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Hong-Bin Liang,1,2 Wan-You He,2 Yan-Ping Liu,3 Han-Bing Wang1,2 1Graduate School of Guangdong Medical University, Zhanjiang, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Foshan, Foshan, Guangdong Province, People’s Republic of China; 3College of Nursing, Shandong First Medical University (Shandong Academy of Medical Science), Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Han-Bing Wang, Department of Anesthesiology, The First People’s Hospital of Foshan, No. 81 North of Ling Nan Road, Foshan, Guangdong Province, People’s Republic of China, Email fswhbing@126.comAbstract: A negative correlation exists between attention and pain. The cognitive impairments linked to pain can significantly impede a patient’s healing process and everyday tasks, particularly for individuals experiencing persistent pain. Furthermore, it has been demonstrated that diversion can effectively decrease pain levels in individuals. The focus of this review is to analyze clinical trials and fundamental investigations regarding alterations in focus and persistent discomfort. Moreover, we investigated the common neuroanatomy associated with attention and pain. Furthermore, we examined the impact of various neuromodulators on the transmission of pain and processes related to attention, while also considering the potential neural mechanisms that contribute to the co-occurrence of pain and attention deficits. Further investigation in this field will enhance our comprehension of patient symptoms and the underlying pathophysiology, ultimately resulting in more objective approaches to treatment.Keywords: pain, attention deficit, brain, neuromodulator

Significance: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H 2 S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential therapeutic significance for these diseases. Recent Advances: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, muscle contraction under high fever, arthritis, and disc herniation, can be alleviated by treatment with H 2 S. H 2 S may be conducive to the development of multiple myeloma. The mechanism of action of H 2 S in the musculoskeletal system has been partly elucidated. A variety of H 2 S donors and nano-delivery systems provide promising prospects for H 2 S-based therapies. Critical Issues: Related research remains at the level of cell or animal experiments, but clinical research is lacking. The roles of H 2 S in more musculoskeletal disorders remain largely unknown. The serious consequences of musculoskeletal diseases have not been widely concerned. Targeted delivery of H 2 S remains a challenging task in musculoskeletal diseases. Future Directions: Develop therapeutic drugs for musculoskeletal diseases based on H 2 S and test their safety, efficacy, and tolerance. Explore the combination of current drugs for musculoskeletal diseases with H 2 S-releasing components to improve the therapeutic efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use. Antioxid. Redox Signal. 00, 000-000.

Extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSC-EVs) hold great promise for ischemic stroke treatment, but their therapeutic efficacy is greatly limited due to insufficient targeting ability. Previous reports focused on single ischemic targeting or blood-brain barrier (BBB) penetration, precise delivery to the brain parenchyma has not been fully considered. This study leveraged the targeting ability of RGD peptide and the cell penetrating ability of Angiopep-2 peptide to deliver ADSC-EVs precisely to the impaired brain parenchyma. We found that dual-modified EVs (RA-EVs) significantly enhanced the transcellular permeability across BBB in vitro, and not only targeted ischemic blood vessels but also achieved rapid accumulation in the ischemic lesion area after intravenous administration in vivo. RA-EVs further decreased the infarct volume, apoptosis, BBB disruption, and neurobehavioral deficits. RNA sequencing revealed the molecular regulation mechanism after administration. These findings demonstrate that dual-modification optimizes brain parenchymal targeting and highlights the significance of recruitment and penetration as a previously unidentified strategy for harnessing EVs for therapeutic delivery in ischemic stroke., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To propose a method to determine the unreasonableness of the fixed angle in posterior atlantoaxial fusion surgery based on the ratio of line segments between anatomical landmarks of the atlantoaxial joint. Methods: A cross-sectional study was conducted. According to the inclusion criteria, a screening was performed on the database of asymptomatic volunteers who had full-spine lateral X-ray films taken at the Second Affiliated Hospital of Wenzhou Medical University from May 2016 to May 2021. A total of 207 volunteers were included, comprising 98 males with an age of (40.68±13.87) years and 109 females with an age of (42.64±14.45) years. On the lateral X-ray film, a line (L) parallel to the posterior margin of the odontoid process was drawn at the posterior edge of the lower articular surface of the axis (a), intersecting the atlas at points b, c, and d. The line segments ab, bd, bc, and the C 1 -C 2 angle were measured, and the ratios of bd/ab and bc/ab were calculated. The ability of bd/ab and bc/ab to predict the unreasonable fixed angle of the atlantoaxial joint (≥22°) was analyzed by receiver operating characteristic (ROC) curve analysis in both male and female. The areas under the ROC curves (AUC) were calculated, and the performance of the two prediction methods was compared using the Delong's test. The cutoff value for distinguishing the unreasonableness of the C 1 -C 2 angle and the sensitivity and specificity were calculated. Results: The ROC curve analysis in the male group showed that the AUC of bc/ab for predicting the unreasonable C 1 -C 2 angle was 0.791 (95% CI : 0.696-0.867, P <0.001), with a cutoff value of 0.449, sensitivity of 97.3%, and specificity of 70.0%. The performance was significantly better than that of bd/ab (cutoff value 1.100, AUC=0.532, 95% CI : 0.428-0.634, sensitivity 26.3%, specificity 83.3%, P <0.001). The ROC curve analysis in the female group showed that the AUC of bc/ab for predicting the unreasonable C 1 -C 2 angle was 0.804 (95% CI : 0.745-0.852, P <0.001), with a cutoff value of 0.488, sensitivity of 90.5%, and specificity of 58.6%. The performance was significantly better than that of bd/ab (cutoff value 0.960, AUC=0.687, 95% CI : 0.624-0.748, sensitivity 90.5%, specificity 44.8%, P =0.041). Conclusions: The bc/ab value can be used as an effective indicator to predict the unreasonable C 1 -C 2 angle in posterior atlantoaxial fusion surgery with high diagnostic accuracy. The cutoff value for males is<0.449, and for females is<0.488.

