1.Analysis of Specific Chromatogram of Classical Formula Qianghuo Shengshi Tang Reference Samples
Wenya GAO ; He XU ; Mingli LI ; Haiyu ZHAO ; Yanyan ZHOU ; Hongjie WANG ; Jian YANG ; Xiaolu WEI ; Zhikun FAN ; Nan SI ; Baolin BIAN
Chinese Journal of Modern Applied Pharmacy 2024;41(10):1350-1356
OBJECTIVE
To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample.
METHODS
The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode.
RESULTS
There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids.
CONCLUSION
The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.
2. Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis
Rui GUAN ; Jiashu YAO ; Yeyu ZHAO ; Jiannan ZHENG ; Qing QI ; Jing YU ; Mingli GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):26-36
AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.
3.Atypical antipsychotic drugs with strong alpha 1 receptor antagonism resulting in self-perceived hot in patients with schizophrenia:a case report
Linyuan SUN ; Yang GAO ; Bin SU ; Mingli LI
Sichuan Mental Health 2024;37(3):267-269
This article reported a case of a patient with schizophrenia who experienced self-perceived fever and discomfort after taking atypical antipsychotic drugs with strong alpha 1 receptor antagonism,which included olanzapine,risperidone,paliperidone and clozapine.Such phenomenon was believed to be a medication side effect.Therefore,the patient switched to aripiprazole and the fever disappeared.This case report is intended to remind psychiatrists to pay attention to the side effects caused by atypical antipsychotic drugs with strong alpha 1 receptor antagonism as well as to suggest that various factors should be considered,including mechanisms of drug action,patient pathophysiology and individual differences,in order to improve treatment compliance and prognosis.
4.Investigation on the safety of regular plasma donors aged 56-60 years
Yang GAO ; Kecheng DONG ; Mingli MA ; Yan DONG ; Donghong FANG ; Yumeng SU ; Rong ZHOU ; Demei DONG
Chinese Journal of Blood Transfusion 2024;37(7):812-815
Objective To investigate the safety of regular plasma donors aged 55 to 60,so as to provide reference for retention and recruitment of elderly plasma donors in China.Methods Plasma donors from 9 blood products manufacturing enterprises from 2018 to 2020 and the local general population were selected as the research objects.The total protein level,albumin and globulin ratio(ALB/GLB,A/G)and adverse reactions of plasma donation of regular plasma donors and local general population were retrospectively analyzed.Results The total protein level(g/L)and A/G of plasma donors aged 56 to 60 and the general population were 61.21±5.62 vs 60.04±6.93 and 1.610±0.299 vs 1.635±0.330,respectively,and the differences were statistically significant.The total protein level of regular plasma donors was higher than that of general popu-lation,but A/G was slightly lower than that of general population.From 2018 to 2020,there were a total of 23 056 302 plas-ma donations in 108 plasma stations,and adverse reactions occurred in 20 932 donations,with a total incidence of 0.09%,with no serious adverse reactions.Conclusion It is safe for regular plasma donors aged 55 to 60 to donate plasma,and the retention of them can alleviate the pressure of plasma supply.
5.Rheumatoid arthritis with Castleman-like histopathology in lymph nodes:A case report
Dongwu LIU ; Jie CHEN ; Mingli GAO ; Jing YU
Journal of Peking University(Health Sciences) 2024;56(5):928-931
Rheumatoid arthritis(RA)is a common chronic autoimmune inflammatory disease,charac-terized by persistent polyarthritis.Patients with RA may exhibit varying degrees of B lymphocyte activa-tion,clinically manifested as enlarged lymph nodes.Disease-modifying anti-rheumatic drugs and glu-cocorticoid are often used to treat RA.Biological agents targeting tumor necrosis factor alpha,interleukin-6(IL-6),and B lymphocytes are often used to treat rheumatoid arthritis.Castleman disease(CD)is a rare benign lymphoproliferative disorder.Histopathological examination is the most important method to diagnose this disease.Based on the different lymph node involvement areas CD can be divided into uni-centric CD(UCD)and multicentric CD(MCD).Surgical removal of lymph nodes is a common treatment method for UCD.MCD often requires chemotherapeutic drugs combined with glucocorticoid therapy.For the most recent years,biological agents targeting IL-6 and B lymphocytes have shown good curative effects on CD.In the past,patients with rheumatic immune disease accompanied by Castleman like histo-pathology in lymph nodes were commonly referred to as rheumatic immune disease combined with CD.In 2021,experts unanimously agreed that autoimmune diseases with Castleman like lymphadenopathy should be diagnosed as rheumatic autoimmune diseases with Castleman like histopathology in lymph nodes.This report introduces a 65-year-old female patient with rheumatoid arthritis who was admitted to the hospital due to joint swelling and pain.Physical and chemical examinations after admission showed that rheuma-toid arthritis was in an active phase.Chest CT revealed multiple enlarged lymph nodes in the right arm-pit.Then it was removed by surgery.The histopathological report showed that the lymphatic sinus disappeared,the lymphoid tissue proliferated,the lymphoid follicles increased,and the size was incon-sistent.The small lymphocytes around the germinal centers of some follicles were concentric circles,and the follicular interstitial blood vessels proliferated.She was diagnosed with rheumatoid arthritis with Cas-tleman like histopathology in lymph nodes and was treated with methotrexate and hydroxychloroquine sul-fate combined with glucocorticoids.The patient was followed up for 2 years.In the first year after sur-gery,the patient's condition remained stable and there was no growth of lymph nodes in the right axilla.The patient passed away due to severe infection in the second year after the surgery.
