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ObjectiveCarnation is a plant that holds high value in terms of its edibility, medicinal properties, and ornamental appeal. Creating no sense he aim of this study was to evaluate the antioxidant and antitumor properties of extracts derived from various parts of the carnation plant. Metabolomics technology was employed to identify the primary chemical constituents.MethodsInitially, we measured the total phenolic and total flavonoid contents in carnation roots, stems, leaves, and flowers, followed by assessing the antioxidant and anti-tumor capabilities of each component using diverse experimental methods. Subsequently, UPLC-MS/MS was employed to identify metabolites in different parts of carnation and investigate their roles in antioxidant and anti-tumor activities.ResultsMention numerical value- for better underatnding- Results of the study indicated that the methanol extract obtained from carnation flowers and roots exhibited superior antioxidant capacity compared to that from the stems and leaves. This disparity may be attributed to the abundance of polyphenols, flavonoids, and antioxidants present in the flowers, including methyl ferulate and luteolin-4’-O-glucoside. Furthermore, the significant presence of the anthraquinone compound rhein-8-O-glucoside in carnation roots may contribute to their enhanced antioxidant properties. Ten distinct compounds were isolated and recognized in carnation flowers, with Isoorientin 2”-O-rhamnoside and Kurarinone demonstrating notable antioxidant activity and binding affinity to SOD1 and SOD3, as validated through antioxidant screening and molecular docking.ConclusionOverall, the findings from this study have expanded our knowledge of the phytochemical composition across different anatomical regions of the carnation plant, providing valuable insights for its holistic utilization.

Calcium (Ca2+) is a second messenger for many signal pathways, and changes in intracellular Ca2+ concentration ([Ca2+]i) are an important signaling mechanism in the oocyte maturation, activation, fertilization, function regulation of granulosa and cumulus cells and offspring development. Ca2+ oscillations occur during oocyte maturation and fertilization, which are maintained by Ca2+ stores and extracellular Ca2+ ([Ca2+]e). Abnormalities in Ca2+ signaling can affect the release of the first polar body, the first meiotic division, and chromosome and spindle morphology. Well-studied aspects of Ca2+ signaling in the oocyte are oocyte activation and fertilization. Oocyte activation, driven by sperm-specific phospholipase PLCζ, is initiated by concerted intracellular patterns of Ca2+ release, termed Ca2+ oscillations. Ca2+ oscillations persist for a long time during fertilization and are coordinately engaged by a variety of Ca2+ channels, pumps, regulatory proteins and their partners. Calcium signaling also regulates granulosa and cumulus cells’ function, which further affects oocyte maturation and fertilization outcome. Clinically, there are several physical and chemical options for treating fertilization failure through oocyte activation. Additionally, various exogenous compounds or drugs can cause ovarian dysfunction and female infertility by inducing abnormal Ca2+ signaling or Ca2+ dyshomeostasis in oocytes and granulosa cells. Therefore, the reproductive health risks caused by adverse stresses should arouse our attention. This review will systematically summarize the latest research progress on the aforementioned aspects and propose further research directions on calcium signaling in female reproduction.

BackgroundPsychological distress is highly prevalent and has a severe impact on the quality of life among breast cancer survivors. This type of distress is associated with cognitive failure. However, previous studies have focused solely on the total scale scores of these two concepts while ignoring the unique relationship between specific components. In the present study, we utilized network analysis to explore the relationship between psychological distress and cognitive failure in breast cancer survivors.MethodsThe network analysis approach was adopted to estimate the regularized partial correlation network in a cross-sectional sample of 409 breast cancer survivors. All participants were assessed using the Depression Anxiety Stress Scale and the Cognitive Failure Questionnaire. The Gaussian Graphical Model was employed to estimate the network, centrality indices, and edge weights, providing a description of the characteristics of the network.ResultsThe results indicated that anxiety–stress and depression–stress were the strongest edges in the community of psychological distress. Distractibility–memory was the strongest edge in the community of cognitive failure. Distractibility and memory were the most central nodes, with the highest expected influence in the network. Depression and motor coordination acted as important bridge nodes with the highest bridge expected influence.ConclusionDistractibility and memory in cognitive failure played important roles in activating and maintaining the relationship network. Motor coordination was identified as the crucial pathway for the impact of cognitive failure on psychological distress. Interventions targeting these specific issues might be more effective in improving cognitive failure and reducing psychological distress among breast cancer survivors.

Background/objectiveWhile Physical Literacy has been highlighted as a determinant in health in recent study, there is a dearth of studies examining its effect on physical health, and there is a little in the way of empirical data linking Physical Literacy to health outcomes. Accordingly, further empirical research is needed to clarify the mechanisms by which Physical Literacy affects physical health. The purpose of this study was to verify the role of medical students’ Physical Literacy on Health-related quality of life as well as to explore the chain mediating role of Physical Activity and Subjective Well-being in it.MethodsThis study utilized a cross-sectional study design. The Physical Literacy, Health-related Quality of Life, Physical Activity ratings, and Subjective Well-being of students at Shanxi Medical University were all measured using an online survey administered in September 2023. A total of 1968 valid questionnaires were returned. First, descriptive statistics and correlation analysis were performed using SPSS software. Second, PROCESS was used to test the mediating role. Finally, we used structural equation modeling (Amos) to test the model fit.ResultsThere is a significant correlation between all variables. After mediation effects analysis, we found that there were three indirect pathways of physical literacy on health-related quality of life: a single mediating effect of physical activity, a single mediating effect of subjective well-being, and a chained mediating effect of physical activity-subjective well-being.ConclusionThe mediating role of physical activity and subjective well-being on the relationship between physical literacy and health-related quality of life has been confirmed. Our research results support the integration of physical literacy into physical education teaching and the modification of curriculum content by physical education teachers as part of efforts to enhance students’ physical activity levels, subjective well-being levels, and overall health. This study provides a new perspective for intervention in improving the health of medical students.

The significance of point-of-care testing (POCT) in early clinical diagnosis and personalized patient care is increasingly recognized as a crucial tool in reducing disease outbreaks and improving patient survival rates. Within the realm of POCT, biosensors utilizing magnetic nanoparticles (MNPs) have emerged as a subject of substantial interest. This review aims to provide a comprehensive evaluation of the current landscape of POCT, emphasizing its growing significance within clinical practice. Subsequently, the current status of the combination of MNPs in the Biological detection has been presented. Furthermore, it delves into the specific domain of MNP-based biosensors, assessing their potential impact on POCT. By combining existing research and spotlighting pivotal discoveries, this review enhances our comprehension of the advancements and promising prospects offered by MNP-based biosensors in the context of POCT. It seeks to facilitate informed decision-making among healthcare professionals and researchers while also promoting further exploration in this promising field of study.

Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile, there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C. amabile, including botanical characteristics, geographical distribution, traditional applications, phytochemistry, pharmacological activities, toxicology, and clinical applications. The results have shown that C. amabile has been traditionally used for medicinal, edible, and ornamental purposes in China for many centuries. The whole plant, root, and leaf of C. amabile are used by different ethnic groups, such as Lisu, Bai, Naxi, Yi, Jinuo, and Han, to treat malaria, hepatitis, dysentery, leucorrhea, tuberculosis cough, fracture, joint dislocation, trauma bleeding, and skin carbuncle abscess. A total of 47 chemical components, including alkaloids (pyrrolizidine alkaloids, PAs), sterols, organic acids, and saccharides, were isolated from C. amabile. Pharmacological studies show that the chemical extracts of C. amabile possess various biological activities, such as anti-inflammatory, anti-tumor, anti-microbial, cardiovascular effects, ganglionic action, and acetylcholinesterase inhibition. However, it is important to note that C. amabile exhibits hepatotoxicity, with its toxicity being linked to its primary PAs components. Although preliminary studies suggest potential applications in the treatment of prostate diseases and alopecia, further research is needed to validate these clinical uses. Our review highlights the traditional uses, phytochemistry, biological activity, toxicity, and clinical applications of C. amabile. It emphasizes the essential guiding role of the indigenous medicinal knowledge system in developing new drugs. Previous studies have shown that the phytochemical and pharmacological characteristics of C. amabile are significantly related to its traditional medicinal practices. Cynoglossum amabile has excellent market potential and can be further analyzed in terms of phytochemistry, pharmacology, and toxicology, which are critical for its clinical drug safety, quality evaluation, and resource development.

BackgroundThe systemic immune-inflammation index (SII) has emerged as a promising marker predicting the prognosis of some cancers, while its role in urothelial carcinoma (UC) remains uncertain, especially in upper urinary tract urothelial carcinoma (UTUC). This meta-analysis aimed to investigate the association of SII with the prognosis of UC and the response to intravesical Bacillus Calmette-Guerin (BCG) therapy of non-muscle invasive bladder cancer (NMIBC).MethodsA systematic search in PubMed, Embase, Web of Science, and the Cochrane Library was performed to identify relevant studies. The extracted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the association between SII and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) of patients with UC. Additionally, we pooled odds ratios (ORs) and 95% CIs to assess the relationship between SII and BCG response in patients with NMIBC. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity.ResultsTwenty studies comprising a total of 12,645 patients were eligible. This meta-analysis revealed that high SII levels independently increased the risk of OS (HR 1.55, 95%CI 1.25–1.92), CSS (HR 1.82, 95%CI 1.36–2.45), and RFS (HR 1.26, 95% CI 1.18–1.35) in patients with UC, including those with upper tract urothelial carcinoma. Additionally, elevated SII levels could predict a lower response to intravesical BCG treatment (OR 0.18, 95%CI 0.07–0.45) and higher disease recurrence (HR 1.61, 95%CI 1.31–1.98) in patients with NMIBC. Furthermore, elevated SII levels were positively associated with advanced age, lymphovascular invasion, hydronephrosis, and high tumor grade and stage (pT ≥ 3).ConclusionsElevated preoperative SII levels are associated with poor survival outcomes in patients with UC, as well as worse response to BCG treatment in patients with NMIBC. Therefore, SII can serve not only as an independent prognostic predictor of patients with UC but also as a guide for BCG therapy in NMIBC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023409077, identifier CRD42023409077.

Introduction:A. truncatum Bunge (Sapindaceae or formerly Aceraceae) is a tall deciduous tree native to China. Traditionally, the leaves of A. truncatum are decocted and used by Chinese Mongolians, Koreans, and Tibetans to treat skin itching, dry cracks, and other skin ailments, which indicates A. truncatum leaves may have a potential inhibitory effect on various skin inflammations.Methods: To examine the protective effect against skin inflammations of A. truncatum leaf extract (ATLE), an in vitro dermatitis model was established using sodium dodecyl sulfate (SLS)-induced HaCaT cells. The anti-inflammatory effect of ATLE was evaluated by analyzing cell viability, apoptosis, reactive oxygen species (ROS), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) levels.Results: Orthogonal experiments showed that the pretreatment with ATLE can reduce the IL-6 levels, PGE2 levels, and apoptosis increased in SLS-stimulated HaCaT cells, which indicates that ATLE has positive efficacy for dermatitis. Furthermore, three flavonoid compounds kaempferol-3-O-α-L-rhamnoside, quercetin-3-O-α-L-rhamnopyranoside, kaempferol-3,7-di-O-α-L-rhamnoside, and 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG) were isolated and identified. Among them, kaempferol-3,7-di-O-α-L-rhamnoside was isolated from this plant for the first time. These compounds have been proven to have an anti-inflammatory effect. They may contribute to the efficacy of A. truncatumin treating skin inflammation.Discussion: The results revealed that ATLE has the potential to be used as an additive in various skin care products to prevent skin inflammations and may be incorporated in formulations for topical application as a therapeutic approach against dermatitis.

Influenza A viruses (IAVs) can infect a wide variety of bird and mammal species. Their genome is characterized by 8 RNA single stranded segments. The low proofreading activity of their polymerases and the genomic reassortment between different IAVs subtypes allow them to continuously evolve, constituting a constant threat to human and animal health. In 2009, a pandemic of an IAV highlighted the importance of the swine host in IAVs adaptation between humans and birds. The swine population and the incidence of swine IAV is constantly growing. In previous studies, despite vaccination, swine IAV growth and evolution were proven in vaccinated and challenged animals. However, how vaccination can drive the evolutionary dynamics of swine IAV after coinfection with two subtypes is poorly studied. In the present study, vaccinated and nonvaccinated pigs were challenged by direct contact with H1N1 and H3N2 independent swine IAVs seeder pigs. Nasal swab samples were daily recovered and broncho-alveolar lavage fluid (BALF) was also collected at necropsy day from each pig for swine IAV detection and whole genome sequencing. In total, 39 swine IAV whole genome sequences were obtained by next generation sequencing from samples collected from both experimental groups. Subsequently, genomic, and evolutionary analyses were carried out to detect both, genomic reassortments and single nucleotide variants (SNV). Regarding the segments found per sample, the simultaneous presence of segments from both subtypes was much lower in vaccinated animals, indicating that the vaccine reduced the likelihood of genomic reassortment events. In relation to swine IAV intra-host diversity, a total of 239 and 74 SNV were detected within H1N1 and H3N2 subtypes, respectively. Different proportions of synonymous and nonsynonymous substitutions were found, indicating that vaccine may be influencing the main mechanism that shape swine IAV evolution, detecting natural, neutral, and purifying selection in the different analyzed scenarios. SNV were detected along the whole swine IAV genome with important nonsynonymous substitutions on polymerases, surface glycoproteins and nonstructural proteins, which may have an impact on virus replication, immune system escaping and virulence of virus, respectively. The present study further emphasized the vast evolutionary capacity of swine IAV, under natural infection and vaccination pressure scenarios.

Constructed wetlands (CWs) are artificial systems that use natural processes to treat wastewater containing organic pollutants. This approach has been widely applied in both developing and developed countries worldwide, providing a cost-effective method for industrial wastewater treatment and the improvement of environmental water quality. However, due to the large organic carbon inputs, CWs is produced in varying amounts of CH4 and have the potential to become an important contributor to global climate change. Subsequently, research on the mitigation of CH4 emissions by CWs is key to achieving sustainable, low-carbon dependency wastewater treatment systems. This review evaluates the current research on CH4 emissions from CWs through bibliometric analysis, summarizing the reported mechanisms of CH4 generation, transfer and oxidation in CWs. Furthermore, the important environmental factors driving CH4 generation in CW systems are summarized, including: temperature, water table position, oxidation reduction potential, and the effects of CW characteristics such as wetland type, plant species composition, substrate type, CW-coupled microbial fuel cell, oxygen supply, available carbon source, and salinity. This review provides guidance and novel perspectives for sustainable and effective CW management, as well as for future studies on CH4 reduction in CWs.

