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Calibration is a critical component for the reliability, accuracy, and precision of mass spectrometry measurements. Optimal practice in the construction, evaluation, and implementation of a new calibration curve is often underappreciated. This systematic review examined how calibration practices are applied to liquid chromatography-tandem mass spectrometry measurement procedures.The electronic database PubMed was searched from the date of database inception to April 1, 2022. The search terms used were "calibration," "mass spectrometry," and "regression." Twenty-one articles were identified and included in this review, following evaluation of the titles, abstracts, full text, and reference lists of the search results.The use of matrix-matched calibrators and stable isotope-labeled internal standards helps to mitigate the impact of matrix effects. A higher number of calibration standards or replicate measurements improves the mapping of the detector response and hence the accuracy and precision of the regression model. Constructing a calibration curve with each analytical batch recharacterizes the instrument detector but does not reduce the actual variability. The analytical response and measurand concentrations should be considered when constructing a calibration curve, along with subsequent use of quality controls to confirm assay performance. It is important to assess the linearity of the calibration curve by using actual experimental data and appropriate statistics. The heteroscedasticity of the calibration data should be investigated, and appropriate weighting should be applied during regression modeling.This review provides an outline and guidance for optimal calibration practices in clinical mass spectrometry laboratories.

Parkinson's disease (PD) represents the second most common neurodegenerative disease.To evaluate the effects of dance therapy (DT) aimed at improving non-motor symptoms in PD.Studies were performed through PubMed, Web of Science, The Cochrane Library, Embase, and Science Direct from inception to October 27, 2021. The data were screened independently by two reviewers, and the quality of the papers was assessed using the Cochrane manual. The included studies were randomized controlled trials and quasi-randomized controlled trials, reporting random-effects standardized mean differences, and 95% confidence intervals as the effect size. INine literatures were analyzed for the meta-analysis with a total of 307 patients. Random effects showed that DT significantly improved cognitive of PD (MD = 1.50, 95% CI [0.52, 2.48], P = 0.0003; IThe meta-analysis suggests that dance can improve cognitive function in PD.

While studies on youth's purpose have flourished in the last two decades, the work was mostly cross-sectional and derived from Western settings. This research examined the developmental trajectories of purpose exploration and commitment of Taiwanese youth during middle adolescence, with a focus on how they associate with youth's psychological functioning in terms of life satisfaction and depressive symptoms and whether social support moderates such development. A total of 369 vocational high school students in Taiwan (45% females; M

Primary aldosteronism (PA) is a disease characterized by hypertension and hypokalemia due to the excessive aldosterone secretion from the adrenal cortex, which leads to the retention of both water and sodium, and the inhibition of the renin-angiotensin system as well. Familial hyperaldosteronism type II (FH-II) is known as an autosomal dominant hereditary disease, which is a scarce cause of PA. In this report, we cllected the clinical data of a patient with repeated hypertension and hypokalemia of uncertain diagnosis since 2014. Nevertheless, we discovered by genetic sequencing in 2021 that the CLCN2 and WFS1 gene mutation of the patient, whose mother belongs to heterozygote genotype and father belongs to wild-type genotype. Combined with a series of endocrine function tests and imaging studies, the patient was finally certified her suffering from FH-II and WFS1 gene mutation. By summarizing and analyzing the characteristics and genetic test results of this case, we recommended gene sequencing for patients with PA whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.原发性醛固酮增多症(primary aldosteronism, PA)又简称原醛症，是指肾上腺皮质分泌过量醛固酮(aldosterone，ALD)，导致水钠潴留及肾素-血管紧张素系统受抑制，从而引起高血压、低血钾的一类疾病。家族性醛固酮增多症II型(familial hyperaldosteronism type II, FH-II)是PA的少见病因，为常染色体显性遗传病。本文收集1例自2014年起病以来反复高血压、低血钾的病例，该患者诊断结果一直未明确。2021年通过基因检测证实该患者存在CLCN2及WFS1基因突变，其母亲为杂合携带，父亲为野生型。结合内分泌功能试验结果及影像学资料，考虑患者为FH-II，同时合并WFS1基因突变。通过总结分析该病例特点及基因检测结果，对于临床难以明确病因的PA建议可行基因测序。该病例也为后续遗传学研究提供临床资料。.

The paper aimed to explore the mechanism of miR-137 in modulating glioma.qRT-PCR detected miR-137 and E2F7 mRNA expression in cells. The protein expression of E2F7 was measured using Western blot assay. Cell proliferation, scratch healing, transwell and programmed cell death assays were conducted to examine the influences of the genes on the biological function of glioma cells. The dual-luciferase assay verified the interaction between miR-137 and E2F7.MiR-137 was lowly expressed in glioma cells, and E2F7 was highly expressed. MiR-137 suppressed progression and promoted programmed cell death of glioma cells. MiR-137 could target and negatively regulate E2F7 expression to further accelerate programmed cell death of glioma cells.It was found that miR-137 could target E2F7 to restrain cell progression and accelerate programmed cell death of glioma cells, which is helpful to search for new molecular therapeutic targets for glioma.

Currently, there have been few studies on the function and molecular mechanism of miR-141-3p in the development of clear cell renal cell carcinoma (CCRCC). This study aimed to explore the relationship between miR-141-3p and NIMA (never in mitosis, gene A)-related kinase-6 (NEK6) and investigate the role of the interaction in CCRCC cell proliferation, migration, invasion and apoptosis.Starbase database was used to predict the target gene of miR-141-3p in CCRCC and dual-luciferase reporter assay was performed to verify the targeting relationship between miR-141-3p and the target gene. Real-time quantitative PCR was conducted to detect the expression of miR-141-3p and NEK6 mRNA in cells. Western blot was carried out to detect the protein level of NEK6 in cells. Cell Counting Kit-8 assay, transwell assay and wound healing assay were conducted to detect CCRCC cell proliferation, invasion and migration abilities. Flow cytometry was performed to detect CCRCC cell apoptosis. miR-141-3p was markedly lowly expressed, and NEK6 was a target of miR-141-3p and was remarkably highly expressed in CCRCC cells. Over-expressing miR-141-3p could inhibit CCRCC cell proliferation, migration, invasion and promote apoptosis. The inhibitory effect of miR-141-3p over-expression on cell proliferation, migration and invasion was significantly weakened by over-expressing NEK6. miR-141-3p could regulate CCRCC cell proliferation, migration, invasion and apoptosis by targeting NEK6. This study lays the basis for the exploration of the molecular mechanism underlying CCRCC pathogenesis and research on targeted therapies for CCRCC.

