Novel spirooxindole alkaloid derivatives from the medicinal insect Blaps japanensis and their biological evaluation.

Blapspirooxindoles A-C (1-3), three novel spirooxindole alkaloids with a unique spiro[chromane-4,3'-indoline]-2,2'-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A-J (6-15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1-11 and 13 exist as racemic mixtures in nature, and their (-)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays.

Five New Cantharidin Derivatives from the Insect Mylabris cichorii L. and Their Potential against Kidney Fibrosis In Vitro.

Five new monoterpenoids including three 1-hydroxymethyl-2-methyl cantharimide-type derivatives (1, 2, and 5) and two 1,2-dimethyl cantharimide-type derivatives (3 and 4), together with three known compounds (6-8) were isolated from the insect Mylabris cichorii Linnaeus. The structures of these new compounds, including their absolute configurations, were characterized by detailed analysis of NMR, chemical derivatization, and quantum chemical ECD calculations. All of the compounds were tested for their biological activity against kidney fibrosis. The results revealed that compounds 2, 4, and 7 could inhibit kidney fibrosis in vitro at 40 µM by inhibiting the expression of fibronectin and collagen I in TGF-ß1-induced NRK-52e cells.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

High-throughput unmanned aerial vehicle-based phenotyping provides insights into the dynamic process and genetic basis of rapeseed waterlogging response in the field.

Waterlogging severely affects the growth, development, and yield of crops. Accurate high-throughput phenotyping is important for exploring the dynamic crop waterlogging response in the field, and the genetic basis of waterlogging tolerance. In this study, a multi-model remote sensing phenotyping platform based on an unmanned aerial vehicle (UAV) was used to assess the genetic response of rapeseed (Brassica napus) to waterlogging, by measuring morphological traits and spectral indices over 2 years. The dynamic responses of the morphological and spectral traits indicated that the rapeseed waterlogging response was severe before the middle stage within 18 d after recovery, but it subsequently decreased partly. Genome-wide association studies identified 289 and 333 loci associated with waterlogging tolerance in 2 years. Next, 25 loci with at least nine associations with waterlogging-related traits were defined as highly reliable loci, and 13 loci were simultaneously identified by waterlogging tolerance coefficients of morphological traits, spectral indices, and common factors. Forty candidate genes were predicted in the regions of 13 overlapping loci. Our study provides insights into the understanding of the dynamic process and genetic basis of rapeseed waterlogging response in the field by a high-throughput UAV phenotyping platform. The highly reliable loci identified in this study are valuable for breeding waterlogging-tolerant rapeseed cultivars.

Salidroside Attenuates Airway Inflammation and Remodeling via the miR-323-3p/SOCS5 Axis in Asthmatic Mice.

INTRODUCTION: Salidroside (Sal) a bioactive component extracted from Rhodiola rosea is remarkable for its anti-asthmatic effects. The study aimed to explore the molecular mechanism of Sal in airway inflammation and remodeling in asthmatic mice and provide a novel theoretical basis for asthma treatment. METHODS: An asthmatic mouse model was established via ovalbumin (OVA) treatment, followed by injection of Sal and transfection of miR-323-3p-mimic and sh- suppressor of cytokine signaling 5 (SOCS5). Expressions of miR-323-3p, SOCS5 mRNA, collagen (COL)-I, and COL-III were detected via reverse transcription quantitative polymerase chain reaction. SOCS5 protein level was detected via Western blot. Levels of IgE, IL-13, IL-4, and IL-5 were detected via enzyme-linked immunosorbent assay. Inflammatory cell infiltration was observed via hematoxylin-eosin staining. Collagen disposition was observed via Masson staining. Resistance index (RI) of airway hyperresponsiveness, and the number of total cells, inflammatory cells (eosinophil, macrophage, neutrophil, and lymphocyte) in bronchoalveolar lavage fluid (BALF) were observed. The binding relationship between miR-323-3p and SOCS5 was predicted through the RNA22 website and verified via dual-luciferase reporter assay. RESULTS: miR-323-3p was highly expressed in OVA-treated mice. Sal treatment reduced inflammatory cell infiltration, COL disposition, miR-323-3p expression, and IgE, IL-13, IL-4, IL-5, COL-I, and COL-III levels, RI value, and the number of total cells and inflammatory cells in BALF. miR-323-3p inhibited SOCS5 transcription. miR-323-3p overexpression or SOCS5 downregulation reversed the protecting role of Sal in asthmatic mice. CONCLUSION: Sal inhibited miR-323-3p expression to promote SOCS5 transcription, thereby attenuating airway inflammation and remodeling in asthmatic mice.

