Publications by authors named "Ming-Hua Li"

209 Publications

Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2.

Signal Transduct Target Ther 2021 09 1;6(1):328. Epub 2021 Sep 1.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.
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http://dx.doi.org/10.1038/s41392-021-00734-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409077PMC
September 2021

Mice Expressing Regulators of G protein Signaling-insensitive Gαo Define Roles of Opioid Receptor Go and Gi Subunit Coupling in Inhibition of Presynaptic GABA Release.

Mol Pharmacol 2021 Sep 16;100(3):217-223. Epub 2021 Jun 16.

Department of Neurologic Surgery, Oregon Health & Science University, Portland, Oregon (C.A.B., K.B.M., M.L., S.L.I.); and Department of Pharmacology and Edward F. Domino Research Center, Medical School, Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.)

Regulators of G protein signaling (RGS) proteins modulate signaling by G protein-coupled receptors. Using a knock-in transgenic mouse model with a mutation in Go that does not bind RGS proteins (RGS-insensitive), we determined the effect of RGS proteins on presynaptic opioid receptor (MOR)-mediated inhibition of GABA release in the ventrolateral periaqueductal gray (vlPAG). The MOR agonists [d-Ala, -MePhe, Gly-ol]-enkephalin (DAMGO) and met-enkephalin (ME) inhibited evoked inhibitory postsynaptic currents (eIPSCs) in the RGS-insensitive mice compared with wild-type (WT) littermates, respectively. Fentanyl inhibited eIPSCs similarly in both WT and RGS-insensitive mice. There were no differences in opioid agonist inhibition of spontaneous GABA release between the genotypes. To further probe the mechanism underlying these differences between opioid inhibition of evoked and spontaneous GABA release, specific myristoylated G peptide inhibitors for Go and Gi that block receptor-G protein interactions were used to test the preference of agonists for MOR-G complexes. The Go inhibitor reduced DAMGO inhibition of eIPSCs, but Gi inhibitors had no effect. Both Go and Gi inhibitors separately reduced fentanyl inhibition of eIPSCs but had no effects on ME inhibition. Gi inhibitors blocked the inhibitory effects of ME and fentanyl on miniature postsynaptic current (mIPSC) frequency, but both Go and Gi inhibitors were needed to block the effects of DAMGO. Finally, baclofen-mediated inhibition of GABA release is unaffected in the RGS-insensitive mice and in the presence of Go and Gi inhibitor peptides, suggesting that GABA receptor coupling to G proteins in vlPAG presynaptic terminals is different than MOR coupling. SIGNIFICANCE STATEMENT: Presynaptic opioid receptors (MORs) in the ventrolateral periaqueductal gray are critical for opioid analgesia and are negatively regulated by RGS proteins. These data in RGS-insensitive mice provide evidence that MOR agonists differ in preference for Gαo versus Gαi and regulation by RGS proteins in presynaptic terminals, providing a mechanism for functional selectivity between agonists. The results further define important differences in MOR and GABA receptor coupling to G proteins that could be exploited for new pain therapies.
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http://dx.doi.org/10.1124/molpharm.121.000249DOI Listing
September 2021

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.

Cell Res 2021 08 10;31(8):847-860. Epub 2021 Jun 10.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
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http://dx.doi.org/10.1038/s41422-021-00519-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190750PMC
August 2021

Electrical Loss Management by Molecularly Manipulating Dopant-free Poly(3-hexylthiophene) towards 16.93 % CsPbI Br Solar Cells.

Angew Chem Int Ed Engl 2021 Jul 21;60(30):16388-16393. Epub 2021 Jun 21.

Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Inorganic cesium lead halide perovskites offer a pathway towards thermally stable photovoltaics. However, moisture-induced phase degradation restricts the application of hole transport layers (HTLs) with hygroscopic dopants. Dopant-free HTLs fail to realize efficient photovoltaics due to severe electrical loss. Herein, we developed an electrical loss management strategy by manipulating poly(3-hexylthiophene) with a small molecule, i.e., SMe-TATPyr. The developed P3HT/SMe-TATPyr HTL shows a three-time increase of carrier mobility owing to breaking the long-range ordering of "edge-on" P3HT and inducing the formation of "face-on" clusters, over 50 % decrease of the perovskite surface defect density, and a reduced voltage loss at the perovskite/HTL interface because of favorable energy level alignment. The CsPbI Br perovskite solar cell demonstrates a record-high efficiency of 16.93 % for dopant-free HTL, and superior moisture and thermal stability by maintaining 96 % efficiency at low-humidity condition (10-25 % R. H.) for 1500 hours and over 95 % efficiency after annealing at 85 °C for 1000 hours.
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http://dx.doi.org/10.1002/anie.202105176DOI Listing
July 2021

Northern pig-tailed macaques ( ) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response.

