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OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of darolutamide and provide a reference for its clinical safe use. METHODS ADEs related to darotamide were collected based on the US FDA adverse event reporting system （FAERS） database from the third quarter of 2019 to the third quarter of 2022. Data mining and analysis were conducted by the report odds ratio （ROR） and proportional reporting ratio （PRR） methods. RESULTS A total of 565 ADE reports related to darolutamide were extracted， 356 ADE reports about darolutamide as the primary suspected drug were included， 38 ADE signals with darolutamide as the primary suspected drug were excavated， involving 15 system organ class （SOC）， mainly concentrated in patients over 65 years old. The SOC of darotamide ADE signal mainly focused on various examinations， systemic diseases and various reactions at the administration site， benign/malignant tumors or those with unknown nature （including cystic and polypoid）， kidney and urinary system diseases. A total of 13 ADE signals not mentioned in the instructions included increased prostate-specific antigen， dysphagia， cognitive impairment， erectile dysfunction， rhabdomyolysis， gynecomastia and decreased platelet count， etc. CONCLUSIONS When using darolutamide， in addition to ADE in the drug instruction， we should pay close attention to potential ADE， such as increased prostate-specific antigen， rhabdomyolysis， gynecomastia and decreased platelet count， so as to avoid drug withdrawal or organ damage caused by ADE.
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Objective:To explore the expression of peptidyl prolyl cis-trans isomerase (Pin1) activity in peripheral blood of patients with rheumatoid arthritis (RA) and the value and correlation of T helper cell 17/regulatory cells (Th17/Treg) cells, and to analyze the effect and influence of all-transretinoic acid (ATRA) on it.Methods:① Comparing the difference of Pin1 expression and absolute counts of Th17 and Treg between RA patients before and after treatment and healthy control group, Kruskal-Wallis rank sum test was used for analysis. ② To analyze the correlation between the expression of Pin1 and its general data, activity indicators [such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score 28 joints (DAS28) scores], Th17, Treg and some cytokines in RA patients, and to use Pearson and Spearman correlation tests. ③ To analyze the difference of Pin1 expression and Th17/Treg in peripheral blood of RA patients treated with low-dose all-trans retinoic acid (10 mg twice a week) and traditional immunosuppressants such as hydroxychloroquine for 3 months respectively. Mann-Whitney U test was used for comparison between the two groups, and the difference was statistically significant with ( P<0.05). Results:① The activity of Pin1 in peripheral blood of the newly treated group of RA was [13.62(9.16, 19.42)] higher than that of the healthy control group [8.97(7.62, 11.45)]( Z=42.82 , P<0.05), and Th17 was [18.28(12.76, 24.08)] higher than that of the healthy control group [6.04(4.96, 4.96)]( Z=48.83 , P<0.05). Treg [11.06(5.31, 21.87). It was lower than that of healthy control group [40.41(24.33, 48.52)]( Z=42.21 , P<0.05). ② the activity of Pin1 in peripheral blood of RA patients was positively correlated with CRP, the number of involved joints, DAS28 score, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) ( r=0.396, P<0.05; r=0.683, P<0.05; r=0.466, P<0.05; r=0.315, P<0.05; r=0.416, P<0.05). ③ Compared with the newly treated RA group, the activity of Pin1 [6.94(5.96, 8.77), Z=42.82 , P<0.05] and Th17 7.38 decreased [7.38(3.85, 11.21), Z=48.83 , P<0.05], while Treg [40.41 (17.77, 33.47)] increased ( Z=42.21 , P<0.05). ④ Compared with the traditional medicine group, Treg [28.9(21.73, 37.36)] was higher in the retinoic acid group, and the difference was statistically significant ( Z=-2.683 , P<0.05). The activity of Pin1 was [6.23(5.58, 8.75)], but there was no statistical significance ( Z=-1.622 , P=0.104). Conclusion:Pin1 in peripheral blood of RA patients is over-expressed. Th17 is increased and Treg is decreased. ATRA combined with other traditional drugs can reduce Pin1 activity, promote Treg growth and improve disease activity of RApatients to a certain extent.
