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Hai-Sheng You,1,* Chun-Xia Gao,1,* Hai-Bin Wang,2 Sai-Sai Luo,1 Si-Ying Chen,1 Ya-Lin Dong,1 Jun Lyu,3 Tao Tian4 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Hangzhou Cognitive N&T. Co., Ltd, Hangzhou, Zhengjiang, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TianDepartment of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-13572206784Fax +86-29-85324086Email tiantao0607@163.comJun LyuClinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86 29 8532 3614Fax +86 29 8532 3473Email lujun2006@xjtu.edu.cnObjective: The disease complexity of metastatic non-small-cell lung cancer (mNSCLC) makes it difficult for physicians to make clinical decisions efficiently and accurately. The Watson for Oncology (WFO) system of artificial intelligence might help physicians by providing fast and precise treatment regimens. This study measured the concordance of the medical treatment regimens of the WFO system and actual clinical regimens, with the aim of determining the suitability of WFO recommendations for Chinese patients with mNSCLC.Methods: Retrospective data of mNSCLC patients were input to the WFO, which generated a treatment regimen (WFO regimen). The actual regimen was made by physicians in a medical team for patients (medical-team regimen). The factors influencing the consistency of the two treatment options were analyzed by univariate and multivariate analyses.Results: The concordance rate was 85.16% between the WFO and medical-team regimens for mNSCLC patients. Logistic regression showed that the concordance differed significantly for various pathological types and gene mutations in two treatment regimens. Patients with adenocarcinoma had a lower rate of “recommended” regimen than those with squamous cell carcinoma. There was a statistically significant difference in EGFR-mutant patients for “not recommended” regimens with inconsistency rate of 18.75%. In conclusion, the WFO regimen has 85.16% consistency rate with medical-team regimen in our treatment center. The different pathological type and different gene mutation markedly influenced the agreement rate of the two treatment regimens.Conclusion: WFO recommendations have high applicability to mNSCLC patients in our hospital. This study demonstrates that the valuable WFO system may assist the doctors better to determine the accurate and effective treatment regimens for mNSCLC patients in the Chinese medical setting.Keywords: metastatic non-small-cell lung cancer, Watson for Oncology, concordance, artificial intelligence, treatment recommendations

In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff value=21.9 ng/mL) and 0.88/0.51 (cutoff value=30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35-15.77) and 7.83 (95% CI: 1.70-36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE. [ABSTRACT FROM AUTHOR]

Background: With the increasing of the global aging population, healthy aging and prevention of age-related diseases have become increasingly important. The liver, a vital organ involved in metabolism, detoxification, digestion, and immunity, holds a pivotal role in the aging process of organisms. Although extensive research on liver aging has been carried out, no bibliometric analysis has been conducted to evaluate the scientific progress in this area., Aim: To analyze basic knowledge, development trends, and current research frontiers in the field via bibliometric methods., Methods: We conducted bibliometric analyses via a range of analytical tools including Python, the bibliometrix package in R, CiteSpace, and VOSviewer. We retrieved publication data on liver aging research from the Web of Science Core Collection Database. A scientific knowledge map was constructed to display the contributions from different authors, journals, countries, institutions, as well as patterns of co-occurrence keywords and co-cited references. Additionally, gene regulation pathways associated with liver aging were analyzed via the STRING database., Results: We identified 4288 articles on liver aging, authored by 24034 contributors from 4092 institutions across 85 countries. Notably, the years 1991 and 2020 presented significant bursts in publication output. The United States led in terms of publications ( n = 1008, 25.1%), citations ( n = 55205), and international collaborations (multiple country publications = 214). Keywords such as "lipid metabolism", "fatty liver disease", "inflammation", "liver fibrosis" and "target" were prominent, highlighting the current research hotspots. Notably, the top 64 genes, each of which appeared in at least 8 articles, were involved in pathways essential for cell survival and aging, including the phosphatidylinositol 3-kinase/protein kinase B, Forkhead box O and p53 signaling pathways., Conclusion: This study highlights key areas of liver aging and offers a comprehensive overview of research trends, as well as insights into potential value for collaborative pursuits and clinical implementations., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: GlcNAc2-epimerase (GNE) myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway., Objective: This multi-centre study aimed to delineate the clinical phenotype and GNE variant spectrum in Chinese patients, enhancing our understanding of the genetic diversity and clinical manifestation across different populations., Methods: We retrospectively analysed GNE variants from 113 patients, integrating these data with external GNE variants from online databases for a global perspective, examining their consequences, distribution, ethnicity and severity., Results: This study revealed 97 distinct GNE variants, including 35 (36.08%) novel variants. Two more patients with deep intronic variant c.862+870C>T were identified, while whole genome sequencing (WGS) uncovered another two novel intronic variants: c.52-8924G>T and c.1505-12G>A. Nanopore long reads sequencing (LRS) and further PCR analysis verified a 639 bp insertion at chr9:36249241. Missense variants predominantly located in the epimerase/kinase domain coding region, indicating the impairment of catalytic function as a key pathogenic consequence. Comparative studies with Japanese, Korean and Jewish, our cohorts showed later onset ages by 2 years. The high allele frequency of the non-catalytic GNE variant, c.620A>T, might underlie the milder phenotype of Chinese patients., Conclusions: Comprehensive techniques such as WGS and Nanopore LRS warrants the identifying of GNE variants. Patients with the non-catalytic GNE variant, c.620A>T, had a milder disease progression and later wheelchair use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To clarify the role of Eomesodermin (EOMES) to serve as a disease-relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4 + T subsets in amyotrophic lateral sclerosis (ALS)., Methods: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T-cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1-year longitudinal follow-ups, the ALSFRS-R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort., Results: In the derivation cohort, the CD4 + EOMES + T-cell subsets were significantly increased (p < 0.001). EOMES + subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4 + EOMES + T-cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p = .010) and worse prognosis (p = .003)., Conclusions: We demonstrated that increased CD4 + EOMES + T-cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS., Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL)., Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage ( p = 0.016 ). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015 )., Conclusion: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.

Background: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated., Methods: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism., Results: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS., Conclusions: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC., (© 2023. The Author(s).)

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet β-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes., (© 2023. The Author(s).)