Zool Res 2021 May;42(3):350-353

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become an unprecedented global health emergency. At present, SARS-CoV-2-infected nonhuman primates are considered the gold standard animal model for COVID-19 research. Here, we showed that northern pig-tailed macaques ( , NPMs) supported SARS-CoV-2 replication. Furthermore, compared with rhesus macaques, NPMs showed rapid viral clearance in lung tissues, nose swabs, throat swabs, and rectal swabs, which may be due to higher expression of interferon (IFN)-α in lung tissue. However, the rapid viral clearance was not associated with good outcome. In the second week post infection, NPMs developed persistent or even more severe inflammation and body injury compared with rhesus macaques. These results suggest that viral clearance may have no relationship with COVID-19 progression and SARS-CoV-2-infected NPMs could be considered as a critically ill animal model in COVID-19 research.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175946PMC
May 2021

Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Edward F. Domino Research Center, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, 48109;

Positive allosteric modulators (PAMs) of the mu-opioid receptor (MOR) have been hypothesized as potentially safer analgesics than traditional opioid drugs. This is based on the idea that PAMs will promote the action of endogenous opioid peptides while preserving their temporal and spatial release patterns and so have an improved therapeutic index. However, this hypothesis has never been tested. Here, we show that a mu-PAM, BMS-986122, enhances the ability of the endogenous opioid Methionine-enkephalin (Met-Enk) to stimulate G protein activity in mouse brain homogenates without activity on its own and to enhance G protein activation to a greater extent than β-arrestin recruitment in Chinese hamster ovary (CHO) cells expressing human mu-opioid receptors. Moreover, BMS-986122 increases the potency of Met-Enk to inhibit GABA release in the periaqueductal gray, an important site for antinociception. We describe in vivo experiments demonstrating that the mu-PAM produces antinociception in mouse models of acute noxious heat pain as well as inflammatory pain. These effects are blocked by MOR antagonists and are consistent with the hypothesis that in vivo mu-PAMs enhance the activity of endogenous opioid peptides. Because BMS-986122 does not bind to the orthosteric site and has no inherent agonist action at endogenously expressed levels of MOR, it produces a reduced level of morphine-like side effects of constipation, reward as measured by conditioned place preference, and respiratory depression. These data provide a rationale for the further exploration of the action and safety of mu-PAMs as an innovative approach to pain management.
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http://dx.doi.org/10.1073/pnas.2000017118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072371PMC
April 2021

Japanese Encephalitis in China in the Period of 1950-2018: From Discovery to Control.

Biomed Environ Sci 2021 Mar;34(3):175-183

Department of Arbovirus, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

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http://dx.doi.org/10.3967/bes2021.024DOI Listing
March 2021

SARS-CoV-2 M inhibitors with antiviral activity in a transgenic mouse model.

Science 2021 03 18;371(6536):1374-1378. Epub 2021 Feb 18.

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (M) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of M in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.
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http://dx.doi.org/10.1126/science.abf1611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099175PMC
March 2021

Tissue distribution of SARS-CoV-2 in non-human primates after combined intratracheal and intranasal inoculation.

Sci China Life Sci 2021 Feb 10. Epub 2021 Feb 10.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

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http://dx.doi.org/10.1007/s11427-020-1877-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882853PMC
February 2021

Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study.

Zool Res 2021 Mar;42(2):161-169

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continue to impact countries worldwide. At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-CoV-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-CoV-2-infected monkeys. We also detected anti-SARS-CoV-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-CoV-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-CoV-2 immunoglobulin M (IgM) and G (IgG) antibodies were not detected in 6.90% of COVID-19 patients. Furthermore, integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-CoV-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus, SARS-CoV-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-CoV-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995275PMC
March 2021

Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.

Zool Res 2020 Sep;41(5):503-516

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( ) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b and CD8 cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b cells, and persistent infiltration of CD8 cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475018PMC
September 2020

COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2.

Zool Res 2020 Sep;41(5):517-526

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/ HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here, different aged Chinese tree shrews (adult group, 1 year old; old group, 5-6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days post-inoculation (dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3, 5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475013PMC
September 2020

Microscopic investigations on the surface-state dependent moisture stability of a hybrid perovskite.

Nanoscale 2020 Apr 25;12(14):7759-7765. Epub 2020 Mar 25.