Background Laparoscopic liver resections (LLR) have been shown a treatment approach comparable to open liver resections (OLR) in hepatocellular carcinoma (HCC). However, the influence of procedural type on body composition has not been investigated. The aim of the current study was to compare the degree of skeletal muscle loss between LLR and OLR for HCC. Methods By using propensity score matching (PSM) analysis, 64 pairs of patients were enrolled. The change of psoas muscle index (PMI) after the operation was compared between the matched patients in the LLR and OLR. Risk factors for significant muscle loss (defined as change in PMI > mean change minus one standard deviation) were further investigated by multivariate analysis. Results Among patients enrolled, there was no significant difference in baseline characteristics between the two groups. The PMI was significantly decreased in the OLR group (P = 0.003). There were also more patients in the OLR group who developed significant muscle loss after the operations (P = 0.008). Multivariate analysis revealed OLR (P = 0.023), type 2 diabetes mellitus, indocyanine green retention rate at 15 min (ICG-15) > 10%, and cancer stage ≧ 3 were independent risk factors for significant muscle loss. In addition, significant muscle loss was associated with early HCC recurrence (P = 0.006). Metabolomic analysis demonstrated that the urea cycle may be decreased in patients with significant muscle loss. Conclusion LLR for HCC was associated with less significant muscle loss than OLR. Since significant muscle loss was a predictive factor for early tumor recurrence and associated with impaired liver metabolism, LLR may subsequently result in a more favorable outcome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019. Several studies reported that SARS-CoV-2 infections may produce false-positive reactions in dengue virus (DENV) serology tests and vice versa. However, it remains unclear whether SARS-CoV-2 and DENV cross-reactive antibodies provide cross-protection against each disease or promote disease severity. In this study, we confirmed that antibodies against the SARS-CoV-2 spike protein and its receptor-binding domain (S1-RBD) were significantly increased in dengue patients compared to normal controls. In addition, anti-S1-RBD IgG purified from S1-RBD hyperimmune rabbit sera could cross-react with both DENV envelope protein (E) and nonstructural protein 1 (NS1). The potential epitopes of DENV E and NS1 recognized by these antibodies were identified by a phage-displayed random peptide library. In addition, DENV infection and DENV NS1-induced endothelial hyperpermeability in vitro were inhibited in the presence of anti-S1-RBD IgG. Passive transfer anti-S1-RBD IgG into mice also reduced prolonged bleeding time and decreased NS1 seral level in DENV-infected mice. Lastly, COVID-19 patients’ sera showed neutralizing ability against dengue infection in vitro. Thus, our results suggest that the antigenic cross-reactivity between the SARS-CoV-2 S1-RBD and DENV can induce the production of anti-SARS-CoV-2 S1-RBD antibodies that cross-react with DENV which may hinder dengue pathogenesis.

Several studies have shown the ability of transcription factor 12 (TCF12) to promote tumor malignant progression, but its function in glioma cells has not been fully elucidated. In this study, we analyzed the data from TCGA by bioinformatics and found that in glioma tissue, TCF12 was conspicuously highly expressed while miR-218-5p was significantly low-expressed. The downregulation of miR-218-5p was correlated with adverse prognosis in patients with glioma. miR-218-5p was found to be negatively associated with TCF12 by Pearson correlation analysis, and dual luciferase assay was employed to verify that miR-218-5p and TCF12 had a targeting relationship. qRT-PCR and Western blot assays were used to verify that the expression of TCF12 was regulated by its upstream regulator miR-218-5p. Moreover, cell experiments validated that overexpressed TCF12 could promote the proliferation, migration, and invasion of glioma cells and inhibit their apoptosis, whereas overexpressing miR-218-5p at the same time could reverse this phenomenon. Our study demonstrates the regulatory mechanism of the miR-218-5p/TCF12 axis in gliomas, which lays a foundation for searching for new therapeutic approaches for glioma.

Neonicotinoid (NEO) pesticides have become a potential risk to ecological safety and human health after application. The combined use of biochar and organic fertilizer (OF) is a promising approach to reduce pesticide adverse effects and improve soil fertility in agricultural soils. However, the combined remediation effects of biochar and OF on immobilization and dissipation of NEOs in soils have not previously been systematically investigated. In this study, biochars derived from peanut shell prepared at low/high pyrolysis temperatures (PS400 and PS900) were combined with composted chicken manure (CCM) as an example for OF to remediate contaminated soils toward six typical NEOs, nitenpyram (NIT), thiamethoxam (THIA), clothianidin (CLO), imidacloprid (IMI), acetamiprid (ACE), thiacloprid (THI). Results shown that both biochars and CCM were effective in improving soil sorption capacity and immobilization efficiency. The Freundlich affinity parameters (K

Drug-induced liver injury (DILI) occurs frequently worldwide. Acetaminophen (APAP) is a common drug causing DILI. Current treatment methods are difficult to achieve satisfactory results. Therefore, there is an urgent need to provide safe and effective treatment for patients. Schizandrin B (Sch B), the main component of Schisandra, has a protective effect on liver. However, the potential mechanism of Sch B in the treatment of APAP induced liver injury has not been elucidated to date. In our research, we studied the effect of Sch B on protecting damaged liver cells and explored the potential mechanism underlying its ability to reduce APAP liver injury. We found that Sch B could reduce hepatocyte apoptosis, oxidative stress injury and inflammatory response. These effects were positively correlated with the dose of Sch B. Sch B regulated glucose 6-phosphate dehydrogenase expression by upregulating the expression of p21-activated kinase 4 and polo-like kinase 1. Sch B could inhibit the mitogen-activated protein kinase (MAPK)-c-Jun N-terminal kinase (JNK)-extracellular signal-regulated kinase (ERK) signaling pathway and regulate the expression of apoptosis-related proteins to reduce the incidence of cell apoptosis. In addition, Sch B reduced the expression levels of reactive oxygen species and inflammatory cytokines in hepatocyte. Consequently, we described for the first time that Sch B could not only activate the pentose phosphate pathway but also inhibit the MAPK-JNK-ERK signaling pathway, thereby achieving antioxidative and anti-inflammatory effects and inhibiting hepatocyte apoptosis. These findings indicated the potential use of Sch B in curing liver damage induced by APAP.

To explore how AADAC functions in the malignant progression of ovarian cancer, and the effect of AADAC on drug therapeutic activity against ovarian cancer cells.AADAC level in tumor and normal samples from TCGA-OV dataset and its survival significance were analyzed by bioinformatics methods. Signaling pathway enrichment analysis for the high- and low-AADAC patients was achieved by using GSEA software. AADAC expression in the cell lines with different treatments was evaluated via qRT-PCR. Cell proliferative ability was assessed via MTT assay Cell migratory and invasive abilities were evaluated via transwell assay. Angiogenesis assay was performed to examine the angiogenetic ability.AADAC was upregulated in ovarian cancer tissues, and patients with high expression of AADAC had favorable survival conditions compared to the low AADAC expression ones. Overexpression of AADAC inhibited the malignant progression of ovarian cancer cells. Both cisplatin and imatinib suppressed cancer cell malignant progression, while overexpressed AADAC synergistically enhanced such inhibition.The study demonstrated that AADAC could somehow suppress the malignant progression of ovarian cancer, especially at the cellular level. In addition, synergic tumor-inhibitory effects between AADAC and the anti-cancer drugs were identified. All the above results proposed a novel idea and candidate biomarker for ovarian cancer therapy.

