Signals mining and analysis of adverse drug events of pazopanib based on FAERS database / 中国药房

OBJECTIVE To mine and analyze adverse drug event （ADE） signals after the marketing of pazopanib and provide references for clinically safe medication. METHODS OpenVigil 2.1 data platform was used to mine ADE signals from the US FDA adverse event reporting system （FAERS） database. ADE reports of pazopanib from October 2009 to June 2022 were collected， and ADE signals were analyzed using proportional reporting ratio （PRR） method and reporting odds ratio （ROR） method in the proportional imbalance method. RESULTS A total of 16 655 ADE reports were identified with pazopanib as the primary suspect drug. Through ROR and PRR analysis， 220 ADE signals involving 19 system organ classes were identified. The top 10 ADE signals by frequency were recorded in the drug instruction. Additionally， 88 new ADE signals were discovered， mainly related to the gastrointestinal system， various investigations， and the renal and urinary system. Decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula were both new ADE signals and the top 10 ADE signals by strength. CONCLUSIONS The occurrence of common ADEs （diarrhea， hair color changes， hypertension， etc.） during the use of pazopanib after marketing is generally consistent with its drug instruction； the number of reported cases for new suspected risk signals （decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula， etc.） is limited， and continuous monitoring is required.

A study on resection extent for medullary thyroid carcinoma / 中华普通外科杂志

Objective:To analyze the relationship between surgical resection range and prognosis of medullary thyroid carcinoma.Methods:Clinical data of 39 patients with medullary thyroid carcinoma treated in Shanghai Sixth People′s Hospital from Jan 2017 to Mar 2020 were retrospectively analyzed.Results:There were 13 males and 26 females, age ranging from 26 to 72 years old. Preoperative calcitonin levels increased from 21.5 to 20 000 ng/L. Tumor stage: stage Ⅰ was 35.9%, stage Ⅱ 23.1%, stage Ⅲ 25.6%, stage Ⅳ 15.4%. The proportion of lymph node metastasis in central region was 53.8% (21/39). The proportion of lateral cervical lymph node metastasis was 43.6% (17/39), which was statistically related with the preoperative calcitonin level ≥200 ng/L. The median follow-up was 10 months, and the biochemical and anatomical cure rates were 66.7% and 33.3% respectively. Transient recurrent laryngeal nerve palsy, temporary and permanent hypothyroidism were 2.6%, 23% and 2.6%, respectively. There was no postoperative hemorrhage, infection, lymphatic leak or death.Conclusions:Bilateral total thyroidectomy, and at least ispilateral central lymph node dissection were advocated for patients with MTC. When preoperative calcitonin level ≥200 ng/L, lateral cervical lymph node dissection is advised.

Establishment and assessment of the early maternal separation combined adult chronic unpredictable mild stress depression animal model / 中华行为医学与脑科学杂志