Unusual sesquilignans with anti-inflammatory activities from the resin of Ferula sinkiangensis.

Sinkianlignans A - D (1-4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ', ß-γ', and γ-γ' linkage pattern, and sinkianlignans E - F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.

Influence of sleep difficulty on post-traumatic stress symptoms among frontline medical staff during COVID-19 pandemic in China.

Being a nurse was demonstrated to be a risk factor for post-traumatic stress symptoms (PTS) and insomnia among frontline staff during COVID-19 pandemic. The unidirectional relationship between insomnia and PTS highly suggested that insomnia could mediate the increasing risk of PTS among frontline nurses. However, no study had tried to clarify this mediation effect of insomnia during COVID-19 pandemic. This study aimed to investigate prevalence of insomnia and PTS among frontline doctors and nurses and to clarify the relationship between career (doctor/nurses), insomnia and PTS. A total of 211 frontline doctors and nurses completed the investigation. Insomnia was measured using a self-drafted questionnaire and PTS was assessed using primary care post-traumatic stress disorder screen (PC-PTSD). Three logistics regression models and one mediation model were performed to explore relationships between career, insomnia and PTS. The prevalence of PTS (PC-PTSD≥2) and insomnia (with 1 item in self-drafted insomnia questionnaire≥2) was 24.17% and 36.97%, respectively. Being a nurse was a shared risk factor of insomnia (OR = 4.16, 95%CI: 1.30 ~ 5.77, P = 0.023) and PTS (OR = 7.51, 95%CI: 1.89 ~ 40.50, P = 0.008). Compared to doctors, nurses had significantly higher prevalence of insomnia (46.32% vs. 20%, χ2 = 13.27, P < 0.001) and PTS (30.14% vs. 13.33%, χ2 = 6.57, P = 0.011). Insomnia was a significant partial mediator (B = 0.101, P = 0.026), which explained 32.53% proportions of relationship between being a nurse and PTS. PTS and insomnia were common symptoms, which should be considered in psychological aids among frontline medical staff. Insomnia might be a possible target of PTS intervention.

Role of collateral embolization in addition to uterine artery embolization followed by hysteroscopic curettage for the management of cesarean scar pregnancy.

BACKGROUND: The aim of this study was to assess the feasibility, safety and outcome of the embolization of non-gonadal collateral supplying gestational sac (GS) in addition to uterine artery embolization (UAE), followed by hysteroscopic curettage for the management of cesarean scar pregnancy (CSP). METHODS: A retrospective study was undertaken from January 2012 to September 2018 in 24 CSP patients in whom non-gonadal collaterals supplying GS were identified by arterial angiography performed immediately after UAE. These patients underwent attempt collateral embolization in addition to UAE, followed by hysteroscopic curettage for the management of CSP. The 24 patients were divided into two groups based on whether they underwent technically successful collateral embolization (UAE-SCE group) or failed collateral embolization (UAE-FCE group) in addition to UAE. The baseline characteristics and clinical outcomes including time for serum ß-human chorionic gonadotropin (ß-hCG) levels normalization, blood loss, secondary anemia, and pelvic pain were compared between the two groups. The paired t test and Man Whitney test were used for comparisons of discrete and numerical variables, respectively. RESULTS: Collateral embolization was techinically successful in 16 (66.7%, 16/24) patients and failed in the other 8 (33.3%, 8/24) patients. There were no significant differences between the two groups in baseline characteristics. The mean blood loss and secondary anemia in the UAE-SCE group were significantly less than UAE-FCE group. No significant difference was found between the two groups in the mean time for ß-hCG levels normalization and pelvic pain. CONCLUSIONS: During the management of UAE combined with hysteroscopic curettage for CSP, additional embolization of non-gonadal collateral supplying GS during UAE is feasible and safe in patients with non-gonadal collateral supplying GS, and the additional embolization of the collateral may reduce blood bloss related to hysteroscopic curettage.

Altered social cognition and connectivity of default mode networks in the co-occurrence of autistic spectrum disorder and attention deficit hyperactivity disorder.