Purpose Risankizumab is a humanized immunoglobulin G1 monoclonal antibody that inhibits the p19 subunit of interleukin 23 from interacting with its receptor for the treatment of moderate to severe plaque psoriasis. The aim of this Phase I biopharmaceutics bridging study was to evaluate the pharmacokinetic comparability, immunogenicity, and tolerability of the risankizumab 90 mg/mL prefilled syringe (PFS) and the risankizumab 150 mg/mL PFS and auto-injector (AI) in healthy subjects. Methods Healthy subjects received one 150-mg dose of risankizumab in 1 of 3 ways (226 subjects randomized 3:3:1 to 3 treatment arms): 150 mg/mL by PFS × 1 SC injection, 90 mg/mL by PFS × 2 SC injections, or 150 mg/mL by AI × 1 SC injection, and were followed up for 140 days after dosing for the collection of pharmacokinetic, immunogenicity, and tolerability data. Findings Risankizumab concentration–time profiles overlapped with comparable pharmacokinetic parameters across all treatment arms, indicating similar pharmacokinetic characteristics. The CIs with both formulations and forms of administration were within the bioequivalence range of 0.80–1.25 across all measures of exposure. The prevalence of treatment-emergent anti-drug antibodies and the percentages of subjects who reported at least 1 treatment-emergent adverse event were comparable across all treatment arms. Implications Bioequivalence was established between risankizumab 150 mg/mL PFS and 90 mg/mL PFS, and between 150 mg/mL PFS and AI, along with comparable immunogenicity profiles across all 3 treatment arms. Risankizumab 150 mg SC delivered by PFS or AI was well tolerated, with comparable safety profiles across all treatment arms, and no new safety risks were identified.

Alzheimer's disease (AD) is the most common cause of dementia. Increasing evidence shows that mitochondrial DNA (mtDNA) methylation plays an essential role in many diseases related to mitochondrial dysfunction. Since mitochondrial impairment is a key feature of AD, mtDNA methylation may also contribute to AD, but few studies have addressed this issue. Methylation changes of the mitochondrial cytochrome b (CYTB) and cytochrome c oxidase II (COX II) genes in AD have not been reported. We analyzed mtDNA methylation changes of the CYTB and COX II genes in an APP/PS1 transgenic mouse model of AD using pyrosequencing. We examined mtDNA copy numbers and the levels of expression by quantitative real-time PCR. Average methylation levels of different CpG sites were ≤ 4.0%. Methylated mtDNA accounted for only a small part of the total mtDNA. We also observed hypermethylation of mitochondrial CYTB and COX II genes with decreased mtDNA copy numbers and expression in the hippocampi of APP/PS1 transgenic mice. mtDNA methylation may play an important role in AD pathology, which may open a new window for AD therapy.

Summary The Coronavirus disease 2019 (COVID-19) outbreak has been brought under control through a nationwide effort, and now it has become a global pandemic and the situation seems grim. We summarized the measures taken in Wuhan and analyzed the effects to comprehensively describe the factors involved in controlling the COVID-19 in China. In China, several measures such as the lockdown of Wuhan, restriction of traffic and communities, increasing hospital beds, nationwide support from medical staff, epidemic prevention equipment and supplies, and establishment of makeshift shelter hospitals have been taken. The lockdown of Wuhan reduced the propagation of cases to other cities in Hubei province and throughout China, traffic and community restrictions reduced the flow of population and the spread of disease, increasing wards and beds and medical personnel reduced the incidence of severe cases and mortality, the establishment of the Fangcang shelter hospitals provided a good isolation and monitoring environment, and further reduced the spread and fatality of the disease. The fact that China was able to control the spread of COVID-19 within three months without a specific drug or vaccine suggests that these measures are more adequate and effective.

The blood-brain barrier (BBB) is a physical barrier that selectively prevents certain substances from entering the brain through the blood. The BBB protects the brain from germs and causes difficulty in intracranial treatment. The chemotherapy drug temozolomide (TMZ), embedded in nanobubbles (NBs) and combined with persistent luminescent nanoparticles (PLNs), has been used to treat glioblastoma (GBM) effectively through image tracking. Through ultrasound induction, NBs produce cavitation that temporarily opens the BBB. Additionally, the PLNs release near-infrared emission and afterglow, which can penetrate deep tissues and improve the signal-to-noise ratio of bioimages. In this work, the nanosystem crossed the BBB for drug delivery and image tracking over time, allowing the enhancement of the drug's therapeutic effect on GBM. We hope that this nanosystem can be applied to the treatment of different brain diseases by embedding different drugs in NBs.

Endometrial cancer (EC) is a common gynecological tumor and the third leading cause of cancer-related death in women. Previous research has proved that long noncoding RNA (lncRNA) FOXCUT acts as an oncogene in several cancers. This study ascertained that lncRNA FOXCUT was highly expressed in endometrial cancer cells. Overexpression of lncRNA FOXCUT promoted EC cell proliferation, invasion, and migration, as well as epithelial-mesenchymal transition (EMT). In addition, overexpression of lncRNA FOXCUT could inhibit the apoptosis of cancer cells and block EC cells in S phase, whereas silencing lncRNA FOXCUT had the opposite effect. Thus, lncRNA FOXCUT had a regulatory effect on promoting the progression of EC cells, which might provide novel potential targets for research on targeted therapy of EC.

The intestines have been recognized as important tissues for metabolic regulation, including glycemic control, but their vital role in promoting the anti-diabetic effects of bitter melon, the fruit of Momordica charantia L, has seldom been characterized, nor acknowledged. Evidence suggests that bitter melon constituents can have substantial interactions with the intestinal epithelial cells before circulating to other tissues. We therefore characterized the effects of bitter melon extract (BME) on intestinal epithelial cells. BME was found to contain substantial amounts of carbohydrates, proteins, and triterpenoids. TNF-α induced insulin resistance in an enterocyte cell line of IEC-18 cells, and BME promoted glucose utilization of the insulin-resistant cells. Further analysis suggested that the increased glucose consumption was a result of the combined effects of insulin sensitizing and insulin substitution functions of BME. The functions of insulin substitution were likely generated due to the activation of AMP-activated protein kinase. Meanwhile, BME acted as a glucagon-like peptide 1 (GLP-1) secretagogue on enteroendocrine cells, which may be mediated by the activation of bitter-taste receptors. Therefore, BME possesses insulin sensitizing, insulin substitution, and GLP-1 secretagogue functions upon intestinal cells. These effects of BME on intestinal cells likely play a significant part in the anti-diabetic action of bitter melon.