Objective:To explore the establishment and assessment of the depression model of adult SD rats induced by early maternal infant separation stress combined with adult chronic unpredictable mild stress(CUMS), and to observe the behavior and synaptic protein expression of SD rats.Methods:Twenty-four male rats were randomly divided into three groups: control group (CON group), chronic unpredictable stress group (CUMS group), maternal infant separation combined with chronic unpredictable stress group (MS + CUMS group). The depression model of rats in cums group was established by CUMS, and the depression model of rats in MS + CUMS group was established by maternal infant separation + CUMS. The depression model was evaluated by body mass and appearance observation, sugar water preference experiment, open field test and forced swimming test.Synapse-associated proteins (PSD-95 and synaptophysin (Syn)) of the hippocampus were assayed using Western blot. Syn protein expression was measured by immunohistochemistry.Results:After modeling, compared with CON group, the rats in CUMS group and MS + CUMS group had significantly lower body mass((126.43±3.88) g, (91.04±3.85) g, (69.89±6.67) g; t=5.03, 8.03, both P<0.01), significantly lower sugar water preference((94.21±0.56)%, (79.30±1.13)%, (72.73±1.82)%; t=8.24, 11.87, both P<0.01) and significantly increased immobility time((3.50±0.84)s, (13.59±2.40)s, (15.70±2.97)s; t=3.16, 3.82, both P<0.01). Among them, the body mass and sugar water preference of MS + CUMS group were lower than those of CUMS group ( t=3.00, 3.63; both P<0.01). (2)The center time of the rats in MS+ CUMS group markedly reduced compared with that of CON group((21.41±4.65) s, (8.96±2.37) s; t=2.66, P<0.05). (3)In the immunohistochemistry experiment, compared with the CON group, the percentage of Syn positive area in hippocampus of rats in CUMS group and MS+ CUMS group decreased significantly ((24.42±0.76)%, (14.00±0.95)%, (10.38±1.38)%; t=6.93, 9.33, P<0.01). (4)The results of Western blot showed that compared with CON group, both the expression of PSD-95 ((1.18±0.02), (0.74±0.06), (0.52±0.05), t=6.29, 9.31; both P<0.05) and Syn ((1.12±0.08), (0.95±0.06), (0.90±0.07); t=3.10, 4.04; both P<0.05) in hippocampus of rats in CUMS group and MS+ CUMS group were significantly decreased.And compared with the CUMS group, the expression of PSD-95 in MS+ CUMS group was lower( t=0.93, P<0.05). Conclusion:The method of MS combined with CUMS can effectively induce depression like behavior and decrease the expression of synaptic plasticity related protein of hippocampus in rats.

Practice and consideration of innovation and entrepreneurship education in higher medical univer-sities / 中华医学教育探索杂志

In the context of Popular Entrepreneurship and Innovation, scientific and systemic implementation of innovation and entrepreneurship education is the focus of higher education reform at present. This paper analyzes the important significances of carrying out innovation and entrepreneurship education in higher education of traditional Chinese Medicine, introduces the specific practices and experi-ences of designing educational concept and constructing education system about innovation and entrepre-neurship education, following the objective laws of modern educational development and the growth pattern of Chinese medicine talents, in order to provide reference for further promoting innovation and entrepreneu-rship education reform.

Research on effect of central 5-HTergic system in early-onset depression / 中国药理学通报

Nowadays the pathogenesis of early-onset depression is still uncertain. Only SSRIs are currently approved for clinical use as antidepressants in children and adolescents, indicating that 5-HT is the most important neurotransmitter involved in the dis-ease. Current studies with regard to central 5-HTergic system in early-onset depression mainly focus on 5-HT synthesis deficien-cy, 5-HT transportation dysregulation, as well as the earlier mat-uration of 5-HT system than norepinephrine system. 5-HT precur-sor tryptophan malabsorption and dysregulation of 5-HT synthesis can contribute to 5-HT deficiency. Moreover, the 5-HTTLPR low-expressing genotypes may increase the risk of early-onset de-pression. It is necessary to make preclinical and clinical studies more widely and deeply about the effect of central 5-HTergic sys-tem in early-onset depression in future.

Effects of Weipixiao on Ultrastructure of Gastric Mucosa Capillaries in Rats with Precancerous Lesions of Gastric Cancer / 广州中医药大学学报