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OBJECTIVE：To establis h the evaluation model of hospital pharmacist post value of dispensing department ，and to provide scientific basis for optimizing the performance management of pharmacists in despensing department in hospital. METHODS：Based on factor counting method ，combined with questionnaire ，Delphi expert correspondence method and so on ，the hospital pharmacist post value evaluation model was established. Based on this ，the relative value scores of the pharmacists in the dispensing department was determined. RESULTS ：Hospital pharmacist post value evaluation model was established with 5 evaluation dimensions （knowledge，skills，responsibility，work autonomy ，work environment and intensity ，of which the first level weight coefficients were 0.194，0.166，0.365，0.216 and 0.058，respectively）and 31 evaluation elements. The above 5 evaluation dimensions contained 5，8，9，3，6 evaluation elements ，respectively，and the corresponding second-level weights were 0.052-0.431 （for example ，responsibility dimension with the highest weight ，including quality and safety control ，decision responsibility，responsibility for finance and assets ，the corresponding second-level weight coefficients were 0.279，0.140，0.132， respectively）. The relative value scores of 13 pharmacist post were 342.9-840.4 in the dispensing department of our hospital with this model ，among which the department responsible person had the highest score （840.4）and the prescription post score was the lowest（342.9）. CONCLUSIONS ：The hospital pharmacist post value evaluation model constructed by factor counting method can provide a scientific and reliable theoretical basis for realizing the rewards of different positions in the dispensing department.
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[Objective] Via an empirical survey, this study is aimed to explore the imparting and mastering of Chinese cultural knowledge in China ’s present col ege English teaching, so as to offer some effective strategies for dealing with“Chinese culture aphasia”in current col ege English teaching in China. [Methods] Resorting to the research methodology of tests, questionnaires and interviews, it carries out an investigation of a number of col ege students and English teachers in Zhejiang Province into their mastering of Chinese cultural knowledge and its conveying in English as wel as the curriculum design of their col eges or departments. The relevant data derived from the research are analyzed qualitatively and quantitatively. [Results] The subjects al demonstrate the phenomenon of“Chinese culture aphasia”concerning both its comprehension and its English translation to varying degrees. Besides, cross-cultural commu-nication is twofold, so it is indispensible for learners to study simultaneously their native culture,which is a solid cornerstone and the crucial foundation for foreign language learning, but has been seriously deficient in col eges’curriculum design and students’textbooks; integrating Chinese as one of the com-pulsory courses and establishing corresponding examining and evaluating systems incorporating formative assessment and summative assessment, are sure to cope with“Chinese culture aphasia”in present col ege English teaching in China effectively. [Conclusion] The research and solution above are expected to shed light on teaching syl abus formulations and curriculum designs, enhance students ’humanistic quality and their communication capabilities in reality, and consequently popularize the excellent Chinese culture.
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Objective To compare Th1/Th2 drift situation in patients with lymphoma with that in patients with solid tumors, and establish the effective immune function detectable criterion of lymphoma in biological treatment process. Methods The whole blood samples of 10 patients with lymphoma, 202 patients with solid tumors including 36 patients with upper digestive tract cancer, 64 colorectal cancer, 43 lung cancer and 20 the other malignancies, and 30 healthy persons as controls were collected. Stimulation agent was used to stimulate the cells in order to increase cell factor expression and fluorescent labeled specific anti-cytokine monoclonal antibody was used to bind with specific antigen. The expression of specific cytokines was detected by flow cytometry. Results Positive percentages of IFN- γ and IL-4 and ratio of IFN- γ /IL-4 in CD+4 T cells of human peripheral blood had statistically differences between in patients with lymphoma and controls (P < 0.05). The ratio of Thl/Th2 (CD+4 intracellular cytokine INF-α/IL-4) in patients with lymphoma was lower than that in patients with upper digestive tract cancers (esophagus and stomach cancers) (P = 0.023), however, had no statistical differences with that in patients with other solid tumors (colorectal, lung, kidney, breast and other tumors), but had a downward trend. Conclusion Immune functions in patients with lymphoma are lower than those in patients with solid tumors and immune treatment is a necessary to adjuvant chemotherapy. The ratio of Th1/Th2 (INF- α/IL-4) is expected to become effective detection criterion.
