AIM: To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS: In this retrospective observational study, we reviewed the inpatient...AIM: To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS: In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g. , gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use). RESULTS: Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that sup-ports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47%) did not have an appropriate indication. CONCLUSION: AST is overused in hospitalized noncritically ill patients and many patients are discharged on unnecessary AST which can increase cost, drug interactions and adverse events. Potential interventions include implementation of institutional protocols and prescriber education.展开更多
BACKGROUND:Interferon-alpha(IFN-α)is an important cytokine with multiple functions,but the target genes transactivated by IFN-αremain largely unknown.A study of such genes will help to understand the mechanism of fu...BACKGROUND:Interferon-alpha(IFN-α)is an important cytokine with multiple functions,but the target genes transactivated by IFN-αremain largely unknown.A study of such genes will help to understand the mechanism of function of IFN-α.To isolate the gene transcripts specifically upregulated by IFN-αin HepG2 cells,we conducted suppressive subtractive hybridization(SSH) analysis. METHODS:SSH was used to analyze the target genes transactivated by recombinant IFN-αprotein,and a subtractive cDNA library was constructed from HepG2 cells treated with recombinant IFN-α(rIFN-α,2000 IU/ml)for 16 hours as tester,and cells not treated with rIFN-αas driver.The SSH PCR products from the library were cloned into pGEM-T easy vector and with BLASTX, the positive clones were randomly selected,sequenced and compared to the database in GenBank of the 35 differentially expressed gene fragments from the library, 6 clones showed significant homology to other known proteins. RESULTS:The subtractive cDNA library of genes upregulated by IFN-αwas constructed successfully. rIFN-αupregulated the expression of the RAN bindingprotein 5(RANBP5),NADH dehydrogenase,exosome component 3(EXOSC3),zinc finger RNA binding protein, Dickkopf homolog 1(DKK1)and acetyl-coenzyme A acetyltransferase 2(ACAT2). CONCLUSIONS:These results suggest that rIFN-αcan upregulate the expression of important genes to exert its functions,and provide new clues for discovering the molecular mechanisms of action of IFN-α.展开更多
BACKGROUND: Stereo-tactic radiation therapy (SRT) is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the ...BACKGROUND: Stereo-tactic radiation therapy (SRT) is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the treatment is quite difficult, and it always leads to a poor outcome. Dexamethasone has certain therapeutic effect on traumatic brain edema, but the biological mechanism is still unclear. OBJECTIVE: To observe the effect of dexamethasone on the neutrophil expression of CD18. DESIGN: A randomized control observation. SETTING: Changhai Hospital of the Second Military Medical University of Chinese PLA. MATERIALS: The experiment was carried out in Changhai Hospital of the Second Military Medical University of Chinese PLA from January 1999 to December 1999. Twenty SD rats (male and female each in half) weighing (250±50) g were used. METHODS: Twenty SD rats were divided into four groups at random. ① Blank control group (n=5): The rats were not treated without dexamethasone or irradiation; ② Irradiation group (n=5): The rats were given irradiation but no dexamethasone treatment; ③ Irradiation+1 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 1 mg/kg; ④ Irradiation+5 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 5 mg/kg. The heads of the rats were irradiated with 10 MeV X-ray (30 Gy), and brain tissue was removed after 2 weeks to observe the pathological changes. Blood samples were taken from the carotid artery, gradient centrifugation was used, and neutrophile layer was obtained, the level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were detected with Northern blot and flow cytometry respectively. MAIN OUTCOME MEASURES: ① Blood cell count; ② Pathological results; ③ level of neutrophile expression of CD18 mRNA and quantity of membrane proteins. RESULTS: All the 20 SD rats were involved in the analysis of results without deletion. At 2 weeks after irradiation, obvious cell injury could be observed under light microscope. The level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were obviously increased, but the severity of cell injury was relieved in the irradiation+1 and 5 mg/kg dexamethasone groups, and the CD18 expression was markedly suppressed (P < 0.05), and the suppression was more obvious in the irradiation+5 mg/kg dexamethasone group than in the irradiation+1 mg/kg dexamethasone group (P < 0.01). CONCLUSION: Dexamethasone can reduce the radiation induced brain edema by inhibiting the expression of CD18.展开更多
