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Ferroptosis is drived by lipid reactive oxygen species, which plays an important role in the development of tumors. It has been found that a variety of clinical medicines, such as artemisinin derivatives, itraconazole, sulfasala zine, cucurbitacin B, paclitaxel, disulfiram/copper can induce ferroptosis and inhibit tumor growth in head and neck cancer (HNC) through different mechanisms. To study the regulatory mechanism of ferroptosis induced by commonly used drugs in the treatment of HNC can provide reference for the targeted treatment of ferroptosis in HNC.
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JAK2-STAT3 signaling pathway, as the main chain of intracellular signal transmission, plays an important role in cell proliferation, apoptosis, invasion, migration and immune response. Triggered by cytokines and interferon, this pathway can quickly transduce extracellular signals into the nucleus, and it has abnormal expression in various tumors, such as squamous cell carcinoma of the head and neck, lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer and myeloproliferative neoplasms. Further understanding of the carcinogenic mechanism of JAK2-STAT3 signaling pathway can provide new ideas for clinical treatment of tumors and prognosis.
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After the outbreak of COVID-19, due to environmental pollution in the isolated ward and operational constraints caused by protective clothing and other factors, intravenous drugs in the designated hospitals should be centralized. Combined with the existing process mode, the process of pharmacy intravenous admixture services was optimized, the operation mode of the operation platform was adjusted, the scheduling mechanism was optimized, and the node control process of " first verify and five checks" was explored and developed, so as to meet the 24 h needs of COVID-19 patients. According to the characteristics of COVID-19 drug treatment, the focus of prescription review was adjusted to ensure the drug safety of patients. Other measures included implementing paperless prescription to reduce unnecessary media; implementing segmented infusion distribution management to ensure no cross infection; hierarchical control and configuration environment, strengthening the protection and management of pharmacists, to avoid the risk of personnel infection; optimizing human resource allocation and improving work efficiency. This process reengineering and optimization established the emergency management mode of centralized intravenous drug deployment under the background of COVID-19, which ensured the intravenous drug demand and safety of COVID-19 patients. The treatment work was carried out orderly, and could provide reference for the pharmaceutical department in medical institutions to deal with major public health emergencies in the future.
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In designated hospitals for critical patients with COVID-19 in Wuhan, time-efficient pharmaceutical emergency protection system was of great significance for epidemic prevention. Described in the paper are measures taken by the pharmaceutical department of the hospital as follows. These measures include launching an emergency response mechanism, formulating a catalogue of COVID-19 key therapeutic drugs, urgently purchasing therapeutic drugs, transforming the processes of emergency pharmacy, establishing a drug donation management system, building a COVID-19 pharmaceutical care team, and setting up a " cloud pharmacy" to meet the drug needs of patients with non-COVID-19 chronic diseases, in addition to strengthening personnel protection of pharmacists. During such an epidemic, the pharmacy administration works in a professional, comprehensive, complex and systematic emergency program, which guaranteed the safety of drug supply, medication and enabled the treatment to be carried out in an orderly manner.
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Objective: To investigate the application characteristics of proton pump inhibitors (PPIs) in 31 hospitals in Wuhan ar-ea from 2014 to 2016 to provide reference for the clinical rational use. Methods: The utilization of PPIs in 31 hospitals in Wuhan area from 2014 to 2016 was statistically analyzed by drug types and dosage form in terms of consumption sum, DDDs, DDC, and consump-tion ranking (B)/DDDs ranking (A), etc. Results: The consumption sum and DDDs of PPIs were rising year by year. As for the dos-age form, the most commonly used one was oral preparation, however, the percent of injection kept high level. Among the different PPIs, oral poptolazole and lansorazole for injection were with the fastest increase in consumption sum and DDDs, while the consumption sum and DDDs of omeprazole for injection significantly decreased. The DDDs of oral poptolazole ranked first in the continuous three years with the B/A value much higher than 1. 0. The synchronicity was good for most of PPIs and the DDC was decreasing year by year. Moreover, PPIs were dominated by domestic products except for esomeprazole. Conclusion: The use of PPIs in 31 hospitals in Wuhan area from 2014 to 2016 was basically reasonable. However, some potential irrational application in clinic may still exist. There-fore, the application monitoring for PPIs should be further strengthened to promote rational drug use in clinics.
