1.Determination method of plasma concentrations of 7 anti-tumor drugs and its application
Jinxiu LYU ; Nan YAN ; Wenjun XU ; Jing ZHAO ; Hua ZHU ; Pengzhou HANG
China Pharmacy 2025;36(4):475-481
OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs (irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate) in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture (1∶ 1, V/V) containing 0.1% formic acid, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the plasma concentration, using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water (containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate) as mobile phase A and acetonitrile (containing 0.1% formic acid) as mobile phase B. The flow rate was 0.6 mL/min, and the column temperature was set at 40 ℃ . The sample size was 10 μL, and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode, and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 (irinotecan), m/z 360.1→244.1 (capecitabine), m/z 876.4→308.0 (paclitaxel), m/z 830.3→304.2 (docetaxel), m/z 372.1→129.1 (tamoxifen), m/z 284.1→242.1 (letrozole), and m/z 455.0→ 308.0 (methotrexate). A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate were 2-1 000 ng/mL (r=0.994 3), 20-10 000 ng/mL (r=0.997 5), 2-1 000 ng/mL (r=0.997 9), 1-500 ng/mL (r=0.995 8), 1-500 ng/mL (r=0.995 2), 1-500 ng/mL (r=0.996 4), 10-5 000 (r=0.997 7), respectively. The quantitative lower limits were 2, 20, 2, 1, 1, 1 and 10 ng/mL; RSDs of intra-assay precision were 0.08%-14.86% (n=6). RSDs of inter-batch precision were 1.51%-11.55% (n=3), and the accuracies were 89.17%-114.93% (n=6). The matrix effects ranged from 89.89%-119.74% (n=6). RSDs of the stability tests were 1.98%-14.88% (n=6). The results of E-mail:hangpengzhou@163.com clinical application showed, the average plasma concentrations of irinotecan, capecitabine, paclitaxel and docetaxel were 704.09, 909.40, 36.45, 150.43 ng/mL, respectively. The values of the coefficient of variation were 25.24%, 62.65%, 122.69%, and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid, and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.
2.Research progress of IDO1-mediated tryptophan metabolism in sepsis
Xiao-di ZHAO ; Cheng-yan MA ; Hua-qing CUI ; Yu-chen WANG ; Xiao-guang CHEN ; Sen ZHANG
Acta Pharmaceutica Sinica 2024;59(2):289-297
Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.
3.Two new dalbergiphenols from Zhuang medicine Dalbergia rimosa Roxb
Cheng-sheng LU ; Wei-yu WANG ; Min ZHU ; Si-si QIN ; Zhao-hui LI ; Chen-yan LIANG ; Xu FENG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(2):418-423
Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of
4.The relationship between activities of daily living and mental health in community elderly people and the mediating role of sleep quality
Heng-Yi ZHOU ; Jing LI ; Dan-Hua DAI ; Yang LI ; Bin ZHANG ; Rong DU ; Rui-Long WU ; Jia-Yan JIANG ; Yuan-Man WEI ; Jing-Rong GAO ; Qi ZHAO
Fudan University Journal of Medical Sciences 2024;51(2):143-150
Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P<0.001;r=0.466,P<0.001);ADL was positively correlated with sleep quality(r=0.294,P<0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P<0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.
