MicroRNA directly enhances mitochondrial translation during muscle differentiation.

MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here, we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq), functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1-mediated translational stimulation in the mitochondria and repression in the cytoplasm.

CDCA5 accelerates progression of breast cancer by promoting the binding of E2F1 and FOXM1.

BACKGROUND: Breast cancer is one of the most common malignant tumors in women. Cell division cycle associated 5 (CDCA5), a master regulator of sister chromatid cohesion, was reported to be upregulated in several types of cancer. Here, the function and regulation mechanism of CDCA5 in breast cancer were explored. METHODS: CDCA5 expression was identified through immunohistochemistry staining in breast cancer specimens. The correlation between CDCA5 expression with clinicopathological features and prognosis of breast cancer patients was analyzed using a tissue microarray. CDCA5 function in breast cancer was explored in CDCA5-overexpressed/knockdown cells and mice models. Co-IP, ChIP and dual-luciferase reporter assay assays were performed to clarify underlying molecular mechanisms. RESULTS: We found that CDCA5 was expressed at a higher level in breast cancer tissues and cell lines, and overexpression of CDCA5 was significantly associated with poor prognosis of patients with breast cancer. Moreover, CDCA5 knockdown significantly suppressed the proliferation and migration, while promoted apoptosis in vitro. Mechanistically, we revealed that CDCA5 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the forkhead box M1 (FOXM1) promoter. Furthermore, the data of in vitro and in vivo revealed that depletion of FOXM1 alleviated the effect of CDCA5 overexpression on breast cancer. Additionally, we revealed that the Wnt/ß-catenin signaling pathway was required for CDCA5 induced progression of breast cancer. CONCLUSIONS: We suggested that CDCA5 promoted progression of breast cancer via CDCA5/FOXM1/Wnt axis, CDCA5 might serve as a novel therapeutic target for breast cancer treatment.

Characteristics of in-hospital mortality of congenital heart disease (CHD) after surgical treatment in children from 2005 to 2017: a single-center experience.

BACKGROUND: To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children's CHD after thoracotomy. METHODS: This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. RESULTS: A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3,P < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P < 0.05). CONCLUSIONS: The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo.

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

High expression of FOXR2 in breast cancer correlates with poor prognosis.

Forkhead box protein R2 (FOXR2) is associated with human central nervous system neoplasms. However, the expression level of FOXR2 in breast cancer specimens remains largely unknown. To identify whether FOXR2 can serve as a biomarker for the diagnosis and prognosis of breast cancer, real-time PCR and immunohistochemistry (IHC) staining were utilized to detect the expression of FOXR2. The messenger RNA (mRNA) and protein levels of FOXR2 in breast cancer samples were novelty higher compared to non-tumorous breast tissues. IHC results revealed FOXR2 expression was significantly correlated to classifications tumor size (p = 0.007) and Ki-67 (p = 0.019). The patients with high expression of FOXR2 had a significantly poor prognosis compared to those of low expression (p = 0.003), especially in the patients with tumor size ≥2 cm (p = 0.006) and lymph node metastasis status (p = 0.004). Furthermore, multivariate analysis indicated that FOXR2 expression was an independent prognostic factor for breast cancer patients (p = 0.035). This study first identifies that FOXR2 may be an important molecular marker for diagnosis and prognosis of breast cancer.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Modeling the spatially heterogeneous relationships between tradeoffs and synergies among ecosystem services and potential drivers considering geographic scale in Bairin Left Banner, China.