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Objective To study the relationship between mental effort and personal time perspective during the process of individual changing bad habits.Methods 230 graduate students were collected to attend this longitudinal study of 21 days by experience sampling method.The data on mental effort and performance were obtained from the process of daily change of the bad behavior.Zimbardo Time Perspective Inventory (ZTPI) was applied to graduate students.The survey results were analyzed by hierarchical linear modeling (HLM).Results In 21 days,the mental effort of subjects showed very clear downward trend,the trend of the change was statistical significant (total score(5.63±2.62),t=-5.590,P＜0.01).Mental effort didn't have significant difference in five kinds of behavioral objectives (keeping early hours,exercising daily,dieting,reading daily,limiting screen time) (P＞0.05).The male obviously put more effort than the female during the study(t=2.743,P＜0.01).Both Present Hedonism and Futurism were inversely related to mental effort,which was statistical significant (t=-2.504,P＜0.05;t=2.39,P＜0.05).Both Present Fatalism and Futurism had the effects on the changing trend of the mental effort regulatory,which was statistical significant (t=-3.099,P＜0.01;t=-2.400,P＜0.05).Conclusion The mental effort of changing the behavior will gradually decline during the process of habit establishment.The mental effort of subjects who had present fatalism or futurism show a faster decline.
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<p><b>OBJECTIVE</b>To investigate the effect of Liuwei Wuling tablets on the cytoplasmic translocation and release of high-mobility group box-1 (HMGB1) in hepatocytes in mice with acute live injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS).</p><p><b>METHODS</b>A Balb/c mouse model of acute liver injury was established by intraperitoneal injection of D-GalN (400 mg/kg) and LPS (5 ug/kg). A total of 24 healthy mice were randomly and equally divided into acute liver injury control group and Liuwei Wuling tablet treatment group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in both groups at each time point within one week. Liver tissues were collected at 36 hours to perform pathological examination. The serum levels of HMGB1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), complement 3a (C3a), and complement 5a (C5a) were measured. Immunohistochemistry was used to determine the expression and cytoplasmic translocation of HMGB1 in hepatocytes.</p><p><b>RESULTS</b>At 6, 12, and 24 hours, the Liuwei Wuling tablet treatment group had significantly lower serum levels of ALT than the control group (225.33±181.64 U/L vs 471.17±174.72 U/L, t = 3.38, P < 0.01; 1509.53±182.51 U/L vs 7149.52±734.25 U/L, t = 25.82, P < 0.01; 162.89±86.51 U/L vs 1318.16±557.71 U/L, t = 7.09, P < 0.01), as well as significantly lower serum levels of AST than the control group (179.22±94.57 U/L vs 561.91±209.6 U/L, t = 5.76, P < 0.01; 590.92±190.92 U/L vs 2266.48±705.64 U/L, t = 7.94, P < 0.01; 231.24±87.7 U/L vs 444.32±117.01 U/L, t = 5.05, P < 0.01). The treatment group had significantly lower levels of HMGB1 than the control group at 6 and 12 hours (54.21±11.89 ng/ml vs 72.07±13.65 ng/ml, t = 3.41, P < 0.01; 49.23±5.97 ng/ml vs 68.71±13.07 ng/ml, t = 4.70, P < 0.01). The treatment group had significantly lower levels of TNF-α, IL-1β, and IL-6 than the control group at 12 hours (163.62±9.12 pg/ml vs 237.09±51.47 pg/ml, t = 4.86, P < 0.01; 15.66±13.13 pg/ml vs 37.43±18.68 pg/ml, t = 3.30, P < 0.01; 7.10±3.06 pg/ml vs 21.42±8.23 pg/ml, t = 5.65, P < 0.01). The treatment group had significantly lower levels of C3a and C5a than the control group at 12 hours (2.52±1.27 pg/ml vs 9.83±2.96 ng/ml, t = 7.86, P < 0.01; 2.16±1.03 ng/ml vs 7.23±1.55 ng/ml, t = 9.67, P < 0.01). Compared with the control group, the treatment group had significantly reduced liver inflammation and necrosis, and a significantly lower cytoplasmic translocation rate of HMGB1 in hepatocytes (38.76%±7.37% vs 8.15%±2.11%, P < 0.01).</p><p><b>CONCLUSION</b>Liuwei Wuling tablets can reduce the cytoplasmic translocation of HMGB1 in hepatocytes and relieve liver inflammation in mice with acute liver injury.</p>
Subject(s)
Animals , Mice , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Complement C3a , Complement C5a , Cytoplasm , Metabolism , Drugs, Chinese Herbal , Pharmacology , Galactosamine , HMGB1 Protein , Metabolism , Hepatocytes , Interleukin-1beta , Blood , Interleukin-6 , Blood , Lipopolysaccharides , Liver Failure, Acute , Drug Therapy , Mice, Inbred BALB C , Protein Transport , Tablets , Tumor Necrosis Factor-alpha , BloodABSTRACT