Objective: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth., Methods: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group ( n =1 654) and euthyroid group ( n =14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del., Results: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment ( β =0.057, 95% CI : 0.014-0.100, P =0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks ( β =0.052, 95% CI : 0.001-0.103, P =0.044), 29-32 weeks ( β =0.055, 95% CI : 0.004-0.107, P =0.035) and 36-40 weeks ( β =0.068, 95% CI : 0.011-0.125, P =0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women., Conclusion: The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

In order to explore the impact of antibiotics (enrofloxacin) on microbial community in aquatic environment, an indoor aquatic ecological model was built, and different concentrations of enrofloxacin (0.05, 0.5, 5, and 50 mg/L) were added in the aquatic ecological model. In addition, the water and sediment samples were collected on the 0, 7, 30, and 60 days, and the changes in microbial community were studied through 16S rDNA high-throughput sequencing. The results showed that when the concentration of enrofloxacin was 50 mg/L, the relative abundance of Actinomycetes was increased. In the water, the bacterial richness and diversity communities first decreased and then gradually recovered with the passage of time; On the 7th day, the diversity and richness index of species in the treatment groups with enrofloxacin at 5 and 50 mg/L decreased to the lowest; On the 30th day, the diversity and richness index of species began to rise; On the 60th day, the diversity index and richness index of water species began to increase, while the diversity index and richness index of sediment species decreased. In conclusion, the addition of enrofloxacin negatively affected the microbial community structure in an indoor aquatic ecological model, 50 mg/L enrofloxacin could increase the relative abundance of Actinomycetes, and decrease the diversity and richness index of water and sediment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dai, Peng, Zhang, Xie, Luo, Liu and Ma.)

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients., Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression., Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination., Conclusion: COVID-19 vaccination has no long-term impact on MG relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ruan, Huan, Su, Tang, Meng, Ren, Li, Hao, Zhao, Luo, Li and Chang.)

Introduction: Phospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A 2 , has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson's disease (namely, PARK14). Compared to idiopathic Parkinson's disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14., Design: This case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson's disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation., Methods: The diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson's disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants' serum using UHPLC-QTOF/MS analysis, a well-established technology., Results: We quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients' serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models., Conclusion: The significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Lou, Sun, Luo, Liu, Luo, Wang and Wang.)

The aim of the study was to investigate the clinical effects of abdominal massage on patients with type 2 diabetes mellitus (T2DM) and its influence on the intestinal microflora. We conducted a randomized, controlled clinical trial. A total of 60 patients with T2DM, who met the inclusion criteria, were randomly allocated to the control group, the routine massage group, and the abdominal massage group. The control group received health education and maintained their hypoglycemic drug treatment plan. The routine massage group and the abdominal massage group received different massage interventions. In addition to glucose and lipid metabolism indicators, we quantitatively analyzed the gut microbiota to assess the effects of massage on the intestinal microflora of patients with T2DM. Compared with the control group, the abdominal massage improved levels of glycated hemoglobin, total cholesterol, Enterobacter, and Bifidobacteria with significant differences ( P = 0.02, P = 0.03, P = 0.03, and P = 0.03). The comparison within group showed that the levels of the four bacterial genera in the abdominal massage group revealed significant differences before and after treatment ( P = 0.006, P < 0.001, P < 0.001, and P = 0.002). The comparison between the routine massage group and the abdominal massage group was not significantly different in all levels of test indices. The abdominal massage group regulated levels of Enterobacter and Lactobacilli to a greater extent than the routine massage group. Additionally, abdominal massage decreased Enterococcus levels. The results of this study showed that abdominal massage has clinical advantages over routine massage. Specifically, this intervention may correct microflora disturbances to a certain extent., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Ying Xie et al.)

Skeletal muscle myogenesis and injury-induced muscle regeneration contribute to muscle formation. Skeletal muscle stem cells, termed satellite cells (SCs), proliferate to repair injured muscle. To identify the molecular mechanism of regeneration after muscle injury as well as the genes related to muscle development in fish, in this study, the immunohistochemistry and the high-throughput RNA sequencing (RNA-seq) analysis were performed after Megalobrama amblycephala muscle was injured by needle stab. The results showed that paired box7-positive (Pax7 + ) SCs increased, and peaked at 96 to 144 h-post injury (hpi). The 6729 differentially expressed genes (DEGs), including 2125 up-regulated and 4604 down-regulated genes were found. GO terms significantly enriched by DEGs contained intercellular connections, signaling transduction and enzyme activity. KEGG enrichment analysis showed that most of the pathways were related to immunity, metabolism and cells related molecules, including actin skeleton regulation, Epstein Barr virus infection and plaque adhesion. The WGCNA results revealed that actin cytoskeleton and lipid metabolism related genes probably played crucial roles during repair after muscle injury. Collectively, all these results will provide new insights into the molecular mechanisms underlying muscle injury repair of fish., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Combining digital information science with metasurface technology is critical for achieving arbitrary electromagnetic wave manipulation. However, there is a scarcity of contemporary scholarly studies on this subject. In this paper, we propose an Ultraviolet (UV) sensing metasurface for programmable electromagnetic scattering field manipulation by combining light control with a microwave field. The active sensing of UV light and the real-time reaction of the scattering are achieved by integrating four UV sensors on the metasurface. On the metasurface, a UV sensor ML8511 and a voltage driver module are coupled to control each row of the Positive-Intrinsic-Negative (PIN) diodes. Due to the light sensing capability of the UV sensor, the on or off state of the PIN diode integrated into the programmable metasurface can be switched efficiently through the change of light. When the incident wave changes, various discrete data are transmitted to the FPGA. Then the FPGA performs the corresponding voltage distribution to control the state of the PIN diode. Finally, different metasurface coding sequences are generated to realize different electromagnetic functions. As a result, the spatial distribution of sensing light by sensors can be used to determine the electromagnetic field and connect sensing optical information with the microwave field. The simulation and measured results show that this design is feasible. This work provides a dimension for electromagnetic waves modulation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of a diverse array of autoantibodies and the dysfunctional activation of the complement system. The specific association between the complement component C3a (C3a) protein and antibodies specific for double-stranded DNA (anti-dsDNA), however, has not been studied in detail to date. This study was thus designed to more fully explore circulating C3a levels in SLE patients. In total, 13 SLE patients were enrolled in this study after having been diagnosed in accordance with the SLICC classification criteria, with 7 and 6 patients respectively exhibiting positivity for anti-dsDNA and anti-Sm autoantibodies. Serum complement component C1q (C1q) and C3a levels in samples from these patients were detected via Western blotting, while other serological, biochemical, and clinical parkers associated with disease activity were detected using standard laboratory techniques. The levels of serum C3a in anti-dsDNA+ patients were significantly elevated as compared to those in anti-Sm+ patients (P < 0.01), and a positive correlation between serum C3a levels and SLE Disease Activity Index scores was detected (P < 0.05, r = 0.6134). C3a levels are correlated with the degree of SLE disease activity and other clinically relevant readouts in SLE patients. C3a levels may also enable the differentiation between inactive and active SLE, while also offering value as an advantageous biomarker for thrombophilia monitoring in SLE patients., (© 2022. The Author(s).)