Somatic symp tom disorders (SSDs) are a group of psychiatric disorders characterized by persistent disproportionate concern and obsessive behaviors regarding physical conditions. Currently, SSDs lack effective treatments and their pathophysiology is unclear. In this paper, we aimed to examine microstructural abnormalities in the brains of patients with SSD using diffusion kurtosis imaging (DKI) and to investigate the correlation between these abnormalities and clinical indicators. Diffusion kurtosis images were acquired from 30 patients with SSD and 30 healthy controls (HCs). Whole-brain maps of multiple diffusion measures, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), mean kurtosis (MK), radial kurtosis (RK), and axial kurtosis (AK), were calculated. To analyze differences between the two groups, nonparametric permutation testing with 10,000 randomized permutations and threshold-free cluster enhancement was used with family-wise error-corrected p values < 0.05 as the threshold for statistical significance. Then, the correlations between significant changes in these diffusion measures and clinical factors were examined. Compared to HCs, patients with SSD had significantly higher FA, MK, and RK and significantly lower MD and RD in the cerebellum, thalamus, basal ganglia, and limbic cortex. The FA in the left caudate and the pontine crossing tract were negatively correlated with disease duration; the MD and the RD in the genu of the corpus callosum were positively correlated with disease duration. Our findings highlight the role of the cerebellum-thalamus-basal ganglia-limbic cortex pathway, especially the cerebellum, in SSDs and enhance our understanding of the pathogenesis of SSDs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear., Methods: In this cross-sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula., Results: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] -0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; P corrected  = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] -0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; P corrected  = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] -0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; P corrected  = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data., Conclusion: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula-Brainstem.L-Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain-based interventions are suggested to consider the dysregulation in the Bilateral Insula-Brainstem.L-Thalamus.L circuits., (© 2023 American Headache Society.)

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease that has become the third leading cause of death worldwide. Cycloastragenol (CAG), which is the genuine sapogenin of the main active triterpene saponins in Astragali radix , is a bioavailable pre-clinical candidate for chronic obstructive pulmonary disease (COPD), and it was investigated in our previous study. In order to progress medical research, it was first efficiently produced on a 2.5-kg scale via Smith degradation from astragaloside IV (AS-IV). Simultaneously, since the impurity profiling of a drug is critical for performing CMC documentation in pre-clinical development, a study on impurities was carried out. As these structures do not contain chromophores and possess weak UV absorption characteristics, HPLC-CAD and UPLC-LTQ-Orbitrap-MS were employed to carry out the quality control of the impurities. Then, column chromatography (CC), preparative thin-layer chromatography (PTLC), and crystallization led to the identification of 15 impurities from CAG API. Among these impurities, compounds 1, 4 , 9 , 10 , 14 , and 15 were elucidated via spectroscopic analysis, and 2 - 3, 5 - 8 , and 11 - 13 were putatively identified. Interestingly, the new compounds 9 and 14 were rare 10, 19-secocycloartane triterpenoids that displayed certain anti-inflammatory activities against LPS-induced lymphocyte cells and CSE-induced MLE-12 cells. Additionally, a plausible structural transformation pathway of the degradation compounds from CAG or AS IV was proposed. The information obtained will provide a material basis to carry out the quality control and clinical safety assurance of API and related prescriptions. Reasonable guidance will also be provided regarding the compounds with weak UV absorption characteristics.

Background: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors., Methods: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed., Results: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy., Conclusion: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023. Published by Elsevier Masson SAS.)

Natural products (NPs) have historically played a primary role in the discovery of small-molecule drugs. However, due to the advent of other methodologies and the drawbacks of NPs, the pharmaceutical industry has largely declined in interest regarding the screening of new drugs from NPs since 2000. There are many technical bottlenecks to quickly obtaining new bioactive NPs on a large scale, which has made NP-based drug discovery very time-consuming, and the first thorny problem faced by researchers is how to dereplicate NPs from crude extracts. Remarkably, with the rapid development of omics, analytical instrumentation, and artificial intelligence technology, in 2012, an efficient approach, known as tandem mass spectrometry (MS/MS)-based molecular networking (MN) analysis, was developed to avoid the rediscovery of known compounds from the complex natural mixtures. Then, in the past decade, based on the classical MN (CLMN), feature-based MN (FBMN), ion identity MN (IIMN), building blocks-based molecular network (BBMN), substructure-based MN (MS2LDA), and bioactivity-based MN (BMN) methods have been presented. In this paper, we review the basic principles, general workflow, and application examples of the methods mentioned above, to further the research and applications of these methods.

A total of eleven species and two subspecies are recognized within the Chinese endemic genus Straneostichus Sciaky, 1994 (Carabidae: Pterostichini), including three new species described in the present paper: Straneostichus politus sp. nov. (Sichuan: Wolong), Straneostichus liupanensis sp. nov. (Ningxia: Liupanshan) and Straneostichus ganqingensis sp. nov. (Qinghai: Mengda and Gansu: Dangchang). Taxonomical notes and new distribution records for all the known species are provided, along with an updated key to the species of Straneostichus.

Background : Lithium is an effective medication approved for the treatment of bipolar disorder (BD). It has a narrow therapeutic index (TI) and requires therapeutic drug monitoring. This study aimed to conduct a population pharmacokinetics (PPK) analysis of lithium and investigate the appropriateness of the dosing regimen according to different patient characteristics. Methods : A total of 476 lithium concentrations from 268 patients with bipolar disorder were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were employed to investigate the influence of covariates, such as weight, creatinine clearance, and daily doses of lithium concentrations, and to determine the individualized dosing regimens for patients. Results : Lithium PK was described by a one-compartment model with first-order absorption and elimination processes. The typical estimated apparent clearance was 0.909 L/h -1 with 16.4% between-subject variability in the 62 kg patients with 116 ml/min creatinine clearance and 600 mg daily doses. To achieve a target trough concentration (0.4-0.8 mmol/L) in the maintenance phase, the regimen of 500 mg than 750 mg daily dose was recommended for patients with renal insufficiency and weighing 100 kg. Conclusion : A PPK model for lithium was developed to determine the influence of patient characteristics on lithium pharmacokinetics. Weight, creatinine clearance, and total daily dose of lithium can affect the drug's clearance. These results demonstrate the nonlinear renal excretion of lithium; hence, dosage adjustments are recommended for patients with renal insufficiency., 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 Jin, Wu, Cui, Liu, Liang, You and Wang.)