OBJECTIVE: As two common neurodevelopmental disorders, autistic spectrum disorder and attention deficit hyperactivity disorder frequently occur together. Until now, only a few studies have investigated the co-occurrence of attention deficit hyperactivity disorder and autistic spectrum disorder, this is due to restrictions associated with previous Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Most previous research has focused on the developmental trajectories for autistic spectrum disorder and attention deficit hyperactivity disorder separately, while the neural mechanisms underpinning the co-occurrence of autistic spectrum disorder and attention deficit hyperactivity disorder remain largely unknown. METHODS: We studied 162 autistic spectrum disorder individuals (including 79 co-attention deficit hyperactivity disorder and 83 non-attention deficit hyperactivity disorder patients) and 177 typical developing individuals using resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange II, an aggregated magnetic resonance imaging dataset from 19 centers. Independent component analysis was used to extract sub-networks from the classic resting-state networks. Functional connectivity values within (intra-iFC) and between (inter-iFC) these networks were then determined. Subsequently, we compared the ASD_coADHD group with the ASD_nonADHD group in relation to the abnormal intra-iFC and inter-iFC of autistic spectrum disorder group relative to the typical developing group. RESULTS: The ASD_coADHD group showed more severe social impairment and decreased intra-iFC in the bilateral posterior cingulate cortex of the default mode network (independent component 17) and increased inter-iFC between the default mode network (independent component 8) and the somatomotor networks (independent component 2) compared to the ASD_nonADHD group. In addition, the strength of the intra-iFC in the default mode network was associated with the severity of autistic traits across the entire autistic spectrum disorder group and particularly the ASD_coADHD group. CONCLUSION: Our results showed that dysfunction of the default mode network is a central feature in the co-occurrence of autistic spectrum disorder and attention deficit hyperactivity disorder, including connectivity within the default mode network as well as between the default mode network and the somatomotor networks, thus supporting the existence of a clinically combined phenotype (autistic spectrum disorder + attention deficit hyperactivity disorder).

Abnormal resting state activity of left middle occipital gyrus and its functional connectivity in female patients with major depressive disorder.

BACKGROUND: Women are more susceptible to major depressive disorder (MDD). A possible explanation is that women have a trait tendency to engage in a ruminative response style. Depending on cognitive model of depression, attention bias, memory bias and self-referential bias were closely related among depressed patients. Previous studies have explored the neural mechanism of the cognitive biases by using amplitude of low frequency fluctuations (ALFF) or functional connectivity (FC), and few combined these two metrics, especially focusing on female patients. METHODS: We assessed 25 female patients diagnosed with MDD and 13 well matched healthy controls (HCs) using Rs-fMRI. Two metrics ALFF and FC based on abnormal ALFF were explored and made comparisons. RESULTS: Compared with HCs, female patients with MDD showed that one cluster with significantly decreased ALFF in the left middle occipital gyrus(L-MOG). Furtherly we founded depressed female subjects showed significantly lower FC between the L-MOG seed and left orbitofrontal cortex, and significantly higher FC between the L-MOG seed and left medial prefrontal gyrus and left hippocampus. CONCLUSIONS: Our results showed L-MOG may act as a connection, which involved in the processing of cognitive biases of MDD by connected with limbic-cortical regions in resting state. These findings may enhance the understanding of the neurobiological mechanism in female patients with MDD.

Long non-coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR-1297.

BACKGROUND: Emerging evidences have verified that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. lncRNAs metastasis associated lung adenocarcinoma transcript 1 (MALAT1) have been found to be up-regulated in some human cancers. The main objective of this study was to investigate the expression level and biological function of MALAT1 in gastric cancer (GC). METHODS: Quantificational real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA levels of MALAT1 in 78 paired gastric carcinoma tissues and adjacent normal tissues, and the associations of MALAT1 expression with the clinicopathological features were analyzed, and the prognosis of gastric carcinoma patients was evaluated. The HMGB2 mRNA and protein expressions were detected by qRT-PCR and western-blot analysis. Luciferase reporter assay was used to determine miR-1297 was a target of MALAT1. RESULTS: In this study, we demonstrated MALAT1 was up-regulation in GC tissues compared with adjacent normal tissues and higher MALAT1 expression was correlated with local invasion, lymph node metastasis and TNM stage. Patients with higher MALAT1 expression predicted a shorter survival and poor prognosis. Functionally, we revealed that MALAT1 promoted cells proliferation and invasion in GC. Mechanistically, our results demonstrated that MALAT1 was negatively correlation with miR-1297 and functioned as a molecular sponging miR-1297, antagonizing its ability to suppress HMGB2 expression. CONCLUSIONS: Taken together, these results demonstrated that MALAT1/miR-1297/HMGB2 axis acted as critical regulator pathway in GC tumorigenesis and progression, which provided a novel therapeutic target for gastric cancer.

Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy.