5.Weight-dependent Fluorescence Lifetime Imaging for Viscosity Detection in Glycerol-water Mixtures
Teng LUO ; Yi-Hua ZHAO ; Yuan LU ; Wei YAN ; Jun-Le QU
Progress in Biochemistry and Biophysics 2024;51(5):1221-1230
ObjectiveBased on fluorescence lifetime imaging technology, a novel method for viscosity detection is proposed and the capability of different weighting of fluorescence lifetimes in distinguishing the viscosity of glycerol-water mixtures is evaluated, aiming to enhance the accuracy and reliability of viscosity differentiation. MethodsThis approach incorporates the principles of electronic weighting, introducing both amplitude-weighted average fluorescence lifetime (τm) and intensity-weighted average fluorescence lifetime (τi). Viscosity changes in glycerol-water mixtures are detected through τm and τi. τm Reflects the relationship between fluorescence signal amplitude and time, while τi focuses on the time-varying characteristics of fluorescence signal intensity. ResultsThe results of both τm and τi mutually corroborate each other, not only enhancing the reliability in detecting viscosity changes in glycerol-water mixtures but also revealing their unique roles in the detection process. Although τm plays a crucial role in capturing changes in fluorescence signal amplitude, τi exhibits higher accuracy in viscosity detection when considering the time-varying characteristics of fluorescence signal intensity. It is particularly noteworthy that, due to τi’s greater sensitivity, microenvironment viscosity detection can be directly analyzed using τi. This provides a more convenient approach for real-time, highly sensitive microfluidic viscosity monitoring. Therefore, through the comprehensive utilization of τm and τi, a more thorough and accurate understanding of the viscosity information in glycerol-water mixtures can be obtained, and specific parameters can be selected for in-depth analysis based on specific needs. ConclusionThe combination of amplitude weighting and intensity weighting allows for a more sensitive identification of subtle changes in viscosity under different conditions. The innovation of this method lies in its simultaneous consideration of multiple parameters, enhancing sensitivity and distinguishability to variations in viscosity. Therefore, this weighted-dependent fluorescence lifetime imaging technique not only introduces a novel approach for viscosity detection in glycerol-water mixtures but also provides a powerful analytical tool for various fields, including microfluidics, rheology, and research on novel functional materials.
6.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
7.Expression and correlation analysis of P53 and mTOR in pterygium
Fanglin ZHANG ; Xinrong ZHAO ; Huijuan WAN ; Yun HUA ; Yan CAI
International Eye Science 2024;24(9):1381-1386
AIM: To detect the expression of P53 and mTOR in pterygium tissues and healthy conjunctival tissues, and to explore the relationship between the expression of P53 and mTOR, and the relationship between the expression of P53 and mTOR and the important clinical features of pterygium.METHODS: The surgical specimens of 43 patients(43 eyes)who underwent pterygium excision and autologous conjunctival transplantation in the First Affiliated Hospital of Shihezi University from November 2022 to May 2023 were collected. Healthy conjunctiva group was selected from the healthy conjunctival tissue that originated from the temporal conjunctiva of 13 patients. Totally 10 pterygium specimens and 6 normal conjunctival specimens were selected and the qPCR was used to detect the mRNA expression levels of P53 and mTOR in pterygium and normal conjunctival tissues. Another 33 cases of pterygium and 7 cases of normal conjunctival tissues were collected and the expression of P53 and mTOR in pterygium and normal conjunctival tissues were detected by immunohistochemistry. IPP6.0 software was used to calculate the average optical density, the correlation between the expression levels of P53 and mTOR, and the correlation between the expression levels of P53 and mTOR and the important clinical features of pterygium were analyzed.RESULTS: According to qPCR results, the mRNA expression levels of TP53 and mTOR in the pterygium group were significantly higher than those in the healthy conjunctiva group(all P<0.05). According to the immunohistochemical staining results, the expression levels of P53 and mTOR proteins in the pterygium group were significantly higher than those in the healthy conjunctiva group(P<0.05). The expression of P53 was positively correlated with the expression of mTOR(r=0.417, P<0.05). The expression of P53 in the group of outdoor activity time > 3 h was higher than that in the group of outdoor activity time ≤3 h(P<0.05). The expression of P53 in the group of pterygium head invasive limbal distance > 2 mm was higher than that in the group of pterygium head invasive limbal distance ≤2 mm(P<0.05). There was no difference in the expression of pterygium between the two groups of patients aged > 40 years and ≤40 years(P>0.05). There was no significant difference in the expression of mTOR between the groups of outdoor activity time > 3 h and ≤3 h, the group of pterygium head invasion distance > 2 mm and ≤2 mm, and the group of > 40 years old and ≤40 years old(all P>0.05). The expression of P53 was positively correlated with the duration of outdoor activities(r=0.484, P<0.01)and the distance of limbal invasion(r=0.479, P<0.01). The expression of mTOR was not correlated with age, duration of outdoor activities, and distance of limbus invasion(all P>0.05).CONCLUSION: The overexpression of P53 and mTOR in pterygium showed a positive correlation, suggesting that the abnormal expression of P53 and mTOR may play a role in the pathogenesis of pterygium, which provides an experimental basis for further exploring the pathogenesis of pterygium; the expression of P53 is positively correlated with the time of outdoor activities and the distance of pterygium invasion. The P53 plays a role in evaluating the severity of pterygium, and provides new ideas for the clinical diagnosis and treatment of pterygium.