Vascular cognitive impairment (VCI) is the most common type of dementia after Alzheimer's disease (AD). Effective treatments for VCI are currently lacking. MicroRNA (miR)- 140-5p is associated with cerebral ischemia and poststroke depression, but its relationship with VCI remains unknown. A VCI model was established by bilateral common carotid artery occlusion (BCCAO) for 17 min in mice. Neurogenesis was evaluated by immunostaining for Nestin/bromodeoxyuridine (BrdU), NeuN/BrdU, and doublecortin (DCX)/BrdU. Neuroplasticity was assessed by quantifying synapsin-I and postsynaptic density protein 95 (PSD-95) protein levels. Predicted target genes were screened and verified using the dual luciferase reporter gene system. MiR-140-5p was upregulated in the hippocampus of the BCCAO mice 2 weeks following ischemia. Compared with control groups, the AAV-miR-140-5p group exhibited poorer cognitive performance alongside lower numbers of DCX/BrdU and NeuN/BrdU and less synapsin-I and PSD-95 in the dentate gyrus (P < 0.05). MiR-140-5p overexpression decreased the predicted target gene Prox1. Dual luciferase reporter system confirmed that Prox1 was a direct target site for miR-140-5p. In conclusion, our results suggest that miR-140-5p inhibits neurogenesis and neuroplasticity via downregulation of Prox1 and aggravates VCI. Our findings highlight that miR-140-5p is involved in the pathological process of VCI and provides information for the development of new treatments, which may need further inhibition tests to verify., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Flexible marine natural products (MNPs), such as eribulin and bryostatin, play an important role in the development of modern marine drugs. However, due to the multiple chiral centers and geometrical uncertainty of flexible systems, configuration determinations of flexible MNPs face great challenges, which, in turn, have led to obstacles in druggability research. To resolve this issue, the comprehensive use of multiple methods is necessary. Additionally, configuration assignment methods, such as X-ray single-crystal diffraction (crystalline derivatives, crystallization chaperones, and crystalline sponges), NMR-based methods (JBCA and Mosher's method), circular dichroism-based methods (ECCD and ICD), quantum computational chemistry-based methods (NMR calculations, ECD calculations, and VCD calculations), and chemical transformation-based methods should be summarized. This paper reviews the basic principles, characteristics, and applicability of the methods mentioned above as well as application examples to broaden the research and applications of these methods and to provide a reference for the configuration determinations of flexible MNPs.

Objective: Recent studies have revealed a strong association between the cerebellum and psychiatric disorders. However, the structural changes in the cerebellar regions and functional connectivity (FC) patterns in patients with somatic symptom disorder (SSD) have not been elucidated., Methods: Thirty-seven patients with SSD (29 drug-naive and 8 medicated patients) and 37 sex- and age-matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging scans. The spatially unbiased infratentorial (SUIT) cerebellar atlas-based voxel-based morphometry was used to investigate the changes in cerebellar regional gray matter (GM). Seed-based FC was further computed to explore the pattern of abnormal FC across the whole brain. Correlations were calculated to investigate the relationship between cerebellar structural (and FC) changes and clinical characteristics., Results: After controlling for age, sex, total intracranial volume, medication, and mean FD covariates, all patients with SSD had increased mean GM volume (GMV) in the posterior lobules of the cerebellum bilaterally when compared with HCs, specifically, in the bilateral cerebellar crura I and II. Patients with SSD showed significantly stronger FC between the right crura I and II and bilateral precuneus inferior parietal region, and postcentral gyrus, extending to the superior parietal lobe, cingulate gyrus, and the white matter subgyral. In addition to the two clusters, right lingual gyrus was also a surviving cluster with significantly higher FC. Partial correlation analysis revealed that the degree of regional GMV increases in the two significant clusters and the Hamilton Depression Scale (HAMD) score was negatively correlated. Moreover, the FC of right crura I and II with the left parietal lobe and right lingual gyrus were also negatively associated with the HAMD score., Conclusions: SSD exhibited significant microstructural changes and changes in FC pattern in the posterior cerebellar lobe. These results shed new light on the psychological and neural substrates of SSD and may serve as a potential treatment target for SSD based on the cerebellar area., 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 Liang, Dong, Cui, Wu, Tang, Du and Liu.)

Background: In attempts to understand the migraine patients' overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine. Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson's correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t -tests were performed on the Pearson's correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region. Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex. Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts., 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 Qin, Liang, Li, Hu, Wu, Qiao, Liu and Du.)

Pancreatic cancer (PC) is one of the most fatal and chemoresistant malignancies with a poor prognosis. The current therapeutic options for PC have not achieved satisfactory results due to drug resistance. Therefore, it is urgent to develop novel treatment strategies with enhanced efficacy. This study sought to investigate the anticancer effect of gemcitabine and XCT790, an estrogen-related receptor alpha (ERRα) inverse agonist, as monotherapies or in combination for the treatment of PC. Here we demonstrated that the drug combination synergistically suppressed PC cell viability, its proliferative, migratory, invasive, apoptotic activities, and epithelial-to-mesenchymal transition (EMT), and it triggered G0/G1 cell cycle arrest and programmed cell death in vitro. In addition, in vivo assays using xenograft and mini-PDX (patient-derived xenograft) models further confirmed the synergistic antitumor effect between gemcitabine and XCT790 on PC. Mechanistically, gemcitabine and XCT790 suppressed PC by inhibiting ERRα and MEK/ERK signaling pathway. In conclusion, our current study demonstrated for the first time that gemcitabine combined with XCT790 displayed synergistic anticancer activities against PC, suggesting that their combination might be a promising treatment strategy for the therapy of PC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: This study aimed to evaluate the outcomes of mechanical thrombectomy for acute ischemic stroke when multiple passes are required and to identify the associated risk factors., Methods: Consecutive patients with acute ischemic stroke treated with mechanical thrombectomy at the Neurology Department of Ninth People's Hospital and the Neurosurgery Department of Xinhua Hospital of Shanghai Jiao Tong University School of Medicine from 2013 to 2018 were included. Patients were divided into 2 groups: those who received ≤2 passes and those who received &gt;2 passes. Outcomes of the 2 groups were compared. Multivariate linear regression was used to determine factors associated with the need for &gt;2 passes. All patient data were reviewed retrospectively., Results: A total of 122 patients were included, of whom 83 patients required ≤2 passes and 39 patients required &gt;2 passes. After adjusting for sex, atrial fibrillation history, smoking history, and involvement of middle cerebral artery and internal cerebral artery, the National Institutes of Health Stroke Scale (NIHSS) score was associated with a 1.08-times greater risk of &gt;2 passes (95% confidence interval [CI]: 1.01-1.17), and internal carotid artery with a 5.13-times greater risk of &gt;2 passes (95% CI: 1.02-25.69). Having more than 2 passes was associated with significantly higher 7-day (25.6% vs. 6%), 90-day mortality rates (34.2% vs. 16%) and a significantly lower recanalization rate (66.7% vs. 89.2%)., Conclusion: Needing more than 2 passes during mechanical thrombectomy is associated with poorer outcomes. Higher preprocedural NIHSS scores and internal carotid artery thrombi are associated with more than 2 passes., (© 2022 S. Karger AG, Basel.)

The Chinese species of subgenus Koreonialoe Park & Kwon, 1996 of the genus Pterostichus are revised, including four species from the eastern part of Jilin and Liaoning provinces. Two new species are described: Pterostichus (Koreonialoe) micropoides sp. nov. (type locality: Jilin, Changbai county), and Pterostichus (Koreonialoe) tetralobatus sp. nov. (type locality: Liaoning, Xiuyan county). Pterostichus (Koreonialoe) bellatrix (Tschitschérine) is newly recorded from China (Jilin). The subgenus Koreonialoe is classified into two groups on account of their differences on the endophallus, and all Chinese species accord with the microps group defined herein. A key to all six species in the microps group is provided., (Wen-Qi Yin, Hong-Liang Shi, Hong-Bin Liang.)

