Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.

Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.

Joint effects of recent stressful life events and adverse childhood experiences on perinatal comorbid anxiety and depression.

BACKGROUND: Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. METHODS: Based on a longitudinal study, 1082 participants receiving prenatal care in Ma'anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. RESULTS: Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p < 0.05). As the number of SLEs increased, the risk of CAD increased (p for trend < 0.05). Specific types of SLEs were associated with CAD in different periods, while only interpersonal events were consistently associated with risks of CAD throughout the whole perinatal period. The joint effects of SLEs with ACEs on CAD were identified throughout the perinatal period, with the highest observed in the first trimester (aOR = 7.47, 95% CI: 3.73-14.95; p for trend < 0.001). CONCLUSION: Our study demonstrated independent associations of recent SLEs and their joint effects with ACEs with risks of perinatal CAD. SLEs combined with ACEs should be recognized as a major risk factor for perinatal CAD and managed at the earliest time to prevent and control CAD.

Association of polycyclic aromatic hydrocarbons exposure with child neurodevelopment and adult emotional disorders: A meta-analysis study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been demonstrated to be neurotoxic. OBJECTIVES: To summarize the existing epidemiological studies to quantify the effects of PAHs exposure on child neurodevelopment and adult emotional disorders. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: We conducted a systematic literature search for studies of child neurodevelopment and adult emotional disorders published in English up to April 2022 in the databases of PubMed, Web of Science and Embase using combinations of MeSH terms and Entry terms, and the articles were filtered out according to data availability. A variety of common PAHs were included in the meta-analysis: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene and benzoapyrene (BaP). STUDY EVALUATION AND SYNTHESIS METHODS: We extracted the content of each article, summarized its design characteristics and performed quality evaluation. We combined the odds ratio (OR) available in various studies to obtain the risk of PAHs exposure and adaptive, language, social, attention, motor skills and child depression/anxiety in children ≤ 15 years old. In addition, we also conducted a meta-analysis on the relationship between PAHs exposure and the risk of depression in adults. RESULTS: We included a total of 16 epidemiological studies (4 cross-sectional studies and 12 cohort studies). The sample size of all included studies ranged from 110 to 9625. Prenatal exposure to PAHs was found to be associated with increased risk of social behavior (OR = 1.60, 95% CI: 1.00-2.54), attention (OR = 2.99, 95% CI: 1.48-6.02), motor skill problems (OR = 1.91, 95% CI: 1.27-2.86) and any adverse neurodevelopmental outcome in children (OR = 2.10, 95% CI: 1.69-2.62). In addition, we found that PAHs exposure could increase the risk of adult depression, with 2-hydroxyfluorene exposure showing the highest combined OR (OR = 1.48, 95% CI: 1.10-2.00). CONCLUSIONS: The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. Steps should be taken to enhance the biomonitoring of PAHs and to reduce the exposure in general population.

Effect of temporary cements and their removal methods on the bond strength of indirect restoration: a systematic review and meta-analysis.

OBJECTIVES: For a conventional indirect restoration, temporary cementation inevitably contaminated collapsed dentin collagen. The purpose of this review was to evaluate the optimal strategy for minimizing its negative effects. MATERIAL AND METHODS: Databases such as PubMed, Web of Science, EMBASE, and the Cochrane Library were searched for in vitro studies, involving the influence of immediate dentin sealing (IDS), different temporary cements, and their removal strategies on dentin bond strength. The meta-analysis used the inverse variance method with effect method of the standardized mean difference and statistical significance at p ≤ 0.05. The I2 value and the Q-test were used to assess the heterogeneity. RESULTS: A total of 14 in vitro trials were subjected to the meta-analysis. Within the study's limitations, we assumed that IDS eliminated the negative effects of temporary bonding, achieving the comparable immediate bond strength with the control (p = 0.46). In contrast, under delayed dentin sealing (DDS), temporary cementation statistically decreased bond strength (p = 0.002). Compared with resin-based and non-eugenol zinc oxide cements, polycarboxylate and calcium hydroxide cements performed better on bond strength with no statistical difference from the control group (p > 0.05). Among the removal methods of temporary cements, the Al2O3 abrasion restored the decreased bond strength (p = 0.07) and performed better than hand instruments alone (p = 0.04), while pumice removal slightly reduced the bond strength in contrast with the control group (p = 0.05, 95% CI = - 1.62 to 0). CONCLUSIONS: The choices of IDS, polycarboxylate and calcium hydroxide temporary cements, Al2O3 abrasion removal method were feasible and efficient to enhance the bond strength. CLINICAL RELEVANCE: It is worthwhile applying IDS technique, polycarboxylate and calcium hydroxide temporary cements during indirect restoration. The Al2O3 abrasion of cleaning dentin can minimize the negative effects of temporary cement.

