Table of Content

    31 August 2020, Volume 29 Issue 8
    Intranasal delivery of rapid-onset antidepressants: a new trend of treating major depressive disorder
    Yuqi Xie, Yushun Dou, Yue Tang
    2020, 29(8):  515-527.  DOI: 10.5246/jcps.2020.08.049
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    Existing antidepressants seem to have an onset time of several weeks. However, newly found depression-related receptors and pathways may enlighten us to find more rapid-onset antidepressants, in which ketamine is one of the most potential antidepressants. By intranasal administration, drugs can be directly delivered to the brain via olfactory nerve route, which is proved to be suitable for some antidepressants. Well-designed rapid-onset antidepressants are the urgent requirements of the patients with depression. Intranasal administration, as a potential strategy to deliver antidepressants to brain, can improve drug efficacy and largely shorten the onset time. In this article, we sorted out some new formulation approaches in treating depression with different mechanisms and pathways compared with traditional treating strategies, along with new findings in clinical studies, proving that the combination of rapid-onset antidepressants with intranasal delivery will lead a new trend in treating depression. 
    Original articles
    Identification of serum biomarkers for evaluating seizure outcome after resective epilepsy surgery
    Qian Chen, Xuyang Zhao, Yujing Song, Shaoyi Li, Wanyu Lei, Weining Ma, Zhuo Huang
    2020, 29(8):  528-541.  DOI: 10.5246/jcps.2020.08.050
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    Although patients with drug-resistant temporal lobe epilepsy (TLE) achieve good seizure control with resective surgery combined with anti-epileptic drugs (AEDs) treatment, it is still not clear when to withdraw AEDs after the surgery due to a lack of objective strategy for assessing the surgery outcome. Our aim is to identify objective and efficient biomarkers for assessment of surgery outcome to guide postoperative pharmacotherapy. Here, we detected 469 proteins differentially expressed between pre- and post-operative sera of TLE patients with postoperative seizure freedom, and identified six candidate proteins (HBA1, HBB, PRDX2, CA1, CAT and BLVRB) for validation. These six proteins were significantly reduced within three months after surgery, indicating these proteins may be potential biomarkers to assess the surgery outcome for TLE patients in the early stage. Interestingly,we found HBA1 to HBB ratio was superior to individual proteins to evaluate the postoperative surgery outcome with 90.0% sensitivity, 90% specificity and area under the curve of 0.960. We also suppose these proteins were derived from epilepsy foci due to the rat experiment results that HBA1, HBB, PRDX2, CA1 and CAT were highly expressed in cerebrospinal fluid of epilepsy rat models. Additionally, HBA1, HBB, PRDX2, CA1 and BLVRB proteins were highly expressed in the sera of TLE patients with postoperative seizure freedom when compared to TLE patients with postoperative seizure and patients with other types of epilepsy, suggesting surgery outcome or the original sites of seizure might be assessed before the operation through monitoring these protein levels in the sera. Our study provides experimental data for establishing objective indicators for assessing seizure freedom after resective surgery and also proposed potential markers for specific diagnoses of TLE and prediction of TLE surgery outcome.
    Cost-effectiveness analysis of second-line chemotherapy strategies for patients with advanced non-squamous non-small cell lung cancer
    Shen Lin, Xin Rao, Yiyuan Li, Xiuhua Weng, Changlian Wang
    2020, 29(8):  542-553.  DOI: 10.5246/jcps.2020.08.051
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    Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world. In this study, we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine, pemetrexed, and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states, progression-free survival, progressed survival and death, was constructed to simulate the progression of the disease in a 6-year horizon. Sensitivity analysis was performed to evaluate the robustness of the model. The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3× per capita GDP of China in 2018 ($29 383). The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233, 0.417 and 0.272 for gemcitabine, pemetrexed and docetaxel, respectively, and the corresponding total costs were $5321.02, $12 143.94, and $9479.42. Gemcitabine, pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of $37 081.09 and $106 625.64 per quality-adjusted life year gained. The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold. One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.   
    Preparation and in vitro evaluation of APT011-loaded sustained-release microspheres
    Chengqun Li, Xia Niu, Jiahui Mu, Xiaomei Wang, Jin Su, Guiling Li
    2020, 29(8):  554-563.  DOI: 10.5246/jcps.2020.08.052
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    In the present study, we aimed to prepare sustained-release microspheres for injection of neurokinin-1 (NK-1) receptor antagonist APT011, and to evaluate their physicochemical properties, in vitro sustained-release effect and preliminary stability. APT011-loaded sustained-release microspheres were prepared using W/O/W double emulsion-solvent evaporation technique. The L9 (34) orthogonal experiment was used to optimize the APT011 sustained-release microsphere formulation. Microscope photographs showed that APT011-loaded microspheres were spherical, and the particle size was ~90 μm with uniform size distribution. XRD results indicated that APT011 existed in the microspheres in an amorphous form. DSC results showed that there was no significant interaction between APT011 and blank microspheres. APT011-loaded microspheres had a significant sustained-release effect, which maintained release for at least 2 months. Preliminary study results indicated that the loading content and release percentage at 0.5 h were not markedly altered below 40 °C and under high lighting condition. APT011-loaded microspheres prepared in our study exhibited excellent physicochemical properties and sustained-release characteristics and preliminary stability, demonstrating real potential for the clinical practice.