Objective To investigate the effect of phenolic alkaloids from Menispermum dauricum( PAMd)on the mRNA expression of the glutamate transporter EAAC1 in hippocampal neurons of rats subjected to focal cerebral ischemia and to elucidate its neuroprotective mechanisms. Methods A total of 42 Sprague Dawley(SD)rats were randomly divided into three groups:sham group,model control group,and PAMd(10 mg·kg-1 ,i.g)group(n = 14 each).The focal cerebral ischemia model of rat was induced by the middle cerebral artery occlusion( MCAO). The 2,3,5-triphenyltetrazolium chloride( TTC) staining was applied to measure the cerebral infarct size and the reverse transcriptase-polymerase chain reaction(RT-PCR)assay to detect EAAC1 mRNA expression in hippocampal neurons. Results After 24 h ischemia,the cerebral infarct volumes were (0.0±0.0)%,(35.3±2.9)% and(21.3±3.8)% in sham group,model control group and PAMd group,respectively(P<0.05). The relative expression levels of EAAC1 mRNA were 0.97±0.04,2.46±0.13,and 1.91±0.15 in the three groups,respectively (P<0. 05). Conclusion PAMd may protect against cerebral ischemia by up-regulating EAAC1 mRNA expression and alleviating the excitotoxicity of glutamic acid.
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<p><b>OBJECTIVE</b>To analyze the impact of platelet count on the prognosis of stage II-III colorectal cancer receiving adjuvant chemotherapy.</p><p><b>METHODS</b>Clinical and follow-up data of 286 patients with stage II-III colorectal cancer receiving adjuvant FOLFOX chemotherapy from March 2003 to October 2011 were analyzed retrospectively. Associations of baseline blood platelet count before chemotherapy and nadir blood platelet count during chemotherapy with relapse and death after adjuvant chemotherapy were analyzed by ROC curve and the optimal cutoff was selected. The association of the blood platelet count and the prognosis was analyzed by Kaplan-Meier and Cox regression model.</p><p><b>RESULTS</b>ROC curve showed the baseline blood platelet count was associated with recurrence (AUC=0.588, P=0.034). The optimal cutoff affecting recurrence was 276×10(9)/L. Kaplan-Meier showed those with baseline platelet count >276×10(9)/L receiving adjuvant chemotherapy had worse disease free survival (DFS) than those with baseline platelet count ≤276×10(9)/L, whose 5-year disease free survival(DFS) was 66% and 80% respectively (P=0.013). Cox regression analysis revealed baseline platelet count >276×10(9)/L was an independent unfavorable factor for DFS of adjuvant chemotherapy in colorectal cancer (HR=1.865, 95% CI: 1.108-3.141, P=0.019).</p><p><b>CONCLUSION</b>Colorectal cancer patients receiving adjuvant chemotherapy with baseline platelet count >276×10(9)/L have worse prognosis.</p>
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Chemotherapy, Adjuvant , Colonic Neoplasms , Colorectal Neoplasms , Disease-Free Survival , Fluorouracil , Leucovorin , Neoplasm Staging , Organoplatinum Compounds , Platelet Count , Prognosis , Recurrence , Retrospective StudiesABSTRACT
Objective To determine the neuroprotective effect of clonidine on primary cultured cortical neurons in rats exposed to oxygen-glucose deprivation ( OGD) injury. Methods Cortical neurons cultured for 8 days were randomly assigned to the three groups: normal control group, model control group, and clonidine pretreatment group. OGD injury model was established by chemical hypoxia and glucose deprivation in incubation liquid for 4 h. Clonidine (1. 0, 3. 0, 10 μmol·L-1 ) was added 24 h before OGD injury. Neuronal injury was evaluated by MTT staining and the release of lactate dehydrogenase ( LDH) . Results Under the microscope, primary cultured cortical neurons in normal control group presented great density, round size, smooth edge, and high diopter,The suvival rate of neurons and the percentage of LDH releasing were (100. 00±32. 12)% and (100. 00 ± 37. 51 )%, respectively. After exposure to OGD injury, cortical neurons showed karyopyknosis, incomplete cell membranes, low diopters and a significant reduction in optical density of MTT staining. In addition, the suvival rate of neurons and the percentage of LDH releasing were (53. 61±7. 62)% and (166. 07±9. 65)% separately compared with normal control group. In the group with pretreatment of different concentrations of clonidine (1. 0, 3. 0, 10μmol·L-1), morphological changes induced by OGD injury were significantly reversed and optical density of MTT staining was dose-dependently raised. The percentages of survival neurons much higher than that of model control group were [(67. 53±10. 54)%, (71. 50±9. 79)% and (87. 48±5. 29)%, separately] and the obvious reductions of LDH releasing were [(136. 45±25. 72)%, (130. 92±24. 94)%and (121. 63±32. 68)%, respectively]. Conclusion Clonidine can exert neuroprotection against OGD-induced injury in primary cultured cortical neurons in rats.