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

Hybrid organic-inorganic perovskite (HOIP) materials have caught significant attention in photovoltaics and photoelectronics for their outstanding photovoltaic properties. However, their instability to various environment, such as illumination, temperature, moisture and oxygen, hinders their way to commercialization. To figure out the interaction mechanism between HO and CHNHPbI (MAPbI), extensive theoretical studies have been carried out; however, the experimental results are insufficient and inconsistent. Here, we systematically investigate and compare the influence of HO on MAPbI perovskite films with or without DMF) post-annealing in dark or light condition. The interaction between HO and the surface of pristine MAPbI leads to the fusion of grain boundaries thus grain growth into micron level in short-time moisture exposure. While the penetration of HO into MAPbI results in swelled crystalline whisker, cracking into smaller grains in long-time exposure upon the release of HO. However, no degradation occurs in dark condition. As the DMF post-annealing treatment changes the surface states of MAPbI, the interactions between the external HO and internal MAPbI significantly varies from the pristine MAPbI. Three different surface states with different topographies have influence on the interaction process and mechanism with HO, leading to different decomposition rates, the striped surface that is the most rough among the three and experiencing the minimum change in surface potential with exposure to 80% humidity decomposes into PbI fastest. However, the addition of light will once again affect the aforementioned process. It is found that even ambient light could severely speed up the moisture-induced decomposition of MAPbI, while the N,N-dimethylformamide (DMF) post-annealing treatment significantly improves the stability of MAPbI films upon exposure to humidity and illumination, benefiting from the MAI-deficient thus HO resistant surface.
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http://dx.doi.org/10.1039/c9nr10137cDOI Listing
April 2020

Direct thiocarbamation of imidazoheterocycles via dual C-H sulfurization.

Org Biomol Chem 2019 08;17(34):7854-7857

Department of Applied Chemistry, College of Materials and Energy, State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, South China Agricultural University, Guangzhou 510642, China.

A copper-catalyzed DTBP oxidative dual C-H sulfurization has been developed for the direct thiocarbamation of imidazopyridines using a combination of elemental sulfur and formamides as carbamothioyl surrogates. NBS (bromo succinimide) was found to promote the thiocarbamation in good yields. This dual C-H sulfurization strategy enables access to a wide range of carbamothioyl imidazoheterocycles without the use of highly toxic phosgene.
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http://dx.doi.org/10.1039/c9ob01403aDOI Listing
August 2019

[Market quality surveillance and analysis of chinese medicinal materials and decoction pieces in 2017].

Zhongguo Zhong Yao Za Zhi 2018 Nov;43(21):4198-4202

National Institutes for Food and Drug Control, Beijing 100050, China.

With the rapid development of traditional Chinese medicine (TCM) in China as well as the implementation of the four most strict requirements, the quality of Chinese medicinal materials and decoction pieces had beem improved in recent years, however new problems and challenges were occurred. All the data of Chinese medicinal materials and decoction piece in special inspection,supervision test and evaluation inspection of drug administration department to were summarized and analyzed evaluate and analyze of the quality of Chinese medicinal materials and decoction pieces in 2017. On this basis, the relevant quality control strategies and suggestions were put forward for the relevant departments of China Food and Drug Administration to formulate and implement regulatory measures, furthermore to improve drug standards, and ensure the safety of medication.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.2018.0110DOI Listing
November 2018

Identification of velvet antler and its mixed varieties by UPLC-QTOF-MS combined with principal component analysis.

J Pharm Biomed Anal 2019 Feb 4;165:18-23. Epub 2018 Oct 4.

Research and Inspection Center of Traditional Chinese Medicine and Ethnomedicine, National Institutes for Food and Drug Control, State Food and Drug Administration, 2 Tiantan Xili, Beijing, 100050, China. Electronic address:

Many species of velvet antler have been used as traditional medicine for thousands of years; however, as medicinal materials, velvet antler derived from different animals have different clinical effects. To distinguish the differences and homologies, ultra-performance liquid chromatography-quadruple-time of flight mass spectrometry (UPLC-QTOF-MS) coupled with principal component analysis (PCA) was developed and applied to identify these antler samples derived from Cervus nippon Temminck, Cervus elaphus Linnaeus and Rangifer tarandus Linnaeus, which were first tested and compared at the molecular level of protein. The UPLC-MS data of the trypsin digested samples were subjected to PCA, and the potential markers based on peptide were depicted to illustrate their differences. With the integrated strategy combining UPLC-QTOF-MS with PCA, the results from this study indicated that the proposed methods could be successfully applied to distinguish reindeer antler from sika deer antler and red deer antler, which were prescribed in the Chinese Pharmacopoeia (2015 edition).
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http://dx.doi.org/10.1016/j.jpba.2018.10.009DOI Listing
February 2019

Rhubarb Protect Against Tubulointerstitial Fibrosis by Inhibiting TGF-β/Smad Pathway and Improving Abnormal Metabolome in Chronic Kidney Disease.

Front Pharmacol 2018 13;9:1029. Epub 2018 Sep 13.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, China.