To explore the mechanism of Shouhui Tongbian Capsules in treating constipation by means of network pharmacology and molecular docking approach. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinfoematics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN) were applied to obtain chemical components and potential targets of eight herbs in Shouhui Tongbian Capsules according to the screening principles of oral availability(OB)≥30% and drug-like property(DL)≥0.18. Disease targets relating to constipation were screened out through GeneCards, PharmGkb and other databases, drug targets were integrated with disease targets, and intersection targets were exactly the potential action targets of Shouhui Tongbian Capsules for treating constipation; PPI network of potential targets was constructed using STRING platform, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) pathway data were obtained to conduct enrichment analysis and predict its mechanism of action. Cytoscape 3.6.1 was used to construct a network of &quot;medicinal materials-chemical components-drug targets&quot;, and the network topology analysis was carried out on the PPI network to obtain its main components and key targets. Molecular docking between components and key targets of Shouhui Tongbian Capsules verified the accuracy of network pharmacological analysis results. The PPI network analysis showed 92 chemical components, including quercetin, stigmaste-rol, aloe-emodin, rhein, and key targets for instance AKT1, MAPK1, IL6, JUN, TNF and TP53. The enrichment analysis of KEGG screened out 157 signal pathways(P&lt;0.01), mainly involving interleukin 17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, thyroid hormone signaling pathway. Quercetin, resveratrol and lysine with top degree value had a rational conformation in docking site of protein crystal complexes. This study preliminarily showed that various active ingredients in Shouhui Tongbian Capsules could regulate multiple signaling pathways, increase intestinal smoothness and peristalsis function, ensure smooth intestinal lumen, and play a role in treating constipation by acting on key targets, such as AKT1, MAPK1, IL6 and JUN.

Four new species of the subgenus Pedrillia Westwood, 1864 are described from southwest and central China: Zeugophora (Pedrillia) euonymorum sp. nov. , Zeugophora (Pedrillia) flavithorax sp. nov. , Zeugophora (Pedrillia) trifasciata sp. nov. and Zeugophora (Pedrillia) yuae sp. nov. Two species are recorded for the first time in China and redescribed: Zeugophora (Zeugophora) turneri Power, 1863 and Zeugophora (Pedrillia) nigricollis Jacoby, 1885. To date, a total of 35 Zeugophorinae species has been recognized in China., (Kai-Qin Li, Hong-Bin Liang.)

Background: Patients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies. To improve outcomes, we retrospectively investigated whether the application of a more comprehensive genetic test of tumor biopsies samples from LABM patients could provide the basis for treatment with more effective tyrosine kinase inhibitors (TKIs) regimens., Methods: Fine needle biopsies were taken from the primary tumor (PT) and a secondary bone metastasis (BM) of 17 LABM patients before treatment. Simple genetic profiles for selecting therapies were initially obtained using an ARMS-PCR test for EGFR and ALK fusion mutations. More detailed genetic profiles of somatic exon SNVs and CNVs in 457 cancer-related genes were retrospectively derived using capture single molecule amplification and resequencing technology (capSMART)., Results: ARMS-PCR identified 14 EGFR positive, 3 EGFR negative and 1 ALK fusion positive patient. A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively. With the exception of two patients, molecular profiling of matching PT and BM biopsies identified a highly shared somatic variant fingerprint, although the BMs exhibited additional genomic instability. In six of 13 EGFR positive patients and in all three EGFR negative patients, examination of the genetic profiles identified additional clinically significant mutations that are known or experimental drug targets for treatment of lung cancer., Conclusion: Our findings firstly suggest that treatment regimens based on comprehensive genetic assessment of newly diagnosed LABM patients should target both the PT and secondary BMs, including rogue clones with potential to form new BMs. Second, the additional information gained should allow clinicians to design and implement more personalized treatment regimens and potentially improve outcomes for LABM patients.

Sesquiterpenoids constitute a marvelously varied group of natural products that feature a vast array of molecular architectures. Among them, the unusual bicyclo [6.3.0] undecane sesquiterpenoids are one of the most representative. To date, only approximately 42 naturally occurring compounds with this unique scaffold, which can be classified into seven different groups, have been reported. As the first-found member of each type, dactylol, asteriscanolide, dumortenol, toxicodenane C, and capillosanane S are characteristic of the four methyl groups on the five-eight-membered ring system. Only 11-hydroxyjasionone and sinuketal decorate the core with an isopropyl group. These natural products exhibit a wide range of bioactivities, including antifouling, anti-inflammatory, immune suppression, cytotoxic, antimutagenic, antiplasmodial, and antiviral activities. It was noted that some total syntheses of precapnellane-sesquiterpenoids (dactylol, poitediol, precapnelladiene), asteriscanolide, and 11-hydroxyjasionone have been achieved, because their cyclooctanoid core represents an important target for the development of synthetic strategies to prepare eight-membered ring-containing compounds. This review focuses on these natural sesquiterpenoids and their biological activities and synthesis, and aims to provide a foundation for further research of these interesting compounds.

Introduction: L-glutamine is an antioxidant that plays a role in a variety of biochemical processes. Given that oxidative stress is a key component of stroke pathology, the potential of L-glutamine in the treatment of ischemic stroke is worth exploring., Aims: In this study, we investigated the effect and mechanisms of action of L-glutamine after cerebral ischemic injury., Results: L-glutamine reduced brain infarct volume and promoted neurobehavioral recovery in mice. L-glutamine administration increased the expression of heat-shock protein 70 (HSP70) in astrocytes and endothelial cells. Such effects were abolished by the coadministration of Apoptozole, an inhibitor of the ATPase activity of HSP70. L-glutamine also reduced oxidative stress and neuronal apoptosis, and increased the level of superoxide dismutase, glutathione, and brain-derived neurotrophic factor. Cotreatment with Apoptozole abolished these effects. Cell culture study further revealed that the conditioned medium from astrocytes cultured with L-glutamine reduced the apoptosis of neurons after oxygen-glucose deprivation., Conclusion: L-glutamine attenuated ischemic brain injury and promoted functional recovery via HSP70, suggesting its potential in ischemic stroke therapy., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