AimTo identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM).MethodsT2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values.ResultsA total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p

Esophageal cancer (EC) is recognized as one of the most common malignant tumors in the word. Based on the biological process of EC occurrence and development, exploring molecular biomarkers can provide a good guidance for predicting the risk, prognosis and treatment response of EC. Proteomics has been widely used as a technology that identifies, analyzes and quantitatively acquires the composition of all proteins in the target tissues. Proteomics characterization applied to construct a prognostic signature will help to explore effective biomarkers and discover new therapeutic targets for EC. This study showed that we established a 8 proteins risk model composed of ASNS, b-Catenin_pT41_S45, ARAF_pS299, SFRP1, Vinculin, MERIT40, BAK and Atg4B via multivariate Cox regression analysis of the proteome data in the Cancer Genome Atlas (TCGA) to predict the prognosis power of EC patients. The risk model had the best discrimination ability and could distinguish patients in the high- and low-risk groups by principal component analysis (PCA) analysis, and the high-risk patients had a poor survival status compared with the low-risk patients. It was confirmed as one independent and superior prognostic predictor by the receiver operating characteristic (ROC) curve and nomogram. K-M survival analysis was performed to investigate the relationship between the 8 proteins expressions and the overall survival. GSEA analysis showed KEGG and GO pathways enriched in the risk model, such as metabolic and cancer-related pathways. The high-risk group presented upregulation of dendritic cells resting, macrophages M2 and NK cells activated, downregulation of plasma cells, and multiple activated immune checkpoints. Most of the potential therapeutic drugs were more appropriate treatment for the low-risk patients. Through adequate analysis and verification, this 8 proteins risk model could act as a great prognostic evaluation for EC patients and provide new insight into the diagnosis and treatment of EC.

Prostate cancer is one of the most common malignant tumors in men. Pyroptosis is related to tumor immune infiltration and tumor microenvironment (TME) and has been confirmed to be related to the progression of a variety of tumors. However, the relationship between prostate cancer and pyroptosis, as well as TME and tumor immune infiltration, has not been discussed yet. We obtained and combined the RNA-seq data of prostate cancer from TCGA and GEO databases, analyzed the differential expression of pyroptosis-related genes (PRGs), and divided them into two groups according to the PRG expression level. The relationship between pyroptosis subtypes and the TME of prostate cancer was further verified, and the differential expression genes (DEGs) in the two subtypes were identified. The relationship between the DEGs and clinicopathology was explored and KEGG and GO enrichment analysis was conducted; it was found that most DEGs were enriched in immune-related pathways. Then, we randomly divided datasets into training and testing sets, performed the LASSO and multicox progression analysis, selected eight genes as prognostic signatures and used the eight genes, calculated the risk score, and then separated the entire cohort into high- and low-risk groups. The prognosis between two groups and the 1-, 3-, and 5-year ROC curves of biochemical relapse (BCR) were verified in training, testing, and the entire cohort, respectively. The TME, CSC index, mutation, and drug susceptibility were also discussed.

Diabetes mellitus (DM), an emerging chronic epidemic, contributes to mortality and morbidity around the world. Diabetic cardiac autonomic neuropathy (DCAN) is one of the most common complications associated with DM. Previous studies have shown that satellite glial cells (SGCs) in the superior cervical ganglia (SCG) play an indispensable role in DCAN progression. In addition, it has been shown that purinergic neurotransmitters, as well as metabotropic GPCRs, are involved in the pathophysiological process of DCAN. Furthermore, one traditional Chinese medicine, naringin may potently alleviate the effects of DCAN. Ferroptosis may be involved in DCAN progression. However, the role of naringin in DCAN as well as its detailed mechanism requires further investigation. In this research, we attempted to identify the effect and relevant mechanism of naringin in DCAN mitigation. We observed that compared with those of normal subjects, there were significantly elevated expression levels of P2Y14 and IL-1β in diabetic rats, both of which were remarkably diminished by treatment with either P2Y14 shRNA or naringin. In addition, abnormalities in blood pressure (BP), heart rate (HR), heart rate variability (HRV), sympathetic nerve discharge (SND), and cardiac structure in the diabetic model can also be partially returned to normal through the use of those treatments. Furthermore, a reduced expression of NRF2 and GPX4, as well as an elevated level of ROS, were detected in diabetic cases, which can also be improved with those treatments. Our results showed that naringin can effectively relieve DCAN mediated by the P2Y14 receptor of SGCs in the SCG. Moreover, the NRF2/GPX4 pathway involved in ferroptosis may become one of the principal mechanisms participating in DCAN progression, which can be modulated by P2Y14-targeted naringin and thus relieve DCAN. Hopefully, our research can supply one novel therapeutic target and provide a brilliant perspective for the treatment of DCAN.

Background: The effect of the adenoviral early region 2 binding factors (E2Fs) target pathway on prostate cancer is not clear. It is necessary to establish an E2F target-related gene signature to predict prognosis and facilitate clinical decision-making.Methods: An E2F target-related gene signature was established by univariate and LASSO Cox regression analyses, and its predictive ability was verified in multiple cohorts. Moreover, the enrichment pathway, immune microenvironment, and drug sensitivity of the activated E2F target pathway were also explored.Results: The E2F target-related gene signature consisted of MXD3, PLK1, EPHA10, and KIF4A. The patients with high-risk scores showed poor prognosis, therapeutic resistance, and immunosuppression, along with abnormal growth characteristics of cells. Tinib drugs showed high sensitivity to the expression of MXD3 and EPHA10 genes.Conclusion: Our research established an E2F target-related signature for predicting the prognosis of prostate cancer. This study provides insights into formulating individualized detection and treatment as well as provides a theoretical basis for future research.

BackgroundGenomic instability (GI) plays a crucial role in the development of various cancers including hepatocellular carcinoma. Hence, it is meaningful for us to use long non-coding RNAs related to genomic instability to construct a prognostic signature for patients with HCC.MethodsCombining the lncRNA expression profiles and somatic mutation profiles in The Cancer Genome Atlas database, we identified GI-related lncRNAs (GILncRNAs) and obtained the prognosis-related GILncRNAs through univariate regression analysis. These lncRNAs obtained risk coefficients through multivariate regression analysis for constructing GI-associated lncRNA signature (GILncSig). ROC curves were used to evaluate signature performance. The International Cancer Genomics Consortium (ICGC) cohort, and in vitro experiments were used for signature external validation. Immunotherapy efficacy, tumor microenvironments, the half-maximal inhibitory concentration (IC50), and immune infiltration were compared between the high- and low-risk groups with TIDE, ESTIMATE, pRRophetic, and ssGSEA program.ResultsFive GILncRNAs were used to construct a GILncSig. It was confirmed that the GILncSig has good prognostic evaluation performance for patients with HCC by drawing a time-dependent ROC curve. Patients were divided into high- and low-risk groups according to the GILncSig risk score. The prognosis of the low-risk group was significantly better than that of the high-risk group. Independent prognostic analysis showed that the GILncSig could independently predict the prognosis of patients with HCC. In addition, the GILncSig was correlated with the mutation rate of the HCC genome, indicating that it has the potential to measure the degree of genome instability. In GILncSig, LUCAT1 with the highest risk factor was further validated as a risk factor for HCC in vitro. The ESTIMATE analysis showed a significant difference in stromal scores and ESTIMATE scores between the two groups. Multiple immune checkpoints had higher expression levels in the high-risk group. The ssGSEA results showed higher levels of tumor-antagonizing immune cells in the low-risk group compared with the high-risk group. Finally, the GILncSig score was associated with chemotherapeutic drug sensitivity and immunotherapy efficacy of patients with HCC.ConclusionOur research indicates that GILncSig can be used for prognostic evaluation of patients with HCC and provide new insights for clinical decision-making and potential therapeutic strategies.

