Table of Content

Volume 24 Issue 11
26 November 2019

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General considerations of population pharmacokinetic/pharmacodynamic study in new drug development

MA Guangli, XU Ling, CHEN Rui, CHEN Yuancheng, ZHAO Wei, LIU Dongyang, JIAO Zheng, LI Jian, JI Shuangmin, LI Li, LI Liang, WANG Yuzhu, YANG Jinbo, WANG Yaning, SUN He, HU Pei, ZHENG Qingshan, LU Wei

2019, 24(11):  1201-1220.  doi:10.12092/j.issn.1009-2501.2019.11.001

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Population pharmacokinetic/pharmacodynamic (PopPK/PD) study and so derived exposure-response study are key components in new drug development and regulatory decision making. Integrating such studies into new drug development will facilitate new drug development and regulatory decision-making processes. As an expert consensus, this document provides the areas of applications, clinical trial designs, modeling analysis methods, quality control concerns and study reporting formats of PopPK/PD studies in new drug development/regulatory submissions. The authors expect this document can be a valuable reference to those scientists and regulatory reviewer who wish to adapt PopPK/PD studies into new drug development and drug approval processes in China.



Effects of melatonin on NO, MDA, GSH and NADPH expression in liver tissues of intrahepatic cholestasis rats

YU Han, ZHONG Xianggen, LI Yunzhou, XU Zongying, SHI Shaohua, DENG Xiulan

2019, 24(11):  1221-1226.  doi:10.12092/j.issn.1009-2501.2019.11.002

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AIM:To investigate the intervention of melatonin on rat intrahepatic cholestasis model and related mechanisms of oxidative stress interference. METHODS: Intraperitoneal injection of alpha-naphthylisothiocyanate was used to establish rat model of intrahepatic cholestasis, and melatonin was administered intragastrically. The biochemical indexes of liver function were detected and liver histopathology were observed and evaluated, the content of NO, MDA, GSH in liver homogenate was detected by TBA and microplate test, the expression of NADPH protein and mRNA in liver homogenate was detected by WES and RT-PCR.RESULTS:The results of biochemical detection of liver function in rat serum and observation of liver pathological sections showed that alpha-naphthylisothiocyanate could successfully reproduce the intraahepatic cholestasis rat model, and melatonin had an ideal intervention effect on the model. Compared with the normal group, the GSH of liver tissue in the model group was significantly lower than that in the normal group (P<0.05), the expression levels of NO and MDA increased significantly (P<0.01). After treatment with melatonin, GSH expression was significantly elevated in the liver tissue of the melatonin group as compared with the model group (P<0.05) while NO, MDA expression levels are significantly reduced (P<0.01). There was no significant difference in NADPH protein/mRNA expression levels in liver tissue of each group of rats (P>0.05).CONCLUSION:The effect of melatonin on intrahepatic cholestasis in rats is significant, which can effectively improve the oxidative stress status of rats with intrahepatic cholestasis. The anti-oxidative stress mechanism may be considered as one of the important mechanisms of melatonin intervention in the Intrahepatic cholestasis rat model, which has important significance for further research.

Effects of fluoxetine on TLR2/NF-κB signaling pathway and inflammatory factors in human conjunctival epithelial cells