Cardiac fibrosis (CF) is an irreversible pathological process that occurs in almost all kinds of cardiovascular diseases. Phosphorylation-dependent activation of c-Jun N-terminal kinase (JNK) induces cardiac fibrosis. However, whether S-nitrosylation of JNK mediates cardiac fibrosis remains an open question. A biotin-switch assay confirmed that S-nitrosylation of JNK (SNO-JNK) increased significantly in the heart tissues of hypertrophic patients, transverse aortic constriction (TAC) mice, spontaneously hypertensive rats (SHRs), and neonatal rat cardiac fibroblasts (NRCFs) stimulated with angiotensin II (Ang II). Site to site substitution of alanine for cysteine in JNK was applied to determine the S-nitrosylated site. S-Nitrosylation occurred at both Cys116 and Cys163 and substitution of alanine for cysteine 116 and cysteine 163 (C116/163A) inhibited Ang II-induced myofibroblast transformation. We further confirmed that the source of S-nitrosylation was inducible nitric oxide synthase (iNOS). 1400 W, an inhibitor of iNOS, abrogated the profibrotic effects of Ang II in NRCFs. Mechanistically, SNO-JNK facilitated the nuclear translocation of JNK, increased the phosphorylation of c-Jun, and induced the transcriptional activity of AP-1 as determined by chromatin immunoprecipitation and EMSA. Finally, WT and iNOS -/- mice were subjected to TAC and iNOS knockout reduced SNO-JNK and alleviated cardiac fibrosis. Our findings demonstrate an alternative mechanism by which iNOS-induced SNO-JNK increases JNK pathway activity and accelerates cardiac fibrosis. Targeting SNO-JNK might be a novel therapeutic strategy against cardiac fibrosis., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Rationale: Aphallia is an extremely rare congenital malformation of unknown cause, with few reports in the literature. It is usually associated with other urogenital and gastrointestinal anomalies and is believed to be a result of either the absence of a genital tubercle or chromosome polymorphism. Herein, we describe an extremely rare case of congenital aphallia with congenital urethrorectal fistula and describe our treatment for this patient., Patient Concerns: An 8-year-old boy was brought to our hospital by his parents because of congenital absence of the penis. The child was male per karyotype and had excess heterochromatin on chromosome 9 (46 XY with 9 qh+). No urethral orifice was identified, and urine passed rectally since birth; thus, urinary tract outlet obstruction led to urine reflux from the anus to the epididymis for a long time. The boy had to be placed on prophylactic antibiotics because he developed urinary tract infection and epididymitis almost every day., Diagnosis: Congenital aphallia (46 XY normal male karyotype) associated with congenital urethroretal fistula., Interventions: We performed urethral exteriorization via perineal urethroplasty and urethrorectal fistula repair. The parents approved for phallic reconstruction when the boy reached puberty., Outcome: A new external urethral orifice was created on the lower scrotum. The urinary reflux was corrected, and the epididymitis symptoms disappeared. The urethral fistula was then closed. At 8 months follow up, the patient was no longer on antibiotics and had no symptoms of urinary tract infection or epididymitis., Conclusions: Compatible treatment should be adopted to address urinary tract drainage and infection. Management requires a stepwise approach to address needs as they arise. Neophalloplasty should be performed by an experienced team in early adolescence., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Growing evidence suggests that adverse intrauterine environments could affect the long-term health of offspring. Recent evidence indicates that gestational diabetes mellitus (GDM) is associated with neurocognitive changes in offspring. However, the mechanism remains unclear. Using a GDM mouse model, we collected hippocampi, the structure critical to cognitive processes, for electron microscopy, methylome and transcriptome analyses. Reduced representation bisulfite sequencing (RRBS) and RNA-seq in the GDM fetal hippocampi showed altered methylated modification and differentially expressed genes enriched in common pathways involved in neural synapse organization and signal transmission. We further collected fetal mice brains for metabolome analysis and found that in GDM fetal brains, the metabolites displayed significant changes, in addition to directly inducing cognitive dysfunction, some of which are important to methylation status such as betaine, fumaric acid, L-methionine, succinic acid, 5-methyltetrahydrofolic acid, and S-adenosylmethionine (SAM). These results suggest that GDM affects metabolites in fetal mice brains and further affects hippocampal DNA methylation and gene regulation involved in cognition, which is a potential mechanism for the adverse neurocognitive effects of GDM in offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Zou, Zhu, Cheng, Yan, Sheng, Huang and Ding.)

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Luo, Cheng, Yan, Zou, Ding, Jin and Huang.)

Objective: We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC)., Methods: The RNA-sequencing (RNA-seq) expression data for 351 GC patients and other relevant clinical data were acquired from The Cancer Genome Atlas (TCGA). Survival analysis and a genome-wide gene set enrichment analysis (GSEA) were performed to define the underlying molecular value of the ADAMTS genes in GC development. Besides, qRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis., Results: The Log rank test with both Cox regression and Kaplan-Meier survival analyses showed that ADAMTS6 expression profile correlated with the GC patients clinical outcome. Patients with a high expression of ADAMTS6 were associated with poor overall survival (OS). Comprehensive survival analysis of the ADAMTS genes suggests that ADAMTS6 might be an independent predictive factor for the OS in patients with GC. Besides, GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was also confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients., Conclusion: In summary, our study demonstrated that ADAMTS6 gene could be used as a potential molecular marker for GC prognosis., (© 2021 The Author(s).)