Hematuria is one of the basic clinical manifestations of IgA nephropathy (IgAN). Isolated microscopic hematuria or microscopic hematuria combined with proteinuria is risk factor for the long-term prognosis of IgAN. Current evidence of the consequences of glomerular hematuria rests on insights from basic research on the molecular mechanisms of hemoglobin and related reactive oxygen species-induced tubular injury as well as on the clinical evidence of macroscopic hematuria-associated acute kidney injury (AKI) in IgAN. These researches may simply elucidate some effects of macroscopic hematuria but not microscopic hematuria. Recent studies conducted on blood and urinary erythrocytes have made progress. Researches have revealed that mature erythrocytes contain abundant, long, non-coding RNA, miRNA (microRNA) and Y RNA. Among the top 50 expressions of erythrocyte-derived miRNAs, 33 (66%) of them may be the potential urinary biomarkers of IgAN. Moreover, when urinary erythrocytes are compressed while exiting out of an impaired nephron, erythrocyte-derived vesicles (including microvesicles and apoptotic vesicles) may increase. Animal models for hematuria and human biopsy tissues confirm renal parenchymal cells could phagocytose red blood cells and erythrocyte-derived vesicles. These vesicles, which contain miRNAs, may alter the transcriptome of recipient cells and impact the occurrence and development of IgAN.

Efficacy and safety of escitalopram in treatment of severe depression in Chinese population.

Severe depression accounts for one-third of depressed patients. Increasing severity of depression usually hinders patients from achieving remission. This study evaluated the efficacy and safety of escitalopram in acute-phase treatment of severe major depressive disorder (MDD). A total of 225 participants with severe MDD (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria), with a current depressive episode and Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥30 were enrolled. Participants received flexible dose escitalopram (10-20 mg/d) treatment for 8 weeks. Symptoms status was assessed by MADRS, Hamilton Depression Rating Scale (HAM-D-17), and Hamilton Anxiety Rating Scale (HAM-A). Quality of life was assessed by Short Form-12 (SF-12) and safety by adverse events, laboratory investigations, vital signs and physical findings. The remission (MADRS total score ≤ 10) rate in the intent-to-treat set (n = 207) was 72.9% at week 8. Significant improvement in symptoms compared to baseline, as evaluated by MADRS, HAMD-17 and HAMA scores at baseline, week 1, week 2, week 4, and week 8 (p < 0.0001 for all), was noted. Mean (SD) reduction from baseline in MADRS total score was 26.6 (11.38). Improvements in SF-12 score were significant (p = 0.000) and positively related to symptom improvement and negatively related to treatment-emergent adverse events (TEAEs). TEAEs were reported in 28.38% of participants. Most common TEAEs (>4%) were somnolence (9.0%), nausea (7.7%), hyperhidrosis (4.5%), dry mouth and dizziness (4.1% each). No serious TEAEs were reported. Escitalopram was effective and well-tolerated for acute-phase treatment of severe depression in Chinese population.

Giant single-molecule anisotropic magnetoresistance at room temperature.

We report an electrochemically assisted jump-to-contact scanning tunneling microscopy (STM) break junction approach to create reproducible and well-defined single-molecule spintronic junctions. The STM break junction is equipped with an external magnetic field either parallel or perpendicular to the electron transport direction. The conductance of Fe-terephthalic acid (TPA)-Fe single-molecule junctions is measured and a giant single-molecule tunneling anisotropic magnetoresistance (T-AMR) up to 53% is observed at room temperature. Theoretical calculations based on first-principles quantum simulations show that the observed AMR of Fe-TPA-Fe junctions originates from electronic coupling at the TPA-Fe interfaces modified by the magnetic orientation of the Fe electrodes with respect to the direction of current flow. The present study highlights new opportunities for obtaining detailed understanding of mechanisms of charge and spin transport in molecular junctions and the role of interfaces in determining the MR of single-molecule junctions.

Epidermal growth factor receptor inhibitor ameliorates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury.