YANG Qingxia，MAO Yiqing，ZHANG Yanfang，BO Xufang

2019, 24(11):  1227-1233.  doi:10.12092/j.issn.1009-2501.2019.11.003

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AIM: To observe the effects of fluoxetine on Toll-like receptor 2 (TLR2)/nuclear transcription factor-kappa B (NF-κB) signaling pathway and inflammatory factors in human conjunctival epithelial cells, and to explore the potential mechanism of SSRI-induced xerophthalmia. METHODS: Conjunctival epithelial cells were divided into blank control group and drug group. Fluoxetine was used to intervene in drug group. CCK-8 method was used to determine the half inhibition rate of fluoxetine on human conjunctival epithelial cells as a follow-up concentration. The levels of TLR2, NF-kappa B, interleukin (IL) -1beta, IL-2, IL-6 and tumor necrosis factor (TNF) -alpha were detected by RT-PCR, the levels of TLR2 and NF-kappa B protein were detected by immunofluorescence and Western-blot, and the levels of IL-1beta, IL-2, IL-6 and TNF-alpha protein were detected by ELISA. RESULTS:Fluoxetine can inhibit the proliferation of conjunctival epithelial cells in a concentration-dependent manner in the range of 10-9 to 10-5 mol/L. RT-PCR results showed that the levels of TLR2, NF-kappa B, IL-1beta, IL-2, IL-6 and TNF-alpha in fluoxetine group were higher than those in blank control group (P＜0.05). The IOD values of TLR2 and NF-kappa B in the drug group were significantly higher than those in the blank control group (P＜0.05), suggesting that the expressions of TLR2 and NF-kappa B in the drug group were higher than those in the blank control group. Western blot analysis showed that the expression levels of TLR2 and NF-kappa B in the drug group were higher than those in the blank control group (P＜0.05). ELISA results showed that the expression levels of IL-1beta, IL-2, IL-6 and TNF-alpha in the drug group were higher than those in the blank control group (P＜0.05). CONCLUSION: Fluoxetine may promote the level of inflammatory factors by activating TLR2/NF- κB signaling pathway in conjunctival epithelial cells. This may be the potential biological mechanism of fluoxetine-induced xerophthalmia.

Study on effects of naringenin on inhibiting proliferationand invasion of ovarian cancer cells and inducing apoptosis by PI3K/AKT/NF-κB pathway

QI Bingli, HUANG Ping, YAN Ruixue, LI Qian

2019, 24(11):  1234-1241.  doi:10.12092/j.issn.1009-2501.2019.11.004

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AIM: To investigate the mechanism of naringenin (NAR) inhibiting the proliferation, apoptosis and invasion ability of ovarian cancer cells by PI3K/AKT/NF-κB pathway. METHODS: Ovarian cancer cells were cultured in vitro. They were divided into blank group (Control), low-dose NAR group, medium-dose NAR group and high-dose NAR group. After pretreatment with NAR, effects of NAR on proliferation, apoptosis, invasion and migration of ovarian cancer cells were detected. The expression of invasion, migration and apoptosis related proteins and PI3K/AKT/NF-κB pathway-related proteins was detected. RESULTS:The proliferation, migration and invasion of ovarian cancer cells were significantly inhibited in groups treated with NAR, while apoptosis was significantly promoted, showing dose-dependence to NAR. Compared with blank group, levels of PCNA, Bcl-2, N-cadherin, MMP-9 and MMP-2 protein were significantly decreased in the groups treated with NAR (P<0.01), while expression levels of Bax, Caspase-3, E-cadherin and PI3K protein, phosphorylation level of AKT and p65 were significantly increased (P<0.01). With increase of NAR dose, there was dose-dependence. There was no significant change in total AKT protein expression (P>0.05). CONCLUSION: NAR may inhibit proliferation and invasion ability of ovarian cancer cells by inhibiting EMT and PI3K/AKT/NF-κB pathway, and promote apoptosis of ovarian cancer cells, showing dose-dependence within a certain dose range.

Expression of miR-19b in osteosarcoma and its effect on invasion and migration of osteosarcoma Saos-2 cells by regulating KLF13