Recently, optically-transparent metasurface based on indium tin oxide (ITO) film has attracted wide attention due to its remarkable optical and electromagnetic characteristics. However, most previous researches on the ITO film mainly focus on the absorption because of its prominent loss-resistance property, but neglecting the further exploration on programmable functions. Here, we present a programmable metasurface based on an optically-transparent ITO glass, on which varactors are integrated to achieve flexible amplitude manipulation range of about 25 dB. More importantly, the presented programmable design can be applied for direct modulation on the carrier incident wave with the desired pre-designed analog wave-form. Within the 10 MHz modulation speed, both programmable amplitude manipulation and analog information modulation are demonstrated in the measurements, showing good agreement with theoretical analysis and simulations. Combining both optical transparency and programmable modulation capability, the presented metasurface will promote the potential applications in wireless communication, internet of things and other smart scenarios.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91-411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54-151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13-9.78] pg/ml, median [IQR]) (p < 0.05). The level of NfL in the remission phase group was higher than in HCs group (p < 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p < 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients.

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin -related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin -related PD patients. Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited ( n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD- Parkin ) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed. Results: PD- Parkin patients had a younger AOO ( p = 0.003) and longer disease duration ( p = 0.005). After adjustment for AOO and disease duration, more dystonia ( p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety ( p = 0.015) and sleep disorders ( p = 0.005) in Non-motor symptoms questionnaire, were found in PD- Parkin comparing with GU-EOPD. PD- Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores ( p = 0.005) and ESS scores ( p = 0.047) were significant determinants of QoL in PD-Parkin . Conclusion: Newly diagnosed PD- Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhou, Liu, Chen, Luo, Zhao, Tang, Shen, Yu, Zuo, Wu, Ding, Wang and Sun.)

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson's disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson's disease in this animal model., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this paper, we present a flexible, breathable and optically transparent metasurface with ultra-wideband absorption. The designed double layer of indium tin oxide (ITO) films with specific carved structure realizes absorption and electromagnetic (EM) isolation in dual-polarization, as well as good air permeability. Under the illumination of x- and y-polarization incidence, the metasurface has low reflectivity and transmission from about 2 to 18 GHz. By employing ITO film based on polyethylene terephthalate (PET), the presented metasurface also processes the excellent flexibility and optically transparency, which can be utilized for wearable device application. In addition, the dual-layer design enables mechanically-reconfigurable property of the metasurface. The transmission and reflection coefficients in two polarizations show distinct difference when arranging the different relevant positions of two layers of the metasurface. A sample with 14*14 elements is designed, fabricated and measured, showing good agreement with the simulation results. We envision this work has various potentials in the wearable costume which demands both EM absorption and isolation.

Purpose : To determine whether the early assessment of temporal lobe microstructural changes using diffusion kurtosis imaging (DKI) can predict late delayed neurocognitive decline after radiotherapy in nasopharyngeal carcinoma (NPC) patients. Methods and Materials : Fifty-four NPC patients undergoing intensity-modulated radiotherapy (IMRT) participated in a prospective DKI magnetic resonance (MR) imaging study. MR imaging was acquired prior to IMRT (-0), 1 month (-1), and 3 (-3) months after IMRT. Kurtosis (Kmean, Kax, Krad) and Diffusivity (Dmean, Dax, Drad) variables in the temporal lobe gray and white matter were computed. Neurocognitive function tests (MoCA) were administered pre-radiotherapy and at 2 years post-IMRT follow-up. All the patients were divided into neurocognitive function decline (NFD group) and neurocognitive function non-decline groups (NFND group) according to whether the MoCA score declined ≥3 2 years after IMRT. All the DKI metrics were compared between the two groups, and the best imaging marker was chosen for predicting a late delayed neurocognitive decline. Results : Kurtosis (Kmean-1, Kmean-3, Kax-1, Kax-3, Krad-1, and Krad-3) and Diffusivity (Dmean-1 and Dmean-3) of white matter were significantly different between the two groups ( p <0.05). Axial Kurtosis (Kax-1, Kax-3) of gray matter was significantly different between the two groups ( p <0.05). By receiver operating characteristic (ROC) curves, Kmean-1 of white matter performed best in predicting of MoCA scores delayed decline ( p <0.05). The radiation dose was also significantly different between NFD and NFND group ( p =0.031). Conclusions : Temporal lobe white matter is more vulnerable to microstructural changes and injury following IMRT in NPC. Metrics derived from DKI should be considered as imaging markers for predicting a late delayed neurocognitive decline. Both temporal lobe white and gray matter show microstructural changes detectable by DKI. The Kmean early after radiotherapy has the best prediction performance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To compare the efficacy between thymectomy plus prednisone and prednisone alone in patients with non-thymoma myasthenia gravis (MG). Methods: Thirty generalized MG patients without thymoma who underwent thymectomy were collected as the operation group, and thirty-nine patients without thymectomy who were treated with prednisone alone were matched as the control group. The start point was the enrollment time and the endpoint event was the "clinical remission" (including complete stabilization remission, drug remission, and poor performance). The survival curve was used to analyze the difference of endpoint event time between the two groups. Besides, a 12-month follow-up study was conducted to compare relevant clinical indicators between the two groups. Results: There was no significant difference in the occurrence time of endpoint events between the two groups ( P= 0.614). After 6-month follow-up, no significant differences were found in clinical remission rate, the dosage of pyridostigmine bromide and prednisone, the peak dosage of prednisone, the use of other immunosuppressive medications and the rate of hospitalization for exacerbation of disease between the two groups (all P> 0.05). After 12-month follow-up, the dosage of prednisone and pyridostigmine in the operation group was significantly lower than that in the control group (5(0,10)mg/d vs 7.5(5,10)mg/d and 30(0,105)mg/d vs 90(15,180)mg/d; P= 0.038, 0.032). Conclusion: In patients with mild to moderate non-thymoma generalized MG, thymectomy does not achieve faster remission, but it does reduce the long-term dosage of prednisone and bromopyrazine.