Recurrent pregnancy loss (RPL), especially the unexplained RPL, is associated with the disruption of maternal immune tolerance. However, little is known about the immune status at the decidua of RPL with embryonic chromosomal aberrations. Herein, mass cytometry (CyTOF) was used to interrogate the immune atlas at the decidua which was obtained from 15 RPL women—six with normal chromosome and nine with chromosomal aberrations—and five controls. The total frequency of CCR2−CD11chigh macrophages increased, while CD39high NK cells and CCR2−CD11clow macrophages decrease significantly in RPL when RPLs were stratified, compared with controls. Pro-inflammatory subsets of CD11chigh macrophages increased, while less pro-inflammatory or suppressive subsets decreased statistically in RPL decidua whenever RPLs were stratified or not. However, CD11chigh NK and CD161highCD8+ T cells increased only in RPL with normal chromosome, while the inactivated and naive CD8+/CD4+ T cells were enriched only in RPL with chromosomal aberrations. A pro-inflammatory signature is observed in RPL decidua; however, differences exist between RPL with and without chromosomal abnormalities.

Hyaluronic acid (HA) is composed of alternating d-glucuronic acid and N-acetyl-d-glucosamine, with excellent biocompatibility and water retention capacity. To achieve heterologous biosynthesis of HA, Corynebacterium glutamicum, a safe GRAS (generally recognized as safe) host, was utilized and metabolically engineered previously. In this work, to achieve further enhancement of HA yield, four strategies were proposed and performed separately first, i.e., (1) improvement of glucose uptake via iolR gene knockout, releasing the inhibition of transporter IolT1/IolT2 and glucokinases; (2) intensification of cardiolipin synthesis through overexpression of genes pgsA1/pgsA2/cls involved in cardiolipin synthesis; (3) duly expressed Vitreoscilla hemoglobin in genome, enhancing HA titer coupled with more ATP and improved NAD+/NADH (>7.5) ratio; and (4) identification of the importance of glutamine for HA synthesis through transcriptome analyses and then enhancement of the HA titer via its supplement. After that, we combined different strategies together to further increase the HA titer. As a result, one of the optimal recombinant strains, Cg-dR-CLS, yielded 32 g/L of HA at 60 h in a fed-batch culture, which was increased by 30% compared with that of the starting strain. This high value of HA titer will enable the industrial production of HA via the engineered C. glutamicum.

Immune regulation plays a vital role in ischemia–reperfusion injury (IRI). Butyric acid (BA) has immunomodulatory effects in many diseases, but its immunomodulatory effects during renal IRI are still unclear. Our research shows that BA protected against IRI and significantly improved renal IRI in vivo. In vitro studies showed that BA inhibits Th17 cell differentiation and induces Treg cell differentiation. Mechanism studies have shown that heme oxygenase 1 (HO-1)/STAT3 signaling pathway was involved in the inhibitory effect of BA on Th17 cell differentiation. HO-1 inhibitors can significantly rescue the BA-mediated inhibition of Th17 cell differentiation. We confirmed that BA promotes the differentiation of Th17 cells into Treg cells by regulating the pathway and reduces renal IRI.

Melatonin acts both as an antioxidant and as a growth regulatory substance in plants. Pseudomonas fluorescens endophytic bacterium has been shown to produce melatonin and increase plant resistance to abiotic stressors through increasing endogenous melatonin. However, in bacteria, genes are still not known to be melatonin-related. Here, we reported that the bacterial phenylalanine 4-hydroxylase (PAH) may be involved in the 5-hydroxytryptophan (5-HTP) biosynthesis and further influenced the subsequent production of melatonin in P. fluorescens. The purified PAH protein of P. fluorescens not only hydroxylated phenylalanine but also exhibited l-tryptophan (l-Trp) hydroxylase activity by converting l-Trp to 5-HTP in vitro. However, bacterial PAH displayed lower activity and affinity for l-Trp than l-phenylalanine. Notably, the PAH deletion of P. fluorescens blocked melatonin production by causing a significant decline in 5-HTP levels and thus decreased the resistance to abiotic stress. Overall, this study revealed a possible role for bacterial PAH in controlling 5-HTP and melatonin biosynthesis in bacteria, and expanded the current knowledge of melatonin production in microorganisms.

Synonymous mutations are generally considered non-pathogenic because it did not alter the amino acids of the encoded protein. Publications of the associations between synonymous mutations and abnormal splicing have increased recently, however, not much observations available described the synonymous mutations at the non-canonical splicing sites leading to abnormal splicing. In this pedigree, the proband was diagnosed Neurofibromatosis type I due to the presence of typical cafe’ au lait macules and pectus carinatum. Whole-exome sequencing identified a synonymous mutation c.6795C > T (p.N2265N) of the NF1 gene which was located at the non-canonical splicing sites. Reverse transcription polymerase chain reaction followed by Sanger sequencing was carried out, and the skipping of exon 45 was observed. Therefore, the pathogenicity of the synonymous mutation c.6795C > T was confirmed. Our finding expanded the spectrum of pathogenic mutations in Neurofibromatosis type I and provided information for genetic counseling.

Objective: The association between cadmium exposure and osteoporosis has been rarely reported in longitudinal studies. In this study, we investigated the association between osteoporosis and cadmium exposure and developed predictive models in women in a longitudinal cohort.Materials and Methods: In total, 488 women living in southeastern China were included at baseline (1998). Cadmium in blood (BCd) and urine (UCd) and also renal dysfunction biomarkers and bone mineral density (BMD) were determined both at baseline and follow-up. A total of 307 subjects were finally included after excluding subjects that did not have exposure or effect biomarkers. Osteoporosis was defined based on T score ≤ −2.5. Multiple linear regression and multivariate logistic analysis were used to show the association between baseline data and follow-up osteoporosis. Based on the identified associated factors, nomograms were developed to graphically calculate the individual risk of osteoporosis.Results: The baseline BMD in subjects with osteoporosis was significantly lower than that in subjects without osteoporosis (0.59 vs. 0.71 g/cm2, p < 0.05). The prevalence of low bone mass at baseline was higher in subjects with osteoporosis than in those without osteoporosis (23.5 vs. 7.2%, p = 0.001). Logistic regression analysis demonstrated that age [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.16–1.27], UCd (OR = 1.03, 95% CI: 1.002–1.06) and the presence of low BMD (OR = 3.84, 95% CI: 1.49–9.89) were independent risk factors for osteoporosis. For those subjects with normal baseline BMD, age, UCd, and baseline BMD were also independent risk factors for osteoporosis. The OR value was 1.16 (95% CI: 1.10–1.22) for age, 2.27 (95% CI: 1.03–4.99) for UCd > 10 μg/g creatinine, and 0.39 (95% CI: 0.21–0.72) for BMDbaseline. We developed two nomograms to predict the risk of osteoporosis. The area under the curve was 0.88 (95% CI: 0.84–0.92) for total population and was 0.88 (95% CI: 0.84–0.92) for subjects with normal baseline BMD, respectively.Conclusion: Baseline age, UCd, and BMD were associated with follow-up osteoporosis in women. Nomograms showed good performance in predicting the risk of osteoporosis.