Objective To observe the effects of Weipixiao on the ultrastructure of gastric mucosa capillaries in rats with precancerous lesions of gastric cancer ( PLGC). Methods The rats were randomized into six groups, including normal group, model group, Vatacoenayme Tablets group ( 0.2 g·kg-1·d-1) , and high-, middle-, and low- dose Weipixiao groups ( 15, 7.5, and 3.75 g·kg-1·d-1 respectively) . The rats received spontaneous intake of N-methyl-N’-nitro-nitrosoguanidine ( MNNG, 200 μg/mL) solution combined with irregular diet and intragastric administration of purgative herbs Xiao Chengqi Decoction ( 2 mL, containing 1 g/mL crude drug) for 18 weeks to induce spleen-deficiency PLGC. The pathological changes in gastric mucosa and the ultrastructure of gastric mucosa capillaries were observed under the transmission electron microscope. Results The model has been established successfully. Transmission electron microscopy results in the model group showed as severely swollen endothelial cells of gastric mucosa capillaries, severely-narrowing or even blocked vascular lumens, rough and discontinuous basement membrane, and swollen, degenerated or even absent pericytes. And the ultrastructure of gastric mucosa capillaries in high-, middle-, and low- dose Weipixiao groups were improved to some degrees, the effect of low-dose Weipixiao group being the best. Conclusion The improvement of the mucosal microcirculation of spleen-deficiency PLGC rats may be one of the pathohistological mechanisms of Weipixiao for spleen-deficiency PLGC.

Construction on curricular system of profession degree for master-disciple postgraduates of traditional Chinese medicine / 中华医学教育探索杂志

A detailed analysis on the curriculum status of profession degree for the fourth batch of master-disciple postgraduates in Guangzhou University of traditional Chinese Medicine (TCM) was provided.The basic idea on the construction of the curriculum system was proposed in view of strengthening TCM clinical thinking,skills and scientific research capacity.The course content was optimized combining the classic TCM theory with clinical skill practice course and innovate teaching methods depending on the inservice and remote learning of students were used.A relatively perfect professional degree curriculum system for master-disciple postgraduates of TCM was built.

Effects of rosuvastatin on matrix metalloproteinase 2 expression and cell migration of rat vascular smooth muscle cells / 中华老年医学杂志

Objective To observe the effects of rosuvastatin on the homocysteine (Hcy)-induced expression of matrix metalloproteinase 2 (MMP 2) and cell migration in rat vascular smooth muscle cells (VSMCs), and to explore the possible mechanism of Hcy-induced atherosclerosis and the role of statins in reversing atherosclerosis. Methods In one cell culture plate, the cultured rat VSMCs were incubated with different concentrations of Hcy (0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L) in vitro for 24 h, 48 h and 72 h. And in another cell culture plate, the different concentrations of rosuvastatin (10-9, 10-8, 10-7, 10-6, 10-5 mol/L and 0 mol/L) were added to the cultured rat VSMCs (while the concentration of Hcy was 1000 μmol/L). The MMP 2 expression and enzyme activity were determined by gelatin zymography and Western blotting. The effects of Hcy and rosuvastatin on cell migration and invasiveness of VSMCs were observed. Results Hcy (50-5000 μmol/L) increased the protein expression, and Hcy (50-1000 μmol/L) increased enzyme activity of MMP 2 significantly. But Hcy (5000 μmol/L) inhibited activity of MMP 2 (F=9.31, 6.44 and 5.97, all P＜0.05). Rosuvastatin (10-9-10-5 mol/L) inhibited Hcy-induced expression and enzyme activity increasing of MMP 2. The counts of cell migration of VSMCs were 18.32±2.17, 32.68±4.34, 44.75±4.08, 61.39±5.21, 79.74±5.54 and 90.78±5.83, while the concentration of Hcy was 0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L respectively (F=5.31, P＜0.05). The counts of cell migration of VSMCs were 79.74±5.54, 62.53±6.41, 48.37±5.66, 31.41±4.79, 19.27±3.62 and 11.17±2.33, while the concentration of rosuvastatin was 10-9, 10-8, 10-7, 10-6 and 10-5 mol/L respectively (F=4.99, P＜0.05). Rosuvastatin could decrease the stimulation of Hcy-induced migration of VSMCs. Conclusions Hcy can influence the MMP 2 protein expression/activity in VSMCs, and rosuvastatin can inhibit augmentation of Hcy-induced MMP 2 expression/activity and migration of VSMCs. It may be one of the multiple-effects of rosuvastatin reducing atherosclerosis.