Understanding the complex relationships of tradeoffs and synergies among ecosystem services (ESs) is essential to achieve a comprehensive, coordinated, and sustainable development for human well-being. However, the quantitative measurement for the properties and intensities within these relationships as well as the deeper exploration of its formation mechanism from a spatial-explicit perspective is still a challenge. In this study, a comprehensive and general methodology was developed to quantitatively illustrate the intensities of tradeoffs/synergies among pairwise ESs and explore the spatially heterogeneous relationships between these relations and several socio-ecological drivers, integrating InVEST, geographical detector and multi-scale geographically weighted regression (MGWR) methods. The results indicated that (1) the properties and intensities of tradeoffs/synergies among various ESs varied greatly over space and presented significant clustered distribution patterns; (2) different relations between ESs were dominated by diverse drivers and the combined effects from multiple factors were stronger than any single one within this process. The tradeoffs/synergies between soil conservation and other ESs were mainly affected by geomorphological drivers including elevation and slope, while relations involved habitat quality could be attributed to vegetation and climate drivers such as precipitation and vegetation fractional cover. The relationships among ESs were more susceptible to topographic and anthropogenic drivers when concerning the carbon storage service; (3) compared to global ordinary least squares and local geographically weighted regression (GWR), the MGWR obtained better performance in explaining relationships between tradeoffs/synergies among ESs and potential drivers by operating different spatial scales. Accordingly, several spatially targeted ecological measures were proposed and recommended to reduce ESs tradeoffs and ultimately achieve better synergies. This research could enrich the methods in revealing the complex evolvement mechanism behind the tradeoffs/synergies among ESs and the proposed framework also provided a new perspective in the field of ESs tradeoffs/synergies studies and might be valuable guidance for other regions worldwide.

Erianin: A phytoestrogen with therapeutic potential.

Erianin, a phytoestrogen with therapeutic potential, is one of the major active components of Dendrobll caulis. Erianin has a variety of pharmacological effects, such as anti-tumor, anti-inflammatory, anti-diabetic retinopathy, anti-psoriasis, and antibacterial effects. Especially, in regard to the anti-tumor effect of erianin, the underlying molecular mechanism has been partly clarified. In fact, the numerous pharmacological actions of erianin are complex and interrelated, mainly including ERK1/2, PI3K/Akt, JAK2/STAT3, HIF-1α/PD-L1, PPT1/mTOR, JNK/c-Jun, and p38 MAPK signal pathway. However, on account of the poor water solubility and the low bioavailability of erianin, greatly affected and limited its further development and application. And it is worthwhile and meaningful to explore more extensive pharmacological effects and mechanisms, clarify pharmacokinetics, and synthesize the derivatives of erianin. Conclusively, in this paper, the pharmacological effects of erianin and its mechanism, pharmacokinetics, and derivatives studies were reviewed, in order to provide a reference for the development and application of erianin.

Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro.

OBJECTIVE: To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs. METHODS: The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined. RESULTS: For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs. CONCLUSION: Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].

LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940/KLLN axis.

Long noncoding RNAs (lncRNAs) play crucial regulatory roles in the progression of various cancers. However, the functional roles of lncRNAs in breast cancer remain unclear. In this study, we investigated the functional role of a novel long noncoding RNA SEMA3B-AS1 (lncRNA SEAS1) in breast cancer progression and the underlying mechanisms. SEAS1 was downregulated in the triple-negative breast cancer (TNBC) tissues compared with the para-carcinoma tissues, which was associated with poor prognosis of TNBC patients. We demonstrated that SEAS1 knockdown significantly increased the proliferation, migration, and invasion of TNBC cell lines, whereas SEAS1 overexpression reversed these effects. Bioinformatics analysis demonstrated that microRNA (miR)-3940-3p was a potential target of SEAS1. Mechanistically, RNA immunoprecipitation (RIP) and luciferase reporter assays confirmed that lncRNA SEMA3B-AS1 acted as sponge for miR-3940-3p, preventing the degradation of its target gene KLLN, which acts as a tumor-inhibiter in TNBC. Moreover, RNA pulldown, mass spectrometry, ChIP, and luciferase reporter assays confirmed that SMAD3 directly interacted with the promoter of SEAS1 and suppressed its transcription, thereby promoting TNBC progression. The clinical samples of TNBC confirmed SEAS1 was correlated inversely with lymphatic and distant metastasis. In conclusion, our findings reveal a novel pathway for TNBC progression via SMAD3/lncRNA SEAS1/miR-3940-3p/KLLN axis, and suggest that SEAS1 may serve as a potential biomarker and therapeutic target for TNBC.