Applying multiple physical fields to artificial manipulate electromagnetic waves is a highly stirring research. In this paper, we creatively combine light control with microwave scattering, realizing an optically coding metasurface for beam deflection based on anomalous reflection. A photoresistor and a voltage-driven module are connected to control each row of PIN-diode-loaded unit cells, endowing the reflection phase of the elements with a strong dependence on light. Owing to the high sensitivity of photoresistor, the digital element state "0" or "1" can be switched effectively via light variation sensed by the photoresistor. By modulating the light signal, the arrangement of digital elements can be reprogrammed, generating the specific scattering field. Therefore, the electromagnetic field can be determined by the spatial distribution of light, which induces the connect with the optical information and microwave field. The simulated and experimental results demonstrate the feasibility of our design. This light-steering approach provides a dimension for electromagnetic wave modulation.

Association of Coagulation factor V ( F5 ) polymorphisms with the occurrence of many types of cancers has been widely reported, but whether it is of prognostic relevance in some cancers remain to be resolved. The RNA-sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA). The potential of F5 genes to predict the survival time of gastric cancer (GC) patients was investigated using univariate and multivariate survival analysis whereas "Kaplan-Meier plotter" (KM-plotter) online tools were employed to validate the outcomes. TCGA data revealed that F5 mRNA levels were significantly upregulated in gastric cancer samples. Survival analysis confirmed that high levels of F5 mRNA correlated with short overall survival (OS) in gastric cancer patients, and the area under the curve (AUC) values of 1-, 2-, and 5-year OS rate were 0.554, 0.593, and 0.603, respectively. Survival analysis by KM-plotter indicated that the high expression of F5 mRNA was significantly associated with a shorter OS compared with the low expression level in all patients with GC, and this was also the case for patients in stage III (hazard ratio (HR) = 1.78, P = 0.017). These findings suggest that the F5 gene is significantly upregulated in GC tumour tissues, and may be a potential prognostic biomarker for GC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yi Liu et al.)

Objective : Using genome-wide screening, this study was aimed at identifying prognostic microRNA (miRNA) in those patients suffering from stomach adenocarcinoma (STAD). Methods : A genome-wide miRNA sequencing dataset and relevant STAD clinical information was obtained via The Cancer Genome Atlas (TCGA). Prognostic miRNA selection was carried out through a whole genome multivariate Cox regression model in order to establish a prognostic STAD signature. Results : Eleven miRNAs (hsa-mir-509-2, hsa-mir-3917, hsa-mir-495, hsa-mir-653, hsa-mir-3605, hsa-mir-2115, hsa-mir-1292, hsa-mir-137, hsa-mir-6511b-1, hsa-mir-145, and hsa-mir-138-2) were recognized as prognostic and used for the construction of a STAD prognostic signature. This signature exhibited good performance in predicting prognosis (adjusted P <0.0001, adjusted hazard ratio= 3.047, and 95% confidence interval=2.148-4.323). The time-dependent receiver operating characteristic examination exhibited area under curve values of 0.711, 0.697, 0.716, 0.733, 0.805, and 0.805, for 1-, 2-, 3-, 4-, 5-, and 10-year overall survival (OS) estimation, respectively. Comprehensive survival analysis suggests that the 11-miRNA prognostic signature acts as an independent feature of STAD prognosis and exhibits superior performance in OS prediction when compared to traditional clinical parameters. Furthermore, fourteen miRNA target genes were linked to STAD OS. These included SERPINE1, MLEC, ANGPT2, C5orf38, FZD7, MARCKS, PDGFD, DUSP6, IRS1, PSAT1, TENM3, TMEM127, BLMH, and TIRAP . Functional and gene set enrichment analysis suggested that target genes and the 11-miRNA prognostic signature were both participate in various biological processes and pathways, including the growth factor beta, Wnt, and Notch signaling pathways. Conclusions : By means of a genome-wide analysis, an 11-miRNA expression signature that may serve as an underlying prognostic indicator for those patients suffering from STAD has been identified and described here., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The control of an upright stance in humans is important in medicine, psychology, and physiology. The maintenance of upright stance balance depends not only on sensory information from proprioceptive, vestibular, cutaneous, and visual sources but also on cognitive resources. The present study investigated the effects of cognitive tasks while standing with eyes open on upright stance balance in adolescents. We hypothesized that performing a cognitive task while standing with eyes open would increase body sway among these adolescents and that the upright posture would thus become less stable., Methods: A static balance assessment system comprising a force platform connected to a computer was used to evaluate the stability of the upright stance among 21 healthy adolescents under six conditions: no cognitive task, a relatively easy cognitive task, or the same cognitive task made more difficult, with each task being performed while the eyes were open and again while the eyes were closed. The participants performed mental calculations as fast as possible by subtracting either 3 or 18 from a random three-digit number continuously, for the simple cognitive task or the difficult cognitive task, respectively. Each calculation was completed within 10 s. The evaluation indexes used to measure upright posture stability were the root mean square (RMS) of the total body sway in the mediolateral and anteroposterior directions, the mean velocity (MV) value of the total body sway, and the Romberg quotient (RQ) of these values., Results: The RMS ( p  < 0.01) and MV ( p  < 0.01) values of the upright posture sway were lower when participants performed no cognitive task and their eyes were open than when their eyes were closed. When their eyes were open, compared with no cognitive task, the values of the measures evaluating upright posture sway were higher, meaning the stance was less stable, while performing either the simple or the more difficult cognitive task (RMS: simple task, p  < 0.01; difficult task, p  < 0.05; MV: simple task, p  < 0.01; difficult task, p  < 0.01) although no significant differences were detected for the RMS or MV values between the simple and more difficult cognitive tasks. The RQs for both the RMS and the total MV values of the upright posture sway during performance of the difficult cognitive task were significantly lower than when the participants performed no task., Conclusion: Performance of a cognitive task significantly reduced the upright posture balance in adolescents during eyes open although increased task difficulty did not show a greater effect. The interference between the performance of a cognitive task and the visual control of an upright stance may be attributable in part to cognitive and visual processing streams competing for common central resources, consistent with the Multiple Resource Theory of information processing., Competing Interests: The authors declare there are no competing interests., (©2019 Meng et al.)