BackgroundHepatocellular carcinoma (HCC) has become the main cause of cancer death worldwide. More than half of hepatocellular carcinoma developed from hepatitis B virus infection (HBV). The purpose of this study is to find the key genes in the transformation process of liver inflammation and cancer and to inhibit the development of chronic inflammation and the transformation from disease to cancer.MethodsTwo groups of GEO data (including normal/HBV and HBV/HBV-HCC) were selected for differential expression analysis. The differential expression genes of HBV-HCC in TCGA were verified to coincide with the above genes to obtain overlapping genes. Then, functional enrichment analysis, modular analysis, and survival analysis were carried out on the key genes.ResultsWe identified nine central genes (CDK1, MAD2L1, CCNA2, PTTG1, NEK2) that may be closely related to the transformation of hepatitis B. The survival and prognosis gene markers composed of PTTG1, MAD2L1, RRM2, TPX2, CDK1, NEK2, DEPDC1, and ZWINT were constructed, which performed well in predicting the overall survival rate.ConclusionThe findings of this study have certain guiding significance for further research on the transformation of hepatitis B inflammatory cancer, inhibition of chronic inflammation, and molecular targeted therapy of cancer.

Introduction: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) in combination with and gemcitabine plus cisplatin (GP) are beneficial. This multidimensional network meta-analysis aimed to compare the clinical efficacy and safety of different CHIs in combination with GP against NSCLC.Methods: Randomized controlled trials (RCTs) for the treatment of NSCLC were retrieved from seven electronic databases from inception to April 30, 2020. Study selection and data extraction were based on a priori criteria. Data analysis was performed using Stata 13.0, WinBUGS 14.0 software. Multidimensional cluster analysis was performed using the “scatterplot3d” package in R 3.6.1 software.Results: This network meta-analysis included 71 eligible RCTs and 10 Chinese herbal injections. Delisheng injection and Kangai injection had the highest probability in terms of clinical effectiveness rate (94.60%) and gastrointestinal reactions (82.62%) when combined with GP compared with the other interventions. Compound Kushen injection combined with GP ranked ahead of the other interventions in terms of performance status (73.36%) and abnormal liver function (87.17%). Shenmai injection combined with GP had the highest probability in terms of leukopenia (94.59%) and thrombocytopenia (99.18%).Conclusion: The current evidence revealed that CHIs combined with GP have a better impact on patients with NSCLC than GP alone. Aidi injection, Compound kushen injection, and Kanglaite injection deserve more attention of clinicians when combined with GP in patients with NSCLC. Additionally, due to the limitations of this network meta-analysis, further well-designed, large-sample, multicenter RCTs are required to support our findings adequately.

Germline mosaicism should be suspected when the same de novo mutations are identified in a second pregnancy with asymptomatic parents. Our study aims to find a feasible approach to reveal the existence of germline mosaicism. Multiplex Ligation-dependent Probe Amplification was performed on a Duchenne muscular dystrophy affected pedigree to detect deletion mutations. Then gap-polymerase chain reaction was performed to amplify the breakpoints junction sequence. Droplet digital polymerase chain reaction was utilized to identify the mutation frequencies in healthy parents. The same deletion in the exon 51 of the dystrophin gene, which was 50,035 bp in size, was detected in the proband and the fetus but not in their parents. Droplet digital polymerase chain reaction analysis of peripheral blood samples revealed mutant alleles of 3.53% in maternal blood cells. We here report a case of maternal low-level mosaicism confirmed by droplet digital polymerase chain reaction in peripheral blood samples, which reveals the existence of germline mosaicism. Gap-polymerase chain reaction combined with droplet digital polymerase chain reaction provide insights into the detection of germline mosaicism.

Introduction: Given the wide utilization of Chinese herbal injections in the treatment of nasopharyngeal carcinoma (NPC), this network meta-analysis (NMA) was devised to compare the clinical efficacy and safety of different Chinese herbal injections combined with concurrent chemoradiotherapy (CCRT) against NPC.Methods: Randomized controlled trials (RCTs) were retrieved from seven electronic databases from the date of database establishment to October 5, 2020. Study selection and data extraction conformed to a priori criteria. Focusing on clinical effective rate, performance status, grade ≥3 oral mucositis, nausea and vomiting, leukopenia, and thrombopenia, this NMA was performed with Review Manager 5.3.5, Stata 13.1, WinBUGS 1.4.3, and R 4.0.3 software.Results: Ten inventions from 37 RCTs involving 2,581 participants with NPC that evaluated the clinical effective rate, nausea and vomiting, leukopenia, thrombopenia, and grade ≥3 oral mucositis were included. Compared with CCRT alone, Elemene injection and Compound Kushen injection were associated with significantly improved clinical effective rates, and Elemene injection plus CCRT had the highest probability in terms of clinical effective rate (78.07%) compared with the other interventions. Shenqifuzheng injection, Xiaoaiping injection, and Shenmai injection ranked the best in terms of performance status (79.02%), nausea and vomiting (86.35%), and grade ≥3 oral mucositis (78.14%) when combined with CCRT. Kangai injection combined with CCRT ranked ahead of the other injections in terms of leukopenia (90.80%) and thrombopenia (91.04%), and had a better impact on improving performance status and reducing leukopenia, thrombopenia, grade ≥3 oral mucositis, and nausea and vomiting in the multidimensional cluster analysis.Conclusion: Current clinical evidence indicates that Elemene injection combined with CCRT has the best clinical effective rate and that Kangai injection might have a comprehensively better impact on improving performance status and reducing adverse reactions against NPC. Additionally, due to the limitations of this NMA, more multicenter, high-quality, and head-to-head RCTs are needed to properly support our findings.

To evaluate the clinical efficiency of non-invasive prenatal screening (NIPS) for fetal aneuploidies in low-risk and twin pregnancies, patients who received NIPS in a tertiary university hospital were enrolled, and their clinical data, NIPS results and pregnancy outcomes were collected. Patients were divided into singleton and twin pregnancies, and then those with singleton pregnancies were divided into low- and high-risk pregnancies. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were estimated. Comparisons were made on the clinical efficiency of NIPS between singleton and twin pregnancies, as well as between low- and high-risk pregnancies. Of 66,172 patients enrolled, 59,962 were eligible for analysis. The sensitivity, specificity and NPV were ≥ 99% in singleton and twin pregnancies. The PPVs were 90.4, 56.6, and 13.0% in singleton pregnancies, while 100, 33.3, and 0% in twin pregnancies for trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), respectively (P > 0.05 for all). The PPVs were 97.4 and 90.0% in high-risk pregnancies, while 78.6 and 16.7% in low-risk pregnancies for T21 and T18, respectively (P < 0.05 for all). In summary, the performance of NIPS in singleton pregnancies was similar to that in twin pregnancies. NIPS can be recommended for all pregnancies regardless of the risks.