    Synthesis of prenylated and geranylated xanthones and their bioactivities
    Beidou Zhou, Zihan Yu, Yugui Tong, Jiali Li, Baocheng Huang, Rongrong Wei, Zhimin Weng, Xin Wang, Zhipeng Ruan, Jian Lin, Caihong Xu, Jianbo Liu
    2020, 29(8):  564-576.  DOI: 10.5246/jcps.2020.08.053
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    Nine prenylated and geranylated xanthones were synthesized in two steps with total yields ranging from 11% to 36%. All of the compounds were first reported. Then, the antitumor, anti-tyrosinase, anti-pancreatic lipase,antifungal and antibacterial activities of all or part of compounds 19 were evaluated. Compound 9 exhibited clear antitumor activity, and its cytotoxicity against MCF-7 and MDA-MB-231 cells was stronger compared with cisplatin. Compounds 14 and 67 alsoexhibited certain activity other than the antitumor activity described above. These results demonstrated that compounds 14, 67and 9 were very promising leads for further structural modification. 
    A series of reviews on the “application of modern instruments and technologies in drug research”
    Surface-assisted laser desorption/ionization mass spectrometry for drug and metabolite analysis
    Wen Ma, Shuxiang Song, Jun Li
    2020, 29(8):  577-590.  DOI: 10.5246/jcps.2020.08.054
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    Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) uses inorganic nanomaterials as matrixes to facilitate desorption and ionization of analytes. Compared with the traditional matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) technique, SALDI-MS has the advantages of less interference in the low mass range, better reproducibility and higher salt tolerance. It is highly suitable for the analysis of small molecule compounds. In recent years, researchers have developed a range of nanomaterials that are successfully applied to the field of small molecule drug and metaboliteanalysis including drug screening and quantification, drug delivery, metabolite profiling, biomarker discovery and so forth. This review summarizes the latest progress of SALDI-MS matrix materials such as metal-based, carbon-based, silica-based nanomaterials and organic framework nanomaterials and their applications. In addition, our perspective of SALDI-MS technology is also discussed for further advancement.
    Case report
    Treatment analysis of acute fatty liver of pregnancy complicated with hematogenous infection of CRKP
    Lixia Li, Feng Chen, Xiaomei Xue, Fan Yang, Bin He
    2020, 29(8):  591-595.  DOI: 10.5246/jcps.2020.08.055
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    Acute fatty liver of pregnancy (AFLP) is an idiopathic disease with acute and critical onset. Although the incidence of AFLP is relatively low, its mortality remains high. When AFLP is complicated with multi-organ dysfunction syndrome (MODS) and severe infection, especially hematogenous infection caused by multidrug-resistant pathogens, treatment becomes extremely difficult with an even lower survival rate. In the present work, we reported a 31-year-old primipara woman who developed AFLP complicated with MODS and severe infection at 37+5 weeks of gestation and received treatment in our hospital. The result of fast blood culture was positive for carbapenem-resistant Klebsiella pneumonia (CRKP). Based on this finding in combination with the results of drug sensitivity test, the quadruple regime using scheme imipenem cilastatin sodium, tigecycline, polymyxin and fosfomycin was implemented, and the patient was successfully cured. Successful treatment of pregnant women with AFLP complicated with MODS and/or hematogenous infection of CRKP can be achieved by using individualized combined antibiotic therapies on the basis of fast blood culture and combined drug sensitivity test. In this case, the patient was in a critical situation. In the treatment process, clinicians, clinical pharmacists and microbiologists should cooperate with each other and discuss the treatment plan together according to the pathophysiological characteristics of the patient, which was one of the key factors for successful treatment of the patient.
    The others
    The group of Yiguang Wang created a new intelligent nano delivery technology in programmed response to tumor molecular signals
    State Key Laboratory of Natural and Biomimetic Drugs
    2020, 29(8):  596-597. 
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    The group of Yiguang Wang created a new intelligent nano delivery technology in programmed response to tumor molecular signals.

    The group of Xinjing Tang developed a novel light-sensitive CRISPR-Cas9 System to realize the light regulation of gene editing
    State Key Laboratory of Natural and Biomimetic Drugs
    2020, 29(8):  598-599. 
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    The group of Xinjing Tang developed a novel light-sensitive CRISPR-Cas9 System to realize the light regulation of gene editing.
    The group of Suwei Dong created a new strategy to simulate complex polysaccharides using self-assembled peptides
    State Key Laboratory of Natural and Biomimetic Drugs
    2020, 29(8):  600-601. 
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    The group of Suwei Dong created a new strategy to simulate complex polysaccharides using self-assembled peptides.
    Special issue calls for papers—Commemoration of the 100th Birthday of Academician Zhicen Lou
    Journal of Chinese Pharmaceutical Sciences
    2020, 29(8):  602-602. 
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    Special issue calls for papers—Commemoration of the 100th Birthday of Academician Zhicen Lou.