6.Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects
Mingli SUN ; Chen LIU ; Yali WEI ; Qian GAO ; Qianying LIU ; Xinghe WANG
Journal of China Pharmaceutical University 2023;54(1):89-94
To evaluate bioequivalence and safety of two kinds of metformin hydrochloride sustained-release tablets (test preparation vs reference preparation) under the condition of fed and single administration.A single center, randomized, open, single-dose, two-period, two-sequence, and double-crossover design was used.32 healthy subjects took 0.5 g of test preparation or reference preparation under fed and single-dose administration.4 mL of venous blood was collected from before administration (0 h) to 1, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 15, 24, 36 and 48 h after administration.The concentration of metformin in plasma samples was detected, and then the pharmacokinetic parameters were calculated by WinNonlin 7.0 software.When the 90% confidence intervals of cmax, AUC0-t and AUC0-∞ geometric mean ratio of test preparation and reference preparation were within 80.00%-125.00% equivalent intervals respectively, the bioequivalence of the two preparations was proved.One subject fell off due to adverse events.The main pharmacokinetic parameters of test preparation and reference preparation as follows: cmax were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC0-t were (7.33 ± 1.65) and (7.00 ± 1.89) h·mg/L, AUC0-∞ were (7.39 ± 1.67) and (7.06 ± 1.91) h·mg/L, respectively.The 90% confidence intervals of the geometric mean ratio of the two main pharmacokinetic parameters were 101.45%-109.14%, 100.08%-112.32% and 100.24%-112.28%, respectively, which fell within the bioequivalence interval of 80.00%-125.00%.There were no serious adverse events and unexpected adverse events during the trial.The results show that test preparation and reference preparation are bioequivalent under fed and single-dose administration, safe and well tolerated in healthy subjects.
7.Effect of Tongdu Xingshen Needling Method (通督醒神针刺法) on Expression of AMPA Receptors and Their Accessory Proteins in the Hippocampus of Rats with Learning Memory Impairment After Cerebral Ischaemia-Reperfusion
Xiaodi RUAN ; Jing GAO ; Zhuan LYU ; Qi LI ; Kaiqi SU ; Yiming GU ; Mingyue YU ; Shikui QI ; Meng LUO ; Mingli WU ; Huiling WANG ; Xin SHEN ; Xiaodong FENG
Journal of Traditional Chinese Medicine 2023;64(23):2435-2442
ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method (通督醒神针刺法) on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group (n=12), a sham surgery group (n=12), a model group (n=12), and a electroacupuncture group (n=13). The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling, the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting (GV 24)” and “Baihui (GV 20)” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention, and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment, hippocampal tissues were taken from each group of rats, and the changes in the volume of cerebral infarction were observed by TTC staining; the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining; protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid (AMPA) receptor including glutamate receptor 1 (GluR1), glutamate receptor 2 (GluR2), glutamate receptor 3 (GluR3) and auxiliary proteins TARPγ2, TARPγ8 in hippocampal tissues of rats in each group; the real-time fluorescence quantitative PCR was used to detect GluR1, GluR2, GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment, compared with the normal group and sham surgery group, the escape latency and total distance of rats in the model group were significantly extended (P<0.05) at day 1, 2, 3, 4, and 5; and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group (P<0.05). In the spatial exploration experiment, compared with the normal group and the sham surgery group, the number of rats crossing the platform in the model group was significantly reduced (P<0.05), and the number of crossings of the platform in the electroacupuncture group increased significantly (P<0.05). The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group (P<0.05), and apparently decreased in the electroacupuncture group compared with the model group (P<0.05). Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group (P<0.05). The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group (P<0.05). The protein relative expression levels of GluR1, GluR2, GluR3, TARPγ2 and TARPγ8, and the mRNA levels of GluR1, GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group (P<0.05). The protein relative expression levels of GluR1, GluR2, GluR3, TARPγ2 and TARPγ8, and the mRNA levels of GluR1, GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group (P<0.05). ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion, which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP, and promoting the synaptic plasticity of hippocampal tissues.
