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Streptococcus pneumoniae is a common diplococcus pathogen found worldwide. The characterization of predominant serotypes, drug resistance, and virulence genes of S. pneumoniae isolates prevailing in different areas and countries is clinically important for choice of antibiotics and improvement of vaccines. In this study, pneumonia (78.7%) and meningitis (37.0%) were the predominant diseases observed in the 282 (children) and 27 (adults) S. pneumoniae-infected patients (p < 0.05) from seven hospitals in different areas of East China. Of the 309 pneumococcal isolates, 90.3% were classified by PCR into 15 serotypes, with serotypes 19F (27.2%) and the 6A/B (19.1%) being most predominant (p < 0.05). Importantly, serotypes 15A and 15B/C combined for a total of 10.4% of the isolates, but these serotypes are not included in the 13-valent pneumococcal capsule conjugate vaccine used in China. Antimicrobial susceptibility analysis by the E-test showed that >95% of the 309 pneumococcal isolates were susceptible to moxifloxacin and levofloxacin, as well as 18.4, 85.8, and 81.6% of the isolates displayed susceptibility to penicillin, cefotaxime, and imipenem, respectively. A significant correlation between the prevalence of predominant serotypes and their penicillin resistance was observed (p < 0.05). In particular, >95% of all the pneumococcal isolates showed resistance to erythromycin and azithromycin. Of the nine detected virulence genes, the lytA, ply, hysA, and nanA were the most common with 95–100% positive rates in the 309 pneumococcal isolates, while the pavA and psaA genes displayed a significant correlation with pneumococcal bacteremia and meningitis (p < 0.05). Overall, our data suggested that the predominant serotypes, drug resistance, and virulence genes of the S. pneumoniae isolates prevailing in East China are distinct from those observed in other areas of China and adjacent countries.

Abstract This study aimed to explore whether APOC1 expression has a function in the biological behavior of clear cell renal cell carcinoma (ccRCC) cells and its possible mechanism. Bioinformatics analysis of data TCGA and OnComine was conducted to explore the expression pattern and prognostic value of APOC1, as well as the relationship between APOC1 expression and clinical indicators. Loss‐ and gain‐ of APOC1 function assays were carried out to assess the biological functions of APOC1. Western blotting was applied to detect protein expression. We revealed that APOC1 was upregulated in ccRCC tissues. APOC1 expression was related to gender, grade, pathologic‐T, pathologic‐stage, and pathologic‐M in patients with ccRCC. Meanwhile, Kaplan–Meier analysis evidenced that the high APOC1 expression indicated unfavorable outcomes of ccRCC. Functional experiments in vitro revealed that upregulation of APOC1 in UT33A cells promoted cell proliferation, invasion, and migration, while downregulation of APOC1 in 786‐O cells had the opposite effect. Furthermore, epithelial mesenchymal transition (EMT) was activated in cells with upregulated APOC1 but inhibited in cells with down‐regulated APOC1. Collectively, our data suggested that APOC1 was overexpressed in ccRCC cells and promoted the malignant biological behaviors and EMT of ccRCC cells.

Purpose: We studied the expression of urotensin II (UII) and its relationships with markers of pyroptosis in preeclampsia. Methods: 48 pregnant subjects were recruited consisting of 28 severe preeclampsia pregnancies (SPE) and 20 healthy pregnancies. We detected expressions of UII and markers of pyroptosis such as NLR-family pyrin domain (PYD)-containing 3 (NLRP-3), caspase-1/4/5, interleukin-1β (IL-1β), and gasdermin D (GSDMD) in placentas of patients with SPE and healthy pregnancies. Results: SPE group have higher expression of UII and NLRP-3, caspase-1, interleukin-1β (IL-1β), and GSDMD than that normal controls by IHC, real-time PCR, and western blot. IHC analysis manifests that the expressions of UII and pyroptosis-related molecules are mainly located in the placental cytotrophoblasts. Expressions of UII mRNA and protein are significantly positively correlated with pyroptosis marker such as NLRP3, caspase-1, GSDMD mRNA and protein by Pearson correlation analysis. Moreover, UII, NLRP-3, caspase-1, interleukin-1β (IL-1β), and GSDMD are positively related with systolic blood pressure, meanwhile caspase-1 and GSDMD are positively correlated with urine protein in SPE patients. We firstly verify that UII has a positive correlation with pyroptosis markers in placentas of preeclampsia patients; besides, pyroptosis-related proteins are positively correlated with systolic blood pressure and urine protein in patients with severe preeclampsia.