QIAN Wanfeng, WANG Xiufeng, CHEN Xuepeng

2019, 24(11):  1242-1248.  doi:10.12092/j.issn.1009-2501.2019.11.005

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AIM: To study the expression of miR-19b in osteosarcoma and its effect on invasion and migration of osteosarcoma by regulating KLF13. METHODS: Realtime PCR was used to detect the expression of miR-19b in osteosarcoma tissues and corresponding normal adjacent tissues.miR-19b inhibitor was transfected into osteosarcoma Saos-2 cells. Transwell chamber was used to detect changes in invasion and migration ability.Western blot was used to detect the difference of MMP-9 and MMP-2 protein expression.Target gene prediction software predicts that KLF13 may be a target gene of miR-19b. Luciferase reporting system was used to identify the targeting relationship.Realtime PCR was used to detect the difference of KLF13 expression between osteosarcoma tissues and corresponding normal adjacent tissues. KLF13 siRNA and miR-19b inhibitor were co-transfected into osteosarcoma cells, the differences of cell invasion, migration and expression of MMP-9 and MMP-2 were detected by the above methods.RESULTS:The expression of miR-19b in osteosarcoma tissues was higher than that in adjacent tissues. In osteosarcoma cells transfected with miR-19b inhibitor, the level of miR-19b decreased, cell invasion, migration and the levels of MMP-9 and MMP-2 protein decreased.miR-19b targeting negatively regulates the expression of KLF13. The expression of KLF13 in osteosarcoma was lower than that in normal adjacent tissues, the expression level of miR-19b was negatively correlated with that of miR-19b. KLF13 siRNA can reverse the inhibitory effect of miR-19b inhibitor on invasion, migration and expression of MMP-9 and MMP-2 in osteosarcoma cells.CONCLUSION: miR-19b is highly expressed in osteosarcoma, downregulation of KLF13 expression can inhibit the invasion and migration of osteosarcoma Saos-2 cells by targeting KLF13 expression.

Study on the improvement of PI3K/AKT pathway in diabetic rats with neurogenic bladder disease by extract of semen plantannical

ZHANG Heng, WU Haixiao, HU Yang, YANG Qing, HUANG Ting

2019, 24(11):  1249-1255.  doi:10.12092/j.issn.1009-2501.2019.11.006

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AIM: To investigate the effects of semen plantain extract on the improvement of neurogenic bladder disease in diabetic rats and the PI3K/AKT pathway. METHODS: Fifty SD rats of the same weight and age were randomly divided into 5 groups, the control group, model group, low dose group, middle dose group and high dose group, 10 in each group. Model group and dosage groups were built of diabetic neurogenic bladder disease model. The blood glucose, food intake, urine volume change, water quantity, and weight were recorded and observed after 4 weeks. After the completion of the model, the low-dose, medium-dose and high-dose groups were treated with plantago extract at the corresponding concentrations from low to high respectively, and the changes in blood glucose from week 5 to 9, metabolism indexes from week 8 and 9, and urodynamic indexes from week 9 were observed. Fluorescence quantitative PCR and Western blot were used to detect the expression of genes related to the PI3K/AKT pathway. RESULTS:Compared with the control group, the blood glucose level in the model group was higher than that in the control group from the first week after modeling (P<0.05), and the blood glucose level in the following three weeks was still higher than those in the control group (P<0.05). At 3th week and 4th week, the food and water intake and urine in the model group was higher than those in the control group (P<0.05), and the body weight of 1st week was lower than that in the control group (P<0.05). At 9th week, the blood glucose level of the middle and high dose groups returned to normal level, and no statistical difference was found between the two groups (P>0.05). The blood glucose level of the high dose group was close to normal level in terms of food and water intake, urine volume and urodynamics, and no statistical difference was observed between the two groups (P>0.05). Compared with the control group, the expressions of PI3K, AKT, p-PI3K and p-AKT in the model group, the low-dose group and the middle-dose group were all significantly decreased (P<0.05), while the differences between the high-dose group and the control group were not significant (P>0.05). CONCLUSION: A certain dose of plantain seed extract can regulate the expression of precursors in the PI3K/AKT pathway, and has significant improvement on neurogenic bladder disease in diabetic rats.