Tubulointerstitial fibrosis is the final common pathway for all kidney diseases leading to chronic kidney disease (CKD). TGF-β/Smad signaling pathway plays a key role in renal fibrosis. Previous studies have revealed that rhubarb extracts attenuated the increase of transforming growth factor-β 1 (TGF-β1) in CKD rats. To gain an in-depth insight into the mechanism of the anti-fibrotic activities of the rhubarb extracts, we investigated the influence of rhubarb extracts on TGF-β/Smad signaling pathway and the influence on metabolome in a rat model of CKD with adenine-induced chronic tubulointerstitial nephropathy. Male Sprague-Dawley rats were divided into four groups, including control, CKD, CKD + petroleum ether extract, CKD + ethyl acetate extract, and CKD + -butanol extract groups. Kidneys harvested on the week three were evaluated for renal fibrosis, the expression of proteins in TGF-β/Smad signaling pathway and metabolomic study. We found rhubarb extracts suppressed TGF-β/Smad3-mediated renal fibrosis by reducing the TGF-β1, transforming growth factor-β receptor I (TGF-β RI), transforming growth factor-β receptor II (TGF-β RII), Smad2, p-Smad2, Smad3, p-Smad3, and Smad4, meanwhile increased Smad7. In addition, rhubarb extracts mitigated renal injury and dysfunction, and either fully or partially reversed the abnormalities of tissue metabolites. Thus, rebalancing the disorder of TGF-β/Smad signaling and metabolic dysfunction by treatment with rhubarb extracts may represent as an effective therapy for CKD associated with fibrosis.
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http://dx.doi.org/10.3389/fphar.2018.01029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146043PMC
September 2018

Feasibility of percutaneous interbody fusion as a treatment for adjacent vertebral stress fracture of ankylosing spondylitis with intervertebral pseudarthrosis formation.

J Pain Res 2018 29;11:1673-1678. Epub 2018 Aug 29.

Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China,

Objective: The objective of this study was to evaluate the feasibility of percutaneous interbody fusion (PIF) using bone cement for adjacent vertebral stress fracture of ankylosing spondylitis (AS) with intervertebral pseudarthrosis formation.

Patients And Methods: From January 2010 to February 2018, eleven consecutive patients (seven men and four women; median age, 56.09±13.64 years; age range, 33-80 years) who underwent PIF as a treatment for adjacent stress fracture of AS with intervertebral pseudarthrosis formation were retrospectively analyzed. The Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) score were assessed before and after the procedure; meanwhile, the procedure duration, length of hospital stay and complications were assessed. Moreover, anterior/lateral and computed tomography (CT) scans were utilized for the assessment of bone cement distribution and interbody fusion.

Results: Technical success was achieved in all patients, and they experienced good interbody fusion with bone cement after PIF. Mean VAS scores declined significantly from 8.82±0.87 before the procedure to 3.36±0.67 1 day after the procedure and 2.73±0.65 1 month after the procedure, while the mean ODI scores decreased from 82.91±3.02 before treatment to 31.64 ±2.66 1 day after treatment and 30.00±3.10 1 month after treatment. The mean procedure duration was 49.73±6.12 minutes (range, 42-65 minutes). The average length of hospital stay was 7.09±1.45 days (range, 5-10 days). Extraosseous cement leakage occurred in one case without causing any clinical complications.

Conclusion: PIF is a feasible therapeutic technique for adjacent vertebral stress fracture of AS with intervertebral pseudarthrosis formation, which can significantly relieve pain and stabilize the fractured spine.
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http://dx.doi.org/10.2147/JPR.S150455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120515PMC
August 2018

Regulators of G-Protein Signaling (RGS) Proteins Promote Receptor Coupling to G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels.

J Neurosci 2018 10 27;38(41):8737-8744. Epub 2018 Aug 27.

Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon 97239,

Regulators of G-protein signaling (RGS) proteins negatively modulate presynaptic μ-opioid receptor inhibition of GABA release in the ventrolateral periaqueductal gray (vlPAG). Paradoxically, we find that G-protein-coupled receptor (GPCR) activation of G-protein-gated inwardly rectifying K channels (GIRKs) in the vlPAG is reduced in an agonist- and receptor-dependent manner in transgenic knock-in mice of either sex expressing mutant RGS-insensitive Gαo proteins. μ-Opioid receptor agonist activation of GIRK currents was reduced for DAMGO and fentanyl but not for [Met]-enkephalin acetate salt hydrate (ME) in the RGS-insensitive heterozygous (Het) mice compared with wild-type mice. The GABA agonist baclofen-induced GIRK currents were also reduced in the Het mice. We confirmed the role of Gαo proteins in μ-opioid receptor and GABA receptor signaling pathways in wild-type mice using myristoylated peptide inhibitors of Gαo and Gαi The results using these inhibitors indicate that receptor activation of GIRK channels is dependent on the preference of the agonist-stimulated receptor for Gαo versus that for Gαi. DAMGO and fentanyl-mediated GIRK currents were reduced in the presence of the Gαo inhibitor, but not the Gαi inhibitors. In contrast, the Gαo peptide inhibitor did not affect ME activation of GIRK currents, which is consistent with results in the Het mice, but the Gαi inhibitors significantly reduced ME-mediated GIRK currents. Finally, the reduction in GIRK activation in the Het mice plays a role in opioid- and baclofen-mediated spinal antinociception, but not supraspinal antinociception. Thus, our studies indicate that RGS proteins have multiple mechanisms of modulating GPCR signaling that produce negative and positive regulation of signaling depending on the effector. Regulators of G-protein signaling (RGS) proteins positively modulate GPCR coupling to GIRKs, and this coupling is critical for opioid- and baclofen-mediated spinal antinociception, whereas μ-opioid receptor-mediated supraspinal antinociception depends on presynaptic inhibition that is negatively regulated by RGS proteins. The identification of these opposite roles for RGS proteins has implications for signaling via other GPCRs.
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http://dx.doi.org/10.1523/JNEUROSCI.0516-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181307PMC
October 2018