AIM:To find out the pathogenesis of dry eye disease(DED)and the possible mechanisms of available effective treatments.METHOD:Here we employed a non-targeted technology, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UHPLC-Q-TOF-MS), to investigate metabolic characterizations for tear samples from 18 patients with DED upon drug or acupuncture treatment. RESULTS:A total of 190 named metabolites were identified, which presented so far the broadest tear metabolome. Further analysis indicated a significantly distinct metabolomics profile among all patients, but very subtle metabolic differences upon drug or acupuncture treatment. On one hand, only six significantly changed metabolites were determined after drug treatment, five of which including inosine, monopalmitin, urate, propionylcarnitine, and nicotinamide were all increased and involved in inflammatory responses. On the other hand, merely four metabolites including alanine, serine, and homoserine were found to be significantly different. Further pathway analysis of those six and four significantly changed metabolites revealed that only one pathway, aminoacyl-tRNA biosynthesis was significantly influenced in acupuncture-treated patients, which were highly associated with the cause of the disease. The results here indicated acupuncture treatment may address the cause rather than the symptoms for dry eye disease, displaying partially better compared with drug treatment.CONCLUSION: Collectively, this work extended our understanding on the key regulatory elements or pathways involved in the potential mechanisms of available effective treatments, and would be useful for providing novel potential targets and therapeutic strategies for DED.

Abstract The role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

Thin structural elements such as large-scale covering plates of aerospace protection structures and vertical stabilizers of aircraft are strongly influenced by gravity (and/or acceleration); thus, exploring how the mechanical behaviors of such structures are affected by gravitational field is necessary. Built upon a zigzag displacement model, this study establishes a three-dimensional vibration theory for ultralight cellular-cored sandwich plates subjected to linearly varying in-plane distributed loads (due to, e.g., hyper gravity or acceleration), with the cross-section rotation angle induced by face sheet shearing accounted for. For selected boundary conditions, the theory enables quantifying the influence of core type (e.g., close-celled metal foams, triangular corrugated metal plates, and metal hexagonal honeycombs) on fundamental frequencies of the sandwich plates. For validation, three-dimensional finite element simulations are carried out, with good agreement achieved between theoretical predictions and simulation results. The validated theory is subsequently employed to evaluate how the geometric parameters of metal sandwich core and the mixture of metal cores and composite face sheets influence the fundamental frequencies. Triangular corrugated sandwich plate possesses the highest fundamental frequency, irrespective of boundary conditions. For each type of sandwich plate considered, the presence of in-plane distributed loads significantly affects its fundamental frequencies and modal shapes.

Superparamagnetic iron oxide nanoparticles (SPIONs) are commonly used as magnetic resonance imaging (MRI) probes/contrast agents in clinical diagnosis because they can significantly improve the sensitivity of MRI. Polymers including natural and synthetic polymers with good biosafety and abundant surface groups are ideal surface coating for SPIONs to overcome their drawbacks such as poor colloidal stability, low relaxivity, and lack of functionality. Several SPIONs' structural properties such as crystal shape and size, charge, shell thickness, and cluster determine their relaxivity, biosafety, and in vivo imaging effect. Therefore, the rational design of SPIONs probes must explore the relationship between polymer structure and SPION properties. In this review, key structural properties of polymers such as surface groups, molecular weight, hydrophilicity, and grafting density are discussed for their effects on key properties of SPIONs. Additionally, some special polysaccharides, polypeptides, and antibodies can be used as targeting molecules to improve the imaging specificity of SPIONs, which is also briefly discussed in this review. [ABSTRACT FROM AUTHOR]