We aimed to explore the circulating microRNAs biomarkers in the acute stage following cerebral ischemia to earlier warn late-onset post-stroke depression (PSD). A total of 251 consecutive patients with acute ischemic stroke were recruited. They were divided into three groups depending on whether PSD had occurred at 2 weeks or 3 months since stroke: early-onset PSD, late-onset PSD, and non-depressed group. Microarray assay was conducted to identify the different expression profiles of plasma miRNAs. Comprehensive bioinformatics analysis for their integrating putative target genes was performed. The key miRNA was validated in a larger cohort and its function was further studied in ischemic mice brain. We screened three differentially expressed miRNAs in the late-onset PSD individuals, miR-140-5p and miR-221-3p were significantly upregulated while miR-1246 was downregulated. The bioinformatics analysis demonstrated that their predicted target genes were mainly enriched in axon development and Ras signaling pathway. Logistic regression analysis revealed that miR-140-5p was an independent risk factor for late-onset PSD (P = 0.017, OR = 2.313, 95%CI 1.158 to 4.617). The miR-140-5p expression on admission was significantly positively correlated with HDRS scores assessed at 3 months after stroke (P = 0.0007). The predictive value of miR-140-5p for late-onset PSD is 83.3% sensitivity and 72.6% specificity (AUC = 0.8127, P < 0.0001). AAV-mediated overexpression of miR-140-5p decreased the protein level of IL1rap, IL1rapl1, VEGF, and MEGF10 in the ischemic mouse hippocampus and inhibited neurogenesis and capillary density. MiR-140-5p might be involved in the pathogenesis of late-onset PSD and used as a novel early warning biomarker., (Copyright © 2019. Published by Elsevier Ltd.)

Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro . With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs ( p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions ( p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs ( p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression ( p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

Aim: To investigate the specific biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke (CRCIS)., Methods: A retrospective study was conducted on CRCIS patients (colorectal cancer patients with ischemic stroke without conventional stroke risk factors) registered at seven centers between January 2007 and December 2017. Clinical data and laboratory and imaging findings were compared with age- and sex- matched patients with colorectal cancer (CRC) without ischemic stroke that were admitted to the same hospital during the same period. Univariate and multivariate analyses were performed to analyze the independent risk factors for CRCIS. A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the products of the independent risk factors for CRCIS., Results: A total of 114 CRCIS patients and 114 CRC patients were included. Multiple lesions in multiple vascular territories were common in CRCIS patients (71, 62.28%). The levels of plasma D-dimer, carcinoembryonic antigen (CEA), cancer antigen 125, and neutrophil count were significantly higher in CRCIS patients than in CRC patients. Multiple logistic regression analysis revealed that plasma D-dimer levels [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.001-1.003, P < 0.001], CEA levels (OR = 1.011, 95%CI: 1.006-1.015, P < 0.001), and neutrophil count levels (OR = 1.626, 95%CI: 1.268-2.087, P < 0.001) were independent risk factors for CRCIS. In addition, receiver operator characteristic curve revealed that the area under curve for the products of plasma D-dimer, CEA, and neutrophil count was 0.889 ± 0.022 (95%CI: 0.847-0.932, P < 0.001), and the optimal cut-off value for the product was 252.06, which was called the CRCIS Index, with a sensitivity of 86.0% and specificity of 79.8%., Conclusion: Hypercoagulability induced by elevated CEA and neutrophils may be an important cause of CRCIS. The CRCIS index, which serves as a biomarker of CRCIS, needs further study., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interest for this article.

External and internal thoracic structures of two carabid species (Trechini) were examined and documented with different techniques. The study has a main focus on the eyeless cave-dwelling specialist Sinaphaenops wangorum, but detailed information is also provided for a species occurring in cave entrances. The phylogenetic background of the structural features of the thoracic skeletomuscular system was addressed. The thoracic morphology of the examined species was compared to conditions observed in previously studied carabids and non-related subterranean leiodids (Staphylinoidea) in order to identify cave adaptations. Main thoracic character complexes linked with cavernicolous habits in Trechini are elongation of the pro- and mesothorax and the legs, and a complete and irreversible reduction of the flight apparatus. The lost flight capacity is linked with a far reaching modification of skeletal elements of the metathorax including a strongly shortened and simplified metanotum, a shortened metaventrite, and completely reduced wings and sclerites of the wing base. The elongate prothorax together with the long and slender head and elongated legs distinctly increases the activity range in the subterranean lightless environment, which likely facilitates foraging of the carnivorous beetles. Some of the observed features like wing loss and elongation of the anterior thorax and legs are also found in some cave-dwelling Leiodidae (Leptodirini), whereas some other subterranean members of the staphylinoid family have a compact body and legs of normal length. In contrast to the predaceous Trechini, Leptodirini are scavengers., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: This study aims to explore the function of blood microRNA-15a (miR-15a) in the pathogenesis of acute cerebral ischemia (AIS)., Methods: Blood samples were collected from healthy control and AIS patients within 72 h after onset. A model of ischemia in human umbilical vein endothelial cells (HUVECs) was established through oxygen and glucose deprivation (OGD). MiR-15a in patients and in cells was measured using real-time quantitative polymerase chain reaction (qPCR). The predicted target of miR-15a such as interleukin-6 (IL-6) and insulin-like growth factors-1 (IGF-1) in plasma was detected by enzyme-linked immunosorbent assay (ELISA). The relations between blood miR-15a and stroke severity, stroke etiology, infarct location, stroke prognosis, predicted targets were analyzed by Statistical Product and Service Solutions (SPSS) software respectively., Results: Higher miR-15a levels were found in AIS patients and ischemic cells within 72 h, compared to control (p < 0.05). Receiver Operating Characteristic (ROC) analysis showed that blood miR-15a predicted stroke onset with 98.67% specificity. Blood miR-15a had a negative correlation with National Institutes of Health Stroke Scale (NIHSS) scores (r = -0.3695, p < 0.01). The AIS patients with increased miR-15a levels had a better prognosis. MiR-15a was up-regulated in anterior circulation infarction and small-artery atherosclerosis stroke. Plasma levels of IL-6 and IGF-1 were associated with blood miR-15a (r = -0.6051, 0.3231, p < 0.05, respectively)., Conclusion: Blood miR-15a associates with IL-6, IGF-1 and acute cerebral ischemia. It could serve as a potential diagnostic biomarker and therapeutic target for stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To explore the associated factors of late-onset post-stroke depression (PSD)., Methods: A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors., Results: 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%., Limitations: The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke., Conclusions: The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To explore the correlationship among white matter hyperintensities (WMHs), miR-92a-3p and early-onset post-stroke depression (PSD). Methods: We recruited consecutively 238 patients with acute cerebral infarction and MRI examination in the Department of neurology, Ruijin hospital, Shanghai Jiaotong University School of Medicine. The diagnosis of early-onset PSD was made in accordance with DSM-IV criteria for depression in 2 weeks after stroke. Clinical information and assessments of stroke severity were recorded on admission. The analysis of plasma miR-92a-3p was performed using quantitative PCR at the same time. WMHs were evaluated by the Fazekas and Scheltens visual rating scales. The relationship among WMHs, miR-92a-3p and PSD were analyzed by SPSS 22.0 software. Results: Logistic regression demonstrated that periventricular WMHs (PVWMHs) in frontal caps was an independent risk factor with early-onset PSD (OR = 1.579, 95% CI: 1.040-2.397, p = 0.032). The age and numbers of lacunes were related to frontal PVWMHs. Plasma miR-92a-3p in the PSD group was higher compared with the non-depressed group. Receiver operating curve analysis revealed that miR-92a-3p could predict early-onset PSD with 90% sensitivity and 90% specificity. The higher miR-92a-3p trended toward association with greater frontal PVWMHs. Conclusion: Acute ischemic stroke patients with frontal PVWMHs or a high plasma miR-92a-3p at baseline were more likely to develop early-onset PSD. MiR-92a-3p might be involved in the white matter impairment and post-stroke depression.

Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC., (© 2017 The Authors.)

Objective: To evaluate the long-term clinical outcomes of intravascular ultrasound(IVUS) in guiding the treatment of non-left main intermediate coronary lesions for patients of acute coronary syndrome (ACS)., Methods: A total of 25 patients with intermediate coronary lesions(stenosis of 40%-70%) confirmed by coronary angiography were performed with IVUS. When MLA≥4 mm 2 , we deferred the PCI treatment and performed optimal medical treatment (OMT). The patient were followed up for 12 month. The primary outcome was target vessel revascularization (TVR) and secondary outcome was major adverse cardiac events (MACEs)., Results: A total of 25 lesions of 25 patients were examined by IVUS. 19(76%) lesions were attenuated plaque, 4(16%)were echo-lucent plaque, 2(8%) were calcified plaque. Most of the plaque (18/25, 72%) were eccentric. Positive remodeling was found in 20(80%) lesions and negative remodeling in 5(20%) lesions with meanremodeling index of 1.17=0.15. Thrombus was found in 1 case, accounting for 4%. The diameter stenosis, area stenosis, minimal lumen area and the reference diameter mea-sured by IVUS were larger than those measured by quantitative coronary angiography (all P<0.05). One patient with non-ST segment elevated myocardiac infarction was performed revascularization because MI attacked again, and 2 patients with Unstable angina were treated with OMT but they were still rehospitalization because of angina occurred repeatedly. The incidence of TVR was 4.00%, so as 16.00% of MACE., Conclusion: IVUS can be used to guide the treatment of non-left main intermediate coronary lesions for patients of acute coronary syndrome.

Objective: To confirm the histological grade of hepatocellular carcinoma (HCC) by gadoxetic acid-enhanced MRI., Methods: Ninety-five HCC patients underwent gadoxetic acid-enhanced MRI before surgical intervention. The correlations among the signal absolute enhancement, contrast enhancement ratio (CER) and tumor histological grade were analyzed., Results: The correlation between CER of tumor-to-liver and the grades of tumor differentiation is the most significant negative. The k-value for the CER of tumor-to-liver and histopathologic analysis is 0.62, which gives evidence of good agreement., Conclusion: The quantitative analysis of gadoxetic acid-enhanced MRI can predict the histological grades of small HCCs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gallbladder cancer (GBC) is a leading cause of cancer-related deaths worldwide, and its prognosis remains poor, with a 5-year survival rate of ~5%. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of the metastasis-associated miRNA miR-29c-5p in GBC.We validated that expression of miR-29c-5p was significantly downregulated in GBC and was closely associated with lymph node metastasis, overall survival and disease-free survival in 40 GBC patients who were followed clinically. Ectopic overexpression of miR-29c-5p dramatically repressed proliferation, metastasis, and colony formation and induced apoptosis in vitro, and it suppressed tumorigenicity in vivo through the MAPK pathway. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) was identified as a critical effector target of miR-29c-5p. Enforced expression of miR-29c-5p significantly inhibited the expression of CPEB4, and restoration of CPEB4 expression reversed the inhibitory effects of miR-29c-5p on GBC cell proliferation and metastasis. Transforming growth factor-β (TGF-β) upregulated CPEB4 by downregulating miR-29c-5p, leading to MAPK pathway activation. In conclusion, the TGF-β/miR-29c-5p/CPEB4 axis has a pivotal role in the pathogenesis and poor prognosis of GBC, suggesting that miR-29c-5p is a tumor-suppressive miRNA that may serve as potential prognostic biomarker or therapeutic target for GBC.

Background: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC., Methods: MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice., Results: MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects., Conclusions: MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

Glass transition theory is an important theory in polymer science, which is used to characterize the physical properties. It refers to the transition of amorphous polymer from the glassy state to the rubber state due to heating or the transition from rubber state to glassy state due to cooling. In this paper, the glassy state and glass transition of food and the similar relationship between the composition of Chinese medicine extract powder and food ingredients were described; the determination method for glass transition temperature (Tg) of Chinese medicine extract powder was established and its main influencing factors were analyzed. Meanwhile, the problems in drying process, granulation process and Chinese medicine extract powder and solid preparation storage were analyzed and investigated based on Tg, and then the control strategy was put forward to provide guidance for the research and production of Chinese medicine solid preparation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Pancreatic ductal adenocarcinoma is a highly aggressive disease with a grim prognosis. Surgical resection offers the best chance for long-term survival. Negative-margin resection still remains the goal, the influence of margin status on outcomes in pancreatic head carcinoma remains controversial, as conflicting data have been plagued by a lack of standardization in R0 resection and margin definitions, pathologic analysis, and reporting. In contrast to common belief, a high rate of R1 resections in pancreatic cancer is not a marker of low-quality surgery but rather of high-quality pathology. The international pathological consensus of pancreatic head carcinoma is still needed to fully understand the prognostic value of margin status in order to optimize treatment strategy for this disease.