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Objective To observe the effect of cinobufotalin freeze-dry powder on heart rate ( HR ) and electrocardiogram ( ECG) of SD rats and to provide experimental basis for monitoring its adverse effect on heart in clinical application. Methods The drug was administered into external jugular vein at constant speed throughout the whole experiment;standard-Ⅱ limb lead monitored the HR and ECG, and then the changes in HR and ECG before and after administration of cinobufotalin were compared. Results Thirty minutes after administration of cinobufotalin injection and cinobufotalin freeze-dry powder at middle dose and high dose, HR of the rats was significantly increased as compared with blank control group[(469±40) bpm, (466±29) bpm and (484±40) bpm vs. (411±17) bpm] (P0. 05). Conclusion Cinobufotalin freeze-dry powder has some side effects on rat heart and can increase HR, even lead to arrhythmia.
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Autophagy is a conserved and programmed catabolic process that degrades damaged proteins and organelles. But the underlying mechanism and functions of autophagy in the ischemia-reperfusion (IR)-induced injury are unknown. In this study, we employed simulated IR of N2a cells as an in vitro model of IR injury to the neurons and monitored autophagic processes. It was found that the levels of Beclin-1 (a key molecule of autophay complex, Beclin-1/class III PI3K) and LC-3II (an autophagy marker) were remarkably increased with time during the process of ischemia and the process of reperfusion after 90 min of ischemia, while the protein kinases p70S6K and mTOR which are involved in autophagy regulation showed delayed inactivation after reperfusion. Administration of 3-methyladenine (3MA), an inhibitor of class III PI3K, abolished autophagy during reperfusion, while employment of rapamycin, an inhibitor of mTORC1 (normally inducing autophagy), surprisingly weakened the induction of autophagy during reperfusion. Analyses of mitochondria function by relative cell viability demonstrated that autophagy inhibition by 3-MA attenuated the decline of mitochondria function during reperfusion. Our data demonstrated that there were two distinct dynamic patterns of autophagy during IR-induced N2a injury, Beclin-1/class III PI3K complex-dependent and mTORC1-dependent. Inhibition of over-autophagy improved cell survival. These suggest that targeting autophagy therapy will be a novel strategy to control IR-induced neuronal damage.
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Animals , Mice , Adenine , Pharmacology , Apoptosis Regulatory Proteins , Genetics , Metabolism , Autophagy , Beclin-1 , Cell Line, Tumor , Cell Survival , Mechanistic Target of Rapamycin Complex 1 , Mitochondria , Metabolism , Multiprotein Complexes , Metabolism , Neurons , Metabolism , Neuroprotective Agents , Pharmacology , Phosphatidylinositol 3-Kinases , Metabolism , Reperfusion Injury , Metabolism , Sirolimus , Pharmacology , TOR Serine-Threonine Kinases , MetabolismABSTRACT
Autophagy is a conserved and programmed catabolic process that degrades damaged proteins and organelles. But the underlying mechanism and functions of autophagy in the ischemiareperfusion (IR)-induced injury are unknown. In this study, we employed simulated IR of N2a cells as an in vitro model of IR injury to the neurons and monitored autophagic processes. It was found that the levels of Beclin-1 (a key molecule of autophay complex, Beclin-1/class III PI3K) and LC-3II (an autophagy marker) were remarkably increased with time during the process of ischemia and the process of reperfusion after 90 min of ischemia, while the protein kinases p70S6K and mTOR which are involved in autophagy regulation showed delayed inactivation after reperfusion. Administration of 3-methyladenine (3MA), an inhibitor of class III PI3K, abolished autophagy during reperfusion, while employment of rapamycin, an inhibitor of mTORC1 (normally inducing autophagy), surprisingly weakened the induction of autophagy during reperfusion. Analyses of mitochondria function by relative cell viability demonstrated that autophagy inhibition by 3-MA attenuated the decline of mitochondria function during reperfusion. Our data demonstrated that there were two distinct dynamic patterns of autophagy during IR-induced N2a injury, Beclin-1/class III PI3K complex-dependent and mTORC1-dependent. Inhibition of over-autophagy improved cell survival. These suggest that targeting autophagy therapy will be a novel strategy to control IR-induced neuronal damage.