AIM: To systematically evaluate the effect of anti-VEGF and laser treatment on type 1 retinopathy of prematurity(ROP). METHODS: Randomized controlled trials(RCTs)comparing the efficacy of anti-VEGF and laser therapy for type 1 ROP were retrieved from PubMed, EMbase, CBM, The Cochrane Library, WanFang Data, CNKI and VIP databases. The search time was from the establishment of the databases to January 2020. The data were extracted according to the inclusion and exclusion criteria. After quality evaluation, then Meta-analysis was made by Revman 5.3 software. RESULTS: A total of 6 RCTs were included. The results of Meta-analysis showed that: there was no statistical difference in the recurrence incidence between anti-VEGF group and laser group [RR=0.94, 95% CI (0.17-5.23), P=0.94]; subgroup analysis revealed a statistical significant in zone Ⅰ[RR=0.17, 95% CI (0.05-0.62), P=0.007], while zone II has no statistical significant [RR=2.20, 95% CI (0.07-73.48), P=0.66]. Compared with the laser group, the retreatment rate [RR=2.36, 95% CI (0.70-7.99), P=0.17]was statistical significant; There was no significant difference in subgroup analysis of zone Ⅰ[RR=0.33, 95% CI (0.01-7.50), P=0.49], while the difference in zone Ⅱ[RR=13, 95% CI (1.84-92.01), P=0.01] was statistically significant. There was no significant difference in the incidence of adverse reactions between the two groups[RR=0.87,95% CI(0.54-1.40),P=0.57]. CONCLUSION: Laser and anti-VEGF treatment are equally effective. Anti-VEGF has less recurrence rate in zone Ⅰ while laser is more effective in the retreatment rate in zone Ⅱ.

Abstract Background Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, including dementia, insomnia and depression. However, the mechanisms underlying SZRD’s improvement in cognitive function remain unclear. In this study, we examined SZRD’s effect on APP/PS1 transgenic mice and mechanisms associated with SZRD’s action in alleviating neuroinflammation and improving synaptic plasticity. Methods The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/day, in L-SZRD and H-SZRD groups, respectively) for 4 weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect synaptic plasticity. ELISA was applied to assess the expression levels of Aβ1−40 and Aβ1−42 in the hippocampus of mice. Western blot (WB) was employed to test the protein expression level of Aβ1−42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect the involvement of JAK2/STAT3 pathway. Besides, we examined the serum and hippocampal contents of IL-1β, IL-6 and TNF-α through ELISA. Results Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (P

Introduction: Vascular calcification (VC), with the mechanisms remaining unclear, is closely related with dialysis patients’ cardiovascular mortality and all-cause mortality. Irisin is a newly identified myokine. This study aims to evaluate the serum irisin levels of peritoneal dialysis (PD) patients and their relationship with VC. Methods: This cross-sectional study enrolled stable PD patients in Peking University Third Hospital who were followed for >6 months. We used plain X-ray films of abdomen to quantitatively evaluate VC of abdominal aorta. VC was evaluated by abdominal aortic calcification (AAC) scores, and PD patients were divided into the high AAC score group (AAC score ≥4) and the low AAC score group (AAC score 2.54 mmol/L) rate, serum ultrasensitive C reactive protein, and AAC scores were significantly higher in the high AAC score group than those of the low AAC score group (p < 0.05). The high AAC score group had lower diastolic blood pressure, serum albumin, and serum carbon dioxide combining power compared with the low AAC score group (p < 0.05). Serum irisin levels of PD patients with a high AAC score were significantly lower than those of PD patients with a low AAC score (109.7 ± 13.1 ng/mL vs. 115.9 ± 10.1 ng/mL, p = 0.010). The multivariate logistic regression analyses showed that serum irisin, diabetic mellitus, serum ultrasensitive C reactive protein, and age were independent factors influencing the occurrence of VC in PD patients. Conclusion: Our results are the first to provide a clinical evidence of the association between serum irisin and abdominal aortic calcification in PD patients. Lower irisin levels, diabetic mellitus, higher serum ultrasensitive C reactive protein, and older age could be potential predictive factors for VC in PD patients.