Yellow wine and red wine inhibit matrix metalloproteinase-2 and improve pathological changes of atherosclerosis in LDL receptor knockout mice / 中国病理生理杂志

AIM: To study the possibility that yellow wine improves the pathological changes of atherosclerosis in vivo. METHODS: Six weeks old LDL receptor knockout mice (n=48) on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. The animals were randomly divided into yellow wine group, red wine group, ethanol group and control group (n=12 in each group) and were sacrificed after 14 weeks. The levels of plasma lipids and homocysteine in serum were examined. The morphological changes of aorta artery and the atherosclerosis of aorta sinus were observed under microscope. The expression and activation of matrix metalloproteinase-2 (MMP-2) were determined by the method of immunohistochemistry. RESULTS: No significant difference of plasma total cholesterol, triglyceride or high density lipoprotein cholesterol among groups was observed. Plasma homocysteine was significantly decreased in yellow wine group as compared to other three groups (P<0.01). Compared to ethanol and control groups, use of yellow wine and red wine significantly reduced the atherosclerosis lesion area (P<0.01). However, no significant discrepancy between the yellow wine group and red wine group was found. Compared to control group, the expression of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 26.3%, 27.6% (P<0.01) and 5.7% (P>0.05), respectively. The activity of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 31.7%, 32.5% (P<0.01) and 6.7% (P>0.05), respectively. CONCLUSION: Yellow wine and red wine inhibit the expression of MMP-2 and improve the pathologic changes of atherosclerosis, indicating that they have benefic effects on cardiovascular system.

Inhibition effects of monoclonal antibody C225 on breast cancer stem cells / 上海交通大学学报（医学版）

Objective To explore the inhibition effects of epidermal growth factor receptor (EGFR) antagonist monoclonal antibody cetuximab (C225) on breast cancer stem cells in human breast cancer cell line MCF-7.Methods The effects of C225 on the proliferation of breast cancer cell line MCF-7 were detected by MTT assay. MCF-7 cells were cultured to generate primary mammospheres, and were divided into control group, C225 group, epidermal growth factor (EGF) group and EGF + C225 group according to whether or not the culture media contained exogenous EGF and C225.Thirteen days after culture, the volume and number of mammospheres of these four groups were observed, and mammosphere-forming efficiency ( MFE) was calculated. The percentages of CD44~+ CD24~- cells in mammospheres of these four groups and in routinely cultured MCF-7 cells were determined by flow cytometry. Results The inhibition rate on MCF-7 cells increased with the concentration of C225.Compared with control group, the volume of mammospheres in C225 group significantly decreased, and MFE and percentages of CD44~+ CD24~- cells in mammospheres significantly decreased [(0.61 ±0.04)% vs (1.44±0.09)%, P<0.01; (3.50±0.29)% vs (9.07 ±0.52) % , P<0.01]. Compared with EGF group, the volume of mammospheres in EGF + C225 group significantly decreased, and MFE and percentages of CD44~+ CD24~- cells in mammospheres significantly decreased [ (0.68 ± 0.04) % vs (1.61 ± 0.05) % , P < 0.01; (4.00 ± 0.58) % vs (10.47 ± 0.79) % , P < 0.01]. The percentage of CD44~+ CD24~- cells in routinely cultured MCF-7 cells was (2.03 ±0.15) % , and was significantly different from those in EGF group and control group (P < 0.01). There was no significant difference in volume of mammospheres, MFE and percentage of CD44~+ CD24~- cells in mammospheres between EGF group and control group (P >0.05). Conclusion C225 has significant inhibition effects on CD44~+ CD24~- cells in MCF cells.