Metaplastic breast cancer: Treatment and prognosis by molecular subtype.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast. However, the effect of molecular subtype on treatment and prognosis of MBC remains unclear. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to analyze patients with MBC between 2010 and 2016. Molecular subtype was stratified to TN group (ER and PR-/HER2-), HER2 group (ER and PR-/HER2+, ER/PR+ and HER2+), and HR group (ER/PR+ and HER2-). The breast cancer-specific survival (BCSS) differences were estimated using multivariate Cox regression model and Kaplan-Meier curves. RESULTS: We included 1665 patients with median follow-up time of 27 months (range 0-83 months). 1154 (69.3%), 65 (3.9%), and 446 (26.8%) patients presented in TN group, HER2 group, and HR group, respectively. On multivariate Cox analysis, the prognosis was related to age, tumor size, regional node metastasis, and surgery. Molecular subtype remained no impact on BCSS. Radiotherapy (RT) was associated with better prognosis. Patients cannot benefit from chemotherapy. In Kaplan-Meier curve, triple-negative (P = 0.047) and HR-positive (P = 0.006) patients receiving RT had a superior BCSS than that not RT. HER2-positive patients cannot benefit from RT. However, adjusted Kaplan-Meier survival model showed that triple-negative (P = 0.019) but not HER2-positive (P = 0.575) or HR-positive (P = 0.574) patients receiving RT had a superior BCSS than that not RT. CONCLUSIONS: Molecular subtype is not associated with the better prognosis of MBC. Patients could benefit from RT. However, triple-negative but not HR-positive or HER2-positive patients have superior survival after receiving RT.

Ecological quality and its relationships with human activities in China-Laos railway economic belt.

Regional ecological quality is largely affected by human activities, which restricts the sustainable development of regional economy. Taking the China-Laos railway economic belt as an example, we investigated the effects of human activities on ecological quality. The remote sensing images of 1999, 2009 and 2019 were selected to calculate remote sensing ecological index (RSEI). Spatial autocorrelation statistics and local G statistics were used to explore the spatial-temporal variations of ecological quality in the study area. Combined with the population density in the same period, a geographically weighted regression model was constructed to quantitatively analyze the ecological effects of different human activity intensities in the study area. The results showed that the ecological quality in the study area presented a trend of increasing firstly and then decreasing later from 1999 to 2019, and that the mean value of RSEI varied from 0.645 (1999) to 0.738 (2009) and then decreasing to 0.721 in 2019. Specially, the ecological quality fluctuated more apparently in the midlands. The results of fitting population density and ecological quality based on geographical weighted regression model (GWR) were significantly better than that of least square method. R2 of different periods based on GWR was higher than 0.7 and the fitting effect was stable. The fitting degree of GWR in 2019 was the best (R2 was 0.785), and R2 in 1999 and 2009 were 0.726 and 0.754, respectively. The ecological quality along the China-Laos railway south area (such as Vientiane) was more sensitive to human activities, with most of these places belonged to moderately sensitive regions. For the highly, moderately and lowly ecological sensitive regions, every 10, 100, 1000-fold increases in population density would lead to a decrease of 0.2, 0.4 and 0.6 to the mean value of RSEI in turn. The development of economic belt would increase population density. During the planning and layout of economic belt, human activities should be controlled to avoid the deterioration of ecological quality in the potential and current sensitive regions.

Water-soluble alkaloids extracted from Aconiti Radix lateralis praeparata protect against chronic heart failure in rats via a calcium signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics. METHODS: Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure. RESULTS: AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and ß-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a. CONCLUSIONS: AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a.

Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein.