8.Mechanism of Huanglian Jiedutang in Inhibiting Activation of NLRP3 Inflammasomes and Ameliorating Acute Liver Injury in Septic Mice
Ruizhu ZHAO ; Zhengyang HUA ; Yuhang WANG ; Xinyue REN ; Dingxing FAN ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):27-34
ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 (NLRP3) inflammasomes and alleviating the acute liver injury (ALI) induced by lipopolysaccharide (LPS) in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank, model, low- (3.08 g·kg-1), medium- (6.15 g·kg-1), and high-dose (12.30 g·kg-1) Huanglian Jiedutang, and positive control (dexamethasone) groups (n=9). The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days, and then LPS (15 mg·kg-1) was injected intraperitoneally for the modeling of sepsis. In the positive control group, dexamethasone (0.05 g·kg-1) was injected intraperitoneally 1.5 h after modeling, and the mouse sepsis score (MSS) was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured by a biochemical analyzer. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD (ASC) was detected by immunohistochemistry. The protein levels of NLRP3, ASC, Caspase-1, and gasdermin D (GSDMD) in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction(Real-time PCR) was employed to determine the mRNA levels of GSDMD, Caspase-1, IL-1β, and IL-18. ResultCompared with the blank group, the model group showed elevated levels of ALT and AST (P<0.01) and risen levels of inflammatory cytokines in the serum (P<0.01). In addition, the modeling resulted in edema and necrosis in the liver, and up-regulated the protein levels of GSDMD, NLRP3, ASC, and Caspase-1 (P<0.01) and the mRNA levels of GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.01). Compared with the model group, the drug intervention groups showed reduced content of inflammatory cytokines (P<0.01), alleviated pathological damage in the liver tissue, and down-regulated protein levels of GSDMD, NLRP3, ASC, and Caspase-1 (P<0.05,P<0.01) and mRNA levels of GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05,P<0.01) in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes, thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.
9.Full-length transcriptome sequencing and bioinformatics analysis of Polygonatum kingianum
Qi MI ; Yan-li ZHAO ; Ping XU ; Meng-wen YU ; Xuan ZHANG ; Zhen-hua TU ; Chun-hua LI ; Guo-wei ZHENG ; Jia CHEN
Acta Pharmaceutica Sinica 2024;59(6):1864-1872
The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of
10.Current research status and application prospects of S1P in asthma
Chen YUAN ; Xia ZHAO ; Jiabao WU ; Hua YAN
The Journal of Practical Medicine 2024;40(7):936-940
Asthma is a chronic inflammatory airway disease,and airway inflammation,airway hyper-respon-siveness and airway remodeling are the major pathological alterations in asthma.Numerous studies have demon-strated sphingosine metabolism disorders exist in asthma patients,and sphingosine-1-phosphate(S1P)is the end product of sphingolipid metabolism,which has become the focus of research as an important mediator of immune and inflammatory diseases,and is closely related to the development of asthma.In this paper,we summarize the role of S1P in the pathological changes of asthma from the relationship between S1P and asthma as well as its application in the clinical diagnosis,treatment and efficacy assessment of asthma,with a view to exploring more directions in the diagnosis and treatment of asthma.

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