoproliferative disorders represent a spectrum of skin lymphatic reticular proliferative diseases, including lymphomatoid papulosis (LYP), primary cutaneous anaplastic large cell lymphoma (PC‐ALCL), and borderline lesions between them. Although they all express CD30 as a phenotypic marker and share overlapping immunophenotypic features, they differ in clinical manifestations, pathological features, treatment, and prognosis. LYP is a kind of benign disease characterized by recurrent papules and nodules, and may spontaneously regress. PC‐ALCL presents with solitary tumor or local grouped nodules characterized by large T‐cells and may completely or partially resolve in fewer than half of cases. We reported a case of patient with clinical manifestation and pathologic features consistent with LYP in its early stages, which later turned into PC‐ALCL. This patient was treated with acitretin combined with NB‐UVB and had an obvious response. [ABSTRACT FROM AUTHOR]