Effects of salidroside injection on pulmonary vascular permeability in rats with septic shock induced lung injury induced by lipopolysaccharide

CHEN Shaozhong, LIN Meise, CHENG Limin, ZHU Lele

2019, 24(11):  1256-1262.  doi:10.12092/j.issn.1009-2501.2019.11.007

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AIM: To investigate the effects of salidroside injection on pulmonary vascular permeability in rats with septic shock induced lung injury induced by lipopolysaccharide.  METHODS: Seventy-five Sprague-Dawley rats were randomly divided into control group, model group, positive control group, Sal-L group and Sal-H group. The control group did not receive any treatment. The model group was modeled by lipopolysaccharide, and the positive control group was modeled. After administration of 5 mg/kg dexamethasone, Sal-L group and Sal-H group were given 0.68 and 1.09 ng/kg salidroside injection, respectively. The lung histopathology and lung injury score (LIS) were compared, as well as lung wet/dry mass ratio (W/D), lung permeability index (LPI), Evans blue content in lung tissue, oxidative stress index ［myeloperoxidase activity (MPO), malondialdehyde (MDA) , superoxide dismutase (SOD)］, inflammation indicators ［interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB inhibitor protein IκBa phosphorylated protein (p-IκBa)］ expression. RESULTS:There were no abnormalities in the lungs of the control group; the general condition and the pathological changes in the lungs were observed in the model group, and the positive control group, the Sal-L group and the Sal-H group were improved to some extents compared with the model group. Compared with the model group, the LIS, W/D, and LPI in the Sal-L group and the Sal-H group were decreased in a dose-dependent manner (P＜0.05). Compared with the model group, the content of Evans blue in the tissue in Sal-L group and Sal-H group decreased in a dose-dependent manner (P＜0.05). Compared with the model group, the MPO and MDA in the Sal-L group and the Sal-H group decreased in a dose-dependent manner, and the SOD was dose-dependently elevated (P＜0.05). Compared with the model group, IL-1, IL-6, TNF-α, NF-κB mRNA and p-NF-κB p65, p-IκBa protein in Sal-L group and Sal-H group was decreased in a dose-dependent manner (P＜0.05). CONCLUSION: Salidroside injection can improve pulmonary vascular permeability and reduce pulmonary edema in rats with septic shock and lung injury. The mechanism may be related to anti-oxidative stress and inhibition of inflammatory response.

Effects of regulation ROS on the pain and the protein of Pink1 in spinal of SNI mice and its mechannism

CAI Miaoguo, SHAO Wei, YU Huijun, HONG Ye, SHI Lili

2019, 24(11):  1263-1268.  doi:10.12092/j.issn.1009-2501.2019.11.008

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AIM: To observe the effect of oxidative stress on the expression of Pink1 in mechanical pain and spinal cord after C57/BL6 mice with spared nerve injury (SNI), and to explore the possible effects and mechanism of oxidative stress on Pink1 in neuropathic pain. METHODS: Sixty mice were randomly divided into Control group, Sham group (Sham), Surgery group (SNI), SNI+Saline, and SNI+phenyl-N-tert-butylnitrone (PBN). The Control group received no treatment. The Sham group was cut the skin and separated the three branches of the sciatic nerve to suture the skin. The SNI group was freed and retained the branches of the sacral nerve, and ligated and cut the phrenic nerve. The mechanical pain threshold was detected after 14 days. After the behavioral test, the SNI group was injected with 0.9% physiological saline and PBN. Behavioral measurements were performed and oxidative stress (GSH, SOD) levels were measured. Western blot was used to detect the expression of Pink1 in the lumbar spinal cord protein in each group. RESULTS:Compared with the Control and Sham groups, the mechanical pain threshold was significantly lower in the SNI group (P<0.001); In the SNI group, the ROS level in the lumbar spinal cord was increased (P<0.05), and the ROS level was decreased after PBN injection (P<0.001); Pink1 expression was increased at the protein level in SNI mice (P<0.001), and the expression of Pink1 in the spinal cord decreased after ROS decreased (P<0.01). CONCLUSION:Pink1 is highly expressed in the protein level in the spared nerve injury, and reduced ROS level can improve the expression of Pink1 in neuropathic pain of mice.

iTRAQ technology based differences of protein expression in sepsis-associated encephalopathy