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<p><b>OBJECTIVE</b>To compare multiple organ dysfunction score (MODS), the sequential organ failure assessment (SOFA) and the logistic organ dysfunction score (LODS) in predicting hospital mortality in severe sepsis.</p><p><b>METHODS</b>Four hundred and three patients admitted to the ICU from December 2004 to November 2007 with a diagnosis of severe sepsis were enrolled in this study. Their MODS, SOFA, LODS and Acute Physiology and Chronic Health Evaluation (APACHE) II at admission and the highest score during hospitalization were respectively recorded and collected in regard to mortality. The discrimination of three multiple organ dysfunction score systems were assessed by the areas under the receiver operating characteristic curves (AUC).</p><p><b>RESULTS</b>The AUC of admission scores was 0.811 for LODS, 0.787 for SOFA, 0.725 for MODS, and 0.770 for APACHE II in predicting hospital mortality. All maximum scores had better power of discrimination than the admission scores (P < 0.01). The power of discrimination of LODS and SOFA were better than the MODS, either the admission or the highest, respectively (P < 0.01). However, no significant difference was observed between the LODS and the SOFA regarding mortality prediction (P > 0.05). The AUC value for the APACHE II score was much lower compared to LODS (P < 0.01). However, there was no difference in AUC value among APACHE II, SOFA and MODS (P > 0.05).</p><p><b>CONCLUSION</b>LODS, SOFA and MODS show a good discrimination power, while maximum LODS is of the highest discrimination power to predict the outcome of patient with severe sepsis.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , APACHE , Hospital Mortality , Intensive Care Units , Multiple Organ Failure , Pathology , Prognosis , Sepsis , Mortality , Severity of Illness IndexABSTRACT
Objective To explore the difference of the level of Th1/Th2 balance and change of CD4+ CD45R cell after treated by laparoseopy-assisted rectal cancer surgery and conventional open rectal cancer surgery, so to compare the effect of the two procedures on immunity function of the patients. Methods CD4+ IFN-γ+ T cell (Thl cell), CD4+ IL-4 + T cell( Th2 cell)and the ratio of Th1/Th2 were detected by flow cytometery ; The levels of IFN-γand IL-4 were measured by ELISA. The changes of CD4 + CD45RA+ T cell and CD4+ CD45RO+ T cell were detected in the different procedures so that the effect of the two procedures on eytoimmunity and immune balance were analyzed. Results Compared with baseline levels, the level of Th1 cells was decreased [ (4.51±1.52 ) %, (7.26 ±2.59) % vs. ( 12.06 ±1.82 ) % ] (P < 0.05 ) ; The level of Th2 cells was increased [ (6.70 ± 2.41 ) %, (6.70 ± 2.41 ) % vs. (4.47 ± 1.90) % ] ( P < 0.05 ) ; The level of IFN-γ was decreased [ (57.15± 23.64) ng/L, (72.70 ± 27. 31 ) ng/L vs. ( 123.47 ± 32. 52) ng/L ] ( P < 0. 01 ) ; The level of IL-4 was increased [(55.55±7.29)ng/L,(57.56 ±7.13)ng/L vs. [(41.87±5.83)ng/L] (P<0.05) on 2nd and 7th day after conventional open reeatal cancer surgery; The level of Thl, Th2, IFN-γ and IL-4 in the laparoscopy-assisted rectal cancer surgery was not different ( P > 0.05 ). At 7 day postoperatively, the level of the CD4+ CD45 RA+ T cells was in-creased (35.11 ±7.82) and the CD4+ CD45RO+T cells was decreased(61.21±9.13) compared with surgery be-fore(31.11±6.72) and (68.11 ±11.42) respectively (P< 0.05). Conclusions The laparoscopy-assisted rec-tal cancer surgery has less influence on immune balance, thus protect systemic cell immunity.