[Combined effect of active smoking history and passive smoking during pregnancy on postpartum depression and anxiety].

OBJECTIVE: To explore the independent and combined effects of smoking and passive smoking during pregnancy on maternal depression, anxiety and depressive anxiety comorbidities. METHODS: From August 2020 to February 2022, women who underwent 42-day postpartum examination in Changfeng Women's Center and Shuangfeng Hospital of Hefei were recruited. Their depression and anxiety symptoms were assessed using EPDS Scale and GAD Scale, respectively, and smoking and passive smoking status during pregnancy were collected. Multivariate Logistic regression was used to analyze the independent and combined effects of smoking and passive smoking during pregnancy on postpartum depression, anxiety and depression and anxiety comorbidities. RESULTS: A total of 2 447 parturients were included, whose mean age was(29.23±4.20) years old.58.6% of parturients lived in urban areas.97.2% parturients had unassisted reproduction and 73.5% pregnancy intention was spontaneous. Among them, 362(14.8%) had depression, 523(21.4%) had anxiety, and 270(11.0%) had depression and anxiety comorbidities. In an independent analysis of effects, maternal smoking during pregnancy was statistically associated with postpartum depression(OR=3.86, 95%CI 2.37-6.28), anxiety(OR =2.58, 95%CI 1.60-4.17) and depressive anxiety comorbidity(OR = 3.34, 95%CI 2.00-5.71). Maternal passive smoking during pregnancy was also positively associated with the risk of postpartum depression(OR = 1.56, 95%CI 2.00-5.71), anxiety(OR=1.71, 95%CI 1.24-2.37) and depression and anxiety comorbidities(OR = 1.52, 95%CI 1.02-2.28), and the higher the frequency of exposure to passive smoking, the higher risk of depression, anxiety, and depressive and anxiety comorbidities. No interaction between smoking during pregnancy and passive smoking exposure on postpartum depression(RERI = 0.69, 95%CI-4.62-6.00; AP = 10.84, 95%CI-73.37-95.04; S= 0.58, 95%CI 0.02-15.18), anxiety(RERI=0.27, 95%CI 0.05-0.49; AP=4.02, 95%CI-0.52-8.57; S=0.78, 95%CI 0.64-0.94) and depression and anxiety comorbidities(RERI = 0.07, 95%CI-0.25-0.39; AP=1.74, 95%CI-6.03-9.52; S=0.93, 95%CI 0.68-1.27)was observed. CONCLUSION: Both smoking and passive smoking during pregnancy were positively associated with the risk of postpartum depression, anxiety and depressive anxiety comorbidity.

Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway.

The mechanisms of chronic intermittent hypoxia (CIH)-induced cognitive deficits remain unclear. Here, our study found that about 3 months CIH treatment induced lipid droplets (LDs) accumulation in hippocampal nerve and glia cells of C57BL/6 mice, and caused severe neuro damage including neuron lesions, neuroblast (NB) apoptosis and abnormal glial activation. Studies have shown that the neuronal metabolism disorders might contribute to the CIH induced-hippocampal impairment. Mechanistically, the results showed that pyruvate dehydrogenase complex E1ɑ subunit (PDHA1) and the pyruvate dehydrogenase complex (PDC) activator pyruvate dehydrogenase phosphatase 1 (PDP1) did not noticeable change after intermittent hypoxia. Consistent with those results, the level of Acetyl-CoA in hippocampus did not significantly change after CIH exposure. Interestingly, we found that CIH produced large quantities of ROS, which activated the JNK/SREBP/ACC pathway in nerve and glia cells. ACC catalyzed the carboxylation of Acetyl-CoA to malonyl-CoA and then more lipid acids were synthesized, which finally caused aberrant LDs accumulation. Therefore, the JNK/SREBP/ACC pathway played a crucial role in the cognitive deficits caused by LDs accumulation after CIH exposure. Additionally, LDs were peroxidized by the high level of ROS under CIH conditions. Together, lipid metabolic disorders contributed to nerve and glia cells damage, which ultimately caused behavioral dysfunction. An active component of Salvia miltiorrhiza, SMND-309, dramatically alleviated these injuries and improved cognitive deficits of CIH mice.