Case series of COVID-19 patients from the Qinghai-Tibetan Plateau Area in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious infection caused by the new coronavirus severe acute respiratory syndrome coronavirus 2. The disease was first identified in December 2019 and has caused significant morbidity and mortality worldwide. AIM: To explore the clinical characteristics and treatments for COVID-19 in the Qinghai-Tibetan Plateau Area in China. METHODS: We retrospectively analyzed the blood cell counts (neutrophils and lymphocytes), blood gas analysis, and thoracic computed tomography changes of patients from Qinghai Province before, during, and after treatment (January 23, 2020 to February 21, 2020). In addition, we summarized and analyzed the information of critical patients. All data were analyzed using SPSS 17.0 (SPSS Inc., Chicago, IL, United States). The quantitative and count variables are represented as the mean ± SD and n (%), respectively. RESULTS: The main symptoms and signs of patients with COVID-19 were fever, dry cough, cough with phlegm, difficulty breathing, and respiratory distress with a respiration rate ≥ 30 times/min, finger oxygen saturation ≤ 93% in the resting state, and oxygenation index less than 200 but greater than 100 (after altitude correction). Eighteen patients with COVID-19, of whom three were critical, and the others were in a mild condition, were included. The main manifestations included fever, dry cough, and fatigue. Three patients developed difficulty breathing and had a fever. They were eventually cured and discharged. Adjuvant examinations showed one case with reduced white cell count (6%) (< 4 × 109/L), six with reduced count of lymphocytes (33%) (< 0.8 × 109/L), and one with abnormal blood glucose level. All 18 patients were discharged, and no death occurred. CONCLUSION: Our findings provide critical insight into assessing the clinical diagnosis and treatment for COVID-19 in the Tibetan plateau area.

Combination of serum lactate dehydrogenase and sex is predictive of severe disease in patients with COVID-19.

Elevated serum lactate dehydrogenase (LDH) was commonly reported in COVID-19 patients. However, the relationship between LDH and the incidence of severe cases has not been characterized in those patients.We retrospectively analyzed the characteristics of patients from a designated isolation medical center for COVID-19 patients diagnosed from February 6 to March 1. Variables accessed within 48 hours on admission were compared between patients with and without the severe disease. Logistic model analyses were performed to examine the prognostic value of LDH for predicting severe disease.52 (28.6%) patients later developed severe disease. Comparing to non-severe cases, severe cases had a higher level of serum LDH (321.85 ±â€Š186.24 vs 647.35 ±â€Š424.26, P < .001), neutrophils (5.42 ±â€Š3.26 vs 9.19 ±â€Š6.33, P < .001), and C-reactive protein (38.63 ±â€Š43.14 vs 83.20 ±â€Š51.01, P < .001). The patients with severe disease tended to be male (44.6% vs 80.8%, P < .001), lower level of serum albumin (31.41 ±â€Š6.20 vs 27.18 ±â€Š5.74, P < .001), and SpO2 (96.30 ±â€Š2.75 vs 92.37 ±â€Š8.29, P < .001). In the multivariate analysis model, LDH and sex remained independent risk factors for severe disease. The serum LDH predicted severe cases with an area under the curve (AUC) of 0.7999. A combination of serum LDH and sex predicted severe cases with an AUC of 0.849. A combination of serum LDH accessed on admission and sex had a better predictive performance than the serum LDH (P = .0238).Serum LDH on admission combined with sex is independently associated with severe disease in COVID-19.

Relationship between expression of vascular endothelial growth factor and cervical lymph node metastasis in papillary thyroid cancer: A meta-analysis.

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor (VEGF) and lymph node metastasis (LNM) in papillary thyroid cancer (PTC). VEGF-related articles that had been published until August 2016 were searched from the PubMed, EMBASE, and MEDLINE to identify the risk factors of LNM in PTC. RevMan 5.3 software was used for the meta-analysis. Finally, 9 articles met the inclusion criteria and were included in our meta-analysis. LNM was found to be present in 176 of 318 patients (57.8%) with high VEGF expression and in 71 of 159 patients (47.0%) with low VEGF expression. The overall OR was 2.81 (95% confidence interval, 1.49-5.29). LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression (P=0.001). Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients' country of origin and the detection methods. Our meta- analysis concluded that the VEGF protein expression is associated with LNM in PTC.

[Pax2 expression in children with steroid-resistant primary nephrotic syndrome].