Lysosomal acid lipase(LAL) cleaves cholesteryl esters(CE) and triglycerides(TG) to generate cholesterol and free fatty acid in lysosomes of cells. The downstream metabolic products of fatty acids are ligands for activ...Lysosomal acid lipase(LAL) cleaves cholesteryl esters(CE) and triglycerides(TG) to generate cholesterol and free fatty acid in lysosomes of cells. The downstream metabolic products of fatty acids are ligands for activation of peroxisome proliferator-activated receptor gamma(PPARγ). Accumulation of CEs and TGs is resulted from lack of functional LAL in lysosomes of cells, especially in myeloid cells. One characteristic phenotype in LAL knock-out(lal-/-) mice is systemic elevation of myeloid-derived suppressive cells(MDSCs). MDSCs infiltrate into multiple distal organs, alter T cell development, and suppress T cell proliferation and lymphokine production in lal-/- mice, which lead to severe pathogeneses in multiple organs. The gene transcriptional profile analysis in MDSCs from the bone marrow has identified multiple defects responsible for MDSCs malformation and malfunction in lal-/- mice, including G protein signaling, cell cycles, glycolysis metabolism, mi-tochondrial bioenergetics, mT OR pathway etc. In a separate gene transcriptional profile analysis in the lung of lal-/- mice, matrix metalloproteinase 12(MMP12) and apoptosis inhibitor 6(Api6) are highly overexpressed due to lack of ligand synthesis for PPARγ. PPARγ negatively regulates MMP12 and Api6. Blocking the PPAR signaling by overexpression of a dominant negative PPARγ(dn PPARγ) form, or overexpressing MMP12 or Api6 in myeloid or lung epithelial cells in inducible transgenic mouse models results in elevated MDSCs and inflammation-induced tumorigenesis. These studies demonstrate that LAL and its downstream effectors are critical for MDSCs development, differentiation and malfunction.展开更多
Sixty-eight cases of sterility due to excessive suppressive syndrome were treated by differential administration of Chinese drugs combined with clomiphene citrate and progesterone. This com-bined therapy was found to ...Sixty-eight cases of sterility due to excessive suppressive syndrome were treated by differential administration of Chinese drugs combined with clomiphene citrate and progesterone. This com-bined therapy was found to be significantly superior in therapeutic effect to administration of Western drugs alone or administration of Chinese drugs supplemented by progesterone. Resultant pregnancy rate was 57.4%.展开更多
The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate...The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.展开更多
文摘AIM: To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS: In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g. , gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use). RESULTS: Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that sup-ports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47%) did not have an appropriate indication. CONCLUSION: AST is overused in hospitalized noncritically ill patients and many patients are discharged on unnecessary AST which can increase cost, drug interactions and adverse events. Potential interventions include implementation of institutional protocols and prescriber education.
文摘BACKGROUND:Interferon-alpha(IFN-α)is an important cytokine with multiple functions,but the target genes transactivated by IFN-αremain largely unknown.A study of such genes will help to understand the mechanism of function of IFN-α.To isolate the gene transcripts specifically upregulated by IFN-αin HepG2 cells,we conducted suppressive subtractive hybridization(SSH) analysis. METHODS:SSH was used to analyze the target genes transactivated by recombinant IFN-αprotein,and a subtractive cDNA library was constructed from HepG2 cells treated with recombinant IFN-α(rIFN-α,2000 IU/ml)for 16 hours as tester,and cells not treated with rIFN-αas driver.The SSH PCR products from the library were cloned into pGEM-T easy vector and with BLASTX, the positive clones were randomly selected,sequenced and compared to the database in GenBank of the 35 differentially expressed gene fragments from the library, 6 clones showed significant homology to other known proteins. RESULTS:The subtractive cDNA library of genes upregulated by IFN-αwas constructed successfully. rIFN-αupregulated the expression of the RAN bindingprotein 5(RANBP5),NADH dehydrogenase,exosome component 3(EXOSC3),zinc finger RNA binding protein, Dickkopf homolog 1(DKK1)and acetyl-coenzyme A acetyltransferase 2(ACAT2). CONCLUSIONS:These results suggest that rIFN-αcan upregulate the expression of important genes to exert its functions,and provide new clues for discovering the molecular mechanisms of action of IFN-α.