Background Low-acuity outpatients constitute the majority of emergency department (ED) patients, and these patients often experience an unpredictable length of stay (LOS). Effective LOS prediction might improve the quality of ED care and reduce ED crowding. Objective The objective of this study was to explore the potential of natural language processing (NLP) of the first ED physicians' clinical notes and to evaluate NLP-based short-term prediction models based on mixed-type clinical data. Methods A retrospective study was conducted at an ED of a tertiary teaching hospital in Taiwan from January 2017 to June 2017. In total, 12,962 low-acuity outpatients were enrolled. Using structured data (e.g., demographic variables and vital signs) and different sections of the first SOAP notes as predictors, we developed six NLP-based prediction models (i.e., term frequency-inverse document frequency (TF-IDF) and truncated singular value decomposition (SVD)) to predict LOS. The metric for model evaluation is the mean squared error (MSE). Results Of the six NLP-based models, the model using structured data and all the sections of the first SOAP notes processed by the TF-IDF and truncated SVD method performed the best, with an MSE of 3.00 [95% CI: 2.94–3.06]. In addition, ten important topics extracted by the TF-IDF and truncated SVD method had significant effects on the LOS (p Conclusion NLP-based models can be used as an early short-term prediction of LOS and have the potential for mixed-type clinical data analysis. The proposed models would likely aid ED physicians' decision-making processes and improve ED quality of care.

The study aimed to explore the relationship between miR-9-5p and ESR1, and clarify the underlying functional mechanism in the occurrence and development of hepatocellular carcinoma (HCC). Expression data including miRNAs and mRNAs of HCC downloaded from TCGA database were processed for differential analysis, and corresponding clinical data were collected for survival analysis to identify the target miRNA miR-9-5p. Bioinformatics databases were applied for predicting downstream target mRNAs of miR-9-5p. qRT-PCR was used to evaluate expression of miR-9-5p. Western blot was used to detect protein expression of ESR1. MTT, wound healing assay and Transwell assay were used to detect HCC cell proliferation, migration and invasion, respectively. Dual-luciferase reporter gene assay was used to identify the targeting relationship between miR-9-5p and ESR1. Research suggested that miR-9-5p was highly expressed in HCC cells but ESR1 was poorly expressed. Overexpression of miR-9-5p could improve the proliferation, invasion and migration of cells. Dual-luciferase reporter assay showed that ESR1 was the downstream target of miR-9-5p in HCC. Overexpression of miR-9-5p markedly reduced ESR1 mRNA and protein levels in HCC cells, whereas inhibition of miR-9-5p expression produced the contrary results. Silencing ESR1 could noticeably reverse the effect of miR-9-5p knockdown on the proliferation, migration and invasion of HCC cells. As an oncogene, miR-9-5p fostered the proliferation, migration and invasion of HCC cells by targeting and inhibiting ESR1 expression.

Background Ovarian malignancy is among the most common lethal cancers in gynaecology. It has been considered that nutrition status and inflammation are two essential factors associated with the poor survival rates of patients suffering from multiple tumours. Methods This research included 174 subjects who suffered from FIGO stage I-IV OC and underwent surgeries between May 2008 and March 2013. Results The results showed that FAR, T3–T4 depth, high CA125, stage III-IV and metastasis were highly associated with low overall survival rates. Moreover, higher FCI was markedly correlated with decreased survival in patients with OC. Conclusions The combination of FAR and CA125 could be a new non-invasive marker in blood and probably assist physicians in evaluating the prognosis of patients.

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG–Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.

For resectable esophageal cancer (EC), it remains controversial whether to place percutaneous endoscopic gastrostomy (PEG) before the curative surgery to provide nutritional support during the neoadjuvant therapy. To compare surgical outcomes for patients who received preoperative PEG and those without PEG placement (No-PEG) insertion prior to surgery in a potentially operable EC. A comprehensive literature search was conducted to identify randomized and non-randomized studies comparing PEG and No-PEG groups. Four retrospective studies with a total number of 1,027 patients were identified and included in this meta-analysis. The differences in anastomotic leakage, anastomotic stricture, morbidity, pulmonary complications, wound infection, and hospital stay were not statistically significant between the two groups. Operation time was significantly shorter in the PEG group. There was no PEG-related gastric conduit failure and no leak from the PEG site in the PEG group. We conclude preoperative PEG for resectable EC is a safe procedure with no adverse effect on the gastric tube construction and anastomosis, it can be selectively inserted for EC patients with marked weight loss and malnutrition or those at risk of developing malnutrition during neoadjuvant therapy.

BACKGROUND There remains an unmet need in objective tests for diagnosing asthma in children. The objective of this study was to investigate the potential of metabolomic profiles of exhaled breath condensate (EBC) to discriminate stable asthma in Asian children in the community. METHODS One hundred and sixty-five Asian children (92 stable asthma and 73 non-asthmatic controls) participating in a population-based cohort were enrolled and divided into training and validation sets. Nuclear magnetic resonance-based metabolomic profiles of EBC samples were analyzed by using orthogonal partial least squares discriminant analysis. RESULTS EBC metabolomic signature (lactate, formate, butyrate, and isobutyrate) had an area under the receiver operator characteristic curve (AUC) of 0.826 in discriminating children with and without asthma in the training set, which significantly outperformed FeNO (AUC = 0.574; P

Introduction Due to diverse symptoms of spinocerebellar ataxia type 3 (SCA3) and the high prevalence of SCA3 in China, a more in-depth study of Chinese SCA3 patients in a large cohort is well merited. Methods During the last 10 years, 730 patients and 133 premanifest individuals from 667 SCA3 families genetically confirmed to have SCA3 were enrolled from three leading academic hospitals in China. The clinical profile and genotype-phenotype correlation were analyzed. Results A quadratic equation best explained the relationship between the logarithmically transformed age at onset (AAO) and expanded CAG repeats (expCAGs) (r2 = 0.634, p 10 years. Intriguingly, onset after parturition happened in 10 female patients with the AAO of 26.7 ± 4.3 years and the expCAG of 77.4 ± 1.4 repeats. Five out of 12 patients with subtype V and larger expCAGs (78.8 ± 4.8 repeats) suffered from spastic gait initially, and 10 out of 12 showed no limb ataxia. Nystagmus happened most frequently (10.5%) in premanifest individuals. Conclusion We demonstrated the genotype-phenotype correlation in the largest cohort of SCA3 individuals to date, and interestingly found some new phenomena in Chinese SCA3 individuals.