Remote Ischemic Conditioning in Cerebral Diseases and Neurointerventional Procedures: Recent Research Progress.

Front Neurol 2018 16;9:339. Epub 2018 May 16.

Mayo Clinic, Rochester, MN, United States.

Cerebral ischemia and stroke are increasing in prevalence and are among the leading causes of morbidity and mortality in both developed and developing countries. Despite the progress in endovascular treatment, ischemia/reperfusion (IR) injury is an important contributor to post-surgical mortality and morbidity affecting a wide range of neurointerventional procedures. However, pharmacological recruitment of effective cerebral protective signaling has been largely disappointing to date. In remote ischemic conditioning (RIC), repetitive transient mechanical obstruction of vessels at a limb remote from the IR injury site protects vital organs from IR injury and confers infarction size reduction following prolonged arterial occlusion. Results of pharmacologic agents appear to be species specific, while RIC is based on the neuroprotective influences of phosphorylated protein kinase B, signaling proteins, nitric oxide, and transcriptional activators, the benefits of which have been confirmed in many species. Inducing RIC protection in patients undergoing cerebral vascular surgery or those who are at high risk of brain injury has been the subject of research and has been enacted in clinical settings. Its simplicity and non-invasive nature, as well as the flexibility of the timing of RIC stimulus, also makes it feasible to apply alongside neurointerventional procedures. Furthermore, despite nonuniform RIC protocols, emerging literature demonstrates improved clinical outcomes. The aims of this article are to summarize the potential mechanisms underlying different forms of conditioning, to explore the current translation of this paradigm from laboratory to neurovascular diseases, and to outline applications for patient care.
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http://dx.doi.org/10.3389/fneur.2018.00339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964135PMC
May 2018

The toxicological mechanisms and detoxification of depleted uranium exposure.

Environ Health Prev Med 2018 May 16;23(1):18. Epub 2018 May 16.

Department of Chemistry, School of Pharmacy, Fourth Military Medical University, No. 169 Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China.

Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.
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http://dx.doi.org/10.1186/s12199-018-0706-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956823PMC
May 2018

No inferiority of Tonbridge thrombectomy device for acute thrombus retrial compared with Solitaire device: an experimental evaluation with a canine distal external carotid-maxillary artery occlusion model.

J Neurointerv Surg 2018 Nov 14;10(11):1085-1091. Epub 2018 Feb 14.

Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Introduction: Mechanical thrombectomy (MT) has been widely accepted as a safe and effective treatment for acute ischemic stroke (AIS). Development of stent retriever devices has been intensively developed over the past two decades. In this study, we compared the effectiveness and safety of a new thrombectomy device with Solitaire FR for the treatment of AIS models.

Methods: Mechanical performance of stent retrievers was tested in vitro. Thrombin-induced thrombus was pre-injected into the right distal external carotid-maxillary artery in 18 dogs to create an acute thrombus occlusion model, and these animals were divided into a Tonbridge group (n=9, with Tonbridge stent Tonbridge Medical Technology) and a Solitaire group as control (n=9, with Solitaire stent, ev3 Neurovascular). Final flow restoration, side branches, recanalization time, distal vessel embolism, and device-related complications were recorded and compared. A post-procedure angiogram was obtained at 30 and 90 days after thrombectomy. Device manipulation-related damage to the arterial walls was evaluated histologically.

Results: In vitro test showed that the maximum friction within the microcatheter was 0.763 for the Tonbridge device and 0.784 n for the Solitaire (P>0.05). Slight increase in radial force was noticed for the Tonbridge (0.035 N/mm vs 0.031 N/mm of Solitaire, P>0.05). Eighteen and 16 retriever attempts were done in the Tonbridge (mean 2.0 attempts) and the Solitaire (mean 1.8 attempts) groups (P=0.74). The Tonbridge device led to good flow restoration in all nine (100%) models compared with eight (88.9%) in the Solitaire group (P=0.30). Side branches' influence (P=0.39), distal thromboembolism (P=0.60), and device-related complications (P=1.00) found no difference between the two groups. The rates of disruption of the internal elastic lamina (IEL) were 8.3% (2/24) and 4.2% (1/24) of the specimens, respectively (P=0.683). TICI 2b/3 flow of the right CCA were similar between the two groups at 1 (6/6 vs 6/6) and 3 months (6/6 vs 6/6) follow-up (P>0.05).