文摘BACKGROUND: Stereo-tactic radiation therapy (SRT) is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the treatment is quite difficult, and it always leads to a poor outcome. Dexamethasone has certain therapeutic effect on traumatic brain edema, but the biological mechanism is still unclear. OBJECTIVE: To observe the effect of dexamethasone on the neutrophil expression of CD18. DESIGN: A randomized control observation. SETTING: Changhai Hospital of the Second Military Medical University of Chinese PLA. MATERIALS: The experiment was carried out in Changhai Hospital of the Second Military Medical University of Chinese PLA from January 1999 to December 1999. Twenty SD rats (male and female each in half) weighing (250±50) g were used. METHODS: Twenty SD rats were divided into four groups at random. ① Blank control group (n=5): The rats were not treated without dexamethasone or irradiation; ② Irradiation group (n=5): The rats were given irradiation but no dexamethasone treatment; ③ Irradiation+1 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 1 mg/kg; ④ Irradiation+5 mg/kg dexamethasone group (n=5): The rats were treated with irradiation and dexamethasone of 5 mg/kg. The heads of the rats were irradiated with 10 MeV X-ray (30 Gy), and brain tissue was removed after 2 weeks to observe the pathological changes. Blood samples were taken from the carotid artery, gradient centrifugation was used, and neutrophile layer was obtained, the level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were detected with Northern blot and flow cytometry respectively. MAIN OUTCOME MEASURES: ① Blood cell count; ② Pathological results; ③ level of neutrophile expression of CD18 mRNA and quantity of membrane proteins. RESULTS: All the 20 SD rats were involved in the analysis of results without deletion. At 2 weeks after irradiation, obvious cell injury could be observed under light microscope. The level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were obviously increased, but the severity of cell injury was relieved in the irradiation+1 and 5 mg/kg dexamethasone groups, and the CD18 expression was markedly suppressed (P < 0.05), and the suppression was more obvious in the irradiation+5 mg/kg dexamethasone group than in the irradiation+1 mg/kg dexamethasone group (P < 0.01). CONCLUSION: Dexamethasone can reduce the radiation induced brain edema by inhibiting the expression of CD18.
基金Supported by National Institutes of Health,No.CA138759,CA152099,to Yan CHL087001,to Du H,and HL-061803 and HL-067862 to Yan C and Du H
文摘Lysosomal acid lipase(LAL) cleaves cholesteryl esters(CE) and triglycerides(TG) to generate cholesterol and free fatty acid in lysosomes of cells. The downstream metabolic products of fatty acids are ligands for activation of peroxisome proliferator-activated receptor gamma(PPARγ). Accumulation of CEs and TGs is resulted from lack of functional LAL in lysosomes of cells, especially in myeloid cells. One characteristic phenotype in LAL knock-out(lal-/-) mice is systemic elevation of myeloid-derived suppressive cells(MDSCs). MDSCs infiltrate into multiple distal organs, alter T cell development, and suppress T cell proliferation and lymphokine production in lal-/- mice, which lead to severe pathogeneses in multiple organs. The gene transcriptional profile analysis in MDSCs from the bone marrow has identified multiple defects responsible for MDSCs malformation and malfunction in lal-/- mice, including G protein signaling, cell cycles, glycolysis metabolism, mi-tochondrial bioenergetics, mT OR pathway etc. In a separate gene transcriptional profile analysis in the lung of lal-/- mice, matrix metalloproteinase 12(MMP12) and apoptosis inhibitor 6(Api6) are highly overexpressed due to lack of ligand synthesis for PPARγ. PPARγ negatively regulates MMP12 and Api6. Blocking the PPAR signaling by overexpression of a dominant negative PPARγ(dn PPARγ) form, or overexpressing MMP12 or Api6 in myeloid or lung epithelial cells in inducible transgenic mouse models results in elevated MDSCs and inflammation-induced tumorigenesis. These studies demonstrate that LAL and its downstream effectors are critical for MDSCs development, differentiation and malfunction.
文摘Sixty-eight cases of sterility due to excessive suppressive syndrome were treated by differential administration of Chinese drugs combined with clomiphene citrate and progesterone. This com-bined therapy was found to be significantly superior in therapeutic effect to administration of Western drugs alone or administration of Chinese drugs supplemented by progesterone. Resultant pregnancy rate was 57.4%.
文摘The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.