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Objective To investigate the correlation of P-gP,bel-2,STAT3,IL-6,IL-10 and the resistance lymphoma cells to chemotherapeutic agents.Methods There were 28 patients,among them were divided into three groups:refractory lymphoma,lymphoma which is sensitive to agents and lymphodenitis.P-glycoprotein(P-gp)on lymphoma cell membrane,STAT3,bcl-2,IL-6 and IL-10 level into lymphonla cell were detected using FCM,and the correlation between them and chemotherapy efficacy were analysed. Results In refractory lymphoma patients,P-gp and hcl-2 are significant higher than that of the group which is sensitive to agents(P:0.01,P=0.039),but STAT3,IL-6 and IL-10 were not significant different between these two groups(P>o.05).P-gp is significant higher in lymphoma than in lymphodenitis(P=0.01).STAT3 in lymphoma is significant lower than that of in lymphodenitis (P=0.04).The level bcl-2,IL-6 and IL-10 between lymphoma and lymphodenitis are not significant different(P>0.05).Conclusion The expression level of bel-2 and p-gP is correlated to resistance to the chemotherapeutic agents in lymphoma cells.STAT3 play a role in lymphoma cell signal transduction,but it is not certain in lymphoma cell muhidrug resistance.
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Objective To investigate the expression of NKG2D peripheral blood of patients with esophageal carcinoma and expression of the soluble form of major histocompatibility complex class Ⅰ-related chain A (MICA). To analyze and discuss the function of NKG2D in anti-esophageal carcinoma mechanism and its relation with escape of immunosurveillance of cancer. Methods Flow cytometry analysis was used to detect NKG2D in the peripheral blood of 50 patients with esophageal carcinoma and 25 normal control individuals. Enzyme-linked immunoabsorbent assay was used to measure serum levels of soluble MICA. Results The expression of NKG2D were(87.25±3.06), (88.38±4.24), (92.46±1.46) respectively. Compared with the normal control individual, the expression of NKG2D in esophageal carcinoma group was significantly low; Among patients categorized according to most disease parameters tested (tumor size, grade of differentiation, regional lymph node status, disease stage), soluble MICA levels in sera did not statistically differ from those in normal control individuals. Patients with stage Ⅳ disease and/or regional lymph node metastasis, exhibited significantly higher serum levels of soluble MICA than control individuals. Conclusion The activity of NK cell and the anti-cancer cellular immunity level reduce in patients with esophageal carcinoma. The decrease of the receptor NKG2D is a reason for the descend of the the activity of NK cells. The escape of immunosurveiilance with esophagal carcinoma may correlate with down-regulate of NKG2D expression and up-regulate of sMICA.
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Objective To investigate the relative activity of multidrug resistance P-glycoprotein in the plasma of breast cancer patients, analyze the expression of P-glycoprotein before and after chemotherapy and evaluate its clinical value. Methods The plasma of patients and chemical reagents were mixed and distributed into the 96-well plate. The plate was read at 340 nm absorbaace before and after reaction. The variation of absorbance for each well was calculated, and then relative activity of each sample was compared to the referent compound activity. The relative activity of over 30 % was taken as positive expression of the P-gp for each sample. Results The frequency of P-glycoprotein expression was significantly increased from 16.2 % before chemotherapy to 43.2 % after chemotherapy (P<0.05). The positive expression of P-glycoprotein before and after chemotherapy were 5/6 and 9/16, respectively, in patients with positive lymph node metastasis, and 1/6 and 7/16, respectively, in patients with negative lymph node metastasis. Conclusion The results of this preliminary study suggest in P-glycoprotein expression in plasma of patients play an important role in the selection of drugs, which may be useful to evaluate the prognosis for treatment of breast cancer patients.