Conclusion: Our preliminary study indicated this new device was technically feasible and effective to be used in thrombectomy for the treatment of acute thrombus occlusion in canine models.
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http://dx.doi.org/10.1136/neurintsurg-2017-013673DOI Listing
November 2018

From discovery to spread: The evolution and phylogeny of Getah virus.

Infect Genet Evol 2017 11 19;55:48-55. Epub 2017 Aug 19.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, People's Republic of China.; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310058, People's Republic of China. Electronic address:

Getah virus (GETV) was first isolated in Malaysia in 1955. Since then, epidemics in horses and pigs caused by GETV have resulted in huge economic losses. At present, GETV has spread across Eurasia and Southeast Asia, including mainland China, Korea, Japan, Mongolia, and Russia. Data show that the Most Recent Common Ancestor (MRCA) of GETV existed about 145years ago (95% HPD: 75-244) and gradually evolved into four distinct evolutionary populations: Groups I-IV. The MRCA of GETVs in Group III, which includes all GETVs isolated from mosquitoes, pigs, horses, and other animals since the 1960s (from latitude 19°N to 60°N), existed about 51years ago (95% HPD: 51-72). Group III is responsible for most viral epidemics among domestic animals. An analysis of the GETV E2 protein sequence and structure revealed seven common amino acid mutation sites. These sites are responsible for the structural and electrostatic differences detected between widespread Group III isolates and the prototype strain MM2021. These differences may account for the recent geographical radiation of the virus. Considering the economic significance of GETV infection in pigs and horses, we recommend the implementation of strict viral screening and monitoring programs.
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http://dx.doi.org/10.1016/j.meegid.2017.08.016DOI Listing
November 2017

Optogenetic Evidence for a Direct Circuit Linking Nociceptive Transmission through the Parabrachial Complex with Pain-Modulating Neurons of the Rostral Ventromedial Medulla (RVM).

eNeuro 2017 May-Jun;4(3). Epub 2017 Jun 26.

Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239.

The parabrachial complex (PB) is a functionally and anatomically complex structure involved in a range of homeostatic and sensory functions, including nociceptive transmission. There is also evidence that PB can engage descending pain-modulating systems, the best characterized of which is the rostral ventromedial medulla (RVM). Two distinct classes of RVM neurons, "ON-cells" and "OFF-cells," exert net pronociceptive and anti-nociceptive effects, respectively. PB was recently shown to be a relay of nociceptive information to RVM ON- and OFF-cells. The present experiments used optogenetic methods in a lightly anesthetized rat and an adult RVM slice to determine whether there are direct, functionally relevant inputs to RVM pain-modulating neurons from PB. Whole-cell patch-clamp recordings demonstrated that PB conveys direct glutamatergic and GABAergic inputs to RVM neurons. Consistent with this, recording showed that nociceptive-evoked responses of ON- and OFF-cells were suppressed by optogenetic inactivation of archaerhodopsin (ArchT)-expressing PB terminals in RVM, demonstrating that a net inhibitory input to OFF-cells and net excitatory input to ON-cells are engaged by acute noxious stimulation. Further, the majority of ON- and OFF-cells responded to optogenetic activation of channelrhodopsin (ChR2)-expressing terminals in the RVM, confirming a direct PB influence on RVM pain-modulating neurons. These data show that a direct connection from the PB to the RVM conveys nociceptive information to the pain-modulating neurons of RVM under basal conditions. They also reveal additional inputs from PB with the capacity to activate both classes of RVM pain-modulating neurons and the potential to be recruited under different physiological and pathophysiological conditions.
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http://dx.doi.org/10.1523/ENEURO.0202-17.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483601PMC
April 2018

Rapamycin enhances the anti-angiogenesis and anti-proliferation ability of YM155 in oral squamous cell carcinoma.

Tumour Biol 2017 Jun;39(6):1010428317706213

1 Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, Shenzhen, China.

YM155, a small molecule inhibitor of survivin, has been studied in many tumors. It has been shown that YM155 inhibited oral squamous cell carcinoma through promoting apoptosis and autophagy and inhibiting proliferation. It was found that YM155 also inhibited the oral squamous cell carcinoma-mediated angiogenesis through the inactivation of the mammalian target of rapamycin pathway. Rapamycin, a mammalian target of rapamycin inhibitor, played an important role in the proliferation and angiogenesis of oral squamous cell carcinoma cell lines. In our study, cell proliferation assay, transwell assay, tube formation assay, and western blot assay were used to investigate the synergistic effect of rapamycin on YM155 in oral squamous cell carcinoma. Either in vitro or in vivo, rapamycin and YM155 exerted a synergistic effect on the inhibition of survivin and vascular endothelial growth factor through mammalian target of rapamycin pathway. Overall, our results revealed that low-dose rapamycin strongly promoted the sensitivity of oral squamous cell carcinoma cell lines to YM155.
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http://dx.doi.org/10.1177/1010428317706213DOI Listing
June 2017

Complications associated with the use of flow-diverting devices for cerebral aneurysms: a systematic review and meta-analysis.