8.Consistency study of FRACTURE sequence and CT in evaluating bone changes of knee and ankle
Nan WANG ; Qingwei SONG ; Ailian LIU ; Lihua CHEN ; Haonan ZHANG ; Mingli GAO ; Jiazheng WANG ; Liangjie LIN ; Qingping GU
Chinese Journal of Radiology 2023;57(3):294-299
Objective:To explore the consistency of MRI fast field echo resembling a CT using restricted echo-spacing (FRACTURE) and CT in the evaluation of knee and ankle bone changes.Methods:From November 2020 to November 2021, seventeen patients who underwent CT and MRI FRACTURE examinations of knee joint or ankle joint in the First Affiliated Hospital of Dalian Medical University were retrospectively collected, including 14 patients with knee joint examinations and 3 patients with ankle joint examinations. According to the number of joint components, 80 components were included, including 14 for femur and patella, 17 for tibia and fibula, and 3 for talus, scaphoid, medial cuneiform, medial cuneiform, lateral cuneiform and calcaneus, respectively. The fracture, hyperosteogeny, and bone destruction of the joint bones were evaluated by two observers using CT and FRACTURE images, respectively. Kappa test was used to analyze the consistency of CT and FRACTURE images between observers in the evaluation of joint bone lesions.Results:The Kappa values (95%CI) of the consistency evaluation of fracture, hyperosteogeny, and bone destruction by CT and FRACTURE images were 0.925 (0.823-1.027), 0.905 (0.799-1.011) and 0.895(0.752-1.038) respectively for observer 1, and were 0.963 (0.892-1.034), 0.933 (0.843-1.023) and 0.886 (0.731-1.041) respectively for observer 2. The Kappa values (95%CI) of the consistency evaluation of fracture, hyperosteogeny, and bone destruction by observers 1 and 2 via CT images were 1.000 (1.000-1.000), 0.937(0.851-1.023) and 0.945 (0.839-1.051) respectively, and that by FRACTURE images were 0.962 (0.888-1.036), 0.966 (0.899-1.033) and 0.836 (0.656-1.016) respectively.Conclusion:For the evaluation of fracture, hyperosteogeny, and bone destruction of knee joint and ankle joint, MRI FRACTURE sequence is highly consistent with CT.
9.Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity.
Mingli DUAN ; Yurui JIA ; Lifang HUO ; Yiting GAO ; Jia WANG ; Wei ZHANG ; Zhanfeng JIA
Acta Pharmaceutica Sinica B 2023;13(8):3365-3381
Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.
10.Analysis of the real situation of medication in the population with gout achieving T2T indicators: a multicentre real-world study
Weiqin GAO ; Xuezhong GONG ; Yuanyuan ZHANG ; Xingchen DU ; Ping JIANG ; Fengyuan GUAN ; Ying LU ; Xiao SU ; Hongze JIANG ; Hongbin LI ; Yongfei FANG ; Hengli ZHAO ; Jiangyun PENG ; Mingli GAO ; Li SU ; Fang HE ; Qingwen TAO ; Chunrong HU ; Peng LI ; Zeguang LI ; Yuelan ZHU ; Ying GU ; Ming ZHANG ; Rongsheng WANG ; Ting JIANG ; Xiaolin YANG ; Qi ZHU ; Quan JIANG ; Jianyong ZHANG ; Xiaolei FAN ; Yu XUE ; Dongyi HE
Chinese Journal of Rheumatology 2023;27(6):361-367
Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.


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