Objective: To explore hormone such as follicle-stimulating hormone (FSH), luteinizing (LH), prolactin (PRL), estradiol (E2), progesterone (PROG) and testosterone (TESTO) levels in first-episode drug-free schizophrenics, and the relationship between clinical symptoms and sex hormones, in order to further study the pathogenesis of schizophrenia., Methods: Eighty-one first-episode drug-free schizophrenics including thirty-nine male and forty-two female from First Affiliated Hospital of Zhengzhou University and seventy healthy subjects (thirty male and forty female) were enrolled.Serum levels of hormone were measured using electrical chemiluminescence immunoassay, and Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function., Results: (1) The serum levels of PRL in male patients group ((24±9) ng/ml) was higher than that of control group ((10±3) ng/ml) (P<0.05), the serum levels of E2, TESTO of male patients group ((29±10) ng/ml), ((3.2±1.7) ng/ml) was lower than that of control group ((35±11) ng/ml), ((4.4±1.6) ng/ml) (P<0.05); The serum levels of PRL, TESTO of female patients group ((29±16) ng/ml), ((0.5±0.4) ng/ml) were dramatically higher than that of control group ((13±5) ng/ml), ((0.3±0.1) ng/ml) (P<0.05), the serum levels of E2 of female patients group ((51±40) ng/ml) was lower than that of control group ((63±66) ng/ml) (P=0.05). (2) The serum levels of PRL, E2, TESTO in male patients group were negatively associated with negative symptoms (r=-0.478,-0.443,-0.576, P<0.05), PRL were negatively related to positive symptoms (r=-0.542, P<0.05); In female patients group, the serum levels of PRL were negatively associated with negative symptoms (r=-0.343, P<0.05), the serum levels of E2 was negatively related to positive symptoms, general psychopathology grade, total PANSS grade (r=-0.351,-0.487,-0.405, P<0.05), TESTO had a positive correlation with positive symptoms (r=0.445, P<0.05). (3) In male patients group, PRL had an negative correlation with working memory P point, reasoning and problem solving P points (r=-0.384,-0.374, P<0.05), the serum levels of E2 was positively related to Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.379, 0.336, 0.407, P<0.05), TESTO had a positive correlation with Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.564, 0.513, 0.552, P<0.05). In female patients group, PRL had an negative correlation with working memory P point, Reasoning and problem solving P points and social cognition P points (r=-0.303,-0.358,-0.368, P<0.05), the serum levels of E2 was positively related to working memory, Reasoning and problem solving P points, social cognition P points (r=0.376, 0.453, 0.355, P<0.05)., Conclusions: Our study shows that first-episode drug-free schizophrenics have hormone secretion abnormal, which suggests that hypothalamus-hypophysis-gonad axis may probably involve in physiopathologic mechanism of first-episode medicine-free schizophrenics.Slightly elevated serum PRL level may be the reaction of stress response in first-episode medicine-free schizophrenics.Endogenous testosterone and estradiol may protect cognitive function against recession, and declining of testosterone and estradiol in blood is the hazards of cognitive dysfunction in first-episode drug-free male schizophrenics. PRL, E2, TESTO may be one of the measurements of the severity of clinical symptoms.

Objective: To investigate the impact of heart valve calcification (HVC) on cardiovascular outcomes in patients on maintenance hemodialysis (MHD)., Methods: We enrolled 302 Chinese patients on MHD between 2009 and 2011 including 99 with HVC identified by echocardiography screening. All the patients were followed up for 2 years and survival analysis was performed with all-cause mortality, cardiovascular mortality and new onset cardiovascular events as the endpoints. Cox regression analysis was used for analyzing the impact of heart valve calcification on the cardiovascular outcomes of the patients., Results: The mean age of the total patients was 58.2∓15.0 years when receiving the initial MHD, and 53.6% were male patients. The overall mortality, cardiovascular mortality and new on-set cardiovascular events in HVC and non-HVC groups were 30.3% vs 16.3%, 22.2% vs 6.9%, and 48.5% vs 25.6%, respectively (P<0.05). Kaplan-Meier survival analysis showed a significant difference in all-cause mortality (P=0.006), cardiovascular mortality (P<0.001) and new-onset cardiovascular events (P<0.001) between HVC and non-HVC groups. After adjustment, Cox regression analysis identified HVC as a risk factor for increased all-cause mortality (HR=1.88; 95%CI: 1.11-3.19), cardiovascular mortality (HR=3.47, 95%CI: 1.76-6.84) and cardiovascular events (HR=1.64, 95% CI: 1.09-2.47)., Conclusions: HVC is an independent risk factor for increased cardiovascular mortality and new cardiovascular events in patients on MHD.

Background: Gallbladder carcinoma (GBC) is the most common malignancy of the bile duct and patients with GBC have extremely poor prognoses. PIK3CA, which encodes the phosphoinositide 3-kinase (PI3K) subunit p110α, is frequently mutated in many cancers, including GBC. The function of the E545K mutation in GBC is not fully understood., Methods: E545K mutation was determined in human GBC tissues by targeted sequencing. The effects of E545K mutation and PI3K selective inhibitor, A66 on GBC cells were evaluated using Cell Counting Kit-8 (CCK-8) cell Viability and transwell assays. The mechanisms of E545K mutation and A66 were analyzed by western blot and co-immunoprecipitation (Co-IP) assay. Subcutaneous xenograft models in nude mice were employed to evaluate the role of E545K mutation and A66 in GBC progression., Results: The rate of PIK3CA E545K mutation in GBC patients was 6.15 %. And the survival of GBC patients was correlated with E545K mutation significantly (P < 0.05). The E545K mutation promoted proliferation, migration and invasion of GBC cells in vitro and tumor proliferation in vivo. A66 suppressed proliferation of GBC cells in vitro and tumor proliferation in vivo., Conclusion: The prognoses of patients with E545K mutation were worse than patients without this mutation. The E545K mutation promoted GBC progression through enhanced binding to EGFR and activating downstream akt activity. The PI3K selective inhibitor, A66, suppressed gallbladder carcinoma proliferation.

Objective: To explore the value of near-infrared technology guided by indolecyanine green(ICG) in planning resection line and real-time surgical navigation in small liver cancer. Methods: From March to September 2015, 11 patients with hepatic tumors received hepatectomy were treated in First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University.There were 5 male and 6 female patients with average age of (55±10)years (range 39-70 years). Among whom, there were 9 cases with hepatocellular carcinoma and 2 cases with colorectal cancer. A near-infrared light camera system was used to detect the liver surfaces before resection, and to plan resection line and surgical specimens. A student's t test was used to compare continuous parametric variables. Results: The ICG-fluorescent imaging and histological examination had been used in the 15 lesions of the 11 patients. Among the 15 lesions, 7 lesions were detected by visual inspections, palpation and ICG-fluorescent imaging, 6 lesions were identified only by ICG-fluorescent imaging, 2 lesions were detected only by ICG-fluorescent imaging after resection.Results of pathologic examination indicated that the total fluorescent type include 5 well differentiated hepatocellular carcinoma and 2 cirrhotic nodule; the partial fluorescent type include 3 moderately differentiated hepatocellular carcinomas and 1 well differentiated hepatocellular carcinomas; the rim fluorescent type included 2 liver metastatic carcinoma and 2 poorly differentiated hepatocellular carcinomas. The average diameter of the tumor size measured by CT was (1.7±0.2)cm, while the average diameter measured by ICG-fluorescent imaging was (1.7±0.3)cm( t =-0.188, P >0.05). Conclusion: Near-infrared technology guided by ICG has important value in planning resection line and real-time surgical navigation in small liver cancer.