Alcoholic hepatitis (AH) is identified as an inflammatory syndrome with high morbidity and mortality as a result of severe hepatocellular dysfunction and liver injury. Accumulated studies indicated that miRNAs are involved in AH. The potential effect of miR‐451a in AH mice was examined in the current study. A mice AH model was established and the miR‐451a expression in AH mice compared with the sham group was tested by real‐time polymerase chain reaction (qRT‐PCR). AH mice were injected with pre‐miR‐451a lentivirus for miR‐451a overexpression and histone deacetylase (HDAC8) lentivirus for HDAC8 overexpression in AH mice. The underlying mechanisms were explored by searching the potential target genes of miR‐451a in miRanda database and then we confirmed this. We found that miR‐451a expression was significantly decreased in AH mice compared with the sham group. Moreover, miR‐451a overexpression alleviated alcohol‐induced liver inflammation and injuries of AH mice. Additionally, further mechanism exploration disclosed that HDAC8 was a target of miR‐451a. The protective effect of miR‐451a on AH in AH mice was abolished by HDAC8 overexpression. In summary, miR‐451a ameliorates AH via repressing HDAC8‐mediated proinflammatory response.

Background Team-based learning (TBL) is increasingly being utilized across medical fields by engaging students in small group discussions. The readiness assurance test (RAT) is an essential feature that differentiates TBL from problem-based learning (PBL) activity sequences. No publication has discussed differences in the RAT in TBL in medical schools. The purpose of this meta-analysis study was to examine the performance of learners in terms of group RAT (GRAT) and individual RAT (IRAT) scores in TBL for students of healthcare professions. Methods Databases, including PubMed and Cochrane were searched using several terms. We assessed the quality of included studies and conducted a meta-analysis. Results In total, 11 studies with 1575 participants were identified. Quality assessment scores of these studies ranged 4 ~ 7. Mean GRAT scores were significantly higher than mean IRAT scores (standardized mean difference (SMD) = 2.027, 95% confidence interval (CI) = 1.657 ~ 2.486, p heterogeneity < 0.001). Although the test of subgroup differences was insignificant (p = 0.113), the nursing-only subgroup showed much better performance in the GRAT than the IRAT (SMD = 2.3CI: 95% CI = 2.0 ~ 2.6, I2 = 48.77%) compared to the others subgroup which included students from different majors. The subgroup analysis explained the heterogeneity in the overall analysis. Because of inadequate information from these 11 studies, a meta-regression could not explore the source of heterogeneity in terms of the mean age, duration of the intervention, preparation time before the RAT, and previous TBL experienced by students. Conclusions Students achieved significantly higher scores for the GRAT than for the IRAT, especially the group which only included nursing students, which implies excellent collaboration in the group of nursing students.

Summary ADP-ribosylation factor-like 4aa (Arl4aa) is a member of the ADP-ribosylation factor family. It is expressed in hematopoietic tissue during embryonic development, but its function was unknown. Zebrafish arl4aa is preferentially expressed in the ventral wall of the dorsal aorta (VDA) at 24 and 36 hpf and in caudal hematopoietic tissue at 48 hpf. Morpholino knockdown and transcription activator-like effector nuclease (TALEN) knockout of arl4aa significantly reduced expression of genes associated with definitive hematopoietic stem cells (HSCs). Golgi complex integrity in VDA was disrupted as shown by transmission electron microscopy and immunostaining of Golgi membrane Giantin. Mechanistically, arl4aa knockdown reduced Notch signaling in the VDA and its target gene expression. Protein expression of NICD was also reduced. Effects of arl4aa knockdown on definitive hematopoiesis could be restored by NICD expression. This study identified arl4aa as a factor regulating initiation of definitive HSCs by maintaining the integrity of Golgi complex and, secondarily, maturation of the Notch receptor., Highlights • arl4aa expressed in ventral wall of dorsal aorta and caudal hematopoietic tissue • arl4aa maintained Golgi complex integrity and Notch signaling in definitive HSCs • Deletion of arl4aa perturbed initiation of definitive HSCs, In this study, Anskar Y.H. Leung and colleagues show that arl4aa was expressed in the ventral wall of the dorsal aorta and caudal hematopoietic tissue during zebrafish embryo development. Deletion of arl4aa disrupted the integrity of the Golgi complex and Notch signaling and perturbed derivation of definitive hematopoietic stem cells from hemogenic endothelium. arl4aa might emerge as a regulator of embryonic hematopoiesis.

Introduction Whereas evidence has shown that a sense of purpose is linked to optimal adjustment, longitudinal work investigating the development of purpose identification as well as its effect on psychological functioning among non-Western samples during adolescence is needed. Methods Three hundred and eighty-seven senior high school students (253 female, 65.37%; mean age = 15.76 years at the first investigation) from Taiwan completed surveys four times beginning in the fall of tenth grade and ending in the spring of eleventh grade with a six-month interval. Using self-ratings, purpose identification was evaluated in all four assessments and psychological functioning was examined through life satisfaction and depressive symptoms in the first and the last survey. Results Growth curve analyses revealed an increased slope in purpose identification over the first two years of high school, and such a trajectory was similar across boys and girls. Additionally, increases in purpose identification predicted enhanced life satisfaction and reduced depressive symptoms among both boys and girls. There was only one gender difference: The negative association between purpose identification trajectory and depressive symptoms was stronger for girls than for boys. Conclusions There is an increase in the development of identified purpose during middle adolescence among high school students in Taiwan. Such change not only promotes life satisfaction in adolescents but is also preventive of adolescent depression. As such, the current findings highlight the significance for adolescents to discover and commit to a purpose.