A longitudinal cohort study of gestational diabetes mellitus and perinatal depression.

BACKGROUND: The association between gestational diabetes mellitus (GDM) and perinatal depression (PND) remains controversial. Our study aimed to comprehensively assess this association in a longitudinal cohort study with repeated measurements of depression. METHODS: Our cohort study was nested in a pilot study of an implementation study aiming to screen and manage perinatal depression within the primary health system in China. Women were recruited in the first trimester from May-September 2019 and followed four times up to 1 year postpartum. Data on sociodemographic characteristics and depression were collected using self-developed questionnaires incorporating the Edinburgh Postnatal Depression Scale (EPDS). Oral glucose tolerance test at 24 ~ 28 weeks and fasting plasma glucose (FPG) data were extracted from medical records. Depression throughout the whole period was divided into different trajectories. Associations of GDM with PND at different time periods and PND of different trajectories were determined by logistic regression. The path of association between blood glucose and depression over time was estimated with an autoregressive cross-lagged model. RESULTS: In total, 1043 women were included in this analysis and 313 (30.0%) were diagnosed with GDM. The prevalence of depression in the first, second, and third trimesters and postpartum period were 17.2, 6.9, 6.8 and 9.0%, respectively. GDM was neither significantly associated with PND at any time point nor with any specific trajectory of depression. Except for autoregressive paths, no cross-lagged path of FPG and scores of EPDS was significant. CONCLUSIONS: Our study indicates no association between GDM/blood glucose and PND.

Isolation of Three Coliphages and the Evaluation of Their Phage Cocktail for Biocontrol of Shiga Toxin-Producing Escherichia coli O157 in Milk.

Shiga toxin-producing Escherichia coli (STEC) O157 is a well-known foodborne pathogen and a leading cause of many intestinal diseases. In this study, we explore the use of a phage cocktail to help control STEC O157 in broth and milk. We isolated three virulent phages from sanitary sewages using a STEC O157 as the indicator bacterium. Phenotypical characterizations revealed that these three phages belong to the Myoviridae family and were stable at different temperatures and pH. They displayed a short latent period between 10 and 20 min, and a burst size (32-65 per infected cell). No virulence factors and drug resistance genes were found in their genomes. Bacterial lysis assays showed that a phage cocktail comprising these three phages was more effective (at least 4.32 log reduction) against STEC O157 at 25 °C with multiplicity of infection (MOI) = 1000 in broth medium. At 4 °C, a 3.8 log reduction in the number of viable STEC O157 after 168-h treatment with phage cocktail at MOI = 1000 was observed in milk, compared to phage-free bacterial control group. Characterizations of phages suggest they could be developed into novel therapeutic agents to control STEC O157 in milk production.

Design, Fabrication, and Performance Test of a New Type of Soft-Robotic Gripper for Grasping.

This investigation presents a novel soft-robotic pneumatic gripper that consists of three newly proposed soft actuators. The newly proposed soft actuators adopt a composite structure of two kinds of pneumatic networks which can work independently and play their respective roles in grasping. The design, analyses, and fabrication of the proposed soft actuators are introduced systematically, and then an experimental system is built to examine the output characteristics of the soft actuator. Compared with the conventional single pneumatic network-based soft actuator, the newly proposed one combines the advantages of the two pneumatic networks, and it employs a larger output force and retains desired bending deformation ability at the same time. The grasping performance test results show that the new soft gripper constituted by the proposed soft actuators has high reliability and stability whether in pinching or in enveloping grasping, and it is also competent for grasping heavier or irregular objects, demonstrating the feasibility and effectiveness of the newly proposed soft actuator, and giving it a good and wide application prospect.

Modeling and Analysis of a Composite Structure-Based Soft Pneumatic Actuators for Soft-Robotic Gripper.

Soft pneumatic actuators are extensively used in soft robots, and their bending angles and kinematic rules at different pressures play a crucial role in practical applications. This investigation aims to model the bending angle and motion of a new type of soft pneumatic actuator that adopts a composite structure consisting of two kinds of pneumatic networks. Based on the structural and deformation characteristics of the proposed soft actuator, the constitutive model is established, and then the moment equilibrium and virtual work principle are combined to model the bending angle of two pneumatic modules. The kinematic model of the proposed soft actuator is co-opted from the kinematic modeling of rigid robots. By employing the piecewise constant curvature method and coordinate transformation, the location of any chamber of the soft actuator can be calculated. The effectiveness of the developed analytical models is then tested, and the calculated results show good agreement with the experimental results. Finally, three soft actuators are used to constitute a soft gripper, and the pinching and enveloping grasping performance are examined. All experimental test results demonstrate that the developed bending angle and kinematic models can explain the bending principle of the proposed soft actuators well.