QIAO Yang, CHEN Qun, YANG Guang,CAO Yingya, LU Weihua

2019, 24(11):  1269-1274.  doi:10.12092/j.issn.1009-2501.2019.11.009

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AIM: To analyze the differential protein expression in brain tissue of septic rats by isobaric tags for relative and absolute quantification(iTRAQ) technology. METHODS: Thirty male Wistar rats were randomly divided into sepsis group and control group, with 15 rats in each group. The brain electrical monitoring electrode was placed 3 days before modeling, and the rat sepsis model was prepared by cecal ligation and puncture (CLP). After 48 hours of modeling, the protein was extracted, iTRAQ labeled, the differential protein was screened, and the difference was analyzed. The relationship between protein and sepsis was also analyzed. RESULTS:Compared with the control group, 91 proteins with differential expression were screened from the brain tissue of the sepsis group. Among them, 68 were up-regulated and 23 were down-regulated. It was related to the related gene functions such as stress response, cell signal transduction, glucocorticoid receptor, immune response, insulin-like growth factor, and cellular material energy metabolism. CONCLUSION: A series of abnormal protein expressions in brain tissue of septic rats can be quickly analyzed by iTRAQ technology.

Study on bioequivalence of gefitinib tablets in healthy Chinese subjects

WANG Mengyao,HUANG Jie, LIU Yanan, YANG Shuang, WU Shuting, YANG Xiaoyan, YE Ling, GUO Can, HUANG Zhijun

2019, 24(11):  1275-1280.  doi:10.12092/j.issn.1009-2501.2019.11.010

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AIM: To evaluate the bioequivalence of two preparations of gefitinib tablets in healthy Chinese subjects. METHODS: This study was a randomized, open-label, double-period, single-center clinical trial after a single-dose oral administration of 250 mg, 56 subjects were divided into groups of fasting bioequivalence study and postprandial bioequivalence study. The blood concentrations of gefitinib tablets in plasma at different time after drug administration were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and analyzed statistically with non compartment model method. RESULTS:The main pharmacokinetic parameters of test and reference(27 subjects) of gefitinib tablets administered fasted were as follows: t1/2 were（20.8±8.3）and（21.5±9.7）h, tmax were（5.63±1.82）and（5.30±1.44）h, Cmax were（200±86）and（203±84）ng/mL, AUC0-t were（4 968±2 268）and（4 853±2 073）ng·h/mL, AUC0-∞ were（5 054±2 325），（4 950±2 111）ng·h/mL, the relative bioavailability calculated by AUC0-tand AUC0-∞were 104.4% and 103.9%, respectively; The main pharmacokinetic parameters of test and reference(28 subjects) of gefitinib tablets administered with food were as follows: t1/2 were（21.1±9.9）and（22.0±10.1）h；tmax were（4.46±2.22）and（4.46±1.82）h；Cmax were（299±106）and（304±119）ng/mL；AUC0-t were（6 700±3 142）and（6 594±3 004 ）ng·h/mL；AUC0-∞ were（6 846±3 265），（6 750±3 136）ng·h/mL , the relative bioavailability calculated by AUC0-t and AUC0-∞ were 101.1% and 100.9%, respectively. CONCLUSION: The two gefitinib tablets administered fasted or with food were bioequivalent in healthy Chinese subjects.

Single-arm,one-center, exploratory clinical trial of albumin-bound paclitaxel second and more line therapy for advanced non-small cell lung cancer