Background: Damp-heat jaundice syndrome (DHJS) is a diagnostic model of traditional Chinese medicine (TCM) that refers to jaundice caused by damp-heat pathogen invasion. DHJS is the most common clinical manifestation of TCM, with yellow skin, yellow eyes and anorexia. ZhiziBaipi Decoction (ZBD) is a classic TCM formula that is effective at treating DHJS and various liver diseases. However, the effective components of ZBD in the context of DHJS and the underlying mechanism are unclear.Purpose: This study of ZBD using the DHJS rat model aimed to elucidate the pathobiology of DHJS and the metabolic targets of therapeutic ZBD, construct the network relationship between the components of ZBD and endogenous biomarkers, and clarify the underlying mechanism of ZBD in preventing and treating DHJS.Methods: Using chinmedomics as the core strategy, an animal model was generated, and the therapeutic effect of ZBD was evaluated based on behavioral, histopathological and biochemical indicators. Metabonomics tools were used to identify biomarkers of DHJS, TCM-based serum pharmacochemistry was used to analyze the effective constituents of ZBD, and chinmedomics technology was used to identify ZBD components highly related to DHJS biomarkers.Results: A total of 42 biomarkers were preliminarily identified, and ZBD significantly affected the levels of 29 of these biomarkers. A total of 59 compounds in ZBD were characterized in vivo. According to chinmedomics analysis, the highly correlated components found in blood were isoformononetin, 3-O-feruloylquinic acid, glycyrrhizic acid, oxyberberine, obaculactone and five metabolites.Conclusions: Chinmedomics combined with UPLC-MS/MS was used to study the targets and effective constituents of ZBD for the treatment of DHJS.

This study explores the relationship between China's reproductive health policy and the rate of return on urban education by using fixed-effect, mediating-effect, and breakpoint regression models. The authors study the impact of China's reproductive health policy on individual years of education, income, return on education, the impact of reproductive health policy on population health, and overall human development. The empirical results show that the implementation of China's reproductive health policy can improve the rate of return on urban education and increase the average length of education of urban residents by 0.29 years. Under the breakpoint regression model, the educational return rate of urban residents is approximately 12.2% higher than the ordinary least squares (OLS) estimate. China's reproductive health policy has significantly promoted the return rate of residents' education and simultaneously effectively promoted the income of urban residents. With the development of the economy, the government should properly adjust reproductive health policies and improve the population health rate so that the adjustment of reproductive health policies can comprehensively promote the health of residents of all ages. The overall relaxation of family restrictions on children's human capital investment will likely reduce the negative impact of the overall relaxation of family planning, not only improving the health of the population but also contributing to sustainable economic development.

Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.

Diabetic retinopathy is one of the serious complications of diabetes, which the leading causes of blindness worldwide, and its irreversibility renders the existing treatment methods unsatisfactory. Early detection and timely intervention can effectively reduce the damage caused by diabetic retinopathy. Metabolomics is a branch of systems biology and a powerful tool for studying pathophysiological processes, which can help identify the characteristic metabolic changes marking the progression of diabetic retinopathy, discover potential biomarkers to inform clinical diagnosis and treatment. This review provides an update on the known metabolomics biomarkers of diabetic retinopathy. Through comprehensive analysis of biomarkers, we found that the arginine biosynthesis is closely related to diabetic retinopathy. Meanwhile, creatine, a metabolite with arginine as a precursor, has attracted our attention due to its important correlation with diabetic retinopathy. We discuss the possibility of the arginine-creatine metabolic pathway as a therapeutic strategy for diabetic retinopathy.