Equipment Identification and Localization Method Based on Improved YOLOv5s Model for Production Line.

Intelligent video surveillance based on artificial intelligence, image processing, and other advanced technologies is a hot topic of research in the upcoming era of Industry 5.0. Currently, low recognition accuracy and low location precision of devices in intelligent monitoring remain a problem in production lines. This paper proposes a production line device recognition and localization method based on an improved YOLOv5s model. The proposed method can achieve real-time detection and localization of production line equipment such as robotic arms and AGV carts by introducing CA attention module in YOLOv5s network model architecture, GSConv lightweight convolution method and Slim-Neck method in Neck layer, add Decoupled Head structure to the Detect layer. The experimental results show that the improved method achieves 93.6% Precision, 85.6% recall, and 91.8% mAP@0.5, and the Pascal VOC2007 public dataset test shows that the improved method effectively improves the recognition accuracy. The research results can substantially improve the intelligence level of production lines and provide an important reference for manufacturing industries to realize intelligent and digital transformation.

The circular RNA circ_GRHPR promotes NSCLC cell proliferation and invasion via interactions with the RNA-binding protein PCBP2.

As the most common malignancy, lung cancer is characterised by high rates of occurrence and mortality. Although circular RNAs (circRNAs) are known to act as important regulators in cancer, their role in lung cancer remains poorly understood. In this study, circ_GRHPR expression was found to be significantly upregulated in the serum of five patients with non-small cell lung cancer (NSCLC), compared to that in healthy controls. It is expressed at high levels in NSCLC cell lines, as revealed by qRT-PCR analysis. Functionally, we demonstrated that circ_GRHPR promotes NSCLC proliferation and invasion in vitro and in vivo by cell proliferation, transwell, cell cycle, and tumour-forming assays. Mechanistically, RNA pull-down and RNA immunoprecipitation assays showed that circ_GRHPR interacts with the RNA-binding protein poly(rC)-binding protein 2 (PCBP2) and regulates its subcellular localisation by forming the circ_GRHPR/PCBP2 complex, localizing PCBP2 mainly in the cytoplasm and reducing the proportion found in the nucleus. Furthermore, we demonstrated that four-and-a-half LIM-only protein 3 (FHL3) is a tumour-stimulating factor in NSCLC that interacts with and is influenced by PCBP2. Circ_GRHPR increased FHL3 expression in the nucleus of NSCLC cells by decreasing PCBP2 expression therein and promoting the proliferation and invasion of NSCLC cells. Therefore, our study identified that circ_GRHPR promotes NSCLC proliferation and invasion, providing a possible explanation for its mechanism of action.

Neurocognitive effects of atypical antipsychotics in patients with first-episode schizophrenia.

Introduction: Cognitive impairment is a core feature of schizophrenia. The effects of atypical antipsychotics on the cognitive functions of patients with first-episode schizophrenia have not been comprehensively investigated so far. This study aims to compare neurocognitive effects of risperidone, olanzapine, and aripiprazole for first-episode schizophrenia.Methods: The study was a multicenter, randomized, open-label clinical trial. 546 patients were randomly divided into three medication groups, and followed up for 1 year. Cognitive performance was evaluated with a neuropsychological test battery. The Clinical trials.gov ID of the study is NCT01057849.Results: At 6 months, treatment resulted in significant improvements in all three groups in most cognitive domains except verbal learning and memory. At 12 months, three treatment groups had further improvements in three cognitive domains, but visual learning and memory performance dropped back to baseline.Conclusion: All three atypical antipsychotics tested in the study can potentially improve cognitive performance in first-episode schizophrenia, but no significant difference in the degree of improvement was found between drugs.

Synthesis of Amides by Mild Palladium-Catalyzed Aminocarbonylation of Arylsilanes with Amines Enabled by Copper(II) Fluoride.