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Objective To observe the levels of Th1 and Th2 type cytokines of peripheral blood CD+4 T lymphocytes at different stage of treatment of colonic cancer,in order to find out the laboratory evidence of tumor immunotherapy.Methods The peripheral blood lymphocytes were stimulated by stimulator in order to enhance the expression of cytokines.Then specific fluorescent-conjugated monoclonal antibodies were added to combine with its specific antigens.Cytokines were detected by flow cytometry.Results At different stage of treatment of colonic cancer,the levels of Th1 type cytokines of each stage was significant.The levels of Th2 type cytokines at each stage were not significant.The IFN-γ//IL-4 ratio were significantly different during tumor immunothempy.Conclusion At different stage of treatment of colonic cancer,the levels of Th,type cytokines were obviously associated with treatment.The levels of Th2 type cytokines had no association with treatment.Among them,the changes of Th1/Th2 ratio (IFN-γ/IL-4) had more correlation with tumor immunotherapy.So the reasonable immunotherapy can reverse Th1/Th2 ratio and immune inhibition.
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Objective To evaluate the diagnosis and the clinical application value of serum soluble MICA protein in patients with esophageal carcinoma or cardiac carcinoma.Methods The serum sMICA was concomitantly determined by ELISA in 50 preoperative patients with esophageal carcinoma or cardiac carcinoma and 20 healthy controls.Results The level of serum sMICA in patients was significantly higher than that in controls[(322.42±9.09)pg/ml,(176.00±11.69)pg/ml](P＜0.01).In patients with TNM stage Ⅱ,Ⅲ,Ⅳ,the level of serum sMICA increased significantly in order(P＜0.05).In patients with lymph node metastasis.the level of serum sMICA was significantly higher than that without lymph node metastasis.The level of serum sMICA in patients with imbricate carcinoma was higher than patients with glandiform carcinoma.In patients with TNM stageⅢ.the level of serum sMICA after operation was significantly lower than that before operation.ConclusionSerum sMICA could be an assistant indicator for esophageal carcinoma or cardiac carcinoma.sMICA could be considered as a new tumour symbol to evaluate the biological behavior and prognosis of esophageal and cardiac carcinoma.
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Objective To detect the levels of Th1 and Th2 type cytokines of peripheral CD+4 T lymphocytes in patients with colonic cancer in order to find out the significance of variance of imbalance in clinical therapy.Methods The peripheral blood lymphocytes were stimulated by stimulator in order to enhance the expression of cytokines.Then a specific fluorochrome-conjugated monoclonal antibody was added to be combined with its specific antigen.Cytokines were detected by flow cytometry.Results The levels of Th1 type cytokines such as interferon-γ/(INF-γ),interleukin-2(IL-2)were significantly lower in patients of colonic cancer than those of normal controls.The levels of Th2 type cytokines such as interleukin-4(IL-4),interleukin-6(IL-6)and interleukin-10(IL-10)were higher in patients of colonic cancer than those of normal controls.Conclusion Th1/Th2 shihs in colonic cancer.It is suggested that the levels of INF-γ/IL-4 in colonic cancer may provide clinical index for the prognosis and evaluation of immunity.
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Objective To study the variety and significance of immune function in lung cancer patients.Methods 68 pretherapy lung cancer patients and 20 healthy volunteers with peripheral blood samples by flow cytometry.Results The proportion of CD+3T cells,CD+4T cells and the ratio of CD4/CD8 decreased in lung cancer patients,while the proportion of CD+8T cells and natural killer cells increased.Serum levels of TNF-α,IL-4,IL-6,IL-10 were significantly increased in patients compared with healthy controls,while the ratio of Th1/Th2 was decreased.(2)The natural killer cells level was negatively correlated with the CD3,CD4,CD8 levels respectively.The CD4 level was negatively correlated with the levels of IL-6,IL-10 respectively.(3)No statistically significant relationship was found between the peripheral blood lymphocyte,Th1-Th2 cytokines and pathological type,lymph node metastasis,distant metastasis.Conclusion Immune suppression was very common in lung cancer patients,particularly cell mediated immunity suppressed markedly.The proportion and function of CD+4T cells decreased significantly.which may resulted from the Th1,Th2 imbalance.Natural killer cells and CD+8T cells increased significantly,but could not prevent tumor development,which may resulted from these factors that suppress immune response in tumor microenvironment.