OBJECTIVE: To investigate the difference of Pax2 and P53 expressions in children with primary nephritic syndrome (PNS) and the effect of Pax2 on glucocorsteroid (GC)-resistance. METHODS: Renal Pax2 and P53 expressions in children with PNS (40 patients) were detected by immunohistochemistry. A semiquantitative score was used to evaluate the injury degree of the glomeruli and the tubulointerstitium, and correlation analysis was done among Pax2, P53 and pathologic score. RESULTS: Pax2 and P53 expressions were not found in the control group. Pax2 expression of renal tubule epithelia exsisted in children with PNS and there was weak or no expression of Pax2 in the podocytes. Pax2 expressions in the proximal tubule and the distal tubule in the GC-resistant group were more intense than those in the GC-intensive group (P <0.01). The more the Pax2 expression in the tubule, the more abnormal structure such as dilation and atrophy. Pax2 expression in the tubule epithelia was positively correlated with pathologic score of tubulointerstitium (P < 0.01). There was no P53 expression in the GC-intensive group, but there exsisted P53 expression in parts of the patients from the GC-resistant group, mainly distributing in the renal tubular epithelia. P53 expression was positively correlated with P53 expression and the pathologic score of tubulointerstitium (P < 0.01). CONCLUSION: Over-expression of Pax2 in the renal tubule epithelia may improve P53 expression to a certain degree, which may aggravate the lesion of the renal tubule. It may be one of the mechanisms resulting in GC-resistant in children with PNS.

[Effect of glucocorticoid on glucocorticoid-resistant children with primary nephrotic syndrome].

OBJECTIVE: Glucocorticoid (GC) is the first therapeutic choice of primary nephrotic syndrome (PNS). The response to GC treatment is an important indicator for the outcome of PNS children. Children with GC-resistant PNS present with incomplete or no response to GC, and may herald the progression to end-stage renal failure. However, the detailed mechanism of GC-resistance or GC-sensitive effect in these PNS children has not been clearly elucidated. The previous study by the authors indicated that there was increased expression of GR beta in PBMCs in GC-resistant children with PNS, and the over expression of GR beta resulted in GC resistance via influencing the ability of GR alpha nuclear translocation. To elucidate the relationship between GR beta expression in renal and in PBMCs and the effect of glucocorticoid on glucocorticoid-resistance children with PNS, the expression of GR alpha and GR beta in renal tissue and in PBMCs were detected by immunohistochemistry. METHODS: Forty children with PNS were divided into two groups, GC-resistant group(20) and GC-sensitive group(20), the expression of GR alpha and GR beta in renal intrinsic cells and in PBMCs were measured with the immunohistochemistry technique. A semiquantitative score was used to evaluate the injury degree of the glomeruli and tubulointerstitium. RESULTS: Compared with GC-sensitive group, the glomerular pathologic scores (6.91 +/- 1.98) and renal tubular pathologic scores (7.12 +/- 1.62) in GC- resistant group were significantly different (P < 0.01, respectively). GR alpha expressions of renal tissue and PBMCs were higher in the control group (58.3 +/- 2.6, 59.1 +/- 7.2) than those in the GC-sensitive group (40.2 +/- 7.2 and 36.6 +/- 5.1, P < 0.01, respectively) and GC-resistant group (35.0 +/- 8.2 and 36.4 +/- 6.6, P < 0.01, respectively). GR beta expressions of renal tissue and PBMCs were higher in the GC-resistant group (13.8 +/- 3.0 and 12.1 +/- 4.1) and in the GC-sensitive group (6.5 +/- 1.9 and 5.9 +/- 1.0) than that in control group (2.3 +/- 0.4 and 3.2 +/- 1.1, P < 0.01, respectively). GR beta expressions in renal tissue and PBMCs were higher in the GC-resistant group than that in the GC-sensitive group (P < 0.01). Compared with control group, GR beta expressions in PBMCs and in renal tissue were lower than those in mild renal lesion group (5.4 +/- 2.8, 6.46 +/- 2.50), midmedium renal lesion group (8.7 +/- 2.4 and 11.4 +/- 3.7) and (17.1 +/- 0.4 and 18.7 +/- 0.7) in severe renal lesion group (F = 5.8, 15.6, P < 0.01, respectively). GR beta expression of PBMCs had a positive correlation with GR beta expression of renal intrinsic cells (r = 0.651, P < 0.01). GR beta expressions by PBMCs and renal intrinsic cells were positively correlated with renal pathologic scores (r = 0.579 and 0.623, P < 0.01, respectively). CONCLUSION: GC-resistant children with PNS were related to the increased GR beta expression in PBMCs and renal intrinsic cells. There was no correlation between the GR alpha expressions in PBMCs and in renal intrinsic cells. Increased GR beta expression might decrease the effect of GC via inhibiting the activity of GR alpha.