YANG Ke, LI Junling, DU Bin, TIAN Zhongqiu, JING Xiujuan

2019, 24(11):  1281-1286.  doi:10.12092/j.issn.1009-2501.2019.11.011

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AIM: To explore the efficacy and safety of second and more line treatment with albumin-bound paclitaxel for advanced non-small cell lung cancer. METHODS: From Oct 2012 to Dec 2015, a total of 63 patients with advanced non-small cell lung cancer who had failed previously first-line and more line treatment were enrolled in this study. The patients were treated with 130 mg/m2 intravenous infusion albumin-binding paclitaxel on day 1 and day 8, 21 days one cycle. The efficacy was evaluated every 2 cycles, and adverse reactions were recorded using the CTCAE4.03 version. Patients were followed up by telephone to obtain prognostic data after disease progression. RESULTS:All of the 63 patients were available for efficacy evaluation, among them, complete remission (CR) 0 case, partial remission (PR) 15 case, stable disease (SD) 21 case, progression disease (PD) 27 case. Objective response rate (ORR) was 23.81%, disease control rate (DCR) was 57.14%, median Progression-free survival (PFS) of the 63 patients was 3.9 months (95%CI: 3.1-5.2), median Overall survival (OS) was 9.3 months (95%CI: 7.8-10.4). In terms of safety analysis, the major grade 2 and above adverse reactions were neutropenia, thrombocytopenia, alopecia and peripheral neurotoxicity, and the overall adverse reactions were tolerable. CONCLUSION:The second and more line treatment with albumin-bound paclitaxel in patients with advanced non-small cell lung cancer has superior efficacy and controllable adverse events, which is expected to become the second-line treatment standard regimens for advanced NSCLC.

Comparison of responses induced by tracheal extubation between different doses of oxycodone after thyroidectomy

LI Jiajia, SHENG Yi, HUANG Mengmeng, HAN Yuan, ZHU Chunchun, LIU Huacheng, LI Jun

2019, 24(11):  1287-1292.  doi:10.12092/j.issn.1009-2501.2019.11.012

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AIM:To investigate the differences of the reaction induced by tracheal extubation between different doses of oxycodone after thyroidectomy. METHODS: After the unified anesthesia induction and maintenance regimen, eighty patients undergoing elective thyroidectomy were randomly divided into four groups receiving 0.05 mg/kg (group Q1), 0.1 mg/kg (group Q2), 0.15 mg/kg(group Q3) of intravenous oxycodone, or the same capacity of normal saline(group C) at 20-40 min before the end of surgery. MAP and HR were measured before anesthesia induction (T0), immediately after extubation(T1), at 5(T2) and 10 min(T3) after extubation. The recovery time of postoperative spontaneous breathe, awakening time, extubated time and the cough reflex caused by extubation were recorded. In addition, the OAA/S and VAS scores were marked at 5 min, 15 min, 30 min after entering the recovery room. RESULTS:Compared with T0, MAP and HR of group C and Q1 at T1, T2 increased significantly (P<0.05), while those of group Q2 and Q3 had no differences (P>0.05). Compared with group C, MAP and HR in group Q2, Q3 were lower (P<0.05) while those of group Q1 had no differences (P>0.05); the cough reflex of group Q2 and Q3 were lighter (P<0.05); the patients in group Q3 had the longer recovery time of postoperative spontaneous breathe and extubated time(P<0.05). Also, the VAS scores in PACU of three Q groups were lower than group C(P<0.05). CONCLUSION:Oxycodone administered at 20-40 min before the end of surgery can alleviate responses induced by extubation of the patients after thyroidectomy. 0.1 mg/kg of intravenous Oxycodone is the best dose for it can offer a better quality of recovery and postoperative analgesia with the fewer side effects.

Short-chain fatty acids as signal molecules in intestinal inflammation

HUANG Xinyi, GUO Fei, ZENG Xiangchang, OUYANG Dongsheng

2019, 24(11):  1293-1299.  doi:10.12092/j.issn.1009-2501.2019.11.013

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The intestinal microbial metabolites short-chain fatty acids（SCFA）act as both extracellular and intracellular signaling molecules to against inflammation. Outside of the cell, they function as agonists for several GPCRs. Inside the cell, SCFA inhibit HDACs. This review mainly discussed the source, composition, synthesis, distribution of SCFA, the effects and the potential molecular mechanisms of SCFA that affecting intestinal inflammation.