A general Pd-catalyzed synthesis of amides by oxidative aminocarbonylation of arylsilanes under mild conditions was accomplished for the first time. The reaction is promoted by a commercially available copper(II) fluoride, which acts as a dual silane activator and mild oxidant, enabling highly efficient aminocarbonylation of versatile arylsilanes at atmospheric CO pressure. The reaction is tolerant of a wide range of arylsilanes and various sensitive halide functional groups as well as a broad scope of amines are compatible with this oxidative process using cheap CO. A significant aspect involves the increased efficiency by the catalyst system. The reaction represents a segue into the powerful Pd-catalyzed oxidative transformations of organosilanes.

Halomonas saliphila sp. nov., a moderately halophilic bacterium isolated from a saline soil.

A novel, Gram-stain-negative, aerobic, rod-shaped, motile and moderately halophilic bacterium, designated strain LCB169T, was isolated from a saline soil sample from Gansu Province, PR China. The cells of LCB169T grew at 10-52 °C (optimum 30 °C), at pH 6.0-10.0 (optimum pH 8.0) and in the presence of 0-17 % (w/v) NaCl (optimum 10-15 %). Phylogenetic analysis based on 16S rRNA gene sequences and concatenated 16S rRNA, gyrB and rpoD genes sequences revealed that LCB169T represented a member of the genus Halomonas in the class Gammaproteobacteria. The most closely related species were Halomonas daqingensis DQD2-30T (98.0 % 16S rRNA gene sequence similarity), Halomonas kenyensis AIR-2T (97.8 %) and Halomonas desiderata FB2T (97.5 %). DNA-DNA relatedness values between LCB169T and H. daqingensis CGMCC 1.6443T, H. desiderata DSM 9502T and H. kenyensis DSM 17331T were 33, 35 and 38 %, respectively. The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and three unidentified phospholipids. The major fatty acids were C18 : 1ω7c, C16 : 0, C16 : 1ω7c and C12 : 0 3-OH. The genomic DNA G+C content was 66.1 mol% and the predominant respiratory quinone was Q-9. On the basis of the results of phenotypic, phylogenetic and chemotaxonomic analyses and DNA-DNA hybridization relatedness values, LCB169T is considered to represent a novel species of the genus Halomonas, for which the name Halomonas saliphila sp. nov. is proposed. The type strain is LCB169T (=CGMCC 1.15818T=KCTC 52618T).

Streptomyces geranii sp. nov., a novel endophytic actinobacterium isolated from root of Geranium carolinianum L.

A novel endophytic actinomycete, designated A301T, was isolated from the root of Geranium carolinianum Linn collected from Mount Emei in China and characterized using a polyphasic approach. Growth occurred at 10-37 °C, pH 6-11 and in the presence of 0-5 % NaCl (w/v). Strain A301T contained ll-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell hydrolysates included galactose and ribose. The predominant menaquinones were MK-9(H6) and MK-9(H8). The major cellular fatty acids were C15 : 0, C16 :  0, anteiso-C15 : 0 and iso-C16 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, two unidentified phospholipids, three unidentified lipids and two unidentified aminophospholipids. Strain A301T shared the highest 16S rRNA gene sequence similarity to Streptomyces cinereorubersubsp. fructofermentans NBRC 15396T (98.1 %) and Streptomyces turgidiscabies ATCC 700248T (98.1 %). The DNA-DNA relatedness values between strain A301T and the two above-mentioned members of the genus Streptomyces were 42.6 % and 47.2 %, respectively. The G+C content of the DNA was 70.5 mol%. On the basis of the polyphasic approach and DNA-DNA hybridization data, strain A301T represents a novel species within the genus Streptomyces, for which the name Streptomyces geranii sp. nov. is proposed. The type strain is A301T (=CGMCC 4.7422T=JCM 32177T).

Epidemiological survey of sheep as potential hosts for Leishmania in China.