Objective: To describe the secular trends of institutional delivery (ID) rate in minority inhabited areas of China from 1996 to 2017 according to national health policies. Methods: The number of live births and IDs for each county/district in 31 provinces of China were derived from the datasets collected by the Office for National Maternal & Child Health Statistics of China. Information on health policies and ethnical areas was derived from official governmental websites. The calendar years were divided into three periods: pre-program period (1996 to 1999), program implementation period (2000 to 2008) and post-program period (2009 to 2017). Minority autonomous regions, autonomous prefectures, and autonomous counties were defined as minority inhabited areas. The ethnic that a county was classified into was determined by a principle of close proximity to the name of the county or its next higher level administrative division. A total of 700 counties in minority inhabited areas were included in the analysis. Results: A total of 45 684 265 live births including 35 098 855 delivered in institutions were analyzed. The ID rate in minority inhabited areas was 37.5% (696 221/1 856 164) in 1996 and 99.2% (2 371 209/2 390 131) in 2017, with an annual growth rate of 4.7%. During the 22-years period, the ID rates in the eastern, central and western regions increased simultaneously, with the annual growth rates of 3.1%, 4.2% and 4.9% respectively. The difference between the eastern and western regions decreased steadily from 16% in 1996 to <1% in 2017 and the difference between the urban and rural areas decreased from 32.1% in 1996 to <1% in 2017. Besides, the ID rates in Tibetan and Yi inhabited areas with lower baseline levels increased 73 and 63 percentage points respectively. The number of counties with the ID rate of <96% were substantially reduced from 589 in 1996 to 72 in 2017; the 71 counties were all located in national deep poverty-stricken areas named Three Districts and Three States , predominantly involving Tibetan (58), Yi (6), Uygur (2) and Lisu (2) ethnics. Conclusion: During the past 22 years, the ID rate in minority inhabited areas in China has dramatically increased, achieving the goal of 2 020 ahead of schedule, but there remains a few western counties where ID rates are still<96%, indicating that minority inhabited western areas should be focused in developing national policies concerning institutional delivery.

Background: The mutation of TANK-binding kinase 1 (TBK1) gene has been regarded as a causative gene of frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) spectrum disease in recent years. So far, more than 70 TBK1 variants have been identified in patients with FTD-ALS spectrum., Methods: We reported a Chinese FTD patient carrying TBK1 p.Ile334Thr variant detected by target sequencing and Sanger sequencing. The patient's clinical materials were collected. The transcription and translation levels of TBK1 mutant were investigated in fibroblast by qPCR and western blot. The effects of TBK1 mutant in inflammation pathway and autophagy were detected by luciferase reporter assay and GST pull-down assay., Results: The patient was diagnosed as behavioral variant FTD (bvFTD) and displayed progressively severe cognitive impairment especially in executive function. A pattern of frontotemporal atrophy and hypometabolism was shown through MRI and PET-CT. In vitro functional experiments of TBK1 p.Ile334Thr variant demonstrated reduced transcription and translation levels, decreased kinase activity but maintenance of interaction with optineurin. The variant was classified as likely pathogenic according to American College of Medical Genetics and Genomics guideline., Conclusion: We proposed the TBK1 mutation p.Ile334Thr as a likely pathogenic variant in bvFTD which also expanded the clinical spectrum of this variant. It can partially abrogate TBK1 functions and be responsible for FTD-ALS spectrum diseases through neuroinflammatory pathway., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Brassinosteroids (BRs) play pivotal roles in modulating plant growth, development, and stress responses. In this study, a Medicago truncatula plant pretreated with brassinolide (BL, the most active BR), enhanced cold stress tolerance by regulating the expression of several cold-related genes and antioxidant enzymes activities. Previous studies reported that hydrogen peroxide (H₂O₂) and nitric oxide (NO) are involved during environmental stress conditions. However, how these two signaling molecules interact with each other in BRs-induced abiotic stress tolerance remain largely unclear. BL-pretreatment induced, while brassinazole (BRZ, a specific inhibitor of BRs biosynthesis) reduced H₂O₂ and NO production. Further, application of dimethylthiourea (DMTU, a H₂O₂ and OH - scavenger) blocked BRs-induced NO production, but BRs-induced H₂O₂ generation was not sensitive to 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO, a scavenger of NO). Moreover, pretreatment with DMTU and PTIO decreased BL-induced mitochondrial alternative oxidase (AOX) and the photosystem capacity. However, pretreatment with PTIO was found to be more effective than DMTU in reducing BRs-induced increases in V alt , V t , and MtAOX1 gene expression. Similarly, BRs-induced photosystem II efficiency was found in NO dependent manner than H₂O₂. Finally, we conclude that H₂O₂ was involved in NO generation, whereas NO was found to be crucial in BRs-induced AOX capacity, which further contributed to the protection of the photosystem under cold stress conditions in Medicago truncatula .

Objective: To describe the spatial distribution characteristics of the HIV prevalence among pregnant women in mainland China in 2016, providing scientific evidence for the prevention of mother-to-child transmission of HIV. Methods: Data on pregnant women and those living with HIV in 2016 for all counties in mainland China is from the National Maternal & Child Health Statistics dataset. To obtain robust estimates, 2 964 counties were merged into 344 cities. Spatial autocorrelation analysis and trend analysis were performed based on the city-level dataset to detailedly describe the characteristics of the spatial distribution. Results: A total of 14 879 082 pregnant women were included in the analysis, among whom 5 051 were diagnosed to be infected with HIV, giving an overall prevalence of 34.0 per 100 000 pregnant women. The prevalence was higher in the south than in the north, and decreased from the west (93.5/100 000) to the east(8.6/100 000 ), more specifically, the prevalence in the West region was 11 times as high as that in the East region(χ(trend)(2)=68.61, P <0.01). Stratified analysis by provinces showed that there were 6 provinces whose prevalence was >50.0 per 100 000, and they (Yunnan, Xinjiang, Sichuan, Guangxi, Guizhou and Chongqing) were all located in the West Region; pregnant women in these provinces accounted for 21% of all pregnant women, but the HIV cases accounted for 76% of all cases diagnosed in mainland China. Stratified analysis by cities showed that there were 30 cities whose prevalence was >100.0 per 100 000, and 28 of these cities were also located in the western provinces above. Furthermore, the global Moran's I (0.5, P <0.01) indeed indicated a strong clustered distribution across mainland China; 2 hot spots were observed in the Midwest of Xinjiang, and Yunnan and its bordering areas (Sichuan, Guizhou, Guangxi and Chongqing), while 1 cold spot in the central and east China. The HIV prevalence in the hot spots (183.6/100 000) was 23 times as much as that in the cold spot (8.1/100 000). Conclusion: The overall HIV prevalence for pregnant women who lived in mainland China in 2016 (34.0/100 000) ranked at low-level worldwide, but varied markedly across the whole country with 2 high-prevalence-clustered areas: the Midwest of Xinjiang Uygur Autonomous Region, and Yunnan province along with its bordering areas, indicating comprehensive intervention strategies especially targeted to the areas with high HIV prevalence should be developed.