Clinical research status of eszopiclone

JIA Min, HUANG Jinsha, LIU Qunhui, WANG Tao

2019, 24(11):  1300-1304.  doi:10.12092/j.issn.1009-2501.2019.11.014

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Eszopiclone is a non-benzodiazepine sedative and hypnotic agent, which plays a sedative and hypnotic effects by regulating GABA receptor through isomerism, with the affinity to the central benzodiazepine receptor in about 50 times stronger than zopiclone, with less adverse reaction and toxicity. Eszopiclone has been approved by Food and Drug Administration (FDA) of United States for the treatment of insomnia in 2004. In recent years, with the popularization of clinical application, relevant clinical research data are constantly updated. In clinical practice, it could be used not only for primary insomnia, but also for the comorbid insomnia accompanied by sleep apnea syndrome, depression, post-traumatic stress disorder, perimenopausal and postmenopausal women. It is worthy to take a brief review on the clinical literatures of eszopiclone in order to provide a updated introduction for the clinicians.

Research progress on the protective mechanisms of curcumin on cerebral ischemia-reperfusion injury

LIU Xiaoyan, TIAN Ye, LIU Jifei, SU Gang, ZHANG Zhenchang

2019, 24(11):  1305-1309.  doi:10.12092/j.issn.1009-2501.2019.11.015

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Ischemic stroke is a major cause of death and disability in the world. Currently, the most effective treatment for ischemic stroke is to prevent ischemia and hypoxia injury and repair damaged tissues by restoring blood flow (reperfusion). Although reperfusion is a signal for the termination of ischemia and hypoxia, it may subsequently increase cell damage and death through excessive production of reactive oxygen species, abnormal recruitment of inflammatory cells, and excessive release of inflammatory factors, autophagy, mitochondrial dysfunction, calcium homeostasis disorder, endoplasmic reticulum stress, glutamate excitotoxicity, apoptosis, destruction of blood-brain barrier and other mechanisms. A large number of studies have shown that curcumin can play a significant neuroprotective effect by slowing down various pathological mechanisms of ischemia-reperfusion injury, and ultimately improving cerebral circulation, reducing infarct volume, reducing cerebral edema, promoting blood-brain barrier repair, and improving neurological function. Therefore, curcumin can improve neurological function by alleviating ischemia-reperfusion injury, and has the potential to supplement the existing treatment methods for ischemic stroke.

Research progress of endoplasmic reticulum stress in heart diseases

WANG Kaiyang, LI Xiaoli, CAI Yongqing

2019, 24(11):  1310-1314.  doi:10.12092/j.issn.1009-2501.2019.11.016

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Endoplasmic reticulum is an important organelle for intracellular protein processing and modification.It produces a series of reactions, including unfolded protein reactions, to maintain intracellular homeostasis and protein quality control.The accumulation of unfolded or misfolded proteins in endoplasmic reticulum will further lead to endoplasmic reticulum stress and cell and organism dysfunction.Recent studies have found that endoplasmic reticulum stress is highly related to the occurrence and development of various heart diseases.This article reviews the role of endoplasmic reticulum stress in the occurrence and development of ischemic heart disease,primary cardiomyopathy,myocardial hypertrophy and heart failure.Based on the mechanism of endoplasmic reticulum stress in cardiac diseases,it can provide theoretical basis and application means for the treatment of cardiac diseases by targeting endoplasmic reticulum stress.

The value of serum calcitonin in bacterial meningitis

LI Wenshu, DONG Huaifu

2019, 24(11):  1315-1320.  doi:10.12092/j.issn.1009-2501.2019.11.017

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Bacterial meningitis (BM) is a common central nervous system disease (CNS) in children, which poses a serious threat to the health of children.Therefore, it is of great importance to timely diagnose the type of encephalitis and promptly start treatment.At present, the gold standard for the diagnosis of BM is still cerebrospinal fluid examination, but the cooperation degree of children is low, the extraction of cerebrospinal fluid is difficult and the loss is large, and the cerebrospinal fluid culture takes a long time and the positive detection rate is low, so the significance of cerebrospinal fluid examination for the early treatment of BM is limited, and there is the possibility of delay of the disease.Serum procalcitonin (S-PCT) has high sensitivity and specificity to early prediction of bacterial infection.A large amount of evidence indicates that S-PCT is a useful tool for evaluating patients with known or suspected CNS infection, which can help diagnose BM and evaluate prognosis.This paper reviewes the current knowledge about S-PCT and its value in diagnosis and prognosis evaluation of BM.