Background/purpose(s): Enterovirus D68(EV-D68) is an emerging disease that affects mostly children. There have been few relevant investigations to clarify transmission and seroprevalence within daycares and kindergartens. Methods: This prospective cohort study investigated respiratory viral transmission among preschool children in a public kindergarten in Taipei City of Taiwan between September 2006 and June 2008. After children were enrolled, daily monitoring of illness and regular biweekly physical examinations were performed. We performed viral isolation to detect acute EV-D68 infection and neutralization tests to detect specific EV-D68 antibodies and to measure the seroprevalence and seroconversion rates. Results: Among 190 kindergarten attendees aged between two to five years old, nine children had acute EV-D68 infection in September 2007. The clinical manifestations included pharyngitis, cough and other unspecified upper respiratory tract infection. None of the infected children had acute flaccid paralysis or severe respiratory illness. The phylogenetic tree of partial viral protein 3 and viral protein 1 was clustered in clade A1. The EV-D68 seropositive rate increased from 19% (25/130) at the beginning to 67% (83/124) at the end of the study. The seroconversion rate of 49 children with initial seronegative and paired sera was 73% (36/49). Conclusions: A high seroconversion rate (73%) for EV-D68 was found among kindergarten attendees, which indicates preschool-aged children are highly susceptible to EV-D68 infection and that the disease burden may be extremely underestimated. Once EV-D 68 circulates, preventive measures may be advocated, especially within kindergartens or daycares, to reduce transmission and subsequent development of severe cases. Keywords: Enterovirus D68, Kindergarten attendees, Manifestation, Seroconversion

Drawing on the information processing model for the development of aggression, children's acquisition of aggressive responses could be associated with parenting that communicated norms favoring aggression. Extending this view, the present study examined the mediating role of children's normative beliefs about relational aggression (NBRA) on the association between psychologically controlling parenting and children's relational aggression (RA), and further explored whether this possible indirect effect would be contingent on the child's gender. 341 upper elementary school students (174 boys and 166 girls) reported perceived paternal psychological control (PPC) and maternal psychological control (MPC) during their fifth-grade fall semester, rated their NBRA during their sixth-grade fall semester, and assessed RA through a peer-nomination procedure during their sixth-grade spring semester. Results demonstrated that the indirect effects of perceived PPC and MPC on children's RA

Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease., Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.

A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other (P Atopobium (P Fusobacterium (P

Papillary thyroid cancer (PTC) has attracted much attention due to its high morbidity and severe metastasis. Long noncoding RNA ENST00000504230 (LncRNA ENST00000504230, known as LINC00958) was overexpressed in many cancers and associated with cancer development. However, its underlying mechanism in PTC remains unclear. PTC tissues and corresponding adjacent tissues were collected for measuring the expression of LINC00958 and miR-627. MiR-627 and TRIM44 expressions were measured in in vitro cultured PTC cell lines (B-cpap and IHH4 cells) transfected with sh-LINC00958 or miR-627 mimic using RT-qPCR and western blot. Cell proliferation, migration, and invasion were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Transwell assays, respectively. Dual-luciferase reporter assay was performed to evaluate the target association between miR-627 and TRIM44. LINC00958 was up-regulated in PTC tissues and cells, while the expression of miR-627 was lowly expressed. Knockdown of LINC00958 inhibited the proliferation, migration, and invasion by elevating miR-627 expression in PTC cells. TRIM44 was confirmed as a target of miR-627. Overexpression of miR-627 in PTC inhibited the proliferation, migration, and invasion by down-regulating the expression of TRIM44. LINC00958 promoted proliferation, migration, and invasion in PTC by down-regulating miR-627 and activating TRIM44, indicating the potential therapeutic effect of LINC00958 on PTC.

Background Although many causative genes have been uncovered in recent years, genetic diagnosis is still missing for approximately 50% of autosomal recessive cerebellar ataxia (ARCA) patients. Few studies have been performed to determine the genetic spectrum and clinical profile of ARCA patients in the Chinese population. Methods Fifty-four Chinese index patients with unexplained autosomal recessive or sporadic ataxia were investigated by whole-exome sequencing (WES) and copy number variation (CNV) calling with ExomeDepth. Likely causal CNV predictions were validated by CNVseq. Results Thirty-eight mutations including 29 novel ones were identified in 25 out of the 54 patients, providing a 46.3% positive molecular diagnostic rate. Ten different genes were involved, of which four most common genes were SACS, SYNE1, ADCK3 and SETX, which accounted for 76.0% (19/25) of the positive cases. The de novo microdeletion in SACS was reported for the first time in China and the uniparental disomy of ADCK3 was reported for the first time worldwide. Clinical features of the patients carrying SACS, SYNE1 and ADCK3 mutations were summarized. Conclusions Our results expand the genetic spectrum and clinical profiles of ARCA patients, demonstrate the high efficiency and reliability of WES combined with CNV analysis in the diagnosis of suspected ARCA, and emphasize the importance of complete bioinformatics analysis of WES data for accurate diagnosis.

Background Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. Case presentation A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). Conclusions In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.

In recent years, skin spectral information has been gradually applied in various fields, such as the cosmetics industry and clinical medicine. However, the high price and the huge size of the skin spectrum measurement device make the related applications of the skin spectrum unable to be widely used in practical applications. We used convolutional neural network (CNN) to achieve a satisfying accuracy of the Fitzpatrick skin-type classification by using a simple self-developed device in 2018. Leveraging on the hardware, firmware, and software app-developing experience, a low-cost miniature skin spectrum measurement system (LMSSMS) using deep neural network (DNN) technology was further studied, and the feasibility of the system is verified in this paper. The developed LMSSMS is divided into three parts: (1) miniature skin spectrum measurement device (MSSMD), (2) DNN model, and (3) mobile app. The MSSMD was developed with innovative low-cost MSSC, 3D printing, and a simple LED light source. The DNN model is designed to enhance measurement accuracy. Finally, the mobile app is used to control and show the measurement results. The developed app also includes a variety of skin-spectrum-related applications, such as erythema index and melanin index (EI/MI) measurement, Fitzpatrick skin-type classification, Pantone SkinTone classification, sun-exposure estimation, and body-fat measurement. In order to verify the feasibility of LMSSMS, we used the standard instrumentation device as a reference. The results show that the accuracy of the LMSSMS can reach 94.7%, which also confirms that this development idea has much potential for further development.

Hepatocellular carcinoma (HCC) is a type of common cancer, often accompanied by tumor recurrence and metastasis after surgery with poor prognosis. Therefore, searching into potential biomarkers that can effectively predict the prognosis and progression of HCC is crucial. In this study, we identified 1,981 differentially expressed genes (DEGs) using mRNA expression profiles from the TCGA-LIHC dataset. Subsequently, weighted gene co-expression network analysis found that the turquoise module closely associated with the pathological grade and clinical stage of HCC was identified. Then, from the key genes in the turquoise module and protein-protein interaction network analysis, 13 hub genes significantly related to the prognosis of HCC were screened. Through co-expression and functional enrichment analyses, these 13 hub genes were found to play an important role in mitosis. Finally, we evaluated the relationship between these hub genes and overall survival and disease-free survival through survival analysis. The result indicated that HCC patients with high hub gene expression had a poorer prognosis than HCC patients with low expression. Receiver operating characteristic curves showed that each hub gene could predict the prognosis of HCC patients. In summary, a total of 13 hub genes were identified that play an important role in the progression of HCC, which can be used as potential biomarkers for HCC patients.