Background: Simple febrile seizures (SFS) and epilepsy are common seizures in childhood. However, the mechanism underlying SFS is uncertain, and the presence of obvious variances in white matter (WM) integrity and glymphatic function between SFS and epilepsy remain unclear. Therefore, this study aimed to investigate the differences in WM integrity and glymphatic function between SFS and epilepsy.Material and Methods: We retrospectively included 26 children with SFS, 33 children with epilepsy, and 28 controls aged 6–60 months who underwent magnetic resonance imaging (MRI). Tract-based spatial statistics (TBSS) were used to compare the diffusion tensor imaging (DTI) metrics of WM among the above-mentioned groups. T2-weighted imaging (T2WI) was used to segment the visible Virchow-Robin space (VRS) through a custom-designed automated method. VRS counts and volume were quantified and compared among the SFS, epilepsy, and control groups. Correlations of the VRS metrics and seizure duration and VRS metrics and the time interval between seizure onset and MRI scan were also investigated.Results: In comparison with controls, children with SFS showed no significant changes in fractional anisotropy (FA), axial diffusivity (AD), or radial diffusivity (RD) in the WM (P > 0.05). Decreased FA, unchanged AD, and increased RD were observed in the epilepsy group in comparison with the SFS and control groups (P < 0.05). Meanwhile, VRS counts were higher in the SFS and epilepsy groups than in the control group (VRS_SFS, 442.42 ± 74.58, VRS_epilepsy, 629.94 ± 106.55, VRS_control, 354.14 ± 106.58; P < 0.001), and similar results were found for VRS volume (VRS_SFS, 6,228.18 ± 570.74 mm3, VRS_epilepsy, 9,684.84 ± 7,292.66mm3, VRS_control, 4,007.22 ± 118.86 mm3; P < 0.001). However, VRS metrics were lower in the SFS group than in the epilepsy group (P < 0.001). In both SFS and epilepsy, VRS metrics positively correlated with seizure duration and negatively correlated with the course after seizure onset.Conclusion: SFS may not be associated with WM microstructural disruption; however, epilepsy is related to WM alterations. Seizures are associated with glymphatic dysfunction in either SFS or epilepsy.

Galectin-14 is specifically expressed in placental trophoblasts, and its expression is reduced in trophoblasts retrieved from the cervix of women destined to develop early pregnancy loss. However, the roles of galectin-14 in regulating trophoblasts and in the pathogenesis of pregnancy complication have never been investigated. In the current research, we aimed to investigate the roles of galectin-14 in the regulation of trophoblasts. Tissues of the placenta and villi were collected. Primary trophoblasts and human trophoblast cell line HTR-8/SVneo were used. Western blotting and RT-PCR were used to quantify gene expression. The siRNA-mediated galectin-14 knockdown and lentivirus-mediated overexpression were performed to manipulate the gene expression in trophoblasts. Transwell migration and invasion assays were used to evaluate cell migration and invasion capacity. Gelatin zymography was used to determine the gelatinase activity. Galectin-14 was significantly decreased in the villi of early pregnancy loss and the placenta of preeclampsia. Knockdown of galectin-14 in primary trophoblasts inhibited cell migration and invasion, downregulated the expression of matrix metalloproteinase (MMP)-9 and N-cadherin, the activity of MMP-9, and decreased the phosphorylation of Akt. Meanwhile, the overexpression of galectin-14 in HTR-8/SVneo promoted cell migration and invasion, upregulated the expression of MMP-9 and N-cadherin, the activity of MMP-9, and increased the phosphorylation of Akt. Increased Akt phosphorylation promoted cell migration and invasion and upregulated the expression and activity of MMP-9, while decreased Akt phosphorylation inhibited cell migration and invasion and downregulated the expression and activity of MMP-9. Thus, galectin-14 promotes trophoblast migration and invasion by enhancing the expression of MMP-9 and N-cadherin through Akt phosphorylation. The dysregulation of galectin-14 is involved in the pathogenesis of early pregnancy loss and preeclampsia.

Background: Prostate cancer (PCa) is currently the most common cancer among males worldwide. It has been reported that OTUB1 plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis. The aim of this research is to investigate the regulatory effect of OTUB1 on PCa proliferation and the underlying mechanism.Methods: Using the TCGA database, we identified that OTUB1 was up-regulated in PCa, and observed severe functional changes in PC3 and C4-2 cells through overexpression or knock down OTUB1. Heterotopic tumors were implanted subcutaneously in nude mice and IHC staining was performed on tumor tissues. The relationship between OTUB1 and cyclin E1 was identified via Western blotting and immunoprecipitations assays.Results: We found that the expression of OTUB1 in PCa was significantly higher than that in Benign Prostatic Hyperplasia (BPH). Overexpression OTUB1 obviously promoted the proliferation and migration of PC3 and C4-2 cells via mediating the deubiquitinated Cyclin E1, while OTUB1 knockout has the opposite effect. The nude mice experiment further explained the above conclusions. We finally determined that OTUB1 promotes the proliferation and progression of PCa via deubiquitinating and stabling Cyclin E1.Conclusions: Our findings reveal the critical role of OTUB1 in PCa, and OTUB1 promotes the proliferation and progression of PCa via deubiquitinating and stabilizing Cyclin E1. Blocking OTUB1/Cyclin E1 axis or applying RO-3306 could significantly repress the occurrence and development of PCa. OTUB1/Cyclin E1 axis might provide a new and potential therapeutic target for PCa.

Background: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) combined with vinorelbine and cisplatin (NP) are beneficial. This multidimensional network meta-analysis was performed to explore the preferable options among different CHIs for treating NSCLC.Methods: A literature search was performed in several databases to identify randomized controlled trials (RCTs) of CHIs in the treatment of NSCLC from inception to January 31, 2019. Final included studies met the eligibility criteria and methodological quality recommendations. Data analysis was performed using Stata 13.0 and WinBUGS 14.0 software. Each outcome was presented as an odds ratio and the surface under the cumulative ranking curve value (SCURA). The “scatterplot3d” package in R 3.6.1 software was used to perform multidimensional cluster analysis.Results: Ultimately, 97 eligible RCTs involving 7,440 patients and 14 CHIs were included in this network meta-analysis. Combined with NP chemotherapy, Kanglaite injection plus NP exhibited a better impact on the clinical effectiveness rate (SCURA probability: 78.34%), and Javanica oil emulsion injection plus NP was better in the performance status (95.44%). Huachansu injection plus NP was dominant in reducing thrombocytopenia (92.67%) and gastrointestinal reactions (92.52%). As to multidimensional cluster analysis, Shenmai injection plus NP was superior considering improving the clinical effectiveness rate, performance status and relieving leukopenia.Conclusions: The combination of CHIs and NP has a better impact on patients with NSCLC than NP alone. Among them, Shenmai injection plus NP, Kanglaite injection plus NP and Javanica oil emulsion injection plus NP were notable. Nevertheless, more multicenter and better designed RCTs are needed to validate our findings.

Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC.Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes.Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status.Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.

Apple (Malus domestica Borkh.), an economically important tree fruit worldwide, frequently suffers from temperature stress during growth and development, which strongly affects the yield and quality. Heat shock protein 20 (HSP20) genes play crucial roles in protecting plants against abiotic stresses. However, they have not been systematically investigated in apple. In this study, we identified 41 HSP20 genes in the apple ‘Golden Delicious’ genome. These genes were unequally distributed on 15 different chromosomes and were classified into 10 subfamilies based on phylogenetic analysis and predicted subcellular localization. Chromosome mapping and synteny analysis indicated that three pairs of apple HSP20 genes were tandemly duplicated. Sequence analysis revealed that all apple HSP20 proteins reflected high structure conservation and most apple HSP20 genes (92.6%) possessed no introns, or only one intron. Numerous apple HSP20 gene promoter sequences contained stress and hormone response cis-elements. Transcriptome analysis revealed that 35 of 41 apple HSP20 genes were nearly unchanged or downregulated under normal temperature and cold stress, whereas these genes exhibited high-expression levels under heat stress. Subsequent qRT-PCR results showed that 12 of 29 selected apple HSP20 genes were extremely up-regulated (more than 1,000-fold) after 4 h of heat stress. However, the heat-upregulated genes were barely expressed or downregulated in response to cold stress, which indicated their potential function in mediating the response of apple to heat stress. Taken together, these findings lay the foundation to functionally characterize HSP20 genes to unravel their exact role in heat defense response in apple.