Except for excision repair cross-complementing 1 (ERCC1), mRNA expression of the remaining ERCC genes has not been investigated in the prognosis of gastric cancer (GC). The present study aimed to explore the mRNA expression and prognostic values of each member of the ERCC family in GC patients by using the Kaplan-Meier (KM) plotter tool. The details of each ERCC family member were entered into a database and GC patients were separated into high and low expression to draw survival plots using the KM plotter. In the present study, we observed that high expression of ERCC1 mRNA was significantly associated with longer overall survival (OS) for all GC patients (hazard ratio [HR]=0.77, 95% confidence intervals [CI]=0.63-0.95, P=0.016) compared with low expression. High expression of ERCC4 and ERCC6 mRNA indicated a worse OS for all GC patients (HR=1.28, 95% CI=1.02-1.6, P=0.035 and HR=1.25, 95% CI=1.02-1.54, P=0.029, respectively) and especially for patients with intestinal-type GC (HR=1.87, 95% CI=1.26-2.79, P=0.0018 and HR=1.62, 95% CI=1.04-2.54, P=0.033, respectively). High ERCC8 mRNA expression indicated a worse OS for all GC patients (HR=1.34, 95% CI=1.02-1.76, P=0.034) and especially for patients with diffuse-type GC (HR=2.25, 95% CI=1.36-3.75, P=0.0013). In conclusion, our findings indicate that ERCC4, ERCC6, and ERCC8 may be potential biomarkers for GC prognosis and may serve as potential therapeutic targets for GC. However, these findings still need further verification.

Background: Perrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically., Case Presentation: We reported a consanguineous family (two affected sisters) with Perrault syndrome. The proband had the characteristics of Perrault syndrome: ovarian dysgenesis, bilateral hearing loss and obvious neurological signs. Target genetic sequencing and triplet repeat primed PCR (TP-PCR) plus capillary electrophoresis was conducted to detect causative mutations in the proband. The detected variant was further confirmed in the proband and tested in other family members by Sanger sequencing. Both the proband and her sister were found homozygous for the novel variant HSD17B4 c.298G > T (p.A100S) with their parents heterozygous. Detected by western blot, the protein expression of HSD17B4 mutant was much lower than that of the wild type in SH-SY5Y cells transfected by HSD17B4 wild type or mutant plasmid, which indicated the pathogenicity of the HSD17B4 mutation., Conclusions: Our findings supported that HSD17B4 was one of the genes contributing to Perrault syndrome with the likely pathogenic variant c.298G > T (p.A100S). Special manifestations of cerebellar impairment were found in cases caused by HSD17B4 mutations. Besides, attention should be paid to distinguish Perrault syndrome from D-bifunctional protein deficiency and hereditary ataxia.

A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is the capacity to survive within host macrophages. Although several factors required for this survival have been identified, a comprehensive knowledge of such factors and how they work together to manipulate the host environment to benefit bacterial survival are not well understood. To systematically identify Mtb factors required for intracellular growth, we screened an arrayed, non-redundant Mtb transposon mutant library by high-content imaging to characterize the mutant-macrophage interaction. Based on a combination of imaging features, we identified mutants impaired for intracellular survival. We then characterized the phenotype of infection with each mutant by profiling the induced macrophage cytokine response. Taking a systems-level approach to understanding the biology of identified mutants, we performed a multiparametric analysis combining pathogen and host phenotypes to predict functional relationships between mutants based on clustering. Strikingly, mutants defective in two well-known virulence factors, the ESX-1 protein secretion system and the virulence lipid phthiocerol dimycocerosate (PDIM), clustered together. Building upon the shared phenotype of loss of the macrophage type I interferon (IFN) response to infection, we found that PDIM production and export are required for coordinated secretion of ESX-1-substrates, for phagosomal permeabilization, and for downstream induction of the type I IFN response. Multiparametric clustering also identified two novel genes that are required for PDIM production and induction of the type I IFN response. Thus, multiparametric analysis combining host and pathogen infection phenotypes can be used to identify novel functional relationships between genes that play a role in infection.