We aimed to evaluate the effect of low-frequency electro-acupuncture (EA) in unmarried women with polycystic ovary syndrome (PCOS).A total of 54 women with PCOS were randomly assigned to either the acupuncture group (n=27) or the sham acupuncture group (control, n=27) for a total of 32 treatments over 16 weeks. In the acupuncture group 26 patients and in the control group 20 patients completed the trial.Main measures were androgen levels including 17-α-hydroxyprogesterone (17-α-OHP), androstenedione (A2), testosterone (T) and dehydroepiandrosterone (DHEA) at 0, 24 and 48 hours after stimulation with a dose of human chorionic gonadotropin (HCG). Other measures included body mass index, waist-to-hip ratio, sex hormone levels, etc.After treatment, there was no significant difference in the main measures between the 2 groups (P.05), except for the DHEA level at 0 h of HCG stimulation (P = .024) and acne score (P.05). Comparison within the acupuncture group found that 17-α-OHP and A2 levels at 0 h and DHEA levels at 24 h of HCG stimulation after treatment were significantly decreased (P.05), whereas T levels at 24 h were significantly increased (P.05). Comparison within the control group showed 17-α-OHP level at 0 h and 17-α-OHP and A2 and DHEA levels at 24 h after treatment were significantly lower (P.05). In addition, weight, BMI, HCG and Ferriman-Gallwey score in the acupuncture group and LH/FSH ratio was significantly reduced in the control group.Traditional EA is slightly more effective than sham acupuncture in reducing DHEA secretion and the acne score. Meanwhile, sham acupuncture is not completely ineffective. The specific mechanism of the two may be different.

Inflammation is usually a tightly regulated process whose termination by mediators including Annexin A1 (AnxA1) results in the resolution of inflammatory responses. In neurodegenerative dementias, chronic neuroinflammation, along with accumulation of aggregated β-amyloid (Aβ) peptides and apoptosis, has long been recognized to be a pathological hallmark; but it is unclear whether a failure of inflammation resolution contributes to this pathophysiological process. In this study, we measured AnxA1 immunoreactivities in postmortem neocortex (Brodmann areas BA9 and BA40) of well characterized Alzheimer's disease (AD), Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) patients as well as aged controls. Inactive cleaved AnxA1 was found to be elevated in AD and DLB in BA40. Levels of cleaved AnxA1 also positively correlated with amyloidogenic brain Aβ, anti-inflammatory markers such as IL10 and IL13, as well as with the pro-apoptotic marker cleaved caspase-3 in BA40. Our findings suggest that elevated cleaved AnxA1 in neurodegenerative dementias may reflect a failure of inflammation resolution in certain regions of the diseased brain, and also support a mechanistic link between AnxA1 and amyloid pathology, neuroinflammation and apoptosis.

The COVID‐19 epidemic and government intervention measures may have adverse effects on people's mental health. To explore the influence of pets on the intervention of people's psychological problems during the COVID‐19 epidemic, an online survey was carried out between April 9 and April 29, 2020. A total of 756 participants replied to this questionnaire. Mental health variables were assessed, and the comparison of behavior changes among pet owners and pets on positive mental well‐being during COVID‐19 epidemic. Comparative analysis was performed; compared with individuals without pets (n = 575), pet owners (n = 181) had a higher prevalence of insomnia (p = 0.006). Living in Wuhan city was a risk factor for people with psychological stress (p

Increasing mitochondrial fusion by intra-tumoral grafting of membrane-fused mitochondria created with Pep-1 conjugation (P-Mito) contributes to breast cancer treatment, but it needs to be validated. Using mitochondrial division inhibitor-1 (Mdivi-1, Mdi) to disturb mitochondrial dynamics, we showed that the antitumor action of P-Mito in a mouse model of triple-negative breast cancer depends upon mitochondrial fusion and that Mdi treatment alone is ineffective. P-Mito significantly enhanced Doxorubicin (Dox) sensitivity by inducing mitochondrial fusion and mitophagy, and the same efficiency was also achieved with Mdi by inhibiting mitophagy. Cell death was induced via the p53 pathway and AIF nuclear translocation in the case of P-Mito, versus the caspase-dependent pathway for Mdi. Notably, both mitochondrial treatments reduced oxidative stress and blood vessel density of xenograft tumors, especially P-Mito, which was accompanied by inhibition of nuclear factor kappa-B activation. Furthermore, through enrichment analysis, four microRNAs in serum microvesicles induced by P-Mito caused expression of predicted targets via the PI3K-Akt pathway, and significantly impacted regulation of nuclear processes and myeloid cell differentiation. Clustering of gene-sets implicated a major steroid catabolic network. This study showed diverse roles of mitochondria in breast cancer and revealed effective adjuvant therapy targeting mitochondrial fusion and mitophagy.

Aim: Hepatocellular carcinoma (HCC) is considered to be the third leading cause of cancer death. The homologous gene of TP53 is significant in the occurrence and development of cancer. This study explored the relationship between TP53 rs28934571 polymorphism and HCC risk in Guangxi, China. Materials & methods: We first screened the association through bioinformatics. Additionally, a case–control study was performed to further verify the relationship between gene polymorphism and HCC risk after collecting clinical characteristics. Results: Results showed that allele A on TP53 rs28934571 was a risk factor for HCC and mutation from C to A on TP53 rs28934571 would increase the risk of poor prognosis of HCC. Conclusion: Therefore, the study concluded that TP53 rs28934571 may become a diagnostic indicator in judging the prognosis of HCC.

Osteoarthritis (OA) is a common chronic disease with increasing prevalence in societies with more aging populations, therefore, it is causing more concern. S-Equol, a kind of isoflavones, was reported to be bioavailable and beneficial to humans in many aspects, such as improving menopausal symptoms, osteoporosis and prevention of cardiovascular disease. This study investigated the effects of S-Equol on OA progress in which rat primary chondrocytes were treated with sodium nitroprusside (SNP) to mimic OA progress with or without the co-addition of S-Equol for the evaluation of S-Equol’s efficacy on OA. Results showed treatment of 0.8 mM SNP caused cell death, and increased oxidative stress (NO and H2O2), apoptosis, and proteoglycan loss. Furthermore, the expressions of MMPs of MMP-2, MMP-3, MMP-9, and MMP-13 and p53 were increased. The addition of 30 μM S-Equol could lessen those caused by SNP. Moreover, S-Equol activates the PI3K/Akt pathway, which is an upstream regulation of p53 and NO production and is associated with apoptosis and matrix degradation. As a pretreatment of phosphoinositide 3-kinases (PI3K) inhibitor, all S-Equol protective functions against SNP decrease or disappear. In conclusion, through PI3K/Akt activation, S-Equol can protect chondrocytes against SNP-induced matrix degradation and apoptosis, which are commonly found in OA, suggesting S-Equol is a potential for OA prevention.