Neurosurg Focus 2017 Jun;42(6):E17

Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai.

OBJECTIVE The objective of this study was to review the literature on the use of flow-diverting devices (FDDs) to treat intracranial aneurysms (IAs) and to investigate the safety and complications related to FDD treatment for IAs by performing a meta-analysis of published studies. METHODS A systematic electronic database search was conducted using the Springer, EBSCO, PubMed, Medline, and Cochrane databases on all accessible articles published up to January 2016, with no restriction on the publication year. Abstracts, full-text manuscripts, and the reference lists of retrieved articles were analyzed. Random-effects meta-analysis was used to pool the complication rates across studies. RESULTS Sixty studies were included, which involved retrospectively collected data on 3125 patients. The use of FDDs was associated with an overall complication rate of 17.0% (95% confidence interval [CI] 13.6%-20.5%) and a low mortality rate of 2.8% (95% CI 1.2%-4.4%). The neurological morbidity rate was 4.5% (95% CI 3.2%-5.8%). No significant difference in the complication or mortality rate was observed between 2 commonly used devices (the Pipeline embolization device and the Silk flow-diverter device). A significantly higher overall complication rate was found in the case of ruptured IAs than in unruptured IA (odds ratio 2.3, 95% CI 1.2-4.3). CONCLUSIONS The use of FDDs in the treatment of IAs yielded satisfactory results with regard to complications and the mortality rate. The risk of complications should be considered when deciding on treatment with FDDs. Further studies on the mechanism underlying the occurrence of adverse events are required.
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http://dx.doi.org/10.3171/2017.3.FOCUS16450DOI Listing
June 2017

Feasibility of Percutaneous Lumbar Discectomy Combined with Percutaneous Cementoplasty for Symptomatic Lumbar Disc Herniation with Modic Type I Endplate Changes.

Pain Physician 2017 05;20(4):E481-E488

Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Treatment of symptomatic lumbar disc herniation with Modic type I endplate changes is complex and challenging, requiring systemic and local therapies which include conservative therapy, epidural infiltrations, percutaneous therapeutic techniques, and surgical options. The clinical management of symptomatic lumbar disc herniation involving Modic type I endplate changes is uniquely challenging because it requires alleviating pain caused by both the herniated disc and the endplate osteochondritis. Through different approaches, percutaneous lumbar discectomy (PLD) and percutaneous cementoplasty (PCP) have been introduced into clinical practice as alternatives to traditional surgical and radiotherapy treatments of symptomatic lumbar disc herniation and other spine diseases.

Objective: To evaluate the feasibility of PLD and PCP for symptomatic lumbar disc herniation with Modic type I endplate changes.

Study Design: PLD and PCP in 7 patients with symptomatic lumbar disc herniation with Modic type I endplate changes and its clinical effects were retrospectively evaluated.

Setting: This study was conducted by an interventional therapy group at a medical center in a major Chinese city.

Methods: Seven consecutive patients (2 men, 5 women; median age, 74.14 ± 5.34 years; age range, 68 - 82 years) who underwent percutaneous lumbar discectomy and cementoplasty for the treatment of symptomatic lumbar disc herniation with Modic type I changes between May 2013 and August 2015 were retrospectively analyzed. The MacNab Criteria, visual analog scale (VAS), and Oswestry Disability Index (ODI) for pain were assessed before and one week, 6 months, and one year after the procedure. Furthermore, the procedure duration, hospital stay length, and complications were assessed.

Results: The VAS of the back and leg decreased from 6.14 ± 0.69 (range, 5 - 7) and 7.29 ± 0.76 (range, 6 - 8) preoperatively to 2.29 ± 1.38 (range, 1 - 5) and 2.71 ± 0.60 (range, 1 - 6) one week, 1.86 ± 0.69 (range, 1 - 3) and 2.00 ± 0.58 (range, 1 - 3) 6 months, and 1.71 ± 0.76 (range, 1 - 3) and 1.85 ± 0.69 (range, 1 - 3) one year postoperatively. The ODI dropped from 76.86 ± 7.45 (range, 70 - 82) preoperatively to 26.29 ± 19.47 (range, 16 - 70) one week, 19.14 ± 2.79 (range, 16 - 24) 6 months, and 18.57 ± 2.99 (range, 16 - 24) one year postoperatively. The mean procedure duration was 55.71 ± 6.07 minutes (range, 50 - 65 minutes). The average length of hospital stay was 7.57 ± 1.27 days (range, 6 - 10 days). No obvious complications were noted.