Adventitious root (AR) formation is indispensable for vegetative asexual propagation. Indole-3-butyric acid (IBA) functioned indirectly as precursor of IAA in regulating AR formation. Ethylene affects auxin synthesis, transport, and/or signaling processes. However, the interactions between auxin and ethylene that control AR formation in apple have not been elucidated. In this study, we investigated the effects of IBA and its interaction with ethylene on AR development in apple. The results revealed that IBA stimulated the formation of root primordia, increased the number of ARs, and upregulated expression of genes (MdWOX11, MdLBD16, and MdLBD29) involved in AR formation. Comparison of different periods of IBA application indicated that IBA was necessary for root primordium formation, while long time IBA treatment obviously inhibited root elongation. RNA-seq analysis revealed that many plant hormone metabolism and signal transduction related genes were differentially expressed. IBA stimulated the production of ethylene during AR formation. Auxin inhibiting ARs elongation depended on ethylene. Together, our results suggest that the inhibitory role of auxin on AR elongation in apples is partially mediated by stimulated ethylene production.

Objective: Brain imaging is important in diagnosing children with cerebral palsy (CP) and in identifying its etiology. To provide study navigation in this field, a bibliometric analysis was conducted by analyzing the most highly cited articles.Methods: The Web of Science All Databases were used for literature search in this study. All original articles on imaging in children with CP were searched. Two reviewers screened the search results independently and eliminated articles based on exclusion criteria such as participants over 20 years old, topics referring to images outside of the brain, or trauma. According to descending order of yearly citation counts, the top 25% of all included articles were considered as highly cited articles. Information such as yearly citations, research purposes, imaging modalities, CP types, and study designs were recorded and analyzed.Results: A total of 50 highly cited articles ranked by yearly citations (from 23.85 to 3.33, 1991–2018) were included in this study. Considering different research purposes, these studies were classified into three categories: diagnosis studies (n = 25; 1991–2017, median: 2011), mechanism studies (n = 15; 1999–2018; median: 2014), and prognosis and therapeutic effect studies (n = 10; 2008–2017; median: 2014.5). First, for diagnosis studies, 22 studies used single modality and three used multi-modalities; the majority of these studies focused on diagnostic value evaluation (n = 10) and image performance (n = 12) of a single type of CP (n = 15) by using descriptive (n = 14) or cross-sectional approaches (n = 10). Second, for mechanism studies, the ratio between single and multi-modality was 8:7; most of these studies concentrated on a single subtype of spastic CP (hemiplegia = 10, quadriplegia = 2) with a cross-sectional study design (n = 10). Third, regarding the prognosis and therapeutic effect studies, the single vs. multi-modality ratio was 5:5, and these studies were dedicated to the efficiency of constraint-induced movement therapy in children with hemiplegia; paired design trials (n = 6) and randomized controlled trials (n = 2) were used more frequently.Conclusion: Studies using multi-modality and high-level evidence-based design to provide information regarding mechanism, prognosis, and therapeutic efficacy may be the potential future research direction in the field of CP research.

BackgroundAcute coronary syndrome, that is a common and serious cardiovascular disease, imposes a huge economic burden on global public health. And Danshen class injections are commonly used in the treatment of acute coronary syndrome in China. Thus, the Bayesian network meta-analysis was devised to investigate the efficacy of different Danshen class injections against acute coronary syndrome.MethodsEligible inclusion and exclusion criteria were established in advance. Then, a systematic literature search was performed in several databases from inception to February 2020. Further, the included randomized controlled trials data were adopted to calculation, prepare graphs and multidimensional cluster analysis by WinBUGS 1.4.3, Stata V.13.0 and R 3.6.1 software, respectively.ResultsA total of 53 eligible randomized controlled trial studies with 6401 patients were obtained that evaluated the clinical effectiveness rate, the level of hypersensitive C-reactive protein, C-reactive protein, interleukin-6, fibrinogen, and adverse reactions after the application of Danshen class injections plus western medicine. Compared with western medicine alone, Danshen class injections combined with western medicine therapy were associated with significantly improved the therapeutic effect. In addition, the results of the multidimensional cluster analysis demonstrated that Danhong injection + western medicine and Danshen injection + western medicine had better therapeutic effects. However, since most eligible randomized controlled trial studies did not focus on the monitoring of adverse reactions, the safety of these Chinese herbal injections needs to be further explored.ConclusionBased on this Bayesian network meta-analysis results, Danhong injection + western medicine and Danshen injection + western medicine might have a better impact on acute coronary syndrome patients. Nevertheless, more large samples, high-quality clinical and multicenter randomized controlled trial studies should be tested and verified in the future.

Aim: Isocitrate dehydrogenase 1 (IDH1) is key enzyme involved in cellular metabolism and DNA repair. Mutations in IDH1 occur in up to 25% of cholangiocarcinomas. The present study aimed to explore the features of cellosaurus REB cells with mutant and wide-type IDH1.Methods: To compare the features of IDH1 knockout and mutation in cholangiocarcinoma, we firstly constructed the IDH1 knockout and IDH1 mutation cell lines. We then evaluated the viability of these cell lines using the cell count assay and MTT assay. Next, we determined cell migration and invasion using the Transwell assay. Additionally, to evaluate the effects of IDH1 on cellular metabolism, the levels of α-ketoglutarate (α-KG) and nicotinamide adenine dinucleotide phosphate (NADPH) were determined using enzyme-linked immunosorbent assay. We then applied ChIPbase dataset to explore the genes that were regulated by IDH1.Results: High frequency of mutated IDH1 was observed in the cholangiocarcinoma and IDH1 R132C was presented in more than 80% of mutations. The results showed that IDH1 knockout decreased cell proliferation, migration and invasion, whereas the overexpression of IDH1 in IDH1 knockout cell line recovered its proliferation, migration and invasion capacities. Additionally, IDH1 mutation reduced the levels of NADPH and α-KG. Furthermore, investigation into the underlying mechanisms revealed that IDH1 overexpression induced the expression of aldehyde dehydrogenase 1 thereby promoting cell proliferation, migration and invasion.Conclusion:IDH1 plays an important role in cholangiocarcinoma and its mutation impairs tumor progression in part by inhibition of isocitrate metabolism.

Gastric cancer (GC), a common type of malignant cancer, remains the fifth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Despite developments in the treatment of GC, the prognosis remains poor. Embryonic stem cell-expressed Ras (ERas), a novel member of the Ras protein family, has recently been identified as an oncogene involved in the tumorigenic growth of embryonic stem cells. A recent study reported that ERas is expressed in most GC cell lines and GC specimens, and it promotes tumorigenicity in GC through induction of the epithelial mesenchymal transition (EMT) and activation of the PI3K/AKT pathway. Here, we found that ERas blocked autophagy flux in BGC-823 and AGS GC cells, which may occur through activation of the AKT/mTOR signaling pathway. Moreover, ERas overexpression suppressed cisplatin-induced apoptosis, and rapamycin treatment significantly attenuated ERas-mediated cisplatin resistance in GC cells. These data suggest that ERas may be a potential therapeutic target to improve the outcomes of GC patients by regulating the autophagy process.