Comparison among the effects of tiaogan recipe, jianpi recipe,bushen recipe and ginsenoside on the contents of amino acids in hypothalamus and hippocampus of rats under repeatedly psychic stress / 中国组织工程研究

BACKGROUND: When one is in a stress state, some amino acids as neurotransmitter in his brain are of important regulating action to his cerebral functions and his psychic behaviors,and some traditional Chinese drugs can regulate the stress state of the body.OBJECTIVE:To observe the content changes of glutamic acid,aspartic acid, γ-aminobutyric acid and taurine in the hypothalamus and hippocampus of rats under repeatedly psychic stress so as to investigate the effects of tiaogan recipe, jianpi recipe, bushen recipe and ginsenoside on them.DESIGN: A randomized grouping and controlled observation trial.SETTING:Department of Basic Theory of Traditional Chinese Medicine(TCM) of Basic Medical Science College, Guangzhou University of TCM.MATERIALS:The experiment was completed from March 2002 to January 2003 at the Animal Center of Guangzhou University of TCM.Totally60 Wistar rats were randomly divided into 6 groups: normal, model, tiaogan, bushen, jianpi and ginsenoside groups, with 10 in each group. Compositions and doses of tiaogan recipe: radix bupleuri 5 g, fruetus gardeniae 5 g,radix paeoniae alba 15 g,fructus lycii 15 g,fructus aurantii 6 g,radix rehmanniae 18 g, concha haliotidis 30 g. Compositions and doses of shenqi pill: radix rehmanniae 30 g, rhizoma dioscoreae 15 g, fructus corni 15 g,rhizoma alismatis 10 g,poria 10 g,cortex moutan radicis 10 g,ramulus cinnamomi 4 g, radix aconiti praeparata 4 g. Compositions and doses of sijunzi decoction:radix codonopsis pilosulae 20 g,rhizoma atractylodis macrocephalae 15 g, poria 15 g, radix glycyrrhizae preparata 6 g.METHODS:① The traditional Chinese medicines were conventionally decocted; and the tiaogan recipe condensed to the liquid containing1.69 g/mL crude drug, shenqi pill containing 1.76 g/mL crude drug,sijunzi decoction containing 1.01 g/mL crude drug.Ginsenoside was prepared as 7 g/L water solution.The rats in the normal and model groups were by gavage given 2 mL of 9.0 g/L sodium chloride injection.The rats in the tiaogan, bushen, jianpi and ginsenoside groups were respectively by gavage given 2 mL of tiaogan recipe, shenqi pill, sijunzi decoction and ginsenoside solution 1 hour before immobilization stress. ② Except for rats in the normal group, those in the rest groups were all conducted for establishment of psychic stress reaction model.The rats were put into an immobilization tube,their action space was gradually reduced by using a mobile insertion piece,they were regulated to a nervous state without prpduction of intense revolting, which was done once a day, starting with 4 hours immobilization on the first day, and later on increased by 30-60 minutes per day, for consecutive 14 days. ③ The whole brain of the rats in each group was collected by decapitation,OPA high-performance liquid chromatography was used for assays of the contents of glutamic acid, aspartic acid, γaminobutyric acid and taurine in hypothalamus and hippocampus of the rats.MAIN OUTCOME MEASURES: The content changes of glutamic acid,aspartic acid,γ-aminobutyric acid and tanrine in the hypothalamus and hippocampus of rats in each group.RESULTS: Totally 60 rats involved all entered into the result analysis. ①The content changes of glutamic acid in the hypothalamus and hippocampus of rats in each group:Compared with normal group,the contents of glutamic acid in hypothalamus of rats in the tiaogan, jianpi,bushen and ginsenoside groups were markedly decreased [(21.85±8.19), (15.76±1.80),(14.68±7.91), (21.46±5.45), (13.43±7.68) μmoL/g]; compared with model group,the contents in the tiaogan, bushen, jianpi and ginsenoside groups were obviously raised [(11.04±3.65), (11.78±2.17), (18.67±2.98), (20.91 ±3.96),(17.71±1.83) μ moL/g, P ＜ 0.05, P ＜ 0.01, P ＜ 0.01, P ＜ 0.05]. ② The content changes of aspartic acid in the hypothalamus and hippocampus of rats in each group:Compared with model group,the contents of aspartic acid in the hypothalamus in the jianpi and ginsenoside groups were obviously decreased [(8.65±1.18), (5.72±1.32), (4.67±1.88) μmoL/g, P ＜ 0.01,P ＜ 0.01], while the contents in the hippocampus of rats in the jianpi,bushen and ginsenoside groups were markedly raised[(2.58 ±0.87),(3.93±0.49), (4.52±0.98), (3.83±0.41) μmoL/g, P ＜ 0.01, P ＜ 0.01, P ＜ 0.05].③ The content changes of γ-aminobutyric acid in the hypothalamus and hippocampus of rats in each group:Compared with model group,the contents of γ-aminobutyric acid in the hypothalamus of rats in the tiaogan,jianpi,bushen and ginsenoside groups were markedly decreased[(20.92±4.96), (15.87±2.90), (13.84±2.63), (14.94±3.98), (10.94±3.68) μ moL/g,P ＜ 0.05, P ＜ 0.05, P ＜ 0.01, P ＜ 0.01], while the contents in the hypothalamus were obviously raised [(4.12±1.66), (4.18±1.04), (6.67±1.29),(6.11±0.99), (6.37±0.78) μmoL/g, P＜ 0.05, P＜ 0.01, P＜ 0.01, P＜ 0.01].④ The content changes of taurine in the hypothalamus and hippocampus of rats in each group: Compared with model group, the contents of taurine in the hypothalamus of rats in the tiaogan, jianpi, bushen and ginsenoside groups were markedly decreased [(10.24±1.72), (7.82±1.14), (8.00±2.05),(6.42±3.17) μmoL/g, P ＜ 0.05, P ＜ 0.05, P ＜ 0.01], while the contents in the hippocampus in the jianpi and ginsenoside groups were obviously raised [(12.61±3.51), (17.03±2.74), (18.04±2.14) μnoL/g, P＜ 0.01, P＜ 0.01].CONCLUSION:The central acting site of tiaogan recipe may mainly be in the hypothalamus,possibly being related with down-regulating amino acids.While the central acting sites ofjianpi recipe,bushen recipe and ginsenoside may include the hippocampus and hypothalamus, being mainly related with up-regulating amino acids,through enhancing the integration of the hippocampus on stress so as to gain the effect of anti-injury of stress.