Limitations: This was a retrospective study with a relatively small sample size.

Conclusion: PLD plus PCP is a feasible technique for symptomatic lumbar disc herniation with Modic type I endplate changes.
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May 2017

Identification of four cornua by ultra-performance liquid chromatography with time-of-flight mass spectrometry coupled with principal component analysis.

J Sep Sci 2017 Apr 17;40(8):1667-1673. Epub 2017 Mar 17.

Institute for Control of Traditional Chinese Medicine and Ethnic Medicine, National Institutes for Food and Drug Control, Beijing, China.

An ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method coupled with principal component analysis was developed and applied to the identification of Cornu Antelopis, Cornu Bubali, Cornu Naemorhedi, and Cornu Bovis. The data obtained from the trypsin-digested samples were subjected to principal component analysis to classify these four cornua. Additionally, marker peptides of the cornua were determined by orthogonal partial least-squares discriminant analysis, and fragmentation tandem mass spectra of these marker peptides were evaluated. The results from this study indicate that the proposed method is reliable, and it has been successfully applied to the identification of variants of cornua commonly used in traditional Chinese medicine.
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http://dx.doi.org/10.1002/jssc.201600902DOI Listing
April 2017

Outflow angle measurement: a simple approach for the differential diagnosis of intracranial protrusion with a branch artery arising from its top.

Surg Radiol Anat 2017 Aug 14;39(8):911-919. Epub 2017 Feb 14.

Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yi Shan Road, Shanghai, 200233, China.

Purpose: Magnetic resonance angiography (MRA) is an important diagnosis method for the detection of intracranial aneurysms (IAs), but it is not useful for differentiating between IA and infundibular dilatation (ID) in patients in whom imaging shows an intracranial protrusion with a branch artery at its top. The objective of this study was to introduce a new approach-measurement of the outflow angle (OA)-for differentiating between IA and ID in such cases.

Methods: The study included 7 patients with a total of 9 protrusions. The protrusions were separately reviewed on MRA and DSA images. We first diagnosed the protrusions using OA approach. An OA ≥90° was considered indicative of an IA and an OA <90° was considered indicative of an ID. The diagnosis by the OA method was compared with diagnosis by the gold standard-DSA.

Results: Among the 9 intracranial protrusions, 5 were IAs and 4 were IDs. The OAs of 5 IAs were all ≥90°; the average OA of the 5 IAs was 115.20°. The OAs of the 4 IDs were all <90°; the average OA of the 4 IDs was 59.50°. The diagnosis results by the OA method were in agreement with DSA diagnosis in all cases.

Conclusion: The OA method can discriminate between IA and ID in patients in whom imaging shows an intracranial protrusion with a branch artery at its top. The method is simple and convenient, and can be easily applied in clinical practice. It can be especially useful for novice neuroradiologists.
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http://dx.doi.org/10.1007/s00276-017-1820-4DOI Listing
August 2017

Compensatory Activation of Cannabinoid CB2 Receptor Inhibition of GABA Release in the Rostral Ventromedial Medulla in Inflammatory Pain.

J Neurosci 2017 01;37(3):626-636

Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon 97239.

The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM, but it is not known whether this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature IPSCs (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA-treated rats compared with naive rats. The reduction in CFA-treated rats correlated with decreased CB1 receptor protein expression and function in the RVM. Paradoxically, the nonselective CB1/CB2 receptor agonist WIN55212 inhibited GABAergic mIPSCs in both naive and CFA-treated rats. However, WIN55212 inhibition was reversed by the CB1 receptor antagonist rimonabant in naive rats but not in CFA-treated rats. WIN55212-mediated inhibition in CFA-treated rats was blocked by the CB2 receptor-selective antagonist SR144528, indicating that CB2 receptor function in the RVM is increased during persistent inflammation. Consistent with these results, CB2 receptor agonists AM1241 and GW405833 inhibited GABAergic mIPSC frequency only in CFA-treated rats, and the inhibition was reversed with SR144528. When administered alone, SR144528 and another CB2 receptor-selective antagonist AM630 increased mIPSC frequency in the RVM of CFA-treated rats, indicating that CB2 receptors are tonically activated by endocannabinoids. Our data provide evidence that CB2 receptor function emerges in the RVM in persistent inflammation and that selective CB2 receptor agonists may be useful for treatment of persistent inflammatory pain.

Significance Statement: These studies demonstrate that endocannabinoid signaling to CB1 and CB2 receptors in adult rostral ventromedial medulla is altered in persistent inflammation. The emergence of CB2 receptor function in the rostral ventromedial medulla provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.
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http://dx.doi.org/10.1523/JNEUROSCI.1310-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242409PMC
January 2017
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