BACKGROUND: Leishmania parasites cause visceral leishmaniasis (VL), an important infectious disease that is endemic to large parts of the world and often leads to epidemics. Sand flies are the primary transmission vector for the parasite in endemic regions. We hypothesized that sheep might serve as an overlooked reservoir for Leishmania transmission to humans due to the asymptomatic nature of infection in many species. As a preliminary test of this hypothesis, the aim of the present study was to investigate sheep in an area of China that is endemic for the desert sub-type of zoonotic VL and establish if they are potential carriers of Leishmania. RESULTS: Sheep tissue samples were collected from abattoirs in VL endemic areas of Jiashi County, China during the non-transmission season. rK39 immunochromatographic tests were performed to detect the presence of the parasite in blood samples. In addition, DNA was extracted from the blood, and used for detection of the Leishmania-specific internal transcribed spacer-1 (ITS-1) genomic region using a nested polymerase chain reaction (PCR) approach. PCR products were further analyzed to identify restriction fragment-length polymorphism patterns and representative sequences of each pattern were selected for phylogenetic analysis. The rK-39 and nested PCR data indicated positive detection rates for Leishmania in sheep of 26.32 and 54.39%, respectively. The phylogenetic analysis revealed that all of the samples belonged to the species L. infantum and were closely related to strains isolated from human infections in the same area. CONCLUSIONS: Sheep could be a potential host for Leishmania in VL endemic areas in China and may be an overlooked reservoir of human VL transmission in this region. To further confirm livestock as a potential host, further verification is required using a sand fly biting experiment.

Metabolomic Profiling of Plasma Samples from Women with Recurrent Spontaneous Abortion.

BACKGROUND Gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS) metabolomics have been deployed to detect novel differential metabolites in cases with recurrent spontaneous abortion (RSA). MATERIAL AND METHODS Fifty patients who had recurrent spontaneous abortions (RSAs) and 51 control patients (age, gestational age, and body mass index (BMI) match) were enrolled in this study. Untargeted GC-MS and targeted LC-MS were combined to discover and validate the different metabolomic profiles between groups. Score plots of orthogonal partial least-squares discriminant analysis (OPLS-DA) clearly separated the RSA group from the control group. The variable importance in projection (VIP) generated in OPLS-DA processing represented the contribution to the discrimination of each metabolite ion between groups. Variables with a VIP >1 and P<0.05 were considered to be different variables. We also used MetaboAnalyst 3.0 to analyze the pathway impact of potential metabolite biomarkers. RESULTS Fifty-four metabolites were significantly different between the two groups, as indicated by a VIP >1 and P<0.05. The metabolic pathways involving glycine, serine, threonine (P=0.00529, impact=0.26), beta-alanine (P=0.0284, impact=0.27), and phenylalanine metabolism (P=0.0217, impact=0.17), along with the tricarboxylic acid (TCA) cycle (P=0.0113, impact=0.19) and the glycolysis pathway (P=0.037, impact=0.1) are obviously related to RSA. Verification by LC-MS showed that the concentration of lactic acid in RSA was higher than that in the control group (P<0.05), while the concentration of 5-methoxytryptamine was significantly lower in the RSA group (P<0.05). CONCLUSIONS In our study, untargeted GC-MS was used to detect disturbance of metabolism occurs in RSA and targeted LC-MS further was used to show that plasma concentrations of two metabolites (lactic acid and 5-methoxytryptamine) were different in the RSA compared to the control group.

A retrospective comparative study evaluating the efficacy of adding intra-arterial methotrexate infusion to uterine artery embolisation followed by curettage for cesarean scar pregnancy.

PURPOSE: The study aimed to compare the efficacy of intra-arterial methotrexate (MTX) infusion combined with uterine artery embolisation (UAE) and uterine curettage with that of UAE and curettage without MTX infusion for the treatment of cesarean scar pregnancy (CSP). METHODS: In this retrospective study, data of CSP patients admitted from January 2011 to July 2015 were obtained from electronic patient records. Clinical information at baseline and after treatment were extracted and analyzed. RESULTS: A total of 93 CSP patients were included, with 57 patients receiving UAE followed by curettage (UC) and 36 patients receiving intra-arterial MTX infusion followed by UAE and curettage (MUC). The baseline characteristics were not significantly different between the two groups. Without additional intervention, 32 (88.9%) patients were successfully treated by MUC, and 49 (86.0%) patients were successfully treated by UC, defined by discontinued ectopic conceptus growth, normalized serum ß-human chorionic gonadotropin (ß-hCG) level, ceased vaginal bleeding and preservation of uterus, with no significant difference between the two groups. Additionally, intra-operative blood loss volume and post-operative bleeding events were not significantly different between the two groups. However, serum ß-hCG decline on the first day after surgery was significantly promoted, and the hospitalization length and the time needed for serum ß-hCG normalization were significantly shortened by addition of intra-arterial MTX infusion. CONCLUSIONS: Adding intra-arterial MTX to UAE and curettage significantly promoted post-operative recovery, though success rate and bleeding events were not significantly affected, suggesting that addition of intra-arterial MTX might not be necessary.

A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease.

Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.