Establishment and Development of the Educational System for Part-time Graduate Students in Chinese Medicine Education / 中华医学教育探索杂志

The part-time graduate student education is the important part of the graduate student system in Chinese medicine education.Developing and regulating the part-time graduate student education in Chinese medicine is helpful to the consummation of Chinese medicine graduate student system,the cultivation of the high lever talents in Chinese medicine,and keeping up with international graduate student educational system.

Effect of Jiawei Sini Decoction on glucocorticoid receptor in thymocytes of chronic psychological stress rats / 中国病理生理杂志

AIM: To observe the effect of Jiawei Sini Decoction (JWSND) on glucocorticoid receptor (GCR) in thymocytes of chronic psychological stress rats. METHODS: The rats were randomly divided into 4 groups, control group (C), model group (M), group treated by JWSND (C 1), group treated by ginsenosides (C 2). The number of thymocyte GCR sites and the GCR nuclear thanslocation rate were detected by radioimmunoassay. RESULTS: Compared with the control group, in the model group, the thymocyte weight index lowered significantly ( P

Effect of Jiawei sinisan on the levels of some amino acids in hippocampus of rats with chronic stress / 中国病理生理杂志

AIM: To observe the effect of Jiawei sinisan (JWSNS) on some amino acids in hippocampus of rats with chronic stress. METHODS: Wistar rats were randomly divided into 3 groups: control, model and JWSNS group. OPA (HPLC) was adopted to detect the contents of amino acids in hippocampus. RESULTS: The contents of Glu and Asp in hippocampus of model group increased significantly ( P