Gallbladder cancer (GBC), the most common malignancy of the bile duct, is highly aggressive and has an extremely poor prognosis, which is a result of early metastasis. As it is regulated being at multiple levels, the metastatic cascade in GBC is complex. Recent evidence suggests that microRNAs (miRNAs) are involved in cancer metastasis and are promising therapeutic targets. In this study, miR-101 was significantly downregulated in tumor tissues, particularly in metastatic tissues. In GBC patients, low miR-101 expression was correlated with tumor size, tumor invasion, lymph node metastasis, TNM stage, and poor survival. Moreover, miR-101 was an independent prognostic marker for GBC. Additionally, miR-101 inhibited GBC cell proliferation, migration, invasion, and TGF-β-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the gene encoding the zinc finger protein X-linked (ZFX) was identified as a direct target of miR-101. More importantly, miR-101 significantly reduced activation of the MAPK/Erk and Smad signaling pathways, resulting in inhibition of TGF-β-mediated induction of EMT. Altogether, our findings demonstrate a novel mechanism by which miR-101 attenuates the EMT and metastasis in GBC cells and suggest that miR-101 can serve as a potential biomarker and therapeutic target for GBC management., Competing Interests: All authors confirm that there are no conflicts of interest to declare.

The use of prasugrel in patients with coronary artery disease (CAD) has been associated with decreased major adverse cardiac events (MACEs) compared with clopidogrel but with an increased risk of bleeding. However, it remains unclear if the risks of bleeding outweigh those of MACEs in patients on prasugrel treatment. We systematically reviewed randomized controlled trials comparing prasugrel with clopidogrel in patients with CAD. We performed a literature search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trial databases from inception to November 25, 2014, and reviewed the reference lists of retrieved articles. A comparative estimate was made for the combined rates of MACEs and bleeding from the same trials in the framework of this meta-analysis and expressed as odds ratios (ORs) and 95% confidence intervals (CIs) in both random- and fixed-effects models. Nine studies involving 25,214 patients were included in our meta-analysis. In both the random- and fixed-effects models, the risks of MACEs outweighed those of major bleeding (OR 7.48, 95% CI 3.75 to 14.94, p <0.0001, random effects) and of minor bleeding (OR 3.77, 95% CI 1.73 to 8.22, p = 0.009, random effects). Results were corroborated in a standard-dose clopidogrel subgroup analysis (OR 7.46, 95% CI 3.54 to 15.68, p <0.0001, and OR 6.44, 95% CI 2.80 to 14.80, p <0.0001, random effects, respectively). In conclusion, despite the increased risk of bleeding associated with prasugrel treatment compared with clopidogrel, the risk of MACEs far outweighed the risk of bleeding., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Nuclear factor-κB (NF-κB), a transcription factor that is activated by various stimuli, is associated with the pathogenesis of several cancers. One functional polymorphism, -94 insertion/deletion ATTG (rs28362491), in the human NFKB1 gene (one member of the NF-κB gene family) is associated with increased risk of various cancers. However, only one study has reported that rs28362491 is significantly associated with ovarian cancer. The aim of this study was to analyze the association between single nucleotide polymorphisms (SNPs) and haplotypes in the NFKB1 gene and the risk of ovarian cancer in a Chinese population. We examined the potential association between ovarian cancer and 15 SNPs (rs28362491, rs3774932, rs1598856, rs230531, rs230530, rs230528, rs230521, rs230498, rs230539, rs1005819, rs3774956, rs4648055, rs4648068, rs3774964, rs3774968) of the NFKB1 gene using the MassARRAY system. Participants included 411 patients with ovarian cancer and 438 healthy controls. The results showed that the allelic or genotypic frequencies of three polymorphisms, including rs28362491 (promoter region), rs230521 (intron 4), and rs4648068 (intron 12), in the patients with ovarian cancer, were significantly different from those in the healthy controls. Strong linkage disequilibrium was observed in four blocks (D' > 0.9). Significantly more A-C (block 2: rs230528-rs230521) haplotypes (P = 0.0003 after Bonferroni's corrections) and G-A-A (block 4: rs4648068-rs3774964-rs3774968) haplotypes (P = 0.021) were found in the patients with ovarian cancer. These findings point to a role of the NFKB1 polymorphism in patients with ovarian cancer among a Chinese Han population, and may be informative for future genetic or biological studies on ovarian cancer.

In this study, two antioxidative substances, a homogeneous polysaccharide [abalone shell polysaccharide (ASP-1), corresponding to the first peak by size exclusion chromatography] and a non-polysaccharide compound [abalone shell compound (ACS-2), corresponding to the second peak by size exclusion chromatography], were extracted from the abalone (Haliotis discus hannai Ino) shell. We primarily focused on the investigation of ASP-1. As a heteropolysaccharide, ASP-1 is comprised of 9.3% uronic acid and 86.4% saccharide, the latter including mannose, ribose, rhamnose, glucose, galactose, arabinose, and two unknown monosaccharides, NO1 and NO2, with a mass ratio of 9.5:10.1:2.2:18.2:21.8:5.5:16.5:16.2. The antioxidant activity assays indicated that 5.0 mg/mL ASP-1 has significant scavenging effects on superoxide radicals (86.2%) compared to the positive control of ascorbic acid (95.6%).

A novel convenient procedure for the resolution of 5,5'-biquinoline-6,6'-diol (BIQOL) was achieved by separating the corresponding diastereomeric mixture of (S)-(+)-camphorsulfonates on a semiprepared XDB-C8 column followed by hydrolysis. The efficient asymmetric addition of triethylaluminium to aromatic aldehydes catalyzed by Ti-(+)/(-)BIQOL complexes under mild conditions is described. The reactions led to the formation of 1-arylpropan-1-ol in up to 87.5% ee., (© 2014 Wiley Periodicals, Inc.)

Objective: To investigate the epidemiological characteristics of tic disorders (TD) among pupils in the Shunde Longjiang area, and their relationship to trace elements., Methods: A cross-sectional study of 4062 children aged 6-12 years, who were selected from the Shunde Longjiang area by stratified cluster sampling to investigate the epidemiological characteristics of TD, was conducted, and blood concentrations of trace elements in children with TD were determined. Forty normal children were selected as controls., Results: The overall prevalence rate of TD was 2.98%; the prevalence rates of transient tic disorder, chronic motor or vocal tic disorder and Tourette's syndrome were 3.62%, 2.39% and 1.21% respectively. Boys had a significantly higher prevalence rate of TD than girls (3.92% vs 1.96%; P<0.05). There were no significant differences in blood copper, manganese and magnesium levels between children with TD and normal children (P>0.05), however, children with TD had a significantly increased blood lead level and significantly decreased blood zinc and iron levels compared with the normal children (P<0.05). No significant differences in trace elements were found between children with different subtypes of TD (P>0.05)., Conclusions: TD is common in children aged 6-12 years and more prevalent in boys than in girls. High blood lead level and zinc and iron deficiencies may be one of the causes of TD, and thus should be considered during therapy.