BACKGROUND: Astrogliosis is a common phenomenon after spinal cord injury (SCI). Although this process exerts positive effects on axonal regeneration, excessive astrogliosis imparts negative effects on neuronal repair and recovery. Epidermal growth factor receptor (EGFR) pathway is critical to the regulation of reactive astrogliosis, and therefore is a potential target of therapeutics to better control the response. In this report, we aim to investigate whether blocking EGFR signaling using an EGFR tyrosine kinase specific inhibitor can attenuate reactive astrogliosis and promote functional recovery after a traumatic SCI. METHOD: The astrocyte scratch injury model in vitro and the weight-drop SCI model in vivo were used as model systems. PD168393 was used to inhibit EGFR signaling activation. Astrocytic activation and phosphorylated EGFR (pEGFR) were observed after immunofluorescence staining and Western blot analysis. The rate of proliferation was determined by immunofluorescence detection of BrdU-incorporating cells located next to the wound. The levels of TNF-α, iNOS, COX-2 and IL-1ß in the culture medium under different conditions were assayed by ELISA. Western blot was performed to semi-quantify the expression of EGFR/pEGFR, glial fibrillary acid protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). Myelin was stained by Luxol Fast Blue Staining. Cresyl violet eosin staining was performed to analyze the lesion cavity volume and neuronal survival following injury. Finally, functional scoring and residual urine recording were performed to show the rats' recovery. RESULTS: EGFR phosphorylation was found to parallel astrocyte activation, and EGFR inhibitor PD168393 potently inhibited scratch-induced reactive astrogliosis and proinflammatory cytokine/mediator secretion of reactive astrocytes in vitro. Moreover, local administration of PD168393 in the injured area suppressed CSPGs production and glial scar formation, and resulted in reduced demyelination and neuronal loss, which correlated with remarkable hindlimb motor function and bladder improvement in SCI rats. CONCLUSIONS: The specific EGFR inhibitor PD168393 can ameliorate excessive reactive astrogliosis and facilitate a more favorable environment for axonal regeneration after SCI. As such, EGFR inhibitor may be a promising therapeutic intervention in CNS injury.

Concentrated sodium chloride catheter lock solution--a new effective alternative method for hemodialysis patients with high bleeding risk.

BACKGROUND: Locking catheter with heparin may increase bleeding risk of some hemodialysis (HD) patients. Hence, the security and effectivity of 10% concentrated sodium chloride (CSC) used as an alternative method for patients with high bleeding risk need to be investigated. METHODS: Seventy-two patients inserted temporary central venous catheters were divided into two groups randomly. A total of 3125 U/mL heparin saline (HS) was used in HS group and 10% CSC in CSC group to lock catheters. Heparin-free HD was used for the first time and plasma specimens were collected to test coagulation indicators before catheter-locking (at the end of HD) and at 30 min after it. Then, blood flow velocities (BFVs), incidences of catheter thrombosis, etc. were followed up at each time of HD. RESULTS: Activated partial thromboplastin time (APTT) of two groups had no difference at the end of heparin-free HD (27.100 [25.675-28.950] vs. 27.250 [25.150-29.575] second, p = 0.933), but at 30 minutes after using different catheter lock solutions, APTT of HS group was obviously longer than CSC group (50.100 [41.275-65.400] vs. 27.500 [25.525-29.875] second, p < 0.001). Catheters' retaining time of two groups were the same (p = 0.306), so did the average BFVs (p > 0.05). But catheters' thrombosis incidence and urokinase usage of HS group were less than CSC group (p < 0.05). CONCLUSION: Comparing with HS group, thrombosis incidences of CSC group increased, but catheters' retaining time and average BFVs remained the same and coagulation indicators of it were unaffected. Therefore, it can be an effective alternative lock method for HD patients with high bleeding risk.

[Evaluations of bronchial and nonbronchial systemic arteries in patients with hemoptysis at dual-source computed tomograph: comparison with conventional angiography].

OBJECTIVE: To retrospectively evaluate the depiction of bronchial and nonbronchial systemic arteries with dual-source computed tomography (DSCT) versus conventional angiography in patients with hemoptysis. METHODS: DSCT and conventional angiography of thorax were performed in 66 patients with hemoptysis. There were 46 males and 20 females with a mean age of 45 (22-72) years. Findings on DSCT, including CT scans, maximal intensity projections and three-dimensional volume-rendered images were used to evaluate the visibility and traceability of bronchial and/or nonbronchial systemic arteries. CT scans were evaluated by two radiologists in consensus. The CT findings were compared with those of conventional angiography. RESULTS: A total of 171 (87 right, 84 left) bronchial arteries and 18 nonbronchial systemic arteries were visible on DSCT. The right bronchial arteries arose from intercostal-bronchial trunk thoracic aorta (n = 46), common trunk of both bronchial arteries (CBT) (n = 32) and thoracic aorta (n = 9) whereas left bronchial arteries arose from thoracic aorta (n = 50), CBT (n = 32) and left subclavian artery (n = 2). Compared with angiography, the accuracy of DSCT in the diagnosis of hemoptysis responsible vessels (i.e. dilatation BA) was approximately 88.7% (133/150). DSCT correctly diagnosed 18 nonbronchial systemic arteries, but missed 7; DSCT correctly diagnosed 5 bronchial-pulmonary vascular fistulas, but missed 15. CONCLUSION: Excellent for evaluating hemoptysis, DSCT may identify the origin and ostial position of bronchial arteries, detect non-bronchial systemic arteries and act as a roadmap for percutaneous transcatheter embolisation.