Objective: To describe the secular trends of institutional delivery (ID) rate in China from 1996 to 2015, and to assess the impacts of national health policies on the ID rate. Methods: Data on the number of live births and IDs for districts/counties in 31 provinces of China was annually collected by the Office for National Maternal & Child Health Statistics of China. Information concerning the relevant policies was from official governmental websites, including the programme to reduce maternal mortality and eliminate neonatal tetanus (2000 to 2008), and ID subsidy programme in rural China (2009 to present). According to the programme to reduce maternal mortality and eliminate neonatal tetanus, the calendar years were categorized into three periods: pre-programme period (1996 to 1999), programme implementation period (2000 to 2008) and post-programme period (2009 to 2015). Results: A total of 244 398 010 live births were included in the analysis, in which 211 605 727 were delivered in institutions. During the 20 years, the ID rate steadily increased from 58.7% (6 309 255/10 739 816) in 1996 to 99.7% (13 583 658/13 626 948) in 2015, with a compound annual growth rate of 2.8%. Analyses stratified by economic regions or urban-rural areas showed notably consistent increases in ID rates, and the regional and urban-rural differences became nearly disappeared by 2015. The largest regional difference between East (71.6%, 2 540 896/3 547 423) and West (44.6%, 1 675 305/3 752 873) was 27% in 1996 and <1% in 2015 (East 99.9%[5 177 865/5 180 636]and West 99.0%[3 925 766/3 964 622]). The urban-rural difference was 22.7% in 1996 (urban 73.5%[2 756 531/3 748 703], rural 50.8%[3 552 724/6 991 113]) and 0.4% in 2015(urban 99.9%[6 257 853/6 262 763], rural 99.5%[7 325 805/7 364 185]). During the programme implementation period and the post-programme period, the ID rates in rural area increased faster than those in urban area, and the corresponding compound annual growth rates in rural area were 2.4 and 2.8 times of those in urban area; the ID rates in Middle and West regions increased faster than those in East region, and the corresponding compound annual growth rates in West region were 3.6 and 6.3 times of those in East region. By 2015, the ID rates in all provinces other than Tibet (90.5%[48 445/53 505]) and Qinghai (97.2%[60 836/62 600]) reached or were close to 100%. However, there were still 112 districts/counties with ID rates <96%, of which 39 with ID rates <80%; the 39 districts/counties were all located in four western provinces (Tibet 19, Sichuan 15, Qinghai 3, and Xinjiang 2). Conclusions: During the past 20 years, the ID rate in China has steadily increased and achieved the goal of the year 2020 ahead of schedule; the regional and urban-rural inequality in ID has nearly disappeared. Given universal two-child policy, it is of significance to strengthen existing achievements, focus on complicated pregnancies and comprehensively improve the capability and quality of ID services; meanwhile, it is also of significance to develop particular policies and explore the medical-aid model for the minority-inhabited western regions with lower ID rates.

Background: Olfactory identification was reported to be better among PD (Parkinson disease) patients with Parkin mutations, but previous studies didn't eliminate the interference of other PD related genes on olfaction, and whether olfaction of Parkin mutations patients was better in Chinese population was still unknown., Objective: To assess olfaction function among PD patients with Parkin mutations in Chinese population., Materials and Methods: A total of 226 PD patients with a positive family history or an early-onset age (<50 years) were enrolled for genetic testing of PD related genes by target sequencing and multiple ligation-dependent probe amplification. The clinical data including olfactory function test were investigated. Linear regression was performed to adjust for the covariates between all groups., Results: There were 68 patients found having a negative result in PD genetic testing and 43 patients carrying homozygous or compound heterozygous Parkin mutations. Among them, 49 PD panel negative patients and 33 PD- Parkin patients had results of olfactory assessment. PD -Parkin patients performed significantly better on the Sniffin' Sticks tests than panel negative patients (8.0 ± 1.7 vs. 5.7 ± 1.9, p  <   .001), but still worse compared to healthy controls (9.4 ± 1.5, p  =   .003). These differences persisted after adjusting for confounders., Conclusions: Among Chinese population, PD -Parkin patients had relatively preserved olfaction compared to PD panel negative patients after eliminating the interference of other PD related genes, but were still worse than healthy controls.

Background: Olfactory dysfunction is common in Parkinson's disease (PD) and idiopathic rapid eye movement sleep behavior disorder (iRBD), which is a risk factor in the development of PD. However, a few studies have conflicting results when comparing dysosmia in the patients with iRBD and PD. There is no study investigating the olfactory function in Chinese patients with iRBD. Additionally, the Sniffin' Sticks screening 12 test (SS-12) contains several odors that are not familiar to people in different cultures., Methods: Odor identification was evaluated in iRBD patients (n = 54), PD patients (n = 54) and healthy controls (n = 54). With the identification data, a brief odor identification test was established and then validated in other subjects., Results: Odor identification scores in iRBD patients were significantly higher than those in PD patients (P<0.001) but lower than those in controls (P<0.001). At the cut-off value of 7.5, the Sniffin' Sticks clearly differentiated iRBD and PD patients from the controls, and the brief test could increase the specificity in diagnosing PD. Neither the Sniffin' Sticks nor the brief test could clearly differentiate PD and iRBD patients from each other., Conclusions: Olfaction is more impaired in PD patients than in iRBD patients, possibly due to the heterogeneity of iRBD patients. The Sniffin' Sticks could be a useful tool for differentiating iRBD patients from the healthy population, and it could be useful for screening people at high-risk of PD in China, especially when combined with polysomnography. To reduce the expense and time required for the Sniffin' Sticks test, this study shows that a brief test is feasible.

Background: Duck viral pathogens primarily include the avian influenza virus (AIV) subtypes H5, H7, and H9; duck hepatitis virus (DHV); duck tembusu virus (DTMUV); egg drop syndrome virus (EDSV); duck enteritis virus (DEV); Newcastle disease virus (NDV); duck circovirus (DuCV); muscovy duck reovirus (MDRV); and muscovy duck parvovirus (MDPV). These pathogens cause great economic losses to China's duck breeding industry., Result: A rapid, specific, sensitive and high-throughput GeXP-based multiplex PCR assay consisting of chimeric primer-based PCR amplification with fluorescent labeling and capillary electrophoresis separation was developed and optimized to simultaneously detect these eleven viral pathogens. Single and mixed pathogen cDNA/DNA templates were used to evaluate the specificity of the GeXP-multiplex assay. Corresponding specific DNA products were amplified from each pathogen. Other pathogens, including duck Escherichia coli, duck Salmonella, duck Staphylococcus aureus, Pasteurella multocida, infectious bronchitis virus, and Mycoplasma gallisepticum, did not result in amplification products. The detection limit of GeXP was 10(3)copies when all twelve pre-mixed plasmids containing the target genes of eleven types of duck viruses were present. To further evaluate the reliability of GeXP, 150 clinical field samples were evaluated. Comparison with the results of conventional PCR methods for the field samples, the GeXP-multiplex PCR method was more sensitive and accurate., Conclusion: This GeXP-based multiplex PCR method can be utilized for the rapid differential diagnosis of clinical samples as an effective tool to prevent and control duck viruses with similar clinical symptoms.