Parkinson's disease (PD), the most common neurodegenerative motor disorder, is currently incurable. Although many studies have provided insights on the substantial influence of genetic factors on the occurrence and development of PD, the molecular mechanism underlying the disease is largely unclear. Previous studies have shown that point mutations in the phospholipase A2 group VI gene (PLA2G6) correlate with young-onset dystonia-parkinsonism type 14 (PARK14). However, limited information is available regarding the pathogenic role of this gene and the mechanism underlying its function. To study the role of PLA2G6 mutations, we first used zebrafish larvae to screen six PLA2G6 mutations and revealed that injection of D331Y, T572I, and R741Q mutation constructs induced phenotypes such as motility defects and reduction in dopaminergic neurons. The motility defects could be alleviated by treatment with L-3, 4-dihydroxyphenylalanine (L-dopa), indicating that these mutations are pathological for PARK14 symptoms. Furthermore, the injection of D331Y and T572I mutation constructs reduced phospholipase activity of PLA2G6 and its lipid metabolites, which confirmed that these two mutations are loss-of-function mutations. Metabolomic analysis revealed that D331Y or T572I mutation led to higher phospholipid and lower docosahexaenoic acid (DHA) levels, indicating that reduced DHA levels are pathological for defective motor functions. Further, a dietary DHA supplement relieved the motility defects in PLA2G6D331Y/D331Y knock-in mice. This result revealed that the D331Y mutation caused defective PLA2G6 phospholipase activity and consequently reduced the DHA level, which is the pathogenic factor responsible for PARK14. The results of this study will facilitate the development of therapeutic strategies for PARK14.

Parthenogenesis, a unique form of reproduction, is normally inhibited in mammals and a human embryo with parthenogenetic origin is not considered capable of producing offspring. The aim of this report is to analyze a parthenogenetic oocyte retrieved from a patient so as to have a better understanding on parthenogenesis and causes of infertility. A 38-year-old woman presented at our center with a history of primary infertility for 10 years and underwent an IVF-ICSI cycle. Three MII oocytes retrieved and one of which presented with 1 pronucleus before conducting ICSI and developed into an embryo 30 h post-retrieval. Blastomere biopsy, genome amplification, copy number variation (CNV) analysis and MultiSNPs analysis was performed on the embryo. The results showed that only one blastomere contains DNA and CNV analysis indicated a genotype of 48, XX, +17, +17 and the genetic contribution of biopsied embryo was of exclusively maternal origin. Such analysis might be beneficial for patients with a history of oocyte spontaneous activation in diagnosing case-specific aberrations and providing individualized therapeutic strategies such as preimplantation genetic diagnosis to choose a genetic normal embryo to transplant.

Background Bronchial carcinoids are neuroendocrine tumors that present as typical (TC) and atypical (AC) variants, the latter being more aggressive, invasive and metastatic. Studies of tumor initiating cell (TIC) biology in bronchial carcinoids has been hindered by the lack of appropriate in-vitro and xenograft models representing the bronchial carcinoid phenotype and behavior. Methods Bronchial carcinoid cell lines (H727, TC and H720, AC) were cultured in serum-free growth factor supplemented medium to form 3D spheroids and serially passaged up to the 3rd generation permitting expansion of the TIC population as verified by expression of stemness markers, clonogenicity in-vitro and tumorigenicity in both subcutaneous and orthotopic (lung) models. Acetazolamide (AZ), sulforaphane (SFN) and the AZ + SFN combination were evaluated for targeting TIC in bronchial carcinoids. Results Data demonstrate that bronchial carcinoid cell line 3rd generation spheroid cells show increased drug resistance, clonogenicity, and tumorigenic potential compared with the parental cells, suggesting selection and expansion of a TIC fraction. Gene expression and immunolabeling studies demonstrated that the TIC expressed stemness factors Oct-4, Sox-2 and Nanog. In a lung orthotopic model bronchial carcinoid, cell line derived spheroids, and patient tumor derived 3rd generation spheroids when supported by a stroma, showed robust tumor formation. SFN and especially the AZ + SFN combination were effective in inhibiting tumor cell growth, spheroid formation and in reducing tumor formation in immunocompromised mice. Conclusions Human bronchial carcinoid tumor cells serially passaged as spheroids contain a higher fraction of TIC exhibiting a stemness phenotype. This TIC population can be effectively targeted by the combination of AZ + SFN. Our work portends clinical relevance and supports the therapeutic use of the novel AZ+ SFN combination that may target the TIC population of bronchial carcinoids.

Objective: To investigate the prognostic value of phenylalanine and leucine in patients with severe infection. Methods: Ninety-three patients with infection who had a quick Sequential Organ Failure Assessment (qSOFA) score ≥2 were enrolled. Plasma phenylalanine, leucine, albumin, C-reactive protein, pre-albumin, and transferrin were measured and the SOFA score at enrollment was calculated after hospitalization. Results: During the 3-month follow-up, 30 (32.3%) patients died. Death was associated with higher SOFA scores, a higher incidence of bacteremia and admission to the intensive care unit, higher C-reactive protein and phenylalanine levels, worse kidney function, and lower pre-albumin and transferrin levels. Patients were categorized into three groups: high-risk type 1 (phenylalanine ≥84 μM), high-risk type 2 (phenylalanine

EAbstract Objective The aim of this meta-analysis was to assess the efficacy and safety of treatment with echinocandins compared with amphotericin B in paediatric patients with invasive candidiasis. Methods PubMed, Embase and Cochrane databases were searched up to August 2018. Only randomized controlled trials (RCTs) evaluating echinocandins and amphotericin B in the treatment of paediatric patients with invasive candidiasis were included. The outcomes were clinical responses and adverse effects. Results Five RCTs of 354 patients (191 patients in the echinocandins group and 163 patients in the amphotericin B group) were included in this study. Overall, no significant differences in clinical response were found between echinocandins and amphotericin B (odds ratio [OR], 1.38; 95% confidence interval [CI], 0.68-2.80; I2 = 39%). Similar results were also observed in the high-risk group (OR, 3.10; 95% CI, 0.10-97.23; I2 = 76%), the low-risk group (OR, 1.29; 95% CI, 0.36-4.62; I2 = 21%) and the neutropenia group (OR, 1.56; 95% CI, 0.75-3.26; I2 = 0%). The risk of discontinuing treatment because of adverse effects was significantly lower in the echinocandins group than in the amphotericin B group (OR, 0.30, 95% CI, 0.12-0.76; I2 = 0%). Conclusions There were no differences in efficacy between the echinocandins group and the amphotericin B group in the treatment of invasive candidiasis in paediatric patients. However, the echinocandins group had a significantly lower risk of discontinuing treatment than the amphotericin B group.

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off—PVO2 − 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2