Bilateral cerebral palsy (BCP) is a common movement disorder in children, which often results in lifelong motor disability. One main symptom of BCP is the limitation of hand function in everyday activities. However, the neuroanatomical basis of this prominent hand impairment is yet to discover. Recent advances mainly focus on the lesions of BCP, but the views on the atypical development of cortical parcellations are extremely lacking. Here, in our study, neuroimaging with network analysis was employed to evaluate the changes of structural covariance networks (SCNs) in BCP children. We aimed to elucidate the alteration of SCNs based on cortical thickness (CT), and to reveal the relationship of CT and hand function in the participants with BCP. SCNs were constructed using covariance between regional CT, which was acquired from T1-weighted images of 19 children with BCP and 19 demographically matched healthy controls (HCs). Compared with HCs, BCP children showed increased CT in several regions involving the bilateral areas (lateral occipital, lingual, and fusiform) and right areas (cuneus, pericalcarine, inferior temporal, middle temporal, superior temporal, and insula). Decreased CT was found in the left superior temporal and right superior parietal cortices. Global network analyses revealed significantly decreased normalized clustering and small-worldness in the BCP network. The area under the curve (AUC) of global network measures varied slightly between the BCP and HC networks. The resistance of the both SCNs to the target and random attack showed no significant difference. Also, the BCP foci (right superior temporal and subtemporal cortex) showed a significantly negative correlation between the CT and manual ability. In this work, we identified the CT-based SCNs changes in children with BCP. The abnormal topological organization of SCNs was revealed, indicating abnormal CT, incongruous development of structural wiring, destructive nodal profiles of betweenness, and moved hub distribution in BCP children. This may provide a neuroanatomical hallmark of BCP in the developing brain. Therefore, our results may not only reflect neurodevelopmental aberrations but also compensatory mechanisms.

Aims: To evaluate the clinical efficacy of Human Urinary Kallidinogenase (HUK) and Maixuekang capsule in the treatment of acute ischemic stroke (AIS) patients.Methods: In this study, from January 2016 to July 2016, 60 patients with acute ischemic stroke were enrolled and 56 patients with complete information of whom 21 patients received HUK+ basic treatment (HUK group), 16 patients received HUK+ Maixuekang capsule + basic treatment (HUK+ Maixuekang group), 19 patients received basic treatment (control group). 0.15 PNA unit of HUK injection plus 100 ml saline in intravenous infusion was performed in the HUK group and HUK+ Maixuekang group, with once a day for 14 consecutive days. 0.75 g Maixuekang capsules were taken in HUK+ Maixuekang group, with three times a day for 14 consecutive days. The National Institutes of Health Stroke Scale (NIHSS) scores in three groups were analyzed 7 days after treatment. The modified Rankin Scale (mRS) scores in three groups were analyzed 12 month after the treatment.Results: No difference was found in the NIHSS scores, age, gender, and comorbidities between three groups before treatment (p > 0.05). Seven days after treatment, the NIHSS scores in the HUK group and HUK+ Maixuekang group were significantly decreased than before (p HUK = 0.001, p HUK+Maixuekang < 0.001), and lower than that in the control group (p HUK = 0.032; p HUK+Maixuekang < 0.001). Twelve months after treatment, good functional outcome rate (12 month mRS score ≤ 2) in the HUK group and HUK+ Maixuekang group was significantly higher than that in the control group (p HUK = 0.049, p HUK+Maixuekang = 0.032).Conclusion: The treatment of HUK or HUK combined with Maixuekang capsule can effectively improve the neurological function and promote long-term recovery for AIS patients.

Background: The systemic immune-inflammation index (SII) has emerged as a promisingmarker predicting the prognosis of some cancers, while its role in urothelial carcinoma (UC) remains uncertain, especially in upper urinary tract urothelial carcinoma (UTUC). This meta-analysis aimed to investigate the association of SII with the prognosis of UC and the response to intravesical Bacillus Calmette-Guerin (BCG) therapy of non-muscle invasive bladder cancer (NMIBC). Methods: A systematic search in PubMed, Embase, Web of Science, and the Cochrane Library was performed to identify relevant studies. The extracted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the association between SII and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) of patients with UC. Additionally, we pooled odds ratios (ORs) and 95% CIs to assess the relationship between SII and BCG response in patients with NMIBC. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity. Results: Twenty studies comprising a total of 12,645 patients were eligible. This meta-analysis revealed that high SII levels independently increased the risk of OS (HR 1.55, 95%CI 1.25-1.92), CSS (HR 1.82, 95%CI 1.36-2.45), and RFS (HR 1.26, 95% CI 1.18-1.35) in patients with UC, including those with upper tract urothelial carcinoma. Additionally, elevated SII levels could predict a lower response to intravesical BCG treatment (OR 0.18, 95%CI 0.07-0.45) and higher disease recurrence (HR 1.61, 95%CI 1.31-1.98) in patients with NMIBC. Furthermore, elevated SII levels were positively associated with advanced age, lymphovascular invasion, hydronephrosis, and high tumor grade and stage (pT = 3). Conclusions: Elevated preoperative SII levels are associated with poor survival outcomes in patients with UC, as well as worse response to BCG treatment in patients with NMIBC. Therefore, SII can serve not only as an independent prognostic predictor of patients with UC but also as a guide for BCG therapy in NMIBC. [ABSTRACT FROM AUTHOR]

Influenza A viruses (IAVs) can infect a wide variety of bird and mammal species. Their genome is characterized by 8 RNA single stranded segments. The low proofreading activity of their polymerases and the genomic reassortment between different IAVs subtypes allow them to continuously evolve, constituting a constant threat to human and animal health. In 2009, a pandemic of an IAV highlighted the importance of the swine host in IAVs adaptation between humans and birds. The swine population and the incidence of swine IAV is constantly growing. In previous studies, despite vaccination, swine IAV growth and evolution were proven in vaccinated and challenged animals. However, how vaccination can drive the evolutionary dynamics of swine IAV after coinfection with two subtypes is poorly studied. In the present study, vaccinated and nonvaccinated pigs were challenged by direct contact with H1N1 and H3N2 independent swine IAVs seeder pigs. Nasal swab samples were daily recovered and broncho-alveolar lavage fluid (BALF) was also collected at necropsy day from each pig for swine IAV detection and whole genome sequencing. In total, 39 swine IAV whole genome sequences were obtained by next generation sequencing from samples collected from both experimental groups. Subsequently, genomic, and evolutionary analyses were carried out to detect both, genomic reassortments and single nucleotide variants (SNV). Regarding the segments found per sample, the simultaneous presence of segments from both subtypes was much lower in vaccinated animals, indicating that the vaccine reduced the likelihood of genomic reassortment events. In relation to swine IAV intra-host diversity, a total of 239 and 74 SNV were detected within H1N1 and H3N2 subtypes, respectively. Different proportions of synonymous and nonsynonymous substitutions were found, indicating that vaccine may be influencing the main mechanism that shape swine IAV evolution, detecting natural, neutral, and purifying selection in the different analyzed scenarios. SNV were detected along the whole swine IAV genome with important nonsynonymous substitutions on polymerases, surface glycoproteins and nonstructural proteins, which may have an impact on virus replication, immune system escaping and virulence of virus, respectively. The present study further emphasized the vast evolutionary capacity of swine IAV, under natural infection and vaccination pressure scenarios. [ABSTRACT FROM AUTHOR]