[Effect of Ningdong Granule on the levels of IL-12 and TNF-alpha in children patients with Tourette's syndrome].

OBJECTIVE: To observe the effect of Ningdong Granule (NG) on serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) of children patients with Tourette's syndrome (TS). METHODS: Totally 90 TS children patients were randomly assigned to the NG group, the NG + Tiapride group (abbreviated as the combined treatment group), and the Tiapride group, 30 in each group. Besides,another 30 healthy children were recruited as the healthy control group. Patients in the NG group were treated with NG (consisting of all gastrodia rhizome, Codonopsis pilosula, Ophiopogon japonicus, white peony root, Rhinocerotidae, oyster, earthworm, licorice root, etc.), one dose daily, administered by dissolving it in boiled water, taken in two portions in the morning and in the evening respectively. Patients in the Tiapride group took Tiapride Tablet, 50 -100 mg each time, twice daily. The dosage was adjusted according to individual difference and changes of pathogenic conditions. The maximal dosage was 300 mg per day. Those in the combined treatment group were treated with equal dose of NG and Tiapride Tablet in combination. The treatment course was 3 months for all. Changes of pathogenic condition before and after treatment were assessed by Yale global tic severity scale (YGTSS). Serum levels of IL-12 and TNF-alpha were detected by enzyme-labeled immunosorbent assay (ELISA) before and after treatment. RESULTS: (1) The total effective rate of the NG group, the combined treatment group, and the Tiapride group was 79.3%, 83.3%, and 67.9%, respectively. It was the lowest in the Tiapride group (P < 0.05). It was significantly higher in the combined treatment group than in the NG group (P < 0.05). (2) The post-treatment YGTSS score was obviously lower in each group after treatment than before treatment (P < 0.05). The posttreatment YGTSS score was obviously lower in the NG group and the combined treatment group than in the Tiapride group (P < 0.05), but with no statistical difference between the fromer two groups (P > 0.05).(3) Compared with the healthy control group before treatment, serum levels of IL-12 and TNF-alpha (pg/mL) were 124.95 +/- 22.78 and 209.52 +/- 21.69 in the NG group, 126.14 +/- 25.65 and 208.97 +/- 22.46 in the combined treatment group, 123.00 +/- 24.26 and 205.10 +/- 26.16 in the Tiapride group, being higher than those in the healthy control group (64.56 +/- 27.59 and 78.13 +/- 33.42; P < 0.05). After treatment, serum levels of of IL-12 and TNF-alpha were 104.67 +/- 16.84 and 183.01 +/- 24.95 in the NG group, 109.04 +/- 16.81 and 179.87 +/- 23.45 in the combined treatment group, significantly lower than before treatment (P < 0.05). But there was no statistical difference in serum levels of IL-12 or TNF-alpha in the Tiapride group between before treatment (123.00 +/- 24.26 and 205.10 +/- 26.16) and after treatment (117.75 +/- 16.79 and 199.76 +/- 33.21; P > 0.05). CONCLUSION: NG could modulate abnormal serum levels of IL-12 and TNF-alpha in TS children patients, which might be one of its pharmacodynamic mechanisms for treating TS.

Aspongopyrimidine A, a N-Peralkylated Histidine Zwitterion from Aspongopus chinensis against Alzheimer's Disease Targeting MAPRE3.

Aspongopyrimidine A (1), a hexa-1,3-diene-histidine-hexanoic acid adduct featuring a 4,5-dihydro-2H-10λ4-imidazo[5,1-f]pyrrolo[2,1-b]pyrimidine motif, was isolated from the insect Aspongopus chinensis. The structure was clarified by spectroscopic and computational methods and X-ray diffraction. Peralkylation of N-atoms in histidine by two C6 units makes 1 an inner salt with a 5/6/5 tricyclic system. Biological evaluation found that 1 exerts activity against Alzheimer's disease targeting MAPRE3 through a chemical proteomics approach. This study revealed unusual modifications of amino acids as the fundamental units of protein.

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy.

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.